FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hosogi, Y Duncan, MJ AF Hosogi, Y Duncan, MJ TI Gene expression in Porphyromonas gingivalis after contact with human epithelial cells SO INFECTION AND IMMUNITY LA English DT Article ID ANAEROBE BACTEROIDES-FRAGILIS; REVERSE TRANSCRIPTION-PCR; BACTERIAL VIRULENCE GENES; OXIDATIVE STRESS; MATRIX METALLOPROTEINASES; VIBRIO-CHOLERAE; TISSUE-CULTURE; IN-VIVO; IDENTIFICATION; CLONING AB Porphyromonas gingivalis, a gram-negative oral anaerobe, is strongly associated with adult periodontitis. The adherence of the organism to host epithelium signals changes in both cell types as bacteria initiate infection and colonization and epithelial cells rally their defenses. We hypothesized that the expression of a defined set of P. gingivalis genes would be consistently up-regulated during infection of HEp-2 human epithelial cells. P. gingivalis genome microarrays were used to compare the gene expression profiles of bacteria that adhered to HEp-2 cells and bacteria that were incubated alone. Genes whose expression was temporally up-regulated included those involved in the oxidative stress response and those encoding heat shock proteins that are essential to maintaining cell viability under adverse conditions. The results suggest that contact with epithelial cells induces in P. gingivalis stress-responsive pathways that promote the survival of the bacterium. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Duncan, MJ (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. EM mduncan@forsyth.org FU NIDCR NIH HHS [DE10510, R01 DE010510, DE12082] NR 52 TC 41 Z9 45 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2005 VL 73 IS 4 BP 2327 EP 2335 DI 10.1128/IAI.73.4.2327-2335.2005 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 911BB UT WOS:000227975000049 PM 15784578 ER PT J AU Weingart, SN AF Weingart, SN TI Beyond Babel: prospects for a universal patient safety taxonomy SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Editorial Material C1 Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Weingart, SN (reprint author), Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02115 USA. FU AHRQ HHS [1K08 HS 11644] NR 8 TC 10 Z9 10 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD APR PY 2005 VL 17 IS 2 BP 93 EP 94 DI 10.1093/intqhc/mzi029 PG 2 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 915AL UT WOS:000228269900001 PM 15772256 ER PT J AU Stout, JE Sens, K Mietzner, S Obman, A Yu, VL AF Stout, JE Sens, K Mietzner, S Obman, A Yu, VL TI Comparative activity of quinolones, macrolides and ketolides against Legionella species using in vitro broth dilution and intracellular susceptibility testing SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article DE Legionella pneumophila; susceptibility; quinolones; ketolides; macrolides ID COMMUNITY-ACQUIRED PNEUMONIA; ANTIMICROBIAL AGENTS; GUINEA-PIGS; HL-60 CELLS; PNEUMOPHILA PNEUMONIA; CHLAMYDIA-PNEUMONIAE; HMR 3647; LEVOFLOXACIN; EFFICACY; ANTIBACTERIAL AB The comparative in vitro activity of quinolones (trovafloxacin, gemifloxacin, levofloxacin, ciprofloxacin, moxifloxacin and grepafloxacin), ketolides (ABT-773 and telithromycin) and macrolides (clarithromycin, azithromycin and erythromycin) were evaluated against Legionella pneumophila by broth dilution and an HL-60 intracellular model. The MIC90 of the quinolones, clarithromycin and ABT-773 were more than eight times lower than for erythromycin. Telithromycin, ABT-773 and azithromycin had significantly greater intracellular activity against L. pneumophila than erythromycin at 1 x MIC and 8 x MIC. The rank order of intracellular activity against L. pneumophila serogroup I was quinolones > ketolides > macrolides. Clinical trials to determine the clinical efficacy of ketolides for the treatment of Legionnaires' disease are warranted. Published by Elsevier B.V. on behalf of the International Society of Chemotherapy. C1 VA Pittsburgh Healthcare Syst, VA Med Ctr, Infect Dis Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Yu, VL (reprint author), VA Pittsburgh Healthcare Syst, VA Med Ctr, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. EM vly+@pitt.edu NR 27 TC 33 Z9 38 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD APR PY 2005 VL 25 IS 4 BP 302 EP 307 DI 10.1016/j.jantimicag.2004.08.019 PG 6 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 916SK UT WOS:000228406100005 PM 15784309 ER PT J AU Noguchi, Y Nagata-Kobayashi, S Stahl, J Wong, J AF Noguchi, Y Nagata-Kobayashi, S Stahl, J Wong, J TI A meta-analytic comparison of echocardiographic stressors SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Review DE meta-analysis; SROC analysis; stress echocardiography; test characteristics ID CORONARY-ARTERY-DISEASE; EMISSION COMPUTED-TOMOGRAPHY; HIGH-DOSE DIPYRIDAMOLE; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; DOBUTAMINE-ATROPINE STRESS; LEFT-VENTRICULAR HYPERTROPHY; ISCHEMIC-HEART-DISEASE; TRANSESOPHAGEAL PACING ECHOCARDIOGRAPHY; TREADMILL EXERCISE ECHOCARDIOGRAPHY; MYOCARDIAL-PERFUSION TOMOGRAPHY AB Background: The relative performance of alternative stressors for stress echocardiography for the diagnosis of coronary artery disease (CAD) is not well established. Methods: All studies published between 1981 to December 2001 who met inclusion criteria were included in this analysis. We performed a summary receiver operator characteristic (SROC) analysis and calculated weighted mean of the likelihood ratio and sensitivity/specificity. A covariate analysis using meta-regression methods was also performed. Results: Forty-four studies presented data on Exercise, 11 on Adenosine, 80 on Dobutamine, 40 on Dipyridamole, 16 on transatrial pacing transesophageal echocardiography (Tap-TEE), and 7 on transatrial pacing transthorasic echocardiography (Tap-TTE). SROC analysis showed that the following order of most discriminatory to least: Tap-TEE, Exercise, Dipyridamole, Dobutamine and Adenosine. Weighted means sensitivity/specificity were Exercise: 82.6/84.4%, Adenosine: 68.4/80.9%, Dobutamine: 79.6/85.1%, Dipyridamole: 71.0/92.2%, Tap-TTE: 90.7/86.1%, and Tap-TEE: 86.2/91.3%. Covariate analysis showed that the discriminatory power of Exercise decreased with increasing mean age. Conclusions: Tap-TEE is a very accurate test for both ruling in and ruling out CAD although its invasiveness may limit its clinical acceptability. Exercise is a well-balanced satisfactory test for both ruling in and ruling out but performance might be lower for the elderly. Dobutamine offers a reasonable compromise for Exercise. Dipyridamole might be good for ruling in but not for ruling out CAD. The incapability in ruling-out CAD was a major problem in clinical application of the stress. Adenosine was the least useful stressor in diagnosing CAD. C1 Fujita Hlth Univ, Sch Med, Dept Med, Div Gen Internal Med, Toyoake, Aichi, Japan. Kyoto Univ, Grad Sch Med, Dept Gen Med & Clin Epidemiol, Kyoto, Japan. Massachusetts Gen Hosp, MGH Inst Technol Assessment, Boston, MA USA. Tufts Univ, Sch Med, Tufts New England Med Ctr, Dept Med,Div Clin Decis Making Informat & Telemed, Boston, MA USA. RP Noguchi, Y (reprint author), Fujita Hlth Univ, Sch Med, Dept Med, Div Gen Internal Med, Toyoake, Aichi, Japan. EM yoshi-noguchi@umin.ac.jp NR 178 TC 10 Z9 13 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD APR PY 2005 VL 21 IS 2-3 BP 189 EP 207 DI 10.1007/s10554-004-5808-x PG 19 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 934SR UT WOS:000229729200003 PM 16015428 ER PT J AU Bauman, ML Kemper, TL AF Bauman, ML Kemper, TL TI Neuroanatomic observations of the brain in autism: a review and future directions SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Review DE brain; neuroanatomy; limbic system; cerebellum; large brain; neurochemistry ID EARLY INFANTILE-AUTISM; STEM EVOKED-RESPONSES; CEREBELLAR CORTEX; CEREBRAL-CORTEX; CELL COUNTS; CHILDREN; ABNORMALITIES; NERVE; LIFE AB Infantile autism is a behaviorally defined disorder associated with characteristic cognitive, language and behavioral features. Several postmortem studies have highlighted areas of anatomic abnormality in the autistic brain. Consistent findings have been observed in the limbic system, cerebellum and related inferior olive. In the limbic system, the hippocampus, amygdala and entorhinal cortex have shown small cell size and increased cell packing density at all ages, suggesting a pattern consistent with development curtailment. Findings in the cerebellum have included significantly reduced numbers of Purkinje cells, primarily in the posterior inferior regions of the hemispheres. A different pattern of change has been noted in the vertical limb of the diagonal band of broca, cerebellar nuclei and inferior olive with plentiful and abnormally enlarged neurons in the brains of young autistic subjects, and in adult autistic brains, small, pale neurons that are reduced in number. These findings combined with reported age-related changes in brain weight and volume, have raised the possibility that the neuropathology of autism may represent an on-going process. (C) 2004 Published by Elsevier Ltd on behalf of ISDN. C1 Massachusetts Gen Hosp, Childrens Neurol Serv, Boston, MA 02114 USA. RP Bauman, ML (reprint author), Massachusetts Gen Hosp, Childrens Neurol Serv, 15 Parkman St, Boston, MA 02114 USA. EM drb@ladders.org NR 36 TC 412 Z9 418 U1 11 U2 61 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD APR-MAY PY 2005 VL 23 IS 2-3 BP 183 EP 187 DI 10.1016/j.ijdevneu.2004.09.006 PG 5 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 910PL UT WOS:000227943900006 PM 15749244 ER PT J AU Rietzel, E Chen, GTY Choi, NC Willet, CG AF Rietzel, E Chen, GTY Choi, NC Willet, CG TI Four-dimensional image-based treatment planning: Target volume segmentation and dose calculation in the presence of respiratory motion SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) CY OCT 19-23, 2003 CL Salt Lake City, UT SP Amer Soc Therapeut Radiol & Oncol (ASTRO) DE four-dimensional (4D) computed tomography; 4D treatment planning; treatment planning; target volumes; organ motion ID LUNG-TUMORS; CT SCANS; ORGAN MOTION; MOVEMENT; ARTIFACTS; LOCATION AB Purpose: To describe approaches to four-dimensional (4D) treatment planning, including acquisition of 4D-CT scans, target delineation of spatio-temporal image data sets, 4D dose calculations, and their analysis. Methods and Materials: The study included patients with thoracic and hepatocellular tumors. Specialized tools were developed to facilitate visualization, segmentation, and analysis of 4D-CT data: maximum intensity volume to define the extent of lung tumor motion, a 4D browser to examine and dynamically assess the 4D data sets, dose calculations, including respiratory motion, and deformable registration to combine the dose distributions at different points. Results: Four-dimensional CT was used to visualize and quantitatively assess respiratory target motion. The gross target volume contours derived from light breathing scans showed significant differences compared with those extracted from 4D-CT. Evaluation of deformable registration using difference images of original and deformed anatomic maps suggested the algorithm is functionally useful. Thus, calculation of effective dose distributions, including respiratory motion, was implemented. Conclusion: Tools and methods to use 4D-CT data for treatment planning in the presence of respiratory motion have been developed and applied to several case studies. The process of 4D-CT-based treatment planning has been implemented, and technical barriers for its routine use have been identified. (c) 2005 Elsevier Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Abt Biophys Gesellschaft Schwerionenforsch, Darmstadt, Germany. RP Rietzel, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM eike@rietzel.net FU PHS HHS [P01 21239] NR 26 TC 228 Z9 242 U1 1 U2 17 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 APR 1 PY 2005 VL 61 IS 5 BP 1535 EP 1550 DI 10.1016/j.ijrobp.2004.11.037 PG 16 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 912SZ UT WOS:000228101400032 PM 15817360 ER PT J AU Gierga, DP Brewer, J Sharp, GC Betke, M Willett, CG Chen, GTY AF Gierga, DP Brewer, J Sharp, GC Betke, M Willett, CG Chen, GTY TI The correlation between internal and external markers for abdominal tumors: Implications for respiratory gating SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) CY OCT 19-23, 2003 CL Salt Lake City, UT SP Amer Soc Therapeut Radiol & Oncol (ASTRO) DE image-guided therapy; gating; fluoroscope; abdomen; tracking ID GATED RADIOTHERAPY; MOTION; LIVER; MOVEMENT; PANCREAS AB Purpose: The correlation of the respiratory motion of external patient markers and abdominal tumors was examined. Data of this type are important for image-guided therapy techniques, such as respiratory gating, that monitor the movement of external fiducials. Methods and Materials: Fluoroscopy sessions for 4 patients with internal, radiopaque tumor fiducial clips were analyzed by computer vision techniques. The motion of the internal clips and the external markers placed on the patient's abdominal skin surface were quantified and correlated. Results: In general, the motion of the tumor and external markers were well correlated. The maximum amount of peak-to-peak craniocaudal tumor motion was 2.5 cm. The ratio of tumor motion to external-marker motion ranged from 0.85 to 7.1. The variation in tumor position for a given external-marker position ranged from 2 to 9 mm. The period of the breathing cycle ranged from 2.7 to 4.5 seconds, and the frequency patterns for both the tumor and the external markers were similar. Conclusions: Although tumor motion generally correlated well with external fiducial marker motion, relatively large underlying tumor motion can occur compared with external-marker motion and variations in the tumor position for a given marker position. Treatment margins should be determined on the basis of a detailed understanding of tumor motion, as opposed to relying only on external-marker information. (c) 2005 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Boston Univ, Dept Comp Sci, Boston, MA 02215 USA. RP Gierga, DP (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Fruit St,Cox 8, Boston, MA 02114 USA. EM dgierga@partners.org NR 16 TC 128 Z9 130 U1 1 U2 14 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 APR 1 PY 2005 VL 61 IS 5 BP 1551 EP 1558 DI 10.1016/j.ijrobp.2004.12.013 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 912SZ UT WOS:000228101400033 PM 15817361 ER PT J AU Jensen, RJ Ziv, OR Rizzo, JF AF Jensen, RJ Ziv, OR Rizzo, JF TI Thresholds for activation of rabbit retinal ganglion cells with relatively large, extracellular microelectrodes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ELECTRICAL-STIMULATION; MORPHOMETRIC ANALYSIS; MACULAR DEGENERATION; RETINITIS-PIGMENTOSA; RECEPTIVE-FIELD; PHOTORECEPTORS; PRESERVATION; PROSTHESIS; ELECTRODES; EXCITATION AB PURPOSE. To investigate the responses of retinal ganglion cells (RGCs) to electrical stimulation, using electrodes comparable in size to those used in human studies investigating the feasibility of an electronic retinal prosthesis. METHODS. Rabbit retinas were stimulated in vitro with current pulses applied to the inner surface with 125- and 500-mu m diameter electrodes while the responses of RGCs were recorded extracellularly. RESULTS. Both short-latency (SL; 3-5 ms) and long-latency (LL; >= 9 ms) responses were observed after electrical stimulation within the receptive field of an RGC. With short, 0.1-ms current pulses, the threshold current for the SL cell response was significantly lower than that for the LL cell response. With long (10- to 20-ms) pulses, the threshold currents for the SL and LL cell responses were very similar. The threshold current for the SL cell response increased more steeply than did the LL cell response when the electrode was displaced from the point of lowest electrical threshold, either above or along the surface of the retina. Stimulation of an RGC axon outside of the cell's receptive field produced only an SL response. For 0.1-ms duration pulses, the threshold current for the axonal response was significantly higher than the threshold current for the SL cell response. At pulse durations > 1 ms, the thresholds were very similar. CONCLUSIONS. RGC responses to electrical stimulation depend on the current pulse duration and location of the stimulating electrode. For an epiretinal prosthesis, short-duration current pulses may be preferable since they result in a more localized activation of the retina. C1 VA Boston Healthcare Syst, Ctr Innovat Visual Rehabil, Boston, MA 02130 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Jensen, RJ (reprint author), VA Boston Healthcare Syst, Ctr Innovat Visual Rehabil, 150 S Huntington Ave,Mail Stop 151E, Boston, MA 02130 USA. EM ralph.jensen@med.va.gov NR 34 TC 88 Z9 89 U1 0 U2 8 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2005 VL 46 IS 4 BP 1486 EP 1496 DI 10.1167/iovs.04-1018 PG 11 WC Ophthalmology SC Ophthalmology GA 910DB UT WOS:000227908900054 PM 15790920 ER PT J AU Radwin, LE Farquhar, SL Knowles, MN Virchick, BG AF Radwin, LE Farquhar, SL Knowles, MN Virchick, BG TI Cancer patients' descriptions of their nursing care SO JOURNAL OF ADVANCED NURSING LA English DT Article DE nursing; media campaign; constant comparative method; patients' perceptions ID CARING BEHAVIORS AB Aim. This paper reports a study of cancer patients' descriptions of nurses and nursing care. Background. Nurses lament their poor representation in the media, and campaigns to improve their portrayal have been initiated. Media portrayal of nurses might be more realistic if patients' descriptions of nursing care were incorporated. Method. Qualitative data from an instrument development study were analysed. A total of 461 patients answered the question, 'In general, how do you feel about nurses?' The data were analysed by the constant comparative method and grounded theory coding techniques. Findings. A typology of four concepts reflecting cancer patients' descriptions of their nursing care emerged from the data. The concepts were: laudable, caring, professional and outcomes. The concept laudable refers to commendable qualities of the nurse and nursing care. Caring refers to the nurse showing compassion, concern and kindness. Professional refers to the nurse as meeting expected standards of knowledge, skill and demeanour. Outcomes refer to the affective, cognitive, or physical effects attributed to nursing care. Both positive and negative instances of the concepts were included in the analysis. Examples of each concept using patients' own words are given. Conclusions. These cancer patients held nurses in relatively high esteem. These findings could be disseminated to the public press as an example of what patients' value about nurses and nursing care. They also could be used in media efforts to recruit and retain nurses. C1 Univ Massachusetts, Coll Nursing & Hlth Sci, Dept Nursing, Boston, MA 02125 USA. Rhode Isl Hosp, Providence, RI USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Radwin, LE (reprint author), Univ Massachusetts, Coll Nursing & Hlth Sci, Dept Nursing, Boston, MA 02125 USA. EM laurel.radwin@umb.edu NR 29 TC 20 Z9 20 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0309-2402 J9 J ADV NURS JI J. Adv. Nurs. PD APR PY 2005 VL 50 IS 2 BP 162 EP 169 DI 10.1111/j.1365-2648.2005.03375.x PG 8 WC Nursing SC Nursing GA 908GT UT WOS:000227776200006 PM 15788080 ER PT J AU Bauer, MS Altshuler, L Evans, DR Beresford, T Williford, WO Hauger, R AF Bauer, MS Altshuler, L Evans, DR Beresford, T Williford, WO Hauger, R CA VA Coopertive Study 430 Team TI Prevalence and distinct correlates of anxiety, substance, and combined comorbidity in a multi-site public sector sample with bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; substance use disorders; anxiety disorders; assessment; function; adherence; post-traumatic stress disorder; panic disorder; obsessive-compulsive disorder; alcohol; cocaine ID POSTTRAUMATIC-STRESS-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; PANIC DISORDER; DRUG-ABUSE; I DISORDER; PSYCHIATRIC COMORBIDITY; UNIPOLAR DEPRESSION; GENERAL-POPULATION; ALCOHOL-ABUSE; PURE-MANIA AB Background: Recent data indicate high prevalence of both anxiety and substance comorbidity in bipolar disorder. However, few studies have utilized public sector samples, and only one has attempted to separate contributions of each type of comorbidity. Methods: 328 inpatient veterans with bipolar disorder across I I sites were assessed using selected Structured Clinical Interview for DSM-IV modules and self-reports. Results: Comorbidity was common (current: 57.3%; lifetime: 78.4%), with multiple current comorbidities in 29.8%. Substance comorbidity rate was comparable to rates typically reported in non-veteran inpatient samples (33.8% current, 72.3% lifetime). Selected anxiety comorbidity rates exceeded those in other inpatient samples and appeared more chronic than episodic/recurrent (38.3% current, 43.3% lifetime). 49% of PTSD was due to non-combat stressors. Major correlates of current substance comorbidity alone were younger age, worse marital status, and higher current employability. Correlates of current anxiety comorbidity alone were early age of onset, greater number of prior-year depressive episodes, higher rates of disability pension receipt, and lower self-reported mental and physical function. Combined comorbidity resembled anxiety comorbidity. Limitations: This is a cross-sectional analysis of acutely hospitalized veterans. Conclusions: Distinct patterns of substance and anxiety comorbidity are striking, and may be subserved by distinct neurobiologic mechanisms. The prevalence, chronicity and functional impact of anxiety disorders indicate the need for improved recognition and treatment of this other dual diagnosis group is warranted. Clinical and research interventions should recognize these divergent comorbidity patterns and provide individualized treatment built "from the patient out." (c) 2005 Elsevier B.V. All rights reserved. C1 VAMC, Providence, RI 02908 USA. Brown Univ, Providence, RI 02908 USA. W LA VAMC, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Augusta VAMC, Augusta, GA USA. Med Coll Georgia, Augusta, GA USA. Denver VAMC, Denver, CO USA. Univ Colorado, Denver, CO USA. Perry Point VAMC, Perry Point, MD USA. Univ Maryland, Perry Point, MD USA. San Diego VAMC, San Diego, CA USA. Univ Calif San Diego, San Diego, CA USA. RP Bauer, MS (reprint author), VAMC, 830 Chalkstone Ave,116R, Providence, RI 02908 USA. EM mark.bauer@med.va.gov NR 84 TC 104 Z9 104 U1 2 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD APR PY 2005 VL 85 IS 3 BP 301 EP 315 DI 10.1016/j.jad.2004.11.009 PG 15 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 916WM UT WOS:000228417300007 PM 15780700 ER PT J AU Regenold, WT Hisley, KC Obuchowski, A Lefkowitz, DM Marano, C Hauser, P AF Regenold, WT Hisley, KC Obuchowski, A Lefkowitz, DM Marano, C Hauser, P TI Relationship of white matter hyperintensities to cerebrospinal fluid glucose polyol pathway metabolites - a pilot study in treatment-resistant affective disorder patients SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE white matter; affective; polyol; sorbitol; glucose ID BIPOLAR AFFECTIVE-DISORDER; SIGNAL HYPERINTENSITIES; MAJOR DEPRESSION; RISK-FACTORS; DIABETIC-NEUROPATHY; RATING-SCALE; LESIONS; PREVALENCE; MRI; ABNORMALITIES AB Background: Magnetic resonance imaging (MRI) white matter hyperintensities (WMHs) are found at higher rates in patients with affective disorders, particularly late-life or treatment-resistant disorders. Studies support a vascular pathogenesis for WMHs in late-life onset disorders; however, pathogenesis in typical early-life onset disorders is less clear. Based on associations between diabetes mellitus and both WMHs and affective disorders, this study investigated the relationship between WMHs and brain glucose metabolism by the polyol pathway-a pathway linked to nervous tissue disease in diabetes. Methods: Burdens of fluid-attenuated inversion recovery (FLAIR) WMHs were quantified and correlated with cerebrospinal fluid (CSF) concentrations of glucose metabolites in 10 nondiabetic inpatients with treatment-resistant bipolar, unipolar, and schizoaffective disorders and 10 nondiabetic control patients who had been investigated clinically for transient neurological symptoms. Results: Deep but not periventricular WMH burden correlated positively and significantly with elevated CSF concentrations of sorbitol, the specific polyol pathway metabolite of glucose (rho=0.86, p=0.002), in the affective disorders but not the control group. Limitations: This was a pilot study with a relatively small number of subjects; therefore, conclusions are tentative. Controls were not healthy subjects; they were patients with transient neurological symptoms. Conclusions: This is the first reported evidence of a relationship between WMHs and increased brain glucose metabolism by the polyol pathway in patients with affective disorders. More extensive studies are necessary to determine whether this preliminary finding represents a pathogenetic relationship. (c) 2004 Elsevier B.V. All rights reserved. C1 Univ Maryland, Sch Med, Dept Psychiat, Div Geriatr Psychiat, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Diagnost Radiol, Baltimore, MD 21201 USA. Oregon Hlth Sci Univ, Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97207 USA. Oregon Hlth Sci Univ, NW Hepatitis C Resource Ctr, Portland, OR 97207 USA. RP Regenold, WT (reprint author), Univ Maryland, Sch Med, Dept Psychiat, Div Geriatr Psychiat, Baltimore, MD 21201 USA. EM wregenol@psych.umaryland.edu NR 53 TC 15 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 APR PY 2005 VL 85 IS 3 BP 341 EP 350 DI 10.1016/j.jad.2004.10.010 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 916WM UT WOS:000228417300012 PM 15780705 ER PT J AU Zhang, J Goodlett, DR Quinn, JF Peskind, E Kaye, JA Zhou, Y Pan, C Yi, E Eng, J Wang, Q Aebersold, RH Montine, TJ AF Zhang, J Goodlett, DR Quinn, JF Peskind, E Kaye, JA Zhou, Y Pan, C Yi, E Eng, J Wang, Q Aebersold, RH Montine, TJ TI Quantitative proteomics of cerebrospinal fluid from patients with Alzheimer disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer disease; biomarkers; cerebrospinal fluid; proteomics ID MASS-SPECTROMETRY; DIAGNOSIS; MARKERS AB Biomarkers to assist in the diagnosis and medical management of Alzheimer disease (AD) are a pressing need. We have employed a proteomic approach, microcapillary liquid chromatography mass spectrometry of proteins labeled with isotope-coded affinity tags (ICAT), to quantify relative changes in the proteome of human cerebrospinal fluid (CSF) obtained from the lumbar cistern. Using CSF from well-characterized AD patients and age-matched controls at 2 different institutions, we quantified protein concentration ratios of 42% of the 390 CSF proteins that we have identified and found differences >= 20% in over half of them. We confirmed our findings by western blot and validated this approach by quantifying relative levels of amyloid precursor protein and cathepsin B in 17 AD patients and 16 control individuals. Quantitative proteomics of CSF from AD patients compared to age-matched controls, as well as from other neurodegenerative diseases, will allow us to generate a roster of proteins that may serve as specific biomarker panels for AD and other geriatric dementias. C1 Univ Washington, Harborview Med Ctr, Sch Med, Div Neuropathol,Dept Pathol, Seattle, WA 98104 USA. Univ Washington, Dept Med Chem, Sch Med, Seattle, WA 98104 USA. Univ Washington, Dept Psychiat & Behav Sci, Sch Med, Seattle, WA 98104 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR USA. VA Puget Sound Hlth Care Syst, Mentall Illness Res Educ & Clin Ctr, Seattle, WA USA. Inst Syst Biol, Seattle, WA USA. RP Montine, TJ (reprint author), Univ Washington, Harborview Med Ctr, Sch Med, Div Neuropathol,Dept Pathol, Box 359791, Seattle, WA 98104 USA. EM tmontine@u.washington.edu RI Eng, Jimmy/I-4202-2012; OI Eng, Jimmy/0000-0001-6352-6737; Kaye, Jeffrey/0000-0002-9971-3478 FU NCRR NIH HHS [RR000334]; NIA NIH HHS [AG024011, AG05136, AG08017, AG16835] NR 14 TC 122 Z9 125 U1 0 U2 10 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PD APR PY 2005 VL 7 IS 2 BP 125 EP 133 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 942KN UT WOS:000230281400005 PM 15851850 ER PT J AU McGuire, M Ling, LM AF McGuire, M Ling, LM TI Ventilatory long-term facilitation is greater in 1-vs. 2-mo-old awake rats SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE respiratory control; plasticity; intermittent; hypoxia; development ID CHRONIC INTERMITTENT HYPOXIA; OBSTRUCTIVE SLEEP-APNEA; SEROTONIN-DEPENDENT PLASTICITY; RESPIRATORY MOTOR OUTPUT; NREM SLEEP; GENOMIC CONSEQUENCES; PERINATAL HYPEROXIA; PHRENIC RESPONSES; EPISODIC HYPOXIA; NEONATAL-PERIOD AB Respiratory long-term facilitation (LTF) declines in middle-aged vs. adult male rats. Chronic intermittent hypoxia (CIH; 5 min 11 - 12% O-2/5 min air, 12 h/night, 7 nights) enhances LTF in adult rats. However, LTF in immature rats and the effect of early CIH are unevaluated. The present study compared LTF in 1- and 2-mo-old rats and examined the effect of neonatal CIH ( initiated at 2 days after birth) on the LTF. Ventilatory LTF, elicited by 5 ( protocol 1) or 10 ( protocol 2) episodes of poikilocapnic hypoxia (5 min 12% O-2/5 min air), was measured twice by plethysmography on the same male conscious rat when it was 1 and 2 mo old. In untreated ( without CIH) rats, both resting ventilation (54.7 +/- 0.6 vs. 43.0 +/- 0.2 ml center dot 100 g(-1) center dot min(-1)) and hypoxic ventilatory response ( 131 +/- 4 vs. 66 +/- 3% above baseline) were greater in 1- vs. 2-mo-old rats. Protocol 1 elicited LTF in 1-mo-old ( 12.5 +/- 1.0% above baseline) but not 2-mo-old rats. Protocol 2 elicited a greater LTF in 1- mo-old (24.3 +/- 0.8%) vs. 2-mo-old rats ( 18.2 +/- 0.5%). In CIH-treated rats, protocol 1 also elicited LTF in 1- mo-old ( 13.1 +/- 1.5%) but not 2-mo-old rats. Protocol 2 elicited LTF in both age groups, but LTF was enhanced by the CIH only in 1- mo-old rats (28.8 +/- 0.9%). These results suggest that ventilatory LTF and hypoxic ventilatory response are greater in male rats shortly before their sexual maturity and that the neonatal CIH somewhat enhances ventilatory LTF similar to 3 wk after CIH, but this enhancement does not last to adulthood. C1 Harvard Univ, Brigham & Womens Hosp, Med Sch,Div Sleep Med, BIDMC, Boston, MA 02115 USA. RP Ling, LM (reprint author), Harvard Univ, Brigham & Womens Hosp, Med Sch,Div Sleep Med, BIDMC, 75 Francis St, Boston, MA 02115 USA. EM lling@partners.org FU NHLBI NIH HHS [HL-64912] NR 50 TC 32 Z9 34 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD APR PY 2005 VL 98 IS 4 BP 1195 EP 1201 DI 10.1152/japplphysiol.00996.2004 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 906TE UT WOS:000227665400007 PM 15591293 ER PT J AU Bragdon, CR Jasty, M Muratoglu, OK Harris, WH AF Bragdon, CR Jasty, M Muratoglu, OK Harris, WH TI Third-body wear testing of a highly cross-linked acetabular liner - The effect of large femoral head size in the presence of particulate poly (methyl-methacrylate) debris SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip arthroplasty; polyethylene; cross-linked; wear; third body; hip simulator ID MOLECULAR-WEIGHT POLYETHYLENE; TOTAL KNEE ARTHROPLASTY; TOTAL HIP-ARTHROPLASTY; SURFACE DAMAGE; REPLACEMENT; PARTICLES; HYDROXYAPATITE; OSTEOLYSIS; COBALT AB The hip simulator wear performance of an electron beam cross-linked and subsequently melted ultrahigh molecular weight polyethylene against femoral heads of 28-, 38-, and 46-mm diameter in the presence of poly (methyl-methacrylate) particulate debris was contrasted with that of conventional polyethylene against a 46-mm diameter head. Over 5 million cycles of testing, the average wear rate of the conventional polyethylene liners was 29.3 +/- 3.0 mg per million cycles. All highly cross-linked components exhibited marked reduction in wear, with the highest wear measuring 0.74 +/- 0.85 mg per million cycles. This study, using a clinically relevant third-body material, showed the electron beam cross-linked material to be far more resistant to this third-body wear than conventional ultrahigh molecular weight polyethylene, even when very large diameter femoral heads were used. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Adult Reconstruct Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bragdon, CR (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Biomech & Biomat Lab, Jackson Bldg 1126, Boston, MA 02114 USA. NR 30 TC 21 Z9 23 U1 0 U2 2 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 APR PY 2005 VL 20 IS 3 BP 379 EP 385 DI 10.1016/j.arth.2004.09.035 PG 7 WC Orthopedics SC Orthopedics GA 919EM UT WOS:000228601100018 PM 15809958 ER PT J AU Truong-Bolduc, QC Dunman, PM Strahilevitz, J Projan, SJ Hooper, DC AF Truong-Bolduc, QC Dunman, PM Strahilevitz, J Projan, SJ Hooper, DC TI MgrA is a multiple regulator of two new efflux pumps in Staphylococcus aureus SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MULTIDRUG TRANSPORTERS; METHICILLIN-RESISTANT; ANTIBIOTIC-RESISTANCE; CONFERS RESISTANCE; EXPRESSION; NORA; PROTEIN; GENES; SYSTEM; AUTOLYSIS AB In an analysis of the resistance mechanisms of an mgrA mutant, we identified two genes encoding previously undescribed transporters, NorB and Tet38. norB was 1,392 bp and encoded a predicted 49-kDa protein. When overexpressed, NorB led to an increase in resistance to hydrophilic quinolones, ethidium bromide, and cetrimide and also to sparfloxacin, moxifloxacin, and tetracycline, a resistance phenotype of the mgrA mutant. NorA and NorB shared 30% similarity, and NorB shared 30 and 41% similarities with the Bmr and Bit transporters of Bacillus subtilis, respectively. The second efflux pump was a more selective transporter that we have called Tet38, which had 46% similarity with the plasmid-encoded TetK efflux transporter of S. aureus. tet38 was 1,353 bp and encoded a predicted 49-kDa protein. Overexpression of tet38 produced resistance to tetracycline but not to minocycline and other drugs. norB and tet38 transcription was negatively regulated by MgrA. Limited binding of MgrA to the promoter regions of norB and tet38 was demonstrated by gel shift assays, suggesting that MgrA was an indirect regulator of norB and tet38 expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant. The mgrA tet38 double mutant became more susceptible to tetracycline than the wild-type parent strain. These data demonstrate that overexpression of NorB and Tet38 contribute, respectively, to the hydrophobic quinolone resistance and the tetracycline resistance of the mgrA mutant and that MgrA regulates expression of norB and tet38 in addition to its role in regulation of norA expression. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Wyeth Res, Dept Infect Dis, Pearl River, NY USA. RP Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU NIAID NIH HHS [R01 AI023988, R01 AI23988] NR 40 TC 106 Z9 112 U1 3 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2005 VL 187 IS 7 BP 2395 EP 2405 DI 10.1128/JB.187.7.2395-2405.2005 PG 11 WC Microbiology SC Microbiology GA 907VJ UT WOS:000227745800021 PM 15774883 ER PT J AU Manchanda, N Lyubimova, A Ho, HYH James, MF Gusella, JF Ramesh, N Snapper, SB Ramesh, V AF Manchanda, N Lyubimova, A Ho, HYH James, MF Gusella, JF Ramesh, N Snapper, SB Ramesh, V TI The NF2 tumor suppressor merlin and the ERM proteins interact with N-WASP and regulate its actin polymerization function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SHIGELLA-FLEXNERI; ARP2/3 COMPLEX; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; INTRACELLULAR MOTILITY; EPITHELIAL-CELLS; F-ACTIN; ASSOCIATION; MECHANISM; ACTIVATION; NUCLEATION AB The function of the NF2 tumor suppressor merlin has remained elusive despite increasing evidence for its role in actin cytoskeleton reorganization. The closely related ERM proteins (ezrin, radixin, and moesin) act as linkers between the cell membrane and cytoskeleton, and have also been implicated as active actin reorganizers. We report here that merlin and the ERMs can interact with and regulate N-WASP, a critical regulator of actin dynamics. Merlin and moesin were found to inhibit N-WASP-mediated actin assembly in vitro, a function that appears independent of their ability to bind actin. Furthermore, exogenous expression of a constitutively active ERM inhibits N-WASP-dependent Shigella tail formation, suggesting that the ERMs may function as inhibitors of N- WASP function in vivo. This novel function of merlin and the ERMs illustrates a mechanism by which these proteins directly exert their effects on actin reorganization and also provides new insight into N-WASP regulation. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Inflammatory Bowel Dis, Boston, MA 02114 USA. Childrens Hosp, Div Immunol, Boston, MA 02115 USA. RP Ramesh, V (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Bldg 149,13th St,Rm 6222, Charlestown, MA 02129 USA. EM ramesh@helix.mgh.harvard.edu FU NHLBI NIH HHS [HL59561]; NIAID NIH HHS [AI052354]; NINDS NIH HHS [NS24279] NR 33 TC 34 Z9 35 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 1 PY 2005 VL 280 IS 13 BP 12517 EP 12522 DI 10.1074/jbc.C400583200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 910HP UT WOS:000227922000055 PM 15699051 ER PT J AU Pierce, JE Li, G AF Pierce, JE Li, G TI Muscle forces predicted using optimization methods are coordinate system dependent SO JOURNAL OF BIOMECHANICS LA English DT Article DE optimization; joint biomechanics; inverse dynamic optimization; elbow joint; joint reaction forces; muscle forces ID INVERSE DYNAMIC OPTIMIZATION; GOAL-DIRECTED MOVEMENTS; ELBOW JOINT; PHYSIOLOGICAL PREDICTION; BIOMECHANICAL ANALYSIS; LOWER-EXTREMITIES; PASSIVE MOTION; MOMENT ARMS; MODEL; KINEMATICS AB Optimization methods are widely used to predict in vivo muscle forces in musculoskeletal joints. Moment equilibrium at the joint center (usually chosen as the origin of the joint coordinate system) has been used as a constraint condition for optimization procedures and the joint reaction moments were assumed zero. This study, through the use of a three-dimensional elbow model, investigated the effect of coordinate system origin (joint center) location on muscle forces predicted using a nonlinear static optimization method. The results demonstrated that moving the origin of the coordinate system medially and laterally along the flexion-extension axis caused dramatic variations in the predicted muscle forces. For example, moving the origin of the coordinate system from a position 5 mm medial to 5 mm lateral of the geometric elbow center caused the predicted biceps force to vary from 12% to 46% and the brachialis force to vary from 80% to 34% of the total muscle loading. The joint reaction force reduced by 24% with this medial to lateral variation of the coordinate system origin location. This data revealed that the muscle forces predicted using the optimization method are sensitive to the coordinate system origin location due to the zero joint reaction moment assumption in the moment constraint condition. For accurate prediction of muscle load distributions using optimization methods, it is necessary to determine the accurate coordinate system origin location where the condition of a zero joint reaction moment is satisfied. (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, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org NR 30 TC 13 Z9 15 U1 0 U2 1 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 APR PY 2005 VL 38 IS 4 BP 695 EP 702 DI 10.1016/j.jbiomech.2004.05.016 PG 8 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 905SQ UT WOS:000227590400006 PM 15713289 ER PT J AU Sakamoto, A Chen, M Kobayashi, T Kronenberg, HM Weinstein, LS AF Sakamoto, A Chen, M Kobayashi, T Kronenberg, HM Weinstein, LS TI Chondrocyte-specific knockout of the G protein G(s)alpha leads to epiphyseal and growth plate abnormalities and ectopic chondrocyte formation and growth plate abnormalities and ectopic chondrocyte formation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE animal models (rodent); PTH/PTH-related peptide; pseudohypoparathyroidism; growth plate; hedgehog ID HORMONE-RELATED PEPTIDE; XL-ALPHA-S; PARATHYROID-HORMONE; INDIAN-HEDGEHOG; PTH/PTHRP RECEPTOR; BONE-FORMATION; IN-VIVO; DIFFERENTIATION; CARTILAGE; GENE AB G(s)alpha is a ubiquitously expressed G protein alpha-subunit that couples receptors to adenylyl cyclase. Mice with chondrocyte-specific ablation of the G,,a gene had severe epiphyseal and growth plate abnormalities and ectopic cartilage formation within the metaphyseal region of the tibia. These results show that G(s)alpha negatively regulates chondrocyte differentiation and is the critical signaling mediator of the PTH/PTH-rP receptor in growth plate chondrocytes. C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Weinstein, LS (reprint author), NIDDK, Metab Dis Branch, NIH, Bldg 10,Rm 8C101, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov FU NIDDK NIH HHS [DK58819] NR 31 TC 58 Z9 60 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 2005 VL 20 IS 4 BP 663 EP 671 DI 10.1359/JBMR.041210 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 907TT UT WOS:000227741600015 PM 15765186 ER PT J AU Massie, BM AF Massie, BM TI Heart failure trials: Are they becoming impractical? SO JOURNAL OF CARDIAC FAILURE LA English DT Editorial Material 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 0 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2005 VL 11 IS 3 BP 161 EP 163 DI 10.1016/j.cardfail.2005.03.001 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919NV UT WOS:000228625700001 PM 15812741 ER PT J AU Little, WC Zile, MR Kitzman, DW Hundley, WG O'Brien, TX Degroof, RC AF Little, WC Zile, MR Kitzman, DW Hundley, WG O'Brien, TX Degroof, RC TI The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE diastolic heart failure; diastolic function; left ventricular mass; glucose cross-link ID PULMONARY-EDEMA; DYSFUNCTION; EXERCISE; ARTERIAL AB Background: Despite its high prevalence, optimal therapy for diastolic heart failure (DHF) has not been determined. Alagebrium chloride (ALT-711) is a novel compound that breaks glucose crosslinks and may improve ventricular and arterial compliance. Methods and Results: A total of 23 patients, mean age 71 years, with stable DHF, ejection fraction (EF) > 50%, were enrolled in a 16-week, open-label trial of alagebrium 420 mg per day. Assessments included: peak exercise oxygen consumption, aortic distensibility, and left ventricular EF and mass by magnetic resonance imaging, Doppler diastolic filling, and quality of life by the Minnesota Living with Heart Failure questionnaire. One patient discontinued treatment because of a myocardial infarction after 12 days of treatment, and a second died suddenly after 10 weeks of treatment. Thus 2 1 patients completed the study. Left ventricular mass was 124 +/- 35 g at baseline and decreased to 119 +/- 34 g at follow up (P =.036). This was accompanied by a decrease in the ratio of Doppler early diastolic flow velocity to Doppler early diastolic mitral annulus velocity (E') from 10.6 +/- 2.7 to 9.4 +/- 1.9 (P =.076) and an increase in E' front 7.3 +/- 1.2 to 8.4 +/- 1.7 cm/s (P =.045). The Minnesota Living with Heart Failure total score improved from 41 +/- 21 to 32 +/- 21 (P =.01). There were no changes in EF (64 +/- 4% at baseline), blood pressure, peak exercise oxygen consumption, and aortic distensibility. Conclusion: Sixteen weeks of treatment with the glucose crosslink breaker, algebrium, resulted in a decrease in left ventricular mass and improvements in left ventricular diastolic filling and quality of life in patient with DHF. C1 Wake Forest Univ, Sch Med, Dept Internal Med, Cardiol Sect, Winston Salem, NC 27157 USA. Med Univ S Carolina, Gazes Cardiac Res Inst, Ralph H Johnson Dept Vet Affairs Med Ctr, Dept Med,Div Cardiol, Charleston, SC 29425 USA. Alteon Inc, Parsippany, NJ USA. RP Little, WC (reprint author), Wake Forest Univ, Sch Med, Dept Internal Med, Cardiol Sect, Med Ctr Blvd, Winston Salem, NC 27157 USA. FU NCRR NIH HHS [M01 RR 07122]; NHLBI NIH HHS [P01 HL 48788]; NIA NIH HHS [AG 18915, P60 AG 10484] NR 15 TC 162 Z9 171 U1 2 U2 9 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 APR PY 2005 VL 11 IS 3 BP 191 EP 195 DI 10.1016/j.cardfail.2004.09.010 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919NV UT WOS:000228625700006 PM 15812746 ER PT J AU Soltero, ER Petersen, NJ Earle, NR Glaeser, DH Urbauer, DL Deswal, A AF Soltero, ER Petersen, NJ Earle, NR Glaeser, DH Urbauer, DL Deswal, A TI Long-term results of coronary artery bypass grafting in patients with ischemic cardiomyopathy: The impact of renal insufficiency and noncardiac vascular disease SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE coronary artery bypass surgery; heart failure; ischemic heart disease; revascularization; renal insufficiency; comorbidities ID CHRONIC HEART-FAILURE; LEFT-VENTRICULAR DYSFUNCTION; SYSTOLIC DYSFUNCTION; EJECTION FRACTIONS; VETERANS-AFFAIRS; RANDOMIZED TRIAL; CARDIAC-SURGERY; REVASCULARIZATION; MORTALITY; SURVIVAL AB Background: We examined outcomes of patients with ischemic cardiomyopathy (ICMP), defined by left ventricular ejection fraction (LVEF) < 35%, compared with patients with better-preserved LVEF, undergoing coronary bypass graft surgery (CABG). In addition, we examined the relative impact of a reduced LVEF in comparison with other comorbidities on long-term mortality in these patients. Methods and Results: We evaluated 1381 patients (114 with ICMP, 1267 with better-preserved LVEF) who underwent isolated CABG at a tertiary Veterans Administration (VA) hospital between 1990 and 2000 using data from the VA Continuous Improvement in Cardiac Surgery Program and other VA databases. The 5-year survival was 74.0% in patients with ICMP and 84.4% in the group with better-preserved LVEF (p =.005). LVEF < 35% remained a significant predictor of long-term mortality in multivariable models (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.02-2.35). However, the presence of comorbidifies, especially renal insufficiency, peripheral vascular disease, and cerebrovascular disease, had a similar or greater impact on long-term mortality. Renal insufficiency (serum creatinine > 1.5 mg/dL) was associated with the highest risk of long-term mortality (HR 2.02, 95% CI 1.46-2.80). The use of a left internal thoracic artery graft reduced the risk of long-term mortality (HR 0.72, 95% Cl 0.54-0.98). Conclusion: Even though severely depressed LVEF is associated with an increased risk of long-term mortality, the presence of comorbid factors, especially renal dysfunction and noncardiac vascular disease, increase the risk of long-term mortality by a similar or even larger magnitude. These comorbid factors should be given important consideration when evaluating the risks and benefits of CABG. C1 Michael E DeBakey Vet Affairs Med Ctr, Sect Cardiothorac Surg, Operat Care Line, Houston, TX USA. Michael E DeBakey Vet Affairs Med Ctr, Dept Surg, Houston, TX USA. Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Michael E DeBakey Vet Affairs Med Ctr, Winters Ctr Heart Failure Res, Houston, TX USA. RP Deswal, A (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Sect Cardiothorac Surg, Operat Care Line, Houston, TX USA. NR 29 TC 4 Z9 4 U1 0 U2 0 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 APR PY 2005 VL 11 IS 3 BP 206 EP 212 DI 10.1016/j.cardfail.2004.07.008 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919NV UT WOS:000228625700009 PM 15812749 ER PT J AU Ludlow, A Yee, KO Lipman, R Bronson, R Weinreb, P Huang, XZ Sheppard, D Lawler, J AF Ludlow, A Yee, KO Lipman, R Bronson, R Weinreb, P Huang, XZ Sheppard, D Lawler, J TI Characterization of integrin beta 6 and thrombospondin-1 double-null mice SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE thrombospondin-1; alpha v beta 6; TGF-beta; inflammation; cancer ID GROWTH-FACTOR-BETA; SQUAMOUS CARCINOMA-CELLS; ACUTE LUNG INJURY; TGF-BETA; HUMAN ENDOMETRIUM; EPITHELIAL-CELLS; UP-REGULATION; IN-VIVO; EXPRESSION; SUBUNIT AB To identify overlapping and non-overlapping functions for TSP-1 and alpha v beta 6, we crossed TSP-1-null and beta 6-null mice and compared the phenotype of the double-null mice with those of wild-type and single-null mice. The double-null mice exhibited focal acute and organizing pneumonia that was more severe than the wild-type and single-null mice as well as a significantly higher incidence of inflammation in tissues other than the lung. The TSP-1-null and beta 6-null mice exhibited a five to eight-fold increase in granulocyte recruitment to the lung three days after exposure to lipopolysaacharide. They also had abnormalities that were infrequently observed in the wild-type and single-null mice, including heart degeneration (8.35% in wild-type and 28.1% in double-null mice), hyperplasia of the glandular epithelium of the stomach (2.8% in wild-type and 21.1% in double-null mice) and endometrial hyperplasia (0% in wild-type and 38.5% in double-null females). Furthermore, the beta 6-null and double-null mice displayed a significant elevation in benign and malignant cancers. Stomach papillomas, squamous cell carcinomas of the ear and stomach, and adenocarcinomas of the lungs, vagina/cervix and colon were observed with the highest frequency. These data demonstrate that TSP-1 and alpha v beta 6 are involved in regulation of the immune system and epithelial homeostasis. They also indicate that alpha v beta 6 functions as a tumor suppressor gene and that activation of TGF beta by TSP-1 and alpha v beta 6 contributes to normal tissue architecture and function. C1 Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Ctr, Rodent Histopathol Core, Boston, MA USA. Biogen Idec Inc, Cambridge Ctr 14, Cambridge, MA USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Lung Biol Ctr, San Francisco, CA USA. RP Lawler, J (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave,Res N 270C, Boston, MA 02215 USA. EM jlawler@bidmc.harvard.edu FU NCI NIH HHS [CA86410, CA92644]; NHLBI NIH HHS [HL53949, HL68003] NR 37 TC 28 Z9 33 U1 0 U2 2 PU CAROL DAVILA UNIV PRESS PI BUCHARESST PA 8 EROILOR SANITARI BLVD, BUCHARESST 76241, ROMANIA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD APR-JUN PY 2005 VL 9 IS 2 BP 421 EP 437 DI 10.1111/j.1582-4934.2005.tb00367.x PG 17 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 945VH UT WOS:000230529900017 PM 15963261 ER PT J AU Faraone, SV Biederman, J Monuteaux, M Spencer, T AF Faraone, SV Biederman, J Monuteaux, M Spencer, T TI Long-term effects of extended-release mixed amphetamine salts treatment of attention-deficit/hyperactivity disorder on growth SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID HYPERACTIVE-CHILDREN; STIMULANT-DRUGS; DOUBLE-BLIND; METHYLPHENIDATE; DEFICITS; WEIGHT AB Objective: The aim of this study was to examine the long-term effects of extended-release mixed amphetamine salts (MAS-XR) with 10-30-mg doses on the growth of children being treated for attention-deficit/hyperactivity disorder (ADHD). Methods: Long-term growth data were collected from 568 children, 6-12 years of age, enrolled in a multicenter, open-label study of the safety of MAS-XR for the treatment of ADHD symptoms over the course of 6-30 months. Results: Children taking MAS-XR grew less than expected, based on the norms provided by the Centers for Disease Control (CDC). The losses in expected weight and body mass index (BMI) were greatest for the heaviest children, and the losses in expected height were greatest for the tallest children. For weight, height, and BMI, we found that nearly all of the growth deficits occurred in year one. For each of these growth parameters, the loss in expected growth was not significant in the second year of treatment. Conclusions: Our results suggest that treatment with MAS-XR can lead to reductions in expected height and weight that are not fully rectified over the course of treatment, although they did show attenuation with treatment over time. Although this does not eliminate the need for clinicians to monitor growth, as they should for all stimulant formulations, it suggests that deficits in growth are not likely to be a clinical concern for most children treated with MAS-XR. C1 SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, 750 E Adams St, Syracuse, NY 13210 USA. EM faraones@upstate.edu OI Faraone, Stephen/0000-0002-9217-3982 NR 20 TC 46 Z9 47 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD APR PY 2005 VL 15 IS 2 BP 191 EP 202 DI 10.1089/cap.2005.15.191 PG 12 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 935MS UT WOS:000229787000008 PM 15910204 ER PT J AU Biederman, J Mick, E Wozniak, J Aleardi, M Spencer, T Faraone, SV AF Biederman, J Mick, E Wozniak, J Aleardi, M Spencer, T Faraone, SV TI An open-label trial of risperidone in children and adolescents with bipolar disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID PROSPECTIVE FOLLOW-UP; MANIA RATING-SCALE; YOUNG; PHARMACOTHERAPY; DEPRESSION; EFFICACY; VALIDITY; VERSION; YOUTHS AB Objective: The aim of this study was to evaluate the potential of risperidone as a treatment of pediatric bipolar disorder. Methods: This was an 8-week, open-label, prospective study of risperidone monotherapy (1.25 +/- 1.5 mg/d) for 30 bipolar youths (manic, mixed, or hypomanic; 6-17 years of age). Results: Twenty-two of the 30 youths (73%) completed the study. Using predefined criteria for improvement (a Clinical Global Impressions Improvement in Mania score of +/- 2 at endpoint), the response rate for manic symptoms was 70%. The significant reduction in symptoms of mania resulted in a mean Young Mania Rating Scale (YMRS) score 13.5 at endpoint, indicating mild residual symptoms. Weight increased significantly from baseline (2.1 +/- 2.0 kg; p < 0.001) and there was a four-fold increase in prolactin levels from baseline (P < 0.001). Conclusions: Open-label risperidone treatment was associated with a significant shortterm improvement of symptoms of pediatric bipolar disorder. Future placebo-controlled, double-blind studies are needed to confirm these preliminary results. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Res Dept, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Johnson & Johnson Ctr Study Pediat Psychopathol, Boston, MA 02114 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Dept, WACC 725,15 Parkman St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 21 TC 63 Z9 66 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD APR PY 2005 VL 15 IS 2 BP 311 EP 317 DI 10.1089/cap.2005.15.311 PG 7 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 935MS UT WOS:000229787000019 PM 15910215 ER PT J AU Mochida, GH AF Mochida, GH TI Cortical malformation and pediatric epilepsy: A molecular genetic approach SO JOURNAL OF CHILD NEUROLOGY LA English DT Article; Proceedings Paper CT International Symposium on Neuronal Migration Disorders and Childhood Epilepsies CY APR 16-17, 2004 CL Tokyo, JAPAN ID BILATERAL FRONTOPARIETAL POLYMICROGYRIA; RECESSIVE MICROCEPHALY MAPS; HUMAN CEREBRAL-CORTEX; HUMAN BRAIN SIZE; MAJOR DETERMINANT; ASPM GENE; LOCUS; EVOLUTION; PROTEIN; MUTATIONS AB Genetic malformations of the cerebral cortex are important causes of neurologic morbidity in children because they are often associated with developmental delay, motor disturbances (cerebral palsy), and epilepsy. Primary autosomal recessive microcephaly is a cortical malformation with a low incidence of epilepsy. One of its causative genes, ASPM, might play an important role in regulating proliferation of neuronal progenitor cells. Mutations in ASPM do not seem to affect later stages of cortical development, such as neuronal migration, and this might be responsible for the low epileptogenicity of this malformation. ASPM might also have played an important role in the evolutionary expansion of the human brain. Bilateral frontoparietal polymicrogyria, on the other hand, is a highly epileptogenic malformation. Its causative gene, GPR56, is also expressed in the neurogenic regions of the cortex, but its primary function might be in the determination of cell fate and/or cortical patterning. Further studies of these genes will likely lead to a better understanding of human brain development and epilepsy. C1 Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. RP Mochida, GH (reprint author), Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, Dept Neurol, 77 Ave Louis Pasteur,NRB-0266, Boston, MA 02115 USA. EM gmochida@bidmc.harvard.edu NR 38 TC 5 Z9 5 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD APR PY 2005 VL 20 IS 4 BP 300 EP 303 DI 10.1177/08830738050200040501 PG 4 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 926FM UT WOS:000229108500005 PM 15921229 ER PT J AU Shiraishi, H Stufflebeam, SM Knake, S Ahlfors, SP Sudo, A Asahina, N Egawa, K Hatanaka, K Kohsaka, S Saitoh, S Grant, PE Dale, AM Halgren, E AF Shiraishi, H Stufflebeam, SM Knake, S Ahlfors, SP Sudo, A Asahina, N Egawa, K Hatanaka, K Kohsaka, S Saitoh, S Grant, PE Dale, AM Halgren, E TI Dynamic statistical parametric mapping for analyzing the magnetoencephalographic epileptiform activity in patients with epilepsy SO JOURNAL OF CHILD NEUROLOGY LA English DT Article; Proceedings Paper CT International Symposium on Neuronal Migration Disorders and Childhood Epilepsies CY APR 16-17, 2004 CL Tokyo, JAPAN ID SURFACE-BASED ANALYSIS; SPATIOTEMPORAL MAPS; CORTICAL ACTIVITY; BRAIN ACTIVITY; MEG; LOCALIZATION; EEG; RECONSTRUCTION AB Our current purpose is to evaluate the applicability of dynamic statistical parametric mapping, a novel method for localizing epileptiform activity recorded with magnetoencephalography in patients with epilepsy. We report four pediatric patients with focal epilepsies. Magnetoencephalographic data were collected with a 306-channel whole-head helmet-shaped sensor array. We calculated equivalent current dipoles and dynamic statistical parametric mapping movies of the interictal epileptiform discharges that were based in the minimum-L2 norm estimate, minimizing the square sum of the dipole element amplitudes. The dynamic statistical parametric mapping analysis of interictal epileptiform discharges can demonstrate the rapid change and propagation of interical epileptiform discharges. According to these findings, specific epileptogenic lesion-focal cortical dysplasia could be found and patients could be operated on successfully. The presurgical analysis of interictal epileptiform discharges using dynamic statistical parametric mapping seems to be promising in patients with a possible underlying focal cortical dysplasia and might help to guide the placement of invasive electrodes. C1 Hokkaido Univ, Grad Sch Med, Dept Pediat, Kita Ku, Sapporo, Hokkaido 0608638, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MIT Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Okayama Univ Sci, Dept Appl Phys, Okayama 700, Japan. RP Shiraishi, H (reprint author), Hokkaido Univ, Grad Sch Med, Dept Pediat, Kita Ku, North 15,West 7, Sapporo, Hokkaido 0608638, Japan. EM siraisi@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010; Shiraishi, Hideaki/A-8427-2012; Ahlfors, Seppo/P-3644-2016; OI Saitoh, Shinji/0000-0001-6911-3351 FU NINDS NIH HHS [R01 NS018741, NS18741] NR 21 TC 14 Z9 14 U1 0 U2 2 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD APR PY 2005 VL 20 IS 4 BP 363 EP 369 DI 10.1177/08830738050200041601 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 926FM UT WOS:000229108500016 PM 15921240 ER PT J AU Hall, JE Sullivan, JP Richardson, GS AF Hall, JE Sullivan, JP Richardson, GS TI Brief wake episodes modulate sleep-inhibited luteinizing hormone secretion in the early follicular phase SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; HUMAN MENSTRUAL-CYCLE; PULSE FREQUENCY; IMMUNOFLUOROMETRIC ASSAY; DEFICIENT MEN; NORMAL WOMEN; PULSATILITY; PATTERN; MIDCHILDHOOD; STIMULATION AB To determine the influence of sleep, sleep stage, and time of day on the dynamics of pulsatile LH secretion in the early follicular phase (EFP) of the menstrual cycle, 11 normal women underwent simultaneous polysomnographic monitoring of sleep and measurement of LH in frequent sampling studies during a 40-h protocol that consisted of one night of normal sleep and one night of sleep deprivation followed by an afternoon nap. The interpulse interval of LH was longer during sleep than wake whether it occurred at night or during the day ( P < 0.002), implying a decrease in GnRH pulse frequency associated with sleep in the EFP. LH pulse amplitude was greater during sleep than wake ( P < 0.001) and greater pulse amplitudes were associated with longer interpulse intervals during sleep ( P < 0.005), but not wake. An interaction between sleep and time of day was observed for mean LH, with lower mean LH levels during sleep than wake at night ( P < 0.02), but not during the day. Wakefulness was more likely to be associated with an LH pulse than were stages I/II, III/IV ( slow wave), or rapid eye movement sleep ( P < 0.005). In addition, the probability of wakefulness within the sleep episode increased 5 - 15 min before the onset of LH pulses ( relative to randomly selected nonpulse LH; P < 0.05), suggesting that wakefulness was the primary event. In the absence of sleep, there was an effect of time of day on mean LH ( P < 0.02) and LH pulse amplitude ( P < 0.03), with greatest values seen during the evening. In conclusion, in the EFP, inhibition of LH pulse frequency is related to sleep rather than time of day. During periods of sleep, LH pulses occur most commonly in association with brief awakenings, suggesting that interruptions from sleep allow escape from the inhibitory effect of sleep on pulsatile GnRH secretion. A separate effect of time of day on LH pulse dynamics in the absence of sleep was also observed with evening augmentation of LH pulse amplitude and mean level; however, additional studies will be required to determine whether this represents a true circadian effect. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Neuroendocrine Lab, Boston, MA 02115 USA. RP Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Bartlett Hall Extens 5,50 Fruit St, Boston, MA 02114 USA. EM jehall@partners.org FU NCRR NIH HHS [M01 RR01066]; NICHD NIH HHS [U54 HD29164, HD-15080] NR 42 TC 25 Z9 26 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2005 VL 90 IS 4 BP 2050 EP 2055 DI 10.1210/jc.2004-2033 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 914BG UT WOS:000228198900021 PM 15671093 ER PT J AU Koutkia, P Canavan, B Breu, J Grinspoon, S AF Koutkia, P Canavan, B Breu, J Grinspoon, S TI Effects of growth hormone-releasing hormone on bone turnover in human immunodeficiency virus-infected men with fat accumulation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; QUANTITATIVE COMPUTED-TOMOGRAPHY; HIV-PROTEASE INHIBITORS; GH REPLACEMENT THERAPY; MINERAL DENSITY; BODY-COMPOSITION; PERIPHERAL LIPODYSTROPHY; CALCIOTROPIC HORMONES; INSULIN-RESISTANCE; DEFICIENT ADULTS AB GHRH is a potentially appealing strategy to simultaneously improve fat distribution and increase bone turnover in HIV-infected patients. We investigated the effects of GHRH (1 mg sc twice a day over 12 wk) in 31 HIV-infected men with abdominal fat accumulation (age 46 +/- 1 yr, body mass index 26.2 +/- 0.6 kg/m(2)) in a randomized, double-blind, placebo-controlled study. We previously reported significant effects of GHRH on IGF-I and truncal fat. In this study, we assessed whether GHRH increased markers of bone turnover. At baseline, 32% of our subjects (n = 10) demonstrated a bone density Z score less than -1.0 SD and greater than or equal to -2.5 SD, and 3% (n = 1) demonstrated a Z score of less than -2.5 SD. IGF-I correlated with N-terminal telopeptide (NTx) (r = 0.49, P = 0.005) and tended to correlate with C-terminal telopeptide (CTx) (r = 0.35, P = 0.06) at baseline. Of the bone resorption markers, CTx increased significantly (0.16 +/- 0.07 vs. -0.03 +/- 0.03 ng/ml, GHRH vs. placebo, P = 0.02), and NTx tended to increase in response to GHRH (2.8 +/- 1.4 vs. -0.5 +/- 1.0 nM bone collagen equivalent, GHRH vs. placebo, P = 0.07). Of the bone formation markers, N-terminal propeptide of type 1 procollagen increased (14.6 +/- 9 vs. -6.8 +/- 3.1 mu g/liter, GHRH vs. placebo, P = 0.03) and osteocalcin tended to increase (8.4 +/- 3.0 vs. 2.0 +/- 1.6 ng/ml, GHRH vs. placebo, P = 0.06) in response to GHRH. The calciotropic hormones, calcium and phosphorus, did not change significantly. The change in IGF-I correlated with the change in NTx (r = 0.45, P = 0.02), CTx (r = 0.38, P = 0.05), and osteocalcin (r = 0.55, P = 0.002). GHRH improves fat distribution and bone metabolism in men with HIV-related fat accumulation. Long-term studies are needed to determine whether the stimulatory effects of GHRH on bone turnover will translate into increased bone density in this population. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Nutr Metab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA 02114 USA. MIT, Gen Clin Res Ctr, Cambridge, MA 02139 USA. RP Grinspoon, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Nutr Metab, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01-RR01066]; NIDDK NIH HHS [R01 DK063639] NR 50 TC 14 Z9 16 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2005 VL 90 IS 4 BP 2154 EP 2160 DI 10.1210/jc.2004-1466 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 914BG UT WOS:000228198900038 PM 15623816 ER PT J AU Zhao, J Dahle, D Zhou, YL Zhang, X Klibanski, A AF Zhao, J Dahle, D Zhou, YL Zhang, X Klibanski, A TI Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; CHROMOSOME 14; ADENOMAS; ORIGIN; HETEROZYGOSITY; IDENTIFICATION; TUMORIGENESIS; CARCINOMA; APOPTOSIS; DELETIONS AB MEG3 is a human homolog of the mouse maternal imprinted gene, Gtl2. Gtl2 has been suggested to be involved in fetal and postnatal development and to function as an RNA. Recently our laboratory demonstrated that a cDNA isoform of MEG3, MEG3a, inhibits cell growth in vitro. Interestingly, MEG3 is highly expressed in the normal human pituitary. In striking contrast, no MEG3 expression was detected in human clinically nonfunctioning pituitary tumors. These data indicate that this imprinted gene may be involved in pituitary tumorigenesis. In the present study we investigated the mechanism underlying the absence of MEG3 expression in human clinically nonfunctioning pituitary tumors. No genomic abnormality was detected in the tumors examined. Instead, we found that two 5'-flanking regions, immediately in front of and approximately 1.6-2.1 kb upstream of the first exon, respectively, were hypermethylated in tumors without MEG3 expression compared with the normal pituitary. Reporter assays demonstrated that these two regions are functionally important in gene expression activation. Furthermore, treatment of human cancer cell lines with a methylation inhibitor resulted in MEG3 expression. We conclude that hypermethylation of the MEG3 regulatory region is an important mechanism associated with the loss of MEG3 expression in clinically nonfunctioning pituitary tumors. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B,55 Fruit St, Boston, MA 02114 USA. EM aklibanski@partners.org FU NIDDK NIH HHS [R01-DK-40947]; NIMH NIH HHS [MH/NS 31862] NR 33 TC 94 Z9 99 U1 1 U2 9 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2005 VL 90 IS 4 BP 2179 EP 2186 DI 10.1210/jc.2004-1848 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 914BG UT WOS:000228198900042 PM 15644399 ER PT J AU Haiman, CA Riley, SE Freedman, ML Setiawan, VW Conti, DV Le Marchand, L AF Haiman, CA Riley, SE Freedman, ML Setiawan, VW Conti, DV Le Marchand, L TI Common genetic variation in the sex steroid hormone-binding globulin (SHBG) gene and circulating SHBG levels among postmenopausal women: The Multiethnic Cohort SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID POLYCYSTIC-OVARY-SYNDROME; BREAST-CANCER; MESSENGER-RNA; INSULIN; EXPRESSION; REPEAT; POLYMORPHISMS; OBESITY; LINE AB SHBG transports sex steroid hormones in the blood, and levels in humans are thought to partially be genetically determined. Recently, studies have found a pentanucleotide (TAAAA)(n) repeat polymorphism in the promoter of the SHBG gene and a missense polymorphism in exon 6 (Asp(327)Asn) to predict circulating SHBG levels. Based on the potential role of common genetic variation in SHBG to serve as a marker of SHBG levels in the general population, we evaluated the association between the (TAAAA) n repeat polymorphism, Asp327Asn polymorphism, and SHBG levels in a population of African-American, Native Hawaiian, Japanese, Latina, and white healthy postmenopausal women from the Multiethnic Cohort Study (n = 372). Mean SHBG levels were not significantly different between carriers and noncarriers of the Asn(327) allele [minor allele frequency range across ethnic groups, 0.02-0.14; Asp/Asn and Asn/Asn genotypes, 33.6 mol/liter; 95% confidence interval (CI), 28.2-40.0; n = 49; Asp/Asp genotype, 30.8 mol/liter (95% CI, 28.7-33.1; n = 296); P = 0.37]. For the repeat polymorphism, we observed six different SHBG repeat alleles segregating in the population (TAAAA(6-11)), and the distribution of these alleles varied widely across populations. We found suggestive evidence of linkage disequilibrium between the Asn(327) allele and the eight-repeat allele in all populations except African-Americans (P > 0.08). In analysis of the repeat polymorphism, SHBG levels among carriers of two short alleles (seven or fewer repeats; 31.2 nmol/liter; 95% CI, 27.3-35.6; n = 82) were not statistically different from those of carriers of two long alleles (more than seven repeats; 32.7 nmol/liter; 95% CI, 29.4-36.3; n = 124; P = 0.59). We did, however, observe individual genotypic classes (n = 16) to contribute modestly to the overall prediction of SHBG levels (by analysis of covariance, P = 0.03). Carriers of the six-repeat allele (27.9 nmol/liter; 95% CI, 25.2-30.8; n = 147) were found to have nominally significantly lower SHBG levels than noncarriers (32.4 nmol/liter; 95% CI, 29.7-35.2; n = 202; P = 0.03). This effect was stronger among the subset of women who also carried the Asn(327) allele (interaction, P = 0.006). In summary, these results suggest that genetic variation at the SHBG locus may contribute to modest differences in SHBG levels among healthy postmenopausal women, and that much larger studies will be needed to better comprehend the effects of common variations at this locus in predicting circulating SHBG levels. C1 Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. Harvard Univ, MIT, Broad Inst, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Univ Hawaii, Canc Res Ctr Hawaii, Etiol Program, Honolulu, HI 96813 USA. RP Haiman, CA (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, 1441 Eastlake Ave, Los Angeles, CA 90089 USA. EM haiman@usc.edu RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NCI NIH HHS [CA-54281, CA-63464] NR 26 TC 51 Z9 54 U1 0 U2 3 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 APR PY 2005 VL 90 IS 4 BP 2198 EP 2204 DI 10.1210/jc.2004-1417 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 914BG UT WOS:000228198900045 PM 15634719 ER PT J AU Aujesky, D Stone, RA Obrosky, DS Yealy, DM Auble, TE Meehan, TP Graff, LG Fine, JM Fine, MJ AF Aujesky, D Stone, RA Obrosky, DS Yealy, DM Auble, TE Meehan, TP Graff, LG Fine, JM Fine, MJ TI Using randomized controlled trial data, the agreement between retrospectively and prospectively collected data comprising the pneumonia severity index was substantial SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE community-acquired pneumonia; risk stratification; Cohen's kappa ID COMMUNITY-ACQUIRED PNEUMONIA; MANAGEMENT; QUALITY; CARE; OUTCOMES; KAPPA AB Objective: To assess the agreement between prospectively and retrospectively determined variables comprising the Pneumonia Severity Index (PSI), assignment to PSI risk class, and designation as low risk, based on these two methods of data collection. Study Design and Setting: We analyzed data from a randomized trial of patients with community-acquired pneumonia managed in 32 hospital emergency departments (EDs). For all enrolled patients, the 20 PSI variables were collected prospectively by ED providers and retrospectively by medical record abstractors. We examined the agreement for each of the 20 PSI variables, assignment to the five PSI risk classes, and classification of patients as low (classes I-III) vs. high (classes IV and V) risk. Agreement was measured using total percent agreement and the K statistic. Results: Among the 3,220 enrolled patients, percent agreement was > 90% for 18 of the 20 variables comprising the PSI, with most unweighted kappa's being > 0.6. Agreement was substantial for assignment to PSI risk class (percent agreement: 92.7%; weighted kappa: 0.79) and for classification as low vs. high risk (percent agreement: 88.5%; unweighted kappa: 0.74). Conclusion: There was substantial agreement between retrospective and prospective assignment to PSI risk class, classification as low vs. high risk, and the-determination of most individual variables that constitute the PSI. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Emergency Med, Pittsburgh, PA 15261 USA. Qualidigm, Middletown, CT USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Connecticut, Sch Med, Dept Emergency Med, Farmington, CT USA. New Britain Gen Hosp, Dept Emergency Med, New Britain, CT USA. Norwalk Hosp, Pulm & Crit Care Med Sect, Norwalk, CT 06856 USA. RP Aujesky, D (reprint author), Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. EM Aujesky@swissonline.ch FU AHRQ HHS [R01 HS10049-03] NR 19 TC 8 Z9 8 U1 0 U2 0 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 APR PY 2005 VL 58 IS 4 BP 357 EP 363 DI 10.1016/j.jclinepi.2004.08.011 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 912CR UT WOS:000228055200004 PM 15862721 ER PT J AU Korzenik, JR AF Korzenik, JR TI Past and current theories of etiology of IBD - Toothpaste, worms, and refrigerators SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Review DE Crohn's disease; ulcerative colitis; etiology; history ID INFLAMMATORY-BOWEL-DISEASE; AVIUM SUBSPECIES PARATUBERCULOSIS; POLYMERASE CHAIN-REACTION; MEASLES-VIRUS INFECTION; CHRONIC ULCERATIVE-COLITIS; SULFATE-REDUCING BACTERIA; PUBLIC-HEALTH TRAGEDY; FIBER-RICH DIET; CROHNS-DISEASE; MYCOBACTERIUM-PARATUBERCULOSIS AB While tremendous advances have improved the understanding of inflammatory bowel disease, with regard to environmental risk factors as well as the biochemical nature of the inflammatory process, a determination of primary etiology remains elusive. Numerous theories have been proposed in the past century concerning the cause of Crohn's disease and ulcerative colitis with implications for specific therapies. On further study, most of these ideas and therapies have failed to be accurate in theory or therapeutic approach. Others remain untested or are the focus of current investigation and controversy. This paper reviews the dominant theories of primary etiology. These hypotheses include infectious causes such as Mycobacteria paratuberculosis and measles. Allergic and nutritionally related causes have been the focus of considerable research. Microparticles, which is part of the concept behind toothpaste as a cause, have been suggested more broadly to be the principal factor initiating Crohn's disease. Several of these concepts rely on the idea that there is an increased intestinal permeability that is the central defect leading to Crohn's disease. Rather than being an excessive T cell driven process, Crohn's has been suggested to be an innate immune deficiency, leading to the use of colony stimulating factors to augment the intestinal barrier function and innate immunity. A variety of changes in the gut flora, ranging from a basic dysbiosis to the absence of helminths, have been proposed as the root cause of inflammatory bowel disease. C1 Chohns & Colitis Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Gastrointestinal Unit, IBD Ctr, Boston, MA 02115 USA. RP Korzenik, JR (reprint author), Chohns & Colitis Ctr, 100 Charles River Pl,9th Floor,Cambridge St, Boston, MA 02114 USA. EM jkorzenik@partners.org NR 112 TC 55 Z9 57 U1 0 U2 3 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 APR PY 2005 VL 39 IS 4 SU 2 BP S59 EP S65 DI 10.1097/01.mcg.0000155553.28348.fc PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 911FY UT WOS:000227989200006 PM 15758661 ER PT J AU Mashimo, H Wagh, MS Goyal, RK AF Mashimo, H Wagh, MS Goyal, RK TI Surveillance and screening for Barrett esophagus and adenocarcinoma SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE Barrett's esophagus; surveillance; adenocarcinoma; dysplasia ID HIGH-GRADE DYSPLASIA; COLUMNAR-LINED ESOPHAGUS; GASTROESOPHAGEAL JUNCTION; UNITED-STATES; RISK; DIAGNOSIS; CANCER; PROGRESSION; PREVALENCE; CARCINOMA AB Current recommendations for screening and surveillance of Barrett esophagus and related lesions are based on recent guidelines by the Practice Parameters Committee of the American College of Gastroenterology. The purpose of this review is to critically examine the rationale and evidence behind these recommendations. There is strong rationale for vigorous initial testing to document the baseline status and identify early adenocarcinoma, and for surveillance of high-grade dysplasia. Recommendations for esophagectomy in patients with high-grade dysplasia need to be individualized. However, recommendations for surveillance of low-grade dysplasia and specialized intestinal metaplasia without dysplasia are largely opinion statements not well supported by objective data. Although cancers identified by surveillance are at earlier stages than those diagnosed without prior endoscopic evaluation, surveillance failures are common. Recommendations for screening and surveillance are not evidence-based and unlikely to alter national mortality from esophageal adenocarcinoma. Their impact on individual patients depends on individual circumstances. Current recommendations are limited by inconsistent endoscopic findings and sampling errors, inconsistent histologic diagnoses of Barrett esophagus and dysplasia, and our poor understanding of the natural history of various histologic lesions. Future directions include validation of methods that reduce these inconsistencies by in vivo detection of abnormalities and by objective diagnostic markers besides grades of dysplasia, such DNA content analysis and molecular markers, and improved understanding of the disease progression. Effective screening programs depend on development of simple, inexpensive, and reliable methods to identify the small group of patients truly at high risk for adenocarcinoma for endoscopic screening. C1 Brigham & Womens Hosp, VA Boston Healthcare Syst, Ctr Swallowing & Motil Disorders, Boston, MA 02115 USA. RP Goyal, RK (reprint author), VAMC Res 151, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM Rajgoyal@comcast.net FU NIDDK NIH HHS [DK62867, DK031092] NR 51 TC 20 Z9 20 U1 0 U2 0 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 APR PY 2005 VL 39 IS 4 SU 2 BP S33 EP S41 DI 10.1097/01.mcg.0000155859.26557.45 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 911FY UT WOS:000227989200002 PM 15758657 ER PT J AU Nathan, DG AF Nathan, DG TI The several Cs of translational clinical research SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INVESTIGATOR AB Perhaps because I am a veteran of the "good old days" (they were really quite bad), young physicians who hope to become clinical investigators often ask me how they might establish their careers. Many are more than a little worried about their futures and often have trouble envisioning a career path that is financially secure for themselves and their families. The grumbling of clinical investigators a few years their senior enhances their angst. So I try to encourage these young physicians because I know the great intellectual (if not monetary) rewards of the field and because I know that the future of medicine absolutely depends on clinical investigators. The following is what I try to say to them. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM david_nathan@dfci.harvard.edu NR 6 TC 22 Z9 22 U1 0 U2 2 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 APR PY 2005 VL 115 IS 4 BP 795 EP 797 DI 10.1172/JCI200524753 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 913IU UT WOS:000228145700006 PM 15841166 ER PT J AU Altshuler, D Hirschhorn, JN AF Altshuler, D Hirschhorn, JN TI MEF2A sequence variants and coronary artery disease: a change of heart? SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID GENETIC ASSOCIATION; MYOCARDIAL-INFARCTION; SUSCEPTIBILITY LOCUS; LINKAGE ANALYSIS; COMMON DISEASE; SCAN AB Rare mutations in MEF2A have been proposed as a cause of coronary artery disease (CAD) and myocardial infarction (MI). in this issue of the JCI, Pennacchio and colleagues report sequencing MEF2A in 300 patients with premature CAD and in controls. Only 1 CAD patient was found to carry a missense mutation not found in controls. The specific 21-bp deletion in MEF2A previously proposed as causal for CAD and/or MI was observed in unaffected individuals and did not segregate with CAD in families (see the related article beginning on page 1016). These results do not support the hypothesis that mutations in MEF2A are a cause of CAD and/or MI but do illustrate general principles regarding the difficulty of connecting genetic variation to common diseases. C1 Massachusetts Gen Hosp, Dept Biol Mol, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. Childrens Hosp, Div Genet, Boston, MA USA. Childrens Hosp, Dept Endocrinol, Boston, MA USA. RP Altshuler, D (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Ctr Human Genet Res, Boston, MA 02114 USA. EM altshuler@molbio.mgh.harvard.edu; joelh@broad.mit.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 15 TC 18 Z9 18 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 APR PY 2005 VL 115 IS 4 BP 831 EP 833 DI 10.1172/JCI200524715 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 913IU UT WOS:000228145700011 PM 15841171 ER PT J AU Luedde, T Assmus, U Wustefeld, T Vilsendorf, AMZ Roskams, T Schmidt-Supprian, M Rajewsky, K Brenner, DA Manns, MP Pasparakis, M Trautwein, C AF Luedde, T Assmus, U Wustefeld, T Vilsendorf, AMZ Roskams, T Schmidt-Supprian, M Rajewsky, K Brenner, DA Manns, MP Pasparakis, M Trautwein, C TI Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID I-KAPPA-B; ISCHEMIA-REPERFUSION INJURY; SEVERE LIVER DEGENERATION; TUMOR-NECROSIS-FACTOR; KINASE COMPLEX; MICE LACKING; REACTIVE OXYGEN; CONCANAVALIN-A; DEFICIENT MICE; BETA SUBUNIT AB The inhibitor of NF-kappa B (I-kappa B) kinase (IKK) complex consists of 3 subunits, IKK1, IKK2, and NF-kappa B essential modulator (NEMO), and is involved in the activation of NF-kappa B by various stimuli. IKK2 or NEMO constitutive knockout mice die during embryogenesis as a result of massive hepatic apoptosis. Therefore, we examined the role of IKK2 in TNF-induced apoptosis and ischemia/reperfusion (I/R) injury in the liver by using conditional knockout mice. Hepatocyte-specific ablation of IKK2 did not lead to impaired activation of NF-kappa B or increased apoptosis after TNF-alpha stimulation whereas conditional NEMO knockout resulted in complete block of NF-kappa B activation and massive hepatocyte apoptosis. In a model of partial hepatic I/R injury, mice lacking IKK2 in hepatocytes displayed significantly reduced liver necrosis and inflammation than wild-type mice. AS602868, a novel chemical inhibitor of IKK2, protected mice from liver injury due to I/R without sensitizing them toward TNF-induced apoptosis and could therefore emerge as a new pharmacological therapy for liver resection, hemorrhagic shock, or transplantation surgery. C1 Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-30625 Hannover, Germany. Hannover Med Sch, Dept Abdominal & Transplantat Surg, D-30625 Hannover, Germany. Univ Hosp Leuven, Dept Pathol, Louvain, Belgium. Harvard Univ, Sch Med, CBR, Inst Biomed Res Inc, Boston, MA USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. European Mol Biol Lab, Mouse Biol Unit, Monterotondo, Italy. RP Trautwein, C (reprint author), Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Carl Neuberg Str 1, D-30625 Hannover, Germany. EM Trautwein.Christian@mh-hannover.de RI Schmidt-Supprian, Marc/F-5893-2011 OI Schmidt-Supprian, Marc/0000-0002-8543-6166 NR 47 TC 128 Z9 132 U1 0 U2 5 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 APR PY 2005 VL 115 IS 4 BP 849 EP 859 DI 10.1172/JCI200523493 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 913IU UT WOS:000228145700016 PM 15776110 ER PT J AU He, CH Waxman, AB Lee, CG Link, H Rabach, ME Ma, B Chen, QS Zhu, Z Zhong, M Nakayama, K Nakayama, KI Homer, R Elias, JA AF He, CH Waxman, AB Lee, CG Link, H Rabach, ME Ma, B Chen, QS Zhu, Z Zhong, M Nakayama, K Nakayama, KI Homer, R Elias, JA TI Bcl-2-related protein A1 is an endogenous and cytokine-stimulated mediator of cytoprotection in hyperoxic acute lung injury SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; BCL-2 FAMILY MEMBER; UP-REGULATES BCL-2; FACTOR-KAPPA-B; CELL-DEATH; INDUCED APOPTOSIS; GROWTH-FACTOR; OXYGEN-TOXICITY; INHIBITS APOPTOSIS; OXIDATIVE STRESS AB Hyperoxic acute lung injury (HALI) is characterized by a cell death response with features of apoptosis and necrosis that is inhibited by IL-11 and other interventions. We hypothesized that Bfl-1/A1, an antiapoptotic Bcl-2 protein, is a critical regulator of HALI and a mediator of IL-11-induced cytoprotection. To test this, we characterized the expression of A1 and the oxygen susceptibility of WT and IL-11 Tg(+) mice with normal and null A1 loci. In WT mice, 100% O-2 caused TUNEL+ cell death, induction and activation of intrinsic and mitochondrial-death pathways, and alveolar protein leak. Bcl-2 and Bcl-xl were also induced as an apparent protective response. A1 was induced in hyperoxia, and in A1-null mice, the toxic effects of hyperoxia were exaggerated, Bcl-2 and Bcl-xl were not induced, and premature death was seen. In contrast, IL-11 stimulated A1, diminished the toxic effects of hyperoxia, stimulated Bcl-2 and Bcl-xl, and enhanced murine survival in 100% O-2. In A1-null mice, IL-11-induced protection, survival advantage, and Bcl-2 and Bc1-x1 induction were significantly decreased. VEGF also conferred protection via an A1 -dependent mechanism. In vitro hyperoxia also stimulated A1, and A1 overexpression inhibited oxidant-induced epithelial cell apoptosis and necrosis. Al is an important regulator of oxidant-induced lung injury, apoptosis, necrosis, and Bcl-2 and Bcl-xl gene expression and a critical mediator of IL-11- and VEGF-induced cytoprotection. C1 Yale Univ, Sch Med, Pulm & Crit Care Med Sect, Dept Internal Med, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Dept Pediat, Portland, OR 97201 USA. Yale Univ, Sch Med, Endocrinol Sect, Dept Internal Med, New Haven, CT 06520 USA. Tohoku Univ, Sch Med, Div Dev Genet, Ctr Translat & Adv Anim Res Human Dis, Sendai, Miyagi 980, Japan. Kyushu Univ, Med Inst Bioregulat, Dept Mol & Cellular Biol, Fukuoka 812, Japan. RP Elias, JA (reprint author), Yale Univ, Sch Med, Pulm & Crit Care Med Sect, Dept Internal Med, 300 Cedar St,S441 TAC, New Haven, CT 06520 USA. EM jack.elias@yale.edu RI yu, yan/C-2322-2012 FU NHLBI NIH HHS [5P01HL56389-08, 1R01HL078744-01, P01 HL056389, R01 HL064242, R01 HL078744, R01HL064242-05]; NIAMS NIH HHS [AR46032, P30 AR046032] NR 55 TC 66 Z9 69 U1 0 U2 0 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 APR PY 2005 VL 115 IS 4 BP 1039 EP 1048 DI 10.1172/JCI23004 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 913IU UT WOS:000228145700036 PM 15841185 ER PT J AU Ning, MM Smirnakis, S Furie, KL Sheen, VL AF Ning, MM Smirnakis, S Furie, KL Sheen, VL TI Adult acute disseminated encephalomyelitis associated with poststreptococcal infection SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE ADEM; ADNB antibody titers; MRI; streptococcal infection; demyelinating diseases AB Acute disseminated encephalomyelitis (ADEM) is a monophasic illness that is thought to develop from antigenic mimicry with antibodies having cross-reactivity to host epitopes in the nervous system.(1) The disorder typically follows an exanthematous or recent viral infection.(2,3) In contrast, complications from bacterial poststreptococcal infections more commonly give rise to disorders in the pediatric population including Sydenham's chorea, pediatric autoimmune neuropsychiatric disorders, and ADEM.(4) We present the novel case of documented streptococcal pharyngitis and elevated antideoxyribonuclease B (ADNB) titers in an adult giving rise to ADEM. Furthermore, the absence of basal ganglia abnormalities on MRI and the degree of leukocytosis in the CSF distinguish the adult form of ADEM from childhood ADEM and adult viral demyelinating diseases. (c) 2004 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany. RP Sheen, VL (reprint author), Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Dept Neurol, HIM 807,4 Blackfan Circle, Boston, MA 02115 USA. EM vsheen@bidmc.harvard.edu FU NIMH NIH HHS [1K08MH/NS63886-01, K08 MH063886]; PHS HHS [K08-1422] NR 6 TC 4 Z9 4 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD APR PY 2005 VL 12 IS 3 BP 298 EP 300 DI 10.1016/j.jocn.2004.03.030 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 929YU UT WOS:000229383400019 PM 15851086 ER PT J AU Peters, WP Rosner, GL Vredenburgh, JJ Shpall, EJ Crump, M Richardson, PG Schuster, MW Marks, LB Cirrincione, C Norton, L Henderson, IC Schilsky, RL Hurd, DD AF Peters, WP Rosner, GL Vredenburgh, JJ Shpall, EJ Crump, M Richardson, PG Schuster, MW Marks, LB Cirrincione, C Norton, L Henderson, IC Schilsky, RL Hurd, DD TI Prospective, randomized comparison of high-dose chemotherapy with stem-cell support versus intermediate-dose chemotherapy after surgery and adjuvant chemotherapy in women with high-risk primary breast cancer: A report of CALGB 9082, SWOG 9114, and NCIC MA-13 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW SUPPORT; PREMENOPAUSAL WOMEN; CLINICAL-TRIALS; TRANSPLANTATION; RADIOTHERAPY; SURVIVAL; CONSOLIDATION; INTENSITY; TOXICITY; THERAPY AB Purpose The prognosis for women with primary breast cancer involving multiple axillary nodes remains poor. High-dose chemotherapy with stem-cell support produced promising results in initial clinical trials conducted at single institutions. Patients and Methods Seven hundred eighty-five women aged 22 to 66 years with stage IIA, IIB, or IIIA breast cancer involving 10 or more axillary lymph nodes were randomized after surgery and standard adjuvant chemotherapy to either high-dose cyclophosphamide, cisplatin, and carmustine (HD-CPB) with stem-cell support or intermediate-dose cyclophosphamide, cisplatin, and carmustine (ID-CPB) with G-CSF support but without stem cells. Planned treatment for all patients included locoregional radiation therapy. Hormone-receptor-positive patients were to receive 5 years of tamoxifen. Event-free survival (EFS) was the primary end point. Results Median follow-up was 7.3 years. Event-free survival was not significantly different between the two treatment groups (P = .24). The probability of being free of an event at 5 years with HD-CPB was 61% (95% CI, 56% to 65%), and was 58% (95% CI, 53% to 63%) for ID-CPB. Thirty-three patients died of causes attributed to HD-CPB deaths among women treated with ID-CPB. Overall survival for the two arms was identical at 71% at 5 years (P = .75). Conclusion HD-CPB with stem-cell support was not superior to ID-CPB for event-free or overall survival among all randomized women with high-risk primary breast cancer. (c) 2005 by American Society of Clinical Oncology. C1 Adherex Technol Inc, Durham, NC USA. Duke Comprehens Canc Ctr, Durham, NC USA. CAI GB Stat Ctr, Durham, NC USA. Duke Univ, Med Ctr, Dept Med JJV, Dept Radiat Oncol LBM, Durham, NC USA. MD Anderson Canc Ctr, Dept Bone & Marrow Transplant, Houston, TX USA. Princess Margaret Hosp, Dept Med Oncol & Hematol, Torrance, CA USA. N Shore Long Isl Jewish Med Ct, Manhasset, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Div Solid Tumor Oncol, New York, NY 10021 USA. Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA. CALGB, Cent Off Chairman, Chicago, IL USA. Wake Forest Univ, Sch Med, Hematol Oncol Sect, Winston Salem, NC 27109 USA. RP Schilsky, RL (reprint author), Canc & Leukemia Grp B, 230 W Monroe St,Suite 2050, Chicago, IL 60606 USA. EM rs27@uchicago.edu FU NCI NIH HHS [CA14028, CA02599, CA03927, CA04326, CA04457, CA04919, CA07968, CA08025, CA11789, CA12046, CA12449, CA16450, CA21060, CA26806, CA31809, CA31946, CA31983, CA32291, CA33601, CA35119, CA35178, CA35192, CA35279, CA37981, CA41287, CA42777, CA45377, CA45807, CA46113, CA46136, CA47559, CA47577, CA47642, CA58415, CA58416, CA58686, CA60138, CA63844, CA76447, CA76462, CA77202, CA77440, CA77651] NR 34 TC 70 Z9 73 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2005 VL 23 IS 10 BP 2191 EP 2200 DI 10.1200/JCO.2005.10.202 PG 10 WC Oncology SC Oncology GA 914XA UT WOS:000228260200011 PM 15767638 ER PT J AU Kimmick, GG Peterson, BL Kornblith, AB Mandelblatt, J Johnson, JL Wheeler, J Heinze, R Cohen, HJ Muss, HB AF Kimmick, GG Peterson, BL Kornblith, AB Mandelblatt, J Johnson, JL Wheeler, J Heinze, R Cohen, HJ Muss, HB TI Improving accrual of older persons to cancer treatment trials: A randomized trial comparing an educational intervention with standard information: CALGB 360001 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol ID CLINICAL-TRIALS; PHYSICIAN PERFORMANCE; BREAST-CANCER; AGE; PARTICIPATION; ONCOLOGISTS; STRATEGIES; BARRIERS AB Purpose To design and test a geriatric educational intervention to improve accrual of cancer patients age 65 years and older to cooperative group-sponsored treatment trials. Methods Washington, DC; and Vermont Cancer Main member institutions of the Cancer and Leukemia Group B (CALGB) and its affiliates were randomly assigned to receive standard information (n = 73) or educational intervention Submitted September 15, 2004; (n = 53). Standard information included CALGB Web site access and periodic notification November 30, 2004, about existing trials. The geriatric educational intervention included standard information in part by grants from the plus: (1) an educational seminar; (2) educational materials; (3) a list of available protocols for use on charts; (4) a monthly e-mail and mail reminders for 1 year; and (5) a case discussion seminar. The main outcome was percentage of accrual of older persons to phase II and III Institute on Aging, treatment protocols after study initiation compared with baseline. Results There were 3,032 patients entered onto trials in the baseline year, and 2,160 and 1,239 during the 2 years postintervention, respectively. Overall percentage of accrual of older and in poster form at the American patients was 37% at baseline, and 33% and 31 % during the first and second years after Society of Clinical Oncology meeting, intervention. There was no improvement in accrual in the intervention versus control arm: The content of this manuscript is solely 36% v 32% in the first year and 31 % v 31 % in the second year. Conclusion Accrual of older patients was not increased by this intervention. Reasons for lack of effect include low intervention intensity, high baseline accrual rates, and closure of several high-accruing protocols during the study. More intense and multifaceted approaches will be of at the end of needed to change physician (and patient) behavior and to increase accrual of older persons to clinical trials. (c) 2005 by American Society of Clinical Oncology. C1 Duke Univ, Med Ctr, Durham, NC 27710 USA. CALGB, Elderly Comm, Chicago, IL USA. CALGB, Ctr Stat, Durham, NC USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Vermont Canc Ctr, Burlington, VT USA. RP Kimmick, GG (reprint author), Duke Univ, Med Ctr, Suite 3800 Duke S,Box 3204, Durham, NC 27710 USA. EM gretchen.kimmick@duke.edu FU NCI NIH HHS [CA31946] NR 20 TC 59 Z9 60 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2005 VL 23 IS 10 BP 2201 EP 2207 DI 10.1200/JCO.2005.01.222 PG 7 WC Oncology SC Oncology GA 914XA UT WOS:000228260200012 PM 15800312 ER PT J AU Brown, JR Yeckes, H Friedberg, JW Neuberg, D Kim, H Nadler, LM Freedman, AS AF Brown, JR Yeckes, H Friedberg, JW Neuberg, D Kim, H Nadler, LM Freedman, AS TI Increasing incidence of late second malignancies after conditioning with cyclophosphamide and total-body irradiation and autologous bone marrow transplantation for non-Hodgkin's lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CA SP Amer Soc Hematol ID STEM-CELL TRANSPLANTATION; HIGH-DOSE THERAPY; 2ND CANCER-RISK; TERM-FOLLOW-UP; MYELODYSPLASTIC SYNDROME; FOLLICULAR LYMPHOMA; APLASTIC-ANEMIA; ACUTE-LEUKEMIA; SOLID CANCERS; DISEASE AB Purpose Although the risk of myelodysplastic syndrome (MDS) has been well-described following autologous bone marrow transplantation (ABMT), the risk of solid tumors has been poorly characterized. We report the incidence and outcome of solid tumors at 10-year follow-up in a large cohort of uniformly treated patients who underwent ABMT for non-Hodgkin's lymphoma (NHL). Patients and Methods Between 1982 and 1997, 605 patients underwent ABMT for B-cell NHL, with uniform conditioning with cyclophosphamide and total-body irradiation followed by reinfusion of autologous bone marrow purged with anti-B-cell monoclonal antibodies. Current information on relapse of disease and second malignancies was obtained via an institutional review board-approved questionnaire sent to the referring oncologists. Results Forty-two solid tumors, six non-MDS hematologic malignancies, 39 nonmelanoma skin cancers, and 68 cases of MDS/acute myelogenous leukemia (AML) were observed at a median follow-up of 9.5 years. A cumulative incidence model using death as a competing risk found that the 10-year incidence of second malignancy is 21%, with 10.0% non-MDS malignancies. The projected incidence of all malignancies at 15 years is 29%. The principal risk factor for second malignancy is increased age at ABMT (P = .0002). In the entire cohort, 9.6% of patients have died of second malignancy. Conclusion Lengthy follow-up demonstrates a significant incidence of second malignancies after ABMT for NHL. Although the incidence of MDS/AML starts to plateau, the incidence of solid tumors continues to rise. Second malignancies are responsible for a significant fraction of overall mortality following ABMT. (c) 2005 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Med Oncol, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. RP Freedman, AS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dept Biostat Sci, 44 Binney St, Boston, MA 02115 USA. EM arnold_freedman@dfci.harvard.edu NR 31 TC 63 Z9 66 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2005 VL 23 IS 10 BP 2208 EP 2214 DI 10.1200/JCO.2005.05.158 PG 7 WC Oncology SC Oncology GA 914XA UT WOS:000228260200013 PM 15753460 ER PT J AU Shenkier, TN Blay, JY O' Neill, BP Poortmans, P Thiel, E Jahnke, K Abrey, LE Neuwelt, E Tsang, R Batchelor, T Harris, N Ferreri, AJM Ponzoni, M O'Brien, P Rubenstein, J Connors, JM AF Shenkier, TN Blay, JY O' Neill, BP Poortmans, P Thiel, E Jahnke, K Abrey, LE Neuwelt, E Tsang, R Batchelor, T Harris, N Ferreri, AJM Ponzoni, M O'Brien, P Rubenstein, J Connors, JM TI Primary CNS lymphoma of T-cell origin: A descriptive analysis from the International Primary CNS Lymphoma Collaborative Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NERVOUS-SYSTEM LYMPHOMA; HIGH-DOSE METHOTREXATE; NON-HODGKINS-LYMPHOMA; CHEMOTHERAPY; RADIOTHERAPY; SURVIVAL; COMBINATION; EXPERIENCE AB Purpose To describe the demographic and tumor related characteristics and outcomes for patients with primary T-cell CNS lymphoma (TPCNSL). Patients and Methods A retrospective series of patients with TPCNSL was compiled from twelve cancer centers in seven countries. Results We identified 45 patients with a median age of 60 years (range, 3 to 84 years). Twenty (44%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. Twenty-six (58%) had involvement of a cerebral hemisphere and sixteen (36%) had lesions of deeper sites in the brain. Serum lactate dehydrogenase was elevated in 7 (32%) of 22 patients, and CSF protein was elevated in 19 of 24 patients (79%) with available data. The median disease-specific survival (DSS) was 25 months (95% CI, 11 to 38 months). The 2- and 5-year DSS were 51% (95% CI, 35% to 66%) and 17% (95% CI, 6% to 34%), respectively. Univariate and multivariate analyses were conducted for age (<= 60 v > 60 years), PS (0 or 1 v 2, 3, or 4), involvement of deep structures of the CNS (no v yes), and methotrexate (MTX) use in the primary treatment (yes v no). Only PS and MTX use were significantly associated with better outcome with hazard ratios of 0.2 (95% CI, 0.1 to 0.4) and 0.4 (95% CI, 0.2 to 0.8), respectively. Conclusion This is the largest series ever assembled of TPCNSL. The presentation and outcome appear similar to that of B cell PCNSL. PS 0 or 1 and administration of MTX are associated with better survival. (c) 2005 by American Society of Clinical Oncology. C1 British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada. Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M4X 1K9, Canada. Hop Edouard Herriot, Univ Cytokines & Canc, Ctr Leon Berard, Lyon, France. Mayo Clin, Ctr Canc, Neurooncol Program, Rochester, MN USA. Dr Bernard Verbeeten Inst, Tilburg, Netherlands. Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. Oregon Hlth & Sci Univ, Dept Neurol & Neurosurg, Portland, OR USA. Harvard Univ, Sch Med, Dept Neurol & Pathol, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Ist Sci San Raffaele, Dept Radiochem & Pathol, Milan, Italy. Newcastle Mater Hosp, Dept Radiat Oncol, Newcastle, NSW, Australia. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP British Columbia Canc Agcy, Div Med Oncol, 600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada. EM tshenkier@bccancer.bc.ca RI Ferreri, Andres Jose Maria/A-6662-2013; Poortmans, P.M.P./L-4581-2015; Blay, Jean-Yves/N-3966-2016 OI Ferreri, Andres Jose Maria/0000-0001-9606-6124; Blay, Jean-Yves/0000-0001-7190-120X NR 20 TC 84 Z9 90 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2005 VL 23 IS 10 BP 2233 EP 2239 DI 10.1200/JCO.2005.07.109 PG 7 WC Oncology SC Oncology GA 914XA UT WOS:000228260200016 PM 15800313 ER PT J AU Kleinerman, RA Tucker, MA Tarone, RE Abramson, DH Seddon, JM Stovall, M Li, FP Fraumeni, JF AF Kleinerman, RA Tucker, MA Tarone, RE Abramson, DH Seddon, JM Stovall, M Li, FP Fraumeni, JF TI Risk of new cancers after radiotherapy in long-term survivors of retinoblastoma: An extended follow-up SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEREDITARY RETINOBLASTOMA; BILATERAL RETINOBLASTOMA; NONOCULAR TUMORS; CHILDHOOD-CANCER; RADIATION; NEOPLASMS; SARCOMAS AB Purpose Many children diagnosed with retinoblastoma (Rb) survive into adulthood and are prone to subsequent cancers, particularly hereditary patients, who have germline Rb-1 mutations. We have extended the follow-up of a large cohort of Rb patients for 7 more years to provide new information on the risk of additional cancers after radiotherapy in long-term survivors. Patients and Methods We analyzed the risk of new cancers through 2000 in 1,601 Rb survivors, diagnosed from 1914 to 1984, at two US medical centers. The standardized incidence ratio (SIR) was calculated as the ratio of the observed number of cancers after hereditary and nonhereditary Rb to the expected number from the Connecticut Tumor Registry. The cumulative incidence of a new cancer after hereditary and nonhereditary Rb and radiotherapy was calculated with adjustment for competing risk of death. Results Subsequent cancer risk in 963 hereditary patients (SIR, 19; 95% Cl, 16 to 21) exceeded the risk in 638 nonhereditary Rb patients (SIR, 1.2; 95% Cl, 0.7 to 2.0). Radiation further increased the risk of another cancer in hereditary patients by 3.1-fold (95% Cl, 2.0 to 5.3). Hereditary patients continued to be at significantly increased risk for sarcomas, melanoma, and cancers of the brain and nasal cavities. The cumulative incidence for developing a new cancer at 50 years after diagnosis of Rb was 36% (95% Cl, 31% to 41 %) for hereditary and 5.7% (95% Cl, 2.4% to 11 %) for nonhereditary patients. Conclusion Hereditary Rb predisposes to a variety of new cancers over time, with radiotherapy further enhancing the risk of tumors arising in the radiation field. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Int Epidemiol Inst, Rockville, MD USA. Mem Sloan Kettering Canc Ctr, Ophthalm Oncol Serv, New York, NY 10021 USA. Massachusetts Eye & Ear Infirm, Dana Farber Canc Inst, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. RP Kleinerman, RA (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, EPS 7044,6120 Execut Ser, Rockville, MD 20852 USA. EM Kleinerr@mail.nih.gov RI Tucker, Margaret/B-4297-2015; OI Kleinerman, Ruth/0000-0001-7415-2478 FU NCI NIH HHS [N02-CP-81121] NR 29 TC 201 Z9 205 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2005 VL 23 IS 10 BP 2272 EP 2279 DI 10.1200/JCO.2005.05.054 PG 8 WC Oncology SC Oncology GA 914XA UT WOS:000228260200021 PM 15800318 ER PT J AU Suntharalingam, M Moughan, J Coia, LR Krasna, MJ Kachnic, L Haller, DG Willet, CG John, MJ Minsky, BD Owen, JB AF Suntharalingam, M Moughan, J Coia, LR Krasna, MJ Kachnic, L Haller, DG Willet, CG John, MJ Minsky, BD Owen, JB TI Outcome results of the 1996-1999 patterns of care survey of the national practice for patients receiving radiation therapy for carcinoma of the esophagus SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PREOPERATIVE CHEMORADIATION; RANDOMIZED-TRIAL; HOSPITAL VOLUME; CANCER; SURGERY; CHEMOTHERAPY; CHEMORADIOTHERAPY; ESOPHAGECTOMY; RADIOTHERAPY; ONCOLOGY AB Purpose A Patterns of Care Study of patients treated from 1996 to 1999 evaluated the national practice for patients receiving radiation therapy for carcinoma of the esophagus in the United States. Methods A national survey was conducted at 59 institutions in a stratified random sample selected from a master list of radiation therapy facilities throughout the United States. Patient, tumor, and treatment characteristics were evaluated. Multivariate comparisons of survival times were made using the Cox proportional hazards model. Results Adenocarcinoma was diagnosed in 51 % of patients and squamous cell carcinoma in 49% of patients. Sixteen percent of patients were clinical stage (CS) I (using the 1983 American Joint Committee on Cancer system), 39% were CS II, and 33% were CS III. Significant variables in the multivariate analysis of survival times included clinical stage, treatment approach, and facility size. Patients with CS III disease had a higher hazard risk of death as compared with CS I patients (hazard ratio [HR], 2.01 ; P =.001), whereas those treated with chemoradio-therapy followed by surgery (HR, 0.32; P <.0001) had a decreased risk of death compared with chemoradiotherapy-only patients. Patients at small centers had a higher risk of death (HR, 1.32; P =.03) compared with patients treated at larger facilities. Conclusion Concurrent chemoradiotherapy continued to be the most commonly utilized treatment approach during the time period studied. The observation that patients undergoing surgical resection following chemoradiation have a decreased HR or chance of death compared with other treatment schemes supports the need for a randomized trial comparing these strategies. C1 Univ Maryland, Sch Med, Dept Radiat Oncol, Baltimore, MD 21230 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Amer Coll Radiol, Philadelphia, PA 19104 USA. Community Med Ctr, Toms River, NJ USA. Boston Univ, Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Canc Ctr St Agnes, Fresno, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Suntharalingam, M (reprint author), Univ Maryland, Sch Med, Dept Radiat Oncol, 22 S Greene St, Baltimore, MD 21230 USA. EM msuntha@umm.edu FU NCI NIH HHS [CA 65435] NR 26 TC 37 Z9 41 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2005 VL 23 IS 10 BP 2325 EP 2331 DI 10.1200/JCO.2005.00.448 PG 7 WC Oncology SC Oncology GA 914XA UT WOS:000228260200026 PM 15800323 ER PT J AU Brodersen, J AF Brodersen, J TI Validity of short-term consequences of cancer prevention and screening activities? (vol 23, pg 244, 2005) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Correction C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. RP Brodersen, J (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2005 VL 23 IS 10 BP 2444 EP 2444 DI 10.1200/JCO.2005.02.905 PG 1 WC Oncology SC Oncology GA 914XA UT WOS:000228260200057 ER PT J AU Cho, D Kocher, O Lee, JC Tenen, DG Meyerson, ML Janne, PA Halmos, B AF Cho, D Kocher, O Lee, JC Tenen, DG Meyerson, ML Janne, PA Halmos, B TI Unusual cases in multiple myeloma and a dramatic response in metastatic lung cancer: CASE 4. Mutation of the epidermal growth factor receptor in an elderly man with advanced, gefitinib-responsive, non-small-cell lung cancer (vol 23, pg 235, 2005) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Correction C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. RP Cho, D (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2005 VL 23 IS 10 BP 2444 EP 2444 DI 10.1200/JCO.2005.02.906 PG 1 WC Oncology SC Oncology GA 914XA UT WOS:000228260200058 ER PT J AU Hussein, MR Haemel, AK Sudilovsky, O Wood, GS AF Hussein, MR Haemel, AK Sudilovsky, O Wood, GS TI Genomic instability in radial growth phase melanoma cell lines after ultraviolet irradiation SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Article ID HUMAN EPIDERMAL LAYERS; INDUCED DNA-DAMAGE; MICROSATELLITE INSTABILITY; B IRRADIATION; HUMAN MELANOCYTES; MOUSE SKIN; UV-LIGHT; APOPTOSIS; CANCER; INDUCTION AB Background/Aims: Although ultraviolet (UV) irradiation, apoptosis, and genomic instability are all potentially involved in the pathogenesis of melanoma, in vitro studies investigating these changes in the radial growth phase of this neoplasm are still lacking; therefore, this study was designed to investigate these changes. Method: An in vitro system consisting of three radial growth phase Wistar melanoma cell lines (WM35, WM3211, and WM1650) was established. Cells were UV irradiated (10 mJ/cm(2) for UVB and 6 J/cm(2) for UVA), harvested after UV exposure, and evaluated for viability and apoptosis using Trypan blue and terminal deoxynucleotidyl transferase mediated dUTP digoxigenin nick end labelling assays, respectively. Polymerase chain reaction based microsatellite assays were used to examine the cell lines for the presence of microsatellite instability (MSI) using 21 markers at the 1p, 2p, 3p, 4q, 9p, and 17p regions. Results: Exposure to UV initiated progressive cell death associated with pronounced apoptosis, with UVA having a greater effect than UVB. MSI was found in UVB (WM35 and WM3211) and UVA (WM35) irradiated cell lines at 1p, 9p, and 17p, but not in non-irradiated cells. The prevalence of MSI was higher after UVB irradiation (14%) than UVA irradiation (4.7%), and was most frequently found at D1S233. Conclusions: The ability of erythemogenic UV irradiation to induce both apoptosis and MSI in radial growth phase melanoma cells is suggestive of its role in melanoma pathogenesis. This instability may reflect a hypermutability state, oxidative stress induced DNA damage, replication infidelity, or a combination of these factors. C1 Assiut Univ, Fac Med, Dept Pathol, Assiut, Egypt. Brown Univ, Sch Med, Providence, RI 02912 USA. Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Univ Wisconsin, Dept Dermatol, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Hussein, MR (reprint author), Assiut Univ Hosp, Dept Pathol, Assiut, Egypt. EM mrh17@swissinfo.org FU NIAMS NIH HHS [AR01326] NR 54 TC 10 Z9 10 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0021-9746 J9 J CLIN PATHOL JI J. Clin. Pathol. PD APR PY 2005 VL 58 IS 4 BP 389 EP 396 DI 10.1136/jcp.2004.021519 PG 8 WC Pathology SC Pathology GA 909PL UT WOS:000227872000011 PM 15790703 ER PT J AU Carvalho, LH D'Avila, GB Leao, A Goncalves, C Haffajee, AD Socransky, SS Feres, M AF Carvalho, LH D'Avila, GB Leao, A Goncalves, C Haffajee, AD Socransky, SS Feres, M TI Scaling and root planing, systemic metronidazole and professional plaque removal in the treatment of chronic periodontitis in a Brazilian population II - microbiological results SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE antibiotics; metronidazole; periodontal disease; periodontal therapy; professional cleaning; scaling and root planing; subgingival plaque; supragingival plaque; treatment ID SUBGINGIVAL MICROBIOTA; DEEP POCKETS; DISEASE; THERAPY; RECOLONIZATION; BACTERIOLOGY; PARAMETERS; COMPLEXES; FREQUENCY; SURGERY AB Objective: The current investigation evaluated changes in levels and proportions of 39 bacterial species in subgingival plaque samples after scaling and root planing (SRP) alone or in combination with systemic metronidazole and/or professional cleaning in subjects with chronic periodontitis. Methods: Forty-four adult subjects (mean age 45 6 years) with periodontitis were randomly assigned in four treatment groups, a control (C, n = 10) that received SRP and placebo and three test groups treated as follows: T1 (n 12): SRP and metronidazole (M, 400 mg tid) for 10 days, T2 (n = 12): SRP, weekly professional supragingival plaque removal for 3 months (PC) and placebo, and T3 (n = 10): SRP, M and PC. Subgingival plaque samples were taken from seven sites per subject at baseline and 90 days post-therapy. Counts of 39 subgingival specie, were determined using checkerboard DNA-DNA hybridization. Significance of differences over time was determined using the Wilcoxon signed ranks test and among groups using ANCOVA. Results: The mean counts of the majority of the species were reduced post-therapy in the 4 treatment groups. Counts ( x 10(5) +/- SEM) of Porphyromonas gingivalis, Tannerella forsythensis and Treponema denticola were significantly reduced in groups T2 and T3. Levels of beneficial species, such as some Actinomyces species, Veillonella parvula, Streptococcus sanguis, Streptococcus oralis and Streprococcus gordonii were minimally affected in levels when the combined therapy was applied (T3). Mean proportions of red complex species decreased from 18.4% at baseline to 3% at 90 days post-therapy in group T3 (p < 0.01), from 25.8% to 2.3% in group T2 (p < 0.01), from 17.7% to 5.6% in group T1 (p<0.05) and from 19.4% to 8.8% in group C (NS). Proportions of the suspected periodontal pathogens from the orange complex were also markedly reduced in groups T2 and T3. Conclusions: All treatments reduced counts and proportions of red complex species. Adjunctive therapy appeared to have a greater effect and also affected members of the orange complex. C1 Univ Guarulhos, CEPPE, Dent Res Div, Dept Periodontol, BR-07023070 Guarulhos, SP, Brazil. Univ Fed Rio de Janeiro, Dept Periodontol, Rio De Janeiro, Brazil. Gama Filho Univ, Dept Periodontol, Rio De Janeiro, Brazil. Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Feres, M (reprint author), Univ Guarulhos, CEPPE, Dent Res Div, Dept Periodontol, Praca Tereza Cristina 1 Ctr, BR-07023070 Guarulhos, SP, Brazil. EM mferes@ung.br RI Feres, Magda/H-7964-2012 FU NIDCR NIH HHS [DE12108] NR 37 TC 23 Z9 24 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI FREDERIKSBERG C PA 1 ROSENORNS ALLE, DK-1970 FREDERIKSBERG C, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD APR PY 2005 VL 32 IS 4 BP 406 EP 411 DI 10.1111/j.1600-051X.2005.00720.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 919UZ UT WOS:000228644400013 PM 15811059 ER PT J AU Poon, IO Braun, U AF Poon, IO Braun, U TI High prevalence of orthostatic hypotension and its correlation with potentially causative medications among elderly veterans SO JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS LA English DT Article DE elderly; medication; orthostatic hypotension; prevalence ID BLOOD-PRESSURE; POSTURAL HYPOTENSION; ATHEROSCLEROSIS RISK; INSTITUTIONAL CARE; GENDER-DIFFERENCES; FOLLOW-UP; FALLS; HYPERTENSION; COMMUNITIES; MORTALITY AB Background: Orthostatic hypotension (OH) is defined as a reduction of systolic blood pressure of at least 20 mmHg, or diastolic blood pressure of at least 10 mmHg from a sitting to a standing position. It is a common physical finding among older adults and associated with significant morbidity and mortality. Use of medications that have the potential to induce OH, particularly concomitant use of several of such medications, is a major factor for the development of OH. Objectives: To describe the prevalence of symptomatic and asymptomatic OH in veterans aged 75 years and older attending a geriatric clinic, and to assess the association between OH and the number of potentially causative medications used. Methods: Charts of all patients who attended a VA geriatric clinic (Michael E. DeBakey VA Medical Center) during the period of 1 June 2002 to 1 June 2003 were reviewed retrospectively for (i) the use of potentially causative medications, i.e. medications that were reported to cause OH in at least 1% of the general population and that were available in the VA formulary, (ii) the presence or absence of OH, and (iii) the presence or absence of symptomatic OH. Patients with primary autonomic dysfunction, Parkinson's disease, and patients who were unable to stand, or who had no assessment for both sitting and standing blood pressure for other reasons were excluded. Results: A total of 505 individual patients attended the clinic during the study period, and 342 patients fit the inclusion criteria. About 189 of these patients (55%) had OH. Among patients with OH, 61 patients (33%) were symptomatic, including 52 patients who had falls. The prevalence of OH in patients receiving zero, one, two, and three or more potentially causative medications was 35, 58, 60 and 65% respectively. Receiving hydrochlorothiazide was associated with the highest prevalence of OH (65%), followed by receiving lisinopril (60%), trazodone (58%), furosemide (56%) and terazosin (54%). Conclusion: The prevalence of OH is very high in older veterans and significantly related to the number of concurrent causative medications used. Providers should be educated to reduce the amount of potentially causative medications in the elderly and better assess patients in which use of such medications is necessary to avoid symptomatic OH. C1 Texas So Univ, Coll Pharm & Hlth Sci, Dept Pharm Practice, Houston, TX 77004 USA. Baylor Coll Med, VA Med Ctr, Houston Ctr Qual Care & Utilizat Study, Sect Geriatr & Hlth Sci Res, Houston, TX 77030 USA. RP Poon, IO (reprint author), Texas So Univ, Coll Pharm & Hlth Sci, Dept Pharm Practice, 3100 Cleburne Ave, Houston, TX 77004 USA. EM chui_io@tsu.edu NR 27 TC 97 Z9 103 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-4727 J9 J CLIN PHARM THER JI J. Clin. Pharm. Ther. PD APR PY 2005 VL 30 IS 2 BP 173 EP 178 DI 10.1111/j.1365-2710.2005.00629.x PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 906NO UT WOS:000227649100012 PM 15811171 ER PT J AU Hollon, SD Jarrett, RB Nierenberg, AA Thase, ME Trivedi, M Rush, AJ AF Hollon, SD Jarrett, RB Nierenberg, AA Thase, ME Trivedi, M Rush, AJ TI Psychotherapy and medication in the treatment of adult and geriatric depression: Which monotherapy or combined treatment? SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID COGNITIVE-BEHAVIOR-THERAPY; COLLABORATIVE RESEARCH-PROGRAM; RANDOMIZED CONTROLLED-TRIAL; MENTAL-HEALTH-TREATMENT; TREATMENT-RESISTANT DEPRESSION; MAJOR DEPRESSION; FOLLOW-UP; RECURRENT DEPRESSION; NATIONAL-INSTITUTE; TREATMENT RESPONSE AB Objective: The authors reviewed the literature with respect to the relative efficacy of medications and psychotherapy alone and in combination in the treatment of depression. Data Sources and Study Selection: Findings from empirical studies comparing medications and psychotherapy alone and in combination were synthesized and prognostic and prescriptive indices identified. We searched both MEDLINE and PsychINFO for items published from January 1980 to October 2004 using the following terms: treatment of depression, psychotherapy and depression, and pharmacotherapy, and depression. Studies were selected that randomly assigned depressed patients to combined treatment versus monotherapy. Data Synthesis: Medication typically has a rapid and robust effect and can prevent symptom return so long as it is continued or maintained, but does little to reduce risk once its use is terminated. Both interpersonal psychotherapy (IPT) and cognitive-behavioral therapy (CBT) can be as effective as medications in the acute treatment of depressed outpatients. Interpersonal psychotherapy may improve interpersonal functioning, whereas CBT appears to have an enduring effect that reduces subsequent risk following treatment termination. Ongoing treatment with either IPT or CBT appears to further reduce risk. Treatment with the combination of medication and IPT or CBT retains the specific benefits of each and may enhance the probability of response over either monotherapy, especially in chronic depressions. Conclusion: Both medication and certain targeted psychotherapies appear to be effective in the treatment of depression. Although several prognostic indices have been identified that predict need for longer or more intensive treatment, few prescriptive indices have yet been established to select among the different treatments. Combined treatment can improve response with selected patients and enhance its breadth (IPT) or stability (CBT). C1 Vanderbilt Univ, Dept Psychol, Nashville, TN 37203 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Pittsburgh, Dept Psychiat, Med Ctr, Pittsburgh, PA USA. Western Psychiat Inst & Clin, Pittsburgh, PA USA. RP Hollon, SD (reprint author), Vanderbilt Univ, Dept Psychol, 306 Wilson Hall, Nashville, TN 37203 USA. EM d.holllon@vanderbilt.edu OI Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [MH01697] NR 110 TC 143 Z9 144 U1 5 U2 43 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 APR PY 2005 VL 66 IS 4 BP 455 EP 468 PG 14 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 917TF UT WOS:000228491400008 PM 15816788 ER PT J AU Albers, LJ Ozdemir, V Marder, SR Raggi, MA Aravagiri, M Endrenyi, L Reist, C AF Albers, LJ Ozdemir, V Marder, SR Raggi, MA Aravagiri, M Endrenyi, L Reist, C TI Low-dose fluvoxamine as an adjunct to reduce olanzapine therapeutic dose requirements - A prospective dose-adjusted drug interaction strategy SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; IN-VITRO; ATYPICAL ANTIPSYCHOTICS; POTENT INHIBITOR; PLASMA; CAFFEINE; SCHIZOPHRENIA; DISPOSITION; METABOLISM; PAROXETINE AB Despite the advances in antipsychotic pharmacotherapy over the past decade, many atypical antipsychotic agents are not readily accessible by patients with major psychosis or in developing countries where the acquisition costs may be prohibitive. Olanzapine is an efficacious and widely prescribed atypical antipsychotic agent. In theory, olanzapine therapeutic dose requirement may be reduced during concurrent treatment with inhibitors of drug metabolism. In vitro studies suggest that smoking-inducible cytochrome P450 (CYP) 1A2 contributes to formation of the metabolite 4'-N-desmethylolanzapine. The present prospective study tested the hypothesis that olanzapine steady-state doses can be significantly decreased by coadministration of a low subclinical dose of fluvoxamine, a potent inhibitor of cytochrome P450 1A2. The study design followed a targeted "at-risk" population approach with a focus on smokers who were likely to exhibit increased cytochrome P450 1A2 expression. Patients with stable psychotic illness (N = 10 men, all smokers) and receiving chronic olanzapine treatment were evaluated for steady-state plasma concentrations of olanzapine and 4'-N-desmethylolanzapine. Subsequently, olanzapine dose was reduced from 17.5 +/- 4.2 mg/d (mean SD) to 13.0 +/- 3.3 mg/d, and a nontherapeutic dose of fluvoxamine (25 mg/d, PO) was added to regimen. Patients were reevaluated at 2, 4, and 6 weeks during olanzapine-fluvoxamine cotreatment. There was no significant change in olanzapine plasma concentration, antipsychotic response, or metabolic indices (eg, serum glucose and lipids) after dose reduction in the presence of fluvoxamine (P > 0.05). 4'-N-desmethylolanzapine/olanzapine metabolic ratio decreased from 0.45 +/- 0.20 at baseline to 0.25 +/- 0.11 at week 6, suggesting inhibition of the cytochrome P450 1A2-mediated olanzapine 4'-N-demethylation by fluvoxamine (P < 0.05). In conclusion, this prospective pilot study suggests that a 26% reduction in olanzapine therapeutic dose requirement may be achieved by coadministration of a nontherapeutic oral dose of fluvoxamine. C1 Univ Calif Irvine, Dept Psychiat & Human Behav, Coll Med, Long Beach, CA USA. So Calif Inst Res & Educ, Long Beach, CA USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Mental Illness Res, Ctr Clin, VISN 22, Los Angeles, CA USA. Univ Bologna, Dept Pharmaceut Sci, Fac Pharm, Alma Mater Studiorum, I-40126 Bologna, Italy. Univ Toronto, Dept Pharmacol, Fac Med, Toronto, ON, Canada. RP Albers, LJ (reprint author), Univ Calif Irvine, Mental Hlth Care Grp, VA Long Beach Heatlhcare Syst, 5901 E 7th St, Long Beach, CA 90822 USA. EM larry.albers@med.va.gov RI Raggi, Maria Augusta/A-4545-2011 NR 27 TC 19 Z9 20 U1 0 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 APR PY 2005 VL 25 IS 2 BP 170 EP 174 DI 10.1097/01.jcp.0000155825.97703.01 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 908TX UT WOS:000227814200010 PM 15738749 ER PT J AU Quirynen, M Vogels, R Pauwels, M Haffajee, AD Socransky, SS Uzel, NG van Steenberghe, D AF Quirynen, M Vogels, R Pauwels, M Haffajee, AD Socransky, SS Uzel, NG van Steenberghe, D TI Initial subgingival colonization of 'pristine' pockets SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE biofilm; colonization; dental plaque; peri-implantitis; microbiology; plaque growth; periodontitis; clinical dental implants ID TETRACYCLINE FIBER THERAPY; PERIODONTAL THERAPY; PLAQUE; MICROBIOTA; IMPLANTS AB The treatment of periodontitis/peri-implantitis involves the reduction/eradication of periopathogens. After therapy, beneficial and pathogenic species recolonize the subgingival area. The dynamics of recolonization and especially the role of the supragingival environment in this process are still not well-understood. This prospective, split-mouth study followed the early colonization of 'pristine' pockets created during implant surgery ( 16 partially edentulous patients), to record the time needed before a complex subgingival flora could be established with the supragingival area as the single source. Four subgingival plaque samples were taken from shallow and medium pockets around implants ( test), and neighboring teeth ( undisturbed microbiota as reference) 1, 2, and 4 wks after abutment connection. Checkerboard DNA-DNA hybridization and culture data revealed a complex microbiota ( including several pathogenic species) in the pristine pockets within a wk, with a minimal increase in counts up to 4 wks. Analysis of these data demonstrated that, even with the supragingival environment as the single source for colonizing bacteria, a complex subgingival microbiota can develop within 1 wk. C1 Catholic Univ Louvain, Dept Periodontol, B-3000 Louvain, Belgium. Catholic Univ Louvain, Fac Med, Sch Dent Oral Pathol & Maxillofacial Surg, Res Grp Microbial Adhes, B-3000 Louvain, Belgium. Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Quirynen, M (reprint author), Catholic Univ Louvain, Dept Periodontol, Kapucijnenvoer 7, B-3000 Louvain, Belgium. EM Marc.Quirynen@med.kuleuven.ac.be FU NIDCR NIH HHS [DE14368] NR 21 TC 67 Z9 69 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD APR PY 2005 VL 84 IS 4 BP 340 EP 344 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 916BH UT WOS:000228357600009 PM 15790740 ER PT J AU Moles, DR Needleman, IG Niederman, R Lau, J AF Moles, DR Needleman, IG Niederman, R Lau, J TI Introduction to cumulative meta-analysis in dentistry: Lessons learned from undertaking a cumulative meta-analysis in periodontology SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE systematic review; clinical trials; periodontal diseases; meta-analysis ID MYOCARDIAL-INFARCTION; ADULT PERIODONTITIS; CONTROLLED-TRIALS; PUBLICATION BIAS; METRONIDAZOLE; DISEASE; AMOXICILLIN; TETRACYCLINE; QUALITY; THERAPY AB Improving health and well-being from the consideration of isolated studies is problematic. Systematic reviews have been developed to address this problem and may include a quantitative data synthesis in the form of a meta-analysis, or a cumulative meta-analysis. The value of systematic reviews depends greatly on the availability and quality of the results of primary research. The objective of the current project was to demonstrate the technique of cumulative meta-analysis in dentistry using data from a previously published systematic review. The process highlights an issue that some trials could not be synthesized due to the lack of reporting of measures of variation. This represents a potential source of bias. Investigators are encouraged to consider their trials as part of an information continuum and to report sufficient detail to permit the trials' incorporation into subsequent syntheses. C1 UCL, Eastman Dent Inst Oral Hlth Care Sci, London WC1X 8LD, England. Forsyth Inst, Dsm Forsyth Ctr Evidence Based Dent, Boston, MA USA. Boston Univ, Goldman Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, Boston, MA 02215 USA. Tufts Univ New England Med Ctr, Ctr Clin Evidence Synth, Boston, MA USA. RP Moles, DR (reprint author), UCL, Eastman Dent Inst Oral Hlth Care Sci, 256 Grays Inn Rd, London WC1X 8LD, England. EM d.moles@eastman.ucl.ac.uk OI Moles, David/0000-0001-9797-6226 FU NIDCR NIH HHS [DE13850] NR 25 TC 6 Z9 7 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD APR PY 2005 VL 84 IS 4 BP 345 EP 349 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 916BH UT WOS:000228357600010 PM 15790741 ER PT J AU Brown, CA Nadel, ES Brown, DFM AF Brown, CA Nadel, ES Brown, DFM TI Penetrating torso trauma SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID CONTRAST HELICAL CT; ABDOMINAL-TRAUMA; PERITONEAL VIOLATION; STAB WOUNDS; LAPAROTOMY; MANAGEMENT; DIAPHRAGM; MORBIDITY; INJURIES C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Brown, CA (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 18 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD APR PY 2005 VL 28 IS 3 BP 325 EP 328 DI 10.1016/j.jemermed.2004.12.007 PG 4 WC Emergency Medicine SC Emergency Medicine GA 908LT UT WOS:000227789200015 PM 15769578 ER PT J AU Henderson, C Roux, AVD Jacobs, DR Kiefe, CI West, D Williams, DR AF Henderson, C Roux, AVD Jacobs, DR Kiefe, CI West, D Williams, DR TI Neighbourhood characteristics, individual level socioeconomic factors, and depressive symptoms in young adults: the CARDIA study SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID DISEASE RISK-FACTORS; MENTAL-HEALTH; ETHNIC DENSITY; ATHEROSCLEROSIS RISK; AREA CHARACTERISTICS; MULTILEVEL ANALYSIS; INCOME INEQUALITY; DISORDERS; CONTEXT; LONDON AB Study objective: To investigate the relation between neighbourhood socioeconomic and ethnic characteristics with depressive symptoms in a population based sample. Design: Cross sectional data from the CARDIA study, including the Center for Epidemiological Studies depression scale score (CES-D). Neighbourhoods were 1990 US census blocks of 1000 people; six census variables reflecting wealth/income, education, and occupation investigated separately and as a summary score; neighbourhood racial composition (percentage white and black) and individual level income and education were also examined. Setting: Participants recruited in 1985/86 from community lists in Birmingham, AL; Chicago, IL; Minneapolis MN; from a health plan in Oakland, CA. Participants: 3437 adults aged 28 - 40 years in 1995/96: 24% white men, 27% white women, 20% black men, 29% black women. Main results: For each race-sex group, CES-D was inversely related to neighbourhood score and individual income and education. Associations of neighbourhood score with CES-D became weak and inconsistent after adjusting for individual level factors; personal income remained strongly and inversely associated with CES-D. Age adjusted mean differences (standard errors) in CES-D between the lowest and highest income categories were 3.41 (0.62) for white men, 4.57 (0.64) for white women, 5.80 (0.87) for black men, and 5.74 (0.83) for black women. For both black and white participants, CES-D was associated negatively with percentage of white people and positively with percentage of black people in their census block, before, but not after, adjustment for individual and neighbourhood socioeconomic variables. Conclusions: Neither neighbourhood socioeconomic characteristics nor ethnic density were consistently related to depressive symptoms once individual socioeconomic characteristics were taken into account. C1 Inst Psychiat, Hlth Serv Res Dept, London, England. Univ Michigan, Ctr Social Epidemiol & Populat Hlth, Ann Arbor, MI 48109 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Oslo, Dept Nutr, Oslo, Norway. Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Univ Michigan, Inst Social Res, Ann Arbor, MI 48109 USA. RP Henderson, C (reprint author), Publ Psychiat Fellowship, Room 317,722 W 168th St, New York, NY 10032 USA. EM hendersc@nypdrat.cpmc.columbia.edu RI Henderson, Claire/E-4664-2010 OI Henderson, Claire/0000-0002-6998-5659 FU NHLBI NIH HHS [N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095]; NIMHD NIH HHS [MD00206 P60] NR 46 TC 70 Z9 70 U1 0 U2 13 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD APR PY 2005 VL 59 IS 4 BP 322 EP 328 DI 10.1136/jech.2003.018846 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 911NL UT WOS:000228010300016 PM 15767387 ER PT J AU Khachemoune, A Lockshin, BN El-Gamal, H AF Khachemoune, A Lockshin, BN El-Gamal, H TI Unilateral rash on a baby girl - A pruritic rash on just the right leg, arm, and flank SO JOURNAL OF FAMILY PRACTICE LA English DT Editorial Material ID ASYMMETRIC PERIFLEXURAL EXANTHEM; LATEROTHORACIC EXANTHEM; CHILDHOOD; CHILDREN; ERYTHEMA; DISEASE C1 Harvard Univ, Sch Med, Boston, MA USA. Indiana Univ, Indianapolis, IN 46204 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. RP Khachemoune, A (reprint author), Harvard Univ, Sch Med,Massachusetts Gen Hosp, CWS,Dept Dermatol, Wellman Ctr Photomed BAR 314, 40 Blossom St, Boston, MA 02114 USA. EM amorkh@pol.net NR 8 TC 0 Z9 0 U1 0 U2 0 PU DOWDEN PUBLISHING CORP PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD APR PY 2005 VL 54 IS 4 BP 341 EP 342 PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 917RU UT WOS:000228487700011 PM 15833225 ER PT J AU Hu, L Stone, V AF Hu, L Stone, V TI A public health curriculum for medical residents SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 27 EP 27 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000008 ER PT J AU Liddicoat, RV Gonzalez, E AF Liddicoat, RV Gonzalez, E TI Creating a dermatology conference for GIM faculty using cases from an urgent care clinic. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 29 EP 29 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000015 ER PT J AU Eckstrom, E Bowen, JL Tanner, C Ririe, M Joseph, C Desai, S AF Eckstrom, E Bowen, JL Tanner, C Ririe, M Joseph, C Desai, S TI Improving care for geriatric patients: Meeting the challenge. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Legacy Emanuel Hosp, Portland, OR USA. Good Samaritan Hosp, Portland, OR 97210 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 33 EP 33 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000029 ER PT J AU Collard, CL Bryant, BL Hanesworth, E Wolinsky, A Rehman, SU AF Collard, CL Bryant, BL Hanesworth, E Wolinsky, A Rehman, SU TI Multidisciplinary primary care morning report. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Ralph H Johnson VAMC, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 35 EP 35 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000036 ER PT J AU Lindner, SA Davoren, JB Vollmer, A Landefeld, C AF Lindner, SA Davoren, JB Vollmer, A Landefeld, C TI Electronic medical record intervention increased nursing home advance directive orders and documentation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 53 EP 53 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000099 ER PT J AU Hoffman, RM Barry, MJ Collins, MM AF Hoffman, RM Barry, MJ Collins, MM TI Health outcomes in older men with localized prostate cancer. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ New Mexico, Albuquerque, NM 87131 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 55 EP 56 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000110 ER PT J AU Lawrence, V Cornell, J Hazuda, HP AF Lawrence, V Cornell, J Hazuda, HP TI Improving eleders' recovery after major abdominal surgery SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 56 EP 56 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000112 ER PT J AU Bair, MJ Richardson, KM Dobscha, SK Yi, EJ Gerrity, MS Kroenke, K AF Bair, MJ Richardson, KM Dobscha, SK Yi, EJ Gerrity, MS Kroenke, K TI Chronic pain management guidelines: A systematic review of content and strength of evidence SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Indiana Univ, Sch Med, Indianapolis, IN USA. Richard L Roudebush VA Med Ctr, Indianapolis, IN USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Regenstrief Inst Hlth Care, Indianapolis, IN USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 62 EP 62 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000134 ER PT J AU Rose, SA Kertesz, SG Safford, MM Palonen, KP Halanych, JH Kiefe, CI AF Rose, SA Kertesz, SG Safford, MM Palonen, KP Halanych, JH Kiefe, CI TI Diabetes diagnostic codes associated with primary care visits: Interpret with caution. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Birmingham VA Med Ctr, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 63 EP 63 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000138 ER PT J AU Yano, E Chaney, EF Simon, B Bonner, L Lanto, AB Campbell, D Rubenstein, LV AF Yano, E Chaney, EF Simon, B Bonner, L Lanto, AB Campbell, D Rubenstein, LV TI Health and health care needs of depressed patients detected in primary care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. Univ Washington, Seattle, WA 98195 USA. VA Greater Los Angeles, Los Angeles, CA USA. VA Puget Sound Healthcare Syst, Seattle, WA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 68 EP 68 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000151 ER PT J AU Safford, MM Kirk, K Kiefe, C AF Safford, MM Kirk, K Kiefe, C TI Reducing cardiovascular risk in diabetes: Room for improved intensity of hypertension medication management. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 71 EP 72 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000163 ER PT J AU Shrank, WH Hoang, T Ettner, S Glassman, PA Nair, K London, R Delapp, D Dirstine, J Avorn, J Asch, SM AF Shrank, WH Hoang, T Ettner, S Glassman, PA Nair, K London, R Delapp, D Dirstine, J Avorn, J Asch, SM TI The implications of choice: Does prescribing generic or preferred pharmaceuticals improve medication adherence for chronic conditions?. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. W Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Anthem Blue Cross Blue Shield, Denver, CO USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RAND, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 73 EP 73 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000168 ER PT J AU Shrank, WH Asch, SM Ettner, S Kirk, A Glassman, PA Fox, SA AF Shrank, WH Asch, SM Ettner, S Kirk, A Glassman, PA Fox, SA TI Putting their mouth where their money is: Are patients enrolled in incentive-based pharmacy plans more likely to talk to their physicians about out-of-pocket costs? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RAND, Los Angeles, CA USA. VA W LA, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 80 EP 80 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000191 ER PT J AU Crivera, C Suh, D Huang, E Cagliero, E Grant, R Vo, L Shin, H Meigs, J AF Crivera, C Suh, D Huang, E Cagliero, E Grant, R Vo, L Shin, H Meigs, J TI The effects of recommended therapy versus real world therapy on the direct medication costs of type 2 diabetes. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Sanofi Aventis, Bridgewater, NJ USA. Rutgers State Univ, Ernest Mario Sch Pharm, Piscataway, NJ USA. Univ Chicago, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 81 EP 81 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000193 ER PT J AU Metlay, JP Maselli, J Camargo, CA Gonzales, R AF Metlay, JP Maselli, J Camargo, CA Gonzales, R TI Trustworthiness of different sources of health information. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Penn, Philadelphia, PA 19104 USA. VA Med Ctr, Philadelphia, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 82 EP 82 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000196 ER PT J AU Gelber, RP Kurth, T Kausz, A Manson, JE Buring, JE Levey, AS Gaziano, JM AF Gelber, RP Kurth, T Kausz, A Manson, JE Buring, JE Levey, AS Gaziano, JM TI Body mass index is associated with increased risk of chronic kidney disease in apparently healthy men. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Tufts Univ, Sch Med, New England Med Ctr, Boston, MA 02111 USA. RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 84 EP 84 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000205 ER PT J AU Holmes, CB Singer, DE Barry, MJ McDermott, SM Atlas, SJ AF Holmes, CB Singer, DE Barry, MJ McDermott, SM Atlas, SJ TI Effectiveness of influenza vaccination in a year of poor match between vaccine and circulating strains of influenza: A case-control study. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 85 EP 85 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000209 ER PT J AU Fang, MC Go, AS Chang, Y Hylek, EM Henault, L Jensvold, N Singer, D AF Fang, MC Go, AS Chang, Y Hylek, EM Henault, L Jensvold, N Singer, D TI Intracranial hemorrhage is the dominant determinant of death and disability from warfarin-associated hemorrhage: The anticoagulation and risk factors in atrial fibrillation (atria) study. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Kaiser Permanente, Div Res, Oakland, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 86 EP 86 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000213 ER PT J AU Holmes, CB Singer, DE Barry, MJ Mcdermott, SM Atlas, SJ AF Holmes, CB Singer, DE Barry, MJ Mcdermott, SM Atlas, SJ TI Spectrum of influenza disease at a large medical center during a year of vaccine mismatch SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 89 EP 89 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000223 ER PT J AU Kelly, PA Haidet, PM DeBakey, ME AF Kelly, PA Haidet, PM DeBakey, ME TI Health literacy: Patients' performance and physicians' perceptions SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 99 EP 99 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000254 ER PT J AU Mohanty, SA Alegria, M Lau, AS Asch, S AF Mohanty, SA Alegria, M Lau, AS Asch, S TI Are Latinos and Asian Americans/Pacific islanders using fewer mental health care services? Findings from the California Health interview SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ So Calif, Los Angeles, CA USA. Cambridge Hlth Alliance, Cambridge, MA USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND Corp, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 108 EP 108 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000286 ER PT J AU Volpp, K Stone, RA Jha, A Lave, JR Pauly, MV Klusaritz, H Chen, H Polsky, D AF Volpp, K Stone, RA Jha, A Lave, JR Pauly, MV Klusaritz, H Chen, H Polsky, D TI Are reverse disparities limited to age-defined subgroups of the VA patient population? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Philadelphia VA Med Ctr, CHERP, Philadelphia, PA USA. Pittsburgh VA Med Ctr, CHERP, Pittsburgh, PA USA. Boston VA Med Ctr, Boston, MA USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 109 EP 109 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000289 ER PT J AU Bharel, M Blackstock, O O'Connell, J AF Bharel, M Blackstock, O O'Connell, J TI Cervical cancer screening among homeless women SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Jamaica Plain, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 111 EP 111 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000296 ER PT J AU Hicks, LS O'Malley, J Landon, B Lieu, T Cook, N Keegan, T Mcneil, BJ Guadagnoli, E AF Hicks, LS O'Malley, J Landon, B Lieu, T Cook, N Keegan, T Mcneil, BJ Guadagnoli, E TI Determinants of quality of diabetes management among community health centers in the US SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 111 EP 112 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000299 ER PT J AU Saha, S Morse, E Jimison, J AF Saha, S Morse, E Jimison, J TI Cultural competence among health professionals: A taxonomy SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 111 EP 111 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000298 ER PT J AU Hicks, LS O'Malley, J Landon, BE Lieu, T Cook, N Keegan, T Mcneil, BJ Guadagnoli, E AF Hicks, LS O'Malley, J Landon, BE Lieu, T Cook, N Keegan, T Mcneil, BJ Guadagnoli, E TI Determinants of quality of hypertension care among community health centers in the US SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 112 EP 112 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000300 ER PT J AU Fultz, SI Goulet, J Weissman, S Rimland, D Leaf, D Gibert, CL Rodriguez-Barradas, M Justice, AC AF Fultz, SI Goulet, J Weissman, S Rimland, D Leaf, D Gibert, CL Rodriguez-Barradas, M Justice, AC TI Differences between infectious disease and general medical providers in comfort with providing primary care. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Yale Univ, Sch Med, West Haven, CT 06516 USA. Hosp St Raphael, New Haven, CT USA. Emory Univ, Decatur, GA 30322 USA. Univ Calif Los Angeles, Los Angeles, CA USA. George Washington Univ, Med Ctr, Vet Affairs Med Ctr, Washington, DC 20052 USA. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 113 EP 113 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000302 ER PT J AU Levine, DA Kiefe, CI Houston, T Allison, JJ Mccarthy, EP Ayanian, JZ AF Levine, DA Kiefe, CI Houston, T Allison, JJ Mccarthy, EP Ayanian, JZ TI Do younger US stroke survivors have reduced access to care and medications?. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RI Houston, Thomas/F-2469-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 113 EP 114 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000305 ER PT J AU Borrero, S Kwoh, K Sartorius, J Ibrahim, SA AF Borrero, S Kwoh, K Sartorius, J Ibrahim, SA TI Gender and total knee/hip arthroplasty utilization rate in the VA system. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 115 EP 115 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000312 ER PT J AU Ngo-Metzger, Q Sorkin, D Phillips, RS Massagli, M Clarridge, B Greenfield, S Kaplan, S AF Ngo-Metzger, Q Sorkin, D Phillips, RS Massagli, M Clarridge, B Greenfield, S Kaplan, S TI Good doctor-patient relationship can overcome language barriers. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Calif Irvine, Irvine, CA 92717 USA. Harvard Univ, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Massachusetts, Boston, MA 01003 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 115 EP 116 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000313 ER PT J AU Kertesz, SG Safford, MM Rose, S Palonen, KP Gordan, AJ Halanych, JH Kirk, K Kiefe, CI AF Kertesz, SG Safford, MM Rose, S Palonen, KP Gordan, AJ Halanych, JH Kirk, K Kiefe, CI TI Outpatient diabetes care for homeless and housed veterans: More equal than not?. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. Univ Pittsburgh, Pittsburgh, PA USA. Pittsburgh VAMC, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 121 EP 122 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000334 ER PT J AU Gordan, HS Street, RL Kelly, PA Sharf, B Soucheck, J AF Gordan, HS Street, RL Kelly, PA Sharf, B Soucheck, J TI Perceptions of physician-patient communication explain racial differences in trust. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Texas A&M Univ, College Stn, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 122 EP 123 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000338 ER PT J AU Mohanty, SA Washington, D Lambe, S Asch, S AF Mohanty, SA Washington, D Lambe, S Asch, S TI Predictors of on-call specialist response times in california emergency departments. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ So Calif, Los Angeles, CA 90089 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RAND Corp, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 123 EP 123 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000340 ER PT J AU Gordon, HS Street, RL Sharf, B Souchek, J Kelly, PA AF Gordon, HS Street, RL Sharf, B Souchek, J Kelly, PA TI Racial differences in doctors' information-giving and patients' participation. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX 77030 USA. Texas A&M Univ, College Stn, TX 77843 USA. RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 125 EP 126 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000348 ER PT J AU Mcginnis, KA Skanderson, M Conigliaro, J Gibert, CL Gandhi, NR Backus, LI Justice, AC AF Mcginnis, KA Skanderson, M Conigliaro, J Gibert, CL Gandhi, NR Backus, LI Justice, AC TI Race/ethnic disparities in health and utilization among human immunodeficiency virus (HIV) positive veterans. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Pittsburgh, Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Univ Ctr Social & Urban Res, Pittsburgh, PA 15260 USA. George Washington Univ, Med Ctr, Vet Affairs Med Ctr, Washington, DC 20052 USA. Ctr Qual Management Publ Hlth Palo Alto, Palo Alto, CA USA. Yale Univ, Vet Aging Cohort Study, VA Connecticut Healthcare Syst, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 125 EP 125 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000347 ER PT J AU Long, JA Metlay, JP AF Long, JA Metlay, JP TI Racial disparities in health care goals for diabetic veterans. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Philadelphia VA CHERP, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 126 EP 126 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000350 ER PT J AU Saha, S Shipman, S AF Saha, S Shipman, S TI The evidence base for diversity in the health professions. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 128 EP 129 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000361 ER PT J AU Liddicoat, RV Zheng, H Golan, Y Internicola, J Rubenstein, EP Freedberg, KA Walensky, RP AF Liddicoat, RV Zheng, H Golan, Y Internicola, J Rubenstein, EP Freedberg, KA Walensky, RP TI The high acceptance rate of routine, voluntary HIV testing in a Massachusetts prison. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Massachusetts Gen Hosp, Boston, MA USA. Tufts Univ, Boston, MA 02111 USA. Suffolk Cty House Correct, Boston, MA USA. Massachusetts Dept Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 129 EP 129 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000362 ER PT J AU Saha, S Morse, E Gipson, T Loudd, R O'Brien, C AF Saha, S Morse, E Gipson, T Loudd, R O'Brien, C TI What is "cultural competence?"- African Americans' perspectives on patient-physician interactions. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR USA. Univ Rochester, Rochester, NY USA. Portland State Univ, Portland, OR USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 131 EP 131 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000369 ER PT J AU Volpp, K Gurmankin, A Gomez, A Asch, DA Berlin, JA Murphy, JJ Zhu, J Lerman, C AF Volpp, K Gurmankin, A Gomez, A Asch, DA Berlin, JA Murphy, JJ Zhu, J Lerman, C TI A randomized control trial of financial incentives for smoking cessation. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Philadelphia VA Med Ctr, Philadelphia, PA USA. Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA USA. Philadelphia VA Med Ctr, Ctr Hlth Equ Clin Epidemiol, Philadelphia, PA USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA USA. Univ Penn, Dept Psychiat, Philadelphia, PA USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 131 EP 132 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000372 ER PT J AU Linas, BP Zheng, H Losina, E Walensky, RP Freedberg, KA AF Linas, BP Zheng, H Losina, E Walensky, RP Freedberg, KA TI Assessing the impact of CDC HIV prevention funding on HIV testing and knowledge. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 133 EP 133 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000376 ER PT J AU Hayes, J Walczak, H Prochazka, AV AF Hayes, J Walczak, H Prochazka, AV TI Comparison of Medicare prescription benefit costs with a discount internet pharmacy: What's a patient's best deal? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 134 EP 135 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000382 ER PT J AU Volpp, K Konetzka, T Sochalski, J Zhu, J AF Volpp, K Konetzka, T Sochalski, J Zhu, J TI Effects of financial stress from price competition on hospital quality of care. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 CHERP Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Chicago, Chicago, IL USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 135 EP 135 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000383 ER PT J AU Solotaroff, R Carlson, M Wright, B Devoe, JE Smith, J Boone, J Edlund, Y AF Solotaroff, R Carlson, M Wright, B Devoe, JE Smith, J Boone, J Edlund, Y TI The impact of Medicaid program changes on a chronically ill, low income population. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Portland VA Med Ctr, Portland, OR USA. Portland State Univ, Portland, OR 97207 USA. Providence Hlth Syst, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Oregon Hlth Policy & Res, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 140 EP 140 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001004 ER PT J AU Mortensen, E Restrepo, M Anzueto, A Pugh, J AF Mortensen, E Restrepo, M Anzueto, A Pugh, J TI An assessment of empiric antimicrobial therapy with a beta-lactam and fluoroquinolone on mortality for patients hospitalized with community-acquired pneumonia. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 141 EP 141 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001008 ER PT J AU Green, AR Miller, E Betancourt, JR Hirsh, D Krupat, E Wilson, R Taylor, WC AF Green, AR Miller, E Betancourt, JR Hirsh, D Krupat, E Wilson, R Taylor, WC TI Designing a cultural competence OSCE experience: Lessons learned from structured interviews with medical students SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 152 EP 152 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001047 ER PT J AU Huang, GC Smith, CC Gordon, CE Weingart, SN AF Huang, GC Smith, CC Gordon, CE Weingart, SN TI Residents' comfort performing inpatient medical procedures. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 162 EP 163 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001086 ER PT J AU Mohanty, SA Diamant, AL Lagomasino, I Asch, S AF Mohanty, SA Diamant, AL Lagomasino, I Asch, S TI Are public/private partnerships delivering better public mental health services for the safety net population?. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ So Calif, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND Corp, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 171 EP 172 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001118 ER PT J AU Seal, KH Kral, AH Lorvick, J Gee, L Tsui, JI Edlin, BR AF Seal, KH Kral, AH Lorvick, J Gee, L Tsui, JI Edlin, BR TI Among injection drug users, interest is high, but access low to HCV antiviral therapy. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 7 Z9 7 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 171 EP 171 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001116 ER PT J AU Hepner, KA Rubenstein, LV Rowe, M Rost, KM Sherbourne, CD Ford, DE AF Hepner, KA Rubenstein, LV Rowe, M Rost, KM Sherbourne, CD Ford, DE CA RAND Corporation TI Does adherence to depression guidelines in primary care improve outcomes?. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 RAND Corp, Santa Monica, CA USA. VA Greater Los Angeles, Los Angeles, CA USA. Univ Colorado, Denver, CO 80202 USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 175 EP 176 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001130 ER PT J AU Hepner, KA Rubenstein, LV Rowe, M Rost, KM Sherbourne, CD Ford, DE AF Hepner, KA Rubenstein, LV Rowe, M Rost, KM Sherbourne, CD Ford, DE TI The importance of primary care practitioners in depression quality of care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 RAND Corp, Santa Monica, CA USA. VA Greater Los Angeles, Los Angeles, CA USA. Univ Colorado, Denver, CO 80202 USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 181 EP 181 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001149 ER PT J AU Jagsi, R Guancial, EA Cooper, CM Henault, L Chang, Y Starr, R Tarbell, NJ Hylek, EM AF Jagsi, R Guancial, EA Cooper, CM Henault, L Chang, Y Starr, R Tarbell, NJ Hylek, EM TI Representation of female physician-investigators in first and senior author positions of published original research: A 35-year perspective SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 183 EP 183 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001156 ER PT J AU Yang, E Soban, L Etzioni, D Parkerton, P AF Yang, E Soban, L Etzioni, D Parkerton, P TI Practice organization determinants of colorectal cancer screening rates SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 187 EP 188 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001172 ER PT J AU Murfi, HJ Syngal, S AF Murfi, HJ Syngal, S TI The family medical history in primary care: Potential lost opportunities for screening and prevention SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Vanderbilt Univ, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 190 EP 191 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001182 ER PT J AU Walter, LC Lindquist, K O'Hare, A Johansen, KL AF Walter, LC Lindquist, K O'Hare, A Johansen, KL TI Use of screening mammography among women on dialysis SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 191 EP 191 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001185 ER PT J AU Aujesky, D Obrosky, DS Stone, RA Auble, TE Fine, MJ AF Aujesky, D Obrosky, DS Stone, RA Auble, TE Fine, MJ TI A prediction rule to identify low-risk patients with pulmonary embolism SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 195 EP 195 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001198 ER PT J AU Atlas, SJ Lasko, TA Chueh, HC Chang, Y Grant, RW Barry, MJ AF Atlas, SJ Lasko, TA Chueh, HC Chang, Y Grant, RW Barry, MJ TI Accurately identifying patients loyal to providers in a primary care practice network: Implications for quality assessment and improvement efforts. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 196 EP 196 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001201 ER PT J AU Gonzales, R Camargo, CA Mackenzie, TD Kersey, AS Maselli, J Levin, SK Mcculloch, CE Metlay, JP AF Gonzales, R Camargo, CA Mackenzie, TD Kersey, AS Maselli, J Levin, SK Mcculloch, CE Metlay, JP TI Antibiotic prescribing patterns for acute respiratory tract infections in acute care settings SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ San Francisco, San Francisco, CA 94117 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Denver Hlth & Hosp Author, Denver, CO USA. Dept Vet Affairs, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 196 EP 196 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001203 ER PT J AU Bean-Mayberry, B Yano, E Judith, N Bayliss, N Weisman, C Scholle, S AF Bean-Mayberry, B Yano, E Judith, N Bayliss, N Weisman, C Scholle, S TI Contrasting the program characteristics at federally supported comprehensive women's health centers. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Pittsburgh, Pittsburgh, PA USA. VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Penn State Univ, Hershey, PA 17033 USA. NCQA, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 198 EP 198 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001209 ER PT J AU Kerr, EA Hofer, TP Hayward, RA Hogan, MM Adams, JL Asch, S AF Kerr, EA Hofer, TP Hayward, RA Hogan, MM Adams, JL Asch, S TI How should we monitor the quality of care?: A comparison of three methods to assess quality differences across sites of care. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Michigan, Ann Arbor, MI 48109 USA. VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. RAND Corp, Santa Monica, CA USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND Corp, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 202 EP 203 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001224 ER PT J AU Steinman, M Kaboli, P Landefeld, C Rosenthal, GE AF Steinman, M Kaboli, P Landefeld, C Rosenthal, GE TI Measures of drug prescribing quality frequently disagree. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 San Francisco VA Med Ctr, San Francisco, CA USA. Iowa City VA Med Ctr, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 203 EP 204 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001228 ER PT J AU Atlas, SJ Grant, RW Chang, Y Ferris, TG Barry, MJ AF Atlas, SJ Grant, RW Chang, Y Ferris, TG Barry, MJ TI Patient loyalty within a primary care practice network: A population-based approach to quality assessment and improvement. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 204 EP 205 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001231 ER PT J AU Steinman, M Covinsky, K AF Steinman, M Covinsky, K TI National patterns of COX-2 inhibitor use SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 204 EP 204 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001229 ER PT J AU Keating, NL Landrum, MB Guadagnoli, E Winer, EP Ayanian, JZ AF Keating, NL Landrum, MB Guadagnoli, E Winer, EP Ayanian, JZ TI Surveillance testing after early-stage breast cancer. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 206 EP 206 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001236 ER PT J AU Roy, CL Poon, EG Karson, AS Ladak-Merchant, Z Maviglia, S Gandhi, TK AF Roy, CL Poon, EG Karson, AS Ladak-Merchant, Z Maviglia, S Gandhi, TK TI Test results that return after hospital discharge: A patient safety concern during transition of care. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med 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 PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 206 EP 206 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001239 ER PT J AU Shrank, WH Asch, SM Adams, J Setodji, C Kerr, EA Keesey, J Malik, S Mcglynn, E AF Shrank, WH Asch, SM Adams, J Setodji, C Kerr, EA Keesey, J Malik, S Mcglynn, E TI The quality of pharmacologic care for adults in the United States. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RAND Corp, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Calif Irvine, Irvine, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 207 EP 207 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001242 ER PT J AU Keating, NL Landrum, MB Guadagnoli, E Winer, EP Ayanian, JZ AF Keating, NL Landrum, MB Guadagnoli, E Winer, EP Ayanian, JZ TI Factors related to underuse of surveillance mammography after breast cancer diagnosis SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 211 EP 211 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001256 ER PT J AU Washington, D Simon, B Sun, S Yano, E AF Washington, D Simon, B Sun, S Yano, E TI Rape and assault of women in the US military - Prevalence, treatment, and health consequences SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 214 EP 215 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001268 ER PT J AU Palonen, KP Kertesz, SG Safford, MM Rose, SA Kirk, K Halanych, JH Kiefe, CI AF Palonen, KP Kertesz, SG Safford, MM Rose, SA Kirk, K Halanych, JH Kiefe, CI TI Utilization of Veteran's Health Administration services among women veterans with diabetes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Natl Qual Scholars, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 216 EP 216 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001273 ER PT J AU Firooz, N Vazirani, S AF Firooz, N Vazirani, S TI Numerous complications of MRSA endocarditis in a single patient SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 254 EP 254 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001420 ER PT J AU Dienstag, JL Wei, LJ Xu, D Cross, A Kreter, B Wilber, R AF Dienstag, JL Wei, LJ Xu, D Cross, A Kreter, B Wilber, R TI Entecavir (ETV) is superior to lamivudine and adefovir in trials of HBeAg-positive and -negative chronic hepatitis B infection: A cross-study analysis with published reports SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 13-17, 2005 CL Paris, FRANCE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Wallingford, CT 06492 USA. Harvard Univ, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2005 VL 42 SU 2 MA 481 BP 174 EP 174 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 925AN UT WOS:000229024000482 ER PT J AU Zhou, XJ Afdhal, N Godofsky, E Dienstag, J Rustgi, V Schick, L McInery, D Fielman, BA Brown, NA AF Zhou, XJ Afdhal, N Godofsky, E Dienstag, J Rustgi, V Schick, L McInery, D Fielman, BA Brown, NA TI Pharmacokinetics and pharmacodynamics of valopicitabine (NM283), a new nucleoside HCV polymerase inhibitor: Results from a phase I/II dose-escalation trial in patients with HCV-1 infection SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 13-17, 2005 CL Paris, FRANCE C1 Idenix Pharmaceut Inc, Cambridge, MA USA. 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, Tacoma, WA USA. NR 0 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2005 VL 42 SU 2 MA 626 BP 229 EP 229 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 925AN UT WOS:000229024000626 ER PT J AU Lichterfeld, M Schmeisser, N Qurishi, N Vogel, M Brackmann, HH Spengler, U Rockstroh, JK AF Lichterfeld, M Schmeisser, N Qurishi, N Vogel, M Brackmann, HH Spengler, U Rockstroh, JK TI Clinical outcomes of HIV-HCV co-infection in a large cohort of hemophiliac patients SO JOURNAL OF INFECTION LA English DT Article DE HIV; AIDS; Hepatitis C; HIV-HCV co-infection; hemophilia ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; STAGE LIVER-DISEASE; NATURAL-HISTORY; ANTIRETROVIRAL THERAPY; POSITIVE HEMOPHILIACS; PROTEASE INHIBITORS; INFECTION; PROGRESSION; AIDS AB Objective. To determine the disease progression of HIV-HCV co-infected hemophitiacs in a large cohort of patients(n = 288) cared for at a single medical institution. Patients and methods. Annual mortality rates for AIDS- and liver-related death were calculated and Kaplan-Meier survival plots were drawn to determine the progression to AIDS and death. Results. Between January 1985 and December 2002, 179 (62.2%) and 195 (67.7%) of these patients had developed AIDS or died, respectively. Overall, AIDS accounted for 128 deaths, which almost entirely (93.7%) occurred prior to the introduction of highly active antiretroviral therapy (HAART) at the end of 1995. A total of 29 patients died of liver failure, most of them (69%) during the years 1991 -1996. Since 1997, only five cases of fatal liver failure were reported. Non-HIV-HCV related reasons were responsible for 38 deaths and occurred predominantly (47%) in the years 1997-2002. Starting November 1995, 72 patients were treated with HAART. However, by December 2002, only 52.5% and 83% of all HAART-treated patients had a stable viremia (< 400 copies/ml) and a sufficient CD4(+) T-cell count (> 200/ mu l), respectively. Conclusion. These data indicate that liver-related mortality peaked in the years 1991 1996, but subsequently tended to decline. Moreover, despite widespread treatment of patients with HAART, a significant proportion of individuals had an unsatisfactory immunological and virological status at the end of 2002. (c) 2004 The British Infection Society. Published by Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Univ Bonn, Dept Gen Internal Med, D-53105 Bonn, Germany. Albertus Magnus Univ, Dept Internal Med 1, D-50924 Cologne, Germany. Rheinische Friedrich Wilhelms, Dept Tansfus Med & Expt Hematol, D-53105 Bonn, Germany. RP Lichterfeld, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Boston, MA 02129 USA. EM mlichterfeld@partners.org NR 27 TC 10 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 J9 J INFECTION JI J. Infect. PD APR PY 2005 VL 50 IS 3 BP 221 EP 228 DI 10.1016/j.jinf.2004.04.003 PG 8 WC Infectious Diseases SC Infectious Diseases GA 915LI UT WOS:000228305300006 PM 15780416 ER PT J AU Musher, DM Ceasar, H Kojic, EM Musher, BL Gathe, JC Romero-Steiner, S White, AC AF Musher, DM Ceasar, H Kojic, EM Musher, BL Gathe, JC Romero-Steiner, S White, AC TI Administration of protein-conjugate pneumococcal vaccine to patients who have invasive disease after splenectomy despite their having received 23-valent pneumococcal polysaccharide vaccine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POSTSPLENECTOMY INFECTION; CAPSULAR POLYSACCHARIDES; STREPTOCOCCUS-PNEUMONIAE; RISK; INDIVIDUALS; PENICILLIN; ASPLENIA; CHILDREN; FAILURE; DEATH AB Patients who undergo splenectomy are at greatly increased risk for overwhelming pneumococcal bacteremia and death. Twenty-three-valent pneumococcal polysaccharide vaccine ( PPV- 23), which contains capsular polysaccharides (PSs) from 23 common serotypes of Streptococcus pneumoniae, is strongly recommended for such patients. The capacity to respond to PPV- 23 by producing immunoglobulin (Ig) G is genetically regulated. Some proportion of adults do not respond and, despite postsplenectomy administration of PPV- 23, may remain susceptible to recurrent pneumococcal sepsis. Here, we describe 2 patients who had recurring pneumococcal bacteremia after undergoing splenectomy despite having received numerous doses of PPV- 23. Heptavalent protein-conjugate pneumococcal vaccine (PCPV-7) was then administered, and it induced high levels of IgG to all 7 PSs; in one of the patients, functional activity against 5 of the 7 PSs was demonstrable, both in vitro and in vivo. Recurrent pneumococcal bacteremia in patients who have undergone splenectomy may indicate a genetically regulated failure to respond to PPV- 23; PCPV-7 may stimulate production of IgG to PSs in such patients. C1 Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Houston, TX USA. Ben Taub Gen Hosp, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Musher, DM (reprint author), Vet Affairs Med Ctr, Infect Dis Sect, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM daniel.musher@med.va.gov OI White, A Clinton/0000-0002-9668-4632; Romero-Steiner, Sandra/0000-0003-4128-7768 NR 22 TC 26 Z9 28 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2005 VL 191 IS 7 BP 1063 EP 1067 DI 10.1086/428135 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 903IB UT WOS:000227418200007 PM 15747240 ER PT J AU Anand, S Taylor, CR Maytin, EV AF Anand, S Taylor, CR Maytin, EV TI The transcription factor CHOP/gadd153 is expressed during UVB-induced ER stress in marine and human epidermis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 APR PY 2005 VL 124 IS 4 SU S MA 133 BP A23 EP A23 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900134 ER PT J AU Arbiser, JL Kau, T Konar, M Ramachandran, R Silver, PA Bain, J Cohen, P Gray, A Whitmire, D Tseng, P Chen, C Furness, S Bowen, PJ AF Arbiser, JL Kau, T Konar, M Ramachandran, R Silver, PA Bain, J Cohen, P Gray, A Whitmire, D Tseng, P Chen, C Furness, S Bowen, PJ TI Solenopsin, the alkaloidal component of the fire ant (Solenopsis invicta), is a naturally occurring inhibitor of phosphoinositol-3 kinase SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Ohio State Univ, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA. Univ N Carolina, Dept Chem & Biochem, Greensboro, NC 27412 USA. Sch Life Sci, Div Signal Transduct Therapy, Dundee, Scotland. Univ Georgia, Dept Chem, Athens, GA 30602 USA. NCI, Pathol Lab, Rockville, MD USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 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 APR PY 2005 VL 124 IS 4 SU S MA 005 BP A1 EP A1 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900006 ER PT J AU Chen, T Bertenthal, D Sen, S Sahay, A Chren, M AF Chen, T Bertenthal, D Sen, S Sahay, A Chren, M TI Predictors of skin-related quality of life after treatment of nonmelanoma skill cancer SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 San Francisco VAMC, San Francisco, CA USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 329 BP A55 EP A55 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900329 ER PT J AU Dadras, SS Large-Asschenfeldt, B Velasco, P Nguyen, L Jahnke, K Hauschild, A Hirakawa, S Mihm, M Detmar, M AF Dadras, SS Large-Asschenfeldt, B Velasco, P Nguyen, L Jahnke, K Hauschild, A Hirakawa, S Mihm, M Detmar, M TI Tumor lymphangiogenesis predicts melanoma metastasis to sentinel lymph nodes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Univ Kiel, Kiel, Germany. 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 017 BP A3 EP A3 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900018 ER PT J AU di Vignano, AT Mammucari, C Sharov, AA Roop, DR Botchkarev, VA Crabtree, GR Dotto, G AF di Vignano, AT Mammucari, C Sharov, AA Roop, DR Botchkarev, VA Crabtree, GR Dotto, G TI Integration of Notch1 and Calcineurin/NFAT signaling pathways in keratinocyte growth and differentiation control SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA USA. Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Stanford Univ, Beckman Ctr, Howard Hughes Med Inst, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR PY 2005 VL 124 IS 4 SU S MA 576 BP A96 EP A96 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901120 ER PT J AU Hirakawa, S Kodama, S Kunstfeld, R Kajiya, K Brown, LF Detmar, M AF Hirakawa, S Kodama, S Kunstfeld, R Kajiya, K Brown, LF Detmar, M TI VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Swiss Fed Inst Technol, Inst Pharmaceut Sci, Zurich, Switzerland. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 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 APR PY 2005 VL 124 IS 4 SU S MA 002 BP A1 EP A1 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900003 ER PT J AU Koo, S Fujii, S Hirakawa, S Kawasumi, M Nghiem, P AF Koo, S Fujii, S Hirakawa, S Kawasumi, M Nghiem, P TI Protection from photodamage by topical application of caffeine following UV irradiation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Harvard Univ, Sch Med, MGH, Charlestown, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 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 APR PY 2005 VL 124 IS 4 SU S MA 775 BP A130 EP A130 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901316 ER PT J AU Koo, S Levine, D Lu, Y Angle-Zahn, A Bradner, J Conney, A Nghiem, P AF Koo, S Levine, D Lu, Y Angle-Zahn, A Bradner, J Conney, A Nghiem, P TI Diminished lifespan but apparently normal skin in K14 transgenic mice expressing dominant negative ATR or Chk1 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Rutgers State Univ, Piscataway, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard MGH, Cutaneous Biol Res Ctr, Charlestown, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 119 BP A20 EP A20 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900120 ER PT J AU Kupper, TS Clark, R Dowgiert, R Hurwitz, D Shibata, M Rich, BE Hirahara, K Jones, DA Eapen, S Yamanaka, K AF Kupper, TS Clark, R Dowgiert, R Hurwitz, D Shibata, M Rich, BE Hirahara, K Jones, DA Eapen, S Yamanaka, K TI Expression of interleukin-18 and caspase-1 in cutaneous T cell lymphoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Harvard Univ, Brigham & Womens Hosp, Skin Dis Res Ctr, Dept Dermatol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dana Farber Harvard Canc Ctr, Biostat Core Facil, Dept Biostat, Boston, MA 02115 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 281 BP A47 EP A47 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900281 ER PT J AU Kwon, E Bashir, MM Zhang, W Lin, JH Werth, VP AF Kwon, E Bashir, MM Zhang, W Lin, JH Werth, VP TI Chloroquine does not affect keratinocyte tumor necrosis factor-a gene expression or secretion induced by ultraviolet-B irradiation and interleukin-1 beta SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 080 BP A14 EP A14 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900081 ER PT J AU Li, W Li, Y Fan, JH Chen, M Woodley, DT AF Li, W Li, Y Fan, JH Chen, M Woodley, DT TI Hypoxia enhances collagen-initiated human dermal fibroblast migration via HIF - induction of a pro-motility autocrine SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Univ So Calif, Los Angeles, CA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 198 BP A33 EP A33 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900198 ER PT J AU Li, Y Fan, JH Chen, M Li, W Woodley, DT AF Li, Y Fan, JH Chen, M Li, W Woodley, DT TI Transforming growth factor alpha and insulin are the two main factors in human serum that promote human keratinocyte migration SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA USA. Univ So Calif, Los Angeles, CA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 573 BP A96 EP A96 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901116 ER PT J AU Niendorf, K Goggins, W Yang, G Tsai, K Shennan, M Bell, D Sober, A Hogg, D Tsao, H AF Niendorf, K Goggins, W Yang, G Tsai, K Shennan, M Bell, D Sober, A Hogg, D Tsao, H TI MELPREDICT: a logistic regression model to estimate CDKN2A carrier probability SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Univ Toronto, Toronto, ON, Canada. 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 475 BP A80 EP A80 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901019 ER PT J AU Niendorf, KB Somoano, B Bevona, C Pirl, W Sober, A Tsao, H AF Niendorf, KB Somoano, B Bevona, C Pirl, W Sober, A Tsao, H TI Familial melanoma patients: genetic counseling and testing SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 902 BP A151 EP A151 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901445 ER PT J AU Qureshi, A Brandling-Bennett, H Wittenberg, E Chen, S Sober, A Kvedar, J AF Qureshi, A Brandling-Bennett, H Wittenberg, E Chen, S Sober, A Kvedar, J TI Willingness-to-pay: a burden of disease outcome reported by patients with melanoma and psoriasis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Emory Univ, Dept Dermatol, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 301 BP A51 EP A51 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900301 ER PT J AU Reddy, V Iuga, A Kounga, K Lerner, EA AF Reddy, V Iuga, A Kounga, K Lerner, EA TI Characterization of pruritogenic molecules from Mucuna pruriens SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Massachusetts Gen Hosp, CBRC, Charlestown, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 541 BP A91 EP A91 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901085 ER PT J AU Roers, A Siewe, L Strittmatter, E Deckert, M Schlueter, D Stenzel, W Gruber, A Krieg, T Rajewsky, K Mueller, W AF Roers, A Siewe, L Strittmatter, E Deckert, M Schlueter, D Stenzel, W Gruber, A Krieg, T Rajewsky, K Mueller, W TI Differential regulation of T cell responses and innate immune responses by T cell-derived interleukin-10 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Univ Cologne, Dept Dermatol, D-5000 Cologne, Germany. Univ Cologne, Dept Neuropathol, Cologne, Germany. Univ Magdeburg, Inst Med Microbiol, D-39106 Magdeburg, Germany. Sch Vet Med, Dept Pathol, Hannover, Germany. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. German Res Ctr Biotechnol, Hannover, Germany. RI Deckert, Martina/P-2842-2016 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 703 BP A118 EP A118 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901247 ER PT J AU Sato, N Anand, S Ortel, B Maytin, EV AF Sato, N Anand, S Ortel, B Maytin, EV TI Vitamin D enhances cellular differentiation and protoporphyrin IX accumulation in rat organotypic keratinocyte cultures treated with aminolevulinic acid: implications for photodynamic therapy SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR PY 2005 VL 124 IS 4 SU S MA 379 BP A64 EP A64 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900379 ER PT J AU Schacht, V Meadows, K Kremer, B Bruckner-Tuderman, L Detmar, M AF Schacht, V Meadows, K Kremer, B Bruckner-Tuderman, L Detmar, M TI A potential role of the lymphatic glycoprotein podoplanin in skin carcinogenesis and inflammation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Swiss Fed Inst Technol, Inst Pharmaceut Sci, Zurich, Switzerland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr,Dept Dermatol, Boston, MA USA. Univ Freiburg, Dept Dermatol, Freiburg, Germany. 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 011 BP A2 EP A2 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900012 ER PT J AU Sharov, AA Sharova, TY Atoyan, R Weiner, L Brissette, JL Botchkarev, VA AF Sharov, AA Sharova, TY Atoyan, R Weiner, L Brissette, JL Botchkarev, VA TI BMP signaling regulates size of the hair follicles via modulating the expression of cell cycle-associated genes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 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 APR PY 2005 VL 124 IS 4 SU S MA 609 BP A102 EP A102 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901152 ER PT J AU Sharova, TY Sharov, AA di Vignano, AT Dotto, G Botchkarev, VA AF Sharova, TY Sharov, AA di Vignano, AT Dotto, G Botchkarev, VA TI Microarray analysis suggests the TNF and Bcl-2 related genes as early response markers activated in the hair follicle after chemotherapy SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 610 BP A102 EP A102 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901155 ER PT J AU Sirota, J Weingarten, G Accili, D Takeda, J Kahn, CR Wertheimer, E AF Sirota, J Weingarten, G Accili, D Takeda, J Kahn, CR Wertheimer, E TI Insulin receptor expression is required for skin tumorigenesis, both in vitro and in vivo. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Osaka Univ, Osaka, Japan. Columbia Univ, New York, NY USA. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 103 BP A18 EP A18 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900104 ER PT J AU Tierney, EP Resneck, JS Kimball, AB AF Tierney, EP Resneck, JS Kimball, AB TI The prevalence and roles of physician extenders in dermatology SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Tufts Univ, Sch Med, Dept Internal Med, Boston, MA 02111 USA. Univ Calif San Francisco, Sch Med, Dept Dermatol, San Francisco, CA 94143 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 311 BP A52 EP A52 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900311 ER PT J AU Tuchinda, C Kerr, HA Taylor, CR Lim, HW AF Tuchinda, C Kerr, HA Taylor, CR Lim, HW TI UVA1 phototherapy for cutaneous diseases: an experience in the United States SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Henry Ford Hosp, Detroit, MI 48202 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 244 BP A41 EP A41 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900244 ER PT J AU Valencia, A Rajadurai, A Carle, AB Redmond, RW Kocheyar, IE AF Valencia, A Rajadurai, A Carle, AB Redmond, RW Kocheyar, IE TI UVA photosensitivity in Smith-Lemli-Optiz syndrome: roles of lipid rafts and oxidative stress SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 783 BP A131 EP A131 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901323 ER PT J AU Wang, LC Gellenthin, M Gupta, S Lee, S Nghiem, P AF Wang, LC Gellenthin, M Gupta, S Lee, S Nghiem, P TI Merkel cell carcinoma: high incidence of lymph node involvement at presentation in 61 patients SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. Charite Univ Hosp, Berlin, Germany. Boston Univ, Sch Med, Boston, MA 02118 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 238 BP A40 EP A40 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900238 ER PT J AU Yamanaka, K Clark, R Rich, B Dowgiert, R Hirahara, K Hurwitz, D Shibata, M Mirchandani, N Jones, DA Eapen, S Kupper, TS AF Yamanaka, K Clark, R Rich, B Dowgiert, R Hirahara, K Hurwitz, D Shibata, M Mirchandani, N Jones, DA Eapen, S Kupper, TS TI Skin-derived interleukin-7 contributes to the proliferation of lesional lymphocytes in cutaneous T cell lymphoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Harvard Univ, Brigham & Womens Hosp, Skin Dis Res Ctr, Dept Dermatol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dana Farber Harvard Canc Ctr, Biostat Core Facil, Dept Biostat, Boston, MA 02115 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 277 BP A47 EP A47 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900277 ER PT J AU Yang, G Rajadurai, A Tsao, H AF Yang, G Rajadurai, A Tsao, H TI Recurrent patterns of dual RB and p53 pathway inactivation in melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 869 BP A145 EP A145 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901408 ER PT J AU Young, H Halin, C Janes, L Min, M Pytowski, B Griffiths, C Detmar, M AF Young, H Halin, C Janes, L Min, M Pytowski, B Griffiths, C Detmar, M TI Blockade of VEGF receptor-3 ameliorates VEGF-A induced chronic cutaneous inflammation. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Univ Manchester, Dermatol Ctr, Manchester, Lancs, England. Imclone Syst Inc, New York, NY USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 010 BP A2 EP A2 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900011 ER PT J AU Melo, N Pitman, MB Rattner, DW AF Melo, N Pitman, MB Rattner, DW TI Bronchogenic cyst of the gastric fundus presenting as a gastrointestinal stromal tumor SO JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES-PART A LA English DT Article ID SURGICAL-MANAGEMENT AB Gastrointestinal stromal tumors (GIST) of the stomach are being recognized with increasing frequency. The diagnosis is usually made on the basis of appearance on computed tomography (CT) and excision is recommended for GIST larger than 5 cm. We report a 39-year-old woman referred for resection of a presumed GIST of the gastric fundus diagnosed by CT scan and upper gastrointestinal (UGI) series. A laparoscopic resection was performed, but upon pathologic examination the mass proved to be a bronchogenic duplication cyst of the stomach. Bronchogenic and esophageal duplication cysts usually arise in the chest or mediastinum. On rare occasions bronchogenic cysts may lose their connection to the tracheobronchial tree and migrate to a subcutaneous position in the neck or descend into the retroperitoneum. The importance of this case is that it demonstrates a rare yet essential component to the differential diagnosis of lesions of the stomach. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. EM drattner@partners.org NR 12 TC 18 Z9 19 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1092-6429 J9 J LAPAROENDOSC ADV A JI J. Laparoendosc. Adv. Part A PD APR PY 2005 VL 15 IS 2 BP 163 EP 165 DI 10.1089/lap.2005.15.163 PG 3 WC Surgery SC Surgery GA 926JW UT WOS:000229120500012 PM 15898909 ER PT J AU Binesh, N Huda, A Bugbee, M Gupta, R Rasgon, N Kumar, A Green, M Han, S Thomas, MA AF Binesh, N Huda, A Bugbee, M Gupta, R Rasgon, N Kumar, A Green, M Han, S Thomas, MA TI Adding another spectral dimension to H-1 magnetic resonance spectroscopy of hepatic encephalopathy SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE hepatic encephalopathy; MR spectroscopy; COSY; cerebral metabolites; neuropsychology ID CORRELATED MR SPECTROSCOPY; NEUROPSYCHOLOGICAL CHARACTERIZATION; CIRRHOTIC-PATIENTS; BRAIN; PROTON; DEFECTS; TAURINE AB Purpose: To evaluate a localized two-dimensional correlated magnetic resonance spectroscopic (L-COSY) technique in patients with hepatic encephalopathy (HE) and healthy subjects, and to correlate the cerebral metabolite changes with neuropsychological (NP) test scores. Materials and Methods: Eighteen minimal hepatic-encephalopathy (MHE) patients and 21 healthy controls have been investigated. A GE 1.5-T magnetic resonance (MR) scanner was used in combination with a body MR coil for transmission and a 3-inch surface coil for reception. A 27-mL voxel was localized by three slice-selective radio frequency (RF) pulses (90 degrees-180 degrees-90 degrees) in the anterior cingulate region. The total duration of each two-dimensional L-COSY spectrum was approximately 25 minutes. The NP battery included a total of 15 tests, which were grouped into six domains. Results: MR spectroscopic results showed a statistically significant decrease in myo-mositol (mI) and choline (Ch) and an increase in glutamate/glutamine (Glx) in patients when compared to healthy controls. There was also an increase in taurine (Tau) in patients. The NP results indicated a significant correlation between motor function assessed by NP tests and mI ratios recorded using two-dimensional L-COSY. Conclusion: The study demonstrated the feasibility of evaluating the two-dimensional L-COSY sequence in a clinical environment. The results showed additional cerebral metabolites that can be measured with the technique in comparison to one-dimensional study. (c) 2005 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90024 USA. Calif State Univ Fresno, Dept Phys, Fresno, CA 93740 USA. Sanjay Gandhi Postgrad Inst Med Sci, Dept Radiol, Lucknow, Uttar Pradesh, India. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Hepatol, Los Angeles, CA USA. RP Binesh, N (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, CHS BL 428,10833 Le Conte Ave, Los Angeles, CA 90024 USA. EM nbinesh@mednet.ucla.edu RI Huda, Amir/I-5987-2015; Thomas, m. albert/A-6176-2012 OI Huda, Amir/0000-0002-0171-3796; FU NIMH NIH HHS [MH06595, MH58284] NR 33 TC 20 Z9 26 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD APR PY 2005 VL 21 IS 4 BP 398 EP 405 DI 10.1002/jmri.20291 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 911UD UT WOS:000228029900012 PM 15779041 ER PT J AU Wu, YY Hong, KX Chenine, AL Whitney, JB Chen, QM Geng, YQ Ruprecht, RM Shao, YM AF Wu, YY Hong, KX Chenine, AL Whitney, JB Chen, QM Geng, YQ Ruprecht, RM Shao, YM TI Molecular cloning and in vitro evaluation of an infectious simian-human immunodeficiency virus containing env of a primary Chinese HIV-1 subtype C isolate SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE Chinese HIV-1; R5 simian-human immunodeficiency virus; subtype C ID RHESUS-MONKEYS; TYPE-1 ISOLATE; ENVELOPE GLYCOPROTEINS; MACAQUES; AIDS; DISEASE; PREVENTION; VACCINE; STRAIN; GENE AB Human immunodeficiency virus (HIV) clade C is the most prevalent subtype and accounts for approximately 50% of all HIV infections worldwide. In China, the prevalent HIV strains are B'/C subtypes, in which the envelope belongs to subtype C. To evaluate potential AIDS vaccines targeting Chinese viral strains in non-human primate models, we constructed an infectious simian-human immunodeficiency virus (SHIV) that expresses most of the envelope of a primary HIV strain, which was isolated from a HIV-positive intravenous drug user from XinJiang province in China. The resulting chimeric SHIV-XJ02170 was infectious in human, rhesus monkey and cynomolgus monkey peripheral blood mononuclear cells (PBMC) and used CCR5 exclusively as coreceptor. C1 Natl Ctr AIDS STD Control & Prevent, Beijing 100050, Peoples R China. Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shao, YM (reprint author), Natl Ctr AIDS STD Control & Prevent, 27 Nanwei Rd, Beijing 100050, Peoples R China. EM yshao@public3.bta.net.cn FU NIAID NIH HHS [U19 AI05915]; NIDCR NIH HHS [R01 DE12937] NR 25 TC 14 Z9 19 U1 1 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD APR PY 2005 VL 34 IS 2 BP 101 EP 107 DI 10.1111/j.1600-0684.2005.00098.x PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 904ES UT WOS:000227479500007 PM 15860117 ER PT J AU Schroeder, FC Kau, TR Silver, PA Clardy, J AF Schroeder, FC Kau, TR Silver, PA Clardy, J TI The psammaplysenes, specific inhibitors of FOXO1a nuclear export SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID IANTHELLA-BASTA; CANCER-THERAPY; METABOLITES; PURPUREA AB A small collection of marine natural product extracts was screened for compounds that would compensate lost tumor suppressor functionality in PTEN-deficient cells. From the most active extract, the previously unreported bromotyrosine derivative, psammaplysene A (1), was identified. Psammaplysene A compensates for PTEN loss by relocalizing the transcription factor FOXO1a to the nucleus. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Clardy, J (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM jon_clardy@hms.harvard.edu RI Schroeder, Frank/H-5026-2012; OI Schroeder, Frank/0000-0002-4420-0237 FU NCI NIH HHS [5T32CA09361, CA24487]; NIGMS NIH HHS [GM36763] NR 14 TC 37 Z9 37 U1 2 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD APR PY 2005 VL 68 IS 4 BP 574 EP 576 DI 10.1021/np049624z PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 920GI UT WOS:000228677000020 PM 15844952 ER PT J AU Doss-Esper, CE Singhal, AB Smith, MSA Henderson, GV AF Doss-Esper, CE Singhal, AB Smith, MSA Henderson, GV TI Reversible posterior leukoencephalopathy, cerebral vasoconstriction, and strokes after intravenous immune globulin therapy in Guillain-Barre syndrome SO JOURNAL OF NEUROIMAGING LA English DT Article DE reversible posterior leukoencephalopathy syndrome (RPLS); intravenous immune globulin (IVIg); vasospasm; stroke; subarachnoid hemorrhage ID VASOSPASM; ENCEPHALOPATHY; IVIG; IMMUNOGLOBULIN; ANGIOPATHY; PATIENT AB The authors report a patient with Guillain-Barre syndrome who developed acute hypertension, reversible posterior leukoencephalopathy syndrome, ischemic and hemorrhagic strokes, and reversible cerebral arterial vasoconstriction shortly after initiating intravenous immune globulin therapy. Possible interrelationships and mechanisms of these complications are discussed. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Neurol, Div Crit Care & Emergency Neurol, Boston, MA 02115 USA. RP Singhal, AB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv, VBK-802, Boston, MA 02114 USA. EM asinghal@partners.org NR 17 TC 36 Z9 38 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 APR PY 2005 VL 15 IS 2 BP 188 EP 192 DI 10.1177/1051228404273820 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 906ZZ UT WOS:000227685400010 PM 15746232 ER PT J AU Baehring, JM Henchcliffe, C Ledezma, CJ Fulbright, R Hochberg, FH AF Baehring, JM Henchcliffe, C Ledezma, CJ Fulbright, R Hochberg, FH TI Intravascular lymphoma: magnetic resonance imaging correlates of disease dynamics within the central nervous system SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID MALIGNANT LYMPHOMATOSIS; MIMICKING; DIAGNOSIS; LESIONS; BRAIN; MRI AB Background: Intravascular lymphoma (IVL) is a rare non-Hodgkin's lymphoma with relative predilection for the central nervous system. In the absence of extraneural manifestations, the disease is not recognised until autopsy in the majority of cases underlining the need for new clinical markers. Methods: This is a retrospective series of five patients with IVL seen at a single institution over three years. An advanced magnetic resonance imaging (MRI) protocol was performed at various time points prior to diagnosis and during treatment. Results: MRI revealed multiple lesions scattered throughout the cerebral hemispheres; the brainstem, cerebellum, and spinal cord were less frequently involved. On initial presentation, hyperintense lesions were seen on diffusion weighted images suggestive of ischaemia in three of four patients in whom the images were obtained at that time point. In four patients lesions were also identifiable as hyperintense areas on fluid attenuated inversion recovery (FLAIR) sequences. Initial contrast enhancement was encountered in three cases. Diffusion weighted imaging lesions either vanished or followed the typical pattern of an ischaemic small vessel stroke with evolution of abnormal FLAIR signal followed by enhancement with gadolinium in the subacute stage and tissue loss in the chronic stage. Diffusion weighted imaging and FLAIR abnormalities proved to be partially reversible, correlating with the response to chemotherapy. Conclusion: We provide the first detailed description of the dynamic pattern of diffusion weighted MRI in IVL. These patterns in combination with systemic findings may facilitate early diagnosis and serve as a new tool to monitor treatment response. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brain Tumor Ctr,Dept Neurol, Boston, MA 02114 USA. Columbia Presbyterian Med Ctr, Dept Neurol, New York, NY 10032 USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06510 USA. RP Hochberg, FH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brain Tumor Ctr,Dept Neurol, Cox 315, Boston, MA 02114 USA. EM Fhochberg@partners.org NR 18 TC 34 Z9 36 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD APR PY 2005 VL 76 IS 4 BP 540 EP 544 DI 10.1136/jnnp.2003.033662 PG 5 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 910RY UT WOS:000227951100018 PM 15774442 ER PT J AU Sheehan, JP Niranjan, A Sheehan, JM Jane, JA Laws, ER Kondziolka, D Flickinger, J Landolt, AM Loeffler, JS Lunsford, LD AF Sheehan, JP Niranjan, A Sheehan, JM Jane, JA Laws, ER Kondziolka, D Flickinger, J Landolt, AM Loeffler, JS Lunsford, LD TI Stereotactic radiosurgery for pituitary adenomas: an intermediate review of its safety, efficacy, and role in the neurosurgical treatment armamentarium SO JOURNAL OF NEUROSURGERY LA English DT Review DE stereotactic radiosurgery; gamma knife; pituitary adenoma; Cushing disease; acromegaly; prolactinoma ID GAMMA-KNIFE RADIOSURGERY; AUTOMATIC POSITIONING SYSTEM; TRANS-SPHENOIDAL SURGERY; CUSHINGS-DISEASE; TRANSSPHENOIDAL SURGERY; FOLLOW-UP; CAVERNOUS SINUS; GROWTH-HORMONE; MODEL-C; FRACTIONATED RADIOTHERAPY AB Object. Pituitary adenomas are very common neoplasms, constituting between 10 and 20% of all primary brain tumors. Historically, the treatment armamentarium for pituitary adenomas has included medical management, microsurgery, and fractionated radiotherapy. More recently, radiosurgery has emerged as a viable treatment option. The goal of this research was to define more fully the efficacy, safety, and role of radiosurgery in the treatment of pituitary adenomas. Methods. Medical literature databases were searched for articles pertaining to pituitary adenomas and stereotactic radiosurgery. Each study was examined to determine the number of patients, radiosurgical parameters (for example, maximal dose and tumor margin dose), duration of follow-up review, tumor growth control rate, complications, and rate of hormone normalization in the case of functioning adenomas. A total of 35 peer-reviewed studies involving 1621 patients were examined. Radiosurgery resulted in the control of tumor size in approximately 90% of treated patients. The reported rates of hormone normalization for functioning adenomas varied substantially. This was due in part to widespread differences in endocrinological criteria used for the postradiosurgical assessment. The risks of hypopituitarism, radiation-induced neoplasia, and cerebral vasculopathy associated with radiosurgery appeared lower than those for fractionated radiation therapy. Nevertheless, further observation will be required to understand the true probabilities. The incidence of other serious complications following radiosurgery was quite low. Conclusions. Although microsurgery remains the primary treatment modality in most cases, stereotactic radiosurgery offers both safe and effective treatment for recurrent or residual pituitary adenomas. In rare instances, radiosurgery may be the best initial treatment for patients with pituitary adenomas. Further refinements in the radiosurgical technique will likely lead to improved outcomes. C1 Univ Virginia, Dept Neurol Surg, Charlottesville, VA 22908 USA. Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. Penn State Univ, Ctr Med, Dept Neurosurg, Hershey, PA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Klin Park, Neurosurg Sect Neuroendocrine Surg, Zurich, Switzerland. RP Sheehan, JP (reprint author), Univ Virginia, Dept Neurol Surg, Box 800-212, Charlottesville, VA 22908 USA. EM jps2f@virginia.edu OI Flickinger, John/0000-0001-6900-1384 NR 123 TC 129 Z9 130 U1 1 U2 3 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 APR PY 2005 VL 102 IS 4 BP 678 EP 691 DI 10.3171/jns.2005.102.4.0678 PG 14 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 918GA UT WOS:000228529100018 PM 15871511 ER PT J AU Lee, KH Kim, HK Paik, JY Matsui, T Choe, YS Choi, Y Kim, BT AF Lee, KH Kim, HK Paik, JY Matsui, T Choe, YS Choi, Y Kim, BT TI Accuracy of myocardial sodium/iodide symporter gene expression imaging with radioiodide: Evaluation with a dual-gene adenovirus vector SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 19-23, 2004 CL Philadelphia, PA SP Soc Nucl Med DE reporter gene; gene therapy; myocardium; radioiodide; scintigraphy ID SODIUM-IODIDE SYMPORTER; POSITRON-EMISSION-TOMOGRAPHY; REPORTER GENE; IN-VIVO; THERAPY; IDENTIFICATION; RATS; NIS AB The sodium/iodide symporter (NIS) gene allows convenient reporter imaging with gamma-cameras and free radioiodide. In this study, we investigated the accuracy of this technique for assessing myocardial gene expression in living rats by using a dual-gene adenovirus that expresses both NIS protein and enhanced green fluorescent protein (EGFP). Methods: Rats underwent myocardial injection with the dual-gene adenovirus (Ad.EGFP.NIS) or a control virus (Ad.EGFP). I-123 scintigraphy was performed at day 4, and ratios of cardiac counts to mediastinal count were measured. The site of radiouptake was localized by use of dual-isotope Tl-201 images, and radioiodide efflux rates were evaluated by dynamic imaging. The dependence of cardiac radiouptake on viral titers and the sensitivity of detection of cardiac radiouptake were investigated at various viral titers. The radioactivity, EGFP, and NIS protein expression sites were compared microscopically. The correlation of image-based uptake with fluorometric measurements of EGFP concentrations was assessed by regression analysis. Results: I-123 scintigraphy demonstrated clear focal myocardial uptake at the Ad.EGFP.NIS injection site, with relatively slow washout rates (3.3% +/- 0.8%/h), despite the absence of organification. Image-based cardiac uptake increased in a viral titer-dependent manner, with a detection threshold of between 3 x 10(6) and 1 x 10(7) plaque-forming units. Western blotting showed titer-dependent increases in myocardial NIS protein expression. Tissue radioactivity levels approached 12.5-fold control levels and correlated closely with image-based uptake (r = 0.91; P < 0.0001). Histologic analysis confirmed the colocalization of radiouptake, EGFP fluorescence, and NIS staining. Image-based uptake showed a strong correlation with fluorometric measurements of myocardial EGFP concentrations (r = 0.81; P < 0.0001). Conclusion: Our results demonstrate that convenient myocardial gene imaging with gamma-cameras and radioiodide is feasible with the NIS gene. Moreover, the use of this technique with a dual-gene vector appears to allow accurate assessment of the level of myocardial expression of a second gene of interest. C1 Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Nucl Med, Seoul, South Korea. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Program Cardiovasc Gene Therap, Boston, MA USA. RP Lee, KH (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Nucl Med, 50 Ilwondong, Seoul, South Korea. EM khnm.lee@samsung.com RI Lee, Kyun Han/C-9648-2011 NR 21 TC 17 Z9 20 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR PY 2005 VL 46 IS 4 BP 652 EP 657 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 914BQ UT WOS:000228200000020 PM 15809488 ER PT J AU Susarla, SM Dodson, TB AF Susarla, SM Dodson, TB TI Estimating third molar extraction difficulty: A comparison of subjective and objective factors SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article AB Purpose: The purpose of this study was to compare and contrast subjective and objective assessments of variables associated with third molar (M3) extraction difficulty. Materials and Methods: To address the research purpose we implemented a prospective cohort study and enrolled a sample of surgeons removing M3s in an ambulatory care setting. Predictor variables were categorized as demographic, anatomic, or operative. The outcome variables were subjective and objective rankings of the importance of the variables in terms of estimating M3 extraction difficulty. Subjective rankings were made by surveying the surgeons and asking them to rank each variable's importance on a scale ranging from 0 (not important) to 100 (extremely important). Objective rankings of each variable's importance were made using the absolute values of coefficients, derived from a multivariate linear regression model with extraction time as the outcome. Appropriate uni-, bi-, and multivariate statistics were computed. Results: The sample consisted of 14 surgeons who removed 450 M3s from 150 subjects from June 2002 to August 2003. Based on the multivariate linear regression model, variables associated with M3 extraction time were gender, arch location, Winter's classification, tooth morphology, number of teeth extracted, procedure type, and surgical experience. For these variables, there was a strong, statistically significant correlation (r = 0.86; P < .01) between the standardized coefficient absolute values and the surgeons' estimates of importance. Conclusion: There was a large, positive correlation between variables that surgeons consider most important in determining M3 extraction difficulty and those exhibiting the most influence over extraction times in a multivariate model. (c) 2005 American Association of Oral and Maxillofacial Surgeons C1 Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Dodson, TB (reprint author), Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, 55 Fruit St Warren 1201, Boston, MA 02114 USA. EM tbdodson@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 FU NIDCR NIH HHS [K24-DE000448] NR 6 TC 16 Z9 20 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 APR PY 2005 VL 63 IS 4 BP 427 EP 434 DI 10.1016/j.joms.2004.12.003 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 911TX UT WOS:000228029200002 PM 15789312 ER PT J AU Albritton, KH Randall, RL AF Albritton, KH Randall, RL TI Prospects for targeted therapy of synovial sarcoma SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article; Proceedings Paper CT 3rd Adolescent and Young Adullt Symposium on Sarcomas in Adolecents and Young Adutls CY APR, 2004 CL Univ Texas M D Anderson Canc Ctr, Houston, TX SP Memorial Sloan Kettering Canc Ctre HO Univ Texas M D Anderson Canc Ctr DE synovial sarcoma; targeted therapy ID GROWTH-FACTOR RECEPTOR; ADVANCED SOFT-TISSUE; SSX FUSION TYPE; SYT-SSX; GENE-EXPRESSION; PROGNOSTIC-SIGNIFICANCE; RETROSPECTIVE ANALYSIS; PROLIFERATIVE ACTIVITY; MULTIVARIATE-ANALYSIS; BCL-2 PROTEIN AB Synovial sarcoma is a distinct tumor with unique promise for targeted therapy It has a diagnostic translocation and a potentially informative fusion protein. It has moderate chemosensitivity, with about 50% response rates to regimens containing ifosfamide and doxorubicin. Therapeutic advances are unlikely to occur by continuing to lump synovial sarcomas in trials with other soft tissue sarcomas and adjusting traditional agents; rather, attention should be turned toward prospective molecular targets and investigation or development of novel agents to exploit them. The SYT-SSX fusion protein that results from the X, 18 translocation is an appealing target, as are the proteins overexpressed in synovial sarcoma: bcl-2, EGFR, and HER-2/neu. C1 Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. RP Albritton, KH (reprint author), 44 Binney St, Boston, MA 02115 USA. EM Karen_albritton@dfci.harvard.edu NR 44 TC 28 Z9 31 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD APR PY 2005 VL 27 IS 4 BP 219 EP 222 DI 10.1097/01.mph.0000163713.46762.72 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 922YV UT WOS:000228876700010 PM 15838395 ER PT J AU Smith, VC Zupancic, JAF McCormick, MC Croen, LA Greene, J Escobar, GJ Richardson, DK AF Smith, VC Zupancic, JAF McCormick, MC Croen, LA Greene, J Escobar, GJ Richardson, DK TI Trends in severe bronchopulmonary dysplasia rates between 1994 and 2002 SO JOURNAL OF PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 03-07, 2002 CL BALTIMORE, MD SP Pediat Acad Soc ID CHRONIC LUNG-DISEASE; LOW-BIRTH-WEIGHT; SURFACTANT THERAPY; PRETERM INFANTS; DEXAMETHASONE; VENTILATION; MORBIDITY; MORTALITY; OUTCOMES; CHILDREN AB Objective To examine temporal trends in the rates of severe bronchopulmonary dysplasia (BPD) between 1994 and 2002. Study design In a retrospective cohort study, all infants with a gestational age (GA) < 33 weeks in a large managed care organization were identified. Annual rates of BPD (defined as an oxygen requirement at 36 weeks corrected GA), severe BPD (defined as respiratory support at 36 weeks corrected GA), and death before 36 weeks corrected GA were examined. Results Of the 5115 infants in the study cohort, 603 (12%) had BPD, including 246 (4.9%) who had severe BPD. There were 481 (9.5%) deaths before 36 weeks corrected GA. Although the decline in BPD in this period was not significant, the rates of severe BPD declined from 9.7% in 1994 to 3.7% in 2002. Controlling for gestational age, the odds ratio (95% Cl) for annual rate of decline in severe BPD was 0.890 (0.841-0.941). Controlling for gestational age, deaths before 36 weeks corrected GA also declined, with the odds ratio (Cl) for the annual decline being 0.944 (0.896-0.996). Conclusions In this study, population, the odds of having of BPD remained constant after controlling for GA. However, the odds of having severe BPD declined on average 11% per year between 1994 and 2002. C1 Beth Israel Deaconess Med Ctr, Dept Neonatol, Boston, MA 02215 USA. Harvard Univ, Newborn Med Program, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Kaiser Permanente, Med Care Program, Div Res, Perinatal Res Unit, Oakland, CA USA. RP Smith, VC (reprint author), 330 Brookline Ave,BIDMC Neonatol Rose 318, Boston, MA 02215 USA. EM vsmithl@bidmc.harvard.edu OI Zupancic, John/0000-0003-1734-7193; McCormmick, Marie/0000-0002-3938-1707 NR 24 TC 68 Z9 69 U1 0 U2 4 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 APR PY 2005 VL 146 IS 4 BP 469 EP 473 DI 10.1016/j.jpeds.2004.12.023 PG 5 WC Pediatrics SC Pediatrics GA 916VJ UT WOS:000228414200007 PM 15812448 ER PT J AU Tanner, ACR Kent, R Van Dyke, T Sonis, ST Murray, LA AF Tanner, ACR Kent, R Van Dyke, T Sonis, ST Murray, LA TI Clinical and other risk indicators for early periodontitis in adults SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE bicuspid; gingival recession/etiology; molar; periodontal attachment loss/etiology; periodontitis/etiology; risk factors ID EARLY-ONSET PERIODONTITIS; ATTACHMENT LOSS; UNITED-STATES; GINGIVAL RECESSION; INTRAORAL DISTRIBUTION; DISEASE PROGRESSION; CIGARETTE-SMOKING; PRETERM BIRTH; OLDER; AGE AB Background: Periodontal diseases affect over half the adults in the U.S., disproportionately affecting minority populations. Periodontitis can be treated in early stages, but it is not clear what features indicate, or could be risk factors for, early stages of periodontal attachment loss. This study aimed to evaluate associations between clinical and other risk indicators of early periodontitis. Methods: A cross-sectional evaluation of 225 healthy and early periodontitis adults aged 20 to 40 years was performed. Clinical measurements, demographic information, and smoking histories were recorded. Analyses evaluated demographic and clinical associations with health and early periodontitis disease categories and periodontal attachment loss. Patterns of attachment loss at interproximal and buccal/lingual sites were evaluated. Results: Subject age, plaque, and measures of gingivitis exhibited associations with attachment loss and probing depth. More periodontal attachment loss was detected in African-American and Hispanic subjects compared to Asian and Caucasian subjects. Smoking history was associated with attachment loss. At interproximal sites, lower molars most frequently had attachment loss, whereas at buccal/lingual sites, higher proportions of lower bicuspid teeth demonstrated attachment loss compared with other sites. Conclusions: In this study of subjects with minimal attachment loss, gingival inflammation was associated with early periodontitis. Lower molar interproximal sites were frequently associated with interproximal attachment loss, whereas lower bicuspid teeth were at risk for gingival recession on buccal surfaces. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Forsyth Inst, Dept Biostat, Boston, MA 02115 USA. Boston Univ, Sch Dent Med, Clin Res Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Oral Med & Oral Pathol, Boston, MA 02115 USA. RP Tanner, ACR (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. EM annetanner@forsyth.org FU NCRR NIH HHS [M01 RR000533, RR00533]; NIDCR NIH HHS [R01 DE009513, DE09513] NR 35 TC 32 Z9 35 U1 0 U2 5 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 APR PY 2005 VL 76 IS 4 BP 573 EP 581 DI 10.1902/jop.2005.76.4.573 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 923AA UT WOS:000228879800012 PM 15857098 ER PT J AU Haddy, C Strack, S Choca, JP AF Haddy, C Strack, S Choca, JP TI Linking personality disorders and clinical syndromes on the MCMI-III SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID COMMON MENTAL-DISORDERS; AXIS-II; MULTIAXIAL INVENTORY; PARALLEL ANALYSIS; SELF-REPORT; DSM-III; NUMBER; DEPRESSION; DIAGNOSIS; PSYCHOPATHOLOGY AB We examined the relationship between personality disorders (PDs) and clinical syndromes (CSs) as measured by the Millon Clinical Multiaxial Inventory-III (MCMI-III; Millon, 1997) in a large, heterogeneous sample of psychiatric patients N = 2,366) who completed the instrument as part of routine assessment following presentation for treatment. Using separate sets of base rate (BR) and nonoverlapping scale scores, we factor analyzed the PD and CS scales together and then separately. We correlated results from the latter analyses to determine how trait dimensions were associated with syndrome dimensions. We also studied co-occurrence at the scale level by examining CS score profiles of patients who were grouped according to their highest PD scale elevation >= BR75. Results for the two score sets were very similar and were consistent with previous research on the MCMI-III and its predecessors that identified 3 underlying dimensions loading both PD and CS scales. Three fourths (76.2%) of the sample had a highest PD scale >= BR75, and among these, 90% had at least 1 CS scale >= BR75, whereas 62.4% had 3 or more CS scales above this elevation. Findings underscore the substantial overlap between PDs and CSs along 3 dimensions that resemble Homey's (1945) tripartite interpersonal distinction of moving toward, away, and against, as well as Eysenck's (1994) higher order factors of neuroticism, extraversion, and psychoticism. C1 Univ So Calif, Dept Counseling Psychol, Los Angeles, CA 90089 USA. US Dept Vet Affairs, Ctr Ambulatory Care, Los Angeles, CA USA. RP Strack, S (reprint author), VA Ambulatory Care Ctr, Psychol Serv 116B, 351 E Temple St, Los Angeles, CA 90012 USA. EM snstrack@aol.com NR 47 TC 9 Z9 11 U1 1 U2 6 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD APR PY 2005 VL 84 IS 2 BP 193 EP 204 DI 10.1207/s15327752jpa8402_09 PG 12 WC Psychology, Clinical; Psychology, Social SC Psychology GA 912KT UT WOS:000228077600009 PM 15799894 ER PT J AU Montoya, ID Schroeder, JR Preston, KL Covi, L Umbricht, A Contoreggi, C Fudala, PJ Johnson, RE Gorelick, DA AF Montoya, ID Schroeder, JR Preston, KL Covi, L Umbricht, A Contoreggi, C Fudala, PJ Johnson, RE Gorelick, DA TI Influence of psychotherapy attendance on buprenorphine treatment outcome SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 14-19, 2003 CL Bal Harbor, FL SP Coll Problems Drug Dependence DE buprenorphine; cocaine; heroin; dual dependence; psychotherapy ID METHADONE-MAINTENANCE TREATMENT; COLLABORATIVE COCAINE TREATMENT; COGNITIVE-BEHAVIORAL THERAPY; VOUCHER-BASED REINFORCEMENT; SUBSTANCE-ABUSE TREATMENT; CONTINGENCY MANAGEMENT; RANDOMIZED-TRIAL; FOLLOW-UP; DEPENDENCE; HEROIN AB We evaluated the influence of psychotherapy attendance on treatment outcome in 90 dually (cocaine and heroin) dependent outpatients who completed 70 days of a controlled clinical trial of sublingual buprenorphine (16 mg, 8 mg, or 2 mg daily, or 16 mg every other day) plus weekly individual standardized interpersonal cognitive psychotherapy. Treatment outcome was evaluated by quantitative urine benzoylecgonine (BZE) and morphine levels (log-transformed), performed three times per week. Repeated-measures linear regression was used to assess the effects of psychotherapy attendance (percent of visits kept), medication group, and study week on urine drug metabolite levels. Mean psychotherapy attendance was 71% of scheduled visits. Higher psychotherapy attendance was associated with lower urine BZE levels, and this association grew more pronounced as the study progressed (p = 0.04). The inverse relationship between psychotherapy attendance and urine morphine levels varied by medication group, being most pronounced for subjects receiving 16 mg every other day (p = 0.02). These results suggest that psychotherapy can improve the outcome of buprenorphine maintenance treatment for patients with dual (cocaine and opioid) dependence. Published by Elsevier Inc. C1 NIDA, Div Pharmacotherapie & Med Consequences Drug Abus, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIDA, Clin Pharmacol & Therapeut Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIDA, Brain Imaging Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21224 USA. Reckitt Benckiser Pharmaceut Inc, Baltimore, MD 21224 USA. RP Montoya, ID (reprint author), NIDA, Div Pharmacotherapie & Med Consequences Drug Abus, NIH, Dept Hlth & Human Serv, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM imontoya@mail.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural NIH HHS [Z99 DA999999] NR 49 TC 20 Z9 21 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD APR PY 2005 VL 28 IS 3 BP 247 EP 254 DI 10.1016/j.jsat.2005.01.004 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 925ZT UT WOS:000229093100005 PM 15857725 ER PT J AU Chan, BP Amann, C Yaroslavsky, AN Title, C Smink, D Zarins, B Kochevar, IE Redmond, RW AF Chan, BP Amann, C Yaroslavsky, AN Title, C Smink, D Zarins, B Kochevar, IE Redmond, RW TI Photochemical repair of Achilles tendon rupture in a rat model SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE photosensitization; tendon repair; tissue bonding; rose bengal ID MEDIAL COLLATERAL LIGAMENT; FIBROBLAST-GROWTH-FACTOR; CORNEAL INCISIONS; PATELLAR TENDON; KERATODESMOS; COLLAGEN; LIGHT AB Background. Photochemical tissue bonding (PTB) is an emerging technique for bonding or sealing tissue surfaces that requires light and a photoactive dye for its effect. The potential of PTB for tendon repair was assessed in a rat model. Materials and methods. The optical properties of bovine tendon were determined ex vivo to gauge the depth of light penetration as a function of wavelength and dosimetry parameters were established for PTB repair of ruptured tendon. PTB was then tested in vivo to repair transected tendons in Sprague-Dawley rats. Repair strengths were measured using a strain gauge up to 14 days post treatment. Results. The effective penetration depth in tendon was estimated to be 0.68 mm at 514 nm. Following PTB treatment of mechanically ruptured tendon, significant bonding was dependent on the presence of both light and dye and attained a plateau strength at a fluence of 125 j/cm(2). In a subsequent in vivo study to investigate PTB for repair of transected rat Achilles tendon, the ultimate stress required to break the repaired tendon was measured immediately after irradiation and at 7 and 14 days post-repair. Results showed that the difference in the ultimate stress between control and PTB treatment groups was statistically significant immediately after treatment and at 7 days (p = 0.04) but not 14 days (p = 0.75) post-repair. Conclusions. PTB provides a benefit to tendon repair at early stages in repair and is worthy of further investigation as a potential surgical adjunct for tendon repair in orthopedic surgeries. (C) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02114 USA. RP Redmond, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp W224, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. EM redmond@helix.mgh.harvard.edu NR 21 TC 30 Z9 36 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD APR PY 2005 VL 124 IS 2 BP 274 EP 279 DI 10.1016/j.jss.2004.09.019 PG 6 WC Surgery SC Surgery GA 915CS UT WOS:000228275800017 PM 15820258 ER PT J AU Barzilai, DA Freiman, A Dellavalle, RP Weinstock, MA Mostow, EN AF Barzilai, DA Freiman, A Dellavalle, RP Weinstock, MA Mostow, EN TI Dermatoepidemiology SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review ID RANDOMIZED CONTROLLED-TRIALS; EVIDENCE-BASED MEDICINE; EVIDENCE-BASED DERMATOLOGY; DISSEMINATING SYSTEMATIC REVIEWS; CUTANEOUS MALIGNANT-MELANOMA; CLINICAL-TRIALS; SKIN-CANCER; HEALTH-CARE; INTERNAL MALIGNANCY; CONSORT STATEMENT C1 Case Western Reserve Univ, Sch Med, Cleveland, OH USA. McGill Univ, Ctr Hlth, Div Dermatol, Montreal, PQ, Canada. Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Dept Dermatol, Denver, CO USA. NE Ohio Univ, Coll Med, Dept Med, Div Dermatol, Akron, OH USA. Dept Vet Affairs Med Ctr, Dermatoepidemiol Unit, Providence, RI USA. RP Barzilai, DA (reprint author), 2185 Cornell Rd, Cleveland, OH 44106 USA. EM david.barzilai@case.edu RI Dellavalle, Robert/L-2020-2013 OI Dellavalle, Robert/0000-0001-8132-088X NR 121 TC 15 Z9 15 U1 1 U2 3 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 APR PY 2005 VL 52 IS 4 BP 559 EP 573 DI 10.1016/j.jaad.2004.09.019 PG 15 WC Dermatology SC Dermatology GA 912WN UT WOS:000228110700001 PM 15793504 ER PT J AU Chan, JL Ehrlich, A Lawrence, RC Moshell, AN Turner, ML Kimball, AB AF Chan, JL Ehrlich, A Lawrence, RC Moshell, AN Turner, ML Kimball, AB TI Assessing the role of race in quantitative measures of skin pigmentation and clinical assessments of photosensitivity SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID ETHNIC SKIN; ERYTHEMA; COLOR; MELANIN; REFLECTANCE; DERMATOLOGY; MEDICINE; GENOMICS; DEEP AB Background: Given the increasing demographic diversity in the United States, clarifying relationships between race, color, ethnicity, and disease processes is critical. Objectives: We sought to examine the correlation between objective measures of skin pigmentation, racial identification, and physician-diagnosed and self-reported skin phototypes. Methods: A total of 558 participants (76 nonwhite) were evaluated. A subset underwent spectrometric readings and digital photography of the upper aspect of the inner arm. Self-identified race was compared with 7 measures of pigmentation. Results: Race correlates best with physician-diagnosed skin phototype (r = 0.55, P <.01), whereas self-reported skin phototype, spectrometry, and colorimetry correlate poorly with race (r = 0.28, < 0.40, and r > -0.31, respectively, P <.01). Associations between race and subjective measures strengthen among patients with darker skin. Conclusion: Objective measures of pigmentation fail to correlate well with race, whereas race correlates moderately with physician-diagnosed skin phototype. including objective methods of analyzing skin color may reduce subjective influences of race in assessing photosensitivity and potential risk for skin cancer. C1 Stanford Univ, Med Ctr, Dept Dermatol, Stanford, CA 94305 USA. George Washington Univ, Dept Dermatol, Washington, DC 20052 USA. NIAMSD, Program Epidemiol, NIH, Bethesda, MD USA. NIAMSD, Skin Dis Branch, NIH, Bethesda, MD USA. NCI, Dermatol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dermatol Clin Studies Unit, 221 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM harvardskinstudies@partners.org OI Ehrlich, Alison/0000-0002-4062-5289 NR 32 TC 18 Z9 18 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 APR PY 2005 VL 52 IS 4 BP 609 EP 615 DI 10.1016/j.jaad.2004.03..051 PG 7 WC Dermatology SC Dermatology GA 912WN UT WOS:000228110700007 PM 15793510 ER PT J AU Grunwaldt, LJ Schwaitzberg, SD Rattner, DW Jones, DB AF Grunwaldt, LJ Schwaitzberg, SD Rattner, DW Jones, DB TI Is laparoscopic inguinal hernia repair an operation of the past? SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; GROIN HERNIA; CLINICAL-TRIAL; MESH REPAIR; SURGERY; METAANALYSIS; HISTORY C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Tufts New England Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jones, DB (reprint author), Beth Israel Deaconess Med Ctr, Shapiro TCC 355, Boston, MA 02215 USA. NR 25 TC 8 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD APR PY 2005 VL 200 IS 4 BP 616 EP 620 DI 10.1016/j.jamcollsurg.2004.10.033 PG 5 WC Surgery SC Surgery GA 912NH UT WOS:000228085200016 PM 15804477 ER PT J AU Boockvar, KS Gruber-Baldini, AL Burton, L Zimmerman, S May, C Magaziner, J AF Boockvar, KS Gruber-Baldini, AL Burton, L Zimmerman, S May, C Magaziner, J TI Outcomes of infection in nursing home residents with and without early hospital transfer SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MD SP Amer Geriatr Soc DE infection; nursing homes; treatment outcome ID RESPIRATORY-TRACT INFECTION; TERM-CARE FACILITIES; ADVERSE EVENTS; PROPENSITY SCORES; ELDERLY-PATIENTS; RISK-FACTORS; DEMENTIA; SURVEILLANCE; DELIRIUM; ILLNESS AB OBJECTIVES: To compare outcomes of infection in nursing home residents with and without early hospital transfer. DESIGN: Observational cohort study. SETTING: Fifty-nine nursing homes in Maryland. PARTICIPANTS: Two thousand one hundred fifty-three individuals admitted to nursing homes between 1992 and 1995. MEASUREMENTS: Incident infection was recorded when a new infectious diagnosis was documented in the medical record or nonprophylactic antibiotic therapy was prescribed. Early hospital transfer was defined as transfer to the emergency department or admission to the hospital within 3 days of infection onset. Infection, resident, and facility characteristics were entered into a multivariate model to create a propensity score for early hospital transfer. Association between early hospital transfer and outcomes of infection, namely pressure ulcers and death between Days 4 and 34 after infection onset, were examined, controlling for propensity score. RESULTS: Four thousand nine hundred ninety infections occurred in 1,301 residents. Genitourinary (28%), skin (19%), upper respiratory (13%), and lower respiratory (12%) were the most common types. Three hundred seventy-five episodes in which residents survived 3 days (7.6%) resulted in early hospital transfer. In multivariate regression, individuals with early hospital transfer had higher mortality (odds ratio (OR) 1.44, 95% confidence interval (CI)=1.04-1.99) and, in 1-month survivors, a greater occurrence of pressure ulcers (OR 1.61, 95% CI=1.17-2.20) than those without, after adjusting for propensity score. CONCLUSION: Using observational data and propensity score methods, outcomes were worse in nursing home residents transferred to the hospital within 3 days of infection onset than in those who remained in the nursing home. C1 Bronx Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY 10468 USA. Mt Sinai Sch Med, Brookdale Dept Geriatr & Adult Dev, New York, NY USA. Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Johns Hopkins Univ, Dept Hlth Policy & Management, Baltimore, MD 21218 USA. Univ N Carolina, Cecil G sheps Ctr Hlth Serv Res, Chapel Hill, NC USA. RP Boockvar, KS (reprint author), Bronx Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, 130 W Kingsbridge Rd,Suite 4 A-17, Bronx, NY 10468 USA. EM kenneth.boockvar@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU NIA NIH HHS [R29 AG 11407, R01 AG 08211] NR 43 TC 56 Z9 58 U1 2 U2 2 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 APR PY 2005 VL 53 IS 4 BP 590 EP 596 DI 10.1111/j.1532-5415.2005.53205.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 909ZM UT WOS:000227899200005 PM 15817003 ER PT J AU Pan, CX Carmody, S Leipzig, RM Granieri, E Sullivan, A Block, SD Arnold, RM AF Pan, CX Carmody, S Leipzig, RM Granieri, E Sullivan, A Block, SD Arnold, RM TI There is hope for the future: National survey results reveal that geriatric medicine fellows are well-educated in end-of-life care SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE end-of-life care; palliative care; medical education; geriatrics ID PALLIATIVE CARE; PROGRAMS AB OBJECTIVES: To assess the status of geriatric medicine (GM) fellows' training experiences in end-of-life care via self-report. DESIGN: Anonymous surveys completed by mail, Web access, and telephone. SETTING: U.S. accredited GM fellowship training programs. PARTICIPANTS: Two hundred ninety-six surveys were sent to graduating GM fellows in 1- and 2-year programs across the Unites States. MEASUREMENTS: Measurements assessed self-reported attitudes, quantity and quality of end-of-life care education, preparation to provide care, and perceived value of caring for dying patients. RESULTS: Response rate was 74%. Ninety-five percent or more of respondents held positive views about physicians' responsibility and ability to help dying patients. Seventy percent of fellows had completed a rotation focused on end-of-life care. Fellows who had done such rotations rated their end-of-life care education as highly as their overall geriatrics training. Fellows frequently received teaching in many end-of-life care topics, with lower rates of teaching how to say goodbye and responding to requests for assisted suicide. Overall, fellows felt well prepared to care for dying patients. Four factors independently predicted such preparedness: having had a palliative or end-of-life care rotation, being female, having been taught how to say goodbye to patients, and perceiving that it is important to attending physicians that fellows learn to care for dying patients. CONCLUSION: GM fellows feel their end-of-life care education is excellent and feel prepared to take care of dying patients. It is critical that geriatricians in training have access to and take advantage of palliative and end-of-life care rotations. C1 CUNY Mt Sinai Sch Med, Brookdale Dept Geriatr & Adult Dev, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Hertzberg Palliat Care Inst, New York, NY 10029 USA. Hennepin Cty Med Ctr, Dept Emergency Med, Minneapolis, MN 55415 USA. Bronx Vet Affairs Med Ctr, Geriatr Res Educ & Care Ctr, Bronx, NY USA. Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Pittsburgh, Med Ctr, Sect Palliat Care & Med Eth, Pittsburgh, PA USA. Univ Pittsburgh, Inst Enhance Palliat Care, Pittsburgh, PA USA. RP Pan, CX (reprint author), CUNY Mt Sinai Sch Med, Brookdale Dept Geriatr & Adult Dev, Annenberg Bldg,Box 1070,1 Gustave L Levy Pl, New York, NY 10029 USA. EM cynthia.pan@mssm.edu NR 16 TC 19 Z9 20 U1 2 U2 4 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 APR PY 2005 VL 53 IS 4 BP 705 EP 710 DI 10.1111/j.1532-5415.2005.53223.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 909ZM UT WOS:000227899200023 PM 15817021 ER PT J AU Abdel-Karim, I Sammel, RB Prange, MA AF Abdel-Karim, I Sammel, RB Prange, MA TI Autopsy findings among patients in an inpatient hospice program. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Univ Texas, Dept Med, Div Geriatr, San Antonio, TX 78285 USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Affairs Hlth Care Syst, Educ & Clin Ctr, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S152 EP S152 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900439 ER PT J AU Alam, T Martin, JL Harker, JO Josephson, KR Alessi, CA AF Alam, T Martin, JL Harker, JO Josephson, KR Alessi, CA TI A pilot study of sleep-wake patterns in assisted living facilities. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 GRECC, VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S210 EP S211 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900606 ER PT J AU Boockvar, KS Mordiglia, T Fridman, B Fried, T AF Boockvar, KS Mordiglia, T Fridman, B Fried, T TI IPFS versus APACHE for predicting hospital outcomes of disabled older adults. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Mt Sinai Sch Med, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. Yale Univ, New Haven, CT USA. Jewish Home & Hosp, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S201 EP S201 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900579 ER PT J AU Briesacher, B Orwig, D Seton, M Omar, MA Kahler, K AF Briesacher, B Orwig, D Seton, M Omar, MA Kahler, K TI Disease burden and treatment costs of elderly patients with Pagets Disease SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Univ Massachusetts, Sch Med, Div Geriatr Med, Worcester, MA USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, New England Registry Pagets Dis Bone, Boston, MA 02114 USA. Novartis Pharmaceut, Hlth Econ & Outcomes Res, E Hanover, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S130 EP S130 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900372 ER PT J AU Chi, R Neuzil, KM Reiber, GE AF Chi, R Neuzil, KM Reiber, GE TI Influenza and pneumococcal vaccine coverage among older veterans: Results from the behavioral risk factor surveillance system. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S83 EP S84 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900237 ER PT J AU Chun, A Granieri, E Fernandez, H AF Chun, A Granieri, E Fernandez, H TI Evaluating fellows as teachers. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Mt Sinai Sch Med, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S37 EP S38 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900104 ER PT J AU DeCherrie, L Penrod, J Ornstein, K Hochman, T Boal, J AF DeCherrie, L Penrod, J Ornstein, K Hochman, T Boal, J TI Predictors of death among a homebound admission cohort of a home-based primary care program. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Mt Sinai Sch Med, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S201 EP S202 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900580 ER PT J AU DuBose, M Sasso, D Kenny, A Pilbeam, C Demay, M Kuchel, GA AF DuBose, M Sasso, D Kenny, A Pilbeam, C Demay, M Kuchel, GA TI Locomotion in vitamin D receptor gene knockout mice. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Univ Connecticut, Ctr Hlth, UConn Ctr Aging, Farmington, CT USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S212 EP S213 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900611 ER PT J AU Fox, AR Conn, V Guthrie, M AF Fox, AR Conn, V Guthrie, M TI Concealed weapons : firearm access among homebound veterans with depression and dementia. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S214 EP S214 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900615 ER PT J AU Hajjar, ER Hanlon, JT Sloane, RJ Lindblad, CI Pieper, CF Ruby, CM Branch, LC Schmader, KE AF Hajjar, ER Hanlon, JT Sloane, RJ Lindblad, CI Pieper, CF Ruby, CM Branch, LC Schmader, KE TI Unnecessary drug use in frail elderly at hospital discharge. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Univ Sci Philadelphia, Philadelphia Coll Pharm, Philadelphia, PA USA. Univ Pittsburgh, Dept Geriatr Med, Pittsburgh, PA USA. Ctr Hlth Equit Res & Promot, Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC USA. Univ Minnesota, Inst Study Geriatr Pharmacotherapy, Minneapolis, MN USA. Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Minneapolis, MN USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. Univ S Florida, Coll Publ Hlth, Tampa, FL USA. FU NIA NIH HHS [R01-AG-14158]; NIAID NIH HHS [K24-AI-51324-01] NR 0 TC 79 Z9 80 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S178 EP S178 DI 10.1111/j.1532-5415.2005.53523.x PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900515 PM 16137281 ER PT J AU Martin, JL Webber, AP Alam, T Harker, JO Josephson, KR Alessi, CA AF Martin, JL Webber, AP Alam, T Harker, JO Josephson, KR Alessi, CA TI Prevalence and correlates of daytime sleepiness in nursing home residents. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles, GRECC, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S178 EP S179 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900517 ER PT J AU Martin, K Rudolph, JL Chew, D AF Martin, K Rudolph, JL Chew, D TI Delirium after vascular surgery SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 VA Boston Healthcare Syst, GRECC, Boston, MA USA. Oklahoma State Sch Osteopath Med, Tulsa, OK USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S119 EP S119 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900340 ER PT J AU Munshi, M Grande, L Ayres, D Capelson, R Suhl, E Milberg, W Weinger, K AF Munshi, M Grande, L Ayres, D Capelson, R Suhl, E Milberg, W Weinger, K TI Subtle executive dysfunction is an important barrier to successful diabetes management in older adults. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Joslin Clin, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Geriatr, Boston, MA 02115 USA. Boston VA Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S213 EP S213 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900612 ER PT J AU Ray, LM Fang, MA Hahn, TJ AF Ray, LM Fang, MA Hahn, TJ TI The role of abnormal DXA results in the evaluation and treatment of low bone density in older male veterans SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S111 EP S111 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900317 ER PT J AU Rodriguez, KL Young, AJ AF Rodriguez, KL Young, AJ TI Patient and healthcare provider understanding of life-sustaining treatment. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Univ Memphis, Dept Commun, Memphis, TN 38152 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S96 EP S96 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900275 ER PT J AU Rudolph, JL Marcantonio, ER Jones, R Levkoff, SE AF Rudolph, JL Marcantonio, ER Jones, R Levkoff, SE TI Impaired frontal function is associated with postoperative delirium. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 VABHS, GRECC, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Rehabil Ctr Aged, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S217 EP S217 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900624 ER PT J AU Sims, RV Ahmed, A Baker, PS Allman, RM AF Sims, RV Ahmed, A Baker, PS Allman, RM TI Self-reported health predicts driving cessation among community-dwelling older adults. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Birmingham VAMC, Birmingham, AL USA. Univ Alabama Birmingham, Ctr Aging, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S195 EP S195 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900563 ER PT J AU Tang, J Atri, A Locascio, JJ Yap, L Growdon, JH AF Tang, J Atri, A Locascio, JJ Yap, L Growdon, JH TI Cognitive benefits of acetylcholinesterase inhibitors (ACHEI) therapy on Alzheimer's disease (AD) are sustained for 1 <+B-1 > 1 <+K20B0 >/<-K0B3 > 2 <-B0 > years of treatment. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Mt Sinai Sch Med, New York, NY USA. Massachusetts Gen Hosp, Alzheimers Dis Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S208 EP S208 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900599 ER PT J AU Walston, J Festa, F Ho, L Morrison, S Pasinetti, GM AF Walston, J Festa, F Ho, L Morrison, S Pasinetti, GM TI From biomarker discovery to clinical diagnostic in age-related frailty SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. Bronx Vet Adm Med Ctr, GRECC Program, Bronx, NY USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S120 EP S120 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900344 ER PT J AU Wong, M AF Wong, M TI Challenges in recruiting research subjects in dementia studies: The impact of undercoding dementia in the electronic medical record SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Massachusetts Gen Hosp, Geriatr Med Unit, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S128 EP S129 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900368 ER PT J AU Wu, P Lorenz, KA Rubenstein, LZ Chodosh, J AF Wu, P Lorenz, KA Rubenstein, LZ Chodosh, J TI Advance planning in the last year of life: How are we doing? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 UMDNJ SOM, Stratford, NJ USA. VA Greater Los Angeles Healthcare Syst, HSR&D, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S202 EP S202 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900582 ER PT J AU Teng, M Wolf, M Ofsthun, MN Lazarus, JM Hernan, MA Camargo, CA Thadhani, R AF Teng, M Wolf, M Ofsthun, MN Lazarus, JM Hernan, MA Camargo, CA Thadhani, R TI Activated injectable vitamin D and hemodialysis survival: A historical cohort study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC-RENAL-FAILURE; CORONARY-ARTERY CALCIFICATION; MARGINAL STRUCTURAL MODELS; RENIN-ANGIOTENSIN SYSTEM; RECEPTOR KNOCKOUT MICE; CANCER-MORTALITY-RATES; PARATHYROID-HORMONE; SECONDARY HYPERPARATHYROIDISM; 1,25-DIHYDROXYVITAMIN D-3; CALCITRIOL THERAPY AB Patients with ESRD commonly experience secondary hyperparathyroidism, a condition primarily managed with activated injectable vitamin D. The biologic effects of vitamin D, however, are widespread, and it is possible that activated injectable vitamin D alters survival in ESRD. This hypothesis was tested in a historical cohort study of incident hemodialysis patients who lived throughout the United States between January 1996 and December 1999. The primary outcome was 2-yr survival among those who survived for at least 90 d after initiation of chronic hemodialysis. During this period, 51,037 chronic hemodialysis patients survived for at least 90 d from the initiation of hemodialysis, and in the ensuing 2 yr, 37,173 received activated injectable vitamin D and 13,864 did not. At 2 yr, mortality rates were 13.8/100 person-years in the group that received injectable vitamin D compared with 28.6/100 person-years in the group that did not (P < 0.001). Cox proportional hazards analyses adjusting for several potential confounders and examining injectable vitamin D therapy as a time-dependent exposure suggested that compared with patients who did not receive injectable vitamin D, the 2-yr survival advantage associated with the group that did receive injectable vitamin D was 20% (hazard ratio, 0.80; 95% confidence interval, 0.76 to 0.83). The incidence of cardiovascular-related mortality was 7.6/100 person-years in the injectable vitamin D group, compared with 14.6/100 person-years in the non-vitamin D group (P < 0.001). The benefit of injectable vitamin D was evident in 48 of 49 strata examined, including those with low serum levels of intact parathyroid hormone and elevated levels of serum calcium and phosphorus, situations in which injectable vitamin D is often withheld. Repeating the entire analysis using marginal structural models to adjust for time-dependent confounding by indication yielded a survival advantage of 26% (hazard ratio, 0.74; 95% confidence interval, 0.71 to 0.79) associated with the injectable vitamin D group. In this historical cohort study, chronic hemodialysis patients in the group that received injectable vitamin D had a significant survival advantage over patients who did not. Randomized clinical trials would permit definitive conclusions. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. Fresenius Med Care N Amer, Lexington, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Thadhani, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Bulfinch 127,55 Fruit St, Boston, MA 02114 USA. EM thadhani.r@mgh.harvard.edu NR 64 TC 558 Z9 584 U1 1 U2 8 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 2005 VL 16 IS 4 BP 1115 EP 1125 DI 10.1681/ASN.2004070573 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 910MO UT WOS:000227935800035 PM 15728786 ER PT J AU Han, WK Alinani, A Wu, CL Michaelson, D Loda, M McGovern, FJ Thadhani, R Bonventre, JV AF Han, WK Alinani, A Wu, CL Michaelson, D Loda, M McGovern, FJ Thadhani, R Bonventre, JV TI Human kidney injury molecule-1 is a tissue and urinary tumor marker of renal cell carcinoma SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Nephrology CY OCT 27-NOV 01, 2004 CL St Louis, MO SP Amer Soc Nephrol ID MONOCLONAL-ANTIBODY; PROGNOSTIC-SIGNIFICANCE; PYRUVATE-KINASE; SUPPRESSOR GENE; CANCER-PATIENTS; TU M2-PK; EXPRESSION; ANTIGEN; CLASSIFICATION; HYPERMETHYLATION AB Human kidney injury molecule-1 (hKIM-1) is a type 1 transmembrane protein that is not detectable in normal kidney tissue but is expressed at high levels in human and rodent kidneys with dedifferentiated proximal tubule epithelial cells after ischemic or toxic injury. Therefore, it was hypothesized that renal tumors express hKIM-1 and release this protein into the urine. Forty renal cell carcinoma (RCC) and 484 nonrenal tumors were analyzed by immunohistochemistry for expression of hKIM-1 (group 1). Urine samples before nephrectomy and nephrectomy tissue samples were collected from an additional 42 patients with renal tumors, from 30 normal control subjects, and also from 10 patients with prostate carcinoma (group 2). In five additional patients with RCC, urine was collected before and after nephrectomy (group 3). Tissue was examined for expression of hKIM-1, and cell-free urine supernatants were analyzed for hKIM-1 by ELISA. Urinary hKIM-1 was normalized to the urinary creatinine concentration (U-Cr). Expression of hKIM-1 was present in 32 tissue sections (91%) of 35 clear cell RCC (group 1). In group 2, the normalized urinary hKIM-1 levels were significantly higher in patients with clear cell RCC (0.39 +/- 0.08 ng/mg U-Cr; n = 21), compared with levels in patients with prostate carcinoma (0.12 +/- 0.03 ng/mg U-Cr; P < 0.02; n = 10), or normal control subjects (0.05 +/- 0.01 ng/mg U-Cr; P < 0.005; n = 30). Tissue sections from 28 (82%) of 34 primary RCC stained positively for the expression of hKIM-1. In all patients with a detectable prenephrectomy urinary hKIM-1 level, there was either complete disappearance or marked reduction after nephrectomy (group 3). In conclusion, the cleaved ectodomain of hKIM-1 can be detected in the urine of patients with RCC and may serve as a new biomarker for early detection of RCC. C1 Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Serv Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Serv Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Serv Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Urol, Boston, MA 02115 USA. Dana Farber Canc Inst, Pathol Dept Med Oncol, Boston, MA 02115 USA. RP Bonventre, JV (reprint author), Harvard Univ, Inst Med, Div Renal, 4 Blackfan Circle,Room 550, Boston, MA 02115 USA. EM joseph_bonventre@hms.harvard.edu FU NIDDK NIH HHS [DK38452, 5F32DK10036, 5KO8DK64075, DK39773, DK46267, F32 DK010036, K08 DK064075, P01 DK038452, R01 DK039773, R01 DK046267, R37 DK039773] NR 45 TC 86 Z9 95 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 2005 VL 16 IS 4 BP 1126 EP 1134 DI 10.1681/ASN.2004070530 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 910MO UT WOS:000227935800036 PM 15744000 ER PT J AU Deans, KJ Haley, M Natanson, C Eichacker, PQ Minneci, PC AF Deans, KJ Haley, M Natanson, C Eichacker, PQ Minneci, PC TI Novel therapies for sepsis: A review SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Review DE glucocorticoids; sepsis; anti-inflammatory agent; anticoagulant agent; antithrombotic agent; steroids ID TUMOR-NECROSIS-FACTOR; FACTOR PATHWAY INHIBITOR; RANDOMIZED CONTROLLED-TRIAL; ACTIVATED PROTEIN-C; SEPTIC SHOCK; ANTITHROMBIN-III; DOUBLE-BLIND; DOSE CORTICOSTEROIDS; CORTISOL RESPONSE; ORGAN DYSFUNCTION AB Background. Over the past 30 years, efforts have been made to identify therapeutic targets in the host response to infection. Methods. A review of the randomized controlled clinical sepsis trials and meta-analyses of glucocorticoids, mediator-specific anti-inflammatory agents, and anticoagulant agents was performed. Results. The effects of glucocorticoids in sepsis appear to be dose-dependent, with high doses decreasing survival and low doses improving survival. As a class, the mediator-specific anti-inflammatory agents have a small beneficial effect on survival; however, no single agent has demonstrated significant benefit. The treatment effects of these agents appear to be related to the patient's risk of death. As a class, the anticoagulant agents do not improve survival; however, the efficacy of these agents may have been confounded by concurrent heparin therapy. Activated protein C demonstrated a beneficial effect on survival that was dependent on severity of illness. Conclusion. Trials of agents directed at altering the host's response during sepsis have had variable results, and it appears that several different factors may alter the efficacy of these agents. C1 NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Minneci, PC (reprint author), NIH, Crit Care Med Dept, Ctr Clin, Bldg 10,Room 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. EM pminneci@mail.cc.nih.gov NR 58 TC 84 Z9 88 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD APR PY 2005 VL 58 IS 4 BP 867 EP 874 DI 10.1097/01.TA.0000158244.69179.94 PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 919VS UT WOS:000228646300051 PM 15824673 ER PT J AU Song, B Javanbakht, H Perron, M Park, DH Stremlau, M Sodroski, J AF Song, B Javanbakht, H Perron, M Park, DH Stremlau, M Sodroski, J TI Retrovirus restriction by TRIM5 alpha variants from old world and new world primates SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CROSS-SPECIES TRANSMISSIONS; BABOON ENDOGENOUS VIRUS; MURINE LEUKEMIA-VIRUS; BROAD-HOST-RANGE; REVERSE TRANSCRIPTION; SIMIAN CELLS; MONKEY CELLS; HIV-1; REPLICATION AB The TRIM5 alpha proteins of humans and some Old World monkeys have been shown to block infection of particular retroviruses following virus entry into the host cell. Infection of most New World monkey cells by the simian immunodeficiency virus of macaques (SIVmac) is restricted at a similar point. Here we examine the antiretroviral activity of TRIM5 alpha orthologs from humans, apes, Old World monkeys, and New World monkeys. Chimpanzee and orangutan TRIM5 alpha proteins functionally resembled human TRIM5 alpha, potently restricting infection by N-tropic murine leukemia virus (N-MLV) and moderately restricting human immunodeficiency virus type 1 (HIV-1) infection. Notably, TRIM5 alpha proteins from several New World monkey species restricted infection by SIVmac and the SIV of African green monkeys, SIVagm. Spider monkey TRIM5 alpha, which has an expanded B30.2 domain v3 region due to a tandem triplication, potently blocked infection by a range of retroviruses, including SIVmac, SIVagm, HIV-1, and N-MLV. Tandem duplications in the TRIM5 alpha B30.2 domain v1 region of African green monkeys are also associated with broader antiretroviral activity. Thus, variation in TRIM5 alpha proteins among primate species accounts for the observed patterns of postentry restrictions in cells from these animals. The TRIM5 alpha proteins of some monkey species exhibit dramatic lengthening of particular B30.2 variable regions and an expanded range of susceptible retroviruses. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Div AIDS,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Div AIDS,Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NHLBI NIH HHS [HL54785, P50 HL054785]; NIAID NIH HHS [AI063987, P030 AI28691, P30 AI028691, R01 AI063987] NR 49 TC 169 Z9 172 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 7 BP 3930 EP 3937 DI 10.1128/JVI.79.7.3930-3937.2005 PG 8 WC Virology SC Virology GA 907UO UT WOS:000227743700004 PM 15767395 ER PT J AU Love, TM de Jesus, R Kean, JA Sheng, Q Leger, A Schaffhausen, B AF Love, TM de Jesus, R Kean, JA Sheng, Q Leger, A Schaffhausen, B TI Activation of CREB/ATF sites by polyomavirus large T antigen SO JOURNAL OF VIROLOGY LA English DT Article ID DNA-BINDING DOMAIN; RAT EMBRYO FIBROBLASTS; HSP70 GENE PROMOTER; SIMIAN VIRUS-40; TUMOR-ANTIGEN; CYCLIN-A; TRANSCRIPTIONAL ACTIVATION; SV40-TRANSFORMED CELLS; RETINOBLASTOMA PROTEIN; MOUSE FIBROBLASTS AB Polyomavirus large T antigen (LT) has a direct role in viral replication and a profound effect on cell phenotype. It promotes cell cycle progression, immortalizes primary cells, blocks differentiation, and causes apoptosis. While much of large T function is related to its effects on tumor suppressors of the retinoblastoma susceptibility (Rb) gene family, we have previously shown that activation of the cyclin A promoter can occur through a non-Rb-dependent mechanism. Here we show that activation occurs via an ATF/CREB site. Investigation of the mechanism indicates that large T can synergize with CREB family members to activate transcription. Experiments with Gal4-CREB constructs show that synergy is independent of CREB phosphorylation by protein kinase A. Examination of synergy with Gal4-CREB deletion constructs indicates that large T acts on the constitutive activation domain of CREB. Large T can bind to CREB in vivo. Genetic analysis shows that the DNA-binding domain (residues 264 to 420) is sufficient to activate transcription when it is localized to the nucleus. Further analysis of the DNA-binding domain shows that while site-specific DNA binding is not required, non-site-specific DNA binding is important for the activation. Thus, CREB binding and DNA binding are both important for large T activation of CREB/ATF sites. In contrast to previous models where large IF transactivation occurred indirectly, these results also suggest that large IF can act directly at promoters to activate transcription. C1 Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Schaffhausen, B (reprint author), Tufts Univ, Sch Med, Dept Biochem, 136 Harrison Ave, Boston, MA 02111 USA. EM brian.schaffhausen@tufts.edu FU NCI NIH HHS [R01 CA034722]; NIAID NIH HHS [AI34722] NR 88 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 7 BP 4180 EP 4190 DI 10.1128/JVI.79.7.4180-4190.2005 PG 11 WC Virology SC Virology GA 907UO UT WOS:000227743700028 PM 15767419 ER PT J AU Ibarrondo, FJ Anton, PA Fuerst, M Ng, HL Wong, JT Matud, J Elliott, J Shih, R Hausner, MA Price, C Hultin, LE Hultin, PM Jamieson, BD Yang, OO AF Ibarrondo, FJ Anton, PA Fuerst, M Ng, HL Wong, JT Matud, J Elliott, J Shih, R Hausner, MA Price, C Hultin, LE Hultin, PM Jamieson, BD Yang, OO TI Parallel human immunodeficiency virus type 1-specific CD8(+) T-lymphocyte responses in blood and mucosa during chronic infection SO JOURNAL OF VIROLOGY LA English DT Article ID COMBINATION ANTIRETROVIRAL THERAPY; IMMUNE-RESPONSES; CELL RESPONSES; HIV-INFECTION; VIRAL LOAD; ESCAPE MUTATION; NEW-GENERATION; SIV INFECTION; TRANSMISSION; VACCINES AB Gut-associated lymphoid tissue is the major reservoir of lymphocytes and human immunodeficiency virus type I (HIV-1) replication in vivo, yet little is known about HIV-1-specific CD8(+) T-lymphocyte (CTL) responses in this compartment. Here we assessed the breadth and magnitude of HIV-1-specific CTL in the peripheral blood and sigmoid colon mucosa of infected subjects not on antiretroviral therapy by enzyme-linked immunospot analysis with 53 peptide pools spanning all viral proteins. Comparisons of blood and mucosal CTL revealed that the magnitude of pool-specific responses is correlated within each individual (mean r(2) = 0.82 +/- 0.04) and across all individuals (r(2) = 0.75; P < 0.001). Overall, 85.1% of screened peptide pools yielded concordant negative or positive results between compartments. CTL targeting was also closely related between blood and mucosa, with Nef being the most highly targeted (mean of 2.4 spot-forming cells [SFC[/10(6) CD8(+) T lymphocytes/amino acid [SFC/CD8/aa]), followed by Gag (1.5 SFC/CD8/aa). Finally, comparisons of peptide pool responses seen in both blood and mucosa (concordant positives) versus those seen only in one but not the other (discordant positives) showed that most discordant results were likely an artifact of responses being near the limit of detection. Overall, these results indicate that HIV-1-specific CTL responses in the blood mirror those seen in the mucosal compartment in natural chronic infection. For protective or immunotherapeutic vaccination, it will be important to determine whether immunity is elicited in the mucosa, which is a key site of initial infection and subsequent HIV-1 replication in vivo. C1 Univ Calif Los Angeles, Ctr Med, Geffen Sch Med, AIDS Inst,Div Infect Dis, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Ctr Med, Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Yang, OO (reprint author), Univ Calif Los Angeles, Ctr Med, Geffen Sch Med, AIDS Inst,Div Infect Dis, 37-121 CHS,10833 LeConte Ave, Los Angeles, CA 90095 USA. EM oyang@mednet.ucla.edu FU NCI NIH HHS [CA-16042, P30 CA016042]; NIAID NIH HHS [P30 AI028697, U01 AI037613, AI37613, AI28697, AI050467, AI043203, AI01620, R01 AI043203]; NIDDK NIH HHS [DK050467] NR 42 TC 42 Z9 44 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 7 BP 4289 EP 4297 DI 10.1128/JVI.79.7.4289-4297.2005 PG 9 WC Virology SC Virology GA 907UO UT WOS:000227743700038 PM 15767429 ER PT J AU Seaman, MS Santra, S Newberg, MH Philippon, V Manson, K Xu, L Gelman, RS Panicali, D Mascola, JR Nabel, GJ Letvin, NL AF Seaman, MS Santra, S Newberg, MH Philippon, V Manson, K Xu, L Gelman, RS Panicali, D Mascola, JR Nabel, GJ Letvin, NL TI Vaccine-elicited memory cytotoxic T lymphocytes contribute to Mamu-A*01-associated control of simian/human immunodeficiency virus 89.6P replication in rhesus monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULE; DISEASE PROGRESSION; IMMUNE-RESPONSES; INFECTION; HIV-1; AIDS; PROTECTION; EPITOPES; PREVENTION AB The expression of particular major histocompatibility complex (MHC) class I alleles can influence the rate of disease progression following lentiviral infections. This effect is a presumed consequence of potent cytotoxic T-lymphocyte (CTL) responses that are restricted by these MHC class I molecules. The present studies have examined the impact of the MHC class I allele Mamu-A*01 on simian/human immunodeficiency virus 89.6P (SHIV-89.6P) infection in unvaccinated and vaccinated rhesus monkeys by exploring the contribution of dominant-epitope specific CTL in this setting. Expression of Mamu-A*01 in immunologically naive monkeys was not associated with improved control of viral replication, CD4(+) T-lymphocyte loss, or survival. In contrast, Mamu-A*01(+) monkeys that had received heterologous prime/boost immunizations prior to challenge maintained higher CD4(+) T-lymphocyte levels and better control of SHIV-89.6P replication than Mamu-A*01(-) monkeys. This protection was associated with the evolution of high-frequency anamnestic CTL responses specific for a dominant Mamu-A*01-restricted Gag epitope following infection. These data indicate that specific MHC class I alleles can confer protection in the setting of a pathogenic SHIV infection by their ability to elicit memory CTL following vaccination. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Therion Biol, Cambridge, MA USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Letvin, NL (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis, 330 Brookline Ave,RE-113, Boston, MA 02215 USA. EM nletvin@bidmc.harvard.edu FU NIAID NIH HHS [N01AI30033, AI30033] NR 29 TC 22 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 4580 EP 4588 DI 10.1128/JVI.79.8.4580-4588.2005 PG 9 WC Virology SC Virology GA 912JJ UT WOS:000228073700003 PM 15795244 ER PT J AU Peretz, Y Alter, G Boisvert, MP Hatzakis, G Tsoukas, CM Bernard, NF AF Peretz, Y Alter, G Boisvert, MP Hatzakis, G Tsoukas, CM Bernard, NF TI Human immunodeficiency virus (HIV)-specific gamma interferon secretion directed against all expressed HIV genes: Relationship to rate of CD4 decline SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; PLASMA VIRAL LOAD; NECROSIS-FACTOR-ALPHA; HLA CLASS-I; CELL RESPONSES; TYPE-1 INFECTION; DISEASE PROGRESSION; IMMUNE ACTIVATION; ESCAPE MUTATIONS; VIREMIA AB Immune responses to human immunodeficiency virus (HIV) are detected at all stages of infection and are believed to be responsible for controlling viremia. This study seeks to determine whether gamma interferon (IFN-gamma)-secreting HIV-specific T-cell responses influence disease progression as defined by the rate of CD4 decline. The study population consisted of 31 subjects naive to antiretroviral therapy. All were monitored clinically for a median of 24 months after the time they were tested for HIV-specific responses. The rate of CD4(+)-T-cell loss was calculated for all participants from monthly CD4 counts. Within this population, 17 subjects were classified as typical progressors, 6 subjects were classified as fast progressors, and 8 subjects were classified as slow progressors. Peripheral blood mononuclear cells were screened for HIV-specific IFN-gamma responses to all expressed HIV genes. Among the detected immune responses, 48% of the recognized peptides were encoded by Gag and 19% were encoded by Nef gene products. Neither the breadth nor the magnitude of HIV-specific responses correlated with the viral load or rate of CD4 decline. The breadth and magnitude of HIV-specific responses did not differ significantly among typical, fast, and slow progressors. These results support the conclusion that although diverse HIV-specific IFN-gamma-secreting responses are mounted during the asymptomatic phase, these responses do not seem to modulate disease progression rates. C1 McGill Univ, Res Inst, Ctr Hlth, Montreal, PQ H3G 1A4, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bernard, NF (reprint author), McGill Univ, Res Inst, Ctr Hlth, 1650 Cedar Ave,Rm C10-160, Montreal, PQ H3G 1A4, Canada. EM nicole.bernard@mcgill.ca NR 68 TC 26 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 4908 EP 4917 DI 10.1128/JVI.79.8.4908-4917.2005 PG 10 WC Virology SC Virology GA 912JJ UT WOS:000228073700035 PM 15795276 ER PT J AU Poon, B Safrit, JT McClure, H Kitchen, C Hsu, JF Gudeman, V Petropoulos, C Wrin, T Chen, ISY Grovit-Ferbas, K AF Poon, B Safrit, JT McClure, H Kitchen, C Hsu, JF Gudeman, V Petropoulos, C Wrin, T Chen, ISY Grovit-Ferbas, K TI Induction of humoral immune responses following vaccination with envelope-containing, formaldehyde-treated, thermally inactivated human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING ANTIBODIES; SOLUBLE CD4; HIV TYPE-1; CHEMICAL INACTIVATION; GP120 GLYCOPROTEIN; SIV VACCINE; IN-VITRO; INFECTIVITY; PROTEINS; MACAQUES AB The lack of success of subunit human immunodeficiency virus type 1 (HIV-1) vaccines to date suggests that multiple components or a complex virion structure may be required. We previously demonstrated retention of the major conformational epitopes of HIV-1 envelope following thermal treatment of virions. Moreover, antibody binding to some of these epitopes was significantly enhanced following thermal treatment. These included the neutralizing epitopes identified by monoclonal antibodies 1b12, 2G12, and 17b, some of which have been postulated to be partially occluded or cryptic in native virions. Based upon this finding, we hypothesized that a killed HIV vaccine could be derived to elicit protective humoral immune responses. Shedding of HIV-1 envelope has been described for some strains of HIV-1 and has been cited as one of the major impediments to developing an inactivated HIV-1 vaccine. In the present study, we demonstrate that treatment of virions with low-dose formaldehyde prior to thermal inactivation retains the association of viral envelope with virions. Moreover, mice and nonhuman primates vaccinated with formaldehyde-treated, thermally inactivated virions produce antibodies capable of neutralizing heterologous strains of HIV in peripheral blood mononuclear cell-, MAGI cell-, and U87-based infectivity assays. These data indicate that it is possible to create an immunogen by using formaldehyde-treated, thermally inactivated HIV-1 virions to induce neutralizing antibodies. These findings have broad implications for vaccine development. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, AIDS Inst, Los Angeles, CA USA. Elizabeth Glaser Pediat AIDS Fdn, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Biostat, Ctr Hlth Sci, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. ViroLog Inc, San Francisco, CA USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. RP Grovit-Ferbas, K (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, 11-934 Factor Bldg, Los Angeles, CA 90095 USA. EM kferbas@ucla.edu FU NCI NIH HHS [CA016042, P30 CA016042]; NCRR NIH HHS [P51 RR000165, RR-00165]; NIAID NIH HHS [1R01AI052012, AI028697, R21AI42687, P30 AI028697, R01 AI052012] NR 46 TC 28 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 4927 EP 4935 DI 10.1128/JVI.79.8.4927-4935.2005 PG 9 WC Virology SC Virology GA 912JJ UT WOS:000228073700037 PM 15795278 ER PT J AU Altfeld, M Allen, TM Kalife, ET Frahm, N Addo, MM Mothe, BR Rathod, A Reyor, LL Harlow, J Yu, XG Perkins, B Robinson, LK Sidney, J Alter, G Lichterfeld, M Sette, A Rosenberg, ES Goulder, PJR Brander, C Walker, BD AF Altfeld, M Allen, TM Kalife, ET Frahm, N Addo, MM Mothe, BR Rathod, A Reyor, LL Harlow, J Yu, XG Perkins, B Robinson, LK Sidney, J Alter, G Lichterfeld, M Sette, A Rosenberg, ES Goulder, PJR Brander, C Walker, BD TI The majority of currently circulating human immunodeficiency virus type 1 clade B viruses fail to prime cytotoxic T-lymphocyte responses against an otherwise immunodominant HLA-A2-restricted epitope: Implications for vaccine design SO JOURNAL OF VIROLOGY LA English DT Article ID PRIMARY INFECTION; IMMUNE-RESPONSES; ESCAPE MUTATION; VIRAL DIVERSITY; HIV-INFECTION; HLA; TRANSMISSION; REVERSION; SELECTION; HLA-A-ASTERISK-0201 AB Human immunodeficiency virus type 1 (HIV-1) mutates to escape immune selection pressure, but there is little evidence of selection mediated through HLA-A2, the dominant class I allelle in persons infected with clade B virus. Moreover, HLA-A2-restrieted responses are largely absent in the acute phase of infection as the viral load is being reduced, suggesting that circulating viruses may lack immunodominant epitopes targeted through HLA-A2. Here we demonstrate an A2-restricted epitope within Vpr (Vpr(59-67)) that is targeted by acute-phase HIV-1-specific CD8(+) T cells, but only in a subset of persons expressing HLA-A2. Individuals in the acute stage of infection with viruses containing the most common current sequence within this epitope (consensus sequence) were unable to mount epitope-specific T-cell responses, whereas subjects infected with the less frequent 16,L variant all developed these responses. The 1,,L variant epitope was a stronger binder to HILA-A2 and was recognized by epitope-specific T cells at lower peptide concentrations than the consensus sequence epitope. These data demonstrate that HLA-A2 is capable of contributing to the acute-phase cytotoxic T-lymphocyte response in infected subjects, but that most currently circulating viruses lack a dominant immunogenic epitope presented by this allele, and suggest that immunodominant epitopes restricted by common HLA alleles may be lost as the epidemic matures. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA USA. Howard Hughes Med Inst, San Diego, CA USA. La Jolla Inst Allergy & Immunol, San Diego, CA USA. Calif State Univ San Marcos, Dept Biol Sci, San Marcos, CA USA. Nuffield Dept Med, Dept Pediat, Oxford, England. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Boston, MA 02129 USA. EM maltfeld@partners.org RI Allen, Todd/F-5473-2011 NR 30 TC 33 Z9 33 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 5000 EP 5005 DI 10.1128/JVI.8.5000-5005.2005 PG 6 WC Virology SC Virology GA 912JJ UT WOS:000228073700044 PM 15795285 ER PT J AU Beeri, MS Silverman, JM Davis, KL Marin, D Grossman, HZ Schmeidler, J Purohit, DP Perl, DP Davidson, M Mohs, RC Haroutunian, V AF Beeri, MS Silverman, JM Davis, KL Marin, D Grossman, HZ Schmeidler, J Purohit, DP Perl, DP Davidson, M Mohs, RC Haroutunian, V TI Type 2 diabetes is negatively associated with Alzheimer's disease neuropathology SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID BLOOD-BRAIN-BARRIER; RISK-FACTORS; COGNITIVE DECLINE; DEMENTIA; MELLITUS; POPULATION; EPSILON-4; GLUCOSE; MEMORY; HYPERINSULINEMIA AB Background. In cross-sectional and longitudinal studies, type 2 diabetes has been positively associated with the risk of Alzheimer's disease (AD). The present descriptive study compared diabetic and nondiabetic Subjects on the severity of neuritic plaques and neurofibrillary tangles (NFTs) in the cerebral cortex and in the hippocampus. Methods. The study included specimens from 385 consecutive autopsies of residents of a nursing home (15.8% diabetics). Mean age at death = 84 years [standard deviation (SD) = 10], 66% were female, Clinical Dementia Rating mean = 3.0 (SD = 1.6), and 32.5% had an APOE4 allele. Additional analyses limited the sample to 268 subjects (14.1% diabetics) without neuropathology other than AD. Results. Analyses of covariance controlling for age at death, dementia severity (Clinical Dementia Rating score), and APOE4 allele indicated that diabetics had significantly fewer neuritic plaques (p = .008) and NFTs (p = .047) in the cerebral cortex than did nondiabetics. In the hippocampus, diabetics had significantly lower plaque ratings than did nondiabetics (p = .019), but the lower ratings of NFTs did not achieve statistical significance (p = .082). In the entire sample, diabetics had significantly less AD-associated neuropathology in all four analyses. Conclusions. These results raise the possibility that the varied associations observed between diabetes and AD may be specific to as yet ill-defined subgroups of dementia and diabetic patients or may be more characteristic Of Younger patients than of those who survive to a mean age of 84 years. Future studies are encouraged to examine a variety of other characteristics such as age that may interact with diabetes affecting the incidence of AD. C1 Bronx Vet Adm Med Ctr, Psychiat Serv, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Mt Sinai Sch Med, Dept Biomath Sci, New York, NY USA. Mt Sinai Sch Med, Dept Pathol, New York, NY USA. Chaim Sheba Med Ctr, Dept Psychiat, IL-52621 Tel Hashomer, Israel. Lilly Res Labs, Indianapolis, IN USA. RP Haroutunian, V (reprint author), Bronx Vet Adm Med Ctr, Psychiat Serv, Psychiat Res 4F-33B,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Vahram.Haroutunian@mssm.edu FU NIA NIH HHS [K01 AG023515, K01 AG023515-05, P01 AG002219, P01-AG02219] NR 41 TC 89 Z9 92 U1 3 U2 9 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 APR PY 2005 VL 60 IS 4 BP 471 EP 475 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 928VX UT WOS:000229300900011 PM 15933386 ER PT J AU Sohn, M Tan, Y Klein, RL Jaffa, AA AF Sohn, M Tan, Y Klein, RL Jaffa, AA TI Evidence for low-density lipoprotein-induced expression of connective tissue growth factor in mesangial cells SO KIDNEY INTERNATIONAL LA English DT Article DE MAPK; TGF-beta; collagen I; JNK ID DEPENDENT DIABETIC-PATIENTS; EARLY NATURAL-HISTORY; FACTOR-BETA; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; RENAL FIBROSIS; HIGH GLUCOSE; KINASE; NEPHROPATHY; DISEASE AB Background. Although hyperlipidemia is a risk factor for the progression of renal damage, the relationship between increased plasma lipoproteins and glomerular injury is poorly defined. Connective tissue growth factor (CTGF) is emerging as a key determinant of progressive fibrotic diseases and its expression is up-regulated by diabetes. To define the mechanisms through which low-density lipoproteins (LDLs) promote glomerular injury, we evaluated whether LDL can modulate the expression of CTGF and collagen I. Methods. The effects of LDL on CTGF and collagen I expression were carried out in rat mesangial cells. Results. Treatment of mesangial cells with LDL for 24 hours produced a significant increase in the protein levels of CTGF and collagen I compared to unstimulated controls. To explore if CTGF and collagen I are downstream targets for regulation by transforming growth factor-beta (TGF-beta), mesangial cells were treated with various concentration of TGF-beta for 24 hours. TGF-beta produced a concentration-dependent increase in the protein levels of CTGF and collagen I. The increase in CTGF and collagen I induced by LDL was significantly inhibited by neutralizing anti-TGF-beta antibodies. Inhibition of p38(mapk) or p42/44(mapk) activities did not affect LDL-induced TGF-beta 1, CTGF, and collagen I expression, whereas inhibition of c-Jun NH2-terminal kinase (JNK) suppressed LDL-induced TGF-beta, CTGF, and collagen I expression. Conclusion. These findings implicate JNK pathway and TGF-beta 1 as key players in LDL signaling leading to CTGF and collagen I expression in mesangial cells. The data also point to a potential mechanistic pathway through which lipoproteins may promote glomerular injury. C1 Med Univ S Carolina, Dept Med Endocrinol Diabet Med Genet, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Jaffa, AA (reprint author), Med Univ S Carolina, Dept Med Endocrinol Diabet Med Genet, 114 Doughty St,POB 250776, Charleston, SC 29425 USA. EM jaffaa@musc.edu FU NHLBI NIH HHS [HL-55782]; NIDDK NIH HHS [DK-46543] NR 47 TC 11 Z9 15 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD APR PY 2005 VL 67 IS 4 BP 1286 EP 1296 DI 10.1111/j.1523-1755.2005.00206.x PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 905UR UT WOS:000227596500008 PM 15780081 ER PT J AU Khan, AM Handzel, O Burgess, BJ Damian, D Eddington, DK Nadol, JB AF Khan, AM Handzel, O Burgess, BJ Damian, D Eddington, DK Nadol, JB TI Is word recognition correlated with the number of surviving spiral ganglion cells and electrode insertion depth in human subjects with cochlear implants? SO LARYNGOSCOPE LA English DT Article DE cochlear implant; depth of insertion; speech perception; spiral ganglion ID SENSORINEURAL HEARING-LOSS; SPEECH-PERCEPTION; HISTOPATHOLOGY; PREDICTORS; RECONSTRUCTION; PERFORMANCE; MONKEYS AB Objectives/Hypothesis: Speech perception scores using cochlear implants have ranged widely in all published series. The underlying determinants of success in word recognition are incompletely defined. Although it has been assumed that residual spiral ganglion cell population in the deaf ear may play a critical role, published data from temporal bone specimens from patients have not supported this hypothesis. The depth of insertion of a multichannel cochlear implant has also been suggested as a clinical variable that may be correlated with word recognition. In the current study these correlations were evaluated in 15 human subjects. Study Design: Retrospective review of temporal bone histopathology. Methods: Temporal bones were fixed and prepared for histological study by standard techniques. Specimens were then serially sectioned and reconstructed by two-dimensional methods. The spiral ganglion cells were counted, and the depth of insertion of the cochlear implant as measured from the round window was determined. Correlation analyses were then performed between the NU6 word scores and spiral ganglion cell counts and the depth of insertion. Results: The segmental and total spiral ganglion cell counts were not significantly correlated (P > .50) with NU6 word scores for the 15 subjects. Statistically significant correlations were not achieved by separate analysis of implant types. Similarly, no significant correlation between the depth of insertion of the electrode array and postoperative NU6 word score was identified for the group. Conclusion: Although it is unlikely that the number of residual spiral ganglion cell counts is irrelevant to the determination of word recognition following cochlear implantation, there are, clearly, other clinical variables not yet identified that play an important role in determining success with cochlear implantation. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. OI Handzel, Ophir/0000-0002-6905-3034 FU NIDCD NIH HHS [5-R01 DC00152-23] NR 31 TC 78 Z9 81 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 2005 VL 115 IS 4 BP 672 EP 677 DI 10.1097/01.mlg.0000161335.62139.80 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 915EI UT WOS:000228280300021 PM 15805879 ER PT J AU Ganz, RA Viveiros, J Ahmad, A Ahmadi, A Khalil, A Tolkoff, MJ Nishioka, NS Hamblin, MR AF Ganz, RA Viveiros, J Ahmad, A Ahmadi, A Khalil, A Tolkoff, MJ Nishioka, NS Hamblin, MR TI Helicobacter pylori in patients can be killed by visible light SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE porphyrin; photodynamic therapy; phototherapy; gastric biopsy; diode laser; endoscopy; gastric ulcer ID PHOTODYNAMIC THERAPY; PROPIONIBACTERIUM-ACNES; BLUE-LIGHT; ERADICATION; BACTERIA; PHOTOSENSITIZER; PORPHYRINS; INFECTION; QUADRUPLE AB Background: Helicobacter pylori colonizes the mucus layer of the human stomach and may cause peptic ulcer and adenocarcinoma. Novel antimicrobial approaches are sought due to the occurrence of antibiotic resistance and consequent treatment failure. We report here that H. pylori is susceptible to inactivation by blue light. Study Design/Materials and Methods: A controlled, prospective, blinded, trial of endoscopically delivered blue light to eradicate H. pylori in regions of the gastric antrum, in 10 patients between the ages of 21 and 80 who tested positive for H. pylori. Light (405 nm) (40 J/cm(2)) was delivered to a I-cm diameter spot in the gastric antrum via optical fiber passed through the endoscope and weighed biopsies were taken from treated and control spots and colonies quantitatively cultured. Results: Blue light killed 5 logs of bacteria in vitro. The mean reduction in H. pylori colonies per gram tissue between treated and control spots was 91% (7.4 +/- 4.8 x 10(6) VS. 8.1 +/- 1.9 x 10(7), two-tailed P < 0.0001). Some patients had reductions approaching 99%. No differences were observed on histological examination of light-treated and control gastric tissue. Conclusion: Blue light phototherapy may represent a novel approach to eradication of H. pylori, particularly, in patients who have failed standard antibiotic treatment. (c) 2005 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, BAR314B, Wellman Ctr Photomed, Boston, MA 02114 USA. Sterilite LLC, Minnetonka, MN USA. Abbott NW Hosp, Dept Gastroenterol, Minneapolis, MN 55407 USA. Seedling Enterprises LLC, Boston, MA USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, BAR314B, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01 AI050875, R01 AI050875-01A2, R01AI050879] NR 27 TC 53 Z9 57 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD APR PY 2005 VL 36 IS 4 BP 260 EP 265 DI 10.1002/lsm.20161 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 922EK UT WOS:000228819000002 PM 15791671 ER PT J AU Whitehead, VM Shuster, JJ Vuchich, MJ Mahoney, DH Lauer, SJ Payment, C Koch, PA Cooley, LD Look, AT Pullen, DJ Camitta, B AF Whitehead, VM Shuster, JJ Vuchich, MJ Mahoney, DH Lauer, SJ Payment, C Koch, PA Cooley, LD Look, AT Pullen, DJ Camitta, B TI Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts and treatment outcome in children with B-progenitor-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study SO LEUKEMIA LA English DT Article DE methotrexate; polyglutamates; acute lymphoblastic leukemia; treatment ID DOSE INTRAVENOUS METHOTREXATE; BONE-MARROW CELLS; CHILDHOOD; THERAPY; RISK; CHEMOTHERAPY; TRIAL; INTENSIFICATION; LINEAGE; PLOIDY AB We reported that children with B-progenitor-cell acute lymphoblastic leukemia (BpALL) treated in the early 1980s whose lymphoblasts accumulated high levels of methotrexate (MTX) and of methotrexate polyglutamates (MTXPGs) in vitro had an improved 5-year event-free survival (EFS) (65% ( standard error (s.e.) 12%) vs 22% (s.e. 9%)). We repeated this study in children with BpALL treated in the early 1990s. The major change in treatment was the addition of 12 24-h infusions of 1 g/M-2 MTX with leucovorin rescue (IDMTX). In 87 children treated on Pediatric Oncology Group (POG) study 9005 and POG 9006, the 5-year EFS for those whose lymphoblasts accumulated high levels of MTX and MTXPGs (79.2%, s.e. 8.3%) was not significantly different from that of patients with lesser accumulation of MTX and MTXPGs (77.7%, s. e. 5.4%). These findings support the notion that higher dose MTX therapy has contributed to increased cure, particularly for patients whose lymphoblasts accumulate the drug less well. C1 McGill Univ, Montreal Childrens Hosp, Res Inst, Penny Cole Hematol Res Lab, Montreal, PQ H3H 1P3, Canada. McGill Univ, Dept Pediat, Montreal, PQ H3A 2T5, Canada. Univ Florida, Childrens Oncol Grp Res Data Ctr, Coll Med, Dept Stat, Gainesville, FL USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. Childrens Mercy Hosp, Med Genet Sect, Dept Pediat, Kansas City, MO 64108 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Mississippi, Med Ctr, Dept Pediat, Jackson, MS 39216 USA. Med Coll Wisconsin, Midwest Childrens Canc Ctr, Dept Pediat, Milwaukee, WI 53226 USA. RP Whitehead, VM (reprint author), 1501 Mont Echo Rd, Sutton, PQ J0E 2K0, Canada. EM vmwhitehead@citenet.net FU NCI NIH HHS [CA-25408, CA-03161, CA-15989, CA-28841, CA-29139, CA-29691, CA-31566, CA-32053, CA-33587, CA-33625, CA-52317, CA-53490] NR 25 TC 11 Z9 12 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 APR PY 2005 VL 19 IS 4 BP 533 EP 536 DI 10.1038/sj.leu.2403703 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 909LB UT WOS:000227860300008 PM 15716987 ER PT J AU Moorman, AV Raimondi, SC Pui, CH Baruchel, A Biondi, A Carroll, AJ Forestier, E Gaynon, PS Harbott, J Harms, DO Heerema, N Pieters, R Schrappe, M Silverman, LB Vilmer, E Harrison, CJ AF Moorman, AV Raimondi, SC Pui, CH Baruchel, A Biondi, A Carroll, AJ Forestier, E Gaynon, PS Harbott, J Harms, DO Heerema, N Pieters, R Schrappe, M Silverman, LB Vilmer, E Harrison, CJ CA Ponte Di Legno Working Grp TI No prognostic effect of additional chromosomal abnormalities in children with acute lymphoblastic leukemia and 11q23 abnormalities SO LEUKEMIA LA English DT Article DE acute lymphoblastic leukemia; childhood; infant; cytogenetics; 11q23; MLL ID FLT3 MUTATIONS; CHILDHOOD; REARRANGEMENTS; ABERRATIONS; T(4-11)(Q21-Q23); TRANSLOCATIONS; MALIGNANCIES; DELETION; INFANT AB This study characterized the additional chromosomal abnormalities (ACA) associated with 11q23 rearrangements in 450 infants and children with acute lymphoblastic leukemia ( ALL) and examined the impact of these ACA on survival. Overall, 213 (47%) cases had ACA but the incidence varied according to patient age and 11q23 subgroup. Infants and patients with t(4; 11)(q21; q23) had the lowest incidence of ACA (50/182 (27%) and 57/216 (26%) respectively), whereas patients with del( 11)( q23) had the highest incidence (66/93 (71%)). Del( 11)( q23) abnormalities were heterogeneous and occasionally secondary to t( 9; 22)(q34; q11.2). Thus, patients with del( 11)( q23) comprised a separate biological entity, which was clearly distinct from those with an 11q23 translocation. The most frequent specific ACA were trisomy X ( n = 38), abnormal 12p ( n = 32), abnormal 9p ( n = 28) and del( 6q) ( n = 19). The presence of ACA did not change the 5 year event-free survival estimates among children (56% (95% CI 46 - 65%) vs 62% (54 - 69%)) or infants (22% ( 15 - 29%) vs 18% ( 9 - 29%)), nor when the different 11q23 subgroups were analyzed separately. This study has conclusively demonstrated that there is no prognostic effect of secondary chromosomal changes in association with 11q23 abnormalities in childhood ALL. However, characterization of these ACA is important to determine their potential role in initiation of MLL driven leukemogenesis. C1 Univ Southampton, Canc Sci Div, LRF Cytogenet Grp, Southampton SO16 6YD, Hants, England. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. Umea Univ, Umea, Sweden. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Moorman, AV (reprint author), Univ Southampton, Southampton Gen Hosp, Canc Sci Div, LRF Cytogenet Grp, MP 822,Duthie Bldg,Tremona Rd, Southampton SO16 6YD, Hants, England. EM avm@soton.ac.uk RI Moorman, Anthony/F-5518-2010; Schrappe, Martin/A-8109-2010; Moorman, Anthony/G-1468-2014 OI Moorman, Anthony/0000-0002-9781-6107 FU NCI NIH HHS [CA21765, CA36401, CA51001, CA60419, CA78224]; NIGMS NIH HHS [GM61393] NR 23 TC 11 Z9 11 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 APR PY 2005 VL 19 IS 4 BP 557 EP 563 DI 10.1038/sj.leu.2403695 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 909LB UT WOS:000227860300012 PM 15744345 ER PT J AU Okuda, K Oda, A Sato, Y Nakayama, A Fujita, H Sonoda, Y Griffin, JD AF Okuda, K Oda, A Sato, Y Nakayama, A Fujita, H Sonoda, Y Griffin, JD TI Signal transduction and cellular functions of the TEL/ARG oncoprotein SO LEUKEMIA LA English DT Article DE leukemia; chimeric oncogene; TEL/ARG; tyrosine kinase; signal transduction ID ABL-RELATED GENE; PROTEIN-TYROSINE KINASE; CHRONIC MYELOMONOCYTIC LEUKEMIA; ACTIN-BINDING DOMAINS; F-ACTIN; C-ABL; BCR-ABL; TRANSFORMING ABILITY; MYELOGENOUS LEUKEMIA; BCR/ABL EXPRESSION AB The TEL/ARG oncogene is formed by t(1; 12)( q25; p13) reciprocal translocation and is associated with human leukemia. We have previously demonstrated that the expression of TEL/ARG in Ba/F3 cells results in prolonged viability and hyper-responsiveness to IL-3. To determine the molecular mechanisms, a series of mutants of TEL/ARG were generated, and each cDNA was expressed in Ba/F3 or CHO cells. The PNT domain in TEL and K317 in ARG were essential for both signaling and biological effects. The SH3 domain in ARG was required for hyper-responsiveness to IL-3, but not for prolonged viability. The opposite was true for the SH2 domain in ARG. Mutation of Y314 in TEL, a putative GRB2-binding site, led to reduced viability, and loss of hyper-responsiveness to IL-3. All biological functions were profoundly impaired with deletion of the C-terminus in ARG, despite maintaining high levels of its kinase activity. When expressed in CHO cells, wild-type TEL/ARG induced the formation of fillopodia, in a fashion dependent on the C-terminal portion and intact kinase activity. Thus, these results suggest several critical domains within TEL/ARG necessary for function, and indicate that the signaling pathways necessary for viability, growth factor hyper-responsiveness and cytoskeletal reorganization are likely to be separate. C1 Kyoto Prefectural Univ Med, Dept Hlth Sci & Prevent Med, Kawaramachi Hirokoji Kamigyo Ku, Kyoto 6028566, Japan. Hokkaido Univ, Sch Med, Dept Prevent Med, Lab Environm Med, Sapporo, Hokkaido 060, Japan. Int Med Ctr Japan, Res Inst, Dept Clin Pathol, Div Mol Cytogenet, Tokyo, Japan. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Okuda, K (reprint author), Kyoto Prefectural Univ Med, Dept Hlth Sci & Prevent Med, Kawaramachi Hirokoji Kamigyo Ku, Kyoto 6028566, Japan. EM keiko_o@koto.kpu-m.ac.jp NR 40 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2005 VL 19 IS 4 BP 603 EP 610 DI 10.1038/sj.leu.2403668 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 909LB UT WOS:000227860300018 PM 15729383 ER PT J AU Germeshausen, M Schulze, H Kratz, C Wilkens, L Repp, R Shannon, K Welte, K Ballmaier, M AF Germeshausen, M Schulze, H Kratz, C Wilkens, L Repp, R Shannon, K Welte, K Ballmaier, M TI An acquired G-CSF receptor mutation results in increased proliferation of CMML cells from a patient with severe congenital neutropenia SO LEUKEMIA LA English DT Article DE G-CSF receptor; RAS mutations; congenital neutropenia; CMML; leukemogenesis ID COLONY-STIMULATING-FACTOR; ACUTE MYELOGENOUS LEUKEMIA; ACUTE MYELOID-LEUKEMIA; POINT MUTATIONS; GENE; ACTIVATION; RAS; AGRANULOCYTOSIS; EXPRESSION; DISTINCT AB Severe congenital neutropenia (CN) is characterized by a maturation arrest of myelopoiesis at the promyelocyte stage. Treatment with pharmacological doses of recombinant human granulocyte colony-stimulating factor (rh-G-CSF) stimulates neutrophil production and decreases the risk of major infectious complications. However, approximately 15% of CN patients develop myeloid malignancies that have been associated with somatic mutations in the G-CSF receptor (G-CSFR) and RAS genes as well as with acquired monosomy 7. We report a CN patient with chronic myelomonocytic leukemia (CMML) who never received rh-G-CSF. Molecular analysis demonstrated a somatic G-CSFR mutation (C2390T), which led to expression of a truncated G-CSFR protein in the CMML. Normal G-CSFR expression was unexpectedly absent in primary and cultured CMML. In addition, CMML cells showed monosomy 7 and an oncogenic NRAS mutation. In vitro culture revealed a G-CSF-dependent proliferation of CMML cells, which subsequently differentiated along the monocytic/macrophage lineage. Our results provide direct evidence for the in vivo expression of a truncated G-CSFR in leukemic cells, which emerged in the absence of rh-G-CSF treatment and transduces proliferative signals. C1 Hannover Med Sch, Dept Pediat Hematol & Oncol, Hannover, Germany. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Hannover Med Sch, Dept Cell & Mol Pathol, Hannover, Germany. Univ Erlangen Nurnberg, Dept Hematol & Oncol, Erlangen, Germany. RP Germeshausen, M (reprint author), Hannover Med Sch, Carl Neuberg Str 1, D-30625 Hannover, Germany. EM Germeshausen.Manuela@mh-hannover.de FU NCI NIH HHS [R01 CA72614] NR 42 TC 18 Z9 18 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 APR PY 2005 VL 19 IS 4 BP 611 EP 617 DI 10.1038/sj.leu.2403663 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 909LB UT WOS:000227860300019 PM 15729385 ER PT J AU Barata, JT Cardoso, AA Boussiotis, VA AF Barata, JT Cardoso, AA Boussiotis, VA TI Interleukin-7 in T-cell acute lymphoblastic leukemia: An extrinsic factor supporting leukemogenesis? SO LEUKEMIA & LYMPHOMA LA English DT Review DE interleukin-7; acute lymphoblastic leukemia; leukemogenesis; T-cell leukemia; cytokines ID RECEPTOR-GAMMA CHAIN; PROTEIN-KINASE-B; NF-KAPPA-B; STIMULATES TYROSINE PHOSPHORYLATION; HUMAN THYMOCYTE PRECURSORS; SERINE-THREONINE KINASE; IN-VIVO; CYCLE PROGRESSION; TRANSCRIPTION FACTORS; SIGNAL-TRANSDUCTION AB The malignant transformation and expansion of tumor cells involve both cell-autonomous mechanisms and microenvironment signals that regulate viability, nutrient utilization, metabolic activity and cell growth. In T-cell acute lymphoblastic leukemia (T-ALL), the co- culture of leukemic cells with stroma or the addition of particular cytokines prevents ex vivo spontaneous apoptosis. Interleukin-7 (IL-7), a cytokine produced by thymic and bone marrow stroma, increases the viability and proliferation of T-ALL cells. IL-7 induces the activation of Jak/STAT, MEK/Erk and PI3K/Akt signaling pathways in TALL cells. PI3K/Akt is the dominant pathway that mediates the effects of IL- 7 on T-ALL. PI3K signaling is required for the induction of Bcl-2, the down-regulation of p27(kip1) and cell cycle progression. PI3K signaling is also required for the expression of the glucose transporter Glut1, uptake of glucose, activation of the metabolic machinery, increase in cell size, and maintenance of mitochondrial integrity. These observations suggest that substrates of molecular pathways activated by microenvironmental factors represent attractive molecular targets for the regulation of the viability and proliferation of TALL cells and provide the means for the development of novel treatment strategies. C1 Univ Lisbon, Fac Med, Inst Mol Med, Tumor Biol Unit,Med Sch, P-1649028 Lisbon, Portugal. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Barata, JT (reprint author), Univ Lisbon, Fac Med, Inst Mol Med, Tumor Biol Unit,Med Sch, Ed Egas Moniz, P-1649028 Lisbon, Portugal. EM Joao_Barata@fm.ul.pt RI Barata, Joao/D-9181-2015 OI Barata, Joao/0000-0002-4826-8976 FU NCI NIH HHS [P01-CA68484]; NIAID NIH HHS [AI 46548] NR 125 TC 40 Z9 42 U1 0 U2 1 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 APR PY 2005 VL 46 IS 4 BP 483 EP 495 DI 10.1080/10428190400027852 PG 13 WC Oncology; Hematology SC Oncology; Hematology GA 921ZQ UT WOS:000228805200001 PM 16019476 ER PT J AU Merrick, DT Haney, J Petrunich, S Sugita, M Miller, YE Keith, RL Kennedy, TC Franklin, WA AF Merrick, DT Haney, J Petrunich, S Sugita, M Miller, YE Keith, RL Kennedy, TC Franklin, WA TI Overexpression of vascular endothelial growth factor and its receptors in bronchial dypslasia demonstrated by quantitative RT-PCR analysis SO LUNG CANCER LA English DT Article DE angiogenesis; precancerous conditions; early detection; tumor progression; chemoprevention; RT-PCR (reverse transcription polymerase chain reaction) ID CELL LUNG CARCINOMAS; EXON 7-ENCODED DOMAIN; FACTOR MESSENGER-RNA; MICROVESSEL DENSITY; TUMOR-CELLS; PRENEOPLASTIC LESIONS; EXPRESSION PATTERN; POSSIBLE RELEVANCE; VEGF EXPRESSION; ORAL-TISSUES AB Neoangiogenesis is required for the growth of invasive lung carcinoma, however, the role of angiogenesis in the progression of premalignant changes to carcinoma of the lung is less clear. We have evaluated vascular endothelial growth factor (VEGF) expression and microvessel densities (MVDs) in 62 bronchoscopic biopsies from normal, reactive (basal cell hyperplasia (BCH)) and dysplastic bronchial epithelium and in tissue from twenty-seven invasive Lung carcinomas in an effort to demonstrate angiogenic activity in these preneoptastic lesions and determine whether it is associated with increased bronchial epithelial VEGF expression. MVDs and VEGF RNA expression measured by quantitative RT-PCR were found to be elevated in comparison to normal bronchial tissue in bronchial dysplasias and invasive lung carcinomas but not in basal cell hyperplasias. Immunohistochemical (IHC) analyses revealed that expression of VEGF arose predominantly from bronchial epithelium. ELISA analysis of lung tumor tissue showed that elevated VEGF protein expression correlated with VEGF RNA levels (r=0.59, p=0.004). Increased expression of VEGF RNA was also found in histologically normal bronchial mucosa from patients with either dysplasia at other sites or a history of heavy tobacco use suggesting a possible field effect in regard to the elaboration of VEGF. Furthermore, analysis of VEGF isoforms and VEGF receptors by semi-quantitative RT-PCR in dysplastic and invasive lesions revealed characteristic altered patterns of expression in dysplasia and early cancer as compared to normal tissue. These results indicate that angiogenesis develops early in lung carcinogenesis and is associated with overexpression of VEGF. (c) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Denver Vet Affairs Med Ctr, Dept Pathol, Denver, CO 80220 USA. Denver Vet Affairs Med Ctr, Dept Pulm Med, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80260 USA. RP Merrick, DT (reprint author), Denver Vet Affairs Med Ctr, Dept Pathol, 1055 Clermont St, Denver, CO 80220 USA. EM Daniel.Merrick@med.va.gov FU NCI NIH HHS [CA 58187] NR 53 TC 30 Z9 32 U1 1 U2 1 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 APR PY 2005 VL 48 IS 1 BP 31 EP 45 DI 10.1016/j.lungcan.2004.07.049 PG 15 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 916WZ UT WOS:000228418600004 PM 15777969 ER PT J AU Schnipper, JL Ackerman, RH Krier, JB Honour, M AF Schnipper, JL Ackerman, RH Krier, JB Honour, M TI Diagnostic yield and utility of neurovascular ultrasonography in the evaluation of patients with syncope SO MAYO CLINIC PROCEEDINGS LA English DT Article AB OBJECTIVE: To determine the diagnostic utility of neurovascular ultrasonography (transcranial Doppler and carotid ultrasonography) in patients with syncope. PATIENTS AND METHODS: We retrospectively identified consecutive patients who underwent neurovascular ultrasonography for the diagnosis of syncope or presyncope at an academic hospital in 1997 and 1998. From medical records we abstracted patient demographic and clinical information, results and consequences of testing, and follow-up data for 3 years. RESULTS: A total of 140 patients participated in the study. The median age of the study patients was 74 years (interquartile range, 66-80 years), and 49% were male. Severe extracranial or intracranial cerebrovascular disease was found on neurovascular ultrasonography in 20 patients (14%; 95% confidence interval [CI], 9.50/21%). Focal neurologic signs or symptoms or carotid bruits were found in 19 (95%) of 20 patients with positive test results compared with 46 (38%) of 3.20 patients without severe disease (P <.001). Ultrasonography identified cerebrovascular lesions that may have contributed to the syncopal process in only 2 (1.4%) of 140 patients (95% CI, 0.39%-5.1%), but the lesions were unlikely to have been the primary cause of syncope in either patient. CONCLUSION: In this predominantly stroke-age population, neurovascular ultrasonography had a low yield for diagnosing vascular lesions that contributed to the pathophysiology of syncope. However, In patients with focal signs or symptoms or carotid bruits, it detected incidental lesions that typically require treatment or follow-up. In patients with syncope, neurovascular ultrasonography should be reserved for this subset. The data suggest enhancements to the American College of Physicians guideline for the use of neurovascular ultrasonography in patients with syncope. C1 Brigham & Womens Hosp, Div Gen Med, Boston, MA 02120 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Schnipper, JL (reprint author), Brigham & Womens Hosp, Div Gen Med, 1620 Tremont St, Boston, MA 02120 USA. EM jschnipper@partners.org FU BHP HRSA HHS [5T32PE11001] NR 12 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD APR PY 2005 VL 80 IS 4 BP 480 EP 488 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 912HZ UT WOS:000228069600006 PM 15819284 ER PT J AU Levin, M AF Levin, M TI Left-right asymmetry in embryonic development: a comprehensive review (vol 122, pg 3, 2005) SO MECHANISMS OF DEVELOPMENT LA English DT Correction C1 Harvard Univ, Sch Dent Med, Forsyth Inst, Cytokine Biol Dept, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Harvard Univ, Sch Dent Med, Forsyth Inst, Cytokine Biol Dept, 140 The Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org NR 1 TC 1 Z9 1 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD APR PY 2005 VL 122 IS 4 BP 621 EP 621 DI 10.1016/j.mod.2005.02.001 PG 1 WC Developmental Biology SC Developmental Biology GA 921VZ UT WOS:000228794900011 ER PT J AU Groeneveld, PW Laufer, SB Garber, AM AF Groeneveld, PW Laufer, SB Garber, AM TI Technology diffusion, hospital variation, and racial disparities among elderly Medicare beneficiaries 1989-2000 SO MEDICAL CARE LA English DT Article DE race and ethnicity; disparities; variation; hospital; diffusion of innovation ID ACUTE MYOCARDIAL-INFARCTION; VENA-CAVAL FILTERS; UNITED-STATES; REVASCULARIZATION PROCEDURES; CORONARY-REVASCULARIZATION; SOCIOECONOMIC-STATUS; GEOGRAPHIC-VARIATION; VETERANS-AFFAIRS; CLINICAL-TRIAL; HEALTH-CARE AB Background: Low rates of technology utilization in hospitals with high proportions of black inpatients may be a remediable cause of healthcare disparities. Objectives: Our objective was to determine how differences in technology utilization among hospitals contributed to racial disparity and if temporal reduction in hospital procedure rate variation resulted in decreased racial disparity for these technologies. Methods: We identified 2,348,952 elderly Medicare beneficiaries potentially eligible for 1 of 5 emerging medical technologies from 1989-2000 and determined if these patients had received the indicated procedure within 90 days of their qualifying hospital admission. Initial multivariate regression models adjusted for age, race, sex, admission year, clinical comorbidity, community levels of education and income, and academic/urban hospital admission. The inpatient racial composition of each patient's admitting hospital and time-race interactions were added as covariates to subsequent models. Results: Blacks had significantly lower adjusted rates (P < 0.001) compared with whites for tissue replacement of the aortic valve, internal mammary artery coronary bypass grafting, dual-chambered pacemaker implantation, and lumbar spinal fusion. Hospitals with > 20% black inpatients were less likely to perform these procedures on both white and black patients than hospitals with < 9% black inpatients, and racial disparity was greater in hospitals with larger black populations. There were no temporal reductions in racial disparities. Conclusions: Blacks may be disadvantaged in access to new procedures by receiving care at hospitals that have both lower procedure rates and greater racial disparity. Policies designed to ameliorate racial disparities in health care must address hospital variation in the provision of care. C1 Vet Affairs Med Ctr, Philadelphia, PA USA. Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA USA. Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, Stanford, CA USA. Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. Natl Bur Econ Res, Stanford, CA USA. RP Groeneveld, PW (reprint author), 1122 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM peter.groeneveld@med.va.gov RI Garber, Alan/F-1476-2010 FU AHRQ HHS [T32-HS000028]; NIA NIH HHS [P30-AG017253, P01-AG005842] NR 44 TC 88 Z9 88 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 2005 VL 43 IS 4 BP 320 EP 329 DI 10.1097/01.mlr.0000156849.15166.ec PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 910EU UT WOS:000227914000003 PM 15778635 ER PT J AU Rietzel, E Pan, TS Chen, GTY AF Rietzel, E Pan, TS Chen, GTY TI Four-dimensional computed tomography: Image formation and clinical protocol SO MEDICAL PHYSICS LA English DT Article DE 4D computed tomography; 4D imagine; time resolved imaging ID CT SCANS; RADIOTHERAPY; MOVEMENT; IMPROVEMENT; ARTIFACTS; MOTION AB Respiratory motion can introduce significant errors in radiotherapy. Conventional CT scans as commonly used for treatment planning can include severe motion artifacts that result from interplay effects between the advancing scan plane and object motion. To explicitly include organ/target motion in treatment planning and delivery, time-resolved CT data acquisition (4D Computed Tomography) is needed. 4DCT can be accomplished by oversampled CT data acquisition at each slice. During several CT tube rotations projection data are collected in axial cine mode for the duration of the patient's respiratory cycle (plus the time needed for a full CT gantry rotation). Multiple images are then reconstructed per slice that are evenly distributed over the acquisition time. Each of these images represents a different anatomical state during a respiratory cycle. After data acquisition at one couch position is completed, x rays are turned off and the couch advances to begin data acquisition again until full coverage of the scan length has been obtained. Concurrent to CT data acquisition the patient's abdominal surface motion is recorded in precise temporal correlation. To obtain CT volumes at different respiratory states, reconstructed images are sorted into different spatio-temporally coherent volumes based on respiratory phase as obtained from the patient's surface motion. During binning, phase tolerances are chosen to obtain complete volumetric information since images at different couch positions are reconstructed at different respiratory phases. We describe 4DCT image formation and associated experiments that characterize the properties of 4DCT. Residual motion artifacts remain due to partial projection effects. Temporal coherence within resorted 4DCT volumes is dominated by the number of reconstructed images per slice. The more images are reconstructed, the smaller phase tolerances can be for retrospective sorting. From phantom studies a precision of about 2.5 mm. for quasiregular motion and typical respiratory periods could be concluded. A protocol for 4DCT scanning was evaluated and clinically implemented at the MGH. Patient data are presented to elucidate how additional patient specific parameters can impact 4DCT imaging. (c) 2005 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Gesell Schwerionenforsch mbH, Biophys Abt, Darmstadt, Germany. Univ Texas, MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX 77030 USA. RP Rietzel, E (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. FU PHS HHS [P01-21239] NR 15 TC 272 Z9 284 U1 4 U2 24 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD APR PY 2005 VL 32 IS 4 BP 874 EP 889 DI 10.1118/1.1869852 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920AP UT WOS:000228659700006 PM 15895570 ER PT J AU Waters, G Caplan, D AF Waters, G Caplan, D TI The relationship between age, processing speed, working memory capacity, and language comprehension SO MEMORY LA English DT Article ID SENTENCE COMPREHENSION; INDIVIDUAL-DIFFERENCES; COGNITION; COMPLEXITY; RESOURCES; ADULTS AB A total of 50 elderly individuals and 48 college students were tested on several measures of processing speed and of working memory capacity. Language processing was tested with an on-line measure of sentence processing efficiency, an end-of-sentence acceptability judgement task, and a paragraph comprehension test. Elderly individuals performed more poorly than college students on the speed of processing and working memory measures and had longer listening times overall on the sentence processing measures. Elderly individuals did not, however, have overall longer listening times at the most capacity-demanding regions of the harder sentence type and the measures of working memory capacity. The data are argued to provide evidence that the WM system used to structure sentences syntactically is separate from that used in other aspects of language comprehension. C1 Boston Univ, Dept Commun Disorders, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Waters, G (reprint author), Boston Univ, Dept Commun Disorders, 635 Commonwealth Ave, Boston, MA 02215 USA. EM gwaters@bu.edu FU NIA NIH HHS [AGO9661] NR 39 TC 57 Z9 60 U1 1 U2 8 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0965-8211 J9 MEMORY JI Memory PD APR-MAY PY 2005 VL 13 IS 3-4 BP 403 EP 413 DI 10.1080/09658210344000459 PG 11 WC Psychology, Experimental SC Psychology GA 929OT UT WOS:000229356200022 PM 15952262 ER PT J AU Kraml, PJ Klein, RL Huang, Y Nareika, A Lopes-Virella, MF AF Kraml, PJ Klein, RL Huang, Y Nareika, A Lopes-Virella, MF TI Iron loading increases cholesterol accumulation and macrophage scavenger receptor I expression in THP-1 mononuclear phagocytes SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; ISCHEMIC-HEART-DISEASE; ATHEROSCLEROSIS; OXIDATION; STORES; RISK; CELL; LDL; TRANSCRIPTION; METABOLISM AB Epidemiological studies have established that a high level of iron body stores is associated with increased risk of acute coronary heart disease. To explain this association, it has been proposed that iron catalyzes the production of highly reactive forms of free oxygen species, and thus, promotes low-density lipoprotein (LDL) oxidation, a lipoprotein that plays a critical role in atherogenesis. However, few studies have provided evidence to support this hypothesis. In the present study, we determined the effect of iron loading of THP-1 mononuclear phagocytes on LDL metabolism. We demonstrated that iron loading of THP-1 cells stimulated conjugated diene formation in LDL in the culture medium. In addition, iron loading of THP-1 cells significantly increased cholesteryl ester accumulation in cells exposed to native LDL, suggesting that during the incubation of the cells with native LDL, the LDL became oxidized and was taken up by the cells. We further demonstrated that the degradation of I-125-oxidized LDL was significantly increased in iron-loaded THP-1 cells. Lastly, we demonstrated that iron loading of THP-1 cells stimulated scavenger receptor expression in these cells. In conclusion, this study demonstrates that loading of mononuclear phagocytes with iron leads to oxidization of LDL, increased cellular cholesterol accumulation and scavenger receptor expression, and supports the hypothesis that increased macrophage iron levels promote atherogenesis. (c) 2005 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Dept Med, Div Endocrinol Metab & Med Genet, Charleston, SC 29425 USA. Charles Univ Prague, Fac Med 3, Div Metab Diabet & Endocrinol, Dept Med 2, Prague 10034, Czech Republic. Med Univ S Carolina, Div Endocrinol Metab & Med Genet, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Dept, Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. RP Lopes-Virella, MF (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Metab & Med Genet, POB 250770, Charleston, SC 29425 USA. EM virellam@musc.edu FU NHLBI NIH HHS [HL55782] NR 27 TC 30 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD APR PY 2005 VL 54 IS 4 BP 453 EP 459 DI 10.1016/j.metabol.2004.10.012 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 916AE UT WOS:000228352600005 PM 15798950 ER PT J AU Rozen, S Cudkowicz, ME Bogdanov, M Matson, WR Kristal, BS Beecher, C Harrison, S Vouros, P Flarakos, J Vigneau-Callahan, K Matson, TD Newhall, KM Beal, MF Brown, RH Kaddurah-Daouk, R AF Rozen, Steve Cudkowicz, Merit E. Bogdanov, Mikhail Matson, Wayne R. Kristal, Bruce S. Beecher, Chris Harrison, Scott Vouros, Paul Flarakos, Jimmy Vigneau-Callahan, Karen Matson, Theodore D. Newhall, Kristyn M. Beal, M. Flint Brown, Robert H., Jr. Kaddurah-Daouk, Rima TI Metabolomic analysis and signatures in motor neuron disease SO METABOLOMICS LA English DT Article DE amyotrophic lateral sclerosis; motor neuron disease; coulometric array; metabolic profiling AB Motor neuron diseases (MND) are a heterogeneous group of disorders that includes amyotrophic lateral sclerosis (ALS) and result in death of motor neurons. These diseases may produce characteristic perturbations of the metabolome, the collection of small-molecules (metabolites) present in a cell, tissue, or organism. To test this hypothesis, we used high performance liquid chromatography followed by electrochemical detection to profile blood plasma from 28 patients with MND and 30 healthy controls. Of 317 metabolites, 50 were elevated in MND patients and more than 70 were decreased (p < 0.05). Among the compounds elevated, 12 were associated with the drug Riluzole. In a subsequent study of 19 subjects with MND who were not taking Riluzole and 33 healthy control subjects, six compounds were significantly elevated in MND, while the number of compounds with decreased concentration was similar to study 1. Our data also revealed a distinctive signature of highly correlated metabolites in a set of four patients, three of whom had lower motor neuron (LMN) disease. In both datasets we were able to separate MND patients from controls using multivariate regression techniques. These results suggest that metabolomic studies can be used to ascertain metabolic signatures of disease in a non-invasive fashion. Elucidation of the structures of signature molecules in ALS and other forms of MND should provide insight into aberrant biochemical pathways and may provide diagnostic markers and targets for drug design. C1 [Rozen, Steve; Beecher, Chris; Harrison, Scott; Kaddurah-Daouk, Rima] Metabolon Inc, Res Triangle Pk, NC 27709 USA. [Rozen, Steve] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Cudkowicz, Merit E.; Newhall, Kristyn M.] Massachusetts Gen Hosp, Neurol Clin Trial Unit, Charlestown, MA 02129 USA. [Bogdanov, Mikhail; Kristal, Bruce S.; Beal, M. Flint] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Matson, Wayne R.; Vigneau-Callahan, Karen] ESA Inc, Chelmsford, MA 01824 USA. [Kristal, Bruce S.] Burke Med Res Inst, Dementia Res Serv, White Plains, NY 10605 USA. [Vouros, Paul; Flarakos, Jimmy] Northeastern Univ, Dept Chem, Boston, MA 02115 USA. [Matson, Theodore D.] Univ Chicago, Dept Chem, Chicago, IL 60637 USA. [Brown, Robert H., Jr.] Massachusetts Gen Hosp E, MGH, Charlestown, MA 02129 USA. RP Kaddurah-Daouk, R (reprint author), Duke Univ, Med Ctr, Dept Psychiat, POB 3950, Durham, NC 27710 USA. EM kaddu001@mc.duke.edu OI Rozen, Steven G./0000-0002-4288-0056 FU Al-Athel ALS Research Foundation; ALS Therapy Alliance; Angel Fund; DeBourgknect ALS Research Fund; National Institutes of Health (NINDS and NIA); Project ALS; U. S. Department of Defense; ALS Foundation FX This work was supported in part by the Al-Athel ALS Research Foundation, the ALS Therapy Alliance, the Angel Fund, the DeBourgknect ALS Research Fund, the National Institutes of Health (NINDS and NIA), Project ALS, and the U. S. Department of Defense. We thank L. Bruijn of the ALS Foundation, D. W. Cleveland, J. Rebek Jr., J. D. Rothstein, and P. Schimmel for scientific discussions. NR 37 TC 96 Z9 100 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1573-3882 J9 METABOLOMICS JI Metabolomics PD APR PY 2005 VL 1 IS 2 BP 101 EP 108 DI 10.1007/s11306-005-4810-1 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V63QN UT WOS:000204301700001 PM 18820733 ER PT J AU Grotzke, JE Lewinsohn, DM AF Grotzke, JE Lewinsohn, DM TI Role of CD8(+) T lymphocytes in control of Mycobacterium tuberculosis infection SO MICROBES AND INFECTION LA English DT Review DE tuberculosis; CD8-positive T-lymphocytes; antigen presentation; immunologic surveillance ID BACILLUS-CALMETTE-GUERIN; NITRIC-OXIDE SYNTHASE; CLASS-I PRESENTATION; CELL-DEFICIENT MICE; INTERFERON-GAMMA; DENDRITIC CELLS; PULMONARY TUBERCULOSIS; EXOGENOUS ANTIGENS; CROSS-PRESENTATION; PROCESSING PATHWAY AB Tuberculosis remains a global health concern. Control of infection is dependent on cell-mediated immune responses, with CD4(+) T lymphocytes playing a central role. In this article, data supporting the importance of CD8(+) T lymphocytes is reviewed, with an emphasis on the unique functional roles that this lymphocyte subset may play. (c) 2005 Elsevier SAS. All rights reserved. C1 Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland VA Med Ctr, Portland, OR 97239 USA. RP Lewinsohn, DM (reprint author), Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM lewinsod@OHSU.edu RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 NR 114 TC 64 Z9 74 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD APR PY 2005 VL 7 IS 4 BP 776 EP 788 DI 10.1016/j.micinf.2005.03.001 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 932DO UT WOS:000229534600025 PM 15823514 ER PT J AU Dieperink, M Erbes, C Leskela, J Kaloupek, D Farrer, MK Fisher, L Wolf, E AF Dieperink, M Erbes, C Leskela, J Kaloupek, D Farrer, MK Fisher, L Wolf, E TI Comparison of treatment for post-traumatic stress disorder among three Department of Veterans Affairs medical centers SO MILITARY MEDICINE LA English DT Article ID PHARMACOTHERAPY; EFFICACY; PLACEBO; TRIAL; PTSD AB The objective of the present study was to compare three specialized treatment programs for post-traumatic stress disorder (PTSD) in different Veterans Affairs medical centers, in terms of the format of therapeutic services and the medications prescribed for PTSD. Chart review methods were used to examine medical records for 50 patients from each facility over a 6-month period. Results indicated that the medications prescribed were fairly consistent across sites, although they were not always consistent with treatment recommendations. Therapy formats for two of the facilities were quite different, with one offering more case management services and the other offering more intensive individual and group therapy services. Additional research is needed to broaden our knowledge of how PTSD is being treated currently and to study the effectiveness of the treatment strategies being used. C1 Dept Vet Affairs Med Ctr, Minneapolis, MN 55417 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA 02130 USA. RP Dieperink, M (reprint author), Dept Vet Affairs Med Ctr, 116A6,1 Vet Dr, Minneapolis, MN 55417 USA. NR 22 TC 8 Z9 8 U1 0 U2 0 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 APR PY 2005 VL 170 IS 4 BP 305 EP 308 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 019JK UT WOS:000235831200012 PM 15916300 ER PT J AU Yantiss, RK Rosenberg, AE Sarran, L Besmer, P Antonescu, CR AF Yantiss, RK Rosenberg, AE Sarran, L Besmer, P Antonescu, CR TI Multiple gastrointestinal stromal tumors in type I neurofibromatosis: a pathologic and molecular study SO MODERN PATHOLOGY LA English DT Article DE vonRecklinghausen's disease; GIST; PDGFRA; KIT ID C-KIT GENE; AUTONOMIC NERVE TUMORS; OF-FUNCTION MUTATION; VON-RECKLINGHAUSENS-DISEASE; GERMLINE MUTATION; INTERSTITIAL-CELLS; VONRECKLINGHAUSENS DISEASE; SKEINOID FIBERS; ACTIVATING MUTATION; MYENTERIC PLEXUS AB Multiple gastrointestinal stromal tumors typically occur in familial form associated with KIT receptor tyrosine kinase or platelet-derived growth factor receptor-alpha (PDGFRA) germline mutations, but may also develop in the setting of type 1 neurofibromatosis. The molecular abnormalities of gastrointestinal stromal tumors arising in neurofibromatosis have not been extensively studied. We identified three patients with type 1 neuro. fibromatosis and multiple small intestinal stromal tumors. Immunostains for CD117, CD34, desmin, actins, S-100 protein, and keratins were performed on all of the tumors. DNA was extracted from representative paraffin blocks from separate tumor nodules in each case and subjected to a nested polymerase chain reaction, using primers for KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18, followed by direct sequencing. The mean patient age was 56 years (range: 37-86 years, male/female ratio: 2/1). One patient had three tumors, one had five, and one had greater than 10 tumor nodules, all of which demonstrated histologic features characteristic of gastrointestinal stromal tumors and stained strongly for CD117 and CD34. One patient died of disease at 35 months, one was disease free at 12 months and one was lost to follow-up. DNA extracts from 10 gastrointestinal stromal tumors (three from each of two patients and four from one patient) were subjected to polymerase chain reactions and assessed for mutations. All of the tumors were wild type for KIT exons 9, 13, and 17 and PDGFRA exons 12 and 18. Three tumors from one patient had identical point mutations in KIT exon 11, whereas the other tumors were wild type at this locus. We conclude that, although most patients with type 1 neurofibromatosis and gastrointestinal stromal tumors do not have KIT or PDGFRA mutations, KIT germline mutations might be implicated in the pathogenesis of gastrointestinal stromal tumors in some patients. C1 UMass Mem Hlth Care, Dept Pathol, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Sloan Kettering Inst, Dev Biol Program, New York, NY USA. RP Yantiss, RK (reprint author), UMass Mem Hlth Care, Dept Pathol, 55 Lake Ave N, Worcester, MA 01655 USA. EM yantissr@ummhc.org NR 59 TC 61 Z9 68 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD APR PY 2005 VL 18 IS 4 BP 475 EP 484 DI 10.1038/modpathol.3800334 PG 10 WC Pathology SC Pathology GA 908ZB UT WOS:000227827600003 PM 15540118 ER PT J AU Nishi, M Werner, ED Oh, BC Frantz, JD Dhe-Paganon, S Hansen, L Lee, J Shoelson, SE AF Nishi, M Werner, ED Oh, BC Frantz, JD Dhe-Paganon, S Hansen, L Lee, J Shoelson, SE TI Kinase activation through dimerization by human SH2-B SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROWTH-FACTOR-RECEPTOR; PHOSPHOLIPASE-C-GAMMA; PROTEIN-TYROSINE-PHOSPHATASE; AFFINITY PHOSPHOTYROSYL PEPTIDE; INDUCED DNA-SYNTHESIS; SEA-URCHIN EGGS; INSULIN-RECEPTOR; ADAPTER PROTEIN; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION AB The isoforms of SH2-B, APS, and Lnk form a family of signaling proteins that have been described as activators, mediators, or inhibitors of cytokine and growth factor signaling. We now show that the three alternatively spliced isoforms of human SH2-B readily homodimerize in yeast two-hybrid and cellular transfections assays, and this is mediated specifically by a unique domain in its amino terminus. Consistent with previous reports, we further show that the SH2 domains of SH2-B and APS bind JAK2 at Tyr813. These findings suggested a model in which two molecules of SH2-B or APS homodimerize with their SH2 domains bound to two JAK2 molecules, creating heterotetrameric JAK2-(SH2-B)(2)-JAK2 or JAK2-(APS)(2)-JAK2 complexes. We further show that APS and SH2-B isoforms heterodimerize. At lower levels of SH2-B or APS expression, dimerization approximates two JAK2 molecules to induce transactivation. At higher relative concentrations of SH2-B or APS, kinase activation is blocked. SH2-B or APS homodimerization and SH2-B/APS heterodimerization thus provide direct mechanisms for activating and inhibiting JAK2 and other kinases from the inside of the cell and for potentiating or attenuating cytokine and growth factor receptor signaling when ligands are present. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM steven.shoelson@joslin.harvard.edu FU NIDDK NIH HHS [DK09393, DK09908, DK36836, DK43123, DK45943, F32 DK009393, F32 DK009908, P30 DK036836, R01 DK043123, R01 DK045943] NR 83 TC 42 Z9 45 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2005 VL 25 IS 7 BP 2607 EP 2621 DI 10.1128/MCB.25.7.2607-2621.2005 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 906XU UT WOS:000227679000008 PM 15767667 ER PT J AU Arco, PGD Koipally, J Georgopoulos, K AF Arco, PGD Koipally, J Georgopoulos, K TI Ikaros SUMOylation: Switching out of repression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-BINDING PROTEINS; TRANSCRIPTION FACTOR; SUMO-1 MODIFICATION; GENE FAMILY; CENTROMERIC HETEROCHROMATIN; LYMPHOCYTE DEVELOPMENT; NUCLEAR-BODIES; ACTIVATION; UBIQUITIN; COMPLEXES AB Ikaros plays a key role in lymphocyte development and homeostasis by both potentiating and repressing gene expression. Here we show that Ikaros interacts with components of the SUMO pathway and is SUMOylated in vivo. Two SUMOylation sites are identified on Ikaros whose simultaneous modification results in a loss of Ikaros' repression function. Ikaros SUMOylation disrupts its participation in both histone deacetylase (HDAC)-dependent and HDAC-independent repression but does not influence its nuclear localization into pericentromeric heterochromatin. These studies reveal a new dynamic way by which Ikaros-mediated gene repression is controlled by SUMOylation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Georgopoulos, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM katia.georgopoulos@cbrc2.mgh.harvard.edu RI Gomez-del Arco, Pablo/L-2728-2013 OI Gomez-del Arco, Pablo/0000-0001-6748-7157 NR 51 TC 13 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2005 VL 25 IS 7 BP 2688 EP 2697 DI 10.1128/MCB.25.7.2688-2697.2005 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 906XU UT WOS:000227679000015 ER PT J AU Stavropoulos, N Rowntree, RK Lee, JT AF Stavropoulos, N Rowntree, RK Lee, JT TI Identification of developmentally specific enhancers for Tsix in the regulation of X chromosome inactivation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID XIST GENE; BLOCKING ACTIVITY; PROTEIN CTCF; CHOICE; LOCUS; TRANSCRIPTION; METHYLATION; EXPRESSION; PROMOTER; REGION AB X chromosome inactivation silences one of two X chromosomes in the mammalian female cell and is controlled by a binary switch that involves interactions between Xist and Tsix, a sense-antisense pair of noncoding genes. On the future active X chromosome, Tsix expression suppresses Xist upregulation, while on the future inactive X chromosome, Tsix repression is required for Xist-mediated chromosome silencing. Thus, understanding the binary switch mechanism depends on ascertaining how Tsix expression is regulated. Here we have taken an unbiased approach toward identifying Tsix regulatory elements within the X chromosome inactivation center. First, we defined the major Tsix promoter and found that it cannot fully recapitulate the developmental dynamics of Tsix expression, indicating a requirement for additional regulatory elements. We then delineated two enhancers, one classical enhancer mapping upstream of Tsix and a bipartite enhancer that flanks the major Tsix promoter. These experiments revealed the intergenic transcription element Xite as an enhancer of Tsix and the repeat element DXPas34 as a component of the bipartite enhancer. Each enhancer contains DNase I-hypersensitive sites and appears to confer developmental specificity to Tsix expression. Characterization of these enhancers will facilitate the identification of trans-acting regulatory factors for X chromosome counting and choice. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Sch Med, Dept Genet, Wellman 913,50 Blossom St, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu OI Stavropoulos, Nicholas/0000-0001-5915-2760 NR 41 TC 58 Z9 61 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 APR PY 2005 VL 25 IS 7 BP 2757 EP 2769 DI 10.1128/MCB.25.7.2757-2769.2005 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 906XU UT WOS:000227679000021 PM 15767680 ER PT J AU Okuno, Y Huang, G Rosenbauer, F Evans, EK Radomska, HS Iwasaki, H Akashi, K Moreau-Gachelin, F Li, YL Zhang, P Gottgens, B Tenen, DG AF Okuno, Y Huang, G Rosenbauer, F Evans, EK Radomska, HS Iwasaki, H Akashi, K Moreau-Gachelin, F Li, YL Zhang, P Gottgens, B Tenen, DG TI Potential autoregulation of transcription factor PU.1 by an upstream reaulatory element SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC STEM-CELLS; ONCOGENE FAMILY MEMBER; C/EBP-ALPHA; LINEAGE COMMITMENT; TRANSGENIC MICE; FACTOR-RECEPTOR; ETS ONCOGENE; DNA-BINDING; ARTIFICIAL CHROMOSOME AB Regulation of the hematopoietic transcription factor PU.1 (Spi-1) plays a critical role in the development of white cells, and abnormal expression of PU.1 can lead to leukemia. We previously reported that the PU.1 promoter cannot induce expression of a reporter gene in vivo, and cell-type-specific expression of PU.1 in stable lines was conferred by a 3.4-kb DNA fragment including a DNase I hypersensitive site located 14 kb upstream of the transcription start site. Here we demonstrate that this kb - 14 site confers lineage-specific reporter gene expression in vivo. This kb -14 upstream regulatory element contains two 300-bp regions which are highly conserved in five mammalian species. In Friend virus-induced erythroleukemia, the spleen focus-forming virus integrates into the PU.1 locus between these two conserved regions. DNA binding experiments demonstrated that PU.1 itself and Elf-1 bind to a highly conserved site within the proximal homologous region in vivo. A mutation of this site abolishing binding of PU.1 and Elf-1 led to a marked decrease in the ability of this upstream element to direct activity of reporter gene in myelomonocytic cell lines. These data suggest that a potential positive autoregulatory loop mediated through an upstream regulatory element is essential for proper PU.1 gene expression. C1 Harvard Univ, Harvard Inst Med, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Canc Immunol & AIDS, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Kumamoto Univ, Sch Med, Dept Hematol, Kumamoto 860, Japan. INSERM, Sect Rech, Inst Curie, U528, Paris, France. Univ Cambridge, Dept Hematol, Cambridge Inst Med Res, Cambridge, England. RP Tenen, DG (reprint author), Harvard Univ, Harvard Inst Med, Sch Med, Room 954,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM dtenen@bidmc.harvard.edu FU NCI NIH HHS [CA41456, R01 CA041456]; NIDDK NIH HHS [DK62064, K01 DK062064] NR 67 TC 97 Z9 97 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 APR PY 2005 VL 25 IS 7 BP 2832 EP 2845 DI 10.1128/MCB.25.7.2832-2845.2005 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 906XU UT WOS:000227679000027 PM 15767686 ER PT J AU Frolov, MV Moon, NS Dyson, NJ AF Frolov, MV Moon, NS Dyson, NJ TI dDP is needed for normal cell proliferation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CYCLIN-DEPENDENT KINASES; E2F TRANSCRIPTION FACTOR; DNA-REPLICATION; FAMILY-MEMBER; S-PHASE; DROSOPHILA; GENE; DP; COMPLEX; EXPRESSION AB To gain insight into the essential functions of E2F, we have examined the phenotypes caused by complete inactivation of E2F and DP family members in Drosophila. Our results show that dDP requires dE2F1 and dE2F2 for DNA-binding activity in vitro and in vivo. In tissue culture cells and in mutant animals, the levels of dE2F and dDP proteins are strongly interdependent. In the absence of dDP, the levels of dE2F1 and dE2F2 decline dramatically, and vice versa. Accordingly, the cell cycle and transcriptional phenotypes caused by targeting dDP mimic the effects of targeting both dE2F1 and dE2F2 and are indistinguishable from the effects of inactivating all three proteins. Although trans-heterozygous dDP mutant animals develop to late pupal stages, the analysis of somatic mutant clones shows that dDP mutant cells are at a severe proliferative disadvantage when compared directly with wild-type neighbors. Strikingly, the timing of S-phase entry or exit is not delayed in dDP mutant clones, nor is the accumulation of cyclin A or cyclin B. However, the maximal level of bromodeoxyuridine incorporation is reduced in dDP mutant clones, and RNA interference experiments show that dDP-depleted cells are prone to stall in S phase. In addition, dDP mutant clones contain reduced numbers of mitotic cells, indicating that dDP mutant cells have a defect in G(2)/M-phase progression. Thus, dDP is not essential for developmental control of the G(1)-to-S transition, but it is required for normal cell proliferation, for optimal DNA synthesis, and for efficient G(2)/M progression. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL USA. RP Dyson, NJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM dyson@helix.mgh.harvard.edu FU NCI NIH HHS [P01 CA95281, P01 CA095281]; NIGMS NIH HHS [R01 GM053203, GM53203] NR 40 TC 28 Z9 28 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2005 VL 25 IS 8 BP 3027 EP 3039 DI 10.1128/MCB.25.8.3027-3039.2005 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 913GB UT WOS:000228138500014 PM 15798191 ER PT J AU Jenna, S Caruso, ME Emadali, A Nguyen, DT Dominguez, M Li, S Roy, R Reboul, J Vidal, M Tzimas, GN Bosse, R Chevet, E AF Jenna, S Caruso, ME Emadali, A Nguyen, DT Dominguez, M Li, S Roy, R Reboul, J Vidal, M Tzimas, GN Bosse, R Chevet, E TI Regulation of membrane trafficking by a novel Cdc42-related protein in Caenorhabditis elegans epithelial cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID GTPASE-ACTIVATING PROTEIN; C-ELEGANS; RHO GTPASES; FINE-STRUCTURE; AXON GUIDANCE; DAUER LARVA; HEPG2 CELLS; FAMILY; MIGRATION; RAC AB Rho GTPases are mainly known for their implication in cytoskeleton remodeling. They have also been recently shown to regulate various aspects of membrane trafficking. Here, we report the identification and the characterization of a novel Caenorhabditis elegans Cdc42-related protein, CRP-1, that shows atypical enzymatic characteristics in vitro. Expression in mouse fibroblasts revealed that, in contrast with CDC-42, CRP-1 was unable to reorganize the actin cytoskeleton and mainly localized to trans-Golgi network and recycling endosomes. This subcellular localization, as well as its expression profile restricted to a subset of epithelial-like cells in C. elegans, suggested a potential function for this protein in polarized membrane trafficking. Consistent with this hypothesis, alteration of CRP-1 expression affected the apical trafficking of CHE-14 in vulval and rectal epithelial cells and sphingolipids (C-6-NBD-ceramide) uptake and/or trafficking in intestinal cells. However, it did not affect basolateral trafficking of myotactin in the pharynx and the targeting of IFB-2 and AJM-1, two cytosolic apical markers of intestine epithelial cells. Hence, our data demonstrate a function for CRP-1 in the regulation of membrane trafficking in a subset of cells with epithelial characteristics. C1 McGill Univ, Organelle Signaling Lab, Dept Surg, Montreal, PQ H3A 1A1, Canada. McGill Univ, Montreal Proteom Network, Montreal, PQ H3A 1A1, Canada. HyperOm Farma Inc, Montreal, PQ H9H 4K8, Canada. McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA. Perkin Elmer Biosignal, Montreal, PQ H3J 1R4, Canada. RP Jenna, S (reprint author), McGill Univ, Organelle Signaling Lab, Dept Surg, Montreal, PQ H3A 1A1, Canada. EM sarah.jenna@mcgill.ca; eric.chevet@mcgill.ca RI Emadali, Anouk/A-4462-2008; Emadali, Anouk/N-4334-2013; Reboul, Jerome/P-9103-2016 OI Reboul, Jerome/0000-0002-5513-4546 NR 47 TC 14 Z9 35 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD APR PY 2005 VL 16 IS 4 BP 1629 EP 1639 DI 10.1091/mbc.E04-08-0760 PG 11 WC Cell Biology SC Cell Biology GA 913QA UT WOS:000228166700006 PM 15659649 ER PT J AU Chauhan, D Hideshima, T Mitsiades, C Richardson, P Anderson, KC AF Chauhan, D Hideshima, T Mitsiades, C Richardson, P Anderson, KC TI Proteasome inhibitor therapy in multiple myeloma SO MOLECULAR CANCER THERAPEUTICS LA English DT Review ID NF-KAPPA-B; MARROW STROMAL CELLS; LUNG-CANCER CELLS; PHASE-I TRIAL; HEMATOLOGIC MALIGNANCIES; INDUCED APOPTOSIS; CHEMOTHERAPEUTIC-AGENTS; MOLECULAR-MECHANISMS; REFRACTORY MYELOMA; CARCINOMA-CELLS AB Multiple myeloma remains incurable despite available therapies, and novel therapies that target both tumor cell and bone marrow microenvironment are urgently needed. Preclinical in vitro and in vivo studies show remarkable anti-multiple myeloma activity of the proteasome inhibitor bortezomib/PS-341 even in multiple myeloma cells refractory to multiple prior therapies, including dexamethasone, melphalan, and thalidomide. Based on these findings, the U.S. Food and Drug Administration recently approved the first proteasome inhibitor bortezomib (Velcade), formerly known as PS-341, for the treatment of relapsed/refractory multiple myeloma. Bortezomib therapy has set an outstanding example of translational research in the field of oncology. Genomics and proteomic studies further provide rationale for combining bortezomib with conventional and novel agents to inhibit multiple myeloma growth, overcome drug resistance, reduce attendant toxicity, and improve patient outcome in multiple myeloma. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [CA 78373, P01 CA078378-06, P50 CA100707-01]; PHS HHS [50947] NR 71 TC 113 Z9 117 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD APR PY 2005 VL 4 IS 4 BP 686 EP 692 DI 10.1158/1535-7163.MCT-04-0338 PG 7 WC Oncology SC Oncology GA 915GR UT WOS:000228286600021 PM 15827343 ER PT J AU Skorija, K Cox, M Sisk, JM Dowd, DR MacDonald, PN Thompson, CC Demay, MB AF Skorija, K Cox, M Sisk, JM Dowd, DR MacDonald, PN Thompson, CC Demay, MB TI Ligand-independent actions of the vitamin D receptor maintain hair follicle homeostasis SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID D-DEFICIENCY RICKETS; COACTIVATOR INTERACTION; TARGETED ABLATION; TRANSGENIC MICE; KNOCKOUT MICE; ANIMAL-MODEL; NULL MICE; ALOPECIA; GENE; EXPRESSION AB Alopecia is a feature of vitamin D receptor (VDR) mutations in humans and in VDR null mice. This alopecia results from an inability to initiate the anagen phase of the hair cycle after follicle morphogenesis is complete. Thus, once the initial hair is shed it does not regrow. VDR expression in the epidermal component of the hair follicle, the keratinocyte, is critical for maintenance of the hair cycle. To determine which functional domains of the VDR are required for hair cycling, mutant VDR transgenes were targeted to the keratinocytes of VDR null mice. Keratinocyte-specific expression of a VDR transgene with a mutation in the hormone-binding domain that abolishes ligand binding restores normal hair cycling in VDR null mice, whereas a VDR transgene with a mutation in the activation function 2 domain that impairs nuclear receptor coactivator recruitment results in a partial rescue. Mutations in the nuclear receptor corepressor Hairless are also associated with alopecia in humans and mice. Hairless binds the VDR, resulting in transcriptional repression. Neither VDR mutation affects Hairless interactions or its ability to repress transcription. These studies demonstrate that the effects of the VDR on the hair follicle are ligand independent and point to novel molecular and cellular actions of this nuclear receptor. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA. RP Demay, MB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman 501,50 Blossom St, Boston, MA 02114 USA. EM demay@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK 46974, DK53980, R01 DK046974]; NINDS NIH HHS [NS41313] NR 38 TC 79 Z9 81 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 APR PY 2005 VL 19 IS 4 BP 855 EP 862 DI 10.1210/me.2004-0415 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 908YN UT WOS:000227826200003 PM 15591533 ER PT J AU Dunn, SL Bjornholm, M Bates, SH Chen, ZB Seifert, M Myers, MG AF Dunn, SL Bjornholm, M Bates, SH Chen, ZB Seifert, M Myers, MG TI Feedback inhibition of leptin receptor/Jak2 signaling via Tyr(1138) of the leptin receptor and suppressor of cytokine signaling 3 SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID DIET-INDUCED OBESITY; SH2 DOMAIN; TYROSINE KINASE; GROWTH-HORMONE; OB RECEPTOR; TRANSDUCTION; SOCS3; ACTIVATION; GP130; SHP2 AB Leptin is an adipocyte-derived hormone that communicates the status of body energy stores to the brain to regulate feeding and energy balance. The inability of elevated leptin levels to adequately suppress feeding in obesity suggests attenuation of leptin action under these conditions; the activation of feedback circuits due to high leptin levels could contribute to this leptin resistance. Using cultured cells exogenously expressing the long form of the leptin receptor (LRb) or an erythropoietin receptor/LRb chimera, we show that chronic stimulation results in the attenuation of LRb signaling and the establishment of a state in which the receptor is refractory to reactivation. Mutation of LRb Tyr(1138) (the site that recruits signal transducer and activator of transcription 3) alleviated this feedback inhibition, suggesting that signal transducer and activator of transcription 3 mediates the induction of a feedback inhibitor, such as suppressor of cytokine signaling 3 (SOCS3), during chronic LRb stimulation. Indeed, manipulation of the expression or activity of the LRb-binding tyrosine phosphatase, SH2-domain containing phosphatase-2, by overexpression of wild-type and dominant negative isoforms or RNA interference-mediated knockdown did not alter the attenuation of LRb signals. In contrast, SOCS3 overexpression repressed LRb signaling, whereas RNA interference-mediated knockdown of SOCS3 resulted in increased LRb signaling that was not attenuated during chronic ligand stimulation. These data suggest that Tyr(1138) of LRb and SOCS3 represent major effector pathways for the feedback inhibition of LRb signaling. Furthermore, we show that mice expressing an LRb isoform mutant for Tyr(1138) display increased activity of the leptin-dependent growth and immune axes, suggesting that Tyr(1138)-mediated feedback inhibition may regulate leptin sensitivity in vivo. C1 Univ Michigan, Sch Med, Dept Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Myers, MG (reprint author), Univ Michigan, Sch Med, Dept Med, Div Metab Endocrinol & Diabet, 1150 W Med Ctr Dr,4301 MSRB 3,Box 0638, Ann Arbor, MI 48109 USA. EM mgmyers@umich.edu FU NIDDK NIH HHS [DK56731, R01 DK57768] NR 46 TC 87 Z9 99 U1 0 U2 11 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 APR PY 2005 VL 19 IS 4 BP 925 EP 938 DI 10.1210/me.2004-0353 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 908YN UT WOS:000227826200009 PM 15604114 ER PT J AU Newhall, KJ Cummings, DE Nolan, MA McKnight, GS AF Newhall, KJ Cummings, DE Nolan, MA McKnight, GS TI Deletion of the RII beta-subunit of protein kinase A decreases body weight and increases energy expenditure in the obese, leptin-deficient ob/ob mouse SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID BROWN ADIPOSE-TISSUE; MELANIN-CONCENTRATING HORMONE; UNCOUPLING PROTEIN; MESSENGER-RNA; ADAPTIVE THERMOGENESIS; TARGETED DISRUPTION; GENE-EXPRESSION; MUTANT MICE; FOOD-INTAKE; OB PROTEIN AB Disruption of the RII beta regulatory subunit of protein kinase A (PKA) results in mice with a lean phenotype, nocturnal hyperactivity, and increased resting metabolic rate. In this report, we have examined whether deletion of RII beta would lead to increased metabolism and rescue the obese phenotype of the leptin-deficient ob/ob (ob) mouse. Body weight gain and food consumption were decreased, whereas basal oxygen consumption and nocturnal locomotor activity were increased in the double mutant animals compared with ob mice. The ob mice are unable to maintain body temperature when placed in a cold environment due to a loss of brown adipose tissue activation, and this cold sensitivity was partially rescued by concomitant disruption of RII beta. These findings indicate that PKA modifies the phenotype of the leptin-deficient mouse, leading to increases in both thermogenesis and energy expenditure. C1 Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Metab, Seattle, WA 98195 USA. Wyeth Res, Collegeville, PA 19426 USA. RP McKnight, GS (reprint author), Univ Washington, Dept Pharmacol, Box 357750, Seattle, WA 98195 USA. EM mcknight@u.washington.edu OI Nolan, Michael/0000-0002-2581-0814 FU NIGMS NIH HHS [GM32875, T32 GM07270] NR 41 TC 20 Z9 21 U1 0 U2 0 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 APR PY 2005 VL 19 IS 4 BP 982 EP 991 DI 10.1210/me.2004-0343 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 908YN UT WOS:000227826200014 PM 15618289 ER PT J AU Petryshen, TL Middleton, FA Kirby, A Aldinger, KA Purcell, S Tahl, AR Morley, CP McGann, L Gentile, KL Rockwell, GN Medeiros, HM Carvalho, C Macedo, A Dourado, A Valente, J Ferreira, CP Patterson, NJ Azevedo, MH Daly, MJ Pato, CN Pato, MT Sklar, P AF Petryshen, TL Middleton, FA Kirby, A Aldinger, KA Purcell, S Tahl, AR Morley, CP McGann, L Gentile, KL Rockwell, GN Medeiros, HM Carvalho, C Macedo, A Dourado, A Valente, J Ferreira, CP Patterson, NJ Azevedo, MH Daly, MJ Pato, CN Pato, MT Sklar, P TI Support for involvement of neuregulin 1 in schizophrenia pathophysiology SO MOLECULAR PSYCHIATRY LA English DT Article DE linkage disequilibrium; haplotypes; oligonucleotide array sequence analysis; gene expression; single nucleotide-polymorphisms; transcript variant ID FAMILY-BASED ASSOCIATION; GENOME-WIDE SEARCH; AT-RISK HAPLOTYPE; GENETIC-VARIATION; SUSCEPTIBILITY GENES; POPULATION STRATIFICATION; BIPOLAR DISORDER; CHROMOSOME 8P21; NO ASSOCIATION; DYSBINDIN GENE AB Schizophrenia is a common, multigenic psychiatric disorder. Linkage studies, including a recent meta-analysis of genome scans, have repeatedly implicated chromosome 8p12-p23.1 in schizophrenia susceptibility. More recently, significant association with a candidate gene on 8p12, neuregulin 1 (NRG1), has been reported in several European and Chinese samples. We investigated NRG1 for association in schizophrenia patients of Portuguese descent to determine whether this gene is a risk factor in this population. We tested NRG1 markers and haplotypes for association in 111 parent-proband trios, 321 unrelated cases, and 242 control individuals. Associations were found with a haplotype that overlaps the risk haplotype originally reported in the Icelandic population ('Hap(ICE)'), and two haplotypes located in the 30 end of NRG1 ( all P<0.05). However, association was not detected with Hap(ICE) itself. Comparison of NRG1 transcript expression in peripheral leukocytes from schizophrenia patients and unaffected siblings identified 3.8-fold higher levels of the SMDF variant in patients ( P = 0.039). Significant positive correlations ( P<0.001) were found between SMDF and HRG-beta 2 expression and between HRG-gamma and ndf43 expression, suggesting common transcriptional regulation of NRG1 variants. In summary, our results suggest that haplotypes across NRG1 and multiple NRG1 variants are involved in schizophrenia. C1 MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. SUNY Syracuse, Ctr Neuropsychiat Genet, Syracuse, NY USA. SUNY Syracuse, Dept Psychiat, Syracuse, NY USA. SUNY Syracuse, Dept Neurosci & Physiol, Syracuse, NY USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Georgetown Univ, Dept Psychiat, Washington, DC USA. Univ Coimbra, Coimbatore, Tamil Nadu, India. Psychiat Serv, Azores, Portugal. Vet Adm Med Ctr, Washington, DC 20422 USA. Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. RP Sklar, P (reprint author), Psychiat & Neurodev Genet Unit, 149 13th St, Charlestown, MA 02129 USA. EM sklar@psych.mgh.harvard.edu RI macedo santos, antonio/M-5737-2013; Morley, Christopher P/K-1907-2014; OI macedo santos, antonio/0000-0003-2180-2718; Morley, Christopher P/0000-0003-0185-7148; de Oliveira Barreto Coimbra Carvalho, Celia Maria/0000-0003-4453-8139 FU NIMH NIH HHS [MH 52618, MH 058693] NR 50 TC 126 Z9 134 U1 3 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD APR PY 2005 VL 10 IS 4 BP 366 EP 374 DI 10.1038/sj.mp.4001608 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 911MQ UT WOS:000228007600008 PM 15545978 ER PT J AU Horowitz, SH AF Horowitz, SH TI What happens when cutaneous nerves are injured during venipuncture? SO MUSCLE & NERVE LA English DT Editorial Material ID WHOLE-BLOOD DONATION; NEUROPATHIC PAIN; MECHANISMS C1 Massachusetts Gen Hosp, Dept Neurol, Nerve Injury Unit, Boston, MA 02114 USA. RP Horowitz, SH (reprint author), Massachusetts Gen Hosp, Dept Neurol, Nerve Injury Unit, 55 Fruit St, Boston, MA 02114 USA. EM shhorowitz@partners.org NR 12 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD APR PY 2005 VL 31 IS 4 BP 415 EP 417 DI 10.1002/mus.20287 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 908ZT UT WOS:000227829400001 PM 15704141 ER PT J AU Katz, MS Schapira, L Harisinghani, MG Hughes, KS AF Katz, MS Schapira, L Harisinghani, MG Hughes, KS TI Palpable right breast mass in a pregnant woman SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Article DE mastectomy; chemotherapy and radiotherapy ID ADJUVANT CHEMOTHERAPY; PREMENOPAUSAL WOMEN; CANCER; RADIOTHERAPY; IRRADIATION; THERAPY AB Background A 29-year-old female presented with a palpable right breast mass at a 12-week prenatal visit. She had no family history of breast or ovarian cancer. Ultrasound revealed a 3 cm lobulated mass, which was confirmed to be malignant by a core biopsy. Postmastectomy pathology at 15 weeks'gestation demonstrated this mass to be a stage T2N0M0 high-grade invasive ductal carcinoma with 0/20 axillary nodes involved. A staging CT scan postpartum showed an enlarged right internal mammary lymph node, confirmed by MRI as suspicious for malignancy. Investigations Physical examination, breast ultrasound, core biopsy, mastectomy, CT scan, MRI. Diagnosis Pregnancy-associated breast carcinoma. Management Mastectomy, chemotherapy and radiotherapy. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Avon Fdn, Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Breast & Ovarian Canc Genet & Risk Assessment Pro, Boston, MA 02114 USA. RP Katz, MS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St COX 3, Boston, MA 02114 USA. EM mskatz@partners.org OI Hughes, Kevin/0000-0003-4084-6484 NR 13 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD APR PY 2005 VL 2 IS 4 BP 218 EP 221 DI 10.1038/ncponc0135 PG 4 WC Oncology SC Oncology GA 926JI UT WOS:000229119100014 PM 16264937 ER PT J AU Zietman, AL AF Zietman, AL TI Do patients with low-risk and intermediate-risk prostate cancer benefit from androgen deprivation? SO NATURE CLINICAL PRACTICE UROLOGY LA English DT Editorial Material DE androgen deprivation; brachytherapy; prostatectomy; radiation ID RADIATION-THERAPY; TRIAL; RADIOTHERAPY C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Zietman, AL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM azietman@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1743-4270 J9 NAT CLIN PRACT UROL JI Nat. Clin. Pract. Urol. PD APR PY 2005 VL 2 IS 4 BP 160 EP 161 DI 10.1038/ncpuro0148 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 927GI UT WOS:000229180000003 ER PT J AU Daly, MJ Altshuler, D AF Daly, MJ Altshuler, D TI Partners in crime SO NATURE GENETICS LA English DT Editorial Material ID GENETIC ASSOCIATION; DISEASE AB The genetic culprits that contribute to common diseases remain at large, despite dedicated sleuthing by many laboratories. A new study evaluates the power of genome-wide searches for variants acting in combination, with results that are both unexpected and encouraging. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Broad Inst Harvard, Cambridge, MA USA. MIT, Cambridge, MA 02139 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Daly, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. EM mjdaly@broad.mit.edu; altshuler@molbio.mgh.harvard.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 14 TC 19 Z9 19 U1 0 U2 1 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 APR PY 2005 VL 37 IS 4 BP 337 EP 338 DI 10.1038/ng0405-337 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 911XL UT WOS:000228040000005 PM 15800643 ER PT J AU Schonberger, J Wang, L Shin, TJ Kim, SD Depreux, FFS Zhu, H Zon, L Pizard, A Kim, JB MacRae, CA Mungall, AJ Seidman, JG Seidman, CE AF Schonberger, J Wang, L Shin, TJ Kim, SD Depreux, FFS Zhu, H Zon, L Pizard, A Kim, JB MacRae, CA Mungall, AJ Seidman, JG Seidman, CE TI Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss SO NATURE GENETICS LA English DT Article ID DROSOPHILA-EYES-ABSENT; PROTEIN; GENE; PHOSPHATASE; HOMOLOGS; REVEALS; DFNA10 AB We identified a human mutation that causes dilated cardiomyopathy and heart failure preceded by sensorineural hearing loss (SNHL). Unlike previously described mutations causing dilated cardiomyopathy that affect structural proteins, this mutation deletes 4,846 bp of the human transcriptional coactivator gene EYA4. To elucidate the roles of eya4 in heart function, we studied zebrafish embryos injected with antisense morpholino oligonucleotides. Attenuated eya4 transcript levels produced morphologic and hemodynamic features of heart failure. To determine why previously described mutated EYA4 alleles(1,2) cause SNHL without heart disease, we examined biochemical interactions of mutant Eya4 peptides. Eya4 peptides associated with SNHL, but not the shortened 193 amino acid peptide associated with dilated cardiomyopathy and SNHL, bound wild-type Eya4 and associated with Six proteins. These data define unrecognized and crucial roles for Eya4-Six-mediated transcriptional regulation in normal heart function. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Hosp Wurzburg, Dept Med, D-97080 Wurzburg, Germany. Inst Clin Biochem & Pathobiochem, D-97080 Wurzburg, Germany. Massachusetts Gen Hosp, Dev Biol Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Childrens Hosp, Div Pulm Med, Boston, MA 02115 USA. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. RP Seidman, CE (reprint author), Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cseidman@genetics.med.harvard.edu RI Tang, Macy/B-9798-2014; OI Zhu, Hao/0000-0002-8417-9698 NR 16 TC 106 Z9 116 U1 1 U2 11 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 APR PY 2005 VL 37 IS 4 BP 418 EP 422 DI 10.1038/ng1527 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 911XL UT WOS:000228040000026 PM 15735644 ER PT J AU von Boehmer, H AF von Boehmer, H TI Mechanisms of suppression by suppressor T cells SO NATURE IMMUNOLOGY LA English DT Review ID DOMINANT TRANSPLANTATION TOLERANCE; IMMUNOLOGICAL SELF-TOLERANCE; IN-VIVO; DENDRITIC CELLS; REGULATORY CELLS; CUTTING EDGE; IMMUNE-RESPONSES; GENE-EXPRESSION; ANTIGEN; RECEPTOR AB Mechanisms of immunosuppression by CD4(+)CD25(+) suppressor T cells have been addressed using many in vitro and in vivo conditions. However, those studies have not yielded a single mode of action. This review will discuss the mechanisms of suppression, which include the local secretion of cytokines such as TGF-beta and direct cell contact through binding of cell surface molecules such as CTLA-4 on suppressor T cells to CD80 and CD86 molecules on effector T cells. Suppression requires the appropriate colocalization of suppressor and effector T cells in different tissue and may involve the interference with T cell receptor signaling that triggers transcription factors important in regulating effector cell function. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu FU NIAID NIH HHS [R37AI51378] NR 72 TC 699 Z9 729 U1 5 U2 17 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 APR PY 2005 VL 6 IS 4 BP 338 EP 344 DI 10.1038/ni1180 PG 7 WC Immunology SC Immunology GA 909KY UT WOS:000227860000004 PM 15785759 ER PT J AU Langenau, DM Zon, LI AF Langenau, DM Zon, LI TI The zebrafish: A new model of T-cell and thymic development SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID RECEPTOR-BETA-CHAIN; RECOMBINATION ACTIVATING GENE-1; HUMAN NASAL-MUCOSA; DANIO-RERIO; CHANNEL CATFISH; RAINBOW-TROUT; PARALICHTHYS-OLIVACEUS; TRANSGENIC ZEBRAFISH; JAPANESE FLOUNDER; IMMUNE-SYSTEM AB T-cell and thymic development are processes that have been highly conserved throughout vertebrate evolution. Mammals, birds, reptiles and fish share common molecular signalling pathways that regulate the development of the adaptive immune system. This Review article focuses on defining the similarities and differences between zebrafish and mammalian T-cell immunobiology, and it highlights the advantages of using the zebrafish as a genetic model to uncover mutations that affect T-cell and thymic development. Finally, we summarize the use of the zebrafish as a new model for assessing stem-cell function and for drug discovery. C1 Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zon, LI (reprint author), Childrens Hosp, Stem Cell Program, 1 Blackfan Circle,Karp Bldg,7th Floor, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu NR 105 TC 79 Z9 81 U1 1 U2 10 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 APR PY 2005 VL 5 IS 4 BP 307 EP 317 DI 10.1038/nri1590 PG 11 WC Immunology SC Immunology GA 912PX UT WOS:000228092800014 PM 15803150 ER PT J AU Kang, HJ Yoon, WJ Moon, GJ Kim, DY Sohn, S Kwon, HJ Gwag, BJ AF Kang, HJ Yoon, WJ Moon, GJ Kim, DY Sohn, S Kwon, HJ Gwag, BJ TI Caspase-3-mediated cleavage of PHF-1 tau during apoptosis irrespective of excitotoxicity and oxidative stress: an implication to Alzheimer's disease SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Alzheimer's disease; neurofibrillary tangles; caspase-3; apoptosis; tau; glutamate ID CULTURED CORTICAL-NEURONS; NEUROFIBRILLARY PATHOLOGY; GLUTAMATE TRANSPORT; TRANSGENIC MICE; CELL-DEATH; IN-VITRO; PROTEIN; PHOSPHORYLATION; NECROSIS; NEURODEGENERATION AB Excitotoxicity, oxidative stress, and apoptosis have been recognized as routes to neuronal death in various neurological diseases. We examined the possibility that PHF-1 tau, a substrate for various proteases, would be selectively cleaved depending upon routes of neuronal death. Cleavage form of PHF-1 tau was not observed in cortical cell cultures exposed to excitotoxins or oxidative stress that cause neuronal cell necrosis. PHF-1 tau was cleaved within 8 h following exposure of cortical cell cultures to apoptosis-inducing agents. This cleavage was blocked by inclusion of zDEVD-fmk, an inhibitor of caspase-3, and accompanied by activation of caspase-3. Levels and cleavage of PHF-1 tau were markedly increased in AD brain compared with control. Moreover, PHF-1 tau and active caspase-3 were colocalized mostly in tangle-bearing neurons. The current findings suggest that PHF-1 tau is cleaved by caspase-3 during apoptosis and neurodegenerative process in AD. (c) 2005 Elsevier Inc. All rights reserved. C1 Ajou Univ, Dept Pharmacol, Sch Med, Suwon 442749, Kyungkido, South Korea. Ajou Univ, Dept Neurosci, Sch Med, Suwon 442749, Kyungkido, South Korea. Ajou Univ, Ctr Intervent Therapy Stroke & Alzheimers Dis, Sch Med, Suwon 442749, Kyungkido, South Korea. Ajou Univ, Cell Biol Lab, Sch Med, Suwon 442749, Kyungkido, South Korea. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Charlestown, MA 01219 USA. Harvard Univ, Sch Med, Neurobiol Dis Lab, Genet & Aging Res Unit,Dept Neurol, Charlestown, MA 01219 USA. RP Gwag, BJ (reprint author), Ajou Univ, Dept Pharmacol, Sch Med, San 5, Suwon 442749, Kyungkido, South Korea. EM bjgwag@ajou.ac.kr NR 44 TC 20 Z9 24 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD APR PY 2005 VL 18 IS 3 BP 450 EP 458 DI 10.1016/j.nbd.2004.12.004 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 908WI UT WOS:000227820500004 PM 15755671 ER PT J AU Anselmi, L Cervio, E Guerrini, S Vicini, R Agazzi, A Dellabianca, A Reeve, JRJ Tonini, M Sternini, C AF Anselmi, L Cervio, E Guerrini, S Vicini, R Agazzi, A Dellabianca, A Reeve, JRJ Tonini, M Sternini, C TI Identification of galanin receptor 1 on excitatory motor neurons in the guinea pig ileum SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE enteric neurons; ascending and descending pathways; interneurons; intrinsic primary afferent neurons ID SMALL-INTESTINE; SYNAPTIC-TRANSMISSION; MYENTERIC NEURONS; MOTILITY REFLEXES; ENTERIC NEURONS; CL-SECRETION; SUBTYPES; EXPRESSION; IMMUNOREACTIVITY; ACETYLCHOLINE AB Exogenously administered galanin inhibits cholinergic transmission to the longitudinal muscle and reduces peristaltic efficiency in the guinea pig ileum with a mechanism partially mediated by galanin receptor 1 (GAL-R1). We investigated the effect of exogenous galanin 1-16, which has high affinity for GAL-R1, on the ascending excitatory reflex of the circular muscle elicited by radial distension in isolated segments of guinea pig ileum. We used a three-compartment bath that allows dissecting the ascending pathway into the oral (site of excitatory motor neurons), intermediate (site of ascending interneurons) and caudal compartment (site of intrinsic primary afferent neurons). Galanin 1-16 (0.3-3 mu mol L-1) applied to the oral compartment inhibited in a concentration-dependent manner the ascending excitatory reflex elicited by the wall distension in the caudal compartment. This effect was antagonized by the GAL-R1 antagonist, RWJ-57408 (1 and 10 mu mol L-1). By contrast, galanin 1-16 was ineffective when added to the intermediate or caudal compartment up to 3 mu mol L-1. GAL-R1 immunoreactive neurons did not contain neuron-specific nuclear protein, a marker for intrinsic primary afferent neurons. These findings indicate that GAL-R1s are present on motor neurons responsible for the ascending excitatory reflex, but not on ascending interneurons and intrinsic primary afferent neurons. C1 Vet Adm Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, Div Digest Dis, CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA USA. Univ Pavia, Dept Pharmacol & Physiol Sci, I-27100 Pavia, Italy. Univ Bologna, Dept Internal Med, Bologna, Italy. S Maugeri Fdn, Pavia, Italy. RP Anselmi, L (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, Div Digest Dis, CURE, Bldg 115,Room 224,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM lanselmi@mednet.ucla.edu OI Cervio, Elisabetta/0000-0002-9922-077X FU NIDDK NIH HHS [DK41301, DK57037] NR 36 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD APR PY 2005 VL 17 IS 2 BP 273 EP 280 DI 10.1111/j.1365-2982.2004.00590.x PG 8 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 912TU UT WOS:000228103600015 PM 15787947 ER PT J AU Ojanen, V Mottonen, R Pekkola, J Jaaskelainen, IP Joensuu, R Autti, T Sams, M AF Ojanen, V Mottonen, R Pekkola, J Jaaskelainen, IP Joensuu, R Autti, T Sams, M TI Processing of audiovisual speech in Broca's area SO NEUROIMAGE LA English DT Article DE Broca's area; audiovisual vowel; brain ID PARAMETRIC MANIPULATION; RESPONSE COMPETITION; MAGNETIC STIMULATION; CROSSMODAL BINDING; PREMOTOR CORTEX; MIRROR NEURONS; BRAIN IMAGES; PERCEPTION; FMRI; ACTIVATION AB We investigated cerebral processing of audiovisual speech stimuli in humans using functional magnetic resonance imaging (fMRI). Ten healthy volunteers were scanned with a 'clustered volume acquisition' paradigm at 3 T during observation of phonetically matching (e.g., visual and acoustic /y/) and conflicting (e.g., visual /a/ and acoustic /y/) audiovisual vowels. Both stimuli activated the sensory-specific auditory and visual cortices, along with the superior temporal, inferior frontal (Broca's area), premotor, and visual-parietal regions bilaterally. Phonetically conflicting vowels, contrasted with matching ones, specifically increased activity in Broca's area. Activity during phonetically matching stimuli, contrasted with conflicting ones, was not enhanced in any brain region. We suggest that the increased activity in Broca's area reflects processing of conflicting visual and acoustic phonetic inputs in partly disparate neuron populations. On the other hand, matching acoustic and visual inputs would converge on the same neurons. (c) 2004 Elsevier Inc. All rights reserved. C1 Aalto Univ, Lab Computat Engn, FIN-02015 Helsinki, Finland. Aalto Univ, Adv Magnet Imaging Ctr, Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Radiol, Helsinki, Finland. Massachusetts Gen Hosp, Charlestown, MA USA. MIT, Charlestown, MA USA. Harvard Univ, Med Sch, A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Ojanen, V (reprint author), Aalto Univ, Lab Computat Engn, POB 3000, FIN-02015 Helsinki, Finland. EM viloja@lce.hut.fi RI Jaaskelainen, Iiro/C-7392-2012; Sams, Mikko/G-7060-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950; FU NICHD NIH HHS [R01 HD40712] NR 47 TC 88 Z9 88 U1 2 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 1 PY 2005 VL 25 IS 2 BP 333 EP 338 DI 10.1016/j.neuroimage.2004.12.001 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 915XI UT WOS:000228344300001 PM 15784412 ER PT J AU Ahmed, SU Martin, NM Chang, YC AF Ahmed, SU Martin, NM Chang, YC TI Patient selection and trial methods for intraspinal drug delivery for chronic pain: A national survey SO NEUROMODULATION LA English DT Article DE chronic pain; intraspinal drug delivery; trial protocol ID INTRATHECAL MORPHINE INFUSION; SPINAL-CORD STIMULATION; MANAGEMENT; OUTCOMES; THERAPY; CANCER AB Objectives Intraspinal drug delivery via indwelling pump is an effective means of treating refractory pain. Before a patient is selected for pump implantation, an intraspinal drug delivery trial must be performed to establish side-effects and efficacy profiles. No consensus protocol currently exists for such trials. As a preliminary step in this process, we surveyed a group of interventional pain physicians to explore attitudes on patient selection criteria, drug choice, trial techniques, and efficacy assessment. Methods The questionnaire was sent for self-administration to 1500 interventional pain physicians, each of whom had implanted one or more Medtronic((R)) implantable infusion pumps. Results We received 205 completed surveys. Among the respondents, most were anesthesiologists (76%) and in private practice (82%). Nearly half (45%) of the respondents use the continuous intrathecal infusion technique to select patients for permanent implants. Conclusions Trial practices vary widely in terms of patient selection, medication choice, technique, and efficacy evaluation. We hope that our findings will encourage a concerted effort to evaluate existing trial protocols in order to establish a reliable standard of care. C1 Massachusetts Gen Hosp, Pain Ctr, Dept Anesthesia & Crit Care, Boston, MA 02144 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ahmed, SU (reprint author), Massachusetts Gen Hosp, Pain Ctr, Dept Anesthesia & Crit Care, WACC 324,15 Parkman St, Boston, MA 02144 USA. EM sahmed@partners.org NR 19 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1094-7159 J9 NEUROMODULATION JI Neuromodulation PD APR PY 2005 VL 8 IS 2 BP 112 EP 120 DI 10.1111/j.1525-1403.2005.00227.x PG 9 WC Medicine, Research & Experimental; Clinical Neurology SC Research & Experimental Medicine; Neurosciences & Neurology GA 909YM UT WOS:000227896600006 PM 22151440 ER PT J AU Pontikis, CC Cotman, SL Alexander, N MacDonald, ME Cooper, JD AF Pontikis, CC Cotman, SL Alexander, N MacDonald, ME Cooper, JD TI The mild neurodegenerative phenotype of CLN3(Delta ex7/8) knock-in mice is accompanied by prominent astrocytosis at the advanced stages of murine JNCL SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Meeting Abstract CT 106th Annual Meeting of the British-Neuropathological-Society CY JAN 12-14, 2005 CL Inst Child Hlth, London, ENGLAND SP British Neuropathol Soc HO Inst Child Hlth C1 Univ London Kings Coll, Pediat Storage Disorders Lab, Inst Psychiat, London SE5 8AF, England. Univ London Kings Coll, Dept Neurosci, Inst Psychiat, London SE5 8AF, England. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. EM j.cooper@iop.kcl.ac.uk NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD APR PY 2005 VL 31 IS 2 BP 228 EP 228 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 905VA UT WOS:000227597500039 ER PT J AU Hedley-Whyte, ET AF Hedley-Whyte, ET TI West Nile encephalopoliomyelitis in a man with chronic lymphocytic leukaemia SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Meeting Abstract CT 106th Annual Meeting of the British-Neuropathological-Society CY JAN 12-14, 2005 CL Inst Child Hlth, London, ENGLAND SP British Neuropathol Soc HO Inst Child Hlth C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuropathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD APR PY 2005 VL 31 IS 2 BP 235 EP 235 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 905VA UT WOS:000227597500056 ER PT J AU Habecker, BA Gritman, KR Willison, BD Van Winkle, DM AF Habecker, BA Gritman, KR Willison, BD Van Winkle, DM TI Myocardial infarction stimulates galanin expression in cardiac sympathetic neurons SO NEUROPEPTIDES LA English DT Article DE vasoactive intestinal peptide; substance P; neuropeptide Y; galanin; axotomy ID VASOACTIVE-INTESTINAL-PEPTIDE; SUPERIOR CERVICAL-GANGLION; NERVE GROWTH-FACTOR; SUBSTANCE-P; NEUROPEPTIDE EXPRESSION; SENSORY NEURONS; ANESTHETIZED CATS; MESSENGER-RNAS; CANINE HEART; RAT-HEART AB Cardiac ischemia-reperfusion alters sympathetic neurotransmission in the heart, but little is known about its effect on neuropeptide expression in sympathetic neurons. Ischemia followed by reperfusion induces the production of inflammatory cytokines in the heart, including interleukin-6 and cardiotrophin-1. These cytokines and related molecules inhibit the expression of neuropeptide Y (NPY), and stimulate the expression of vasoactive intestinal peptide (VIP), substance P (SubP), and galanin (GAL) in cultured sympathetic neurons. Therefore, we quantified NPY, VIP, SubP, and GAL mRNA in neurons of the stellate ganglia I week after ischemia-reperfusion to determine if neuropeptide expression was altered in cardiac sympathetic neurons. NPY, VIP, and SubP mRNAs were unchanged compared to unoperated control animals, but GAL mRNA was increased significantly. The increased GAL mRNA was not accompanied by elevated GAL peptide content in the stellate ganglia. Galanin content was increased significantly in the heart, however, indicating that elevated GAL mRNA led to increased peptide production. GAL content was increased in the left ventricle below the coronary artery ligation, but was not increased significantly in the atria or the base of the heart above the ligation. The buildup of GAL specifically in the damaged left ventricle is consistent with previous reports that GAL is transported to regenerating nerve endings after axon damage. (c) 2004 Elsevier Ltd. All rights reserved. C1 Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Anesthesiol, Portland, OR 97239 USA. Portland VA Med Ctr, Anesthesiol Serv, Portland, OR 97239 USA. RP Habecker, BA (reprint author), Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM habecker@ohsu.edu OI Habecker, Beth/0000-0002-4658-8730 FU NHLBI NIH HHS [HL68231, R01 HL068231] NR 53 TC 19 Z9 20 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD APR PY 2005 VL 39 IS 2 BP 89 EP 95 DI 10.1016/j.npep.2004.11.003 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 909MC UT WOS:000227863000004 PM 15752542 ER PT J AU Curry, WT Sethi, MK Ogilvy, CS Carter, BS AF Curry, WT Sethi, MK Ogilvy, CS Carter, BS TI Factors associated with outcome after hemicraniectomy for large middle cerebral artery territory infarction SO NEUROSURGERY LA English DT Article DE hemicraniectomy; outcome; stroke; surgery ID DECOMPRESSIVE CRANIECTOMY; MAGNETIC-RESONANCE; HEMISPHERIC INFARCTION; ACUTE STROKE; SURGERY; SCALE; INDEX; RATS AB OBJECTIVE: Large or malignant middle cerebral artery infarction is associated with a high mortality rate. Hemicraniectomy reduces intracranial pressure and has been demonstrated to increase survival. Questions remain regarding selection of patients for surgery and functional outcomes. METHODS: We retrospectively reviewed the charts, operative reports, and images of patients who underwent hemicraniectomy for cerebral infarction at our institution between 1990 and 2002. Stroke volume and craniectomy area image analyses were performed with National Institutes of Health image J software. Short-term outcome was measured with the Glasgow Outcome Scale. The requirement for second surgical decompression was also used as a measure of short-term outcome. Outcome 1 year after stroke was assessed with mailed self-report questionnaires to patients or providers with answers yielding information pertinent to the Barthel index for physical disability, the Reintegration to Normal Living Index, and the Zung Depression Index. Univariate and multivariate logistic regression analyses were used to consider factors associated with outcome. RESULTS: Thirty-eight patients with large hemispheric infarcts (average volume, 407 cm(3)) were treated with hemicraniectomy during the study period. Thirty-two patients survived more than 1 year after surgery. Twenty patients responded to a questionnaire scoring late physical disability (Barthel Index), quality of life (Reintegration to Normal Living Index), and depression (Zung Depression Index). The average Barthel Index score was 67. Barthel Index score and ability to walk were strongly correlated with age but not time to surgery, volume of infarction, or craniectomy size. Patients exhibited moderate to severe decrements in quality of life and increased incidence of depression across all age groups. Reoperation, an indicator for early operative failure, was required in six patients. These patients were significantly younger and had significantly higher volumes of cerebral infarction. CONCLUSION: Hemicraniectomy is life-saving treatment for large middle cerebral artery infarction. Good functional outcomes can be obtained but are less likely in older patients. Younger patients with large-volume strokes may benefit from multiple decompressions, if necessary. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pappas Ctr Neurooncol Y9E,Neurosurg Serv, Boston, MA 02114 USA. RP Carter, BS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pappas Ctr Neurooncol Y9E,Neurosurg Serv, 55 Fruit St, Boston, MA 02114 USA. EM bcarter@partners.org NR 33 TC 67 Z9 72 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD APR PY 2005 VL 56 IS 4 BP 681 EP 691 DI 10.1227/01.NEU.0000156604.41886.62 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 915EH UT WOS:000228280200009 PM 15792506 ER PT J AU Binder, DK Rau, GM Starr, PA AF Binder, DK Rau, GM Starr, PA TI Risk factors for hemorrhage during microelectrode-guided deep brain stimulator implantation for movement disorders SO NEUROSURGERY LA English DT Article DE deep brain stimulation; globus pallidus; hemorrhage; microelectrode recording; subthalamic nucleus; thalamus ID ADVANCED PARKINSONS-DISEASE; CHRONIC ELECTRICAL-STIMULATION; VENTRALIS INTERMEDIUS NUCLEUS; SUBTHALAMIC NUCLEUS; TECHNICAL APPROACH; ESSENTIAL TREMOR; GLOBUS-PALLIDUS; POSTEROVENTRAL PALLIDOTOMY; THALAMIC-STIMULATION; FOLLOW-UP AB OBJECTIVE: Although hemorrhage is a well-known complication of microelectrodeguided deep brain stimulation (DBS) surgery, risk factors for the development of hemorrhage have not been well defined. We analyzed the risk factors for symptomatic and asymptornatic hemorrhage in a large series of DBS implantations into the subthalamic nucleus, ventrolateral thalamus, and internal globus pallidus. METHODS: All DBS procedures performed by a single surgeon at our institution between June 1998 and May 2004 were included in this study. All patients had postoperative imaging (magnetic resonance imaging or computed tomography) 4 to 24 hours after surgery. Hematomas were noted and scored as symptomatic or asymptomatic. Statistical correlation of factors affecting risk of hematoma formation was performed by use of logistic regression analysis. RESULTS: The total number of lead implantations was 481. There were 6 symptomatic hematomas and 10 asymptornatic hematomas. Three of the symptomatic hematomas resulted in permanent new neurological deficit. The risk of hematorna (of any type) per lead implantation was 3.3%, whereas the risk of permanent deficit from hematoma was 0.6%. Patients who developed hematomas had a slightly greater number of microelectrode recording penetrations than patients who did not have hematomas, but this difference did not reach statistical significance. There was not a statistically significant relationship between risk of hematoma and patient age or diagnosis. There was a significant effect of brain target (P = 0.001), with only I hemorrhage detected after thalamic DBS. CONCLUSION: DBS is generally safe, with only 0.6% of implantations associated with permanent neurological deficit. The incremental risk of successive serial microelectrode penetrations is small. C1 Univ Calif San Francisco, Moffitt Hosp, Dept Neurol Surg, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Care Ctr, San Francisco, CA USA. RP Binder, DK (reprint author), Univ Calif San Francisco, Moffitt Hosp, Dept Neurol Surg, M779,Box 0112, San Francisco, CA 94143 USA. EM dbinder@itsa.ucsf.edu NR 38 TC 127 Z9 135 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X EI 1524-4040 J9 NEUROSURGERY JI Neurosurgery PD APR PY 2005 VL 56 IS 4 BP 722 EP 728 DI 10.1227/01.NEU.0000156473.57196.7E PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 915EH UT WOS:000228280200019 PM 15792511 ER PT J AU Conroy, MB Majchrzak, NE Silverman, CB Chang, YC Regan, S Schneider, LI Rigotti, NA AF Conroy, MB Majchrzak, NE Silverman, CB Chang, YC Regan, S Schneider, LI Rigotti, NA TI Measuring provider adherence to tobacco treatment guidelines: A comparison of electronic medical record review, patient survey, and provider survey SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SMOKING-CESSATION; DOCUMENTATION; PHYSICIANS; QUALITY AB An accurate method of measuring primary care providers' tobacco counseling actions is needed for monitoring adherence to clinical practice guidelines. We compared three methods of measuring providers' tobacco counseling practices: electronic medical record (EMR) review, patient survey, and provider survey. We mailed a survey to 1,613 smokers seen by 114 Boston-area primary care providers during a 2-month period to assess what tobacco counseling actions had occurred at the visit (N = 766; 47% response rate). Smokers' reports were compared with the EMR and with their providers' self-reported usual tobacco counseling practices, derived from a provider survey (N = 110; 96% response rate). Patients reported receiving each counseling action more frequently than providers documented it in the EMR. Agreement between the patient survey and the EMR was poor for all 5A steps (kappa statistic = 0.01-0.22). Providers reported that they often or always performed each 5A action at a higher rate than indicated by EMR or patient report. However, providers who said they often or always performed individual 5A steps did not have consistently higher mean rates of EMR documentation or patient report than those who said they performed the 5A's less frequently. Little agreement was found among the three methods of measuring primary care providers' tobacco counseling actions. Implementing an EMR does not necessarily improve providers' documentation of tobacco interventions, but EMR adaptations that would standardize provider documentation of tobacco counseling might make the EMR a more reliable tool for monitoring providers' delivery of tobacco treatment services. C1 Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM nrigotti@partners.org OI Regan, Susan/0000-0003-0940-2017 FU NHLBI NIH HHS [HL04440]; PHS HHS [5T32-HP-11001-14] NR 22 TC 60 Z9 60 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD APR PY 2005 VL 7 SU 1 BP S35 EP S43 DI 10.1080/14622200500078089 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 927UN UT WOS:000229226100006 PM 16036268 ER PT J AU Conroy, MB Majchrzak, NE Regan, S Silverman, CB Schneider, LI Rigotti, NA AF Conroy, MB Majchrzak, NE Regan, S Silverman, CB Schneider, LI Rigotti, NA TI The association between patient-reported receipt of tobacco intervention at a primary care visit and smokers' satisfaction with their health care SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID PRACTITIONERS; PHYSICIANS; SMOKING AB U.S. Public Health Service (USPHS) clinical guidelines for tobacco treatment recommend that providers routinely counsel smokers using a five-step algorithm (5A's): ask about tobacco use, advise smokers to quit, assess interest in quitting, assist with treatment, and arrange follow-up. A potential barrier to compliance is providers' concern that addressing smoking might alienate smokers, especially those not ready to quit. A survey was mailed to 1,985 patients seen at one of eight Boston-area primary care practices from January I to March 31, 2003, and identified as smokers by chart review. The survey assessed respondents' receipt of the 5A's at their visit and their satisfaction with the provider's tobacco treatment and with their overall health care. We used multivariable logistic regression models to assess the association between satisfaction with care and patient-reported receipt of each 5A step, adjusted for age, sex, education, race, health status, smoking intensity, readiness to quit, and length of relationship with provider. Of 1,160 respondents (58% response rate), 765 reported that they smoked at the time of the visit. They reported high levels of satisfaction with their tobacco-related care and overall care. Patient-reported receipt of each 5A step was significantly associated with greater patient satisfaction with tobacco-related care and with overall health care, even after adjusting for a smoker's readiness to quit smoking. Satisfaction with overall health care increased as counseling intensity increased. Patient reports of smoking cessation interventions delivered during primary care practice are associated with greater patient satisfaction with their health care, even among smokers not ready to quit. Providers can follow USPHS guidelines with smokers without fear of alienating those not yet considering quitting. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM nrigotti@partners.org OI Regan, Susan/0000-0003-0940-2017 FU NHLBI NIH HHS [HL04440]; PHS HHS [5T32-HP-11001-14] NR 19 TC 37 Z9 37 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD APR PY 2005 VL 7 SU 1 BP S29 EP S34 DI 10.1080/14622200500078063 PG 6 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 927UN UT WOS:000229226100005 PM 16036267 ER PT J AU Bradley, RL Mansfield, JPR Maratos-Flier, E AF Bradley, RL Mansfield, JPR Maratos-Flier, E TI Neuropeptides, including neuropeptide Y and melanocortins, mediate lipolysis in murine adipocytes SO OBESITY RESEARCH LA English DT Article DE adipose tissue; free fatty acids; alpha-melanocyte-stimulating-hormone; neuropeptide Y ID WHITE ADIPOSE-TISSUE; RABBIT ADIPOCYTES; RAT ADIPOCYTES; FAT-CELLS; OBESITY; LEPTIN; ENDOCRINE; RECEPTORS; GENE; NPY AB Objective: To determine whether key appetite-regulating neuropeptides such as melanin-concentrating hormone (MCH), neuropeptide Y (NPY), and alpha-melanocyte-stimulating hormone (alpha-MSH), which are known to mediate energy balance through centrally mediated pathways, also have direct acute effects on the lipolytic activity of murine adipocytes. Research Methods and Procedures: Fully differentiated 3T3-L1 adipocytes serum starved overnight in Dulbecco's modified Eagle medium containing 2% bovine serum albumin or freshly isolated mouse adipocytes were incubated for up to 2 hours in the absence and presence of 100 nM each of NPY, MCH, alpha-MSH, the melanocortin receptor agonist MTII, or isoproterenol as a control. Free fatty acids secreted into the incubation medium Were measured using a commercially available nonesterified fatty acid C test kit. Results: Treatment of 3T3-L1 cells with 100 nM NPY decreased basal free fatty acid secretion (basal, 0.006 +/- 0.001 vs. NPY, 0.001 +/- 0.0003 nM at 90 minutes,: p < 0.05), whereas both a-MSH and MTII stimulated up to a 7-fold increase in free fatty acid release (MTII, 0.238 +/- 0.004 vs. basal, 0.024 +/- 0.002 nM at 2 hours; p < 0.05; and a-MSH, 0.22 +/- 0.005 vs. basal, 0.04 +/- 0.003 nM at 2 hours; p < 0.05). Treatment with 100 nM MCH had no effect on basal free fatty acid release or on alpha-MSH-induced lipolysis during concurrent treatment. Conversely, concurrent treatment with 100 nM NPY dramatically inhibited (by similar to 90%) alpha-MSH-induced lipolysis. Similar treatment of freshly isolated mouse adipocytes showed virtually identical results. Discussion: In addition to their centrally mediated actions, appetite-regulating neuropeptides modulate adipose tissue mass through direct peripheral effects. Systemic administration of pharmacological agents altering the effects of these neuropeptides may form the basis of future obesity therapies. Thus, some of these agents will likely have direct effects on adipocytes that may serve to alter their therapeutic effectiveness. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Bradley, RL (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,RN 380A, Boston, MA 02215 USA. EM rbradley@bidmc.havard.edu FU NIDDK NIH HHS [DK56113, K01 DK-063080, R01 DK-56113, DK-53978] NR 47 TC 39 Z9 44 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD APR PY 2005 VL 13 IS 4 BP 653 EP 661 DI 10.1038/oby.2005.73 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 929QV UT WOS:000229361800003 PM 15897473 ER PT J AU Allen, RH Plati, A Viguera, AC Cohen, LS Ecker, JL AF Allen, RH Plati, A Viguera, AC Cohen, LS Ecker, JL TI Change in mood in association with obstetric event and outcome SO OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 53rd Annual Clinical Meeting of the American-College-of-Obstetricians-and-Gynecologists CY MAY 07-11, 2005 CL San Francisco, CA SP Amer Coll Obstetricans & Gynecol, Organon Pharmaceut US Inc, Novo Nordisk Pharmaceut C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2005 VL 105 IS 4 SU S BP 31S EP 31S PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 912GP UT WOS:000228065900070 ER PT J AU Cohen, LS Kornstein, S Entsuah, R Ortega-Leon, W Rummala, R Heller, VL AF Cohen, LS Kornstein, S Entsuah, R Ortega-Leon, W Rummala, R Heller, VL TI Gender-based differences in response to antidepressant therapy with venlafaxine or SSRIs SO OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 53rd Annual Clinical Meeting of the American-College-of-Obstetricians-and-Gynecologists CY MAY 07-11, 2005 CL San Francisco, CA SP Amer Coll Obstetricans & Gynecol, Organon Pharmaceut US Inc, Novo Nordisk Pharmaceut C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2005 VL 105 IS 4 SU S BP 85S EP 86S PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 912GP UT WOS:000228065900197 ER PT J AU Kassan, H Cohavy, O Rosenbaum, JT Braun, J Gordon, LK AF Kassan, H Cohavy, O Rosenbaum, JT Braun, J Gordon, LK TI Uveitis seroreactivity to candidate pANCA antigens: Mycobacterial HupB and histone H1(69-171) SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE uveitis; inflammation; pANCA; HupB; histone H1(69-171) ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; INFLAMMATORY-BOWEL-DISEASE; CHROMOSOMAL-PROTEINS HMG1; ULCERATIVE-COLITIS; CROHNS-DISEASE; AUTOIMMUNE HEPATITIS; TARGET ANTIGENS; ANCA; AUTOANTIBODIES; IDENTIFICATION AB Purpose: Certain uveitis patients express the disease-marker antibody pANCA. Histone H1 ( H1) and mycobacterial HupB ( HupB) are recently identified candidate pANCA antigens. This study addresses the hypothesis that H1 and HupB are targets of disease-associated seroreactivity in pANCA+ uveitis. Methods: Sera from 293 uveitis patients were categorized for pANCA activity. H1(69-171) and HupB recombinant proteins were used as antigenic targets in ELISA studies. Selected sera were analyzed for reactivity by Western blot. Results: Seroreactivities to ANCA, H1(69-171), and HupB were frequently detected in uveitis patients. No significant relationship existed between the level of ANCA antibody and reactivity to either recombinant antigen. There was, however, a significant, positive correlation between H1(69-171) and HupB seroreactivities. Conclusions: Correlation between H1(69-171) and HupB reactivities suggests the presence of a shared dominant epitope, which is recognized by antibodies in a substantial number of uveitis patients. Seroreactivities to ANCA and HupB/H1 are independent immunologic markers that may identify biologically distinctive subsets of uveitis. C1 Univ Calif Los Angeles, Jules Stein Eye Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Ophthalmol Sect, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. Oregon Hlth Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. RP Gordon, LK (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, David Geffen Sch Med, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM lgordon@ucla.edu FU NEI NIH HHS [EY13708, EY00360] NR 33 TC 4 Z9 4 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD APR-JUN PY 2005 VL 13 IS 2-3 BP 191 EP 198 DI 10.1080/09273940490912452 PG 8 WC Ophthalmology SC Ophthalmology GA 935DM UT WOS:000229759700009 PM 16019678 ER PT J AU Androudi, S Letko, E Meniconi, M Papadaki, T Ahmed, M Foster, CS AF Androudi, S Letko, E Meniconi, M Papadaki, T Ahmed, M Foster, CS TI Safety and efficacy of intravitreal triamcinolone acetonide for uveitic macular edema SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE uveitis; Macular edema; triamcinolone acetonide ID PARS-PLANA VITRECTOMY; INTRAOCULAR INFLAMMATORY DISEASE; CRYSTALLINE CORTISONE; INTERMEDIATE UVEITIS; ADJUNCTIVE TREATMENT; INJECTION; ACETAZOLAMIDE; TOXICITY; PHARMACOKINETICS; CORTICOSTEROIDS AB Background: To evaluate the safety and efficacy of intravitreal triamcinolone acetonide ( TA) for treating macular edema secondary to noninfectious uveitis. Methods: Retrospective review of sixteen patients ( 20 eyes) with chronic cystoid macular edema (CME) as a consequence of controlled intermediate uveitis, posterior uveitis, or panuveitis who received at least one intravitreal injection of TA. Main outcome measures were visual acuity (VA), intraocular pressure (IOP), formation or progression of an existing cataract, and CME resolution during the follow-up period. Results: At last follow-up, VA showed improvement ( compared to baseline) in 11 eyes (55%), deterioration in three eyes (15%), remained completely unchanged in one eye (5%), and showed improvement initially but returned to baseline levels in five eyes (25%). At last follow-up, CME had relapsed or was still present in 10 of the eyes (50%). The remaining eyes showed complete resolution of the CME, without evidence of recurrence during the follow-up time. Mean VA at last follow-up showed statistically significant improvement (p = 0.02) in nonvitrectomized eyes ( mean baseline VA: 1.14 +/- 0.58; mean final VA: 0.96 +/- 0.66) compared to the almost unaltered mean visual acuity for vitrectomized eyes ( mean baseline VA: 0.76 +/- 0.41; mean final VA: 0.71 +/- 0.48)( p = 0.40, paired samples t-test). Elevation of IOP was transient in all cases and responded well to topical medications, except for one patient who required placement of an Ahmed valve. Preexisting cataract progressed in three of the 15 phakic eyes (20%). One patient developed a retinal detachment and required additional surgery to reattach it. Patients were followed for a mean of 34 weeks ( median: 32 weeks; range: 19 - 56 weeks). Conclusions: Intravitreal TA may play a role in the treatment of uveitis-related CME. Further controlled studies are necessary to test this hypothesis. C1 Massachusetts Eye Res & Surg Inst, Boston, MA 02114 USA. Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Immunol & Uveitis Serv,Dept Ophthalmol, Boston, MA USA. RP Foster, CS (reprint author), Massachusetts Eye Res & Surg Inst, 100 Charles River Plaza,Suite 301, Boston, MA 02114 USA. EM fosters@uveitis.org NR 43 TC 41 Z9 41 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD APR-JUN PY 2005 VL 13 IS 2-3 BP 205 EP 212 DI 10.1080/09273940590933511 PG 8 WC Ophthalmology SC Ophthalmology GA 935DM UT WOS:000229759700011 PM 16019680 ER PT J AU Hertl, M Cosimi, AB AF Hertl, M Cosimi, AB TI Liver transplantation for malignancy SO ONCOLOGIST LA English DT Article DE hepatic malignancy; liver transplantation; HCC; MELD ID SMALL HEPATOCELLULAR-CARCINOMA; METASTATIC NEUROENDOCRINE TUMORS; HEPATIC RESECTION; LIVING-DONOR; FIBROLAMELLAR CARCINOMA; CIRRHOTIC-PATIENTS; UNITED-STATES; FREE SURVIVAL; RISK-FACTORS; EXPERIENCE AB Liver transplantation for hepatic malignancies has emerged from an exotic and desperate approach to a well-documented and proven treatment modality for these unfortunate patients. However, early unsatisfactory results emphasized that only a highly selected patient population would benefit from transplantation. Currently, < 10 % of all liver transplants performed are for hepatocellular cancer (HCC). There is no controversy that hepatoblastoma is an excellent indication in pediatric patients with unresectable tumors. Similarly, liver transplantation for HCC in the adult population yields good results for patients whose tumor masses do not exceed the Milan criteria. It remains to be determined whether patients with more extensive tumors can be reliably selected to benefit from the procedure. Adjunctive procedures like radiofrequency ablation, chemoembolization, or cryotherapy might be indicated to limit tumor progression for patients on waiting lists. Epitheloid hemangioendothelioma is also an appropriate indication for liver transplantation, unlike angiosarcoma. Metastatic liver disease is not an indication for liver transplantation, with the exception of cases in which the primary is a neuroendocrine tumor, for which liver transplantation can result in long-term survival and even cure in a number of patients. And finally, while gallbladder cancers are never an indication for liver transplantation, rare cases of cholan-giocellular cancer might qualify if aggressive combination therapies, including chemotherapy and radiotherapy followed by OLT, are carried through. Survival in these selected patients can approach that for patients with cholestatic liver disease. C1 Massachusetts Gen Hosp, Transplant Unit, Boston, MA 02114 USA. RP Hertl, M (reprint author), Transplant Unit, 55 Fruit St,Blake 655, Boston, MA 02114 USA. EM mhertl@partners.org NR 61 TC 66 Z9 74 U1 1 U2 4 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD APR PY 2005 VL 10 IS 4 BP 269 EP 281 DI 10.1634/theoncologist.10-4-269 PG 13 WC Oncology SC Oncology GA 919PI UT WOS:000228629600004 PM 15821247 ER PT J AU Kantoff, P AF Kantoff, P TI Recent progress in management of advanced prostate cancer SO ONCOLOGY-NEW YORK LA English DT Article ID MITOXANTRONE PLUS PREDNISONE; ESTRAMUSTINE PHOSPHATE; PHASE-II; TRIAL; CHEMOTHERAPY; THERAPIES; DOCETAXEL; MEN AB Androgen-deprivation therapy, usually with combined androgen blockade, is standard initial treatment for advanced prostate cancer. With failure of initial treatment, as indicated by rising prostate-specific antigen (PSA) levels, second-line hormonal therapy is usually instituted. Over the past several years, it has become increasingly clear that systemic chemotherapy has an important role in hormone-refractory disease. Phase II trials have demonstrated high PSA and measurable disease response rates with taxane single-agent and combination treatments. One recent phase III trial showed that docetaxel (Taxotere)l estramustine (Emcyt) significantly improved overall survival, progression-free survival, and PSA response rate compared with mitoxantrone (Novantrone) plus prednisone. Another phase III trial demonstrated that docetaxel given every 3 weeks plus prednisone significantly improved overall survival, PSA response rate, pain relief response rate, and quality of life compared with mitoxantrone and prednisone. On the basis of these findings, every-3-week docetaxel plus prednisone is now considered standard first-line therapy for metastatic hormone-refractory disease. There is considerable optimism that treatment can be further improved. Studies of taxane combinations with bevacizumab (Avastin), thalidomide (Thalomid), bortezomib (Velcade), antisense Bcl-2 oligonucleotide, mTOR inhibitors, epidermal growth factor receptor inhibitors, and KDR inhibitors are under way. Randomized phase III trials in progress or planned are examining docetaxel in combination with imatinib mesylate (Gleevec) or calcitriol and docetaxel/prednisone in combination with bevacizumab and an antisense clusterin compound. Other promising systemic agents include epothilones and atrasentan, and promising vaccines include Provenge, GVAX, and Prostvac. C1 Dana Farber Canc Inst, Dept Med, Div Solid Tumor Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kantoff, P (reprint author), Dana Farber Canc Inst, Dept Med, Div Solid Tumor Oncol, 44 Binney St, Boston, MA 02215 USA. NR 12 TC 31 Z9 34 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD APR PY 2005 VL 19 IS 5 BP 631 EP 636 PG 6 WC Oncology SC Oncology GA 052EH UT WOS:000238213700005 PM 15945343 ER PT J AU Milton, RC Clemons, TE Kurinij, N Sperduto, RD AF Milton, RC Clemons, TE Kurinij, N Sperduto, RD CA Age Related Eye Dis Study Res Grp TI Risk factors for the incidence of advanced age-related macular degeneration in the age-elated eye disease study (AREDS) - AREDS report no.19 SO OPHTHALMOLOGY LA English DT Article ID BLUE-MOUNTAINS-EYE; BEAVER-DAM EYE; BODY-MASS INDEX; CIGARETTE-SMOKING; POOLED FINDINGS; DIETARY-FAT; 10-YEAR INCIDENCE; CATARACT-SURGERY; BETA-CAROTENE; UNITED-STATES AB Purpose: To describe the association of demographic, behavioral, medical, and nonretinal ocular factors with the incidence of neovascular age-related macular degeneration (AMD) and central geographic atrophy (CGA) in the Age-Related Eye Disease Study (AREDS), a randomized trial of antioxidants and zinc supplementation prophylaxis for development of advanced AMD. Design: Clinic-based prospective cohort study. Participants: Of individuals with early or intermediate AMD at baseline with a median follow-up of 6.3 years, 788 were at risk of developing advanced AMD in one eye (the fellow eye had advanced AMD), and 2506 were at risk in both eyes. Methods: The incidence of neovascular AMD and CGA was assessed from stereoscopic color fundus photographs taken at baseline and at annual visits beginning at year 2. Main Outcome Measures: Neovascular AMD was defined as photocoagulation for choroidal neovascularization, or photographic documentation at the reading center of any of the following: nondrusenoid retinal pigment epithelial detachment, serous or hemorrhagic retinal detachment, hemorrhage under the retina or the retinal pigment epithelium, and subretinal fibrosis. Central geographic atrophy was defined as geographic atrophy involving the center of the macula. Results: In multivariable models, in persons at risk of advanced AMD in both eyes, while controlling for age, gender, and AREDS treatment group, the following variables were statistically significantly associated with the incidence of neovascular AMD: race (odds ratio [OR], white vs. black, 6.77; 95% confidence interval [CI], 1.24-36.9) and larger amount smoked (OR, > 10 vs. <= 10 pack-years [a pack-year is an average of 1 pack of cigarette smoked per day for a year], 1.55; 95% CI, 1.15-2.09). The following were statistically significantly associated with the incidence of CGA: less education (OR, high school graduate or less vs. college graduate, 1.75; 95% CI, 1.10-2.78), greater body mass index (BMI) (OR, obese vs. nonobese, 1.93; 95% CI, 1.25-2.65), larger amount smoked (OR, > 10 pack-years vs. <= 10 pack-years, 1.82; 95% CI, 1.25-2.65), and antacid use (OR, 0.29; 95% CI, 0.09-0.91). In persons at risk of developing advanced AMD in one eye, the incidence of neovascular AMD was associated with diabetes (OR, 1.88; 95% CI, 1.07-3.31), and the incidence of CGA was associated with use of anti inflammatory medications (OR, 0.22; 95% Cl, 0.08-0.59). Conclusions: Results suggest that, among persons with early or intermediate AMD, smoking and BMI are modifiable factors associated with progression to advanced AMD, and suggest other associations (e.g., use of antacids and anti inflammatory medications) that warrant further study. Ophthalmology 2005;112:533-539 (c) 2005 by the American Academy of Ophthalmology. C1 EMMES Corp, AREDS Coordinating Ctr, Rockville, MD 20850 USA. Univ Wisconsin, Madison, WI USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NEI, Bethesda, MD 20892 USA. RP Milton, RC (reprint author), EMMES Corp, AREDS Coordinating Ctr, 701 N Washington St,Suite 700, Rockville, MD 20850 USA. EM rmilton@emmes.com; aredspub@emmes.com NR 52 TC 314 Z9 319 U1 3 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 2005 VL 112 IS 4 BP 533 EP 539 DI 10.1016/j.ophtha.2004.10.047 PG 7 WC Ophthalmology SC Ophthalmology GA 910WF UT WOS:000227962200002 ER PT J AU Friedlander, A AF Friedlander, A TI Carotid artery atheromatosis after radiation therapy for head and neck tumors. Diagnosis, clinical implications and preventive measures SO ORAL ONCOLOGY LA English DT Meeting Abstract CT 10th International Congress on Oral Cancer CY APR 19-24, 2005 CL Crete, GREECE C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD APR PY 2005 VL 1 IS 1 SU S BP 35 EP 35 DI 10.1016/S1744-7895(05)80029-X PG 1 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 000XE UT WOS:000234494900028 ER PT J AU Karakoyun-Celik, O Norris, CM Tishler-, R Mahadevan, A Clark, JR Sullivan, C Goldberg, S Devlin, P Busse, PM AF Karakoyun-Celik, O Norris, CM Tishler-, R Mahadevan, A Clark, JR Sullivan, C Goldberg, S Devlin, P Busse, PM TI Management of oral tongue carcinoma with external beam radiotherapy and interstitial brachytherapy boost: is limited surgery necessary to improve outcome? SO ORAL ONCOLOGY LA English DT Meeting Abstract CT 10th International Congress on Oral Cancer CY APR 19-24, 2005 CL Crete, GREECE C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 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 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD APR PY 2005 VL 1 IS 1 SU S BP 125 EP 125 DI 10.1016/S1744-7895(05)80311-6 PG 1 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 000XE UT WOS:000234494900307 ER PT J AU Bhattacharyya, T AF Bhattacharyya, T TI Evidence-based approaches to minimizing malpractice risk in orthopedic surgery SO ORTHOPEDICS LA English DT Review ID ADVERSE EVENTS; MEDICAL MALPRACTICE; HOSPITALIZED-PATIENTS; CLAIMS; CARE; NEGLIGENCE; LAWYERS AB The malpractice crisis continues unabated in the United States. However, there are many strategies with foundations in scientific study that physicians can use to reduce their malpractice risk. Studies have shown technical error has little relationship with malpractice claims. Patients with higher education levels and socioeconomic status are more likely to file lawsuits. Surgeons should be aware of how to respond in the event a claim is filed. Improving physician-patient communication is the cornerstone of any strategy to reduce malpractice claims. C1 Massachusetts Gen Hosp, Partners Orthoped Trauma Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02114 USA. RP Bhattacharyya, T (reprint author), Massachusetts Gen Hosp, Partners Orthoped Trauma Serv, 15 Parkman St, Boston, MA 02114 USA. NR 21 TC 6 Z9 6 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD APR PY 2005 VL 28 IS 4 BP 378 EP 381 PG 4 WC Orthopedics SC Orthopedics GA 919MO UT WOS:000228622400006 PM 15887584 ER PT J AU Veilleux, N Spector, M AF Veilleux, N Spector, M TI Effects of FGF-2 and IGF-1 on adult canine articular chondrocytes in type II collagen-glycosaminoglycan scaffolds in vitro SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE cartilage; collagen; FGF; IGF ID FIBROBLAST-GROWTH-FACTOR; MUSCLE ACTIN EXPRESSION; CARTILAGINOUS TISSUE; FACTOR-BETA; MATRIX; CONTRACTION; CULTURE; CHONDROGENESIS; METABOLISM; EXPANSION AB Objective: Chondrocyte-seeded tissue engineering scaffolds hold the promise of enhancing certain cartilage repair procedures. The objective of this study was to evaluate the effects of selected growth factors [fibroblast growth factor (FGF)-2 and insulin-like growth factor (IGF)-1] individually and in combination on adult canine articular chondrocyte-seeded type II collagen-glycosaminoglycan (GAG) scaffolds grown in serum-free (SF) medium. Design: Approximately 500,000 second passage chondrocytes were seeded into discs of the scaffold, 4 mm diameter X 2 mm thick. The constructs were grown in the following media: serum-containing medium; a basal SF medium; SF with 5 ng/ml FGF-2; SF with 25 ng/ml FGF-2; SF with 100 ng/ml IGF-1; and SF with 5 ng/ml FGF-2 plus 100 ng/ml IGF-1. The DNA and GAG contents of the scaffolds were determined after 1 day and 2 weeks and the protein and GAG synthesis rates determined at 2 weeks using radiolabels. Histology and type II collagen immunohistochemistry were also performed. Results: FGF-2 at 5 ng/ml was found to substantially increase the biosynthetic activity of the cells and the accumulation of GAG. The histology demonstrated chondrocytes uniformly distributed through a matrix that stained intensely for GAG and type II collagen after only 2 weeks. Of interest were the rapid degradation of the collagen scaffold, despite the fact that the scaffold was carbodiimide cross-linked, and the contraction of the constructs. There were less pronounced effects using the higher dose of FGF-2 and the combination with IGF-1. Conclusions: Chondrocyte-seeded type II collagen scaffolds cultured in SF medium supplemented with 5 ng/ml FGF-2 undergo contraction, demonstrate an increase in construct incorporation of radiolabeled sulfate, and display qualitative signs of chondrogenesis. Published by Elsevier Ltd on behalf of OsteoArthritis Research Society International. C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Boston Campus,Room D1-152,Mail Stop 151 Res,150 S, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu FU NIDCR NIH HHS [5 T32 DE07311] NR 36 TC 50 Z9 59 U1 2 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD APR PY 2005 VL 13 IS 4 BP 278 EP 286 DI 10.1016/j.joca.2004.12.013 PG 9 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 914GQ UT WOS:000228216200002 PM 15780641 ER PT J AU Hutter, MM Wick, EC Day, AL Maa, J Zerega, EC Richmond, AC Jordan, TH Grady, EF Mulvihill, SJ Bunnett, NW Kirkwood, KS AF Hutter, MM Wick, EC Day, AL Maa, J Zerega, EC Richmond, AC Jordan, TH Grady, EF Mulvihill, SJ Bunnett, NW Kirkwood, KS TI Transient receptor potential vanilloid (TRPV-1) promotes neurogenic inflammation in the pancreas via activation of the neurokinin-1 receptor (NK-1R) SO PANCREAS LA English DT Article DE pancreatitis; capsaicin; capsaicin receptor; capsazepine; substance P; rats; Evans blue ID PRIMARY SENSORY NEURONS; CAPSAICIN-RECEPTOR; SUBSTANCE-P; PAIN PATHWAY; RATS; RESPONSES; RELEASE; MICE AB Objectives: The transient receptor potential vanilloid 1 (TRPV-1) is an ion channel found on primary sensory afferent neurons. Activation of TRPV-1 leads to the release of the proinflammatory neuropeptide substance P (SP). SP then binds to the neurokinin-1 receptor (NK1-R) on endothelial cells and promotes extravasation of plasma and proteins into the interstitial tissue and neutrophil infiltration, a process called neurogenic inflammation. We tested 2 hypotheses: ( 1) activation of TRPV-1 in the pancreas leads to interstitial edema and neutrophil infiltration and ( 2) TRPV-1-induced plasma extravasation is mediated by the release of SP and activation of the NK1-R in the rat. Methods: We measured extravasation of the intravascular tracer Evans blue as an index of plasma extravasation and quantified pancreas tissue myeloperoxidase activity (MPO) as a marker of neutrophil infiltration. The severity of inflammation following intravenous infusion of the secretagogue cerulein (10 mg/kg/h x 4 hours) was assessed using a histologic scoring system. Results: Intravenous injection of the TRPV-1 agonist capsaicin induced a dose-dependent increase in Evans blue accumulation in the rat pancreas (P < 0.05 vs. vehicle control). This effect was blocked by pretreatment with the TRPV-1 antagonist capsazepine (1.8 mg/kg), or the NK1-R antagonist CP 96,345 (1 mg/kg). Capsazepine also reduced cerulein-induced Evans blue, MPO, and histologic severity of inflammation in the pancreas but had no effect on serum amylase. Conclusion: Activation of TRPV-1 induces SP-mediated plasma extravasation in the rat pancreas via activation of the NK1-R. TRPV-1 mediates neurogenic inflammation in cerulein-induced pancreatitis in the rat. C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ Utah, Dept Surg, Salt Lake City, UT USA. RP Kirkwood, KS (reprint author), Univ Calif San Francisco, Dept Surg, 513 Parnassus Ave,Room C317, San Francisco, CA 94143 USA. EM Kirkwoodk@surgery.ucsfr.edu FU NIDDK NIH HHS [R01 DK 52388, R01 DK 46285, R01 DK 39957]; PHS HHS [10063] NR 21 TC 45 Z9 47 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD APR PY 2005 VL 30 IS 3 BP 260 EP 265 DI 10.1097/01.mpa.0000153616.63384.24 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 911MO UT WOS:000228007300013 PM 15782105 ER PT J AU Mansbach, JM Emond, JA Camargo, CA AF Mansbach, JM Emond, JA Camargo, CA TI Bronchiolitis in US emergency departments 1992 to 2000 - Epidemiology and practice variation SO PEDIATRIC EMERGENCY CARE LA English DT Article DE bronchiolitis; practice variation; hospitalization rates ID RESPIRATORY SYNCYTIAL VIRUS; ACUTE VIRAL BRONCHIOLITIS; SALINE SOLUTION TREATMENT; PLACEBO-CONTROLLED TRIAL; HOSPITALIZED INFANTS; DOUBLE-BLIND; NEBULIZED EPINEPHRINE; HEALTHY INFANTS; CHILDREN; MANAGEMENT AB Objective: To describe the epidemiology of US emergency department (ED) visits for bronchiolitis, including the characteristics of children presenting to the ED and the variability in bronchiolitis care in the ED. Methods: Data were obtained from the 1992 to 2000 National Hospital Ambulatory Medical Care Survey. Cases had International Classification of Diseases, Ninth Revision, Clinical Modification code 466 and were younger than 2 years. National estimates were obtained using assigned patient visit weights; 95% confidence intervals were calculated using the relative standard error of the estimate; analysis used chi(2) and logistic regression. Results: From 1992 to 2000, bronchiolitis accounted for approximately 1,868,000 ED visits for children younger than 2 years. Among this same age group, the overall rate was 26 (95% confidence interval 22-31) per 1000 US population and 31 (95% confidence interval 26-36) per 1000 ED visits. These rates were stable over the 9-year period. Comparing children with bronchiolitis to those presenting with other problems, children with bronchiolitis were more likely boys (61% vs. 53%; P = 0.01) and Hispanic (27% vs. 20%; P = 0.008). Therapeutic interventions varied and 19% were admitted to the hospital. The multivariate predictor for receiving systemic steroids was urgent/emergent status at triage (odds ratio 4.0, 1.9-8.4). Multivariate predictors for admission were Hispanic ethnicity (odds ratio 2.3, 1.1-5.0) and urgent/emergent status at triage (odds ratio 3.7, 2.0-6.9). Conclusions: ED visit rates for bronchiolitis among children younger than 2 years were stable between 1992 and 2000. The observed ED practice variation demonstrates that children are receiving medications for which there is little supporting evidence. Boys and Hispanics are at-risk groups for presentation to the ED, and Hispanics are more likely to be hospitalized. C1 Childrens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. RP Mansbach, JM (reprint author), Childrens Hosp, Dept Med, Hunnewell 131, Boston, MA 02115 USA. EM Jonathan.Mansbach@childrens.harvard.edu NR 43 TC 60 Z9 63 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-5161 J9 PEDIATR EMERG CARE JI Pediatr. Emerg. Care PD APR PY 2005 VL 21 IS 4 BP 242 EP 247 DI 10.1097/01.pec.0000161469.19841.86 PG 6 WC Emergency Medicine; Pediatrics SC Emergency Medicine; Pediatrics GA 917XF UT WOS:000228501900004 PM 15824683 ER PT J AU Kleta, R Kaskel, F Dohil, R Goodyer, P Guay-Woodford, LM Harms, E Ingelfinger, JR Koch, VH Langman, CB Leonard, MB Mannon, RB Sarwal, M Schneider, JA Skovby, F Sonies, BC Thoene, JG Trauner, DA Gahl, WA AF Kleta, R Kaskel, F Dohil, R Goodyer, P Guay-Woodford, LM Harms, E Ingelfinger, JR Koch, VH Langman, CB Leonard, MB Mannon, RB Sarwal, M Schneider, JA Skovby, F Sonies, BC Thoene, JG Trauner, DA Gahl, WA TI First NIH/office of rare diseases conference on cystinosis: Past, present, and future SO PEDIATRIC NEPHROLOGY LA English DT Article C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIH, Off Rare Dis, Bethesda, MD 20892 USA. Yeshiva Univ Albert Einstein Coll Med, Childrens Hosp Montefiore, Bronx, NY 10461 USA. Univ Calif San Diego, Div Pediat Gastroenterol & Hepatol, San Diego, CA 92103 USA. McGill Univ, Med Ctr, Dept Pediat, Montreal, PQ, Canada. Univ Alabama, Div Genet & Translat Med, Birmingham, AL USA. Univ Childrens Hosp, Munster, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA USA. Sao Paulo Med Sch, Hosp Clin, Inst Crianca, Pediat Nephrol Unit, Sao Paulo, Brazil. Childrens Mem Med Ctr, Chicago, IL USA. Childrens Hosp Philadelphia, Div Nephrol, Philadelphia, PA 19104 USA. NIDDK, Transplantat Branch, Bethesda, MD USA. Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Copenhagen Univ Hosp, Dept Clin Genet, Copenhagen, Denmark. NIH, Ultrasound Imaging Lab, Dept Rehabil Med, Bethesda, MD 20892 USA. Tulane Univ, Sch Med, Hayward Genet Ctr, New Orleans, LA 70112 USA. Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. NIH, Sect Human Biochem Genet, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1851,Bldg 10,Room 10C103, Bethesda, MD 20892 USA. EM bgahl@helix.nih.gov NR 2 TC 18 Z9 19 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD APR PY 2005 VL 20 IS 4 BP 452 EP 454 DI 10.1007/s00467-004-1777-5 PG 3 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 903RA UT WOS:000227442100003 PM 15747161 ER PT J AU Chung, JH Des Roches, CM Meunier, J Eavey, RD AF Chung, JH Des Roches, CM Meunier, J Eavey, RD TI Evaluation of noise-induced hearing loss in young people using a web-based survey technique SO PEDIATRICS LA English DT Article DE noise-in-induced hearing loss ID HEALTH; CHILDREN; EXPOSURE AB Objective. Many adolescents and young adults consciously expose themselves to loud music for entertainment. We hypothesized that these individuals might not be aware that exposure to loud music could result in hearing loss. Furthermore, we wished to assess the feasibility of a web-based survey to collect health information from this group. Methods. A 28-question survey was designed to target adolescents and young adults. The survey contained questions about views toward general health issues, including hearing loss, and was presented to random visitors at the MTV web site. Results. In 3 days, 9693 web surveys were completed. Hearing loss was defined on a Likert scale as "a very big problem" by 8% of respondents compared with other health issues: sexually transmitted diseases, 50%; alcohol/ drug use, 47%; depression, 44%; smoking, 45%; nutrition and weight issues, 31%; and acne, 18%. Notably, most respondents had experienced tinnitus or hearing impairment attending concerts (61%) and clubs (43%). Only 14% of respondents had used earplugs; however, many could be motivated to try ear protection if they were aware of the potential for permanent hearing loss (66%) or were advised by a medical professional (59%). Conclusions. A majority of young adults have experienced tinnitus and hearing impairment after exposure to loud music. Fortunately, many of these individuals could be motivated to wear ear protection. This novel web-based survey technique rapidly generated a large database and is a feasible method to obtain health data from this group. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Pediat Otolaryngol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Survey Res Ctr, Boston, MA 02115 USA. Cogent Res, Cambridge, MA USA. RP Eavey, RD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Pediat Otolaryngol Serv, 243 Charles St, Boston, MA 02114 USA. EM roland_eavey@meei.harvard.edu NR 24 TC 90 Z9 100 U1 0 U2 13 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2005 VL 115 IS 4 BP 861 EP 867 DI 10.1542/peds.2004-0173 PG 7 WC Pediatrics SC Pediatrics GA 912VL UT WOS:000228107900024 PM 15805356 ER PT J AU Winickoff, JP Tanski, SE McMillen, RC Klein, JD Rigotti, NA Weitzman, M AF Winickoff, JP Tanski, SE McMillen, RC Klein, JD Rigotti, NA Weitzman, M TI Child health care clinicians' use of medications to help parents quit smoking: A national parent survey SO PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 01-04, 2004 CL San Francisco, CA SP Pediat Acad Soc DE smoking; tobacco; pediatrics; family practice; parent; smoking cessation; secondhand smoke; environmental tobacco smoke; tobacco control; nicotine replacement medication ID ADOLESCENT SMOKING; TRANSDERMAL NICOTINE; ADVISING PARENTS; STOP SMOKING; TOBACCO USE; CESSATION; PEDIATRICIANS; INTERVENTION; PHYSICIANS; SAFETY AB Background. Smokers who use cessation medications when they attempt to quit double their likelihood of success. No prior survey has assessed the acceptability to parents of receiving smoking cessation medication prescriptions in the context of their child's primary care visits. Objective. To assess acceptability to parents of receiving smoking cessation medication prescriptions and to compare that with the reported rate of actually receiving smoking cessation medication prescriptions in the context of the child's health care visit. Methods. Data were collected through a national random-digit dial telephone survey of households from July to September 2003. The sample was weighted according to race and gender, on the basis of the 2002 US Census, to be representative of the US population. Results. Of 3990 eligible respondents contacted, 3010 (75%) completed surveys; 1027 (34%) of those were parents. Of those parents, 211 (21%) were self-identified smokers. One half would consider using a smoking cessation medication and, of those, 85% said that it would be acceptable if the child's doctor prescribed or recommended it to them. In contrast, of the 143 smoking parents who accompanied their child to the doctor, only 15% had pharmacotherapy recommended and only 8% received a prescription for a smoking cessation medication. These results did not vary according to parent age, gender, race, or child age. Conclusions. Child health care clinicians have low rates of recommending and prescribing cessation therapies that have proved effective in other settings. The recommendation or provision of cessation medications would be acceptable to the majority of parents in the context of their child's health care visit. C1 Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Amer Acad Pediat, Ctr Child Hlth Res, Rochester, NY USA. Univ Rochester, Strong Childrens Res Ctr, Rochester, NY USA. Mississippi State Univ, Social Sci Res Ctr, Starkville, MS USA. RP Winickoff, JP (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM jwinickoff@partners.org RI McMillen, Robert/A-9326-2009 FU NCI NIH HHS [K07 CA100213-A01]; NHLBI NIH HHS [HL04440] NR 48 TC 37 Z9 39 U1 4 U2 6 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2005 VL 115 IS 4 BP 1013 EP 1017 DI 10.1542/peds.2004-1372 PG 5 WC Pediatrics SC Pediatrics GA 912VL UT WOS:000228107900047 PM 15805379 ER PT J AU Yuan, PQ Kimura, H Million, M Bellier, JP Wang, LX Ohning, GV Tache, Y AF Yuan, PQ Kimura, H Million, M Bellier, JP Wang, LX Ohning, GV Tache, Y TI Central vagal stimulation activates enteric cholinergic neurons in the stomach and VIP neurons in the duodenum in conscious rats SO PEPTIDES LA English DT Article DE peripheral choline acetyltransferase; vagus; enteric nervous system; cold; duodenum; vasoactive intestinal peptide ID THYROTROPIN-RELEASING-HORMONE; GENE-RELATED PEPTIDE; GASTRIC MYENTERIC NEURONS; NERVOUS-SYSTEM ACTION; DORSAL MOTOR NUCLEUS; TRH ANALOG; INTRACISTERNAL TRH; COLD-RESTRAINT; FOS EXPRESSION; GUINEA-PIG AB The influence of central vagal stimulation induced by 2 h cold exposure or intracisternal injection of thyrotropin-releasing hormone (TRH) analog, RX-77368, on gastro-duodenal enteric cholinergic neuronal activity was assessed in conscious rats with Fos and peripheral choline acetyltransferase (pChAT) immunoreactivity (IR). pChAT-IR was detected in 68%, 70% and 73% of corpus, antrum and duodenum submucosal neurons, respectively, and in 65% of gastric and 46% of duodenal myenteric neurons. Cold and RX-77368 induced Fos-IR in over 90% of gastric submucosal and myenteric neurons, while in duodenum only 25-27% of submucosal and 50-51% myenteric duodenal neurons were Fos positive. In the stomach, cold induced Fos-IR in 93% of submucosal and 97% of myenteric pChAT IR neurons, while in the duodenum only 7% submucosal and 5% myenteric pChAT IR neurons were Fos positive. In the duodenum, cold induced Fos in 91% of submucosal and 99% of myenteric VIP-IR neurons. RX-77368 induces similar percentages of Fos/pChAT-IR and Fos/VIP-IR neurons. These results indicate that increased central vagal outflow activates cholinergic neurons in the stomach while in the duodenum, VIP neurons are preferentially stimulated. (c) 2004 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, VA Greater Los Angeles Healthcare Syst, Digest Dis Div,Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. Shiga Univ Med Sci, Mol Neurosci Res Ctr, Otsu, Shiga 5202192, Japan. RP Yuan, PQ (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Bldg 115,Room 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM pqyuan@ucla.edu OI Bellier, Jean-Pierre/0000-0002-8758-8075 FU NIDDK NIH HHS [R01 DK-33061, DK 41301] NR 51 TC 15 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD APR PY 2005 VL 26 IS 4 BP 653 EP 664 DI 10.1016/j.peptides.2004.11.015 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 909WD UT WOS:000227890500016 PM 15752581 ER PT J AU Solomon, DH Finkelstein, JS Wang, PS Avorn, J AF Solomon, DH Finkelstein, JS Wang, PS Avorn, J TI Statin lipid-lowering drugs and bone mineral density SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE bone density; statin lipid-lowering drugs; t-scores; epidemiology ID COA REDUCTASE INHIBITORS; RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL WOMEN; IN-VITRO; FRACTURE; RISK; OSTEOPOROSIS; TURNOVER AB Background HMG Co-A reductase inhibitors (statin lipid-lowering drugs) have been associated with a reduced rate of fractures in some studies, but not in others. We examined the relationship between statin use and bone density among postmenopausal women. Methods We conducted a cross-sectional survey at one academic medical center. Postmenopausal women who underwent bone densitometry and agreed to a telephone interview were surveyed about osteoporosis risk factors, use of hormone replacement therapy and osteoporosis medications and statin exposure. We then developed linear regression models adjusting for known counfounders to assess the relationship between statin use and bone mineral density (BMD). Results Of 339 women studied, 162 were current or past users of statins, and 177 were not. Statin users and non-users were similar with respect to age, race, prior fracture history, the presence of medical conditions associated with osteoporosis, use of medications for osteoporosis, use of tobacco and use of oral glucocorticoids. Statin users had significantly higher body mass index (BMI) and rates of thiazide use, and were more likely to abstain from alcohol. After adjusting for important confounders, we found that statin use was associated with a significantly higher t-score at the total hip (-0.53 +/- 0.17) compared with non-users (-0.83 +/- 0.18; p = 0.02). At the lumbar spine, there was a trend toward higher t-scores in statin users (-0.91 +/- 0.24) compared with non-users (-1.21 +/- 0.23; p = 0.08). Conclusions These results support the hypothesis that statin use is associated with higher BMD. While it is unclear whether their relationship is causal, further controlled studies examining bone formation and resorption would help determine the clinical implications of these findings. Copyright (c) 2004 John Wiley & Sons, Ltd. C1 Brigham & Womens Hosp, Div Pharmacoepidemiol, Boston, MA 02120 USA. Brigham & Womens Hosp, Div Pharmacoecon, Boston, MA 02120 USA. Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. RP Solomon, DH (reprint author), Brigham & Womens Hosp, Div Pharmacoepidemiol, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM dhsolomon@partners.org FU NIAMS NIH HHS [K23 AR48616]; PHS HHS [K24 KD02759] NR 21 TC 28 Z9 36 U1 0 U2 3 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD APR PY 2005 VL 14 IS 4 BP 219 EP 226 DI 10.1002/pds.984 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 916QU UT WOS:000228401500001 PM 15386702 ER PT J AU Knofler, M Sooranna, SR Daoud, G Whitley, GS Markert, UR Xia, Y Cantiello, H Hauguel-de Mouzon, S AF Knofler, M Sooranna, SR Daoud, G Whitley, GS Markert, UR Xia, Y Cantiello, H Hauguel-de Mouzon, S TI Trophoblast signalling: Knowns and unknowns - A workshop report SO PLACENTA LA English DT Article; Proceedings Paper CT 1st Meeting of the Placenta-Association-of-the-Americas/10th International-Federation-of-Placenta-Associations CY SEP 25-29, 2005 CL Pacific Grove, CA SP Placenta Assoc Amer, Int Federat Placenta Assoc DE signal transduction; MAP kinase; calcineurin; p13 kinase; PKA; calcium; cAMP ID KINASE; DIFFERENTIATION; ACTIVATION; CASCADES; TARGETS; PATHWAY C1 Med Univ Vienna, Dept Obstet & Gynecol, A-1090 Vienna, Austria. Imperial Coll Sci, London, England. Univ Quebec, Lab Physiol Maternofoetale, Montreal, PQ H3C 3P8, Canada. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. Univ Jena, Dept Obstet, D-6900 Jena, Germany. Univ Texas, Sch Med, Houston, TX USA. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Knofler, M (reprint author), Med Univ Vienna, Dept Obstet & Gynecol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM martin.knoefler@meduniwien.ac.at NR 17 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD APR PY 2005 VL 26 SU A BP S49 EP S51 DI 10.1016/j.placenta.2005.02.001 PG 3 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 924LP UT WOS:000228980600010 PM 15837068 ER PT J AU Holden, MK Dyar, TA Schwamm, L Bizzi, E AF Holden, MK Dyar, TA Schwamm, L Bizzi, E TI Virtual-environment-based telerehabilitation in patients with stroke SO PRESENCE-TELEOPERATORS AND VIRTUAL ENVIRONMENTS LA English DT Article ID MOTOR TASK; REHABILITATION; REALITY; FEEDBACK; SYSTEM AB We describe a telerehabilitation system that has been developed in our laboratory, and initial results following use of the system on 2 patients with stroke. The system allows a therapist in a remote location to conduct treatment sessions, using a virtual-environment-based motor-training system, with a patient who is located at home. The system consists of a patient computer with motion-capture equipment and video camera, a therapist computer with video camera, and virtual-environment software that is synchronized over a high-speed Internet connection. The patient's movements are animated within the context of a virtual scene as she attempts to imitate a prerecorded movement, while the therapist can direct and monitor the activity in real time, as displayed in the animated virtual scene and via videoconference. The design, technical testing, and clinical feasibility testing of the system are reported. Results from the first 2 stroke patients to use the system indicate that patients made significant gains in upper-extremity function as measured by standard clinical tests and by their subjective report. As well, both patients demonstrated gains on quantitative kinematic measures of upper-extremity trajectories performed in the real world, indicating transfer of training from VE to real-world performance. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Holden, MK (reprint author), MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. EM holden@mit.edu OI Schwamm, Lee/0000-0003-0592-9145 NR 37 TC 41 Z9 44 U1 2 U2 4 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 1054-7460 J9 PRESENCE-TELEOP VIRT JI Presence-Teleoper. Virtual Env. PD APR PY 2005 VL 14 IS 2 BP 214 EP 233 DI 10.1162/1054746053967058 PG 20 WC Computer Science, Cybernetics; Computer Science, Software Engineering SC Computer Science GA 932FF UT WOS:000229538900009 ER PT J AU Mahmood, U Josephson, L AF Mahmood, U Josephson, L TI Molecular MR imaging probes SO PROCEEDINGS OF THE IEEE LA English DT Article DE magnetic resonance imaging (MRI); molecular imaging; multimodality imaging; optical imaging ID STEM-CELL MIGRATION; OVARIAN TUMOR XENOGRAFTS; VEGF SIGNALING INHIBITOR; SINGLE MAMMALIAN-CELLS; IN-VIVO ASSESSMENT; CONTRAST AGENTS; NONINVASIVE DETECTION; TAT PEPTIDE; PROSTATE-CANCER; GENE-EXPRESSION AB Magnetic resonance imaging (MRI) has been successfully applied to many of the applications of molecular imaging. This review discusses by example some of the advances in areas such as multimodality MR-optical agents, receptor imaging, apoptosis imaging, angiogenesis imaging, noninvasive cell tracking, and imaging of MRI marker genes. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. FU NIBIB NIH HHS [R01 EB001872, R01 EB001872-03] NR 83 TC 4 Z9 4 U1 1 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9219 J9 P IEEE JI Proc. IEEE PD APR PY 2005 VL 93 IS 4 BP 800 EP 808 DI 10.1109/JPROC.2005.844264 PG 9 WC Engineering, Electrical & Electronic SC Engineering GA 910UB UT WOS:000227956600008 PM 19194516 ER PT J AU Hengerer, A Wunder, A Wagenaar, DJ Vija, AH Shah, M Grimm, J AF Hengerer, A Wunder, A Wagenaar, DJ Vija, AH Shah, M Grimm, J TI From genomics to clinical molecular imaging SO PROCEEDINGS OF THE IEEE LA English DT Article DE in vivo diagnostics; molecular imaging; magnetic resonance (MR); nanoparticles; near IR fluorescence imaging (NIRF); positron emission tomography (PET); single photon emission computed tomography (SPECT); small-animal imaging (SAI); targeted contrast agents ID POSITRON-EMISSION-TOMOGRAPHY; IRON-OXIDE PARTICLES; GENE-EXPRESSION; TELOMERASE ACTIVITY; REPORTER GENE; CANCER; MICE; APOPTOSIS; THERAPY; TUMORS AB Molecular imaging, as applied to clinical practice today, is in its early stages. Encouraging advances achieved in clinical positron emission tomography (PET) and small-animal imaging indicate that this technique is evolving into an indispensable diagnostic. c tool. When employed with complementary morphological imaging procedures, molecular imaging results in substantial diagnostic capability. It will enable the physician to unveil topographic biochemistry in situ and reduce invasive testing. While this is at least in part futuristic, it is clear already today that a comprehensive set of imaging modalities will be required. Imaging modalities most appropriate for molecular imaging are PET single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), optical imaging, and ultrasound. The foundation for advances in molecular imaging, however is not primarily imaging hardware development but scientific advancements in molecular biology and progress in probe development. Other factors to consider are postprocessing software and, inevitably, market dynamics. Thus. it implies efficient collaborations across disciplines, agencies, and industries to develop molecular imaging tools for the clinic. C1 Siemens Med Solut AG, MR Grp, D-91050 Erlangen, Germany. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Siemens Med Solut USA, Nucl Med Grp, Hoffman Estates, IL 60195 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Hengerer, A (reprint author), Siemens Med Solut AG, MR Grp, D-91050 Erlangen, Germany. EM douglas.wagenaar@siemens.com RI Grimm, Jan/B-1937-2008 NR 41 TC 14 Z9 17 U1 1 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9219 J9 P IEEE JI Proc. IEEE PD APR PY 2005 VL 93 IS 4 BP 819 EP 828 DI 10.1109/JPROC.2005.845052 PG 10 WC Engineering, Electrical & Electronic SC Engineering GA 910UB UT WOS:000227956600010 ER PT J AU Emsley, JG Mitchell, BD Kempermann, G Macklis, JD AF Emsley, JG Mitchell, BD Kempermann, G Macklis, JD TI Adult neurogenesis and repair of the adult CNS with neural progenitors, precursors, and stem cells SO PROGRESS IN NEUROBIOLOGY LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; FIBROBLAST GROWTH FACTOR-2; NEWLY GENERATED NEURONS; TARGETED APOPTOTIC DEGENERATION; MAMMALIAN SUBSTANTIA-NIGRA; SUBVENTRICULAR ZONE CELLS; ROSTRAL MIGRATORY STREAM; MOUSE DENTATE GYRUS; RADIAL GLIAL-CELLS; RAT SPINAL-CORD AB Recent work in neuroscience has shown that the adult central nervous system contains neural progenitors, precursors, and stem cells that are capable of generating new neurons, astrocytes, and oligodendrocytes. While challenging previous dogma that no new neurons are born in the adult mammalian CNS, these findings bring with them future possibilities for the development of novel neural repair strategies. The purpose of this review is to present current knowledge about constitutively occurring adult mammalian neurogenesis, to highlight the critical differences between "neurogenic" and "non-neurogenic" regions in the adult brain, and to describe the cardinal features of two well-described neurogenic regions-the subventricular zone/olfactory bulb system, and the dentate gyrus of the hippocampus. We also provide an overview of currently used models for studying neural precursors in vitro, mention some precursor transplantation models, and emphasize that, in this rapidly growing field of neuroscience, one must take caution with respect to a variety of methodological considerations for studying neural precursor cells both in vitro and in vivo. The possibility of repairing neural circuitry by manipulating neurogenesis is an intriguing one, and, therefore, we also review recent efforts to understand the conditions under which neurogenesis can be induced in non-neurogenic regions of the adult CNS. This work aims toward molecular and cellular manipulation of endogenous neural precursors in situ, without transplantation. We conclude this review with a discussion of what the function might be of newly generated neurons in the adult brain and provide a summary Of Current thinking about the consequences of disturbed adult neurogenesis and the reaction of neurogenic regions to disease. (c) 2005 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH HMS Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Program Neurosci, Boston, MA 02114 USA. Charite Univ Med Berlin, Volkswagenstiftung Res Grp Neurogen Permiss, D-13125 Berlin, Germany. Max Delbruck Ctr Mol Med, Res Grp Neuronal Stem Cells, D-13125 Berlin, Germany. RP Macklis, JD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH HMS Ctr Nervous Syst Repair,Dept Neurosurg, Edwards 410 EDR 410,50 Blossom St, Boston, MA 02114 USA. EM jeffrey_macklis@hms.harvard.edu RI Kempermann, Gerd/F-5416-2010 OI Kempermann, Gerd/0000-0002-5304-4061 FU NICHD NIH HHS [HD18655]; NINDS NIH HHS [NS41590, NS45523, NS49553] NR 211 TC 260 Z9 287 U1 3 U2 28 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD APR PY 2005 VL 75 IS 5 BP 321 EP 341 DI 10.1016/j.pneurobio.2005.04.002 PG 21 WC Neurosciences SC Neurosciences & Neurology GA 939DA UT WOS:000230051300002 PM 15913880 ER PT J AU Flick, KC Orendurff, MS Berge, JS Segal, AD Klute, GK AF Flick, KC Orendurff, MS Berge, JS Segal, AD Klute, GK TI Comparison of human turning gait with the mechanical performance of lower limb prosthetic transverse rotation adapters SO PROSTHETICS AND ORTHOTICS INTERNATIONAL LA English DT Article ID AMPUTATION; PAIN AB Given the importance of minimizing transverse plane shear stress on soft tissue, several transverse rotational adapters (TRAs) are available for incorporation in lower limb prostheses. This study compares kinetic and kinematic data from human subjects during straight and turning gaits to the mechanical performance of several TRAs. Physiological data were collected from three individuals walking straight and turning at self-selected speeds around a 1m radius circle. The average peak torques and range of motion for normal subjects while turning were 8.2 Nm and 26 degrees (outside leg), 11.8Nm and 20 degrees (inside leg), and 11.4Nm and 20 degrees (right leg) during straight gait. Each TRA was mechanically tested without axial loading in a servo-hydraulic material testing system (MTS) over its rotational range at 0.5 degrees/s and 60 degrees/s. The TRAs with axial compression were also tested at 0.5 degrees/s under a 736N (75kg mass) axial load. Applying these torques to the different TRAs yielded 3 to 35 degrees rotation, depending on the elastomer installed. Some TRAs had nearly constant stiffness, while others stiffened with rotation. The TRAs also varied in their average maximum stiffness from 0.4Nm/degrees to 2.7Nm/degrees. Normal subjects exhibit interior vs. exterior asymmetrical torques and displacements; however, only one of the TRAs is designed to allow asymmetrical stiffness, and none have asymmetric ranges. Prosthetists and physicians can use these data to better interpret amputees' qualitative remarks and to prescribe the correct TRA and/or elastomer. This information also forms a basis for further design and development of novel torque absorbing prosthetic adapters. C1 Vet Adm Rehabil Res & Dev Ctr Excellence Limb Los, Seattle, WA USA. Univ Washington, Dept Biol, Seattle, WA 98195 USA. RP Flick, KC (reprint author), VA Puget Sound, 1660 S Columbian Way,MS 151, Seattle, WA 98108 USA. EM kflick@u.washington.edu NR 10 TC 14 Z9 14 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0309-3646 J9 PROSTHET ORTHOT INT JI Prosthet. Orthot. Int. PD APR PY 2005 VL 29 IS 1 BP 73 EP 81 DI 10.1080/03093640500088120 PG 9 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 944WG UT WOS:000230461000008 PM 16180379 ER PT J AU Caroff, SN Stinnett, JL AF Caroff, SN Stinnett, JL TI Medically unexplained symptoms SO PSYCHIATRIC ANNALS LA English DT Editorial Material C1 Univ Penn, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Inpatient Psychiat Serv, Philadelphia, PA 19104 USA. Hosp Univ Penn, Psychiat Consultat Serv, Philadelphia, PA 19104 USA. RP Caroff, SN (reprint author), Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD APR PY 2005 VL 35 IS 4 BP 281 EP 282 PG 2 WC Psychiatry SC Psychiatry GA 948MP UT WOS:000230720300002 ER PT J AU Verduin, ML Carter, RE Brady, KT Myrick, H Timmerman, MA AF Verduin, ML Carter, RE Brady, KT Myrick, H Timmerman, MA TI Health service use among persons with comorbid bipolar and substance use disorders SO PSYCHIATRIC SERVICES LA English DT Article; Proceedings Paper CT 157th Annual Meeting of the American-Psychiatric-Association CY MAY 01-06, 2004 CL New York, NY SP Amer Psychiat Assoc ID ABUSE DISORDERS; ILLNESS; CARE; COSTS AB Objective: This study tested the hypothesis that patients with comorbid bipolar and substance use disorders use health services to a greater extent than patients with either bipolar or substance use disorder alone. Methods: A retrospective chart review was conducted among patients who used health services at the Ralph H. Johnson Department of Veterans Affairs medical center in Charleston, South Carolina, and had bipolar disorder alone, substance use disorder alone, and comorbid bipolar and substance use disorders. Patients with a psychiatric admission between 1999 and 2003 were included in the study. Information was collected on the use of health services one year before and including the index admission. Results: The records of 106 eligible patients were examined for this study: 18 had bipolar disorder alone, 39 had substance use disorder alone, and 49 had both bipolar and substance use disorders. Compared with the other two groups, the group with comorbid bipolar and substance use disorders was significantly more likely to be suicidal. Compared with the group with bipolar disorder alone, the group with comorbid disorders had significantly fewer outpatient psychiatric visits and tended to have shorter psychiatric hospitalizations. Among patients with an alcohol use disorder, those who also had bipolar disorder were significantly less likely than those with an alcohol use disorder alone to have had an alcohol-related seizure. Patients with comorbid bipolar and substance use disorders were significantly less likely than those with substance use disorder alone to be referred for intensive substance abuse treatment, even though both groups were equally likely to enter and complete treatment when they were referred. Conclusions: Despite significant functional impairment among patients with comorbid bipolar and substance use disorders, they had significantly fewer psychiatric outpatient visits than those with bipolar disorder alone and were referred for intensive substance abuse treatment significantly less often than those with substance use disorder alone. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Dept Psychiat, Charleston, SC USA. RP Verduin, ML (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St,POB 250861, Charleston, SC 29425 USA. EM verduim@musc.edu NR 17 TC 16 Z9 16 U1 4 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2005 VL 56 IS 4 BP 475 EP 480 DI 10.1176/appi.ps.56.4.475 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 913KP UT WOS:000228150800018 PM 15812100 ER PT J AU Sorrentino, R AF Sorrentino, R TI Posttraumatic stress disorder in litigation: Guidelines for forensic assessment, 2nd edition SO PSYCHIATRIC SERVICES LA English DT Book Review ID SEPTEMBER 11 C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2005 VL 56 IS 4 BP 496 EP 497 DI 10.1176/appi.ps.56.4.496-a PG 2 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 913KP UT WOS:000228150800028 ER PT J AU Goff, DC Herz, L Posever, T Shih, V Tsai, GC Henderson, DC Freudenreich, O Evins, AE Yovel, I Zhang, H Schoenfeld, D AF Goff, DC Herz, L Posever, T Shih, V Tsai, GC Henderson, DC Freudenreich, O Evins, AE Yovel, I Zhang, H Schoenfeld, D TI A six-month, placebo-controlled trial of D-cycloserine co-administered with conventional antipsychotics in schizophrenia patients SO PSYCHOPHARMACOLOGY LA English DT Article ID TREATMENT-RESISTANT SCHIZOPHRENIA; GLYCINE MODULATORY SITE; D-ASPARTATE RECEPTOR; HIGH-DOSE GLYCINE; NEGATIVE SYMPTOMS; ADJUVANT THERAPY; CROSSOVER TRIAL; DOUBLE-BLIND; D-SERINE; DEFICIT SYNDROME AB Rationale: D-Cycloserine, a partial agonist at the glycine site of the N-methyl-D-aspartate receptor, has demonstrated inconsistent efficacy for negative and cognitive symptoms of schizophrenia. The strongest evidence for efficacy has come from studies using D-cycloserine at a dose of 50 mg/day added to conventional antipsychotics in trials of 8 weeks duration or less. Objective: To assess the efficacy for negative symptoms and cognitive impairment of D-cycloserine augmentation of conventional antipsychotics in a 6-month trial. Methods: Fifty-five schizophrenia patients with prominent negative symptoms, treated with conventional antipsychotics, were randomly assigned to treatment with D-cycloserine 50 mg/day or placebo for 6 months in a double-blind, parallel group design. Results: Twenty-six subjects completed the 6-month trial; drop-out rates did not differ between treatment groups. D-Cycloserine treatment did not differ from placebo treatment on any primary outcome measure at 8 or 24 weeks, including response of negative symptoms and performance on a cognitive battery. Serum D-cycloserine concentrations did not correlate with response of negative symptoms. Conclusion: D-Cycloserine did not exhibit therapeutic effects in this trial, possibly reflecting the high drop-out rate, a narrow range of therapeutic serum concentrations, a modest magnitude of therapeutic effect for the selected outcome measures, or loss of efficacy over time. Because D-cycloserine is a partial agonist with relatively low affinity for the glycine site, the magnitude of potential therapeutic effect may be smaller than that achieved by the higher-affinity full agonists, glycine and D-serine. C1 Freedom Trail Clin, Boston, MA 02114 USA. Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Bedford Vet Affairs Med Ctr, Boston, MA 02118 USA. Tufts Med Sch, Lemuel Shattuck Hosp, Boston, MA USA. Massachusetts Gen Hosp, Pediat Neurol Serv, Boston, MA 02114 USA. McLean Hosp, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goff, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM goff@psych.mgh.harvard.edu FU NIMH NIH HHS [K24 MH02025, P50 MH60450, R01 MH54245] NR 37 TC 67 Z9 67 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD APR PY 2005 VL 179 IS 1 BP 144 EP 150 DI 10.1007/s00213-004-2032-2 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 915GE UT WOS:000228285300013 PM 15502972 ER PT J AU Hart, S Fonareva, I Merluzzi, N Mohr, DC AF Hart, S Fonareva, I Merluzzi, N Mohr, DC TI Treatment for depression and its relationship to improvement in quality of life and psychological well-being in multiple sclerosis patients SO QUALITY OF LIFE RESEARCH LA English DT Article DE depression; multiple sclerosis; quality of life ID MAJOR DEPRESSION; DISABILITY; SYMPTOMS; FATIGUE; DISEASE; PEOPLE; IMPACT; PSYCHOTHERAPY; DISTRESS; OUTCOMES AB Depression, a common problem in multiple sclerosis (MS), is generally associated with poorer quality of life (QOL). However, it is unclear whether treating depression also extends to better perceived QOL. Understanding QOL in MS has been limited by narrow definitions and exclusive focus on symptomology, with little emphasis on positive aspects of QOL. This study examined the impact of treating depression on QOL in 60 patients with a relapsing form of MS and moderate to severe depression, who were randomly assigned to one of three validated 16-week treatments for depression: individual cognitive-behavioral therapy, group psychotherapy, or sertraline. QOL was measured by the MSQOL-54, a version of the SF-36 adapted for MS, and Ryff's scales of psychological well-being, which measure positive attitudes and functioning. Depression and QOL were measured at baseline and immediately following treatment completion. Controlling for baseline neurological impairment and baseline QOL scores, regression analyses showed treating depression was significantly associated with improvements in the MSQOL-54 scales (R(2)s = 0.19-0.55, p < 0.001) and in four of the six scales of psychological well-being: environmental mastery (R-2 = 0.13, p < 0.001), positive relations (R-2 = 0.08, p < 0.001), purpose in life (R-2 = 0.16, p < 0.001), and self-acceptance (R-2 = 0.26, p < 0.001). Findings suggest treating depression influences both the negative and positive aspects of QOL and underscore the importance of examining QOL with two complementary approaches. C1 Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Hart, S (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, 4150 Clement St 116-A, San Francisco, CA 94121 USA. EM slhart@itsa.ucsf.edu RI Hart, Stacey/E-4819-2011 FU NIMH NIH HHS [R01 MH-59708, R01 MH059708, R01 MH059708-06] NR 51 TC 51 Z9 53 U1 4 U2 14 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD APR PY 2005 VL 14 IS 3 BP 695 EP 703 DI 10.1007/s11136-004-1364-z PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 942VJ UT WOS:000230310700011 PM 16022063 ER PT J AU Thrall, JH AF Thrall, JH TI Prevalence and costs of chronic disease in a health care system structured for treatment of acute illness SO RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM jthrall@partners.org NR 26 TC 19 Z9 19 U1 1 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2005 VL 235 IS 1 BP 9 EP 12 DI 10.1148/radiol.2351041768 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 910SN UT WOS:000227952600004 PM 15798162 ER PT J AU Delille, JP Slanetz, PJ Yeh, ED Kopans, DB Halpern, EF Kopans, DB AF Delille, JP Slanetz, PJ Yeh, ED Kopans, DB Halpern, EF Kopans, DB TI Hormone replacement therapy in postmenopausal women: Breast tissue perfusion determined with MR imaging - Initial observations SO RADIOLOGY LA English DT Article ID CONTRAST-MEDIUM ENHANCEMENT; CORONARY-HEART-DISEASE; MENSTRUAL-CYCLE; MAMMOGRAPHIC DENSITY; PRIMARY PREVENTION; GD-DTPA; CANCER; ESTROGEN; RISK; AGE AB PURPOSE: To use magnetic resonance (MR) imaging to evaluate tissue perfusion in the normal breast parenchyma of postmenopausal women with current or recent hormone replacement therapy (HRT). MATERIALS AND METHODS: The study was approved by the institutional subcommittee on human studies, and informed consent was obtained from all patients prior to MR imaging. Sixty postmenopausal women (age range, 44-77 years) were grouped according to HRT received: estrogen replacement therapy (ERT) (n = 13), combined (estrogen and progesterone) replacement therapy (CRT) (n = 16), selective estrogen receptor modulator (SERM) therapy (n = 8), and no (hormone replacement) therapy (NT) (n = 23). MR imaging with a 1.5-T magnet was performed by using gradient-echo and dynamic contrast material-enhanced echoplanar pulse sequences before and after gadopentetate dimeglumine injection. Precontrast T1 relaxation times were measured, after which extraction-flow product (EFP) maps were calculated with a multicompartmental model. Analysis of variance was performed. RESULTS: Age did not significantly differ between the groups (P>.3). Women receiving ERT or CRT at the time of MR imaging had higher EFP values (7.3 m L . 100 g(-1). min(-1) +/- 2.6 and 7.1 mL . 100 g(-1) . min(-1) +/- 3.8, respectively) than did women receiving NT (4.4 mL . 100 g(-1) . min(-1) +/- 2.1) (P =.012 and P =.008, respectively) or SERM therapy (3.9 mL . 100 g(-1) . min(-1) +/- 1.1) (P =.015 and P =.013, respectively). Women who ended ERT or CRT 1-47 months before MR examination had lower EFP values than did women with current ERT or CRT and had higher EFP values than did women receiving NT or SERM therapy (6.2 mL . 100 g(-1) . min(-1) +/- 2.4 and 5.9 ML . 100 g(-1). min(-1) +/- 3.8, respectively), but the observed differences were not significant (P > .1). Differences in T1 between all groups were not significant (P > .5). CONCLUSION: Higher breast tissue perfusion is observed in postmenopausal women receiving HRT. (C) RSNA, 2005. C1 Caritas St Elizabeths Med Ctr, Dept Radiol, Brighton, MA 02135 USA. Massachusetts Gen Hosp, Div Breast Imaging, Boston, MA 02114 USA. Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Tufts Univ, Sch Med, Brighton, MA 02135 USA. RP Slanetz, PJ (reprint author), Caritas St Elizabeths Med Ctr, Dept Radiol, 736 Cambridge St, Brighton, MA 02135 USA. EM priscilla_slanetz@cchcs.org RI Garrido, Leoncio/K-3092-2014; OI Garrido, Leoncio/0000-0002-7587-1260; Slanetz, Priscilla/0000-0003-1248-5116 NR 42 TC 35 Z9 37 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2005 VL 235 IS 1 BP 36 EP 41 DI 10.1148/radiol.2351040012 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 910SN UT WOS:000227952600009 PM 15798166 ER PT J AU Horkan, C Dalal, K Coderre, JA Kiger, JL Dupuy, DE Signoretti, S Halpern, EF Goldberg, SN AF Horkan, C Dalal, K Coderre, JA Kiger, JL Dupuy, DE Signoretti, S Halpern, EF Goldberg, SN TI Reduced tumor growth with combined radiofrequency ablation and radiation therapy in a rat breast tumor model SO RADIOLOGY LA English DT Article ID FOCAL LIVER-TUMORS; CELL LUNG-CANCER; LIPOSOMAL DOXORUBICIN; HEPATOCELLULAR-CARCINOMA; HEPATIC METASTASES; COLORECTAL-CANCER; PULMONARY MALIGNANCIES; INCREASED NECROSIS; THERMAL ABLATION; HYPERTHERMIA AB PURPOSE: To determine whether use of combined radiofrequency (RF) ablation and external-beam radiation therapy increases end-point survival beyond that with either RF ablation or radiation therapy alone in an animal tumor model. MATERIALS AND METHODS: With a protocol approved by the institutional animal care and use committee, R3230 mammary adenocarcinoma (12.5 mm +/- 0.6 [standard deviation]) was implanted subcutaneously into 107 female Fischer 344 rats. Initially, 42 tumors were randomized into four treatment groups: (a) RF ablation (70 degrees C for 5 minutes) alone, (b) RF ablation followed by radiation therapy (c) 20-Gy radiation alone, and (d) no treatment. Another with a total dose of 20 Gy, 19 tumors were randomized to receive (e) RF ablation (70 degrees C for 5 minutes) followed by 5-Gy radiation, (0 5-Gy radiation alone, or (g) no treatment. Animals were followed up until survival end point (either until tumor growth to 30 mm in diameter, or for 120 days if no tumor was seen in mammary fat pad or chest wall). Results were analyzed with the Kaplan-Meier method. Histopathologic analysis was performed in 15 additional tumors at survival end point and 18 other representative tumors at other specified end points. RESULTS: Combined RF ablation and 20-Gy radiation resulted in complete local control in nine (82%) of 11 tumors, compared with one (9%) of 11 tumors treated with RF ablation alone and one (17%) of six treated with RF ablation and 5-Gy radiation (P < .001). No local control was achieved in rats with radiation therapy alone or in controls. Median end-point survival was 12 days for controls, 20 days with RF ablation or 5-Gy radiation alone, 30 days with RF ablation plus 5-Gy radiation, 40 days with 20-Gy radiation alone, and 120 days with RF ablation plus 20-Gy radiation. Mean end-point survival was 13 days 5 (standard deviation) for the control group, 34 days 31 with RF ablation alone, and 43 days 16 with 20-Gy radiation alone. Mean survival was significantly greater with 20-Gy radiation and RF ablation combined: 94 days 34 (P < .001 compared with all other groups). Mean survival for rats that received 5-Gy radiation with RF ablation versus without was 46 days 37 versus 24 days 11, respectively. CONCLUSION: Combined RF ablation and external-beam radiation therapy increased animal survival compared with that with either of the treatments alone or with no treatment. (C) RSNA 2005. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol,Minimally Invas Tumor Therapy Lab, Boston, MA 02215 USA. MIT, Dept Nucl Engn, Cambridge, MA 02139 USA. Rhode Isl Hosp, Dept Radiol, Providence, RI USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Inst Technol Assessment, Boston, MA USA. RP Goldberg, SN (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol,Minimally Invas Tumor Therapy Lab, 1 Deaconess Rd,WCC 308B, Boston, MA 02215 USA. EM sgoldber@bidmc.harvard.edu OI Dupuy, Damian/0000-0003-0524-5982 NR 47 TC 40 Z9 40 U1 1 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2005 VL 235 IS 1 BP 81 EP 88 DI 10.1148/radiol.2351040269 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 910SN UT WOS:000227952600015 PM 15731375 ER PT J AU Eroglu, A Elliott, G Wright, DL Toner, M Toth, TL AF Eroglu, A Elliott, G Wright, DL Toner, M Toth, TL TI Progressive elimination of microinjected trehalose during mouse embryonic development SO REPRODUCTIVE BIOMEDICINE ONLINE LA English DT Article DE cryopreservation; freezing; glucose; HPLC; oocyte; sugar; trehalose ID HUMAN OOCYTES; DESICCATION TOLERANCE; PREIMPLANTATION DEVELOPMENT; SACCHAROMYCES-CEREVISIAE; GLUCOSE TRANSPORTERS; ENERGY-METABOLISM; MAMMALIAN-CELLS; MEIOTIC SPINDLE; CRYOPRESERVATION; ORGANIZATION AB Recently, sugars such as trehalose have been introduced into mammalian cells by overcoming the permeability barrier of cell membranes, and have provided improved tolerance against stresses associated with freezing and drying. However, the fate of the intracellular sugars has remained an open question. To address this issue, mouse oocytes were microinjected with 0.1 mol/l trehalose, and intracellular trehalose and glucose concentrations were determined during embryonic development using a high performance liquid chromatography and pulsed amperometric detection protocol. Trehalose was not detected in non-injected controls at any stage of development. In the microinjection group, the amount of intracellular trehalose progressively decreased as embryos developed. There was a corresponding increase in intracellular glucose concentration at the two-cell stage, suggesting cleavage of trehalose to two glucose molecules. In summary, this study presents a simple, highly sensitive protocol to determine intracellular sugars. The data reveal rapid elimination of microinjected trehatose during embryonic development. These findings have implications for designing osmolarity-optimized culture media for sugar-injected oocytes. C1 Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. Univ N Carolina, Dept Mech Engn & Engn Sci, Charlotte, NC 28223 USA. Harvard Univ, Sch Med, Vincent Obstet & Gynecol Serv, Massachusetts Gen Hosp, Boston, MA 02189 USA. Harvard Univ, Sch Med, Ctr Engn Med & Surg Serv, Massachusetts Gen Hosp,Shriners Hosp Children, Boston, MA 02189 USA. RP Eroglu, A (reprint author), Med Coll Georgia, Inst Mol Med & Genet, 1120 15th St,CB 2803, Augusta, GA 30912 USA. EM tltoth@partners.org NR 62 TC 18 Z9 19 U1 0 U2 0 PU REPRODUCTIVE HEALTHCARE LTD PI CAMBRIDGE PA DUCK END FARM, DRY DRAYTON, CAMBRIDGE, CB3 8DB, ENGLAND SN 1472-6483 J9 REPROD BIOMED ONLINE JI Reprod. Biomed. Online PD APR PY 2005 VL 10 IS 4 BP 503 EP 510 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 913ML UT WOS:000228155800017 PM 15901459 ER PT J AU Darabi, K Torres, G Chewaproug, D AF Darabi, K Torres, G Chewaproug, D TI Nephrolithiasis as primary symptom in sarcoidosis SO SCANDINAVIAN JOURNAL OF UROLOGY AND NEPHROLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Physicians-Pennsylvania-Chapter CY OCT 24-26, 2003 CL Harrisburg, PA SP Amer Coll Physicians, Pennsylvania Chap DE angiotensin-converting enzyme; extrapulmonary sarcoidosis; urolithiasis AB A 30-year-old black woman presented with a 1-year history of repeated episodes of worsening weight loss and fatigue. Physical examination showed no skin lesions and a chest roentgenogram was normal. Workup showed no obvious cause of recurrent renal stones. Finally, the detection of lymphadenopathy led to the diagnosis of extrapulmonary sarcoidosis. Up to 4% of all cases of sarcoidosis may present with urolithiasis only. Renal stones may be more common in severe cases of sarcoidosis, which affect blacks most frequently. Although not generally recommended for diagnostic purposes in sarcoidosis, in this case determination of the angiotensin-converting enzyme level was helpful in making the correct diagnosis. It is important that physicians are aware of the possibility that sarcoidosis may present as urolithiasis, even in the presence of a negative chest roentgenogram. C1 Albert Einstein Med Ctr, Dept Med, Philadelphia, PA 19141 USA. RP Darabi, K (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, GRJ 148,55 Fruit St, Boston, MA 02114 USA. EM kamrandarabi@yahoo.com NR 9 TC 3 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0036-5599 J9 SCAND J UROL NEPHROL JI Scand. J. Urol. Nephrol. PD APR PY 2005 VL 39 IS 2 BP 173 EP 175 DI 10.1080/00365590510007667 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 915SJ UT WOS:000228326200014 PM 16019774 ER PT J AU Waldo, MC Woodward, LA Cawthra, EM Adler, LE AF Waldo, MC Woodward, LA Cawthra, EM Adler, LE TI The virtual water maze, P50 sensory gating, and cognitive functioning SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 20th International Congress on Schizophernia Research CY APR 02-06, 2005 CL Savannah, GA C1 Denver VAMC, VISN 19, MIRECC, Denver, CO USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD APR PY 2005 VL 31 IS 2 BP 346 EP 346 PG 1 WC Psychiatry SC Psychiatry GA 914PY UT WOS:000228241201115 ER PT J AU Steinhauer, SR Condray, R Siegle, GJ Gurklis, JA AF Steinhauer, SR Condray, R Siegle, GJ Gurklis, JA TI Cognitive inhibition of the pupillary light reaction in schizophrenia and alcoholism: Physiological evidence for effortful processing SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 20th International Congress on Schizophernia Research CY APR 02-06, 2005 CL Savannah, GA C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD APR PY 2005 VL 31 IS 2 BP 378 EP 378 PG 1 WC Psychiatry SC Psychiatry GA 914PY UT WOS:000228241201211 ER PT J AU Tapp, A Wood, AE Kilzieh, N Kennedy, A AF Tapp, A Wood, AE Kilzieh, N Kennedy, A TI Double-blind comparison of quetiapine and haloperidol on cognitive functioning in patients with schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 20th International Congress on Schizophernia Research CY APR 02-06, 2005 CL Savannah, GA C1 VA Puget Sound Hlth Care Syst, Tacoma, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD APR PY 2005 VL 31 IS 2 BP 379 EP 379 PG 1 WC Psychiatry SC Psychiatry GA 914PY UT WOS:000228241201214 ER PT J AU Levitt, JJ Connor, EE Woolston, SL Ungar, LP Kuroki, N Kikinis, R Jolesz, FA McCarley, RW Shenton, ME AF Levitt, JJ Connor, EE Woolston, SL Ungar, LP Kuroki, N Kikinis, R Jolesz, FA McCarley, RW Shenton, ME TI The limbic striatum in schizophrenia: An MRI study SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 20th International Congress on Schizophernia Research CY APR 02-06, 2005 CL Savannah, GA C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD APR PY 2005 VL 31 IS 2 BP 397 EP 397 PG 1 WC Psychiatry SC Psychiatry GA 914PY UT WOS:000228241201266 ER PT J AU Holt, DJ Kunkel, L Weiss, AP Goff, DC Wright, CI Shin, LM Rauch, SL Hootnick, J Heckers, S AF Holt, DJ Kunkel, L Weiss, AP Goff, DC Wright, CI Shin, LM Rauch, SL Hootnick, J Heckers, S TI Increased medial temporal lobe responses to emotional and neutral facial expressions in schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 20th International Congress on Schizophernia Research CY APR 02-06, 2005 CL Savannah, GA C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD APR PY 2005 VL 31 IS 2 BP 422 EP 423 PG 2 WC Psychiatry SC Psychiatry GA 914PY UT WOS:000228241201337 ER PT J AU Nagamoto, HT Adler, LE Kisley, MA Hea, RA Cawthra, E Griffith, JM McRae, KA Freedman, R AF Nagamoto, HT Adler, LE Kisley, MA Hea, RA Cawthra, E Griffith, JM McRae, KA Freedman, R TI P50 gating in schizophrenia at 500 and 100 MSEC intervals in typical antipsychotics versus clozapine SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 20th International Congress on Schizophernia Research CY APR 02-06, 2005 CL Savannah, GA ID AUDITORY P50 C1 Denver VA Med Ctr, MHS, Denver, CO USA. Denver VA Med Ctr, VISN 19 MIRECC, Denver, CO USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD APR PY 2005 VL 31 IS 2 BP 460 EP 460 PG 1 WC Psychiatry SC Psychiatry GA 914PY UT WOS:000228241202046 ER PT J AU Yao, JK Magan, S Gurklis, J Sonel, A Reddy, R AF Yao, JK Magan, S Gurklis, J Sonel, A Reddy, R TI Effect of omega-3 fatty acid on clinically-stable schizophrenic patients with a high risk for coronary artery disease SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 20th International Congress on Schizophernia Research CY APR 02-06, 2005 CL Savannah, GA C1 VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD APR PY 2005 VL 31 IS 2 BP 507 EP 507 PG 1 WC Psychiatry SC Psychiatry GA 914PY UT WOS:000228241202183 ER PT J AU Gaither, ML Nazzaro, D Huegel, S Jacoby, A Haas, G AF Gaither, ML Nazzaro, D Huegel, S Jacoby, A Haas, G TI Cognitive-behavioral treatment applications in individuals with chronic schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 20th International Congress on Schizophernia Research CY APR 02-06, 2005 CL Savannah, GA C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD APR PY 2005 VL 31 IS 2 BP 524 EP 525 PG 2 WC Psychiatry SC Psychiatry GA 914PY UT WOS:000228241202230 ER PT J AU Wood, AE Tapp, A Kennedy, A Kilzieh, N AF Wood, AE Tapp, A Kennedy, A Kilzieh, N TI Use of the independent living scales to measure community functioning in patients with schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 20th International Congress on Schizophernia Research CY APR 02-06, 2005 CL Savannah, GA C1 VA Puget Sound Healthcare Syst, Tacoma, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD APR PY 2005 VL 31 IS 2 BP 535 EP 536 PG 2 WC Psychiatry SC Psychiatry GA 914PY UT WOS:000228241202263 ER PT J AU Winckler, W Myers, SR Richter, DJ Onofrio, RC McDonald, GJ Bontrop, RE McVean, GAT Gabriel, SB Reich, D Donnelly, P Altshuler, D AF Winckler, W Myers, SR Richter, DJ Onofrio, RC McDonald, GJ Bontrop, RE McVean, GAT Gabriel, SB Reich, D Donnelly, P Altshuler, D TI Comparison of fine-scale recombination rates in humans and chimpanzees SO SCIENCE LA English DT Article ID YEAST SACCHAROMYCES-CEREVISIAE; GLOBIN GENE-CLUSTER; MEIOTIC RECOMBINATION; HUMAN GENOME; DNA-SEQUENCE; HOT-SPOT; HOTSPOT; CONVERSION; CROSSOVER AB We compared fine-scale recombination rates at orthologous loci in humans and chimpanzees by analyzing polymorphism data in both species. Strong statistical evidence for hotspots of recombination was obtained in both species. Despite similar to 99% identity at the level of DNA sequence, however, recombination hotspots were found rarely (if at all) at the same positions in the two species, and no correlation was observed in estimates of fine-scale recombination rates. Thus, local patterns of recombination rate have evolved rapidly, in a manner disproportionate to the change in DNA sequence. C1 Univ Oxford, Dept Stat, Oxford OX1 3TG, England. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02141 USA. MIT, Cambridge, MA 02141 USA. Biomed Primate Res Ctr, Dept Comparat Genet & Refinement, NL-2280 GH Rijswijk, Netherlands. RP Donnelly, P (reprint author), Univ Oxford, Dept Stat, Oxford OX1 3TG, England. EM donnelly@stats.ox.ac.uk; attshuler@molbio.mgh.harvard.edu RI Altshuler, David/A-4476-2009; Bontrop, Ronald/J-3628-2012; Myers, Simon/A-6792-2015 OI Altshuler, David/0000-0002-7250-4107; Bontrop, Ronald/0000-0003-0874-6467; Myers, Simon/0000-0002-2585-9626 NR 23 TC 248 Z9 256 U1 2 U2 19 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 APR 1 PY 2005 VL 308 IS 5718 BP 107 EP 111 DI 10.1126/science.1105322 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 914IQ UT WOS:000228221500043 PM 15705809 ER PT J AU Schapira, L AF Schapira, L TI Palliative information: Doctor-patient communication SO SEMINARS IN ONCOLOGY LA English DT Review ID MEDICAL ONCOLOGY FELLOWS; BREAKING BAD-NEWS; CANCER-PATIENTS; INTERVIEWING SKILLS; HEALTH OUTCOMES; TRAINING MODEL; BREAST-CANCER; CARE; PHYSICIANS; PROGNOSIS C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Schapira, L (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 55 Fruit St,Yawkey 9072, Boston, MA 02114 USA. EM lschapira@partners.org NR 69 TC 5 Z9 5 U1 2 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2005 VL 32 IS 2 BP 139 EP 144 DI 10.1053/j.seminoncol.2004.11.016 PG 6 WC Oncology SC Oncology GA 915MI UT WOS:000228307900003 PM 15815958 ER PT J AU Gilman, MD Aquino, SL AF Gilman, MD Aquino, SL TI State-of-the-art FDG-PET imaging of lung cancer SO SEMINARS IN ROENTGENOLOGY LA English DT Article DE PET; FDG-PET; lung cancer; dual imaging; CT/PET ID POSITRON-EMISSION-TOMOGRAPHY; CONGESTIVE-HEART-FAILURE; BRONCHOGENIC-CARCINOMA; F-18 FLUORODEOXYGLUCOSE; COMPUTED-TOMOGRAPHY; MEDIASTINAL LYMPHADENOPATHY; GLUCOSE-TRANSPORT; PULMONARY NODULES; TALC PLEURODESIS; ADIPOSE-TISSUE C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM saquino@partners.org NR 80 TC 14 Z9 19 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 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD APR PY 2005 VL 40 IS 2 BP 143 EP 153 DI 10.1053/j.ro.2005.01.008 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 917OY UT WOS:000228473300009 PM 15898411 ER PT J AU Robson, SC Wu, Y Sun, XF Knosalla, C Dwyer, K Enjyoji, K AF Robson, SC Wu, Y Sun, XF Knosalla, C Dwyer, K Enjyoji, K TI Ectonucleotidases of CD39 family modulate vascular inflammation and thrombosis in transplantation SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Review DE antibodies; CD39; endothelial cell; kidney; NTPDase; platelets; transplantation; vasculature ID ENDOTHELIAL-CELL ACTIVATION; ATP-DIPHOSPHOHYDROLASE ACTIVITY; ISCHEMIA-REPERFUSION INJURY; DELAYED XENOGRAFT REJECTION; RENAL-ALLOGRAFT REJECTION; DECAY-ACCELERATING FACTOR; ORGAN-TRANSPLANTATION; TRANSGENIC PIGS; THERAPEUTIC STRATEGIES; PLATELET-AGGREGATION AB Transplantation results in exposure of the graft vasculature to warm and cold ischemia, followed by perfusion by circulating blood constituents and obligatory oxidant stress. Further graft injury occurs as consequences of acute Immoral cellular rejection or chronic transplant vasculopathy, or both. Extracellular nucleotide stimulation of purinergic type 2 (P2) receptors are key components of platelet, endothelial cell (EC), and leukocyte activation resulting in vascular thrombosis and inflammation in vivo. CD39, the prototype nucleoside triphosphate diphosphohydrolase (NTPDase-1) is highly expressed on endothelium; in contrast, CD39L1/NTPDase-2 (a preferential adenosine triphosphatase [ATPase]) is found on vascular adventitial cells. Both ectoenzymes influence thrombogenesis by the regulated hydrolysis of extracellular nucleotides that differentially regulate P2-receptor activity and function in platelets and vascular cells. The intracytoplasmic domains of NTPDase-1 may also independently influence cellular activation and proliferation. NTPDase activity is substantively lost in the vasculature of injured or rejected grafts. A role for NTPDase-1 in thromboregulation has been validated by generation of mutant mice either null for cd39 or overexpressing human CD39. Administration of soluble NTPDase or induction of CD39 by adenoviral vectors, or both, are also of benefit in several models of transplantation. Administration of soluble CD39 or targeted expression may have future therapeutic application in transplantation-associated and other vascular diseases. C1 Beth Israel Deaconess Med Ctr, Transplantat Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Med Ctr, Dept Med,Vasc Biol & Transplantat Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Robson, SC (reprint author), Beth Israel Deaconess Med Ctr, Transplantat Ctr, Res N 99 Brookline Ave,Room 301, Boston, MA 02215 USA. EM srobson@bidmc.harvard.edu FU NHLBI NIH HHS [HL 57307, HL 63872]; NIAID NIH HHS [AI 45897] NR 145 TC 124 Z9 125 U1 1 U2 5 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD APR PY 2005 VL 31 IS 2 BP 217 EP 233 DI 10.1055/s-2005-869527 PG 17 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 923HP UT WOS:000228901300011 PM 15852225 ER PT J AU Kattapuram, TM Suri, R Rosol, MS Rosenberg, AE Kattapuram, SV AF Kattapuram, TM Suri, R Rosol, MS Rosenberg, AE Kattapuram, SV TI Idiopathic and diabetic skeletal muscle necrosis: evaluation by magnetic resonance imaging SO SKELETAL RADIOLOGY LA English DT Article DE myonecrosis; diabetes; muscle necrosis; MRI; idiopathic; diabetic myonecrosis; skeletal muscle necrosis ID MUSCULAR INFARCTION; MRI; PATIENT; BIOPSY AB Objective: Idiopathic and diabetic-associated muscle necrosis are similar, uncommon clinical entities requiring conservative management and minimal intervention to avoid complications and prolonged hospitalization. An early noninvasive diagnosis is therefore essential. We evaluated the magnetic resonance imaging (MRI) characteristics of muscle necrosis in 14 patients, in eight of whom the diagnoses were confirmed histologically. Design and patients: Two experienced musculoskeletal radiologists performed retrospective evaluations of the MRI studies of 14 patients with the diagnoses of skeletal muscle infarction. In 10 cases gadolinium-enhanced (T1-weighted fat-suppressed) sequences were available along with T1-weighted, T2-weighted images and STIR sequences, while in four cases contrast-enhanced images were not available. Results: Eight patients had underlying diabetes and in six patients the cause of the myonecrosis was considered idiopathic. T1-weighted images demonstrated isointense swelling of the involved muscle, with mildly displaced fascial planes. There was effacement of the fat signal intensity within the muscle. Fat-suppressed T2-weighted images showed diffuse heterogeneous high signal intensity in the muscles suggestive of edema. Perifascial fluid collection was seen in eight cases. Subcutaneous edema was present in seven patients. Following intravenous gadolinium administration, MRI demonstrated a focal area of heterogeneously enhancing mass with peripheral enhancement. Within this focal lesion, linear dark areas were seen with serpentine enhancing streaks separating them in eight cases. In two cases, a central relatively nonenhancing mass with irregular margins and peripheral enhancement was noted. The peripheral enhancement involved a significant part of the muscle. No focal fluid collection was noted. Conclusions: We believe that the constellation of imaging findings on T1- and T2-weighted images and post-gadolinium sequences is highly suggestive of muscle necrosis. We consider certain specific findings on gadolinium-enhanced images to be characteristic. The findings reported here should provide radiologists with useful information in making the diagnosis of skeletal muscle necrosis without resorting to invasive procedures. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Kattapuram, SV (reprint author), Massachusetts Gen Hosp, WACC 515,15 Parkman St, Boston, MA 02114 USA. EM skattapuram@partners.org NR 23 TC 47 Z9 49 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD APR PY 2005 VL 34 IS 4 BP 203 EP 209 DI 10.1007/s00256-004-0881-8 PG 7 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 907WH UT WOS:000227748300003 PM 15700181 ER PT J AU Malhotra, A Jordan, A AF Malhotra, A Jordan, A TI Surface tension and sleep apnea: a sticky business SO SLEEP LA English DT Editorial Material ID UPPER AIRWAY; PHARYNGEAL MECHANICS; MUSCLE-ACTIVITY; LINING LIQUID; COLLAPSIBILITY; ACTIVATION; ANESTHESIA; ANATOMY C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Malhotra, A (reprint author), BIDMC, Sleep Med Div, 75 Francis St, Boston, MA 02115 USA. EM amalhotra1@partners.org OI Jordan, Amy/0000-0001-8561-9766 FU NHLBI NIH HHS [R01 HL073146-02, R01 HL073146]; NIA NIH HHS [K23 AG024837, K23 AG024837-03] NR 27 TC 1 Z9 1 U1 0 U2 2 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 1 PY 2005 VL 28 IS 4 BP 392 EP 393 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 913ER UT WOS:000228134900004 PM 16171283 ER PT J AU Black, JE Hirshkowitz, M AF Black, JE Hirshkowitz, M TI Modafinil for treatment of residual excessive sleepiness in nasal continuous positive airway pressure-treated obstructive sleep apnea/hypopnea syndrome SO SLEEP LA English DT Article DE modafinil; obstructive sleep apnea/hypopnea syndrome; sleepiness; wakefulness ID APNEA-HYPOPNEA SYNDROME; QUALITY-OF-LIFE; DAYTIME SLEEPINESS; BLOOD-PRESSURE; APNOEA/HYPOPNOEA SYNDROME; RANDOMIZED-TRIAL; ADJUNCT THERAPY; PARALLEL TRIAL; CPAP THERAPY; ASSOCIATION AB Objectives: Nasal continuous positive airway pressure (nCPAP) usually reduces sleepiness in patients with obstructive sleep apnea/hypopnea syndrome. However, even with regular use of nCPAP, some patients experience residual excessive sleepiness. We evaluated the efficacy and safety of the wake-promoting agent modafinil for treating residual excessive sleepiness in nCPAP-treated patients. Design: 12-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. Patients: Patients aged 18 to 70 years diagnosed with obstructive sleep apnea/hypopnea syndrome and having residual excessive sleepiness during nCPAP therapy were eligible. Interventions: Once-daily modafinil, 200 mg or 400 mg, or placebo. Measurements and Results: Assessments included the Maintenance of Wakefulness Test, Epworth Sleepiness Scale, Clinical Global Impression of Change, and Functional Outcomes of Sleep Questionnaire. Both doses of modafinil significantly improved mean (SD) sleep latency on the Maintenance of Wakefulness Test at weeks 4, 8, and 12 compared with placebo (week 12: modafinil 400 mg, 15.0 [5.3] minutes; 200 mg, 14.8 [5.3] minutes; placebo, 12.6 [5.8] minutes; P < .0001). The Epworth Sleepiness Scale score decreased more in patients taking modafinil compared with those in the placebo group (week 12: modafinil 400 mg, -4.5 [4.3]; 200 mg, -4.5 [4.7]; placebo, -1.8 [3.5]; P < .0001). At week 12, overall clinical condition improved for 61% and 68% of patients treated with modafinil 200 mg and 400 mg, respectively, versus 37% of placebo-treated patients (P < .001). Modafinil was generally well tolerated and did not adversely affect nighttime sleep or nCPAP use. Conclusions: These results confirm previous shorter-term controlled trials, indicating modafinil is a useful adjunct therapy for improving wakefulness in patients with residual excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome who were treated with nCPAP. C1 Stanford Univ, Stanford Sleep Disorder Clin, Stanford, CA 94305 USA. VA Med Ctr, Sleep Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Black, JE (reprint author), Stanford Univ, Stanford Sleep Disorder Clin, 401 Quarry Rd,Suite 3301, Stanford, CA 94305 USA. EM jedblack@stanford.edu NR 44 TC 70 Z9 73 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 1 PY 2005 VL 28 IS 4 BP 464 EP 471 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 913ER UT WOS:000228134900012 PM 16171291 ER PT J AU Kapur, VK Baldwin, CM Resnick, HE Gottlieb, DJ Nieto, FJ AF Kapur, VK Baldwin, CM Resnick, HE Gottlieb, DJ Nieto, FJ TI Sleepiness in patients with moderate to severe sleep-disordered breathing SO SLEEP LA English DT Article DE sleep; apnea; sleepiness; syndrome; subjective ID HEART HEALTH; DAYTIME SLEEPINESS; HYPERTENSION; ASSOCIATION; DISEASE; ADULTS; SCALE; APNEA AB Background: Population-based studies suggest that complaints of sleepiness are absent in many individuals with sleep-disordered breathing. We investigated the prevalence of sleepiness as well as factors associated with sleepiness in individuals with moderate to severe sleep-disordered breathing (apnea-hypopnea index >= 15). Design: Cross-sectional study. Setting: The Sleep Heart Health Study. Participants: Sleep Heart Health Study participants (N = 6440). Measurements and Results: Sleepiness was defined as an Epworth Sleepiness Scale score > 10 or a report of at least frequently feeling unrested or sleepy. Forty-six percent of participants with moderate to severe sleep-disordered breathing (n = 1149) reported sleepiness. Characteristics associated with sleepiness after adjustment for confounders included presence of respiratory disease, shorter self-reported weekday and weekend sleep, sleep durations, complaints of insufficient sleep, complaints of sleep maintenance insomnia, early morning awakening, habitual snoring, and complaints of awakening with leg cramps or leg jerks. Some respiratory polysomnography measures were associated with sleepiness, but sleep-stage percentages and measures of sleep disruption were not. Conclusions: In this community-based cohort, subjective sleepiness is absent in many individuals with significant sleep-disordered breathing. Comorbid conditions, including respiratory disease, sleep restriction, insomnia, and nocturnal leg complaints, are important risk factors for sleepiness in individuals with moderate to severe sleep-disordered breathing. C1 Univ Washington, Sleep Disorders Ctr, Dept Med, Seattle, WA 98104 USA. Arizona State Univ, Coll Nursing SW Borderlands, Tempe, AZ USA. MedStar Res Inst, Hyattsville, MD USA. Boston Univ, Dept Med, Boston, MA 02215 USA. VA Boston HCS, Boston, MA USA. Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA. RP Kapur, VK (reprint author), Univ Washington, Sleep Disorders Ctr, Dept Med, Box 359803,325 9th Ave, Seattle, WA 98104 USA. EM vkapur@u.washington.edu RI Kapur, Vishesh/K-1054-2014; OI Kapur, Vishesh/0000-0002-5417-1097; Baldwin, Carol/0000-0002-0732-2307 NR 18 TC 114 Z9 120 U1 0 U2 3 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 1 PY 2005 VL 28 IS 4 BP 472 EP 477 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 913ER UT WOS:000228134900013 PM 16171292 ER PT J AU Kushida, CA Littner, MR Morgenthaler, T Alessi, CA Bailey, D Coleman, J Friedman, L Hirshkowitz, M Kapen, S Kramer, M Lee-Chiong, T Loube, DL Owens, J Pancer, JP Wise, M AF Kushida, CA Littner, MR Morgenthaler, T Alessi, CA Bailey, D Coleman, J Friedman, L Hirshkowitz, M Kapen, S Kramer, M Lee-Chiong, T Loube, DL Owens, J Pancer, JP Wise, M TI Practice parameters for the indications for polysomnography and related procedures: An update for 2005 SO SLEEP LA English DT Review DE practice parameters; practice guidelines; standards of practice; polysomnography; sleep related breathing disorders; sleep disorders; narcolepsy; parasomnias; restless legs syndrome; periodic limb movement sleep disorder; insomnia; circadian rhythm sleep disorders ID OBSTRUCTIVE SLEEP-APNEA; POSITIVE AIRWAY PRESSURE; AMYOTROPHIC-LATERAL-SCLEROSIS; CONGESTIVE-HEART-FAILURE; CHEYNE-STOKES RESPIRATION; RESTLESS LEGS SYNDROME; NOCTURNAL NASAL VENTILATION; PULMONARY-DISEASE PATIENTS; BRAIN-COMPUTER INTERFACE; HYPOPNEA SYNDROME AB These practice parameters are an update of the previously-published recommendations regarding the indications for polysomnography and related procedures in the diagnosis of sleep disorders. Diagnostic categories include the following: sleep related breathing disorders, other respiratory disorders, narcolepsy, parasomnias, sleep related seizure disorders, restless legs syndrome, periodic limb movement sleep disorder, depression with insomnia, and circadian rhythm sleep disorders. Polysomnography is routinely indicated for the diagnosis of sleep related breathing disorders; for continuous positive airway pressure (CPAP) titration in patients with sleep related breathing disorders; for the assessment of treatment results in some cases; with a multiple sleep latency test in the evaluation of suspected narcolepsy; in evaluating sleep related behaviors that are violent or otherwise potentially injurious to the patient or others; and in certain atypical or unusual parasomnias. Polysomnography may be indicated in patients with neuromuscular disorders and sleep related symptoms; to assist in the diagnosis of paroxysmal arousals or other sleep disruptions thought to be seizure related; in a presumed parasomnia or sleep related seizure disorder that does not respond to conventional therapy; or when there is a strong clinical suspicion of periodic limb movement sleep disorder. Polysomnography is not routinely indicated to diagnose chronic lung disease; in cases of typical, uncomplicated, and noninjurious parasomnias when the diagnosis is clearly delineated; for patients with seizures who have no specific complaints consistent with a sleep disorder; to diagnose or treat restless legs syndrome; for the diagnosis of circadian rhythm sleep disorders; or to establish a diagnosis of depression. C1 Stanford Univ, Ctr Excellence Sleep Disorders, Stanford, CA 94305 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Sepulveda, CA USA. Mayo Clin, Mayo Sleep Disorders Ctr, Rochester, MN USA. Univ Calif Los Angeles, Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Greenwood Dent Assoc, Englewood, CO USA. Middle Tennessee ENT, Murfreesboro, TN USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX 77030 USA. VA Med Ctr, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. Maimonides Hosp, Dept Psychiat, Brooklyn, NY 11219 USA. NYU, Sch Med, New York, NY USA. Natl Jewish Med & Res Ctr, Sleep Clin, Denver, CO USA. Swedish Med Ctr, Sleep Med Inst, Seattle, WA USA. Brown Univ, Rhode Isl Hosp, Dept Pediat, Providence, RI 02903 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. RP Stanford Univ, Ctr Excellence Sleep Disorders, Stanford, CA 94305 USA. OI Morgenthaler, Timothy/0000-0002-2614-3793 NR 150 TC 583 Z9 622 U1 2 U2 30 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD APR 1 PY 2005 VL 28 IS 4 BP 499 EP 521 PG 23 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 913ER UT WOS:000228134900015 PM 16171294 ER PT J AU Mulley, AG AF Mulley, AG TI Lumbar disc herniation - Evaluation of information on the internet - Point of view SO SPINE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Div Gen Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mulley, AG (reprint author), Harvard Univ, Sch Med, Div Gen Med, Massachusetts Gen Hosp, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM amulley@partners.org NR 4 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD APR 1 PY 2005 VL 30 IS 7 BP 830 EP 830 DI 10.1097/01.brs.0000157779.65222.af PG 1 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 912FK UT WOS:000228062800018 PM 15803088 ER PT J AU Singhal, AB Benner, T Roccatagliata, L Koroshetz, WJ Schaefer, PW Lo, EH Buonanno, FS Gonzalez, RG Sorensen, AG AF Singhal, AB Benner, T Roccatagliata, L Koroshetz, WJ Schaefer, PW Lo, EH Buonanno, FS Gonzalez, RG Sorensen, AG TI A pilot study of normobaric oxygen therapy in acute ischemic stroke SO STROKE LA English DT Article DE magnetic resonance imaging; neuroprotection; oxygen; stroke ID FOCAL CEREBRAL-ISCHEMIA; HYPERBARIC-OXYGEN; INFARCT SIZE; THROMBOLYSIS; HYPEROXIA; MRI; REPERFUSION; INJURY; TRIAL; RATS AB Background and Purpose - Therapies that transiently prevent ischemic neuronal death can potentially extend therapeutic time windows for stroke thrombolysis. We conducted a pilot study to investigate the effects of high-flow oxygen in acute ischemic stroke. Methods - We randomized patients with acute stroke (<12 hours) and perfusion-diffusion "mismatch" on magnetic resonance imaging (MRI) to high-flow oxygen therapy via facemask for 8 hours ( n = 9) or room air ( controls, n = 7). Stroke scale scores and MRI scans were obtained at baseline, 4 hours, 24 hours, 1 week, and 3 months. Clinical deficits and MR abnormalities were compared between groups. Results - Stroke scale scores were similar at baseline, tended to improve at 4 hours ( during therapy) and 1 week, and significantly improved at 24 hours in hyperoxia-treated patients. There was no significant difference at 3 months. Mean ( +/- SD) relative diffusion MRI lesion volumes were significantly reduced in hyperoxia-treated patients at 4 hours (87.8 +/- 22% versus 149.1 +/- 41%; P = 0.004) but not subsequent time points. The percentage of MRI voxels improving from baseline "ischemic" to 4-hour "non-ischemic" values tended to be higher in hyperoxia-treated patients. Cerebral blood volume and blood flow within ischemic regions improved with hyperoxia. These "during-therapy" benefits occurred without arterial recanalization. By 24 hours, MRI showed reperfusion and asymptomatic petechial hemorrhages in 50% of hyperoxia-treated patients versus 17% of controls ( P = 0.6). Conclusions - High-flow oxygen therapy is associated with a transient improvement of clinical deficits and MRI abnormalities in select patients with acute ischemic stroke. Further studies are warranted to investigate the safety and efficacy of hyperoxia as a stroke therapy. C1 Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, VBK-802, Boston, MA 02114 USA. EM asinghal@partners.org FU NINDS NIH HHS [R01 NS38731, R01 NS38477-04, R01 NS40529]; PHS HHS [R01 37074] NR 30 TC 154 Z9 159 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2005 VL 36 IS 4 BP 797 EP 802 DI 10.1161/01.STR.0000158914.66827.2e PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 911XI UT WOS:000228039700025 PM 15761201 ER PT J AU Pawlik, TM Poon, RT Abdalla, EK Ikai, I Nagorney, DM Belghiti, M Kianmanesh, R Ng, IOL Curley, SA Yamaoka, Y Lauwers, GY Vauthey, JN AF Pawlik, TM Poon, RT Abdalla, EK Ikai, I Nagorney, DM Belghiti, M Kianmanesh, R Ng, IOL Curley, SA Yamaoka, Y Lauwers, GY Vauthey, JN TI Hepatectomy for hepatocellular carcinoma with major portal or hepatic vein invasion: Results of a multicenter study SO SURGERY LA English DT Article; Proceedings Paper CT 6th World Congress of the International-Hepato-Pancreato-Biliary-Association CY JUN 03-06, 2004 CL Washington, DC SP Int Hepato-Pancreato Biliary Assoc ID TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; LIVER-TRANSPLANTATION; SAMPLING VARIABILITY; MULTIVARIATE-ANALYSIS; TREATMENT STRATEGY; PROGNOSTIC FACTORS; NATURAL-HISTORY; RESECTION; CIRRHOSIS; SURGERY AB Background. The role of hepatic resection in patients with hepatocellular carcinoma (HCC) and invasion of a main portal or hepatic vein branch is controversial. We evaluated the efficacy of hepatic resection and the factors affecting survival after resection in such patients. Methods. The records of 102 patients who underwent resection for HCC with major vascular invasion between 1984 and 1999 were reviewed. Prognostic factors were evaluated by univariate and multivariate analysis. Results. The study included 87 men and 15 women. The median age was 59 years. The perioperative mortality rate, was 5.9%. Median survival was 11 months (median follow-up, 93 months). The 1-, 3-, and 5-year survival rates were 45%, 17%, and 10%; the longest-living survivor was still alive at 14.8 years. Absence of moderate to severe fibrosis and absence of high nuclear grade were associated with a better 5-year survival rate (23% vs 5%; P = .001. and 21% vs 9%; P = .04, respectively). On multivariate analysis, moderate to severe fibrosis remained a significant predictor of both short-term (<= 6 months) and long-term (> 6 months) survival (P < .03 and P < .01, respectively). Conclusions. Hepati c resection for HCC with major vascular invasion is associated with median survival exceeding historical survival in patients not treated surgically. Patients with HCC and major vascular invasion who derive long-term benefit from resection,have no or minimal underlying fibrosis. C1 Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Unit 444,Int Cooperat Study Grp Hepatocellular Ca, Houston, TX 77030 USA. Univ Hong Kong, Med Ctr, Dept Surg, Hong Kong, Hong Kong, Peoples R China. Univ Hong Kong, Med Ctr, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. Queen Mary Hosp, Dept Surg, Hong Kong, Hong Kong, Peoples R China. Kyoto Univ, Grad Sch Med, Dept Surg, Kyoto, Japan. Mayo Clin & Mayo Fdn, Dept Gastroenterol & Gen Surg, Rochester, MN 55905 USA. Hop Beaujon, Dept Surg, Paris, France. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Vauthey, JN (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Unit 444,Int Cooperat Study Grp Hepatocellular Ca, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM jvauthey@mdanderson.org RI Poon, Ronnie/C-4383-2009 NR 49 TC 121 Z9 130 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD APR PY 2005 VL 137 IS 4 BP 403 EP 410 DI 10.1016/j.surg.2004.12.012 PG 8 WC Surgery SC Surgery GA 914PZ UT WOS:000228241300003 PM 15800485 ER PT J AU Longo, GM Buda, SJ Fiotta, N Xiong, WF Griener, T Shapiro, S Baxter, BT AF Longo, GM Buda, SJ Fiotta, N Xiong, WF Griener, T Shapiro, S Baxter, BT TI MMP-12 has a role in abdominal aortic aneurysms in mice SO SURGERY LA English DT Article ID MATRIX METALLOPROTEINASES; PERIARTERIAL APPLICATION; MACROPHAGE ELASTASE; CALCIUM-CHLORIDE; LOCALIZATION; INFLAMMATION; PROTEOLYSIS; GELATINASE; EXPRESSION; CELLS AB Background. Matrix metalloproteinase (MMP)-12 levels are increased in the abdominal aortic aneurysm (AAA), implicating this protease in AAA pathogenesis. The Purpose of this study was to assess the role of MMP-12 in aneurysm formation. Methods. A murine aneurysm model was gene-rated by periaortic application of 0.25 mol/L calcium chloride (CaCl2) for 15 minutes. Aortic diameters were measured and compared before and 10 weeks after aneurysm induction. Aortic diameter changes for wild type (WT) and MMP-12 knockout (MMP12(-/-)) mice were determined. MW-12 production in mouse aorta was analyzed by casein zymography. MMP-2 and MMP-9 expressions were examined by gelatin zymography. Immunohistochemical study was used to measure macrophage infiltration into the aorta. Results. There is an increase of 63 +/- 5% (mean +/- SEM) in aortic diameters of WT mice after CaCl2 inductions, while MMP-12(-/-) mice increased only 26 +/- 14%. Connective tissue staining of aortic sections from WT mice showed disruption and fragmentation of medial elastic fibers, while MMP-12(-/-) mice showed only focal elastic lamellae breakdown. MMP-12 levels in WT mice were significantly increased after CaCl2 treatment, whereas no MMP-12 was detected in MMP-12(-/-) mice. There was no difference in the MMP-2 and MMP-9 productions between WT and MMP-12(-/-) mice. Immunnhistochemical analysis demonstrated that infiltrating macrophages in the aorta of MMP-12(-/-) mice were significantly less than WT controls. Conclusions. MMP-12 deficiency attenuates aneurysm growth, possibly by decreasing macrophage recruitment. C1 Univ Nebraska, Med Ctr, Dept Surg, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Cell Biol & Anat, Omaha, NE USA. Methodist Hosp, Omaha, NE USA. Brigham & Womens Hosp, Pulm & Crit Care Med Sect, Boston, MA 02115 USA. RP Baxter, BT (reprint author), 8111 Dodge St, Omaha, NE 68114 USA. EM btbaxter@unmc.edu FU NHLBI NIH HHS [5R01 HL 62400-02] NR 24 TC 83 Z9 86 U1 0 U2 7 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD APR PY 2005 VL 137 IS 4 BP 457 EP 462 DI 10.1016/j.surg.2004.12.004 PG 6 WC Surgery SC Surgery GA 914PZ UT WOS:000228241300012 PM 15800495 ER PT J AU Ross, EL Abrahm, J AF Ross, EL Abrahm, J TI Preparation of the patient for palliative procedures SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article ID MALIGNANT PLEURAL EFFUSIONS; TERMINALLY-ILL PATIENTS; BOWEL OBSTRUCTION; MANAGEMENT; CANCER; CARE; LIFE; END; CARCINOMA; PAIN AB Palliative surgery is used often to treat intractable symptoms. This approach to symptom management relies on a different premise than the usual goal of an invasive procedure. Surgical procedures traditionally have been used for diagnosis and treatment of disease, whereas palliative surgical procedures have been considered when the goal of curing was no longer possible, but a patient's symptoms suggested that an intervention was needed [1-4]. C1 Brigham & Womens Hosp, Pain Management Ctr, Boston, MA 02467 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA USA. Dana Farber Canc Inst, Palliat Care Programs, Boston, MA 02115 USA. RP Ross, EL (reprint author), Brigham & Womens Pain Management Ctr, 850 Boylston St,Suite 320, Boston, MA 02467 USA. EM elross@partners.org NR 45 TC 2 Z9 2 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 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD APR PY 2005 VL 85 IS 2 BP 191 EP + DI 10.1016/j.suc.2004.12.005 PG 18 WC Surgery SC Surgery GA 926QE UT WOS:000229136900003 PM 15833466 ER PT J AU Barker, FG AF Barker, FG TI Surgical and radiosurgical management of brain metastases SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article ID CELL LUNG-CANCER; GAMMA-KNIFE RADIOSURGERY; NERVOUS-SYSTEM METASTASES; PROPHYLACTIC CRANIAL IRRADIATION; THERAPY-ONCOLOGY-GROUP; STEREOTACTIC-RADIOSURGERY; CEREBRAL METASTASES; RADIATION-THERAPY; RANDOMIZED-TRIAL; PRIMARY TUMOR AB Approximately 10% to 15% of all patients who have cancer will be diagnosed with brain metastases in the Course of their illness, although the incidence in autopsy studies is greater [1,2]. Most patients live less than a year after diagnosis of brain metastases; however, it probably is the specter of physical and mental disability during that time that is feared most by patients and families. Not all morbidity from brain metastases can be avoided or reversed, but aggressive local treatment is now known to benefit many patients who have one or a few brain metastases. These treatments (surgical resection or focused radiation) are the main subject of this article. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, 32 Fruit St,Cox 315, Boston, MA 02114 USA. EM barker@helix.mgh.harvard.edu NR 92 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 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD APR PY 2005 VL 85 IS 2 BP 329 EP + DI 10.1016/j.suc.2004.11.003 PG 18 WC Surgery SC Surgery GA 926QE UT WOS:000229136900012 PM 15833475 ER PT J AU Richards, WO Rattner, DW AF Richards, WO Rattner, DW TI Endoluminal and transluminal surgery - No longer if, but when SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Editorial Material C1 Vanderbilt Univ, Med Ctr, Dept Laparoendoscop Surg, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Ctr Surg Weight Loss, Nashville, TN 37232 USA. Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. RP Richards, WO (reprint author), Vanderbilt Univ, Med Ctr, Dept Laparoendoscop Surg, Nashville, TN 37232 USA. NR 4 TC 18 Z9 20 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD APR PY 2005 VL 19 IS 4 BP 461 EP 463 DI 10.1007/s00464-005-8100-9 PG 3 WC Surgery SC Surgery GA 924YN UT WOS:000229017500001 PM 15791359 ER PT J AU Curry, WT Hoh, BL Amin-Hanjani, S Eskandar, EN AF Curry, WT Hoh, BL Amin-Hanjani, S Eskandar, EN TI Spinal epidural abscess: clinical presentation, management, and outcome SO SURGICAL NEUROLOGY LA English DT Article DE antibiotics; epidural abscess; infection; spine; surgery ID NONOPERATIVE TREATMENT; CARE AB Background: We sought to describe the clinical characteristics of patients with spinal epidural abscess and to relate presentation and treatment to short-term clinical and neurologic outcome. Methods: We retrospectively reviewed the records and radiographic images of all patients admitted to our institution with a diagnosis of spinal epidural abscess between January 1995 and March 2001. Results: Thirty males and 18 females were admitted with spinal epidural abscess. Median age was 61 years (range, 31-84). Twenty-three of 48 patients were febrile at presentation and the mean white blood cell (WBC) count was 15.5 (range, 4.0-38.7). Twenty-seven patients presented with motor deficits, 17 with pain alone, 2 with sepsis, 1 with dysphagia, and 1 incidentally on spinal imaging. Intravenous drug abuse was the most common risk factor (13 patients) followed by the presence of nonspinal infection, including endocarditis (10 patients). Blood cultures were positive in 29 patients. Staphylococcus aureus was the most common organism cultured from abscesses. Collections were located in the cervical spine in 11 patients, cervicothoracic in 4, thoracic in 7, thoracolumbar in 4, and lumbosacral in 22. One patient harbored both cervical and lumbar epidural abscesses. Twenty-three patients initially received nonoperative therapy with antibiotics alone; 25 underwent urgent surgery. Eleven patients initially treated with antibiotics eventually deteriorated and required delayed surgery. Patients receiving antibiotics suffered a significantly greater number of unfavorable outcomes (clinical deterioration or death) than those in the early surgical group (P < 0.005). Conclusions: Patients with spinal epidural abscess may be normothermic and have normal WBC counts. Urgent surgery was more likely to be offered to patients presenting with neurologic deficits than with pain alone. Patients treated without early surgery were significantly more likely to deteriorate and suffer poor outcomes. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Illinois, Dept Neurosurg, Inst Neuropsychiat, Chicago, IL 60612 USA. Harvard Univ, Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Amin-Hanjani, S (reprint author), Univ Illinois, Dept Neurosurg, Inst Neuropsychiat, Chicago, IL 60612 USA. EM hanjani@uic.edu NR 32 TC 93 Z9 97 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD APR PY 2005 VL 63 IS 4 BP 364 EP 371 DI 10.1016/j.surneu.2004.08.081 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 916EY UT WOS:000228369400028 PM 15808726 ER PT J AU Ueno, T Sugino, M Nemoto, H Shoji, H Kakita, A Watanabe, M AF Ueno, T Sugino, M Nemoto, H Shoji, H Kakita, A Watanabe, M TI Effect over time of endotoxin adsorption therapy in sepsis SO THERAPEUTIC APHERESIS AND DIALYSIS LA English DT Article DE adsorption; endotoxin; PMX-DHP; sepsis; severity assessment ID B-IMMOBILIZED FIBER; MULTIPLE ORGAN FAILURE; SEPTIC SHOCK; POLYMYXIN-B; DOUBLE-BLIND; DIRECT HEMOPERFUSION; CRITICAL CARE; PHASE-III; TRIAL; CYTOKINES AB Despite the use of potent antibiotics and intensive supportive care, the mortality among patients with sepsis and Gram-negative bacteremia remains high. In recent years, endotoxin adsorption therapy (PMX-DHP, polymyxin-direct hemoperfusion) has been widely used in Japan to remove endotoxin, a causative agent of sepsis. In septic patients whose clinical condition may change at any moment, the decision of when to perform blood purification in addition to conventional intensive care is a critical factor in the therapeutic strategy and prognosis. In the present study, we investigated the effect over time of PMX-DHP in sepsis. The subjects were 16 patients with systemic inflammatory response syndrome (SIRS) who required surgical treatment including a surgical operation and drainage. The following six parameters were compared between the first and second PMX-DHP: mean blood pressure and time-restricted urine at four time points - at baseline and at 6, 24 and 72 h after PMX-DHP; and white blood cell count, platelet count, base excess and Septic Severity Score (SSS) at 24 and 72 h after PMX-DHP. Mean blood pressure improved over time up to 24 h after both the first and second PMX-DHP. Time-restricted urine volume improved only at 6 h after the first PMX-DHP. White blood cell count improved over time up to 24 h after both the first and second PMX-DHR The SSS improved at all time points studied except for 3 days after the second PMX-DHP. We conclude that PMX-DHP is expected to have important implications in terms of (i) correction of clinical conditions (by severity assessment); (ii) improvement of hemodynamics; (iii) possible anti-inflammatory effect; and (iv) possible improvement of oxygen metabolism in tissues. C1 Kitasato Univ, Sch Med, Dept Surg, Kanagawa, Japan. Asoka Hosp, Dept Surg, Tokyo, Japan. Toray Med Co Ltd, Dept Blood Purificat Med Devices, Tokyo, Japan. RP Ueno, T (reprint author), Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, Suite 478,15 Parkman St, Boston, MA 02114 USA. EM tueno@partners.org NR 28 TC 12 Z9 15 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1744-9979 J9 THER APHER DIAL JI Ther. Apher. Dial. PD APR PY 2005 VL 9 IS 2 BP 128 EP 136 DI 10.1111/j.1774-9987.2005.00230.x PG 9 WC Hematology; Urology & Nephrology SC Hematology; Urology & Nephrology GA 931KY UT WOS:000229485400002 PM 15828924 ER PT J AU Antkiewicz, DS Burns, CG Carney, SA Peterson, RE Heideman, W AF Antkiewicz, DS Burns, CG Carney, SA Peterson, RE Heideman, W TI Heart malformation is an early response to TCDD in embryonic zebrafish SO TOXICOLOGICAL SCIENCES LA English DT Article DE 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD toxicity; zebrafish; heart; development ID ARYL-HYDROCARBON RECEPTOR; LIFE STAGE TOXICITY; LAKE TROUT; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TOXICITY; DEVELOPMENTAL TOXICITY; AROMATIC-HYDROCARBONS; DANIO-RERIO; EXPOSURE; EXPRESSION; GROWTH AB The zebrafish (Danio rerio) has become an attractive vertebrate model for studying developmental processes, and is emerging as a model system for studying the mechanisms by which toxic compounds perturb normal development. When exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) shortly after fertilization, zebrafish embryos exhibit pericardial edema and reduced blood flow by 72 h post fertilization (hpf). To better understand the progression of dioxin toxicity in zebrafish, we have examined the effects of TCDD on heart development. At 72 hpf, TCDD-treated embryos exhibited altered looping, with the atria positioned distinctly posterior to the ventricles, contrary to the looping of control hearts, where the two chambers lied side by side. Moreover, the ventricles in dioxin-exposed hearts became more compact, and the atria elongated in comparison to controls. These defects are not secondary to pericardial edema because they were observed when edema formation was suppressed with osmotic support. In addition to morphological changes, TCDD produced functional deficits in the developing hearts, including blood regurgitation and a striking ventricular standstill that became prevalent by 120 hpf. We also assessed the effect of TCDD on the heart size using stereological measurements, which demonstrated significant reduction in heart tissue volume at 72 hpf. Perhaps our most significant finding was a decrease in the total number of cardiomyocytes in TCDD-exposed embryos by 48 hpf, one day prior to observable effects on peripheral blood flow. We conclude that the developing heart is an important target for TCDD in zebrafish. C1 Univ Wisconsin, Sch Pharm, Mol & Environm Toxicol Ctr, Madison, WI 53705 USA. Massachusetts Gen Hosp, Dev Biol Lab, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA. RP Heideman, W (reprint author), Univ Wisconsin, Sch Pharm, Mol & Environm Toxicol Ctr, 777 Highland Ave, Madison, WI 53705 USA. EM wheidema@facstaff.wisc.edu RI Perez , Claudio Alejandro/F-8310-2010; Antkiewicz, Dagmara/D-4998-2015 OI Perez , Claudio Alejandro/0000-0001-9688-184X; Antkiewicz, Dagmara/0000-0003-1282-5483 FU NHLBI NIH HHS [5T32HL007208-27]; NIA NIH HHS [K01 AG023562]; NIEHS NIH HHS [T32 ES07015] NR 42 TC 130 Z9 141 U1 2 U2 32 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD APR PY 2005 VL 84 IS 2 BP 368 EP 377 DI 10.1093/toxsci/kfi073 PG 10 WC Toxicology SC Toxicology GA 911AQ UT WOS:000227973900020 PM 15635151 ER PT J AU Wagner, M Garzotto, M Lemmon, D Eilers, KM Beer, TM AF Wagner, M Garzotto, M Lemmon, D Eilers, KM Beer, TM TI Prostate-specific antigen decline after gonadotropin-releasing hormone antagonist withdrawal in androgen-independent prostate cancer SO UROLOGY LA English DT Article ID ANTIANDROGEN WITHDRAWAL; MEGESTROL-ACETATE; FLUTAMIDE; DISCONTINUATION; NILUTAMIDE; EXPRESSION; RECEPTORS; CASODEX; CELLS AB A 66-year-old man with androgen-independent prostate cancer was treated with abarelix, a gonadotropin-releasing hormone antagonist, for 20 weeks in an experimental protocol. He did not respond to therapy, but his serum prostate-specific antigen level dropped from 15.8 ng/mL to a confirmed 0.8 ng/mL after abarelix was stopped. His prostate-specific antigen level did not return to greater than 15.8 ng/mL for 14 months. This is the first report of a withdrawal response after therapy with a gonadotropin-releasing hormone antagonist, a new class of agents for prostate cancer. Additional observations are needed to determine whether this is an isolated case or a harbinger of a more common phenomenon. (c) 2005 Elsevier Inc. C1 Oregon Hlth Sci Univ, Dept Med, Div Urol, Portland, OR USA. Oregon Hlth Sci Univ, Div Hematol, Portland, OR USA. Oregon Hlth Sci Univ, Div Med Oncol, Portland, OR USA. Portland Vet Affairs Med Ctr, Div Urol, Portland, OR USA. RP Beer, TM (reprint author), Oregon Hlth Sci Univ, Dept Med, Div Urol, Mail Code CR145,3181 SW Sam Jackson Pk Rd, Portland, OR USA. EM beert@ohsu.edu NR 16 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD APR PY 2005 VL 65 IS 4 BP E37 EP E39 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 918OQ UT WOS:000228557900047 ER PT J AU Heller, HM Telford, SR Branda, JA Harris, NL Goodson, JD Ryan, ET Bloom, D AF Heller, HM Telford, SR Branda, JA Harris, NL Goodson, JD Ryan, ET Bloom, D TI A Man with weakness and pain in the legs - Human granulocytic ehrlichiosis (A-phagocytophilum infection) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ANAPLASMATACEAE; RHABDOMYOLYSIS; AGENT; EQUI C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Tufts Univ, Sch Vet Med, Div Infect Dis, North Grafton, MA 01536 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Lab Publ Hlth Entomol, Boston, MA 02115 USA. RP Heller, HM (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. FU NIAID NIH HHS [AI 39002] NR 16 TC 4 Z9 5 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 31 PY 2005 VL 352 IS 13 BP 1358 EP 1364 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 911JL UT WOS:000227998300014 PM 15800232 ER PT J AU Koroshetz, WJ AF Koroshetz, WJ TI Warfarin, aspirin, and intracranial vascular disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ATHEROSCLEROSIS; MANAGEMENT C1 Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP Koroshetz, WJ (reprint author), Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. NR 9 TC 12 Z9 13 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 31 PY 2005 VL 352 IS 13 BP 1368 EP 1370 DI 10.1056/NEJMe058022 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 911JL UT WOS:000227998300016 PM 15800233 ER PT J AU Brown, RH AF Brown, RH TI Amyotrophic lateral sclerosis - A new role for old drugs SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brown, RH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 7 Z9 8 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 31 PY 2005 VL 352 IS 13 BP 1376 EP 1378 DI 10.1056/NEJMcibr050274 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 911JL UT WOS:000227998300019 PM 15800236 ER PT J AU Walsh, SR Parada, NA AF Walsh, SR Parada, NA TI Uremic frost SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. RP Walsh, SR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 4 Z9 5 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 31 PY 2005 VL 352 IS 13 BP E13 EP E13 DI 10.1056/NEJMicm030792 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 911JL UT WOS:000227998300013 PM 15800220 ER PT J AU Mashour, GA Drissel, SN Frahm, S Farassati, F Martuza, RL Mautner, VF Rohrborn, AK Kurtz, A AF Mashour, GA Drissel, SN Frahm, S Farassati, F Martuza, RL Mautner, VF Rohrborn, AK Kurtz, A TI Differential modulation of malignant peripheral nerve sheath tumor growth by omega-3 and omega-6 fatty acids SO ONCOGENE LA English DT Article DE neurofibromatosis type 1; malignant peripheral nerve sheath tumor; essential fatty acids; fatty-acid binding protein; tumor growth regulation ID LIPID-BINDING PROTEIN; NEUROFIBROMATOSIS TYPE-1; DOCOSAHEXAENOIC ACID; RHESUS-MONKEYS; SCHWANN-CELLS; CANCER CELLS; BRAIN; TUMORIGENESIS; EXPRESSION; OMEGA-3-FATTY-ACIDS AB Neurofibromatosis type 1 (NF1) is a common genetic disorder of the nervous system resulting in neurofibromas and malignant peripheral nerve sheath tumors (MPNST). In this study, we report the modulation of murine and human MPNST cell growth by the fatty acids docosahexaenoic acid (DHA) and arachidonic acid (AA). DHA demonstrated a tendency to stimulate cell growth at low doses and induce apoptosis at high doses, paralleled by the activation of ERK and caspase-3. Furthermore, high-dose DHA reversed the stimulation of MPNST cell growth by a number of growth factors suggested to have a pathogenic effect in NF1 and inhibited MPNST growth in vivo. AA was found to have a reciprocal activity in vitro, stimulating MPNST cell growth at comparable concentrations and reducing DHA activation of ERK. These findings introduce fatty acids as a possible regulator of MPNST development in NF1 patients. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurosurg Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA USA. Univ Bonn, Inst Neuropathol, D-5300 Bonn, Germany. Univ Hamburg, Dept Neurosurg, Hamburg, Germany. Klinikum Nord, Dept Neurol, Hamburg, Germany. RP Kurtz, A (reprint author), RKI, Stem Cells, Seestr 10, D-13353 Berlin, Germany. EM kurtza@rki.de FU NINDS NIH HHS [NS37895] NR 36 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 31 PY 2005 VL 24 IS 14 BP 2367 EP 2374 DI 10.1038/sj.onc.1208425 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 909RC UT WOS:000227877400009 PM 15735744 ER PT J AU Guertin, AD Zhang, DP Mak, KS Alberta, JA Kim, HA AF Guertin, AD Zhang, DP Mak, KS Alberta, JA Kim, HA TI Microanatomy of axon/glial signaling during Wallerian degeneration SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Wallerian degeneration; Schwann cell; neuregulin; erbB2; PKI166; demyelination ID PERIPHERAL NERVOUS-SYSTEM; SCHWANN-CELL MYELINATION; NEURON-DERIVED FACTOR; DORSAL-ROOT GANGLIA; GROWTH-FACTOR; SCIATIC-NERVE; SYMPATHETIC NEURONS; ERBB3 RECEPTORS; LOCAL-CONTROL; CANCER CELLS AB How do myelinated axons signal to the nuclei of cells that enwrap them? The cell bodies of oligodendrocytes and Schwann cells are segregated from axons by multiple layers of bimolecular lipid leaflet and myelin proteins. Conventional signal transduction strategies would seem inadequate to the challenge without special adaptations. Wallerian degeneration provides a model to study axon-to-Schwann cell signaling in the context of nerve injury. We show a hitherto undetected rapid, but transient, activation of the receptor tyrosine kinase erbB2 in myelinating Schwann cells after sciatic nerve axotomy. Deconvolving microscopy using phosphorylation state-specific antibodies shows that erbB2 activation emanates from within the microvilli of Schwann cells, in direct contact with the axons they enwrap. To define the functional role of this transient activation, we used a small molecule antagonist of erbB2 activation (PKI166). The response of myelinating Schwann cells to axotomy is inhibited by PKI166 in vivo. Using neuron/Schwann cell cocultures prepared in compartmentalized cell culture chambers, we show that even transient activation of erbB2 is sufficient to initiate Schwann cell demyelination and that the initiating functions of erbB2 are localized to Schwann cells. C1 Rutgers State Univ, Dept Biol Sci, Newark, NJ 07102 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Kim, HA (reprint author), Rutgers State Univ, Dept Biol Sci, 101 Warren St, Newark, NJ 07102 USA. EM haekim@andromeda.rutgers.edu FU NINDS NIH HHS [R01-NS45939-01] NR 58 TC 88 Z9 91 U1 1 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 30 PY 2005 VL 25 IS 13 BP 3478 EP 3487 DI 10.1523/JNEUROSCI.3766-04.2005 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 911WU UT WOS:000228038200025 PM 15800203 ER PT J AU Mitchell, DA Erwin, PA Michel, T Marletta, MA AF Mitchell, DA Erwin, PA Michel, T Marletta, MA TI S-nitrosation and regulation of inducible nitric oxide synthase SO BIOCHEMISTRY LA English DT Article ID AMINO-ACID-RESIDUES; ELECTRON-TRANSFER; L-ARGININE; ENDOTHELIAL-CELLS; CRYSTAL-STRUCTURE; ENZYME-ACTIVITY; HEME DOMAIN; ZINC; DIMER; TETRAHYDROBIOPTERIN AB The inducible isoform of nitric oxide synthase (iNOS) and three zinc tetrathiolate mutants (C104A, C109A, and C104A/C109A) were expressed in Escherichia coli and purified. The mutants were found by ICP-AES and the zinc-specific PAR colorimetric assay to be zinc free, whereas the wild-type iNOS zinc content was 0.38 +/- 0.01 mol of Zn/mol of iNOS dimer. The cysteine mutants (C104A and C109A) had an activity within error of wild-type iNOS (2.24 +/- 0.12 mu mol of NO min(-1) mg(-1)), but the double cysteine mutant had a modestly decreased activity (1.75 +/- 0.14 mu mol of NO min(-1) mg(-1)). To determine if NO could stimulate release of zinc and dimer dissociation, wild-type protein was allowed to react with an NO donor, DEA/NO, followed by buffer exchange. ICP-AES of samples treated with 10 mu M DEA/NO showed a decrease in zinc content (0.23 +/- 0.01 to 0.09 +/- 0.01 mol of Zn/mol of iNOS dimer) with no loss of heme iron. Gel filtration of wild-type iNOS treated similarly resulted in similar to 20% more monomeric iNOS compared to a DEA-treated sample. Only wild-type iNOS had decreased activity (42 +/- 2%) after reaction with 50 mu M DEA/NO compared to a control sample. Using the blotin switch method under the sarne conditions, only wild-type iNOS had increased levels of S-biotinylation. S-Biotinylation was mapped to C104 and C109 on wild-type iNOS using LysC digestion and MALDIZ TOF/TOF MS. Immunoprecipitation of iNOS from the mouse rnacrophage cell line, RAW-264.7, and the biotin switch method were used to confirm endo-enOLIS S-nitrosation of iNOS, The data show that S-nitrosation of the zinc tetrathiolate cysteine results in zinc release frorn the dimer interface and formation of inactive monorners, suggesting that this mode of inhibition might occur in vivo. C1 Univ Calif Berkeley, Dept Chem, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. Univ Calif Berkeley, Div Phys Biosci, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. Harvard Univ, Sch Med, Div Cardiovasc, Brigham & Womens Hosp, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA 02132 USA. RP Marletta, MA (reprint author), Univ Calif Berkeley, Dept Chem, Lawrence Berkeley Lab, 211 Lewis Hall, Berkeley, CA 94720 USA. EM marletta@berkeley.edu RI Mitchell, Douglas/C-4400-2011; Mitchell, Doug/B-6349-2012 OI Mitchell, Doug/0000-0002-9564-0953 FU NHLBI NIH HHS [HL 46457]; NIGMS NIH HHS [GM 36259] NR 63 TC 48 Z9 50 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 29 PY 2005 VL 44 IS 12 BP 4636 EP 4647 DI 10.1021/bi0474463 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 909EH UT WOS:000227842500004 PM 15779890 ER PT J AU Lee-Huang, S Maiorov, V Huang, PL Ng, A Lee, HC Chang, YT Kallenbach, N Huang, PL Chen, HC AF Lee-Huang, S Maiorov, V Huang, PL Ng, A Lee, HC Chang, YT Kallenbach, N Huang, PL Chen, HC TI Structural and functional modeling of human lysozyme reveals a unique nonapeptide, HL9, with anti-HIV activity SO BIOCHEMISTRY LA English DT Article ID SITE CLEFT; PEPTIDES; PROTEINS; CELLS; INFECTION; DEFENSE; ASSAY; GENE AB We previously reported that lysozyme accounts for anti-HIV activity associated with the beta-core fraction of human chorionic gonadotropin [Lee-Huang, S., Huang, P. L., Sun, Y., Kuna, H. F., Blithe, D. L. W Chen, H. C. (1999) Proc Natl Acad Sci U S A 96, 2678-81]. To define the structural and sequence requirements for anti-HIV activity, we carried out peptide fragmentation and activity mapping of human lysozyme. We identified two peptides that consist of 18 and 9 amino acids of human lysozyme (HL18 and HL9), corresponding to residues 98-115 and 107-115. HLI 8 and HL9 are potent inhibitors of HIV-1 infection and replication with EC50S of 50 to 55 nM, comparable to intact lysozyme. Scrambling the sequence or substitution of key arginine or tryptophan residues results in loss of antiviral activity. HL9, with the sequence RAWVAWRNR, is the smallest peptide we identified with full anti-HIV activity. It forms a pocket with its basic residues on the surface of the molecule. HL9 exists as an alpha-helix in native human lysozyme, in a region of the protein distinct from the muramidase catalytic site. Monte Carlo peptide folding energy minimizing simulation modeling and CD studies indicate that helical propensity does not correlate with antiviral activity. HL9 blocks HIV-1 viral entrance and replication, and modulates gene expression of HIV-infected cells, affecting pathways involved in survival, stres;s, TGF beta, p53, NF kappa B, protein kinase C and hedgehog signaling. C1 NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. Amer Biosci, Boston, MA 02114 USA. NYU, Dept Chem, New York, NY 10003 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Lee-Huang, S (reprint author), NYU, Sch Med, Dept Biochem, 550 1St Ave, New York, NY 10016 USA. RI Chang, Young-Tae/B-2780-2010 OI Chang, Young-Tae/0000-0002-1927-3688 FU NCCIH NIH HHS [R01 AT001383, R01 AT001383-01A2, R01 AT001383-02, R01 AT001383-03, R01-AT01383]; NIAID NIH HHS [R01 AI031343-03, R01 AI031343, R01 AI031343-03S1, R01 AI031343-06] NR 28 TC 50 Z9 52 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 29 PY 2005 VL 44 IS 12 BP 4648 EP 4655 DI 10.1021/bi0477081 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 909EH UT WOS:000227842500005 PM 15779891 ER PT J AU Jang, IK Tearney, GJ MacNeill, B Takano, M Moselewski, F Iftima, N Shishkov, M Houser, S Aretz, HT Halpern, EF Bouma, BE AF Jang, IK Tearney, GJ MacNeill, B Takano, M Moselewski, F Iftima, N Shishkov, M Houser, S Aretz, HT Halpern, EF Bouma, BE TI In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography SO CIRCULATION LA English DT Article DE arteriosclerosis; coronary disease; imaging; plaque ID INTRAVASCULAR ULTRASOUND; ISCHEMIC DEATH; STABLE ANGINA; THROMBOSIS; RUPTURE; CLASSIFICATION; VISUALIZATION; ANGIOSCOPY; LESIONS AB Background - The current understanding of the pathophysiology of coronary artery disease is based largely on postmortem studies. Optical coherence tomography (OCT) is a high-resolution ( approximate to 10 mu m), catheter-based imaging modality capable of investigating detailed coronary plaque morphology in vivo. Methods and Results Patients undergoing cardiac catheterization were enrolled and categorized according to their clinical presentation: recent acute myocardial infarction ( AMI), acute coronary syndromes (ACS) constituting non - ST-segment elevation AMI and unstable angina, or stable angina pectoris ( SAP). OCT imaging was performed with a 3.2F catheter. Two observers independently analyzed the images using the previously validated criteria for plaque characterization. Of 69 patients enrolled, 57 patients ( 20 with AMI, 20 with ACS, and 17 with SAP) had analyzable images. In the AMI, ACS, and SAP groups, lipid-rich plaque ( defined by lipid occupying >= 2 quadrants of the cross-sectional area) was observed in 90%, 75%, and 59%, respectively ( P = 0.09). The median value of the minimum thickness of the fibrous cap was 47.0, 53.8, and 102.6 mu m, respectively ( P = 0.034). The frequency of thin-cap fibroatheroma ( defined by lipid-rich plaque with cap thickness <= 65 mu m) was 72% in the AMI group, 50% in the ACS group, and 20% in the SAP group ( P = 0.012). No procedure-related complications occurred. Conclusions - OCT is a safe and effective modality for characterizing coronary atherosclerotic plaques in vivo. Thin-cap fibroatheroma was more frequently observed in patients with AMI or ACS than SAP. This is the first study to compare detailed in vivo plaque morphology in patients with different clinical presentations. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Gray Bigelow 800,55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org FU NHLBI NIH HHS [R01 HL070039-02, R01 HL076398, R01 HL076398-02, R01-HL70039, R01 HL070039] NR 25 TC 456 Z9 483 U1 1 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 29 PY 2005 VL 111 IS 12 BP 1551 EP 1555 DI 10.1161/01.CIR.0000159354.43778.69 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 911EH UT WOS:000227984800016 PM 15781733 ER PT J AU Aksan, A Morris, SC Toner, M AF Aksan, A Morris, SC Toner, M TI Analysis of desiccation and vitrification characteristics of carbohydrate films by shear-wave resonators SO LANGMUIR LA English DT Article ID QUARTZ-CRYSTAL MICROBALANCE; TREHALOSE; STABILIZATION; LIQUID; ANHYDROBIOSIS; PRESERVATION; FREQUENCY; MEMBRANES; RESPONSES; EXPOSURE AB Desiccated state preservation of mammalian cells and tissues in the presence of carbohydrates has started to show promise in the last two decades. Certain carbohydrates play a major role in preservation by reducing molecular mobility in the desiccated state. In this communication, the feasibility of utilizing shear-wave resonators to collect real-time molecular mobility information during desiccation and vitrification of carbohydrate based thin films was demonstrated. Simultaneous quartz crystal microbalance experimentation and optical imaging were utilized to determine the conditions for thin film formation and the vitrification kinetics of certain carbohydrate solutions of biological importance. Using the technique presented here, it was possible to gain insight into the vitrification characteristics of carbohydrate solutions establishing the basics for future research with quantitative analysis of film properties and experimentation with live mammalian cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. Univ Notre Dame, Dept Aerosp & Mech Engn, Notre Dame, IN 46556 USA. RP Aksan, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. RI Aksan, Alptekin/A-7187-2008; Morris, Scott/A-7218-2013; Aksan, Alptekin/C-1579-2014 OI Aksan, Alptekin/0000-0001-9891-1715 FU NIDDK NIH HHS [DK46270] NR 36 TC 14 Z9 14 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD MAR 29 PY 2005 VL 21 IS 7 BP 2847 EP 2854 DI 10.1021/la047760y PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 911YI UT WOS:000228042400035 PM 15779957 ER PT J AU Cobb, JP Mindrinos, MN Miller-Graziano, C Calvano, SE Baker, HV Xiao, WZ Laudanski, K Brownstein, BH Elson, CM Hayden, DL Herndon, DN Lowry, SF Maier, RV Schoenfeld, DA Moldawer, LL Davis, RW Tompkins, RG AF Cobb, JP Mindrinos, MN Miller-Graziano, C Calvano, SE Baker, HV Xiao, WZ Laudanski, K Brownstein, BH Elson, CM Hayden, DL Herndon, DN Lowry, SF Maier, RV Schoenfeld, DA Moldawer, LL Davis, RW Tompkins, RG CA Inflammation Host Response Injury TI Application of genome-wide expression analysis to human health and disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE clinical studies; gene expression; inflammation; microarray; trauma ID CANCER; BLOOD AB The application of genome-wide expression analysis to a large-scale, multicentered program in critically ill patients poses a number of theoretical and technical challenges. We describe here an analytical and organizational approach to a systematic evaluation of the variance associated with genome-wide expression analysis specifically tailored to study human disease. We analyzed sources of variance in genome-wide expression analyses performed with commercial oligonucleotide arrays. In addition, variance in gene expression in human blood leukocytes caused by repeated sampling in the same subject, among different healthy subjects, among different leukocyte subpopulations, and the effect of traumatic injury, were also explored. We report that analytical variance caused by sample processing was acceptably small. Blood leukocyte gene expression in the same individual over a 24-h period was remarkably constant. In contrast, genome-wide expression varied significantly among different subjects and leukocyte subpopulations. Expectedly, traumatic injury induced dramatic changes in apparent gene expression that were greater in magnitude than the analytical noise and interindividual variance. We demonstrate that the development of a nation-wide program for gene expression analysis with careful attention to analytical details can reduce the variance in the clinical setting to a level where patterns of gene expression are informative among different healthy human subjects, and can be studied with confidence in human disease. C1 Massachusetts Gen Hosp, Dept Surg & Biostat, Boston, MA 02115 USA. Washington Univ, Dept Surg, St Louis, MO 63130 USA. Stanford Univ, Med Ctr, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. Univ Rochester, Dept Surg, Rochester, NY 14627 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Surg, New Brunswick, NJ 08903 USA. Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32611 USA. Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32611 USA. Harvard Univ, Sch Med, Shriners Burn Hosp, Boston, MA 02115 USA. Univ Texas, Med Branch, Dept Surg, Galveston, TX 77555 USA. Univ Texas, Med Branch, Shriners Burn Hosp, Galveston, TX 77555 USA. Univ Washington, Sch Med, Dept Surg, Harborview Gen Hosp, Seattle, WA 98104 USA. RP Tompkins, RG (reprint author), Massachusetts Gen Hosp, Dept Surg & Biostat, Boston, MA 02115 USA. EM rtompkins@partners.org OI Laudanski, Krzysztof /0000-0002-7373-0851; xiao, wenzhong/0000-0003-4944-6380; Remick, Daniel/0000-0002-2615-3713; Baker, Henry/0000-0002-8273-5320 FU NIGMS NIH HHS [U54 GM-62119-03, U54 GM062119] NR 16 TC 171 Z9 173 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 29 PY 2005 VL 102 IS 13 BP 4801 EP 4806 DI 10.1073/pnas.0409768102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 912JM UT WOS:000228074000027 PM 15781863 ER PT J AU Morra, M Barrington, RA Abadia-Molina, AC Okamoto, S Julien, A Gullo, C Kalsy, A Edwards, MJ Chen, G Spolski, R Leonard, WJ Huber, BT Borrow, P Biron, CA Satoskar, AR Carroll, MC Terhorst, C AF Morra, M Barrington, RA Abadia-Molina, AC Okamoto, S Julien, A Gullo, C Kalsy, A Edwards, MJ Chen, G Spolski, R Leonard, WJ Huber, BT Borrow, P Biron, CA Satoskar, AR Carroll, MC Terhorst, C TI Defective B cell responses in the absence of SH2D1A SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Epstein-Barr virus; germinal center; immunoglobulin; SLAM/CD150 ID LINKED LYMPHOPROLIFERATIVE-DISEASE; COMMON VARIABLE IMMUNODEFICIENCY; INOSITOL PHOSPHATASE; IMMUNE RECEPTORS; MICE DEFICIENT; ENCODING GENE; SLAM FAMILY; SAP; EXPRESSION; MEMORY AB More than half of patients with X-linked lympho-proliferative disease, which is caused by a defect in the intracellular adapter protein SH2D1A, suffer from an extreme susceptibility to Epstein-Barr virus. One-third of these patients, however, develop dysgammaglobulenemia without an episode of severe mononucleosis. Here we show that in SH2D1A(-/-) mice, both primary and secondary responses of all Ig subclasses are severely impaired in response to specific antigens. Because germinal centers were absent in SH2D1A(-/-) mice upon primary immunization, and because SH2D1A was detectable in wt germinal center B cells, we examined whether SH2D1A(-/-) B cell functions were impaired. Using the adoptive cotransfer of B lymphocytes from hapten-primed SH2D1A(-/-) mice with CD4(+) T cells from primed wt mice into irradiated wt mice provided evidence that signal transduction events controlled by SH2D1A are essential for B cell activities resulting in antigen specific IgG production. Defects in naive SH2D1A(-/-) B cells became evident upon cotransfer with non-primed wt CD4(+) cells into Rag2(-/-) recipients. Thus, both defective T and B cells exist in the absence of SH2D1A, which may explain the progressive dysgammaglobulinemia in a subset of X-linked lympho-proliferative disease patients without involvement of Epstein-Barr virus. C1 Harvard Univ, Sch Med, Div Immunol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, CBR, Inst Biomed Res, Boston, MA 02215 USA. Harvard Univ, Dept Pathol, Boston, MA 02215 USA. Edward Jenner Inst Vaccine Res, Newbury RG20 7NN, Berks, England. Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA. Ohio State Univ, Dept Microbiol, Columbus, OH 43210 USA. RP Morra, M (reprint author), Harvard Univ, Sch Med, Div Immunol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM mmorra@bidmc.harvard.edu; terhorst@bidmc.harvard.edu FU NIAID NIH HHS [P01 AI035714, AI-35714] NR 40 TC 51 Z9 56 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 29 PY 2005 VL 102 IS 13 BP 4819 EP 4823 DI 10.1073/pnas.0408681102 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 912JM UT WOS:000228074000030 PM 15774582 ER PT J AU Dryja, TP McGee, TL Berson, EL Fishman, GA Sandberg, MA Alexander, KR Derlacki, DJ Rajagopalan, AS AF Dryja, TP McGee, TL Berson, EL Fishman, GA Sandberg, MA Alexander, KR Derlacki, DJ Rajagopalan, AS TI Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bipolar cell; glutamate receptor; retina ID METABOTROPIC GLUTAMATE-RECEPTOR; FAMILIAL HYPOCALCIURIC HYPERCALCEMIA; CELL INPUT MECHANISMS; RETINITIS-PIGMENTOSA; MAMMALIAN RETINA; GANGLION-CELLS; A-WAVE; PHOTOPIC ELECTRORETINOGRAM; FUNCTIONAL ARCHITECTURE; CONTRAST SENSITIVITY AB We report three unrelated patients with mutations in the GRM6 gene that normally encodes the glutamate receptor mGluR6. This neurotransmitter receptor has been shown previously to be present only in the synapses of the ON bipolar cell dendrites, and it mediates synaptic transmission from rod and cone photoreceptors to this type of second-order neuron. Despite the synaptic defect, best visual acuities were normal or only moderately reduced (20/15 to 20/40). The patients were night blind from an early age, and when maximally dark-adapted, they could perceive lights only with an intensity equal to or slightly dimmer than that normally detected by the cone system (i.e., 2-3 log units above normal). Electroretinograms (ERGs) in response to single brief flashes of light had clearly detectable a-waves, which are derived from photoreceptors, and greatly reduced b-waves, which are derived from the second-order inner retinal neurons. ERGs in response to sawtooth flickering light indicated a markedly reduced ON response and a nearly normal OFF response. There was no subjective delay in the perception of suddenly appearing white vs. black objects on a gray background. These patients exemplify a previously unrecognized, autosomal recessive form of congenital night blindness associated with a negative ERG waveform. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. RP Dryja, TP (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. EM thaddeus_dryja@meei.harvard.edu FU NEI NIH HHS [EY08301, EY08683, EY14104, P30 EY014104, R01 EY000169, R01 EY008301, R01 EY008683, R37 EY000169] NR 57 TC 129 Z9 133 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 29 PY 2005 VL 102 IS 13 BP 4884 EP 4889 DI 10.1073/pnas.0501233102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 912JM UT WOS:000228074000041 PM 15781871 ER PT J AU Pearlman, RA Starks, H Cain, KC Cole, WG AF Pearlman, RA Starks, H Cain, KC Cole, WG TI Improvements in advance care planning in the veterans affairs system - Results of a multifaceted intervention SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID LIFE-SUSTAINING TREATMENT; RANDOMIZED CONTROLLED TRIAL; FAMILY DECISION-MAKING; HOSPITALIZED-PATIENTS; PATIENT PREFERENCES; HEALTH-CARE; DIRECTIVES; END; COMPLETION; PHYSICIANS AB Background: Advance care planning (ACP) aims to 0 Guide health care in the event of decisional incapacity. Interventions to promote ACP have had limited effectiveness. We conducted an educational and motivational intervention in Department of Veterans Affairs outpatient clinics to increase ACP use and proxy and health care provider understanding of patients' preferences and values. Methods: We recruited 23 providers and up to 14 of each of their patients; the patients were randomized to the control or intervention group. Eligibility criteria included a preexisting relationship with the provider, age 55 years or older, chronic health condition(s), and no recorded advance directive. The intervention group (n = 119) received an ACP workbook, motivational counseling by social workers, and cues to providers to discuss ACP. The control group (n = 129) received an advance directive booklet. Results: The intervention patients reported more ACP discussions with their providers (64% vs 38%; P <.001). Living wills were filed in the medical record twice as often in the intervention group (48% vs 23%; P <.001). Provider-patient dyads in the intervention group had higher agreement scores than the control group for treatment preferences, values, and personal beliefs (58% vs 48%, 57% vs 46%, and 61% vs 47%, respectively; P <.01. for all comparisons). The agreement scores for the proxy-patient dyads did not differ between groups for treatment preferences and values, but were higher in the intervention than the control group for personal beliefs (67% vs 56%). Conclusion: This intervention demonstrates mixed results and highlights the ongoing challenges of helping health care providers and potential proxy decision makers represent patient preferences and values. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Med Hist & Eth, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Lewis & Clark Coll, Dept Psychol, Portland, OR 97219 USA. RP Pearlman, RA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, S-182-IGP,1660 S Columbian Way, Seattle, WA 98108 USA. EM robert.pearlman@med.va.gov NR 38 TC 53 Z9 54 U1 2 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 28 PY 2005 VL 165 IS 6 BP 667 EP 674 DI 10.1001/archinte.165.6.667 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 909WW UT WOS:000227892400011 PM 15795344 ER PT J AU Hagopian, K Ramsey, JJ Weindruch, R AF Hagopian, K Ramsey, JJ Weindruch, R TI Serine utilization in mouse liver: Influence of caloric restriction and aging SO FEBS LETTERS LA English DT Article DE caloric restriction; serine dehydratase; serine : pyruvate transaminase; glycerate dehydrogenase; glycerate kinase ID AMINO-ACID METABOLISM; RAT-LIVER; PYRUVATE AMINOTRANSFERASE; ENZYME-ACTIVITIES; GLYCERATE KINASE; NEONATAL RAT; GLUCONEOGENESIS; DIETARY; MITOCHONDRIAL; DEHYDRATASE AB The influence of caloric restriction (CR) on the activities of hepatic serine metabolizing enzymes in young (3 months) and old (30 months) mice was studied. Serine dehydratase (SDH) activity increased markedly with age in both diet groups and in old mice was higher in the CR group. No effects of CR were observed in the young. Serine:pyruvate transaminase (SPT) and glycerate kinase activities were unaffected by age and diet. However, glycerate dehydrogenase activity was decreased in old CR mice but not in young CR. The results of this study show that long-term CR influenced serine utilization only in the pathway catalyzed by SDH. This suggests that in mouse liver this pathway is critical for serine utilization in gluconeogenesis, while the SPT pathway plays a minor role. The increase in SDH activity with long-term CR is consistent with sustained increase in gluconeogenesis. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, Davis, CA 95616 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. RP Hagopian, K (reprint author), Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, 1 Shields Ave, Davis, CA 95616 USA. EM khagopian@ucdavis.edu FU NIA NIH HHS [P01 AG11915, R01 AG17902] NR 36 TC 10 Z9 10 U1 1 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 MAR 28 PY 2005 VL 579 IS 9 BP 2009 EP 2013 DI 10.1016/j.febslet.2005.02.062 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 913LJ UT WOS:000228152800021 PM 15792811 ER PT J AU Adair, BD Xiong, JP Maddock, C Goodman, SL Arnaout, MA Yeager, M AF Adair, BD Xiong, JP Maddock, C Goodman, SL Arnaout, MA Yeager, M TI Three-dimensional EM structure of the ectodomain of integrin alpha V beta 3 in a complex with fibronectin SO JOURNAL OF CELL BIOLOGY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; CRYSTAL-STRUCTURE; ELECTRON-MICROSCOPY; CELL-ADHESION; EXTRACELLULAR SEGMENT; DIVALENT-CATIONS; ACTIVATION; RECEPTOR; AFFINITY; BINDING AB Integrins are alpha beta heterodimeric cell surface receptors that mediate transmembrane signaling by binding extracellular and cytoplasmic ligands. The ectodomain of integrin alpha V beta 3 crystallizes in a bent, genuflexed conformation considered to be inactive ( unable to bind physiological ligands in solution) unless it is fully extended by activating stimuli. We generated a stable, soluble complex of the Mn2+ -bound alpha V beta 3 ectodomain with a fragment of fibronectin ( FN) containing type III domains 7 to 10 and the EDB domain ( FN7-EDB-10). Transmission electron microscopy and single particle image analysis were used to determine the three-dimensional structure of this complex. Most alpha V beta 3 particles, whether unliganded or FN-bound, displayed compact, triangular shapes. A difference map comparing ligand-free and FN-bound alpha V beta 3 revealed density that could accommodate the RGD-containing FN10 in proximity to the ligand-binding site of beta 3, with FN9 just adjacent to the synergy site binding region of alpha V. We conclude that the ectodomain of alpha V beta 3 manifests a bent conformation that is capable of stably binding a physiological ligand in solution. C1 Massachusetts Gen Hosp, Struct Biol Program, Leukocyte Biol & Inflammat Program, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Merck KGaA, D-64271 Darmstadt, Germany. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Struct Biol Program, Leukocyte Biol & Inflammat Program, Renal Unit, Charlestown, MA 02129 USA. EM arnaout@receptor.mgh.harvard.edu; yeager@scripps.edu FU NIAID NIH HHS [AI-07354, T32 AI007354]; NIDDK NIH HHS [R01 DK048549] NR 37 TC 125 Z9 128 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR 28 PY 2005 VL 168 IS 7 BP 1109 EP 1118 DI 10.1083/jcb.200410068 PG 10 WC Cell Biology SC Cell Biology GA 913WV UT WOS:000228187200014 PM 15795319 ER PT J AU Sykes, M AF Sykes, M TI Commentary: World health assembly resolution 57.18 on Xenotransplantation SO TRANSPLANTATION LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH E Bldg 149-5102,13th St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu NR 9 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 27 PY 2005 VL 79 IS 6 BP 636 EP 637 DI 10.1097/01.TP.0000157523.17977.A1 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 910ZZ UT WOS:000227972100003 PM 15785364 ER PT J AU Delmonico, FL AF Delmonico, FL TI Commentary: The WHO resolution on human organ and tissue transplantation SO TRANSPLANTATION LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Delmonico, FL (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, White Bldg 505,55 Fruit St, Boston, MA 02114 USA. EM francis_delmonico@neob.org NR 9 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 27 PY 2005 VL 79 IS 6 BP 639 EP 640 DI 10.1097/01.TP.0000157524.61834.EC PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 910ZZ UT WOS:000227972100005 PM 15785366 ER PT J AU Shaywitz, DA Melton, DA AF Shaywitz, DA Melton, DA TI The molecular biography of the cell SO CELL LA English DT Editorial Material ID EMBRYONIC STEM-CELLS; DIFFERENTIATION C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Howard Hughes Med Inst, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Shaywitz, DA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457,55 Fruit St, Boston, MA 02114 USA. EM dshaywitz@mcb.harvard.edu; dmelton@harvard.edu NR 11 TC 7 Z9 7 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 25 PY 2005 VL 120 IS 6 BP 729 EP 731 DI 10.1016/j.cell.2005.03.002 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 912HF UT WOS:000228067500001 PM 15797372 ER PT J AU Shi, YJ Sharma, A Wu, H Lichtenstein, A Gera, J AF Shi, YJ Sharma, A Wu, H Lichtenstein, A Gera, J TI Cyclin D1 and c-myc internal ribosome entry site (IRES)-dependent translation is regulated by AKT activity and enhanced by rapamycin through a p38 MAPK- and ERK-dependent pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RIBONUCLEOPROTEIN-K PROTEIN; 5' UNTRANSLATED REGION; MESSENGER-RNA; MAMMALIAN TARGET; GENE-EXPRESSION; KINASE-B; IN-VITRO; SEGMENT; INITIATION; BINDING AB The macrolide antibiotic rapamycin inhibits the mammalian target of rapamycin protein (mTOR) kinase resulting in the global inhibition of cap-dependent protein synthesis, a blockade in ribosome component biosynthesis, and G(1) cell cycle arrest. G1 arrest may occur by inhibiting the protein synthesis of critical factors required for cell cycle progression. Hypersensitivity to mTOR inhibitors has been demonstrated in cells having elevated levels of AKT kinase activity, whereas cells containing quiescent AKT activity are relatively resistant. Our previous data suggest that low AKT activity induces resistance by allowing continued cap-independent protein synthesis of cyclin D1 and c-Myc proteins. In support of this notion, the current study demonstrates that the human cyclin D1 mRNA 5 similar to untranslated region contains an internal ribosome entry site (IRES) and that both this IRES and the c-myc IRES are negatively regulated by AKT activity. Furthermore, we show that cyclin D1 and c-myc IRES function is enhanced following exposure to rapamycin and requires both p38 MAPK and RAF/MEK/ERK signaling, as specific inhibitors of these pathways reduce IRES-mediated translation and protein levels under conditions of quiescent AKT activity. Thus, continued IRES-mediated translation initiation may permit cell cycle progression upon mTOR inactivation in cells in which AKT kinase activity is relatively low. C1 Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Res & Dev, Los Angeles, CA 91343 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 91343 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 91343 USA. Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 91343 USA. Univ Calif Los Angeles, David Geffen Sch Med, Howard Hughes Med Inst, Los Angeles, CA 91343 USA. RP Gera, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Res & Dev, Los Angeles, CA 91343 USA. EM gera@ucla.edu FU NCI NIH HHS [CA096920] NR 53 TC 98 Z9 102 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 25 PY 2005 VL 280 IS 12 BP 10964 EP 10973 DI 10.1074/jbc.M407874200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 908BI UT WOS:000227761800012 PM 15634685 ER PT J AU Jensen, PH Weilguny, D Matthiesen, F McGuire, KA Shi, L Hojrup, P AF Jensen, PH Weilguny, D Matthiesen, F McGuire, KA Shi, L Hojrup, P TI Characterization of the oligomer structure of recombinant human mannan-binding lectin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CARBOHYDRATE-RECOGNITION DOMAINS; PULMONARY SURFACTANT APOPROTEIN; COLLAGEN-LIKE DOMAIN; ACTIVATES COMPLEMENT; CLASSICAL PATHWAY; SERINE-PROTEASE; SERUM LECTIN; PROTEINS; LIVER; GENE AB Mannan-binding lectin (MBL) belongs to a family of proteins called the collectins, which show large differences in their ultrastructures. These differences are believed to be determined by different N-terminal disulfide-bonding patterns. So far only the bonding pattern of two of the simple forms (recombinant rat MBL-C and bovine CL-43) have been determined. Recombinant MBL expressed in human cells was purified, and the structure of the N-terminal region was determined. Preliminary results on human plasma-derived MBL revealed high similarity to the recombinant protein. Here we report the structure of the N-terminal part of recombinant human MBL and present a model to explain the oligomerization pattern. Using a strategy of consecutive enzymatic digestions and matrix-assisted laser desorption ionization mass spectrometry, we succeeded in identifying a number of disulfide-linked peptides from the N-terminal cysteine-rich region. Based on these building blocks, we propose a model that can explain the various oligomeric forms found in purified MBL preparations. Furthermore, the model was challenged by the production of cysteine to serine mutants of the three N-terminally situated cysteines. The oligomerization patterns of these mutants support the proposed model. The model indicates that the polypeptide dimer is the basic unit in the oligomerization. C1 Univ So Denmark, Dept Biochem & Mol Biol, DK-5230 Odense, Denmark. NatImmune AS, DK-2100 Copenhagen, Denmark. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Dev Immunol, Boston, MA 02144 USA. RP Hojrup, P (reprint author), Univ So Denmark, Dept Biochem & Mol Biol, Campusvej 55, DK-5230 Odense, Denmark. EM php@bmb.sdu.dk FU NIGMS NIH HHS [GM62580] NR 40 TC 37 Z9 40 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 25 PY 2005 VL 280 IS 12 BP 11043 EP 11051 DI 10.1074/jbc.M412472200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 908BI UT WOS:000227761800021 PM 15653690 ER PT J AU Raina, D Pandey, P Ahmad, R Bharti, A Ren, J Kharbanda, S Weichselbaum, R Kufe, D AF Raina, D Pandey, P Ahmad, R Bharti, A Ren, J Kharbanda, S Weichselbaum, R Kufe, D TI c-Abl tyrosine kinase regulates caspase-9 autocleavage in the apoptotic response to DNA damage SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; CELLULAR-RESPONSE; FUNCTIONAL INTERACTION; CATALYTIC SUBUNIT; APAF-1; OLIGOMERIZATION; 1-BETA-D-ARABINOFURANOSYLCYTOSINE; PROCASPASE-9; INHIBITION; PHOSPHORYLATION AB Activation of the initiator caspase- 9 is essential for induction of apoptosis by developmental signals, oncogenic transformation, and genotoxic stress. The c- Abl tyrosine kinase is also involved in the apoptotic response to DNA damage. The present results demonstrate that c- Abl binds directly to caspase- 9. We show that cAbl phosphorylates caspase- 9 on Tyr- 153 in vitro and in cells treated with DNA damaging agents. Moreover, inhibition of c- Abl with STI571 blocked DNA damage- induced autoprocessing of caspase- 9 to the p35 subunit and activation of caspase- 3. Caspase- 9( Y153F) also attenuated DNA damage- induced processing of caspase- 9 to p35, activation of caspase- 3, and apoptosis. These findings indicate that caspase- 9 autoprocessing is regulated by c- Abl in the apoptotic response to genotoxic stress. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Univ Chicago, Sch Med, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA29431] NR 39 TC 31 Z9 37 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 25 PY 2005 VL 280 IS 12 BP 11147 EP 11151 DI 10.1074/jbc.M413787200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 908BI UT WOS:000227761800035 PM 15657060 ER PT J AU Weissman, JS AF Weissman, JS TI The trouble with uncompensated hospital care SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Partners Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Weissman, JS (reprint author), Massachusetts Gen Hosp, Partners Inst Hlth Policy, Boston, MA 02114 USA. NR 5 TC 13 Z9 13 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 24 PY 2005 VL 352 IS 12 BP 1171 EP 1173 DI 10.1056/NEJMp048280 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 909AW UT WOS:000227832300001 PM 15788492 ER PT J AU Sabatine, MS Cannon, CP Gibson, CM Lopez-Sendon, JL Montalescot, G Theroux, P Claeys, MJ Cools, F Hill, KA Skene, AM McCabe, CH Braunwald, E Braunwald, E Cannon, C Sabatine, M McCabe, C McCagg, A Job, B Gaudin, C Thizon-de Gaulle, I Blumenthal, M Saini, R Delaet, I Townes, L Anhalt, D van Holder, K Skene, A Hill, K Braunwald, E Cannon, C Sabatine, M McCabe, C Job, B Gaudin, C Thizon-de Gaulle, I Blumenthal, M Saini, R Delaet, I Townes, L Skene, A Ardissino, D Aylward, P Bertrand, M Bode, C Budaj, A Claeys, M Dellborg, M Ferreira, R Gershlick, A Huber, K Keltai, M Kleiman, N Lewis, B Lopez-Sendon, J Marx, J Montalescot, G Nicolau, J Ongen, Z Paolasso, E Pons, JL Ruda, M Theroux, P Van de Werf, F Verheugt, F Wilcox, R Zeymer, U Braunwald, E Cannon, C Sabatine, M Gibson, M McCabe, C McCagg, A Job, B Gaudin, C Thizon-de Gaulle, I Blumenthal, M Saini, R Froehlich, J Delaet, I Townes, L Anhalt, D van Holder, K Pieters, A Skene, A Hill, K Charlesworth, A Goulder, M Stead, S Wiviott, S Aroesty, J Berger, C Garcia, L Greer, D Leeman, D Lyle, H Philippides, G Schwamm, L Gibson, M Marble, S Aroesty, J Buros, J Ciaglo, L Kirtane, A Shui, A Wilson, A Scirica, B Morrow, D Giugliano, R Wiviott, S Morrow, D Ridker, P Rifai, N Sabatine, M Kucherlapati, R Kwiatkowski, D Stone, P Maccallum, G Lucier, M Garriga, A Anderson, J Fox, K Kelsey, S Batalla, A Areses, ELD Fiol, M Bethencourt, A Lozano, I Figueras, J Cortes, JG Jimenez, AG Fernandez, AR Montero, IF Casasnovas, J Aso, FO de Blas, RC Audicana, J Errazti, IE Montero, JS Rohlfs, I Pinero, C Rodriguez, MM Alvarez, LV Belras, AC Barros, S Fernandez, JD Tobaruela, A Bonneau, A Soulat, L Lambert, Y Caussanel, J Livareck, B Ramaut, C Ricome, J Lapostolle, F Beruben, A Thieleux, F Martelli, J Martelet, M Mouallem, J Ahmed, F Galley, D Alhabaj, S Doucos, D Bearez, E Spetebroodt, S Gully, C Dujardin, J Averland, B Emmonot, B Pollet, D Vallet, P Mossaz, R Marquand, A Kermarrec, A Le Lay, C Douillet, R Olliver, L Matas, O Kassam, S Halperin, F Parsons, P Bovak, B Hart, B Sussex, B Newman, S Gosselin, G David, M Sidhar, K Wiseman, D Lefkowitz, C Thornley, M Bhargava, R McCullum, A Grandmond, D Carignan, D Kouz, S Roy, M Polasek, P Stedham, V Lai, K Paquette, B Raco, D Sayles, M Sridhar, K Wiseman, D Tremblay, B Darveau, C Sussex, B Newman, S Senaratne, M Holland, M Bata, I Hulan, M Constance, C Pouliot, S Gossard, D Day, L Glanz, A Vilag, C Hui, W Kvill, L Dion, D Morisette, A Sandrin, F Mitges, S Cools, F Vanhagendoren, S De Meester, A Marcovitch, O Allaf, E Gits, F Verrostte, J Thoeng, J Quinonez, M Appeltants, H D'Hooghe, G Eycken, M Swennen, I Hollanders, G Michael, E Decroly, P Rombaut, E Carlaire, D Vermander, D Marenne, SF Gavray, C Michel, P Poth, A Paquay, J Lutasu, S Dirk, D Vermeulen, J Govaerts, E Boldueva, S Sherenkov, A Ruda, M Kostenko, V Tereschenko, S Zalevsky, G Boyarkin, M Tankhilevitch, B Glezer, M Gratsiansky, N Shlyakhto, E Sidorenko, B Zadiontchenko, V Perepech, N Gruzdev, A Chernov, S Pollock, B Andresen, D Hoffmann, S Andresen, D Arntz, H Klein, H Neuss, H Wilhelms, E Henzgen, R Kuckuck, H Darius, H Hausdorf, C Ochs, H Olbrich, H Willenbrock, R Hepp, A Wucherpfennig, P Wiechmann, H Schmidtendorf, H Kohler, B Sehnert, W Ueberreiter, A Uebis, R Stockmann, M Rommele, U Meissner, A Schneider, L Adgey, J McAllister, T McEneaney, D Mackin, A Sulke, N Dixon, R Wilcox, R Congreave, S Flapan, A Flint, L Purvis, J McCorkell, G Stubbs, P Steer, C McKkee, P Senior, R Chester, L Levy, T Kennard, S Bishop, A Hlaing, S de Belder, M Cunningham, N Gilbert, T Young, J Henderson, R Falcon-Lang, D Gershlick, A Fairbrother, K Rosenfeld, T Atar, S Lewis, B Yuval, R Meisel, S Alony, I Rozenman, Y Logrineuko, S Goldhammer, E Harel, S David, D Erez, N Jafari, J Tubul, O Marmor, A Pritulo, L Caspi, A Roitberg, N Kaluski, E Amar, R Tzivoni, D Rojanski, A Yedid-Am, S Keren, A Datiashvily, L Saraiva, JK Garcia, CT Markman, M Chaves, A Vaz, RC Dutra, O Coelho, OR Sciampaglia, R da Cunha, CP de Brito, MR Lotufo, P Ribeiro, E Cicogna, A Michalaros, YL Ornellas, CE Santos, SCD Rosatelli, P Pimentel, W Grudzinski, M Guimaraes, F Gustavo, C Moreira, M Gosmao, J Hertzberger, D Schut, A van der Zwaan, C Havenaar, H van Wijngaarden, J Verheij, H Wajon, E Bosschaart, M Oomen, A Daniels, M Coppes, A Vergeught, F Dieker, H Jochemsen, D Fijlstra, I Leenders, C Gelder, T Janicke, D Bass, J Hamroff, G Keeler, K Chandra, M Van Hoose, B Minor, S Mock, P Chandra, M Olliges, M Unwala, A Fisher, C French, W Barillas, O Chandna, H Holly, D Chandna, H Holly, D Grewal, G Gurnsey, L Mehta, P Cruse, A Perlman, R Palazzo, D Puma, J Payne, C Torres, J Patten, L Lefkovic, L Viswanathan, N Rees, A Yoches, A Rodriguez-Ospina, L Santos, J Chohan, A Kemp, A Perlman, R Palazzo, D Weiss, R Brennan, B Aude, Y Harrison, P Brogan, G Ayan, J Cragg, D Murawka, A Garg, M McKelvy, J Hulyalkar, A Kuchenrither, C Jackson, S Whitaker, J Richardson, J Vicari, R Howard, M Aude, Y Harrison, P Chadow, H Hauptman, R Gelormini, J Giambra, T Lakkis, N Jiang, S Hernandez, I Vazquez, A Rosas, EL Lawrenz, JC Bustamante, F Martinez, CA Alcocer, MA Hernandez, EG Dogre, CW Bustillos, MDB Alvarado, R Ramirez, MC Hinojosa, P Rivera, OO Pons, JL Carrillo, J Velasco, JA Quintana, F Petersen, F Palomera, R Ibarra, M Sanchez, CJ Delgado, L Bayram, E Machado, GM Berli, MA Vinuela, JC Allall, O Fuentealba, V Reguero, M Covelli, G San Martin, E Francia, E Gadaleta, F Haehnel, M Iglesias, R Blumberg, S de Lima, AA Henquin, R Estrada, JN de Arenaza, D Fernandez, R Abud, M Becker, C Milesi, R Schamuck, R Doyharzabal, JM Caime, DG Teresa, LC Kuschnir, E Sgammini, H Sgammini, J David, J Sosa, CH Redcozub, E Avalos, V Nul, D Ramos, S Castro, PT Rodriguez, A Sosa, C Lopez, JG Novo, F Diez, F Piraino, R Godoy, G Weller, C Pomposiello, J Sanchez, A Karlsson, J Collberg, K Malmqvist, K Cedergren, E Dellborg, M Coops, G Kallryd, A Laudon, P Bandh, S Andersson, C Soome, S Classon, H Lugnegard, J Ahlmark, H Risenfors, M Ortgren, L Fjelstad, B Osberg, S Frisell, J Sandstrom, M Silvestri, O Sasso, A Rolli, A Paoli, G Chiarella, F Olivotte, L Doronzo, B Coppolino, A Pivoccari, G Pesaresi, A Ambrosio, G Del Pinto, M De Luca, I Laico, M De Ferrari, G Baldini, E Guiducci, U Tortorella, G Romano, M Villani, R Casazza, F Capozi, A Moretti, L Del Pinto, M Perelli, S Sinagra, G Maras, P Porcu, M Scorcu, G Proietti, F Severi, S Gessek, J Pawlowicz, L Szelemej, R Gorski, M Janion, M Sielski, J Kleinrok, A Rodzik, J Hiczkiewicz, J Pasler, MM Soltsiak, M Gorny, J Huber, K Jordanova, N Heigert, M Kopp, K Frank, H Laggner, A Schreiber, W Weihs, W Drexel, MH Doubell, A Burgess, L Bennett, J Snyders, F Ebrahim, I Bobak, C Marx, J deBeer, M Schmidt, S Cyster, H van der Berg, P Groenewald, W Herbst, L Britz, A Snyman, M Schonken, M Badenhorst, J Blomerus, P Mpe, M Bobak, C Mynhardt, J Groenewald, C van Dyk, C Meiring, J Steingo, L Glaeser, L Whelan, A Tulloch, G Gunalingham, B Conway, B Soward, A Hales, S Lefkovits, J Sallaberger, M Owesby, D Kesby, J Amerena, J Fogarty, K Chew, D Austin, M Kovaricek, S Banham, N Tulloch, G Jobbagy, L Dinnyes, J Lippai, J Oze, B Szakal, I Bartal, G Foldi, A Foley, D McGrath, F Meany, B Geraghty, M Daly, K Henessey, S Mulvihill, N Schilling, C Kearney, P Kelly, P Kearney, P Kelly, P Ongen, Z Vura, A Kozan, O Ozaydin, E Kultursay, H Kayikcioglu, M Degertekin, M Mutlu, B Monteiro, F Ferreira, D Carrageta, M AF Sabatine, MS Cannon, CP Gibson, CM Lopez-Sendon, JL Montalescot, G Theroux, P Claeys, MJ Cools, F Hill, KA Skene, AM McCabe, CH Braunwald, E Braunwald, E Cannon, C Sabatine, M McCabe, C McCagg, A Job, B Gaudin, C Thizon-de Gaulle, I Blumenthal, M Saini, R Delaet, I Townes, L Anhalt, D van Holder, K Skene, A Hill, K Braunwald, E Cannon, C Sabatine, M McCabe, C Job, B Gaudin, C Thizon-de Gaulle, I Blumenthal, M Saini, R Delaet, I Townes, L Skene, A Ardissino, D Aylward, P Bertrand, M Bode, C Budaj, A Claeys, M Dellborg, M Ferreira, R Gershlick, A Huber, K Keltai, M Kleiman, N Lewis, B Lopez-Sendon, J Marx, J Montalescot, G Nicolau, J Ongen, Z Paolasso, E Pons, JL Ruda, M Theroux, P Van de Werf, F Verheugt, F Wilcox, R Zeymer, U Braunwald, E Cannon, C Sabatine, M Gibson, M McCabe, C McCagg, A Job, B Gaudin, C Thizon-de Gaulle, I Blumenthal, M Saini, R Froehlich, J Delaet, I Townes, L Anhalt, D van Holder, K Pieters, A Skene, A Hill, K Charlesworth, A Goulder, M Stead, S Wiviott, S Aroesty, J Berger, C Garcia, L Greer, D Leeman, D Lyle, H Philippides, G Schwamm, L Gibson, M Marble, S Aroesty, J Buros, J Ciaglo, L Kirtane, A Shui, A Wilson, A Scirica, B Morrow, D Giugliano, R Wiviott, S Morrow, D Ridker, P Rifai, N Sabatine, M Kucherlapati, R Kwiatkowski, D Stone, P Maccallum, G Lucier, M Garriga, A Anderson, J Fox, K Kelsey, S Batalla, A Areses, ELD Fiol, M Bethencourt, A Lozano, I Figueras, J Cortes, JG Jimenez, AG Fernandez, AR Montero, IF Casasnovas, J Aso, FO de Blas, RC Audicana, J Errazti, IE Montero, JS Rohlfs, I Pinero, C Rodriguez, MM Alvarez, LV Belras, AC Barros, S Fernandez, JD Tobaruela, A Bonneau, A Soulat, L Lambert, Y Caussanel, J Livareck, B Ramaut, C Ricome, J Lapostolle, F Beruben, A Thieleux, F Martelli, J Martelet, M Mouallem, J Ahmed, F Galley, D Alhabaj, S Doucos, D Bearez, E Spetebroodt, S Gully, C Dujardin, J Averland, B Emmonot, B Pollet, D Vallet, P Mossaz, R Marquand, A Kermarrec, A Le Lay, C Douillet, R Olliver, L Matas, O Kassam, S Halperin, F Parsons, P Bovak, B Hart, B Sussex, B Newman, S Gosselin, G David, M Sidhar, K Wiseman, D Lefkowitz, C Thornley, M Bhargava, R McCullum, A Grandmond, D Carignan, D Kouz, S Roy, M Polasek, P Stedham, V Lai, K Paquette, B Raco, D Sayles, M Sridhar, K Wiseman, D Tremblay, B Darveau, C Sussex, B Newman, S Senaratne, M Holland, M Bata, I Hulan, M Constance, C Pouliot, S Gossard, D Day, L Glanz, A Vilag, C Hui, W Kvill, L Dion, D Morisette, A Sandrin, F Mitges, S Cools, F Vanhagendoren, S De Meester, A Marcovitch, O Allaf, E Gits, F Verrostte, J Thoeng, J Quinonez, M Appeltants, H D'Hooghe, G Eycken, M Swennen, I Hollanders, G Michael, E Decroly, P Rombaut, E Carlaire, D Vermander, D Marenne, SF Gavray, C Michel, P Poth, A Paquay, J Lutasu, S Dirk, D Vermeulen, J Govaerts, E Boldueva, S Sherenkov, A Ruda, M Kostenko, V Tereschenko, S Zalevsky, G Boyarkin, M Tankhilevitch, B Glezer, M Gratsiansky, N Shlyakhto, E Sidorenko, B Zadiontchenko, V Perepech, N Gruzdev, A Chernov, S Pollock, B Andresen, D Hoffmann, S Andresen, D Arntz, H Klein, H Neuss, H Wilhelms, E Henzgen, R Kuckuck, H Darius, H Hausdorf, C Ochs, H Olbrich, H Willenbrock, R Hepp, A Wucherpfennig, P Wiechmann, H Schmidtendorf, H Kohler, B Sehnert, W Ueberreiter, A Uebis, R Stockmann, M Rommele, U Meissner, A Schneider, L Adgey, J McAllister, T McEneaney, D Mackin, A Sulke, N Dixon, R Wilcox, R Congreave, S Flapan, A Flint, L Purvis, J McCorkell, G Stubbs, P Steer, C McKkee, P Senior, R Chester, L Levy, T Kennard, S Bishop, A Hlaing, S de Belder, M Cunningham, N Gilbert, T Young, J Henderson, R Falcon-Lang, D Gershlick, A Fairbrother, K Rosenfeld, T Atar, S Lewis, B Yuval, R Meisel, S Alony, I Rozenman, Y Logrineuko, S Goldhammer, E Harel, S David, D Erez, N Jafari, J Tubul, O Marmor, A Pritulo, L Caspi, A Roitberg, N Kaluski, E Amar, R Tzivoni, D Rojanski, A Yedid-Am, S Keren, A Datiashvily, L Saraiva, JK Garcia, CT Markman, M Chaves, A Vaz, RC Dutra, O Coelho, OR Sciampaglia, R da Cunha, CP de Brito, MR Lotufo, P Ribeiro, E Cicogna, A Michalaros, YL Ornellas, CE Santos, SCD Rosatelli, P Pimentel, W Grudzinski, M Guimaraes, F Gustavo, C Moreira, M Gosmao, J Hertzberger, D Schut, A van der Zwaan, C Havenaar, H van Wijngaarden, J Verheij, H Wajon, E Bosschaart, M Oomen, A Daniels, M Coppes, A Vergeught, F Dieker, H Jochemsen, D Fijlstra, I Leenders, C Gelder, T Janicke, D Bass, J Hamroff, G Keeler, K Chandra, M Van Hoose, B Minor, S Mock, P Chandra, M Olliges, M Unwala, A Fisher, C French, W Barillas, O Chandna, H Holly, D Chandna, H Holly, D Grewal, G Gurnsey, L Mehta, P Cruse, A Perlman, R Palazzo, D Puma, J Payne, C Torres, J Patten, L Lefkovic, L Viswanathan, N Rees, A Yoches, A Rodriguez-Ospina, L Santos, J Chohan, A Kemp, A Perlman, R Palazzo, D Weiss, R Brennan, B Aude, Y Harrison, P Brogan, G Ayan, J Cragg, D Murawka, A Garg, M McKelvy, J Hulyalkar, A Kuchenrither, C Jackson, S Whitaker, J Richardson, J Vicari, R Howard, M Aude, Y Harrison, P Chadow, H Hauptman, R Gelormini, J Giambra, T Lakkis, N Jiang, S Hernandez, I Vazquez, A Rosas, EL Lawrenz, JC Bustamante, F Martinez, CA Alcocer, MA Hernandez, EG Dogre, CW Bustillos, MDB Alvarado, R Ramirez, MC Hinojosa, P Rivera, OO Pons, JL Carrillo, J Velasco, JA Quintana, F Petersen, F Palomera, R Ibarra, M Sanchez, CJ Delgado, L Bayram, E Machado, GM Berli, MA Vinuela, JC Allall, O Fuentealba, V Reguero, M Covelli, G San Martin, E Francia, E Gadaleta, F Haehnel, M Iglesias, R Blumberg, S de Lima, AA Henquin, R Estrada, JN de Arenaza, D Fernandez, R Abud, M Becker, C Milesi, R Schamuck, R Doyharzabal, JM Caime, DG Teresa, LC Kuschnir, E Sgammini, H Sgammini, J David, J Sosa, CH Redcozub, E Avalos, V Nul, D Ramos, S Castro, PT Rodriguez, A Sosa, C Lopez, JG Novo, F Diez, F Piraino, R Godoy, G Weller, C Pomposiello, J Sanchez, A Karlsson, J Collberg, K Malmqvist, K Cedergren, E Dellborg, M Coops, G Kallryd, A Laudon, P Bandh, S Andersson, C Soome, S Classon, H Lugnegard, J Ahlmark, H Risenfors, M Ortgren, L Fjelstad, B Osberg, S Frisell, J Sandstrom, M Silvestri, O Sasso, A Rolli, A Paoli, G Chiarella, F Olivotte, L Doronzo, B Coppolino, A Pivoccari, G Pesaresi, A Ambrosio, G Del Pinto, M De Luca, I Laico, M De Ferrari, G Baldini, E Guiducci, U Tortorella, G Romano, M Villani, R Casazza, F Capozi, A Moretti, L Del Pinto, M Perelli, S Sinagra, G Maras, P Porcu, M Scorcu, G Proietti, F Severi, S Gessek, J Pawlowicz, L Szelemej, R Gorski, M Janion, M Sielski, J Kleinrok, A Rodzik, J Hiczkiewicz, J Pasler, MM Soltsiak, M Gorny, J Huber, K Jordanova, N Heigert, M Kopp, K Frank, H Laggner, A Schreiber, W Weihs, W Drexel, MH Doubell, A Burgess, L Bennett, J Snyders, F Ebrahim, I Bobak, C Marx, J deBeer, M Schmidt, S Cyster, H van der Berg, P Groenewald, W Herbst, L Britz, A Snyman, M Schonken, M Badenhorst, J Blomerus, P Mpe, M Bobak, C Mynhardt, J Groenewald, C van Dyk, C Meiring, J Steingo, L Glaeser, L Whelan, A Tulloch, G Gunalingham, B Conway, B Soward, A Hales, S Lefkovits, J Sallaberger, M Owesby, D Kesby, J Amerena, J Fogarty, K Chew, D Austin, M Kovaricek, S Banham, N Tulloch, G Jobbagy, L Dinnyes, J Lippai, J Oze, B Szakal, I Bartal, G Foldi, A Foley, D McGrath, F Meany, B Geraghty, M Daly, K Henessey, S Mulvihill, N Schilling, C Kearney, P Kelly, P Kearney, P Kelly, P Ongen, Z Vura, A Kozan, O Ozaydin, E Kultursay, H Kayikcioglu, M Degertekin, M Mutlu, B Monteiro, F Ferreira, D Carrageta, M CA CLARITY-TIMI 28 Investigators TI Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED-TRIAL; PLASMINOGEN-ACTIVATOR; REPERFUSION THERAPY; FOLLOW-UP; TIMI; THROMBOLYSIS; HEPARIN; TENECTEPLASE; COMBINATION; REOCCLUSION AB BACKGROUND: A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death. METHODS: We enrolled 3491 patients, 18 to 75 years of age, who presented within 12 hours after the onset of an ST-elevation myocardial infarction and randomly assigned them to receive clopidogrel (300-mg loading dose, followed by 75 mg once daily) or placebo. Patients received a fibrinolytic agent, aspirin, and when appropriate, heparin (dispensed according to body weight) and were scheduled to undergo angiography 48 to 192 hours after the start of study medication. The primary efficacy end point was a composite of an occluded infarct-related artery (defined by a Thrombolysis in Myocardial Infarction flow grade of 0 or 1) on angiography or death or recurrent myocardial infarction before angiography. RESULTS: The rates of the primary efficacy end point were 21.7 percent in the placebo group and 15.0 percent in the clopidogrel group, representing an absolute reduction of 6.7 percentage points in the rate and a 36 percent reduction in the odds of the end point with clopidogrel therapy (95 percent confidence interval, 24 to 47 percent; P<0.001). By 30 days, clopidogrel therapy reduced the odds of the composite end point of death from cardiovascular causes, recurrent myocardial infarction, or recurrent ischemia leading to the need for urgent revascularization by 20 percent (from 14.1 to 11.6 percent, P=0.03). The rates of major bleeding and intracranial hemorrhage were similar in the two groups. CONCLUSIONS: In patients 75 years of age or younger who have myocardial infarction with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel improves the patency rate of the infarct-related artery and reduces ischemic complications. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Hosp Univ Gregorio Maranon, Madrid, Spain. Hop La Pitie Salpetriere, Inst Cardiol, Paris, France. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. Univ Antwerp Hosp, Dept Cardiol, Edegem, Belgium. Acad Ziekenhuis Klina, Brasschaat, Belgium. Nottingham Clin Res Grp, Nottingham, England. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org RI Nicolau, Jose/E-1487-2012; Verheugt, F.W.A./H-8105-2014; Lotufo, Paulo/A-9843-2008 OI Lotufo, Paulo/0000-0002-4856-8450 FU NHLBI NIH HHS [R01 HL072879] NR 34 TC 1050 Z9 1148 U1 2 U2 39 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 24 PY 2005 VL 352 IS 12 BP 1179 EP 1189 DI 10.1056/NEJMoa050522 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 909AW UT WOS:000227832300004 PM 15758000 ER PT J AU Systrom, DM Wittram, C Harris, NL Thorner, AR Mark, EJ AF Systrom, DM Wittram, C Harris, NL Thorner, AR Mark, EJ TI A 67-year-old man with acute respiratory failure - Hypersensitivity pneumonitis due to M-avium complex infection (hot-tub lung). SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RESOLUTION COMPUTED-TOMOGRAPHY; COMMUNITY-ACQUIRED PNEUMONIA; THIN-SECTION CT; INTERSTITIAL PNEUMONIA; MYCOPLASMA-PNEUMONIAE; EXPOSURE; DISEASE C1 Massachusetts Gen Hosp, Dept Pulm & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP Systrom, DM (reprint author), Massachusetts Gen Hosp, Dept Pulm & Crit Care, Boston, MA 02114 USA. NR 23 TC 10 Z9 11 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 24 PY 2005 VL 352 IS 12 BP 1238 EP 1246 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 909AW UT WOS:000227832300012 PM 15788501 ER PT J AU Moses, H Thier, SO Matheson, DHM AF Moses, H Thier, SO Matheson, DHM TI Why have academic medical centers survived? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article AB Over the past decade, many observers predicted the demise of the academic medical center (AMC) due to competition from community hospitals and physicians, fragile finances, inefficiency, and organizational complexity. In 2004, we interviewed 23 AMC and community hospital administrators to determine why those predictions have proven unfounded, learn the leaders' current concerns and priorities, and to identify desirable changes. Chief concerns were reimbursement uncertainty, federal research policy, ineffective internal decision-making, and clinical quality (mentioned in more than 75% of interviews). Priorities included ensuring sufficient investment capital, revising undergraduate and graduate curricula, strengthening ties with physicians and community hospitals, attracting faculty, and meeting regulatory requirements. We advocate that the AMC: (1) modify the re-search model to allow greater collaboration with institutions and researchers; (2) enhance free and open export of new and proven clinical techniques and knowledge; (3) devote greater attention to meeting patients' increasing needs for counsel and guidance, not just intervention, given the plethora of complex new technologies and their promotion in the popular media; and (4) simplify their organizations. To accomplish this, it is desirable for future leaders to gain experience outside the AMC, and for faculty and institutions to be less inwardly focused and more attentive to preserving the public's trust. C1 Aler Inst, N Garden, VA 22959 USA. Boston Consulting Grp Inc, Bethesda, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Moses, H (reprint author), Aler Inst, POB 150, N Garden, VA 22959 USA. EM hm@alerion.us NR 23 TC 23 Z9 23 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 23 PY 2005 VL 293 IS 12 BP 1495 EP 1500 DI 10.1001/jama.293.12.1495 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 908KA UT WOS:000227784700030 PM 15784874 ER PT J AU Gastfriend, DR AF Gastfriend, DR TI Physician substance abuse and recovery - What does it mean for physicians-and everyone else? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID IMPAIRED PHYSICIANS; HEALTH-PROGRAM; USE DISORDERS; PREVALENCE; ADDICTION C1 Massachusetts Gen Hosp, Dept Psychiat, Addict Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Gastfriend, DR (reprint author), Alkermes Inc, 64 Sidney St, Cambridge, MA 02139 USA. EM david.gastfriend@alkermes.com FU NIDA NIH HHS [DA00427] NR 24 TC 24 Z9 25 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 23 PY 2005 VL 293 IS 12 BP 1513 EP 1515 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 908KA UT WOS:000227784700033 PM 15784877 ER PT J AU Lim, GP Calon, F Morihara, T Yang, FS Teter, B Ubeda, O Salem, N Frautschy, SA Cole, GM AF Lim, GP Calon, F Morihara, T Yang, FS Teter, B Ubeda, O Salem, N Frautschy, SA Cole, GM TI A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model SO JOURNAL OF NEUROSCIENCE LA English DT Article DE DHA; polyunsaturated fatty acid; A beta; APP; secretase; Alzheimer ID N-3 FATTY-ACIDS; ALPHA-SECRETASE CLEAVAGE; RETINOID-X-RECEPTOR; PRECURSOR PROTEIN; TRANSGENIC MICE; OXIDATIVE STRESS; PLAQUE-FORMATION; DISINTEGRIN METALLOPROTEASE; DOCOSAPENTAENOIC ACID; LIPID-PEROXIDATION AB Epidemiological studies suggest that increased intake of the omega-3 ( n-3) polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) is associated with reduced risk of Alzheimer's disease (AD). DHA levels are lower in serum and brains of AD patients, which could result from low dietary intake and/or PUFA oxidation. Because effects of DHA on Alzheimer pathogenesis, particularly on amyloidosis, are unknown, we used the APPsw (Tg2576) transgenic mouse model to evaluate the impact of dietary DHA on amyloid precursor protein (APP) processing and amyloid burden. Aged animals (17-19 months old) were placed in one of three groups until 22.5 months of age: control (0.09% DHA), low-DHA (0%), or high-DHA (0.6%) chow. beta-Amyloid (A beta) ELISA of the detergent-insoluble extract of cortical homogenates showed that DHA-enriched diets significantly reduced total A beta by > 70% when compared with low-DHA or control chow diets. Dietary DHA also decreased A beta 42 levels below those seen with control chow. Image analysis of brain sections with an antibody against A beta (amino acids 1-13) revealed that overall plaque burden was significantly reduced by 40.3%, with the largest reductions (40-50%) in the hippocampus and parietal cortex. DHA modulated APP processing by decreasing both alpha- and beta-APP C-terminal fragment products and full-length APP. BACE1 (beta-secretase activity of the beta-site APP-cleaving enzyme), ApoE (apolipoprotein E), and transthyretin gene expression were unchanged with the high-DHA diet. Together, these results suggest that dietary DHA could be protective against beta-amyloid production, accumulation, and potential downstream toxicity. C1 Vet Affairs Healthcare Syst, North Hills, CA 91343 USA. Geriatr Res Educ Clin Ctr, North Hills, CA 91343 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. NIAAA, Sect Nutrit Neurosci, Lab Membrane Biochem & Biophys, Div Intramural Clin & Biol Res,NIH, Rockville, MD 20852 USA. RP Cole, GM (reprint author), Greater Los Angeles Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, 11E,16111 Plummer St, Sepulveda, CA 91343 USA. EM gmcole@ucla.edu FU NCCIH NIH HHS [R01 AT003008]; NIA NIH HHS [AG13471, AG16793, P50 AG016570] NR 68 TC 375 Z9 394 U1 2 U2 69 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 23 PY 2005 VL 25 IS 12 BP 3032 EP 3040 DI 10.1523/JNEUROSCI.4225-04.2005 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 909JP UT WOS:000227856500004 PM 15788759 ER PT J AU Wang, TJ Evans, JC Meigs, JB Rifai, N Fox, CS D'Agostino, RB Levy, D Vasan, RS AF Wang, TJ Evans, JC Meigs, JB Rifai, N Fox, CS D'Agostino, RB Levy, D Vasan, RS TI Low-grade albuminuria and the risks of hypertension and blood pressure progression SO CIRCULATION LA English DT Article DE blood pressure; risk factors; hypertension; epidemiology ID INSULIN-RESISTANCE SYNDROME; CLINICALLY HEALTHY-SUBJECTS; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; ENDOTHELIAL DYSFUNCTION; CHOLESTEROL LEVELS; DIABETES-MELLITUS; HEART-DISEASE; MICROALBUMINURIA; EXCRETION AB Background-It has been postulated that glomerular hyperfiltration and endothelial dysfunction are early features of essential hypertension that may antedate blood pressure elevation. Microalbuminuria, a marker of glomerular hyperfiltration and endothelial dysfunction, has been described in individuals with established hypertension, but its role as a biomarker of preclinical stages of this disease has not been investigated prospectively. Methods and Results-We examined the association between urinary albumin excretion and the risks of hypertension and blood pressure progression in 1499 nonhypertensive individuals (58% women) without diabetes. During a mean follow-up of 2.9 years, 230 participants (15%) developed hypertension and 499 (33%) progressed to a higher blood pressure category (defined by the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure). In multivariable logistic regressions that adjusted for known risk factors, the urine albumin-creatinine ratio (UACR) was a significant predictor of incident hypertension (adjusted OR 1.20, 95% CI 1.01 to 1.44, per 1-SD increment in log UACR). Compared with those in the lowest UACR quartile, participants in the highest quartile (men: >6.66 mg/g; women: >15.24 mg/g) had an approximate to 2-fold risk of developing hypertension (adjusted OR 1.93, P=0.006) and 1.5-fold risk of blood pressure progression (adjusted OR 1.45, P=0.03). Conclusions-Urinary albumin excretion predicts blood pressure progression in nondiabetic, nonhypertensive individuals incrementally over established risk factors and at levels well below the conventional threshold for microalbuminuria. UACR may be a useful biomarker for identifying individuals most likely to develop hypertension. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Endocrinol Hypertens & Diabet, Boston, MA USA. Boston Univ, Dept Math, Stat & Consulting Unit, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Boston Med Ctr, Prevent Med Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston Med Ctr, Cardiol Sect, Boston, MA 02118 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [2K24-HL-04334, K23-HL-074077, N01-HC-25195] NR 47 TC 143 Z9 157 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 22 PY 2005 VL 111 IS 11 BP 1370 EP 1376 DI 10.1161/01.CIR.0000158434.69180.2D PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 908RB UT WOS:000227805700004 PM 15738353 ER PT J AU Wyszynski, DF Nambisan, M Surve, T Alsdorf, RM Smith, CR Holmes, LB AF Wyszynski, DF Nambisan, M Surve, T Alsdorf, RM Smith, CR Holmes, LB CA Antiepileptic Drug Pregnancy Regis TI Increased rate of major malformations in offspring exposed to valproate during pregnancy SO NEUROLOGY LA English DT Article ID NEURAL-TUBE DEFECTS; SODIUM VALPROATE; SPINA-BIFIDA; ANTIEPILEPTIC DRUGS; CONGENITAL-MALFORMATIONS; INUTERO EXPOSURE; BIRTH-DEFECTS; CHILDREN BORN; LIMB DEFECTS; FOLIC-ACID AB Objective: To determine the rate of occurrence of major malformations in infants whose mothers had taken the drug valproic acid (VPA) as monotherapy during the first trimester of pregnancy and had enrolled in the North American Antiepileptic Drug Pregnancy Registry. Methods: Data were collected from pregnant women throughout the United States and Canada through telephone-based interviews. Each woman was interviewed at enrollment, at 7 months' gestation, and postpartum. With her written permission, the medical records of each mother and her infant were obtained. The major malformations tabulated were those identified at or before 5 days of age. The prevalence of congenital malformations among offspring of monotherapy VPA-exposed women was compared with that among infants of women exposed to all other antiepileptic drugs ( internal comparison group) and with that among newborns in the Active Malformations Surveillance Program at Brigham and Women's Hospital ( external comparison group). Results: Sixteen affected cases were identified among 149 VPA-exposed women ( proportion: 10.7%; 95% CI: 6.3 to 16.9%). The prevalence in the internal comparison group was 2.9% ( 95% CI: 2.0 to 4.1%; odds ratio: 4.0, 95% CI: 2.1 to 7.4; p < 0.001). Assuming a 1.62% prevalence in the external comparison group, the relative risk of having an affected offspring for VPA- exposed women was 7.3 ( 95% CI: 4.4 to 12.2; p < 0.001). Conclusion: Maternal exposure to valproic acid during the first trimester of pregnancy significantly increased the risk of major malformations. C1 Boston Univ, Sch Med, Dept Med, Genet Program, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Boston, MA 02114 USA. RP Wyszynski, DF (reprint author), Boston Univ, Sch Med, Dept Med, Genet Program, 715 Albany St,L-320, Boston, MA 02118 USA. EM dfw@bu.edu NR 44 TC 201 Z9 205 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 22 PY 2005 VL 64 IS 6 BP 961 EP 965 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 908RH UT WOS:000227806600006 PM 15781808 ER PT J AU Singhal, AB Topcuoglu, MA Dorer, DJ Ogilvy, CS Carter, BS Koroshetz, WJ AF Singhal, AB Topcuoglu, MA Dorer, DJ Ogilvy, CS Carter, BS Koroshetz, WJ TI SSRI and statin use increases the risk for vasospasm after subarachnoid hemorrhage SO NEUROLOGY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; DELAYED CEREBRAL-ISCHEMIA; ACUTE CORONARY SYNDROMES; COCAINE USE; STROKE; WITHDRAWAL; PRETREATMENT; ANEURYSM; ASPIRIN; MICE AB Background: Use of medications with vasoconstrictive or vasodilatory effects can potentially affect the risk for vasospasm after aneurysmal subarachnoid hemorrhage ( SAH). Methods: Using International Classification of Diseases - 9 diagnostic codes followed by medical record review, the authors identified 514 patients with SAH admitted between 1995 and 2003 who were evaluated for vasospasm between days 4 and 14. The authors determined risks for vasospasm, symptomatic vasospasm, and poor clinical outcomes in patients with documented pre-hemorrhagic use of calcium channel blockers, beta- receptor blockers, ACE inhibitors, aspirin, selective serotonin reuptake inhibitors ( SSRIs), non- SSRI vasoactive antidepressants, or statins. Results: Vasospasm developed in 62%, and symptomatic vasospasm in 29% of the cohort. On univariate analysis, the risk for all vasospasm tended to increase in patients taking SSRIs ( p = 0.09) and statins ( p = 0.05); SSRI use increased the risk for symptomatic vasospasm ( p = 0.028). The Cochran-Armitage trend test showed that the proportion of patients taking SSRIs and statins increased significantly across three worsening categories ( none, asymptomatic, symptomatic) of vasospasm. Logistic regression analysis showed that SSRI use tended to predict all vasospasm (O.R. 2.01 [0.91 to 4.45]), and predicted symptomatic vasospasm (O. R. 1.42 [1.06 to 4.33]). Statin exposure increased the risk for vasospasm (O. R. 2.75 [1.16 to 6.50]), perhaps from abrupt statin withdrawal ( O. R. 2.54 [0.78 to 8.28]). Age < 50 years, Hunt-Hess grade 4 or 5, and Fisher Group 3 independently predicted all vasospasm, symptomatic vasospasm, poor discharge clinical status, and death. Conclusion: Selective serotonin reuptake inhibitor and statin users have a higher risk for subarachnoid hemorrhage - related vasospasm. Whether the underlying disease indication, direct actions, or rebound effects from abrupt drug withdrawal account for the associated risk warrants further investigation. C1 Massachusetts Gen Hosp, Stroke Serv, VBK 802, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Stroke Serv, VBK 802, Dept Neurol, Boston, MA 02114 USA. EM asinghal@partners.org NR 35 TC 67 Z9 67 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 22 PY 2005 VL 64 IS 6 BP 1008 EP 1013 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 908RH UT WOS:000227806600016 PM 15781818 ER PT J AU Sarazin, M Stern, Y Berr, C Riba, A Albert, M Brandt, J Dubois, B AF Sarazin, M Stern, Y Berr, C Riba, A Albert, M Brandt, J Dubois, B TI Neuropsychological predictors of dependency in patients with Alzheimer disease SO NEUROLOGY LA English DT Article ID MINI-MENTAL-STATE; COGNITIVE IMPAIRMENT; DEMENTIA; DECLINE; ATROPHY; MEMORY; ONSET; DEATH; ASSOCIATION; DYSFUNCTION AB Objective: To determine whether specific cognitive deficits can predict the progression of Alzheimer disease ( AD). Methods: Two hundred fifty- two patients with AD enrolled in the Predictors Study were followed at 6-month intervals for up to 4.5 years with neurologic, cognitive, and psychiatric examinations. Neuropsychological functions were assessed by the Modified Mini-Mental State Examination ( mMMSE). Items of mMMSE were divided into five cognitive domains: temporospatial orientation, short-term memory, long-term memory, language, and visuoconstructive functions. Loss of autonomy was assessed by both the Dependency Scale ( DS) and the Equivalent Institutional Care ( EIC) rating. Cox proportional hazards models, adjusted for age, sex, estimated duration of illness at entry into the study, and presence of extrapyramidal signs and behavioral disturbances, were used to determine the predictive value of each neuropsychological domain on dependency outcomes. Results: Global mMMSE, temporospatial orientation, and short- term memory scores were associated with a greater relative risk of moderate or severe dependency. The visuoconstructive score predicted the development of severe dependency. Long-term memory and language scores were not predictive of the EIC or DS endpoints. Conclusions: The presence of certain neuropsychological deficits at a patient's initial visit, such as short- term memory, temporospatial orientation, and constructive apraxia, predict more rapid dependency in patients with Alzheimer disease. Neuropsychological items have different weights in term of predictive power, and these effects are independent of the influence of age and disease duration at baseline. C1 Hop La Pitie Salpetriere, Fed Neurol, Ctr Neuropsychol, F-75013 Paris, France. Hop La Pitie Salpetriere, INSERM, U610, F-75013 Paris, France. Hop Colombiere, INSERM, E361, Montpellier, France. Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, Gertrude H Sergieysky Ctr, New York, NY USA. Columbia Univ, Coll Phys & Surg, Taub Alzheimers Dis Res Ctr, New York, NY USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Behav Sci, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Alzheimers Dis Res Ctr, Baltimore, MD USA. RP Sarazin, M (reprint author), Hop La Pitie Salpetriere, Fed Neurol, Ctr Neuropsychol, 47 Bd Hop, F-75013 Paris, France. EM marie.sarazin@brt.ap-hop-paris.fr RI berr, Claudine/D-5238-2014; OI berr, Claudine/0000-0001-5254-7655; Brandt, Jason/0000-0001-7381-6244 NR 42 TC 23 Z9 25 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 22 PY 2005 VL 64 IS 6 BP 1027 EP 1031 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 908RH UT WOS:000227806600019 PM 15781821 ER PT J AU Fox, RM Von Stetina, SE Barlow, SJ Shaffer, C Olszewski, KL Moore, JH Dupuy, D Vidal, M Miller, DM AF Fox, RM Von Stetina, SE Barlow, SJ Shaffer, C Olszewski, KL Moore, JH Dupuy, D Vidal, M Miller, DM TI A gene expression fingerprint of C-elegans embryonic motor neurons SO BMC GENOMICS LA English DT Review ID EGG-LAYING BEHAVIOR; SYNAPTIC SIGNALING NETWORK; PROTEIN-COUPLED RECEPTORS; C-ELEGANS; NEUROPEPTIDE GENE; HOMEODOMAIN PROTEIN; AXON GUIDANCE; NEUROMUSCULAR-JUNCTIONS; TRANSMEMBRANE PROTEIN; ACETYLCHOLINE-RELEASE AB Background: Differential gene expression specifies the highly diverse cell types that constitute the nervous system. With its sequenced genome and simple, well-defined neuroanatomy, the nematode C. elegans is a useful model system in which to correlate gene expression with neuron identity. The UNC-4 transcription factor is expressed in thirteen embryonic motor neurons where it specifies axonal morphology and synaptic function. These cells can be marked with an unc-4:: GFP reporter transgene. Here we describe a powerful strategy, Micro-Array Profiling of C. elegans cells (MAPCeL), and confirm that this approach provides a comprehensive gene expression profile of unc-4:: GFP motor neurons in vivo. Results: Fluorescence Activated Cell Sorting (FACS) was used to isolate unc-4:: GFP neurons from primary cultures of C. elegans embryonic cells. Microarray experiments detected 6,217 unique transcripts of which similar to 1,000 are enriched in unc-4:: GFP neurons relative to the average nematode embryonic cell. The reliability of these data was validated by the detection of known cell-specific transcripts and by expression in UNC-4 motor neurons of GFP reporters derived from the enriched data set. In addition to genes involved in neurotransmitter packaging and release, the microarray data include transcripts for receptors to a remarkably wide variety of signaling molecules. The added presence of a robust array of G-protein pathway components is indicative of complex and highly integrated mechanisms for modulating motor neuron activity. Over half of the enriched genes ( 537) have human homologs, a finding that could reflect substantial overlap with the gene expression repertoire of mammalian motor neurons. Conclusion: We have described a microarray-based method, MAPCeL, for profiling gene expression in specific C. elegans motor neurons and provide evidence that this approach can reveal candidate genes for key roles in the differentiation and function of these cells. These methods can now be applied to generate a gene expression map of the C. elegans nervous system. C1 Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37232 USA. Vanderbilt Univ, CHGR, Nashville, TN 37232 USA. Dartmouth Coll Sch Med, Computat Genet Lab, Lebanon, NH 03756 USA. Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37232 USA. EM rebecca.fox@vanderbilt.edu; steve.vonstetina@vanderbilt.edu; sue.ruff@vanderbilt.edu; shaffer@chgr.mc.vanderbilt.edu; kellen.l.olszewski@vanderbilt.edu; jason.h.moore@dartmouth.edu; denis_dupuy@dfci.harvard.edu; Marc_Vidal@dfci.harvard.edu; david.miller@vanderbilt.edu RI Dupuy, Denis/M-7299-2014 FU NCI NIH HHS [P30 CA68485, CA68485, R33 CA097516, P30 CA068485]; NEI NIH HHS [P30 EY08126, EY08126, P30 EY008126]; NHLBI NIH HHS [1 P01 HL6744-01]; NICHD NIH HHS [P30 HD015052, HD15052]; NIDDK NIH HHS [DK58749, DK58404, P60 DK020593, P30 DK58404, P60 DK20593, P30 DK020593, DK20593, P01 DK58212, P01 DK058212, P30 DK058404]; NINDS NIH HHS [R01 NS26115, F31 NS046923, R01 NS026115, F31 NS043068] NR 107 TC 74 Z9 167 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD MAR 21 PY 2005 VL 6 AR 42 DI 10.1186/1471-2164-6-42 PG 23 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 914PM UT WOS:000228239900001 PM 15780142 ER PT J AU Vidal, M AF Vidal, M TI Interactome modeling SO FEBS LETTERS LA English DT Review DE ORFeome; interactome; network biology; systems; biology; integrative omics; reverse two-hybrid system; interaction-defective alleles ID PROTEIN-PROTEIN INTERACTIONS; REVERSE 2-HYBRID SYSTEM; ORFEOME VERSION 1.1; C-ELEGANS; CAENORHABDITIS-ELEGANS; SACCHAROMYCES-CEREVISIAE; INTERACTION MAP; GENE-EXPRESSION; MAPPING DATA; YEAST AB A long-term goal of the field of interactome modeling is to understand how global and local properties of complex macromolecular networks impact on observable biological properties, and how changes in such properties can lead to human diseases. The information available at this stage of development of the field provides strong evidence for the existence of such interesting global and local properties, but also demonstrates that many more datasets will be needed to provide accurate models with increasingly predictive capacity. This review focuses on an early attempt at mapping a multicellular interactome network and on the lessons learned from that attempt. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. 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. RP Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, 44 Binney St, Boston, MA 02115 USA. EM marc_vidal@dfci.harvard.edu NR 63 TC 81 Z9 87 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-5793 EI 1873-3468 J9 FEBS LETT JI FEBS Lett. PD MAR 21 PY 2005 VL 579 IS 8 SI SI BP 1834 EP 1838 DI 10.1016/j.febslet.2005.02.030 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 906QT UT WOS:000227657800012 PM 15763560 ER PT J AU Krane, SM AF Krane, SM TI Identifying genes that regulate bone remodeling as potential therapeutic targets SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID RECEPTOR-RELATED PROTEIN-5; ZINC-FINGER PROTEIN; OSTEOBLAST DIFFERENTIATION; OSTEOPOROSIS; OSTEOPROTEGERIN; EXPRESSION; DECREASE; BIOLOGY; DENSITY; CATENIN AB Bone remodeling, a coupled process involving bone resorption and formation, is initiated by mechanical signals and is controlled by local and systemic factors that regulate osteoblast and osteoclast differentiation and function. An excess of resorption over formation leads to the bone loss and increased propensity to fracture that is characteristic of osteoporosis. A newly described inhibitor of osteoblast differentiation, Ciz, interferes with bone morphogenic protein signaling. As a consequence, Ciz-deficient mice develop increased bone mass. C1 Harvard Univ, Sch Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, Boston, MA 02129 USA. RP Krane, SM (reprint author), Harvard Univ, Sch Med, Boston, MA 02129 USA. EM krane.stephen@mgh.harvard.edu NR 24 TC 32 Z9 37 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 21 PY 2005 VL 201 IS 6 BP 841 EP 843 DI 10.1084/jem.20050354 PG 3 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 912FG UT WOS:000228062400003 PM 15781576 ER PT J AU Katsumoto, TR Duda, J Kim, A Wardak, Z Dranoff, G Clapp, DW Shannon, K AF Katsumoto, TR Duda, J Kim, A Wardak, Z Dranoff, G Clapp, DW Shannon, K TI Granulocyte/macrophage colony-stimulating factor and accessory cells modulate radioprotection by purified hematopoietic cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID COMMON BETA-SUBUNIT; BONE-MARROW; DEFICIENT MICE; STEM; DIFFERENTIATION; TRANSPLANTATION; INTERLEUKIN-3; ENGRAFTMENT; EXPRESSION; RECEPTORS AB Granulocyte/macrophage colony-stimulating factor (GM-CSF) promotes the survival, proliferation, and differentiation of myeloid lineage cells and regulates chemotaxis and adhesion. However, mice in which the genes encoding GM-CSF (Gmcsf) or the beta common subunit of the GM-CSF receptor (beta c) are inactivated display normal steady-state hematopoiesis. Here, we show that host GM-CSF signaling strongly modulates the ability of donor hematopoietic cells to radioprotect lethally irradiated mice. Although bone marrow mononuclear cells efficiently rescue Gmcsf mutant recipients, fetal liver cells and Sca1 + lin(-/dim) marrow cells are markedly impaired. This defect is partially attributable to accessory cells that are more prevalent in bone marrow. In contrast, Gmcsf-deficient hematopoietic stem cells demonstrate normal proliferative potentials. Short-term survival is also impaired in irradiated Pc mutant recipients transplanted with fetal liver or bone marrow. These data demonstrate a nonredundant function of GM-CSF in radioprotection by donor hematopoietic cells that may prove relevant in clinical transplantation. C1 Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Internal Med, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Herman B Wells Ctr, Indianapolis, IN 46202 USA. RP Shannon, K (reprint author), Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. EM kevins@itsa.ucsf.edu FU NCI NIH HHS [CA72614, CA092625, CA66996, CA74886, P01 CA066996, P01 CA092625, R01 CA072614, R01 CA074886, R37 CA072614] NR 25 TC 7 Z9 9 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 21 PY 2005 VL 201 IS 6 BP 853 EP 858 DI 10.1084/jem.20041504 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 912FG UT WOS:000228062400005 PM 15781578 ER PT J AU Leslie, A Kavanagh, D Honeyborne, I Pfafferott, K Edwards, C Pillay, T Hilton, L Thobakgale, C Ramduth, D Draenert, R Le Gall, S Luzzi, G Edwards, A Brander, C Sewell, AK Moore, S Mullins, J Moore, C Mallal, S Bhardwaj, N Yusim, K Phillips, R Klenerman, P Korber, B Kiepiela, P Walker, B Goulder, P AF Leslie, A Kavanagh, D Honeyborne, I Pfafferott, K Edwards, C Pillay, T Hilton, L Thobakgale, C Ramduth, D Draenert, R Le Gall, S Luzzi, G Edwards, A Brander, C Sewell, AK Moore, S Mullins, J Moore, C Mallal, S Bhardwaj, N Yusim, K Phillips, R Klenerman, P Korber, B Kiepiela, P Walker, B Goulder, P TI Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; IMMUNE-RESPONSES; TYPE-1 INFECTION; CELL RECOGNITION; SLOW PROGRESSORS; SELECTION; IMMUNODOMINANT; SPECIFICITY; EPITOPE AB Human immunodeficiency virus (HIV)-1 amino acid sequence polymorphisms associated with expression of specific human histocompatibility leukocyte antigen (HLA) class I alleles suggest sites of cytotoxic T lymphocyte (CTL)-mediated selection pressure and immune escape. The associations most frequently observed are between expression of an HLA class I molecule and variation from the consensus sequence. However, a substantial number of sites have been identified in which particular HLA class I allele expression is associated with preservation of the consensus sequence. The mechanism behind this is so far unexplained. The current studies, focusing on two examples of "negatively associated" or apparently preserved epitopes, suggest an explanation for this phenomenon: negative associations can arise as a result of positive selection of an escape mutation, which is stable on transmission and therefore accumulates in the population to the point at which it defines the consensus sequence. Such negative associations may only be in evidence transiently, because the statistical power to detect them diminishes as the mutations accumulate. If an escape variant reaches fixation in the population, the epitope will be lost as a potential target to the immune system. These data help to explain how HIV is evolving at a population level. Understanding the direction of HIV evolution has important implications for vaccine development. C1 Univ Oxford, Oxford OX1 3SY, England. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Univ Natal, Doris Duke Med Res Inst, HPP, ZA-4015 Durban, South Africa. Wycombe Gen Hosp, Dept Genitourinary Med, High Wycombe HP11 2TT, Bucks, England. Radcliffe Infirm, Harrison Clin, Oxford OX2 6HE, England. Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. Royal Perth Hosp, Ctr Clin Immunol & Biomed Sci, Perth, WA 6000, Australia. Los Alamos Natl Lab, Theoret Biol & Biophys Grp, Los Alamos, NM 87545 USA. RP Goulder, P (reprint author), Univ Oxford, Peter Medawar Bldg, Oxford OX1 3SY, England. EM Philip.goulder@ndm.ox.ac.uk OI Brander, Christian/0000-0002-0548-5778; Sewell, Andrew/0000-0003-3194-3135; Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [AI46995-01A1, R01 AI046995]; PHS HHS [N01-AL-15422] NR 43 TC 172 Z9 177 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 21 PY 2005 VL 201 IS 6 BP 891 EP 902 DI 10.1084/jem.20041455 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 912FG UT WOS:000228062400009 PM 15781581 ER PT J AU Lambrecht, NWG Yakubov, I Scott, D Sachs, G AF Lambrecht, NWG Yakubov, I Scott, D Sachs, G TI Identification of the K efflux channel coupled to the gastric H-K-ATPase during acid secretion SO PHYSIOLOGICAL GENOMICS LA English DT Article DE parietal cell; oligonucleotide expression microarray; potassium channel; KCNQ1; KCNE2 ID CARDIAC POTASSIUM CHANNELS; I-KS; PARIETAL-CELLS; APICAL MEMBRANE; OXYNTIC CELLS; PUMP; INHIBITION; SUBUNITS; BLOCKER; BINDING AB Genomic microarray analysis of genes specifically expressed in a pure cell isolate from a heterocellular organ identified the likely K efflux channel associated with the gastric H-K-ATPase. The function of this channel is to supply K to the luminal surface of the pump to allow H for K exchange. KCNQ1-KCNE2 was the most highly expressed and significantly enriched member of the large variety of K channels expressed in the gastric epithelium. The function of this K channel in acid secretion was then shown by inhibition of secretion in isolated gastric glands with specific KCNQ inhibitors and by colocalization of the channel with the H-K-ATPase in the secretory canaliculus of the parietal cell. KCNQ1-KCNE2 appears to be the K efflux channel that is essential for gastric acid secretion. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Lab Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Membrane Biol Lab, Los Angeles, CA 90073 USA. RP Lambrecht, NWG (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. EM nilslam@ucla.edu OI Lambrecht, Nils/0000-0002-1275-1384 FU NIDDK NIH HHS [DK-41301, DK-46917, DK-53462] NR 34 TC 51 Z9 53 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD MAR 21 PY 2005 VL 21 IS 1 BP 81 EP 91 DI 10.1152/physiolgenomics.00212.2004 PG 11 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 916LW UT WOS:000228387500007 PM 15613615 ER PT J AU Isomoto, H Furusu, H Ohnita, K Wen, CY Inoue, K Kohno, S AF Isomoto, Hajime Furusu, Hisashi Ohnita, Ken Wen, Chun-Yang Inoue, Kenichiro Kohno, Shigeru TI Sofalcone, a mucoprotective agent, increases the cure rate of Helicobacter pylori infection when combined with rabeprazole, amoxicillin and clarithromycin SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Helicobacter pylori; Sofalcone; Mucoprotective agents ID INFRARED SPECTROMETRIC ANALYSIS; PROTON PUMP INHIBITOR; TRIPLE THERAPY; ANTIULCER AGENT; CAMPYLOBACTER-PYLORI; COMBINATION THERAPY; ERADICATION THERAPY; ULCER RECURRENCE; ECABET SODIUM; PEPTIC-ULCER AB AIM: The mucoprotective agents, sofalcone and polaprezinc have anti-Helicobacter pylori (H pylori) activities. We determined the therapeutic effects of sofalcone and polaprezinc when combined with rabeprazole, amoxicillin and clarithromycin for Helicobacter pylori infection. METHODS: One hundred and sixty-five consecutive outpatients with peptic ulcer and H pylori infection were randomly assigned to one of the following three groups and medicated for 7 d. Group A: triple therapy with rabeprazole (10 mg twice daily), clarithromycin (200 mg twice daily) and amoxicillin (750 mg twice daily). Group B: sofalcone (100 mg thrice daily) plus the triple therapy. Group C: polaprezinc (150 mg twice daily) plus the triple therapy. Eradication was considered successful if C-13-urea breath test was negative at least 4 wk after cessation of eradication regimens or successive famotidine in the cases of active peptic ulcer. RESULTS: On intention-to-treat basis, H pylori cure was achieved in 43 of 55 (78.2%) patients, 47 of 54 (87.0%) and 45 of 56 (80.4%) for the groups A, B and C respectively. Using per protocol analysis, the eradication rates were 81.1% (43/53), 94.0% (47/50) and 84.9% (45/53) respectively. There was a significant difference in the cure rates between group A and B. Adverse events occurred in 10, 12 and 11 patients, from groups A, B and C respectively, but the events were generally mild. CONCLUSION: The addition of sofalcone, but not polaprezinc, significantly increased the cure rate of H pylori infection when combined with the rabeprazole-amoxicillin-clarithromycin regimen. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved. C1 [Isomoto, Hajime; Furusu, Hisashi; Ohnita, Ken; Kohno, Shigeru] Nagasaki Univ, Sch Med, Dept Internal Med 2, Nagasaki 852, Japan. [Wen, Chun-Yang] Nagasaki Univ, Sch Med, Dept Mol Pathol, Atom Bomb Dis Inst, Nagasaki 852, Japan. [Wen, Chun-Yang] Nanjing Univ, Sch Med, Nanjing Drum Tower Hosp, Dept Digest Dis, Nanjing 210008, Jiangsu Provinc, Peoples R China. [Isomoto, Hajime; Inoue, Kenichiro] 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. EM hajimei2002@yahoo.co.jp NR 38 TC 16 Z9 20 U1 0 U2 2 PU BAISHIDENG PUBL GRP CO LTD PI BEIJING PA RM 903, BLDG D, OCEAN INTERNATIONAL CTR, NO 62 DONGSIHUAN ZHONGLU, BEIJING, CHAOYANG DISTRICT 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD MAR 21 PY 2005 VL 11 IS 11 BP 1629 EP 1633 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V19WK UT WOS:000208102300011 PM 15786539 ER PT J AU Poplin, EA Benedetti, JK Estes, NC Haller, DG Mayer, RJ Goldberg, RM Weiss, GR Rivkin, SE Macdonald, JS AF Poplin, EA Benedetti, JK Estes, NC Haller, DG Mayer, RJ Goldberg, RM Weiss, GR Rivkin, SE Macdonald, JS TI Phase III Southwest Oncology Group 9415/Intergroup 0153 randomized trial of fluorouracil, leucovorin, and levamisole versus fluorouracil continuous infusion and levamisole for adjuvant treatment of stage III and high-risk stage II colon cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Cancer-Society CY MAY 20-23, 2000 CL New Orleans, LA SP Amer Cancer Soc ID ADVANCED COLORECTAL-CANCER; FOLINIC ACID; ORAL CAPECITABINE; PLUS LEUCOVORIN; RECTAL-CANCER; DUKES-B; THERAPY; CARCINOMA; BOLUS; CHEMOTHERAPY AB Purpose Modest toxicity and possibly enhanced activity makes continuous-infusion fluorouracil (FU) an attractive alternative to FU plus leucovorin (FU/LV) for the adjuvant treatment of colorectal cancer. Intergroup trial 0153 (Southwest Oncology Group trial 9415) was developed to compare the efficacy of continuous-infusion FU (CIFU) plus levamisole to FU/LV plus levamisole in the adjuvant treatment of high-risk Dukes' B2 and C1 or C2 colon cancer. Patients and Methods After surgery, patients were randomly assigned to CIFU 250 mg/m(2)/d for 56 days every 9 weeks for three cycles or FU 425 mg/m(2) and LV 20 mg/m(2) daily for 5 days every 28 to 35 days for six cycles. All patients received levamisole 50 mg tid for 3 days every other week. The primary end point was overall survival (OS). Results The study closed in December 1999 after an interim analysis demonstrated little likelihood of CIFU showing superiority to FU/LV within the stipulated hazard ratio. A total of 1, 135 patients were registered. At least one grade 4 toxicity occurred in 39% of patients receiving FU/LV and 5% of patients receiving CIFU. However, almost twice as many patients receiving CIFU discontinued therapy early compared with those receiving FU/LV. The 5-year OS is 70% (95% CI, 66% to 74%) for FU/LV and 69% (95% CI, 64% to 73%) for CIFU. The corresponding 5-year disease-free survival (DFS) is 61% (95% CI, 56% to 65%) and 63% (95% CI, 59% to 68%), respectively. For all patients, 5-year OS is 83%, 74%, and 55%; 5-year DFS is 78%, 67%, and 47% for N0, N1, and N2-3, respectively. Conclusion CIFU had less severe toxicity but did not improve DFS or OS in comparison with bolus FU/LV. (c) 2005 by American Society of Clinical Oncology. C1 Canc Inst New Jersey, New Brunswick, NJ USA. SW Oncol Grp Stat Ctr, Puget Sound Oncol Consortium, Seattle, WA USA. Univ Illinois, Coll Med, Peoria, IL 61656 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. St Vincents Comprehens Canc Ctr, New York, NY USA. RP Poplin, EA (reprint author), SWOG 9415, Operat Off, 14980 Omicron Dr, San Antonio, TX 78245 USA. EM pubs@swog.org RI Goldberg , Richard/M-1311-2013 FU NCI NIH HHS [CA46368, CA04919, CA04920, CA12213, CA12644, CA13612, CA14028, CA15488, CA16385, CA20319, CA21115, CA22433, CA25224, CA27057, CA28862, CA32102, CA32291, CA35090, CA35119, CA35176, CA35178, CA35192, CA35261, CA35262, CA35281, CA35431, CA35996, CA37981, CA38926, CA42777, CA45377, CA45450, CA45461, CA45560, CA45807, CA46113, CA46136, CA46282, CA46441, CA52654, CA58348, CA58415, CA58416, CA58658, CA58686, CA58723, CA58861, CA58882, CA63844, CA63845, CA63850, CA67575, CA67663, CA68183, CA74647, CA76429, CA76447, CA76462]; PHS HHS [35128] NR 38 TC 85 Z9 88 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 20 PY 2005 VL 23 IS 9 BP 1819 EP 1825 DI 10.1200/JCO.2005.04.169 PG 7 WC Oncology SC Oncology GA 911SK UT WOS:000228024800007 PM 15774775 ER PT J AU Bellon, JR Come, SE Gelman, RS Henderson, IC Shulman, LN Silver, BJ Harris, JR Recht, A AF Bellon, JR Come, SE Gelman, RS Henderson, IC Shulman, LN Silver, BJ Harris, JR Recht, A TI Sequencing of chemotherapy and radiation therapy in early-stage breast cancer: Updated results of a prospective randomized trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05, 2001 CL San Francisco, CA SP Amer Soc Therapeut Radiol Oncol ID LOCAL-CONTROL; CONSERVATIVE SURGERY; MARGIN STATUS; RECURRENCE; RADIOTHERAPY; IMPACT; IRRADIATION; DELAY; RISK AB Purpose The optimal integration of chemotherapy with radiation (RT) for patients with early-stage breast cancer remains uncertain. We present the long-term results of a prospective randomized trial to address this question. Patients and Methods Two hundred forty-four patients were randomly assigned after conservative breast surgery to receive 12 weeks of cyclophosphamide, doxorubicin, methotrexate, fluorouracil, and prednisone (CAMFP) before RT (CT-first) or after RT (RT-first). Median follow-up for surviving patients was 135 months. Results There were no significant differences between the CT-first and RT-first arms in time to any event, distant metastasis, or death. Sites of first failure were also not significantly different. Conclusion Among breast cancer patients treated with conservative surgery, there is no advantage to giving RT before adjuvant chemotherapy. However, this study does not have enough statistical power to rule out a clinically important survival benefit for either sequence. (c) 2005 by American Society of Clinical Oncology. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Bellon, JR (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM jbellon@lroc.harvard.edu NR 20 TC 100 Z9 107 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 20 PY 2005 VL 23 IS 9 BP 1934 EP 1940 DI 10.1200/JCO.2005.04.032 PG 7 WC Oncology SC Oncology GA 911SK UT WOS:000228024800020 PM 15774786 ER PT J AU Taghian, AG Abi-Raad, R Assaad, SI Casty, A Ancukiewicz, M Yeh, E Molokhia, P Attia, K Sullivan, T Kuter, I Boucher, Y Powell, SN AF Taghian, AG Abi-Raad, R Assaad, SI Casty, A Ancukiewicz, M Yeh, E Molokhia, P Attia, K Sullivan, T Kuter, I Boucher, Y Powell, SN TI Paclitaxel decreases the interstitial fluid pressure and improves oxygenation in breast cancers in patients treated with neoadjuvant chemotherapy: Clinical implications SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the European-Society-for-Therapeutic-Radiology-and-Oncology (ESTRO 23) CY OCT 24-28, 2004 CL Amsterdam, NETHERLANDS SP European Soc Therapeut Radiol Oncol ID TUMOR BLOOD-FLOW; SOLID TUMORS; VASCULAR-PERMEABILITY; RADIATION RESPONSE; RANDOMIZED-TRIAL; DOXORUBICIN; HYPERTENSION; MACROMOLECULES; CLASSIFICATION; HETEROGENEITY AB Purpose It has been hypothesized that tumors with high interstitial fluid pressure (IFP) and/or hypoxia respond poorly to chemotherapy (CT) because of poor drug delivery. Preclinical studies have shown that paclitaxel reduces the IFP and improves the oxygenation (pO(2)) of tumors. Our aim is to evaluate the IFP and pO(2) before and after neoadjuvant CT using sequential paclitaxel and doxorubicin in patients with breast cancer tumors of >= 3 cm. Patients and Methods Patients were randomly assigned, according to an institutional review board-approved phase 11 protocol, to receive neoadjuvant sequential CT consisting of either four cycles of dose-dense doxorubicin at 60 mg/m 2 every 2 weeks followed by nine cycles of weekly paclitaxel at 80 mg/m(2) (group 1) or vice versa, with paclitaxel administered before doxorubicin (group 2). Patients were re-evaluated clinically and radiologically. The IFP (wick-in-needle technique) and pO(2) (Eppendorf) were measured in tumors at baseline and after completing the administration of the first and second drug. Results IFP and pO(2) were measured in 54 patients at baseline and after the first I Twenty-nine and 25 patients were randomly assigned to groups 1 and 2, respectively. Paclitaxel, when administered first, decreased the mean IFP by 36% (pO(2)) and improved the tumor PO2 by almost 100% (P = .003). In contrast, doxorubicin did not have a significant effect on either parameter. This difference was independent of the tumor size or response measured by ultrasound. Conclusion Paclitaxel significantly decreased the IFP and increased the pO(2) whereas doxorubicin did not cause any significant changes. Tumor physiology could potentially be used to optimize the sequence of neoadjuvant CT in breast cancer. (c) 2005 by American Society of Clinical Oncology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Canc Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Canc Ctr,Div Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Canc Ctr, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Canc Ctr, Boston, MA 02114 USA. EM ataghian@partners.org FU NCI NIH HHS [P50 CA89393] NR 41 TC 103 Z9 105 U1 1 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 20 PY 2005 VL 23 IS 9 BP 1951 EP 1961 DI 10.1200/JCO.2005.08.119 PG 11 WC Oncology SC Oncology GA 911SK UT WOS:000228024800022 PM 15774788 ER PT J AU Baron, F Maris, MB Sandmaier, BM Storer, BE Sorror, M Diaconescu, R Woolfrey, AE Chauncey, TR Flowers, MED Mielcarck, M Maloney, DG Storb, R AF Baron, F Maris, MB Sandmaier, BM Storer, BE Sorror, M Diaconescu, R Woolfrey, AE Chauncey, TR Flowers, MED Mielcarck, M Maloney, DG Storb, R TI Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; HLA-IDENTICAL SIBLINGS; BLOOD STEM-CELL; DONOR LYMPHOCYTE INFUSIONS; HOST-DISEASE; HEMATOLOGIC MALIGNANCIES; APLASTIC-ANEMIA; AUTOLOGOUS TRANSPLANTATION; COMPARING METHOTREXATE; ENGRAFTMENT KINETICS AB Purpose We have used a nonmyelorablative conditioning regimen consisting of total-body irradiation (2 Gy) with or without fludarabine (30 mg/m(2)/d for 3 days) for related and unrelated hematopoietic cell transplantation (HCT) in patients with hematologic malignancies who were not candidates for conventional HCT because of age, medical comorbidities, or preceding high-dose HCT. This approach relied on graft-versus-tumor (GVT) effects for control of malignancy. Patients and Methods We analyzed GVT effects in 322 patients given grafts from HILA-matched related (n = 192) or unrelated donors (n = 130). Results Of the 221 patients with measurable disease at HCT, 126 (57%) achieved complete (n = 98) or partial (n = 28) remissions. In multivariate analysis, there was a higher probability trend of achieving complete remissions in patients with chronic extensive graft-versus-host disease (GVHD, P = .07). One hundred eight patients (34%) relapsed or progressed. In multivariate analysis, achievement of full donor chimerism was associated with a decreased risk of relapse or progression (P = .002). Grade 2 to 4 acute GVHD had no significant impact on the risk of relapse or progression but was associated with increased risk of nonrelapse mortality and decreased probability of progression-free survival (PFS). Conversely, extensive chronic GVHD was associated with decreased risk of relapse or progression (P = .006) and increased probability of PFS (P = .003). Conclusion New approaches aimed at reducing the incidence of grade 2 to 4 acute GVHD might improve survival after allogeneic HCT after nonmyeloablative conditioning. (c) 2005 by American Society of Clinical Oncology. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Childrens Hosp & Reg Med Ctr, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Liege, Dept Hematol, Liege, Belgium. RP Storb, R (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. EM rstorb@fhcrc.org FU NCI NIH HHS [P01 CA078902, CA15704, CA18029, CA78902, CA92058]; NHLBI NIH HHS [HL36444]; NIDDK NIH HHS [DK064715] NR 56 TC 214 Z9 219 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 20 PY 2005 VL 23 IS 9 BP 1993 EP 2003 DI 10.1200/JCO.2005.08.0136 PG 11 WC Oncology SC Oncology GA 911SK UT WOS:000228024800027 PM 15774790 ER PT J AU Muss, HB Von Roenn, J Damon, LE Deangelis, LM Flaherty, LE Harari, PM Kelly, K Kosty, MP Loscalzo, MJ Mennel, R Mitchell, BS Mortimer, JE Muggia, F Perez, EA Pisters, PWT Saltz, L Schapira, L Sparano, J AF Muss, HB Von Roenn, J Damon, LE Deangelis, LM Flaherty, LE Harari, PM Kelly, K Kosty, MP Loscalzo, MJ Mennel, R Mitchell, BS Mortimer, JE Muggia, F Perez, EA Pisters, PWT Saltz, L Schapira, L Sparano, J TI ACCO: ASCO core curriculum outline SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article C1 Univ Vermont, Burlington, VT USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif San Diego, Scripps Clin, Moores Canc Ctr, San Diego, CA 92103 USA. Mem Sloan Kettering Canc Ctr, Bronx, NY USA. NYU, Med Ctr, New York, NY 10016 USA. Albert Einstein Canc Ctr, Bronx, NY USA. Wayne State Univ, Detroit, MI USA. Univ Wisconsin, Madison, WI USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. Texas Oncol PA, Dallas, TX USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Mayo Clin, Jacksonville, FL 32224 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Muss, HB (reprint author), Amer Soc Clin Oncol, 1900 Duke St,Suite 200, Alexandria, VA 22314 USA. OI Saltz, Leonard/0000-0001-8353-4670 NR 0 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 20 PY 2005 VL 23 IS 9 BP 2049 EP 2077 DI 10.1200/JCO.2005.99.008 PG 29 WC Oncology SC Oncology GA 911SK UT WOS:000228024800033 PM 15728218 ER PT J AU Provot, S Schipani, E AF Provot, S Schipani, E TI Molecular mechanisms of endochondral bone development SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Review ID HORMONE-RELATED PEPTIDE; JANSENS METAPHYSEAL CHONDRODYSPLASIA; PARATHYROID-HORMONE; INDIAN-HEDGEHOG; CHONDROCYTE DIFFERENTIATION; GROWTH-PLATE; TGF-BETA; BLOMSTRAND-CHONDRODYSPLASIA; PTH/PTHRP RECEPTOR; OSTEOBLAST DIFFERENTIATION AB Endochondral bone development is a complex process in which undifferentiated mesenchymal cells differentiate into chondrocytes, which then undergo well-ordered and controlled phases of proliferation, hypertrophic differentiation, death, blood vessel invasion, and finally replacement of cartilage with bone. The process recapitulates basic and fundamental mechanisms of cell biology with a highly specific spatial and temporal pattern, and it thus constitutes an excellent model for the analysis of such mechanisms. In recent years, the tools provided by modern genetic both in mice and men have been instrumental in the process of identifying and dissecting basic molecular mechanisms of endochondral bone formation. This review is a brief summary of the current knowledge about some of the crucial factors involved in growth plate development. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Schipani, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. EM schipani@helix.mgh.harvard.edu NR 85 TC 220 Z9 235 U1 0 U2 23 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 18 PY 2005 VL 328 IS 3 BP 658 EP 665 DI 10.1016/j.bbrc.2004.11.068 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 899JK UT WOS:000227140500003 PM 15694399 ER PT J AU Gensure, RC Gardella, TJ Juppner, H AF Gensure, RC Gardella, TJ Juppner, H TI Parathyroid hormone and parathyroid hormone-related peptide, and their receptors SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Review ID JANSENS METAPHYSEAL CHONDRODYSPLASIA; PHOTOAFFINITY CROSS-LINKING; PTH-RELATED PEPTIDE; FAMILIAL ISOLATED HYPOPARATHYROIDISM; (PTH)/PTH-RELATED PROTEIN-RECEPTOR; PSEUDOHYPOPARATHYROIDISM TYPE IB; CARBOXYL-TERMINAL FRAGMENTS; PRE-PROPARATHYROID HORMONE; AMINO ACID SEQUENCE; PTH/PTHRP RECEPTOR AB Parathyroid hormone (PTH) has a central role in the regulation of serum calcium and phosphate, while parathyroid hormone-related peptide (PTHrP) has important developmental roles. Both peptides signal through the same receptor, the PTH/PTHrP receptor (a class B G-protein-coupled receptor). The different biological effects of these ligands result from their modes of regulation and secretion, endocrine vs. paracrine/autocrine. The importance of PTH and PTHrP is evident by the variety of clinical syndromes caused by deficiency or excess production of either peptide, and the demonstration that intermittent injection of PTH increases bone mass, and thus provides a means to treat osteoporosis. This, in turn, has triggered increased interest in understanding the mechanisms of PTH/PTHrP receptor action and the search for smaller peptide or non-peptide agonists that have efficacy at this receptor when administered non-parenterally. (C) 2004 Published by Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, MassGen Hosp Children, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Nephrol Lab, MassGen Hosp Children, Boston, MA 02114 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. EM jueppner@helix.mgh.harvard.edu NR 116 TC 154 Z9 161 U1 4 U2 18 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 18 PY 2005 VL 328 IS 3 BP 666 EP 678 DI 10.1016/j.bbrc.2004.11.069 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 899JK UT WOS:000227140500004 PM 15694400 ER PT J AU Waeckel, L Mallat, Z Potteaux, S Combadiere, C Clergue, M Duriez, M Bao, L Gerard, C Rollins, BJ Tedgui, A Levy, BI Silvestre, JS AF Waeckel, L Mallat, Z Potteaux, S Combadiere, C Clergue, M Duriez, M Bao, L Gerard, C Rollins, BJ Tedgui, A Levy, BI Silvestre, JS TI Impairment in postischemic neovascularization in mice lacking the CXC chemokine receptor 3 SO CIRCULATION RESEARCH LA English DT Article DE inflammation; angiogenesis; ischemia; chemokine receptor ID ISCHEMIA-INDUCED ANGIOGENESIS; COLLATERAL ARTERY GROWTH; I-TAC; HINDLIMB; INTERLEUKIN-10; ACTIVATION; EXPRESSION; OCCLUSION; CELLS; IP-10 AB Inflammatory cell infiltration is a feature of postischemic neovascularization. However, mechanisms leading to leukocyte attraction to the site of neovascularization are still undefined. We hypothesized that the CXC chemokine receptor 3 (CXCR3) may contribute to leukocyte accumulation and subsequently to blood vessel growth in the ischemic area. Ischemia induced by femoral artery ligature improved the number of CXCR3-expressing cells and the level of its ligand, CXCL10. Angiographic score, blood flow recovery measurement, and capillary density analysis showed a significant decrease of ischemic/nonischemic leg ratio in CXCR3-deficient mice when compared with controls (P<0.05), at day 21 after ischemia. Interestingly, this impairment was as important as that observed in mice deficient for the well known CC-chemokine monocyte chemoattractant protein-1 (MCP-1). At day 7 of ischemic injury, the number of CD3-positive T cells and Mac-3-positive monocytes/macrophages was 38% and 45% lower, respectively, in the ischemic leg of CXCR3-deficient mice compared with the control group (P<0.05), suggesting an important role for CXCR3 in leukocyte recruitment into the ischemic area. VEGF protein content, a classical proangiogenic factor, was also markedly reduced (80% reduction) in ischemic leg of CXCR3-deficient mice (P<0.01). Injection of bone marrow-derived mononuclear cells (BM-MNCs) isolated from wild-type animals restored the neovascularization reaction in CXCR3-deficient mice whereas BM-MNCs from CXCR3-deficient mice was ineffective. In conclusion, CXCR3 plays a key role in neovascularization and provides novel information on the mechanisms leading to leukocyte infiltration in the vessel growth area. C1 Univ Paris 07, Hop Lariboisiere, IFR Circulat Lariboisiere,INSERM, U541, F-75475 Paris, France. Hop La Pitie Salpetriere, INSERM, U543, Lab Immunol Cellulaire & Tissulaire, Paris, France. Harvard Univ, Childrens Hosp, Sch Med, Ina Sue Perlmutter Lab, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Med, Boston, MA 02115 USA. RP Silvestre, JS (reprint author), Univ Paris 07, Hop Lariboisiere, IFR Circulat Lariboisiere,INSERM, U541, 41 Bd Chapelle, F-75475 Paris, France. EM Jean-Sebastien.Silvestre@larib.inserm.fr RI Mallat, Ziad/D-4041-2012; Combadiere, Christophe/I-5639-2013; OI Combadiere, Christophe/0000-0002-1755-4531; Mallat, Ziad/0000-0003-0443-7878 NR 16 TC 32 Z9 32 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAR 18 PY 2005 VL 96 IS 5 BP 576 EP 582 DI 10.1161/01.RES.0000159389.55544.20 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 907JR UT WOS:000227713500012 PM 15718500 ER PT J AU Huang, WQ Zhao, SJ Ammanamanchi, S Brattain, M Venkatasubbarao, K Freeman, JW AF Huang, WQ Zhao, SJ Ammanamanchi, S Brattain, M Venkatasubbarao, K Freeman, JW TI Trichostatin a induces transforming growth factor ss type II receptor promoter activity and acetylation of Sp1 by recruitment of PCAF/p300 to a Sp1 center dot NF-Y complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BREAST-CANCER CELLS; HISTONE DEACETYLASE INHIBITOR; TRANSCRIPTION FACTOR; PANCREATIC-CANCER; NF-Y; BETA RECEPTOR; FUNCTIONAL INTERACTION; GENETIC ALTERATIONS; ACTIVATION; EXPRESSION AB Transforming growth factor beta type II receptor (T beta RII) is a tumor suppressor gene that can be transcriptionally silenced by histone deacetylases (HDACs) in cancer cells. In this report, we demonstrated the mechanism by which trichostatin A (TSA), an inhibitor of HDAC, induces the expression of T beta RII in human pancreatic cancer cell lines by modulating the transcriptional components that bind a specific DNA region of the T beta RII promoter. This region of the T beta RII promoter possesses Sp1 and NF-Y binding sites in close proximity ( located at -102 and -83, respectively). Treatment of cells with TSA activates the T beta RII promoter in a time-dependent manner through the recruitment of p300 and PCAF into a Sp1(.)NF-Y(.)HDAC complex that binds this DNA element. The recruitment of p300 and PCAF into the complex is associated with a concomitant acetylation of Sp1 and an overall decrease in the amount of HDAC associated with the complex. Transient overexpression of p300 or PCAF potentiated TSA-induced T beta RII promoter activity. The effect of PCAF was dependent on its histone acetyltransferase activity, whereas that of p300 was independent. Stable transfection of PCAF caused an increase in T beta RII mRNA expression, the association of PCAF with T beta RII promoter, and the acetylation of Sp1. Taken together, these results showed that TSA treatment of pancreatic cancer cells leads to transcriptional activation of the T beta RII promoter through modulation of the components of a Sp1(.)NF-Y(.)p300(.)PCAF(.)HDAC-1 multiprotein complex. Moreover, the interaction of NF-Y with the Sp1-associated complex may further explain why this specific Sp1 site mediates transcriptional responsiveness to TSA. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA. Audie L Murphy Mem Vet Adm Med Ctr, Res & Dev, San Antonio, TX 78229 USA. RP Freeman, JW (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM freemanjw@uthscsa.edu RI Huang, Weiqi/E-4341-2010 FU NCI NIH HHS [CA96122] NR 41 TC 91 Z9 96 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 18 PY 2005 VL 280 IS 11 BP 10047 EP 10054 DI 10.1074/jbc.M408680200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 905HQ UT WOS:000227559600039 PM 15647279 ER PT J AU Ben-Yehuda, S Fujita, M Liu, XS Gorbatyuk, B Skoko, D Yan, J Marko, JF Liu, JS Eichenberger, P Rudner, DZ Losick, R AF Ben-Yehuda, S Fujita, M Liu, XS Gorbatyuk, B Skoko, D Yan, J Marko, JF Liu, JS Eichenberger, P Rudner, DZ Losick, R TI Defining a centromere-like element in Bacillus subtilis by identifying the binding sites for the chromosome-anchoring protein RacA SO MOLECULAR CELL LA English DT Article ID ASYMMETRIC CELL-DIVISION; CAULOBACTER-CRESCENTUS; BIPOLAR LOCALIZATION; PARTITIONING PROTEIN; BACTERIAL PROTEIN; SPORULATING CELLS; CYCLE PROGRESSION; ESCHERICHIA-COLI; DNA; SEGREGATION AB Chromosome segregation during sporulation in Bacillus subtilis involves the anchoring of sister chromosomes to opposite ends of the cell. Anchoring is mediated by RacA, which acts as a bridge between a centromere-like element in the vicinity of the origin of replication and the cell pole. To define this element we mapped RacA binding sites by performing chromatin immunoprecipitation in conjunction with gene microarray analysis. RacA preferentially bound to 25 regions spread over 612 kb across the origin portion of the chromosome. Computational and biochemical analysis identified a GC-rich, inverted 14 bp repeat as the recognition sequence. Experiments with single molecules of DNA demonstrated that RacA can condense nonspecific DNA dramatically against appreciable forces to form a highly stable protein-DNA complex. We propose that interactions between DNA bound RacA molecules cause the centromere-like element to fold up into a higher order complex that fastens the chromosome to the cell pole. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Hebrew Univ Jerusalem, Fac Med, Dept Mol Biol, IL-911120 Jerusalem, Israel. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Univ Illinois, Dept Phys, Chicago, IL 60607 USA. Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Losick, R (reprint author), Harvard Univ, Dept Mol & Cellular Biol, 16 Divin Ave, Cambridge, MA 02138 USA. EM losick@mcb.harvard.edu RI Yan, Jie/G-2725-2012 OI Yan, Jie/0000-0002-8555-7291 FU NIGMS NIH HHS [GM18568] NR 53 TC 59 Z9 60 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAR 18 PY 2005 VL 17 IS 6 BP 773 EP 782 DI 10.1016/j.molcel.2005.02.023 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 910EF UT WOS:000227912400006 PM 15780934 ER PT J AU Fan, HY Trotter, KW Archer, TK Kingston, RE AF Fan, HY Trotter, KW Archer, TK Kingston, RE TI Swapping function of two chromatin remodeling complexes SO MOLECULAR CELL LA English DT Article ID IN-VIVO; NUCLEAR RECEPTORS; HISTONE OCTAMER; NUCLEOSOME; TRANSCRIPTION; ISWI; SWI/SNF; BRG1; RECONSTITUTION; DISRUPTION AB SWI/SNF- and ISWI-based complexes have distinct yet overlapping chromatin-remodeling activities in vitro and perform different roles in vivo. This leads to the hypothesis that the distinct remodeling functions of these complexes are specifically required for distinct biological tasks. By creating and characterizing chimeric proteins of BRG1 and SNF2h, the motor proteins of human SWI/SNF- and ISWI-based complexes, respectively, we found that a region that includes the ATPase domain specifies the outcome of the remodeling reaction in vitro. A chimeric protein based on BRG1 but containing the SNF2h ATPase domain formed an intact SWI/SNF complex that remodeled like SNF2h. This altered-function complex was active for remodeling and could stimulate expression from some, but not all, SWI/SNF responsive promoters in vivo. Thus, we were able to separate domains of BRG1 responsible for function from those responsible for SWI/SNF complex formation and demonstrate that remodeling functions are not interchangeable in vivo. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM archer1@niehs.nih.gov; kingston@frodo.mgh.harvard.edu NR 34 TC 51 Z9 51 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAR 18 PY 2005 VL 17 IS 6 BP 805 EP 815 DI 10.1016/j.molcel.2005.02.024 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 910EF UT WOS:000227912400009 PM 15780937 ER PT J AU Gebhardt, MC Rosenthal, DI Harris, NL Arnell, PM AF Gebhardt, MC Rosenthal, DI Harris, NL Arnell, PM TI Case 8-2005: A 10-year-old boy with pain in the right thigh - Osteoid osteoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PERCUTANEOUS RADIOFREQUENCY ABLATION; TOMOGRAPHY-GUIDED THERMOCOAGULATION; OSTEOBLASTOMA; BIOPSY; LESIONS; SPINE; BONE; SYNOVITIS; TUMORS; HIP C1 Beth Israel Deaconess Med Ctr, Dept Orthoped, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gebhardt, MC (reprint author), Beth Israel Deaconess Med Ctr, Dept Orthoped, Boston, MA 02215 USA. NR 44 TC 5 Z9 5 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 17 PY 2005 VL 352 IS 11 BP 1122 EP 1129 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 906PU UT WOS:000227655000011 PM 15784666 ER PT J AU Yang, HY Asaad, N Held, KD AF Yang, HY Asaad, N Held, KD TI Medium-mediated intercellular communication is involved in bystander responses of X-ray-irradiated normal human fibroblasts SO ONCOGENE LA English DT Article DE bystander responses; X-ray; fibroblasts; transwell system; reactive oxygen species ID INDUCED GENOMIC INSTABILITY; STRAND BREAK REPAIR; SISTER-CHROMATID EXCHANGES; ALPHA-PARTICLES; MAMMALIAN-CELLS; UNIRRADIATED CELLS; IONIZING-RADIATION; DAMAGE SIGNALS; DNA-DAMAGE; INDUCTION AB Although radiation-induced bystander effects have been demonstrated in a number of cell types, the studies have largely been performed using high linear energy transfer (LET) radiation, such as alpha-particles. The literature is contradictory on whether fibroblasts show bystander responses, especially after low LET radiation such as X- or gamma-rays and whether the same signal transmission pathways are involved. Herein, a novel transwell insert culture dish method is used to show that X- irradiation induces medium-mediated bystander effects in AGO1522 normal human fibroblasts. The frequency of micronuclei formation in unirradiated bystander cells increases from a background of about 6.5% to about 9-13% at all doses from 0.1 to 10Gy to the irradiated cells. Induction of p21(Waf1) protein and foci of gamma-H(2)AX in bystander cells is also independent of dose to the irradiated cells above 0.1 Gy. In addition, levels of reactive oxygen species (ROS) were increased persistently in directly irradiated cells up to 60 h after irradiation and in bystander cells for 30 h. Adding Cu-Zn superoxide dismutase ( SOD) and catalase to the medium decreases the formation of micronuclei and induction of p21(Waf1) and gamma-H(2)AX foci in bystander cells, suggesting oxidative metabolism plays a role in the signaling pathways in bystander cells. The results of clonogenic assay of bystander cells showed that survival of bystander cells decreases from 0 to 0.5 Gy, and then is independent of the dose to irradiated cells from 0.5 to 10 Gy. Unlike the response with p21(Waf1) expression, gamma-H(2)AX foci and micronuclei, adding SOD and catalase has no effect on the survival of bystander cells. The data suggest that irradiated cells release toxic factors other than ROS into the medium. C1 Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Held, KD (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, COX 302,Fruit St, Boston, MA 02114 USA. EM kheld@partners.org NR 52 TC 153 Z9 167 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 17 PY 2005 VL 24 IS 12 BP 2096 EP 2103 DI 10.1038/sj.onc.1208439 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 906YU UT WOS:000227681900014 PM 15688009 ER PT J AU Weissman, JS Annas, CL Epstein, AM Schneider, EC Clarridge, B Kirle, L Gatsonis, C Feibelmann, S Ridley, N AF Weissman, JS Annas, CL Epstein, AM Schneider, EC Clarridge, B Kirle, L Gatsonis, C Feibelmann, S Ridley, N TI Error reporting and disclosure systems - Views from hospital leaders SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ADVERSE DRUG EVENTS; IMPLEMENTATION; PREVENTABILITY; COSTS AB Context The Institute of Medicine has recommended establishing mandatory error reporting systems for hospitals and other health settings. Objective To examine the opinions and experiences of hospital leaders with state reporting systems. Design and Setting Survey of chief executive and chief operating officers (CEOs/ COOs) from randomly selected hospitals in 2 states with mandatory reporting and public disclosure, 2 states with mandatory reporting without public disclosure, and 2 states without mandatory systems in 2002-2003. Main Outcome Measures Perceptions of the effects of mandatory systems on error reporting, likelihood of lawsuits, and overall patient safety; attitudes regarding release of incident reports to the public; and likelihood of reporting incidents to the state or to the affected patient based on hypothetical clinical vignettes that varied the type and severity of patient injury. Results Responses were received from 203 of 320 hospitals (response rate =63%). Most CEOs/COOs thought that a mandatory, nonconfidential system would discourage reporting of patient safety incidents to their hospital's own internal reporting system (69%) and encourage lawsuits (79%) while having no effect or a negative effect on patient safety (73%). More than 80% felt that the names of both the hospital and the involved professionals should be kept confidential, although respondents from states with mandatory public disclosure systems were more willing than respondents from the other states to release the hospital name (22% vs 4%-6%, P=.005). Based on the vignettes, more than 90% of hospital leaders said their hospital would report incidents involving serious injury to the state, but far fewer would report moderate or minor injuries, even when the incident was of sufficient consequence that they would tell the affected patient or family. Conclusions Most hospital leaders expressed substantial concerns about the impact of mandatory, nonconfidential reporting systems on hospital internal reporting, lawsuits, and overall patient safety. While hospital leaders generally favor disclosure of patient safety incidents to involved patients, fewer would disclose incidents involving moderate or minor injury to state reporting systems. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Gen Med & Primary Care, Boston, MA 02115 USA. Massachusetts Dept Publ Hlth, Boston, MA USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Massachusetts Hosp Assoc, Burlington, MA USA. Brown Univ, Ctr Stat Sci & Appl Math, Providence, RI 02912 USA. RP Weissman, JS (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jweissman@partners.org OI Schneider, Eric/0000-0002-1132-5084 FU AHRQ HHS [5 U18 HS11928] NR 17 TC 53 Z9 53 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 16 PY 2005 VL 293 IS 11 BP 1359 EP 1366 DI 10.1001/jama.293.11.1359 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 907EP UT WOS:000227698600024 PM 15769969 ER PT J AU Shankar, P Manjunath, N Lieberman, J AF Shankar, P Manjunath, N Lieberman, J TI The prospect of silencing disease using RNA interference SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID DOUBLE-STRANDED-RNA; HEPATITIS-B-VIRUS; FAS PROTECTS MICE; GENE-THERAPY; IN-VIVO; MAMMALIAN-CELLS; MESSENGER-RNA; INHIBITION; SIRNA; REPLICATION AB The discovery of RNA interference (RNAi), an endogenous cellular gene-silencing mechanism, has already provided a powerful tool for basic science researchers to study gene function. The subsequent finding that RNAi also operates in mammalian cells has generated excitement regarding potential therapeutic applications. In this article we discuss the basic mechanism of RNA! and the therapeutic opportunities and obstacles for harnessing RNAi for therapy of human disease. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI056900, AI058695] NR 70 TC 101 Z9 129 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 16 PY 2005 VL 293 IS 11 BP 1367 EP 1373 DI 10.1001/jama.293.11.1367 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 907EP UT WOS:000227698600025 PM 15769970 ER PT J AU Berezovska, O Lleo, A Herl, LD Frosch, MP Stern, EA Bacskai, BJ Hyman, BT AF Berezovska, O Lleo, A Herl, LD Frosch, MP Stern, EA Bacskai, BJ Hyman, BT TI Familial Alzheimer's disease presenilin 1 mutations cause alterations in the conformation of presenilin and interactions with amyloid precursor protein SO JOURNAL OF NEUROSCIENCE LA English DT Article DE fluorescence lifetime imaging microscopy ( FLIM); presenilin 1; amyloid precursor protein; amyloid beta peptide; familial Alzheimer's disease; gamma-secretase ID GAMMA-SECRETASE ACTIVITY; C-TERMINAL FRAGMENTS; IN-VIVO; CAENORHABDITIS-ELEGANS; DOCKING SITE; BETA-APP; COMPLEX; NOTCH; PROTEOLYSIS; NICASTRIN AB Presenilin 1 (PS1) is a critical component of the gamma-secretase complex, an enzymatic activity that cleaves amyloid beta(A beta) from the amyloid precursor protein (APP). More than 100 mutations spread throughout the PS1 molecule are linked to autosomal dominant familial Alzheimer's disease (FAD). All of these mutations lead to a similar phenotype: an increased ratio of A beta(42) to A beta(40), increased plaque deposition, and early age of onset. We use a recently developed microscopy approach, fluorescence lifetime imaging microscopy, to monitor the relative molecular distance between PS1 N and C termini in intact cells. Weshow that FAD-linked missense mutations located near the N and C termini, in the mid-region of PS1, and the exon 9 deletion mutation all change the spatial relationship between PS 1 N and C termini in a similar way, increasing proximity of the two epitopes. This effect is opposite of that observed by treatment with A beta(42)-lowering nonsteroidal anti-inflammatory drugs (NSAIDs) (Lleo et al., 2004b). Accordingly, treatment of M146L PS1-overexpressing neurons with high-dose NSAIDs somewhat offsets the conformational change associated with the mutation. Moreover, by monitoring the relative distance between a PS1 loop epitope and the APP C terminus, we demonstrate that the FAD PS1 mutations are also associated with a consistent change in the configuration of the PS1 - APP complex. The nonpathogenic E318G PS1 polymorphism had no effect on PS1 N terminus - C terminus proximity or PS1 - APP interactions. We propose that the conformational change we observed may therefore provide a shared molecular mechanism for FAD pathogenesis caused by a wide range of PS1 mutations. C1 Massachusetts Gen Hosp, Alzheimer Res Unit, Charlestown, MA 02129 USA. RP Berezovska, O (reprint author), Massachusetts Gen Hosp, Alzheimer Res Unit, 114 16th St,Room 2750, Charlestown, MA 02129 USA. EM bhyman@partners.org FU NIA NIH HHS [P01 AG15379-06]; NIBIB NIH HHS [EB00768] NR 44 TC 93 Z9 96 U1 0 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 16 PY 2005 VL 25 IS 11 BP 3009 EP 3017 DI 10.1523/JNEUROSCI.0364-05.2005 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 906WD UT WOS:000227674300025 PM 15772361 ER PT J AU Chan, AT Tranah, GJ Giovannucci, EL Hunter, DJ Fuchs, CS AF Chan, AT Tranah, GJ Giovannucci, EL Hunter, DJ Fuchs, CS TI Genetic variants in the UGT1A6 enzyme, aspirin use, and the risk of colorectal adenoma SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/105th Annual Meeting of the American-Gastroenterological-Association CY MAY 16-20, 2004 CL New Orleans, LA SP Amer Gastroenterol Assoc ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; UNITED-STATES; UDP-GLUCURONOSYLTRANSFERASE; RANDOMIZED-TRIAL; CANCER; CYCLOOXYGENASE-2; REPRODUCIBILITY; QUESTIONNAIRE; POLYMORPHISMS; POPULATION AB Genetic variation in the uridine diphosphate glucuronosyltransferase 1A6 (UGT1A6) enzyme is associated with impaired metabolism of aspirin. To determine whether polymorphisms in the UGT1A6 enzyme modulate the protective benefit of regular aspirin use on colorectal adenoma, we conducted a prospective, nested case-control study of 1062 women who provided blood specimens and detailed data on aspirin use before undergoing lower endoscopy. All statistical tests were two sided. Although UGTIA6 genotype was not associated with overall adenoma risk (multivariable odds ratio [OR] = 1.10, 95% confidence interval [CI] = 0.85 to 1.41), functional variant genotypes statistically significantly modified the effect of aspirin on adenoma (Pinteraction =.02). Among the 616 women with variant genotypes, regular use of aspirin (two or more standard tablets per week) was associated with a decreased risk of adenoma (multivariable OR for adenoma = 0.66 [95% Cl = 0.45 to 0.95], OR = 0.63 [95% CI = 0.43 to 0.91] for 0.5-7 standard tablets per week and OR = 0.41 [95% CI = 0.24 to 0.71] for more than 7 tablets per week; P-trend =.001). In contrast, among women with wild-type genotypes, regular aspirin use was not associated with a reduced risk nor did they obtain any additional benefit with higher doses (P-trend =.50). These results were consistent among women with advanced adenomas (Pinteraction =.003). Thus, functional polymorphisms in the UGTIA6 enzyme statistically significantly modify the effect of aspirin on colorectal neoplasia, and certain subsets of the population, defined by genotype, may obtain differential benefit from aspirin chemoprevention. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Canc Epidemiol Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 722, Boston, MA 02114 USA. EM achan@partners.org FU NCI NIH HHS [CA 87969, CA 09001-27, CA 55075]; NHLBI NIH HHS [HL 34594] NR 29 TC 59 Z9 63 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 16 PY 2005 VL 97 IS 6 BP 457 EP 460 DI 10.1093/jnci/dji066 PG 4 WC Oncology SC Oncology GA 907IR UT WOS:000227710600012 PM 15770010 ER PT J AU Ioannou, GN Weiss, NS Kearney, DJ AF Ioannou, GN Weiss, NS Kearney, DJ TI Is Helicobacter pylori seropositivity related to body mass index in the United States? SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PEPTIC-ULCER DISEASE; INFECTION; ERADICATION; OBESITY; LEPTIN; ADULTS; PREVALENCE; GHRELIN; STRAINS; PLASMA AB Background: Helicobacter pylori infection may decrease serum ghrelin and increase gastric leptin levels, which may, in turn, decrease body mass index. Aim: To determine whether H. pylori seropositivity is associated with body mass index. Methods: Serum H. pylori and cytotoxin-associated gene product A (CagA) antibody levels were measured on 6724 adult participants of the third National Health and Nutrition Examination Survey (1988-91). We evaluated the association between H. pylori/CagA antibody status [both negative (-/-), H. pylori-positive/CagA-negative (+/-), or both positive (+/+)] and body mass index, adjusting for sociodemographic factors. We also investigated whether H. pylori/cytotoxin-associated gene product A antibody status was associated with fasting serum leptin levels. Results: H. pylori/CagA antibody status was not associated with obesity (body mass index >= 30 kg/m(2)) [adjusted odds ratio (OR) 1.2, 95% CI: 0.9-1.6 comparing (+/+) to (-/-) and adjusted OR 1.1, 95% CI: 0.8-1.5 comparing (+/-) to (-/-)], overweight (body mass index 25 to < 30 kg/m(2)) [adjusted OR 1.0, 95% CI: 0.7-1.2 comparing (+/+) to (-/-) and adjusted OR 1.0, 95% CI: 0.8-1.3 comparing (+/-) to (-/-)], or fasting serum leptin level in the USA population. Conclusions: H. pylori seropositivity and CagA antibody status are not associated with body mass index or fasting serum leptin level. C1 VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Seattle VA Med Ctr, S-111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu NR 36 TC 31 Z9 31 U1 0 U2 2 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 MAR 15 PY 2005 VL 21 IS 6 BP 765 EP 772 DI 10.1111/j.1365-2036.2005.02369.x PG 8 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 907LX UT WOS:000227720700015 PM 15771763 ER PT J AU Boyko, EJ Fihn, SD Scholes, D Abraham, L Monsey, B AF Boyko, EJ Fihn, SD Scholes, D Abraham, L Monsey, B TI Risk of urinary tract infection and asymptomatic bacteriuria among diabetic and nondiabetic postmenopausal women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE diabetes mellitus; postmenopause; prospective studies; risk factors; urinary tract infection; women ID MELLITUS; PREVALENCE; DIAGNOSIS; NIDDM AB No prospective data exist on the risk of microbiologically confirmed urinary tract infection (UTI) and asymptomatic bacteriuria (AB) in relation to diabetes mellitus and its characteristics. The authors prospectively (1998-2002) followed 218 diabetic and 799 nondiabetic Washington State women aged 55-75 years for UTI and AB. The baseline examination and two annual follow-up examinations included urine culture, measurement of hemoglobin A1c and postvoid residual bladder volume, and a survey of diabetes and other characteristics. Surveillance for UTI included self-reports confirmed by microbiologic culture and medical record review. UTI incidence per 100 person-years was 12.2 for diabetic women and 6.7 for nondiabetic women (relative risk (RR) = 1.8, 95% confidence interval (CI): 1.2, 2.7). AB incidence per 100 person-years was 6.7 for diabetic women and 3.0 for nondiabetic women (RR = 2.3, 95% CI: 1.3, 3.9). In Cox models adjusted for multiple covariates, the increased UTI risk occurred mainly in women taking insulin (RR = 3.7, 95% CI: 1.8, 7.3) and women with a longer diabetes duration (greater than or equal to10 years; RR = 2.6, 95% CI: 1.3, 5.1) compared with nondiabetic women. No clear linear trend between hemoglobin A1c and UTI or AB risk was seen. Postmenopausal women with diabetes have higher risks of UTI and AB in relation to diabetes duration and severity but not to recent glucose control. C1 VA Peget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Program, Seattle, WA USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. RP Boyko, EJ (reprint author), VA Peget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, S-152E,1660 S Columbian Way, Seattle, WA 98108 USA. EM eboyko@u.washington.edu FU NIDDK NIH HHS [R01 DK 43134] NR 38 TC 69 Z9 82 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 2005 VL 161 IS 6 BP 557 EP 564 DI 10.1093/aje/kwi078 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 903DQ UT WOS:000227406100007 PM 15746472 ER PT J AU Tseng, CL Brimacombe, M Xie, M Rajan, M Wang, HW Kolassa, J Crystal, S Chen, TC Pogach, L Safford, M AF Tseng, CL Brimacombe, M Xie, M Rajan, M Wang, HW Kolassa, J Crystal, S Chen, TC Pogach, L Safford, M TI Seasonal patterns in monthly hemoglobin A(1c) values SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE diabetes mellitus; hemoglobin A; glycosylated; seasons; veterans ID TIME PHYSICAL-ACTIVITY; ACUTE MYOCARDIAL-INFARCTION; CORONARY HEART-DISEASE; QUALITY-OF-CARE; BLOOD-PRESSURE; DIETARY-INTAKE; INSULIN SENSITIVITY; AMBIENT-TEMPERATURE; VETERANS-AFFAIRS; RISK-FACTORS AB The purpose of this study was to investigate seasonal variations in population monthly hemoglobin A(1c) (A1c) values over 2 years (from October 1998 to September 2000) among US diabetic veterans. The study cohort included 285,705 veterans with 856,181 A1c tests. The authors calculated the monthly average A1c values for the overall population and for subpopulations defined by age, sex, race, insulin use, and climate regions. A1c values were higher in winter and lower in summer with a difference of 0.22. The proportion of A1c values greater than 9.0% followed a similar seasonal pattern that varied from 17.3% to 25.3%. Seasonal autoregressive models including trigonometric function terms were fit to the monthly average A1c values. There were significant seasonal effects; the seasonal variation was consistent across different subpopulations. Regions with colder winter temperatures had larger winter-summer contrasts than did those with warmer winter temperatures. The seasonal patterns followed trends similar to those of many physiologic markers, cardiovascular and other diabetes outcomes, and mortality. These findings have implications for health-care service research in quality-of-care assessment, epidemiologic studies investigating population trends and risk factors, and clinical trials or program evaluations of treatments or interventions. C1 Ctr Hlth Care Knowledge Management, Dept Vet Affairs New Jersey Hlth Care Syst, E Orange, NJ USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Prevent Med & Community Hlth, Newark, NJ 07103 USA. Rutgers State Univ, Dept Stat, New Brunswick, NJ 08903 USA. CTC Technol Inc, Short Hills, NJ USA. Rutgers State Univ, Hlth Serv Res Inst Hlth Hlth Care Policy & Aging, New Brunswick, NJ USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Tseng, CL (reprint author), E Orange VA Med Ctr, Dept Vet Affairs New Jersey Hlth Care Syst, 385 Tremont Ave,129, E Orange, NJ 07018 USA. EM Tseng@njneuromed.org OI Brimacombe, Michael/0000-0002-3276-9071 NR 73 TC 61 Z9 68 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 2005 VL 161 IS 6 BP 565 EP 574 DI 10.1093/aje/kwi083 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 903DQ UT WOS:000227406100008 PM 15746473 ER PT J AU Birbes, H Luberto, C Hsu, YT Bawab, SEL Hannun, YA Obeid, LM AF Birbes, H Luberto, C Hsu, YT Bawab, SEL Hannun, YA Obeid, LM TI A mitochondrial pool of sphingomyelin is involved in TNF alpha-induced Bax translocation to mitochondria SO BIOCHEMICAL JOURNAL LA English DT Article DE apoptosis; Bax translocation; ceramide; mitochondrion; sphingomyelinase; tumour necrosis factor alpha (TNF alpha) ID CERAMIDE-INDUCED APOPTOSIS; CELL-PERMEABLE CERAMIDE; CYTOCHROME-C; NEUTRAL SPHINGOMYELINASE; FAMILY PROTEINS; ACTIVATION; INHIBITION; PATHWAY; STRESS; DEATH AB We recently showed that targeting bSMase (bacterial sphingomyelinase) specifically to mitochondria caused accumulation of ceramide in mitochondria, and induced cytochrome c release and cell death [Birbes, El Bawab, Hannun and Obeid (2001) FASEB J., 15, 2669-2679]. In the present study, we investigated the role of this mitochondrial pool of ceramide in response to a receptor-mediated event, namely TNF alpha (tumour necrosis factor alpha), and the involvement of this mitochondrial pool of ceramide in Bax translocation to mitochondria, an event that precedes cytochrome c release. Treatment of MCF7 cells with TNF alpha caused an increase in ceramide levels in the mitochondrial fraction which accompanied Bax translocation to mitochondria. Targeting bSMase to mitochondria specifically resulted in Bax translocation to mitochondria, suggesting that the mitochondrial ceramide pool is involved in Bax translocation. Moreover, in a reconstituted cell-free system, treatment of isolated mitochondria with bSMase enhanced Bax association with mitochondrial membranes. Collectively, these results suggest that the generation of ceramide in mitochondria in response to TNF alpha is sufficient to induce Bax translocation to mitochondria and subsequent cytochrome c release and cell death. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Adm, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RP Obeid, LM (reprint author), Inst Natl Sci Appl, INSERM, U585, F-69621 Villeurbanne, France. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NIA NIH HHS [AG16583, R01 AG016583]; NIDDK NIH HHS [P01 DK059340, DK59340]; NINDS NIH HHS [R01 NS040932] NR 38 TC 91 Z9 94 U1 0 U2 1 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAR 15 PY 2005 VL 386 BP 445 EP 451 DI 10.1042/BJ20041627 PN 3 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 912SJ UT WOS:000228099500005 PM 15516208 ER PT J AU Vidalain, PO AF Vidalain, PO TI On the TRAIL of HIV-induced immunosuppression SO BLOOD LA English DT Editorial Material ID APOPTOSIS; CD4(+); LIGAND; ACTIVATION; CELLS AB Several recent reports have documented the critical contribution of TRAIL to T-cell depletion during HIV infection. In this issue of Blood, Herbeuval and colleagues provide evidence that antigen-presenting cells are a major source of this death ligand when stimulated by HIV particles. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Vidalain, PO (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2005 VL 105 IS 6 BP 2241 EP 2241 DI 10.1182/blood-2004-12-4972 PG 1 WC Hematology SC Hematology GA 906HD UT WOS:000227630500003 ER PT J AU Liu, DX Zhang, D Scafidi, J Wu, X Cramer, CC Davis, AE AF Liu, DX Zhang, D Scafidi, J Wu, X Cramer, CC Davis, AE TI C1 inhibitor prevents Gram-negative bacterial lipopolysaccharide-induced vascular permeability SO BLOOD LA English DT Article ID ENDOTHELIAL BARRIER DYSFUNCTION; ESCHERICHIA-COLI ENDOTOXIN; MULTIPLE ORGAN DYSFUNCTION; APOPTOTIC CELL-DEATH; C1-ESTERASE INHIBITOR; HEREDITARY ANGIOEDEMA; SEPTIC SHOCK; PROTEIN; SEPSIS; COMPLEMENT AB Gram-negative bacterial endotoxemia may lead to the pathological increase of vascular permeability with systemic vascular collapse, a vascular leak syndrome, multiple organ failure (MOF), and/or shock. Previous studies demonstrated that C1 inhibitor (C1INH) protects mice from lipopolysaccharide (LPS)-induced lethal septic shock via a direct interaction with LPS. Here, we report that C1INH blocked the LPS-induced increase in transendothelial flux through an endothelial monolayer. In addition, LPS-mediated detachment of cultured endothelial cells was prevented with C1INH. C1INH also inhibited LPS-induced endothelial cell apoptosis as demonstrated by suppression of DNA fragmentation and annexin V expression. As illustrated by laser scanning confocal microscopy, C1INH completely blocked the binding of fluorescein isothlocyanate (FITC)-LPS to human umbilical vein endothelial cells (HUVECs). C1INH protected from localized LPS-induced increased plasma leakage in C57BL/6J mice and in C1INH-deficient mice. Local vascular permeability in response to LIPS was increased to a greater extent in C1INH-deficient mice compared with wild-type littermate controls and was reversed by treatment with C1 INK Systemic administration of LIPS to mice resulted in increased vascular permeability, which was reduced by C1INH. Therefore, these studies demonstrate that C1INH, in addition to its role in suppression of LPS-mediated macrophage activation, may play an important role in the prevention of LPS-mediated increased vascular permeability, endothelial cell injury, and multiple organ failure. (c) 2005 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Inst Biomed Res, CBR, Boston, MA 02115 USA. Childrens Hosp, CBR, Inst Biomed Res, Boston, MA 02115 USA. RP Davis, AE (reprint author), Harvard Univ, Sch Med, Inst Biomed Res, CBR, 800 Huntington Ave, Boston, MA 02115 USA. EM aldavis@cbr.med.harvard.edu FU NICHD NIH HHS [HD22082, HD33727] NR 45 TC 31 Z9 36 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2005 VL 105 IS 6 BP 2350 EP 2355 DI 10.1182/blood-2004-05-1963 PG 6 WC Hematology SC Hematology GA 906HD UT WOS:000227630500027 PM 15522962 ER PT J AU Hirakawa, S Fujii, S Kajiya, K Yano, K Detmar, M AF Hirakawa, S Fujii, S Kajiya, K Yano, K Detmar, M TI Vascular endothelial growth factor promotes sensitivity to ultraviolet B-induced cutaneous photodamage SO BLOOD LA English DT Article ID TRANSGENIC MICE; MOUSE SKIN; MOLECULAR REGULATION; TOPICAL TRETINOIN; FACTOR EXPRESSION; RANDOMIZED-TRIAL; ANGIOGENESIS; VEGF; UVB; OVEREXPRESSION AB Acute ultraviolet B (UVB) Irradiation of the skin results in erythema, vasodilation, edema, and angiogenesis, which Is associated with the expression of vascular endothelial growth factor (VEGF) by epidermal keratinocytes. It is unclear, however, whether VEGF is required for the damage or repair process that occurs in the skin on UVB exposure. We subjected transgenic mice that overexpress VEGF, and their wild-type littermates, to graded doses of acute UVB irradiation. The skin of VEGF-overexpressing mice was highly photosensitive and became erythematic when exposed to half the UVB dose required to induce erythema In wild-type mice. Erythema was associated with proliferating dermal endothelial cells, cutaneous edema, and inflammatory cell infiltration. When subjected to 10 weeks of low-level UVB irradiation, no major changes were observed in wild-type mice, whereas VEGF transgenic mice developed skin damage associated with degradation of the dermal matrix and enhanced vascularization. Systemic treatment with an anti-VEGF blocking antibody reduced the sensitivity of wild-type mice to acute UVB irradiation without inhibiting post-UVB repair. Our results reveal that VEGF promotes the cutaneous damage that occurs after UVB exposure and that the VEGF signaling pathway might serve as a novel target for the prevention of UVB-induced photodamage. (c) 2005 by The American Society of Hematology. C1 Swiss Fed Inst Technol, Inst Pharmaceut Sci, CH-8093 Zurich, Switzerland. Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Shiseido Life Sci Res Ctr, Yokohama, Kanagawa, Japan. RP Detmar, M (reprint author), Swiss Fed Inst Technol, Inst Pharmaceut Sci, Wolfgang Pauli Str 10,HCI H303, CH-8093 Zurich, Switzerland. EM michael.detmar@pharma.ethz.ch FU NCI NIH HHS [CA69184, CA86410, CA92644] NR 34 TC 34 Z9 35 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2005 VL 105 IS 6 BP 2392 EP 2399 DI 10.1182/blood-2004-06-2435 PG 8 WC Hematology SC Hematology GA 906HD UT WOS:000227630500033 PM 15550485 ER PT J AU Jassal, DS Chiasson, M Rajda, M Ostry, A Legare, JF AF Jassal, DS Chiasson, M Rajda, M Ostry, A Legare, JF TI Isolated pulmonic valve endocarditis SO CANADIAN JOURNAL OF CARDIOLOGY LA English DT Article DE infective endocarditis; pulmonic valve AB A 61-year-old man with no known cardiac history presented with septic arthritis of the right knee secondary to group B Streptococcus. During follow-up, echocardiography revealed a 1.8 cm x 1.2 cm mobile vegetation on the pulmonary valve. Despite parenteral antimicrobial therapy, the patient developed recurrent pulmonary emboli with enlargement of the vegetative mass, necessitating surgical debridement and replacement of the pulmonary valve. A diagnosis of pulmonic valve endocarditis should be considered in the differential diagnosis of any febrile patient with multiple pulmonary emboli. C1 Dalhousie Univ, Cardiol Sect, Dept Med, Halifax, NS, Canada. Dalhousie Univ, Sect Anat Pathol, Dept Pathol, Halifax, NS, Canada. Dalhousie Univ, Dept Surg, Sect Cardiac Surg, Halifax, NS, Canada. RP Jassal, DS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab,Dept Cardiol, VBK-508,55 Fruit St, Boston, MA 02114 USA. EM umjassal@hotmail.com NR 3 TC 4 Z9 4 U1 0 U2 0 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 0828-282X J9 CAN J CARDIOL JI Can. J. Cardiol. PD MAR 15 PY 2005 VL 21 IS 4 BP 365 EP 366 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 910WA UT WOS:000227961700007 PM 15838565 ER PT J AU Jagannath, S Barlogie, B Berenson, JR Singhal, S Alexanian, R Srkalovic, G Orlowski, RZ Richardson, PG Anderson, J Nix, D Esseltine, DL Anderson, KC AF Jagannath, S Barlogie, B Berenson, JR Singhal, S Alexanian, R Srkalovic, G Orlowski, RZ Richardson, PG Anderson, J Nix, D Esseltine, DL Anderson, KC CA SUMMIT CREST Investigators TI Bortezornib in recurrent and/or refractory multiple myeloma - Initial clinical experience in patients with impaired renal function SO CANCER LA English DT Article DE bortezomib; myeloma; proteasome; renal failure ID FAILURE; PHASE-2 AB BACKGROUND. Bortezomib is a potent, reversible proteasome inhibitor that has been approved for the treatment of recurrent and/or refractory multiple myeloma, but its activity in patients with renal impairment has not been studied to date. METHODS. Response rates, safety, and 20S proteasome activity were assessed in relation to baseline creatinine clearance (CrCl) among patients with recurrent and/or refractory myeloma (n. = 256 patients) who were treated with bortezomib in 2 Phase 11 trials. Bortezomib was administered by intravenous bolus on Days 1, 4, 8, and 11 of a 21 -day cycle at 2 doses, 1.0 mg/m(2) (n = 28 patients) and 1.3 mg/m2 (n = 228 patients). RESULTS. Of 10 patients with CrCl less than or equal to 30 mL/mmute, 7 patients completed the protocol -specified 8 cycles of treatment; 4 patients received the 1.3 mg/m(2) bortezomib dose, and 3 patients received the 1.0 mg/m2 bortezomib dose. Using the European Group for Blood and Marrow Transplantation criteria, responses were assigned by an independent committee to 3 of the 10 patients (2 partial responses and 1 minimal response), a response rate similar to that of the overall treated population. Patients with CrCl > 80 mL/minute (n = 105 patients), 51-80 mL/ minute (n = 99 patients), and less than or equal to 50 mL/minute (n = 52 patients) had similar rates of discontinuation and similar adverse event profiles. Renal function did not appear to affect the 1-hour postdose proteasome inhibition or its recovery. CONCLUSIONS. Clinical experience in a limited number of patients with impaired renal function suggests that bortezomib provides clinical benefit with manageable toxicities in this high-risk population. Cancer 2005;103:1195-200. (C) 2005 American Cancer Society. C1 St Vincents Comprehens Canc Ctr, New York, NY 10011 USA. Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Myeloma & Transplantat Res Ctr, Little Rock, AR 72205 USA. Inst Myeloma & Bone Canc Res, W Hollywood, CA USA. Robert H Lurie Canc Ctr, Dept Med, Chicago, IL USA. Univ Texas, MD Anderson Canc Ctr, Lymphoma & Myeloma Ctr, Houston, TX 77030 USA. Cleveland Clin Fdn, Sparrow Canc Ctr, Cleveland, OH 44195 USA. Univ N Carolina, Lineberger Canc Ctr, Dept Med Hematol & Oncol, Chapel Hill, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Millennium Pharmaceut Inc, Oncol Clin Dev, 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 19 TC 152 Z9 168 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2005 VL 103 IS 6 BP 1195 EP 1200 DI 10.1002/cncr.20888 PG 6 WC Oncology SC Oncology GA 903LO UT WOS:000227427600013 PM 15690325 ER PT J AU Drapkin, R von Horsten, HH Lin, YF Mok, SC Crum, CP Welch, WR Hecht, JL AF Drapkin, R von Horsten, HH Lin, YF Mok, SC Crum, CP Welch, WR Hecht, JL TI Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometriold ovarian carcinomas SO CANCER RESEARCH LA English DT Article ID CANDIDATE MOLECULAR MARKERS; GENE-EXPRESSION PROFILES; CDNA MICROARRAY; CANCER; IDENTIFICATION; GLYCOSYLATION; HYBRIDIZATION; TUMORS; MALIGNANCY; INHIBITORS AB Among the genes most commonly identified in gene expression profiles of epithelial ovarian carcinomas (EOC) is the gene for human epididymis protein 4 (HE4). To ascertain its clinical utility, we did a comprehensive assessment of HE4 protein expression in benign and malignant ovarian and nonovarian tissues by immunohistochemistry. In comparison with normal surface epithelium, which does not express HE4 we found that cortical inclusion cysts lined by metaplastic Mullerian epithelium abundantly express the protein. its expression in tumors was restricted to certain histologic subtype: 93% of serous and 100% of endometrioid EOCs expressed HE4, whereas only 50% and 0% of clear cell carcinomas and mucinous tumors, respectively, were positive. Tissue microarrays revealed that the majority of nonovarian carcinomas do not express HE4, consistent with our observation that HE4 protein expression is highly restricted in normal tissue to the reproductive tracts and respiratory epithelium. HE4 is predicted to encode a secreted protein. Using reverse transcription-PCR, we identified ovarian cancer cell lines that endogenously overexpress HE4. Cultured medium from these cells revealed a secreted form of HE4 that is N-glycosylated. This observation is consistent with the recent report that HE4 circulates in the bloodstream of patients with EOC. Therefore, HE4 is a secreted glycoprotein that is overexpressed by serous and endometrioid EOCs. Its expression in cortical inclusion cysts suggests that formation of Mullerian epithelium is a prerequisite step in the development of some types of EOCs. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gynecol Oncol, Lab Gynecol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. Texas Tech Univ, Hlth Sci Ctr, Dept Cell Biol & Biochem, Lubbock, TX 79430 USA. RP Drapkin, R (reprint author), Dana Farber Canc Inst, Dept Canc Biol, SM810,1 Jimmy Fund Way, Boston, MA 02115 USA. EM ronny_drapkin@dfci.harvard.edu RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 41 TC 252 Z9 294 U1 4 U2 23 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2005 VL 65 IS 6 BP 2162 EP 2169 DI 10.1158/0008-5472.CAN-04-3924 PG 8 WC Oncology SC Oncology GA 905VW UT WOS:000227600000018 PM 15781627 ER PT J AU Bai, JR Sui, JH Demirjian, A Vollmer, CM Marasco, W Callery, MP AF Bai, JR Sui, JH Demirjian, A Vollmer, CM Marasco, W Callery, MP TI Predominant Bcl-XL knockdown disables antiapoptotic mechanisms: Tumor necrosis factor-related apoptosis-inducing ligand-based triple chemotherapy overcomes chemoresistance in pancreatic cancer cells in vitro SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; HEAT-SHOCK PROTEINS; ADENOCARCINOMA CELLS; DECOY RECEPTOR; HIGH-TITER; DEATH; EXPRESSION; FAMILY; TRAIL; GENE AB Pancreatic cancer is lethal because of its invasiveness, rapid progression, and profound resistance to chemotherapy and radiation therapy. To identify the molecular mechanisms underlying this, we have examined the expression and potency of three major death receptors: tumor necrosis factor receptor (TNF-R), TNF-related apoptosis-inducing ligand receptor (TRAIL-R), and Fas in mediating cytotoxicity in four invasive pancreatic cancer cell lines. We have analyzed the expression of major antiapoptotic factors, cell cycle regulators and death receptor decoys (DcR) in comparison with normal pancreas tissues and five other human malignant tumor cell lines. We have found that different pancreatic cancer cell lines coexpress high-level TRAIL-R, Fas, and TNF-R1 but are strongly resistant to apoptosis triggered by the death receptors. DcR2 and DcR3 overexpression may partly contribute to the resistance of pancreatic cancer cells to TRAIL-R- and Fas-mediated cytotoxicity. BcI-XL and BcI-2 are predominantly overexpressed in pancreatic cancer cell lines, respectively. Bcl-XL is also predominantly overexpressed in prostate, colorectal, and intestinal cancer cells. The knockdown of the predominant Bcl-XL overexpression significantly reduces the viability of pancreatic cancer cells to TNF alpha- and TRAIL-mediated apoptosis by sublethal-dose single and combined antitumor drugs, including geldanamycin, PS-341, Trichostatin A, and doxorubicine. Geldanamyin and PS-341 synergistically block NF kappa B activation, suppress Akt/PKB pathway, and down-regulate Bcl-XL, Bcl-2, cIAP-1, and cyclin D1 expression. This combined regimen dramatically enhances TRAIL cytotoxic effects and breaks through chemoresistance. Bcl-XL plays a vital role in pancreatic cancer chemoresistance. Geldanamycin, PS-341, and TRAIL triple combination may be a novel therapeutic strategy for pancreatic cancer. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg, Boston, MA 02215 USA. Harvard Univ, Dept Canc Immunol & AIDS, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Bai, JR (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg, Res W 857,330 Brookline Ave, Boston, MA 02215 USA. EM jbai@bidmc.harvard.edu OI SUI, JIANHUA/0000-0002-1272-9662 NR 45 TC 88 Z9 94 U1 0 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 MAR 15 PY 2005 VL 65 IS 6 BP 2344 EP 2352 DI 10.1158/0008-5472.CAN-04-3502 PG 9 WC Oncology SC Oncology GA 905VW UT WOS:000227600000040 PM 15781649 ER PT J AU Li, HJ Kantoff, PW Giovannucci, E Leitzmann, MF Gaziano, JN Stampfer, MJ Ma, J AF Li, HJ Kantoff, PW Giovannucci, E Leitzmann, MF Gaziano, JN Stampfer, MJ Ma, J TI Manganese superoxide dismutase polymorphism, prediagnostic antioxidant status, and risk of clinical significant prostate cancer SO CANCER RESEARCH LA English DT Article ID MITOCHONDRIAL TARGETING SEQUENCE; BETA-CAROTENE SUPPLEMENTATION; BASE-LINE CHARACTERISTICS; BREAST-CANCER; SELENIUM SUPPLEMENTATION; GENETIC POLYMORPHISMS; MNSOD POLYMORPHISM; PHYSICIANS HEALTH; ALPHA-TOCOPHEROL; PREVENTION TRIAL AB Oxidative stress may enhance prostatic carcinogenesis. A polymorphism [valine (V) -> alanine (A)] of manganese superoxide dismutase (MnSOD), the primary antioxidant enzyme in mitochondria, has been recently associated with prostate cancer. We examined the relationship between prostate cancer and the MnSOD polymorphism and its interactions with baseline plasma antioxidant levels (selenium, lycopene, and alpha-tocopherol) and beta-carotene treatment among 567 cases and 764 controls nested in the prospective Physicians' Health Study. We found little overall association between MnSOD polymorphism and prostate cancer risk; however, this polymorphism significantly modified risk of prostate cancer associated with prediagnostic plasma antioxidants (P-interaction <= 0.05). Among men with the AA genotype, high selenium level (4th versus 1st quartile) was associated with a relative risk (RR) of 0.3 [95% confidence interval (CI), 0.2-0.7] for total prostate cancer; for clinically aggressive prostate cancer, the RR was 0.2 (95% CI, 0.1-0.5). In contrast, among men with the VV/VA genotype, the RRs were 0.6 (0.4-1.0) and 0.7 (0.4-1.2) for total and clinically aggressive prostate cancer. These patterns were similar for lycopene and alpha-tocopherol and were particularly strong when these antioxidants and selenium were combined; men with the AA genotype had a 10-fold gradient in risk for aggressive prostate cancer across quartiles of antioxidant status. Men with AA genotype who were randomly assigned to beta-carotene treatment (versus placebo) had a RR of 0.6 (95% CI, 0.2-0.9; P-interaction = 0.03) for fatal prostate cancer, but no significant association was observed in men with the VV/VA genotype. Both endogenous and exogenous antioxidants play an important and interdependent role in preventing clinically significant prostate cancer. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Div Solid Tumor Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Massachusetts Vet Epidemiol Res & Informat Ctr, Vet Adm Boston Healthcare Syst, Boston, MA USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Li, HJ (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, Room 452,181 Longwood Ave, Boston, MA 02115 USA. EM haojie.li@channing.harvard.edu FU NCI NIH HHS [CA42182, CA58684, CA90598, R01 CA097193] NR 34 TC 145 Z9 152 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2005 VL 65 IS 6 BP 2498 EP 2504 DI 10.1158/0008-5472.CAN-04-3535 PG 7 WC Oncology SC Oncology GA 905VW UT WOS:000227600000058 PM 15781667 ER PT J AU Sonel, AF Good, CB Mulgund, J Roe, MT Gibler, WB Smith, SC Cohen, MG Pollack, CV Ohman, EM Peterson, ED AF Sonel, AF Good, CB Mulgund, J Roe, MT Gibler, WB Smith, SC Cohen, MG Pollack, CV Ohman, EM Peterson, ED CA CRUSADE Invest TI Racial variations in treatment and outcomes of black and white patients with high-risk non-ST-elevation acute coronary syndromes - Insights from CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA guidelines?) SO CIRCULATION LA English DT Article DE ethnic groups; coronary disease; therapy; myocardial infarction ID ACUTE MYOCARDIAL-INFARCTION; COOPERATIVE CARDIOVASCULAR PROJECT; PLATELET GLYCOPROTEIN IIB/IIIA; OF-VETERANS-AFFAIRS; MEDICARE PATIENTS; ELDERLY-PATIENTS; REVASCULARIZATION PROCEDURES; CARDIAC-CATHETERIZATION; SOCIOECONOMIC-STATUS; NATIONAL REGISTRY AB Background - Black patients with acute myocardial infarction are less likely than whites to receive coronary interventions. It is unknown whether racial disparities exist for other treatments for non-ST-segment elevation acute coronary syndromes (NSTE ACS) and how different treatments affect outcomes. Methods and Results - Using data from 400 US hospitals participating in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines?) National Quality Improvement Initiative, we identified black and white patients with high-risk NSTE ACS (positive cardiac markers and/or ischemic ST-segment changes). After adjustment for demographics and medical comorbidity, we compared the use of therapies recommended by the American College of Cardiology/American Heart Association guidelines for NSTE ACS and outcomes by race. Our study included 37 813 (87.3%) white and 5504 (12.7%) black patients. Black patients were younger; were more likely to have hypertension, diabetes, heart failure, and renal insufficiency; and were less likely to have insurance coverage or primary cardiology care. Black patients had a similar or higher likelihood than whites of receiving older ACS treatments such as aspirin, beta-blockers, or ACE inhibitors but were significantly less likely to receive newer ACS therapies, including acute glycoprotein IIb/IIIa inhibitors, acute and discharge clopidogrel, and statin therapy at discharge. Blacks were also less likely to receive cardiac catheterization, revascularization procedures, or smoking cessation counseling. Acute risk-adjusted outcomes were similar between black and white patients. Conclusions - Black patients with NSTE ACS were less likely than whites to receive many evidence-based treatments, particularly those that are costly or newer. Longitudinal studies are needed to assess the long-term impact of these treatment disparities on clinical outcomes. C1 Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Duke Clin Res Inst, Div Cardiol, Durham, NC USA. Univ Cincinnati, Sch Med, Cincinnati, OH USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Wayne State Univ, Sch Med, Detroit, MI USA. Penn Hosp, Dept Emergency Med, Philadelphia, PA 19107 USA. RP Sonel, AF (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr Div, 111C-U, Pittsburgh, PA 15240 USA. EM ali.sonel@med.va.gov NR 54 TC 123 Z9 123 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 15 PY 2005 VL 111 IS 10 BP 1225 EP 1232 DI 10.1161/01.CIR.0000157732.03358.64 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 906CB UT WOS:000227617000006 PM 15769762 ER PT J AU Sutton-Tyrrell, K Wildman, RP Matthews, KA Chae, C Lasley, BL Brockwell, S Pasternak, RC Lloyd-Jones, D Sowers, MF Torrens, JI AF Sutton-Tyrrell, K Wildman, RP Matthews, KA Chae, C Lasley, BL Brockwell, S Pasternak, RC Lloyd-Jones, D Sowers, MF Torrens, JI CA SWAN Invest TI Sex hormone-binding globulin and the free androgen index are related to cardiovascular risk factors in multiethnic premenopausal and perimenopausal women enrolled in the study of women across the nation (SWAN) SO CIRCULATION LA English DT Article DE hormones; aging; sex; menopause; risk factors ID POLYCYSTIC-OVARY-SYNDROME; CORONARY-ARTERY DISEASE; ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL WOMEN; HEART-DISEASE; CAROTID ATHEROSCLEROSIS; MENOPAUSAL TRANSITION; INSULIN-RESISTANCE; LIPOPROTEINS; SERUM AB Background - Recent clinical trials have shifted attention away from estrogens and toward androgens and sex hormone - binding globulin (SHBG) as potential mediators of increasing cardiovascular (CV) risk in women at midlife. Methods and Results - The correlation between reproductive hormones and CV risk factors was evaluated in a multiethnic (white, black, Hispanic, Chinese, and Japanese) sample of 3297 premenopausal and perimenopausal women. Testosterone and estradiol (E-2) were evaluated along with SHBG and the free androgen index (FAI), the amount of testosterone not bound by SHBG. Low SHBG and high FAI were strongly and consistently related to elevated CV risk factors (higher insulin, glucose, and hemostatic and inflammatory markers and adverse lipids) even after controlling for body mass index (P < 0.001 for all). Low levels of E-2 were associated with elevated CV risk factors to a lesser degree. These observations were consistent across the 5 ethnic groups. Compared with whites, blacks had higher levels of SHBG and lower levels of FAI, and Chinese had lower levels of SHBG and higher levels of FAI. Conclusions - Low SHBG and high FAI are strongly associated with CV risk factors in racially diverse women, and thus, androgens likely play a role in the CV risk profile of perimenopausal women. C1 Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Univ Calif Davis, Dept Populat Hlth & Reprod, Davis, CA 95616 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. Univ Med & Dent New Jersey, Dept Obstet Gynecol & Womens Hlth, Newark, NJ USA. RP Sutton-Tyrrell, K (reprint author), Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, 127 Parran Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. EM Tyrrell@edc.pitt.edu RI Lloyd-Jones, Donald/C-5899-2009; Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NIA NIH HHS [U01 AG012539, U01 AG012495, U01 AG012505, U01 AG012531, U01 AG012535, U01 AG012546, U01 AG012553, U01 AG012554]; NINR NIH HHS [U01 NR04061] NR 34 TC 193 Z9 198 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 15 PY 2005 VL 111 IS 10 BP 1242 EP 1249 DI 10.1116/01.CIR.0000157697.54255.CE PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 906CB UT WOS:000227617000008 PM 15769764 ER PT J AU Werner, RM Asch, DA Polsky, D AF Werner, RM Asch, DA Polsky, D TI Racial profiling - The unintended consequences of coronary artery bypass graft report cards SO CIRCULATION LA English DT Article DE ethnic groups; revascularization; myocardial infarction ID NEW-YORK-STATE; COMORBIDITY MEASURES; PERFORMANCE REPORTS; HEALTH-CARE; SURGERY; QUALITY; RACE; REVASCULARIZATION; DISPARITIES; INFORMATION AB Background - Although public release of quality information through report cards is intended to improve health care, there may be unintended consequences of report cards, such as physicians avoiding high-risk patients to improve their ratings. If physicians believe that racial and ethnic minorities are at higher risk for poor outcomes, report cards could worsen existing racial and ethnic disparities in health care. Methods and Results - To investigate the impact of New York's CABG report card on racial and ethnic disparities in cardiac care, we estimated differences in the use of CABG, PTCA, and cardiac catheterization between white versus black and Hispanic patients hospitalized for acute myocardial infarction in New York before and after New York's first CABG report card was released, adjusting for patient and hospital characteristics and national changes in racial and ethnic disparities in cardiac care. The racial and ethnic disparity in CABG use significantly increased in New York immediately after New York's CABG report card was released, whereas disparities did not change significantly in the comparison states. There was no differential change in racial and ethnic disparities between New York and the comparison states in the use of cardiac catheterization or PTCA after the CABG report card was released. Over time, this increase in racial and ethnic disparities decreased to levels similar to those before the release of report cards. Conclusions - The release of CABG report cards in New York was associated with a widening of the disparity in CABG use between white versus black and Hispanic patients. C1 Univ Penn, Div Gen Internal Med, Sch Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Dept Hlth Care Syst, Wharton Sch, Philadelphia, PA 19104 USA. RP Werner, RM (reprint author), Univ Penn, Div Gen Internal Med, Sch Med, 1208 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rwerner@wharton.upenn.edu FU AHRQ HHS [2-T32-HS-00009, 1-F32-HS-14644-01] NR 32 TC 138 Z9 139 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 15 PY 2005 VL 111 IS 10 BP 1257 EP 1263 DI 10.1116/01.CIR.000157729.59754.09 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 906CB UT WOS:000227617000010 PM 15769766 ER PT J AU Smith, GL Shlipak, MG Havranek, EP Masoudi, FA McClellan, WM Foody, JM Rathore, SS Krumholz, HM AF Smith, GL Shlipak, MG Havranek, EP Masoudi, FA McClellan, WM Foody, JM Rathore, SS Krumholz, HM TI Race and renal impairment in heart failure - Mortality in blacks versus whites SO CIRCULATION LA English DT Article DE ethnic groups; kidney; heart failure; mortality ID LEFT-VENTRICULAR DYSFUNCTION; CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; RENIN-ANGIOTENSIN SYSTEM; RACIAL-DIFFERENCES; AFRICAN-AMERICANS; UNITED-STATES; RISK-FACTOR; CARDIOVASCULAR-DISEASE; CONTEMPORARY TREATMENT AB Background - Renal impairment is an emerging prognostic indicator in heart failure (HF) patients. Despite known racial differences in the progression of both HF and renal disease, it is unclear whether the prognosis for renal impairment in HF patients differs by race. We sought to determine in HF patients the 1-year mortality risks associated with elevated creatinine and impaired estimated glomerular filtration rate (eGFR) and to quantify racial differences in mortality. Methods and Results - We retrospectively evaluated the National Heart Care Project nationally representative cohort of 53 640 Medicare patients hospitalized with HF. Among 5669 black patients, mean creatinine was 1.6 +/- 0.9 mg/dL, and 54% had an eGFR <= 60, compared with creatinine 1.5 +/- 0.7 mg/dL and 68% eGFR <= 60 in 47 971 white patients. Higher creatinine predicted increased mortality risk, although the magnitude of risk differed by race (interaction P = 0.0001). Every increase in creatinine of 0.5 mg/dL was associated with a > 10% increased risk in adjusted mortality for blacks, compared with > 15% increased risk in whites (interaction P = 0.0001), with the most striking racial disparities at the highest levels of renal impairment. Depressed eGFR showed similar racial differences (interaction P = 0.0001). Conclusions - Impaired renal function predicts increased mortality in elderly HF patients, although risks are more pronounced in whites. Distinct morbidity and mortality burdens in black versus white patients underscore the importance of improving patient risk-stratification, defining optimal therapies, and exploring physiological underpinnings of racial differences. C1 Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, Sect Cardiovasc Med,Dept Int Med, New Haven, CT 06520 USA. San Francisco VA Med Ctr, Gen Internal Med Sect, Med Serv, San Francisco, CA USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Denver Hlth Med Ctr, Div Cardiol, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Div Cardiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Div Geriatr Med, Denver, CO 80262 USA. Colorado Fdn Med Care, Aurora, CO USA. Emory Univ, Sch Med, Div Renal, Dept Med, Atlanta, GA USA. Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. RP Krumholz, HM (reprint author), Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, Sect Cardiovasc Med,Dept Int Med, Sterling Hall Med,I Wing,Suite 456,333 Cedar St, New Haven, CT 06520 USA. EM harlan.krumholz@yale.edu FU NIA NIH HHS [K08-AG01011, K08-AG20623-01]; NIGMS NIH HHS [GM-07205] NR 50 TC 50 Z9 53 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 15 PY 2005 VL 111 IS 10 BP 1270 EP 1277 DI 10.1161/01.CIR.0000158131.7881.D5 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 906CB UT WOS:000227617000012 PM 15769768 ER PT J AU Gu, ZN Rubin, MA Yang, Y Deprimo, SE Zhao, HJ Horvath, S Brooks, JD Loda, M Reiter, RE AF Gu, ZN Rubin, MA Yang, Y Deprimo, SE Zhao, HJ Horvath, S Brooks, JD Loda, M Reiter, RE TI Reg IV: A promising marker of hormone refractory metastatic prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION; PROTEIN; FAMILY; DELINEATION; BIOMARKERS; RACEMASE; ANTIGEN; TISSUE; MEMBER; TUMORS AB The diagnosis and management of prostate cancer is hampered by the absence of markers capable of identifying patients with metastatic disease. In order to identify potential new markers for prostate cancer, we compared gene expression signatures of matched androgen-dependent and hormone refractory prostate cancer xenografts. One candidate gene overexpressed in a hormone refractory xenograft was homologous to the regenerating protein gene family, a group of secreted proteins expressed in the gastrointestinal tract and overexpressed in inflammatory bowel disease and cancer. This gene, Reg IV, was confirmed to be differentially expressed in the LAPC-9 hormone refractory xenograft. Consistent with its up-regulation in a hormone refractory xenograft, it is expressed in several prostate tumors after neoadjuvant hormone ablation therapy. As predicted by its sequence homology, it is secreted from transiently transfected cells. It is also expressed strongly in a majority of hormone refractory metastases represented on two high-density tissue microarrays. In comparison, it is not expressed by any normal prostate specimens and only at low levels in similar to 40% of primary tumors. These data support Reg IV as a candidate marker for hormone refractory metastatic prostate cancer. C1 Univ Calif Los Angeles, Hlth Sci Ctr, Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Hlth Sci Ctr, Geffen Sch Med, Dept Stat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Hlth Sci Ctr, Geffen Sch Med, Inst Mol Biol, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Stanford Univ, Dept Urol, Sch Med, Stanford, CA 94305 USA. RP Reiter, RE (reprint author), Univ Calif Los Angeles, Hlth Sci Ctr, Geffen Sch Med, Dept Urol, 66-128,10833 Conte Ave, Los Angeles, CA 90095 USA. EM rreiter@mednet.ucla.edu OI Rubin, Mark/0000-0002-8321-9950 NR 24 TC 37 Z9 42 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2005 VL 11 IS 6 BP 2237 EP 2243 DI 10.1158/1078-0432.CCR-04-0356 PG 7 WC Oncology SC Oncology GA 908EK UT WOS:000227770000019 PM 15788672 ER PT J AU Nutt, CL Betensky, RA Brower, MA Batchelor, TT Louis, DN Stemmer-Rachamimov, AO AF Nutt, CL Betensky, RA Brower, MA Batchelor, TT Louis, DN Stemmer-Rachamimov, AO TI YKL-40 is a differential diagnostic marker for histologic subtypes of high-grade gliomas SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN CARTILAGE GP-39; CHITINASE PROTEIN FAMILY; SERUM YKL-40; DISEASE-ACTIVITY; GENETIC-MARKERS; CELLS; OLIGODENDROGLIOMA; CLASSIFICATION; MACROPHAGES; EXPRESSION AB Purpose and Experimental Design: In modern neurooncology, no variable affects therapeutic decisions and prognostic estimation more than tumor classification. We showed recently that class prediction models, based on gene expression profiles, classify diagnostically challenging malignant gliomas in a manner that better correlates with clinical outcome than standard pathology. In the present study, we used immunohistochemistry to investigate YKL-40 protein expression in independent sets of glioblastomas and anaplastic oligodendrogliomas to determine whether this single marker can aid classification of these high-grade gliomas. Results and Conclusions: Glioblastomas show strikingly more YKL-40 expression than anaplastic oligodendrogliomas. Only 2 of 37 glioblastomas showed completely negative YKL-40 staining in both tumor cells and extracellular matrix, whereas 18 of 29 anaplastic oligodendrogliomas were completely negative in non-microgemistocytic tumor cells and extracellular matrix. Tumor cell staining intensity was also markedly different: 84% of glioblastomas showed strong staining intensities of 2+ or 3+ whereas 76% of anaplastic oligodendrogliomas either did not stain or stained at only 1+. YKL-40 staining provided a better class distinction of glioblastoma versus anaplastic oligodendroglioma than glial fibrillary acidic protein, the current standard immunohistochemical marker used to distinguish diagnostically challenging gliomas. Moreover, a combination of YKL-40 and glial fibrillary acidic protein immunohistochemistry afforded even greater diagnostic accuracy in anaplastic oligodendrogliomas. C1 Massachusetts Gen Hosp, Mol Pathol Unit, Dept Pathol, Ctr Canc, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neurosurg Serv, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Brain Tumor Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Dept Pathol, Ctr Canc, CNY7,149 13th St, Charlestown, MA 02129 USA. EM dlouis@partners.org RI Nutt, Catherine/K-8794-2012 FU NCI NIH HHS [CA 57683] NR 33 TC 72 Z9 73 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2005 VL 11 IS 6 BP 2258 EP 2264 DI 10.1158/1078-0432.CCR-04-1601 PG 7 WC Oncology SC Oncology GA 908EK UT WOS:000227770000022 PM 15788675 ER PT J AU Strahilevitz, J Rahav, G Schroers, HJ Summerbell, RC Amitai, Z Goldschmied-Reouven, A Rubinstein, E Schwammenthal, Y Feinberg, MS Siegman-Igra, Y Bash, E Polacheck, I Zelazny, A Howard, SJ Cibotaro, P Shovman, O Keller, N AF Strahilevitz, J Rahav, G Schroers, HJ Summerbell, RC Amitai, Z Goldschmied-Reouven, A Rubinstein, E Schwammenthal, Y Feinberg, MS Siegman-Igra, Y Bash, E Polacheck, I Zelazny, A Howard, SJ Cibotaro, P Shovman, O Keller, N TI An outbreak of Phialemonium infective endocarditis linked to intracavernous penile injections for the treatment of impotence SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID FUNGAL ENDOCARDITIS; ERECTILE DYSFUNCTION; VALVE ENDOCARDITIS; SELF-INJECTION; THERAPY AB Background. In March 2002, a patient in Tel Aviv, Israel, died of endocarditis caused by Phialemonium curvatum. As part of his therapy for erectile dysfunction, the patient had been trained to self-inject a compound of vasoactive drugs provided by an impotence clinic into his penile corpus cavernosous. Methods. We identified the used prefilled syringes as the source of his infection. Similar cases were investigated as a putative outbreak of P. curvatum invasive disease among customers of this impotence clinic. P. curvatum isolates, cultured from samples obtained from the patients and from prefilled syringes, were compared by DNA sequencing of the nuclear ribosomal internal transcribed spacer. Results. We identified 2 additional customers at the impotence clinic who had P. curvatum endocarditis. In addition, cultures of unused, prefilled syringes and bottles provided by the same clinic to 5 asymptomatic customers tested positive for pathogenic molds ( P. curvatum in 4 cases and Paecilomyces lilacinus in 1). All P. curvatum isolates were of a single genetic type that is known only from this outbreak but is closely related to 3 other P. curvatum genotypes associated with pathogenicity in humans. Conclusions. P. curvatum is an emerging pathogen that can be readily isolated from blood. We identified an outbreak of P. curvatum endocarditis among men who had erectile dysfunction treated by intracavernous penile injections from contaminated prefilled syringes. C1 Tel Aviv Univ, Sackler Sch Med, Chaim Sheba Med Ctr, Infect Dis Unit, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, Chaim Sheba Med Ctr, Microbiol Lab, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, Chaim Sheba Med Ctr, Dept Neurol, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, Chaim Sheba Med Ctr, Dept Med B, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, Chaim Sheba Med Ctr, Inst Heart, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, Chaim Sheba Med Ctr, Sourasky Med Ctr,Infect Dis Unit & Microbiol Lab, IL-69978 Tel Aviv, Israel. Minist Hlth, Dist Hlth Off, Tel Aviv, Israel. Hebrew Univ Jerusalem, Hadassah Med Ctr, Dept Clin Microbiol & Infect Dis, Jerusalem, Israel. CBS Fungal Biodivers Ctr, Utrecht, Netherlands. Hope Hosp, Reg Mycol Reference Ctr, Salford M6 8HD, Lancs, England. RP Strahilevitz, J (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM jstrahilevitz@partners.org NR 26 TC 25 Z9 25 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2005 VL 40 IS 6 BP 781 EP 786 DI 10.1086/428045 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JP UT WOS:000227492800001 PM 15736008 ER PT J AU Kassutto, S Johnston, MN Rosenberg, ES AF Kassutto, S Johnston, MN Rosenberg, ES TI Incomplete HIV type 1 antibody evolution and seroreversion in acutely infected individuals treated with early antiretroviral therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MYCOPHENOLATE-MOFETIL; AIDS; AVIDITY; INFANTS; ABSENCE AB Background. The diagnosis of human immunodeficiency virus type 1 (HIV-1) infection by standard tests relies on the formation of HIV-1-specific antibodies. Early treatment of acute HIV-1 infection may have unique immunologic effects on host cellular and humoral responses. Rare cases of HIV-1 seroreversion have been reported for patients with advanced or rapidly progressive disease. Here, we report seroreversion that occurred in subjects with acute HIV-1 infection who initiated early antiretroviral therapy. Methods. A total of 150 patients with symptomatic acute or early onset HIV-1 infection that was treated with antiretroviral therapy were observed prospectively by means of monthly clinical and laboratory evaluation, which included serial HIV enzyme- linked immunosorbent assay and Western blots, until a fully evolved HIV-1 antibody response was documented. Results. Three patients who initiated antiretroviral therapy a mean interval of 8 days ( range, 1 - 16 days) after presentation and were observed for a mean duration of 50.2 months ( range, 40.2 - 55.7 months) did not develop a fully evolved HIV-1 antibody response or demonstrated complete or partial HIV-1 seroreversion, despite maintenance of cytomegalovirus-specific humoral responses. Virologic suppression and seroreversion (complete or partial) occurred a mean duration of 4.1 months ( range, 2.3 - 5.7 months) and 15.5 months ( range, 6.7-26.3 months), respectively, after the initiation of therapy. All patients maintained complete virologic suppression while receiving therapy and had an undetectable HIV-1 RNA load at the time of seroreversion. Conclusions. Early antiretroviral therapy associated with durable virologic suppression in acute HIV-1 infection may abrogate the formation or detection of HIV-1-specific antibodies. Ongoing antigenic stimulation may be required to maintain HIV-1-specific humoral responses. Incomplete evolution of the HIV-1 antibody response and/or presence of seroreversion (although infrequently observed) underscore the potential unique immunologic effect of early antiretroviral therapy in patients with primary HIV-1 infection. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. RP Rosenberg, ES (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Gray J-504,55 Fruit St, Boston, MA 02114 USA. EM erosenberg1@partners.org FU NIAID NIH HHS [AI040873, R01 AI040873, T-32 AI007433, T32 AI007433] NR 21 TC 38 Z9 39 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2005 VL 40 IS 6 BP 868 EP 873 DI 10.1086/428127 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JP UT WOS:000227492800015 PM 15736021 ER PT J AU Chen, B Pogue, BW Hoopes, PJ Hasan, T AF Chen, B Pogue, BW Hoopes, PJ Hasan, T TI Combining vascular and cellular targeting regimens enhances the efficacy of photodynamic therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE photodynamic therapy; verteporfin; vascular targeting; cellular targeting ID MOUSE-TUMOR MODEL; BENZOPORPHYRIN DERIVATIVE BPD; PROSTATE-CANCER; SOLID TUMORS; PHOTOSENSITIZER; VERTEPORFIN; HYPERICIN; VESSELS; BIODISTRIBUTION; HYPERTHERMIA AB Purpose: Photodynamic therapy (PDT) can be designed to target either tumor vasculature or tumor cells by varying the drug-light interval. Photodynamic therapy treatments with different drug-light intervals can be combined to increase tumor response by targeting both tumor vasculature and tumor cells. The sequence of photosensitizer and light delivery can influence the effect of combined treatments. Methods and Materials: The R3327-MatLyLu rat prostate tumor model was used in this study. Photosensitizer verteporfin distribution was quantified by fluorescence microscopy. Tumor blood flow changes were monitored by laser-Doppler system and tumor hypoxia was quantified by the immunohistochemical staining for the hypoxic marker EF5. The therapeutic effects of PDT treatments were evaluated by the histologic examination and tumor regrowth assay. Results: Fluorescence microscopic studies indicated that tumor localization of verteporfin changed from predominantly within the tumor vasculature at 15 min after injection, to being throughout the tumor parenchyma at 3 h after injection. Light treatment (50 J/cm(2)) at 15 min after verteporfin injection (0.25 mg/kg, i.v.) induced significant tumor vascular damage, as manifested by tumor blood flow reduction and increase in the tumor hypoxic fraction. In contrast, the vascular effect observed after the same light dose (50 j/cm(2)) delivered 3 It after administration of verteporfin (1 mg/kg, i.v.) was an initial acute decrease in blood flow, followed by recovery to the level of control. The EF5 staining revealed no significant increase in hypoxic fraction at I h after PDT using 3 h drug-light interval. The combination of 3-h interval PDT and 15-min interval PDT was more effective in inhibiting tumor growth than each individual PDT treatment. However, it was found that the combined treatment with the sequence of 3-h interval PDT before 15-min interval PDT led to a superior antitumor effect than the other combinative PDT treatments. Histologic studies confirmed that this combined treatment led to damage to both tumor vasculature and tumor cells. Importantly, the combined PDT treatment did not increase normal tissue damage and tissue recovered well at 60 days after treatment. Conclusions: Our results suggest that targeting both tumor vascular and cellular compartments by combining a long-interval PDT with a short-interval PDT can be an effective and safe way to enhance PDT damage to tumor tissue. (c) 2005 Elsevier Inc. C1 Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Dartmouth Coll Sch Med, Dept Surg, Lebanon, NH USA. RP Pogue, BW (reprint author), Dartmouth Coll, Thayer Sch Engn, 8000 Cummings Hall, Hanover, NH 03755 USA. EM pogue@dartmouth.edu FU NCI NIH HHS [P01CA84203] NR 42 TC 78 Z9 79 U1 3 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2005 VL 61 IS 4 BP 1216 EP 1226 DI 10.1016/j.ijrobp.2004.08.006 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 905XI UT WOS:000227604200031 PM 15752904 ER PT J AU Stuart, LM Takahashi, K Shi, L Savill, J Ezekowitz, RAB AF Stuart, LM Takahashi, K Shi, L Savill, J Ezekowitz, RAB TI Mannose-binding lectin-deficient mice display defective apoptotic cell clearance but no autoimmune phenotype SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; IMMUNE-RESPONSES; INNATE IMMUNITY; C1Q DEFICIENCY; IN-VITRO; B1 CELLS; ANTIBODIES; DISEASE; COMPLEMENT; GENE AB Mannose-binding lectin (MBL) is a circulating serum protein that is sequestered to sites of inflammation and infection. MBL is a member of the collectin family with structural similarities to the lung collectins and functional similarities to C1q. Both MBL and C1q activate complement; C1q activates the classical pathway and MBL the lectin pathway. Here we demonstrate that MBL binds apoptotic cells in vitro and confirm a role for MBL in clearance of apoptotic cells in vivo. Despite MBL null mice demonstrating defective apoptotic cell clearance they did not develop spontaneous autoimmunity, lymphoproliferation, or germinal center expansion although increased numbers of peritoneal B1 cells were detected. These data demonstrate an important in vivo role for MBL in clearance of dying cells and adds the MBL null animals to the few animals with demonstrable in vivo apoptotic cell clearance defects. Moreover, it demonstrates that failure of apoptotic cell clearance can be dissociated from autoimmunity. C1 Harvard Univ, Massachusetts Gen Hosp, Lab Dev Immunol, Dept Pediat, Boston, MA 02114 USA. Univ Edinburgh, Ctr Inflammat Res, MRC, Edinburgh, Midlothian, Scotland. RP Stuart, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Lab Dev Immunol, Dept Pediat, Jackson 14,55 Fruit St, Boston, MA 02114 USA. EM lstuart@partners.org FU NIAID NIH HHS [P01 AI52343-03, R01 AI42788] NR 36 TC 143 Z9 153 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2005 VL 174 IS 6 BP 3220 EP 3226 PG 7 WC Immunology SC Immunology GA 904PT UT WOS:000227510900014 PM 15749852 ER PT J AU Attinger, A Devine, L Wang-Zhu, Y Martin, D Wang, JH Reinherz, EL Kronenberg, M Cheroutre, H Kavathas, P AF Attinger, A Devine, L Wang-Zhu, Y Martin, D Wang, JH Reinherz, EL Kronenberg, M Cheroutre, H Kavathas, P TI Molecular basis for the high affinity interaction between the thymic leukemia antigen and the CD8 alpha alpha molecule SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-I MOLECULE; INTESTINAL EPITHELIAL-CELLS; CYTOTOXIC T-LYMPHOCYTES; EXPRESSION; CD8; MHC; PEPTIDES; COMPLEX; MEMORY; ACTIVATION AB The mouse thymic leukemia (TL) Ag is a nonclassical MHC class I molecule that binds with higher affinity to CD8alphaalpha than CD8alphabeta. The interaction of CD8alphaalpha with TL is important for lymphocyte regulation in the intestine. Therefore, we studied the molecular basis for TL Ag binding to CD8alphaalpha. The stronger affinity of the TL Ag for CD8alphaalpha is largely mediated by three amino acids on exposed loops of the conserved alpha(3) domain. Mutant classical class I molecules substituted with TL Ag amino acids at these positions mimic the ability to interact with CD8alphaalpha and modulate lymphocyte function. These data indicate that small changes in the alpha(3) domain of class I molecules potentially can have profound physiologic consequences. C1 Yale Univ, Dept Lab Med, Sch Med, New Haven, CT 06520 USA. Yale Univ, Immunobiol Sect, Sch Med, New Haven, CT 06520 USA. La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. RP Kavathas, P (reprint author), Yale Univ, Dept Lab Med, Sch Med, 300 Cedar St,TAC,S641A, New Haven, CT 06520 USA. EM paula.kavathas@yale.edu FU NCI NIH HHS [CA048115]; NIAID NIH HHS [AI40617, AI50263]; NIDDK NIH HHS [DK54451]; NIGMS NIH HHS [GM56008] NR 36 TC 19 Z9 19 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2005 VL 174 IS 6 BP 3501 EP 3507 PG 7 WC Immunology SC Immunology GA 904PT UT WOS:000227510900048 PM 15749886 ER PT J AU Thompson, CR Iyer, SS Melrose, N VanOosten, R Johnson, K Pitson, SM Obeid, LM Kusner, DJ AF Thompson, CR Iyer, SS Melrose, N VanOosten, R Johnson, K Pitson, SM Obeid, LM Kusner, DJ TI Sphingosine kinase 1 (SK1) is recruited to nascent phagosomes in human macrophages: Inhibition of SK1 translocation by Mycobacterium tuberculosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DEPENDENT SIGNAL-TRANSDUCTION; INTRACELLULAR CA2+ STORES; FUNCTIONAL-CHARACTERIZATION; MOLECULAR-CLONING; J774 MACROPHAGES; LYSOSOME FUSION; SPHINGOSINE-1-PHOSPHATE RECEPTORS; MATURATION ARREST; HUMAN-NEUTROPHILS; PLASMA-MEMBRANE AB Mycobacterium tuberculosis (M.tb) is a leading cause of global infectious mortality. The pathogenesis of tuberculosis involves inhibition of phagosome maturation, leading to survival of M.tb within human macrophages. A key determinant is M.tb-induced inhibition of macrophage sphingosine kinase (SK) activity, which normally induces Ca2+ signaling and phagosome maturation. Our objective was to determine the spatial localization of SK during phagocytosis and its inhibition by M.tb. Stimulation of SK activity by killed M.tb, live Staphylococcus aureus, or latex beads was associated with translocation of cytosolic SKI to the phagosome membrane. In contrast, SK1 did not associate with phagosomes containing live M.tb. To characterize the mechanism of phagosomal translocation, live cell confocal microscopy was used to compare the localization of wild-type SKI, catalytically inactive SK1(G82D), and a phosphorylation-defective mutant that does not undergo plasma membrane translocation (SK1(S225A)). The magnitude and kinetics of translocation of SK1(G82D) and SK1(S225A) to latex bead phagosomes were indistinguishable from those of wild-type SKI, indicating that novel determinants regulate the association of SKI with nascent phagosomes. These data are consistent with a model in which M.tb inhibits both the activation and phagosomal translocation of SK1 to block the localized Ca2+ transients required for phagosome maturation. The Journal of Immunology, 2005, 174: 3551-3561. C1 Univ Iowa, Carver Coll Med, Dept Internal Med, Inflammat Program,Div Infect Dis, Coralville, IA 52241 USA. Univ Iowa, Carver Coll Med, Dept Physiol & Biophys, Coralville, IA 52241 USA. Univ Iowa, Carver Coll Med, Grad Program Immunol, Coralville, IA 52241 USA. Univ Iowa, Carver Coll Med, Grad Program Mol Biol, Coralville, IA 52241 USA. Vet Affairs Med Ctr, Iowa City, IA 52242 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Inst Med & Vet Sci, Div Human Immunol, Hanson Inst, Adelaide, SA 5000, Australia. RP Kusner, DJ (reprint author), Univ Iowa, Carver Coll Med, Dept Internal Med, Inflammat Program,Div Infect Dis, 2501 Crosspk Rd,D156-MTF, Coralville, IA 52241 USA. EM david-kusner@uiowa.edu OI obeid, lina/0000-0002-0734-0847 FU NIAID NIH HHS [R01 AI055916]; NIGMS NIH HHS [R01 GM062887, R01 GM62302] NR 54 TC 60 Z9 67 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2005 VL 174 IS 6 BP 3551 EP 3561 PG 11 WC Immunology SC Immunology GA 904PT UT WOS:000227510900054 PM 15749892 ER PT J AU Allen, L Dockrell, DH Pattery, T Lee, DG Cornelis, P Hellewell, PG Whyte, MKB AF Allen, L Dockrell, DH Pattery, T Lee, DG Cornelis, P Hellewell, PG Whyte, MKB TI Pyocyanin production by Pseudomonas aeruginosa induces neutrophil apoptosis and impairs neutrophil-mediated host defenses in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROLONGED INFLAMMATORY RESPONSE; VENTILATOR-ASSOCIATED PNEUMONIA; AIRWAY EPITHELIAL-CELLS; FC-GAMMA-RIII; CYSTIC-FIBROSIS; LEUKOCYTE RECRUITMENT; SOLUBLE RECEPTOR; IL-6; INTERLEUKIN-8; EXPRESSION AB Clearance of neutrophils from inflamed sites is critical for resolution of inflammation, but pathogen-driven neutrophil apoptosis can impair host defenses. We previously showed that pyocyanin, a phenazine toxic metabolite produced by Pseudomonas aeruginosa, accelerates neutrophil apoptosis in vitro. We compared wild-type and pyocyanin-deficient strains of P. aeruginosa in a murine model of acute pneumonia. Intratracheal instillation of either strain of P. aeruginosa caused a rapid increase in bronchoalveolar lavage neutrophil counts up to 18 h after infection. In wild-type infection, neutrophil numbers then declined steadily, whereas neutrophil numbers increased up to 48 h in mice infected with pyocyanin-deficient P. aeruginosa. In keeping with these differences, pyocyanin production was associated with reduced bacterial clearance from the lungs. Neutrophil apoptosis was increased in mice infected with wild-type compared with the phenazine-deficient strain or two further strains that lack pyocyanin production, but produce other phenazines. Concentrations of potent neutrophil chemokines (MIP-2, KC) and cytokines (IL-6, IL-113) were significantly lower in wild-type compared with phenazine-deficient strain-infected mice at 18 h. We conclude that pyocyanin production by P. aeruginosa suppresses the acute inflammatory response by pathogen-driven acceleration of neutrophil apoptosis and by reducing local inflammation, and that this is advantageous for bacterial survival. The Journal of Immunology, 2005, 174: 3643-3649. C1 Univ Sheffield, Cardiovasc Res Unit, Div Clin Sci N, Sheffield S10 2TN, S Yorkshire, England. Univ Sheffield, Acad Unit Infect Dis, Sheffield S10 2TN, S Yorkshire, England. Univ Sheffield, Acad Unit Resp Med, Div Genom Med, Sheffield S10 2TN, S Yorkshire, England. Free Univ Brussels VIB, Lab Microbial Interact, Dept Mol & Cellular Interact, Brussels, Belgium. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Whyte, MKB (reprint author), Univ Sheffield, Sch Med & Biomed Sci, Acad Unit Resp Med, Royal Hallamshire Hosp, Sheffield S10 2JF, S Yorkshire, England. EM m.k.whyte@sheffield.ac.uk RI Whyte, Moira/E-6210-2010 NR 58 TC 86 Z9 89 U1 1 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2005 VL 174 IS 6 BP 3643 EP 3649 PG 7 WC Immunology SC Immunology GA 904PT UT WOS:000227510900064 PM 15749902 ER PT J AU Liang, MD Bagchi, A Warren, HS Tehan, MM Trigilio, JA Beasley-Topliffe, LK Tesini, BL Lazzaroni, JC Fenton, MJ Hellman, J AF Liang, MD Bagchi, A Warren, HS Tehan, MM Trigilio, JA Beasley-Topliffe, LK Tesini, BL Lazzaroni, JC Fenton, MJ Hellman, J TI Bacterial peptidoglycan-associated lipoprotein: A naturally occurring toll-like receptor 2 agonist that is shed into serum and has synergy with lipopolysaccharide SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 27th Annual Conference of the Shock-Society CY JUN 05-08, 2004 CL Halifax, CANADA SP Shock Soc ID TOLL-LIKE RECEPTORS; MEMBRANE PROTEIN-A; NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; GRAM-NEGATIVE SEPSIS; ESCHERICHIA-COLI J5; OUTER-MEMBRANE; MUREIN LIPOPROTEIN; SIGNAL-TRANSDUCTION; LIPOTEICHOIC ACID AB Sepsis is initiated by interactions between microbial products and host inflammatory cells. Toll-like receptors (TLRs) are central innate immune mediators of sepsis that recognize different components of microorganisms. Peptidoglycan-associated lipoprotein ( PAL) is a ubiquitous gram-negative bacterial outer-membrane protein that is shed by bacteria into the circulation of septic animals. We explored the inflammatory effects of purified PAL and of a naturally occurring form of PAL that is shed into serum. PAL is released into human serum by Escherichia coli bacteria in a form that induces cytokine production by macrophages and is tightly associated with lipopolysaccharide (LPS). PAL activates inflammation through TLR2. PAL and LPS synergistically activate macrophages. These data suggest that PAL may play an important role in the pathogenesis of sepsis and imply that physiologically relevant PAL and LPS are shed into serum and act in concert to initiate inflammation in sepsis. C1 Boston Univ, Med Ctr, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Univ Maryland, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21201 USA. Univ Lyon 1, Lab Microbiol & Genet Mol, F-69365 Lyon, France. RP Hellman, J (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 149 13th St, Charlestown, MA 02129 USA. EM jhellman@partners.org FU NIAID NIH HHS [AI01722, AI58106]; NIGMS NIH HHS [GM59694] NR 58 TC 60 Z9 63 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 15 PY 2005 VL 191 IS 6 BP 939 EP 948 DI 10.1086/427815 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 902UH UT WOS:000227381600016 PM 15717270 ER PT J AU Dracheva, S McGurk, SR Haroutunian, V AF Dracheva, S McGurk, SR Haroutunian, V TI MRNA expression of AMPA receptors and AMPA receptor binding proteins in the cerebral cortex of elderly schizophrenics SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE AMPA receptors; AMPA receptor binding proteins; mRNA expression; real-time PCR; schizophrenia; dorsolateral prefrontal cortex; occipital cortex ID IONOTROPIC GLUTAMATE RECEPTORS; SYNAPSE-ASSOCIATED PROTEIN-97; DORSOLATERAL PREFRONTAL CORTEX; DOMAIN-CONTAINING PROTEIN; SUBUNIT EXPRESSION; MOLECULAR BEACONS; IMMUNOCYTOCHEMICAL LOCALIZATION; DIFFERENTIAL PALMITOYLATION; NEUROPSYCHIATRIC DISORDERS; INTERACTING PROTEIN AB L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate the majority of the fast excitatory transmission in the CNS. To determine whether gene expression of AMPARs and/or AMPAR binding proteins, which control response/sensitivity of AMPAR-bearing neurons to glutamate, are altered in schizophrenia, mRNA expression and abundance of AMPAR subunits (GluR1-4) and several AMPAR binding proteins (SAP97, PICK1, GRIP, ABP) were measured in the dorsolateral prefrontal cortex (DLPFC) and the occipital cortex of elderly schizophrenia patients (n = 36) and matched normal controls (n - 26) by quantitative real-time PCR. The mRNA expression of GluR1, GluR4, and GRIP in the DLPFC and expression of the GluR4, GRIP, and ABP in the occipital cortex were significantly elevated in schizophrenics. GluR1 and ABP mRNA expression in the occipital cortex and GluR2, GluR3, SAP97, and PICK1 expression in either cortical area were not significantly altered. The data also demonstrated significant differences in the abundances of mRNAs encoding GluR1-4 subunits (GluR2 > GluR3 > GluR1 > GluR4) and of AMPAR binding proteins (SAP97 > PICK1 > GRIP > ABP) in both diagnostic groups. GluR2 (58-64%) and GluR3 (24-29%) were the major components of the AMPAR mRNA in both cortical areas, implying that the major AMPAR complexes in the human cortex are probably those containing GluR2 and GluR3 subunits. Small but significant differences in the amounts of GluR2, GluR3, and GRIP mRNAs were detected between the two cortical areas: more GluR3 and GRIP but less GluR2 were detected in the DLPFC than in the occipital cortex. (C) 2005 Wiley-Liss, Inc. C1 Bronx Vet Adm Med Ctr, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Haroutunian, V (reprint author), Bronx Vet Adm Med Ctr, 3F-02,1300 W Kingsbridge Rd, Bronx, NY 10468 USA. EM vahram.haroutunian@mssm.edu FU NIMH NIH HHS [R01-MH064673, MH45212] NR 85 TC 59 Z9 61 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAR 15 PY 2005 VL 79 IS 6 BP 868 EP 878 DI 10.1002/jnr.20423 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 902NV UT WOS:000227364700015 PM 15696539 ER PT J AU Yoerger, DM Marcus, F Sherrill, D Calkins, H Towbin, JA Zareba, W Picard, MH AF Yoerger, DM Marcus, F Sherrill, D Calkins, H Towbin, JA Zareba, W Picard, MH CA Multidisciplinary Study Right Ven TI Echocardiographic findings in patients meeting task force criteria for arrhythmogenic right ventricular dysplasia - New insights from the multidisciplinary study of right ventricular dysplasia SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CARDIOMYOPATHY; DIAGNOSIS; DYSPLASIA/CARDIOMYOPATHY; REGURGITATION AB OBJECTIVES The purpose of this study was to quantify the echocardiographic abnormalities in probands who were newly diagnosed with arrhythmogenic right ventricular dysplasia (ARVD). BACKGROUND The diagnosis of ARVD remains challenging. The Multidisciplinary Study of Right Ventricular Dysplasia was initiated to characterize the cardiac structural, clinical, and genetic aspects of ARVD. METHODS Detailed echocardiograms were performed in 29 probands and compared with echoes from 29 normal control patients matched for age, gender, body size, and year of echo. Right atrial (RA) and right ventricular (RV) chamber dimensions, RV regional function, and the presence of morphologic abnormalities (hyper-reflective moderator band, trabecular derangement, and sacculations) were assessed. The RV systolic function was calculated as RV fractional area change (FAC). RESULTS The RV dimensions were significantly increased, and RV FAC was significantly decreased in probands versus control patients (27.2 +/- 16 mm vs. 41.0 +/- 7.1 mm, p = 0.0003). The right ventricular outflow tract (RVOT) was the most commonly enlarged dimension in ARVD probands (37.9 +/- 6.6 mm) versus control patients (26.2 +/- 4.9 mm, p < 0.00001). A RVOT long-axis diastolic dimension > 30 mm occurred in 89% of probands and 14% of controls. The RV morphologic abnormalities were present in many probands (trabecular derangement in 54%, hyper-reflective moderator band in 34% and sacculations in 17%) but not in controls. CONCLUSIONS Probands with ARVD have significant RA and RV enlargement and decreased RV function, which can be easily assessed on standard echocardiographic imaging. These parameters should be measured when ARVD is suspected and compared with normal values. (c) 2005 by the American College of Cardiology Foundation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Univ Arizona, Tucson, AZ USA. Johns Hopkins Univ, Baltimore, MD USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Rochester, Rochester, NY USA. RP Yoerger, DM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, YAW 5,55 Fruit St, Boston, MA 02114 USA. EM dyoerger@partners.org OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [HL65549] NR 18 TC 126 Z9 133 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 15 PY 2005 VL 45 IS 6 BP 860 EP 865 DI 10.1016/j.jacc.2004.10.070 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 905RF UT WOS:000227586600008 PM 15766820 ER PT J AU Bonetti, M Pagano, M AF Bonetti, M Pagano, M TI The interpoint distance distribution as a descriptor of point patterns, with an application to spatial disease clustering SO STATISTICS IN MEDICINE LA English DT Article DE distance-based methods; Monte Carlo sampling; U-statistics; disease clusters ID INHOMOGENEOUS POPULATIONS; 2ND-ORDER ANALYSIS; TESTS; ASSOCIATION; STATISTICS AB The topic of this paper is the distribution of the distance between two points distributed independently in space. We illustrate the use of this interpoint distance distribution to describe the characteristics of a set of points within some fixed region. The properties of its sample version, and thus the inference about this function, are discussed both in the discrete and in the continuous setting. We illustrate its use in the detection of spatial clustering by application to a well-known leukaemia data set, and report on the results of a simulation experiment designed to study the power characteristics of the methods within that study region and in an artificial homogenous setting. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bonetti, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 665 Huntington Ave, Boston, MA 02115 USA. EM bonetti@jimmy.harvard.edu OI Bonetti, Marco/0000-0003-2304-4180 FU NIAID NIH HHS [AI28076]; NLM NIH HHS [LM07677-01] NR 40 TC 29 Z9 29 U1 0 U2 6 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 15 PY 2005 VL 24 IS 5 BP 753 EP 773 DI 10.1002/sim.1947 PG 21 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 900NX UT WOS:000227222700006 PM 15523703 ER PT J AU Crowley-Matoka, M Switzer, G AF Crowley-Matoka, M Switzer, G TI Nondirected living donation: A survey of current trends and practices SO TRANSPLANTATION LA English DT Article DE organ procurement; preservation; donation; organ banking; procurement ID ALTRUISTIC STRANGERS; TRANSPLANT CENTERS; KIDNEY DONATION; DONORS; ATTITUDES; FRIENDS AB The use of living donors in general is increasing, and there is evidence of increasing willingness among transplant centers to consider nondirected living donation (NDLD) as well. Yet few systematic data are available on the number of centers performing NDLD and the degree to which current policies and practices reflect existing guideline recommendations. We conducted a telephone survey of the 25 highest volume transplant centers and 25 highest volume organ procurement organizations (OPOs) to describe their NDLD-related policies and experiences. Survey responses revealed that inquiries about NDLD from interested potential donors are common, likely to increase, and generally not formally monitored. More than half of transplant centers surveyed currently perform or are willing to perform NDLD (14/25), and although only three OPOs currently facilitate NDLD, the majority of the remaining organizations reported that an NDLD policy was in development. Among those organizations that did facilitate NDLD, the majority applied current living-donor guidelines and practices to NDLDs. Most transplant centers performing NDLD distributed these donations to patients from their own waiting list by using United Network for Organ Sharing criteria. This preliminary description of current NDLD experiences suggests that although NDLD is growing, the policies and practices governing it are being developed on an ad hoc basis at the level of individual organizations. Additional research is needed to characterize the full range of NDLD activity at both higher and lower volume organizations, and to explore a broader range of questions about current NDLD policy and practice in the United States. C1 Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Anthropol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Vet Affairs Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Crowley-Matoka, M (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,151-C, Pittsburgh, PA 15240 USA. EM mcm29@pitt.edu NR 17 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 15 PY 2005 VL 79 IS 5 BP 515 EP 519 DI 10.1097/01.TP.000015501.39936.50 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 905OZ UT WOS:000227580000002 PM 15753839 ER PT J AU Abdel-Motal, UM Gillis, J Manson, K Wyand, M Montefiori, D Stefano-Cole, K Montelaro, RC Altman, JD Johnson, RP AF Abdel-Motal, UM Gillis, J Manson, K Wyand, M Montefiori, D Stefano-Cole, K Montelaro, RC Altman, JD Johnson, RP TI Kinetics of expansion of SIV Gag-specific CD8+ T lymphocytes following challenge of vaccinated macaques SO VIROLOGY LA English DT Article DE simian immunodeficiency virus; live attenuated SIV vaccine; cytotoxic T lymphocytes; neutralizing antibodies; AIDS vaccine; protective immunity; mucosal immunity; nonhuman primates ID SIMIAN IMMUNODEFICIENCY VIRUS; LIVE ATTENUATED SIV; RHESUS MACAQUES; PROTECTIVE IMMUNITY; VIRAL REPLICATION; PATHOGENIC SIVMAC239; ANTIBODY-RESPONSES; VAGINAL CHALLENGE; DELETION MUTANT; CELL RESPONSES AB The ability of memory T cells to mount a recall response plays a key role in the ability of vaccinated animals to contain viral challenge. In this study, we intensively monitored the expansion of SIV Gag-specific CD8+ T cells in peripheral blood and tissues of rhesus macaques vaccinated with the attenuated strain SIVmac239triangle3 and challenged with the pathogenic viruses SIVmac239 or SIVsmE660. Although all vaccinated animals were infected with challenge virus, peak levels of plasma viremia in vaccinees were decreased by 1.5 to 2 logs as compared with naive controls. Decreased levels of plasma viremia in vaccinated animals were evident as early as 7 days post-challenge, well before the expansion of SIV-specific CD8+ T cells. Expansion of SIV-specific CD8+ T cells was not observed in peripheral blood or tissues until at least 14 days after infection and did not occur in most animals until after the initial peak of viral replication. The observation that expansion of SIV-specific CD8+ T cells is delayed until 7 days or more after initial detection of viremia highlights fundamental limitations in the ability of lentivirus-specific CD8+ T cells to mediate protection against challenge. (C) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Div Immunol, New England Primate Res Ctr, Southborough, MA 01772 USA. Primedica, Worcester, MA 01608 USA. Duke Univ, Med Ctr, Dept Surg, Ctr AIDS Res, Durham, NC 27710 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA. Emory Univ, Vaccine Ctr Yerkes, Atlanta, GA 30329 USA. Massachusetts Gen Hosp East, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp East, Infect Dis Unit, Charlestown, MA 02129 USA. RP Johnson, RP (reprint author), Harvard Univ, Sch Med, Div Immunol, New England Primate Res Ctr, 1 Pine Hill Dr,POB 9102, Southborough, MA 01772 USA. EM johnson@hms.harvard.edu FU NCRR NIH HHS [RR00168]; NIAID NIH HHS [AI47758, AI62412, R01 AI047758-02, AI43044, AI43045] NR 52 TC 35 Z9 35 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 0042-6822 J9 VIROLOGY JI Virology PD MAR 15 PY 2005 VL 333 IS 2 BP 226 EP 238 DI 10.1016/j.virol.2004.12.030 PG 13 WC Virology SC Virology GA 903UE UT WOS:000227450300004 PM 15721357 ER PT J AU Gurmankin, AD Domchek, S Stopfer, J Fels, C Armstrong, K AF Gurmankin, AD Domchek, S Stopfer, J Fels, C Armstrong, K TI Patients' resistance to risk information in genetic counseling for BRCA1/2 SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BREAST-CANCER RISK; UNREALISTIC OPTIMISM; FAMILY-HISTORY; RANDOMIZED TRIAL; HEALTH-PROBLEMS; PERCEPTIONS; WOMEN; SUSCEPTIBILITY; SMOKERS; PREDICTION AB Background: Risk information from health care providers is relevant to and used in nearly all medical decisions. Patients often misunderstand their risks, yet little is known about the risk perception that patients derive from risk communications with health care providers. This study examines patients' risk perceptions following communication with health care providers during genetic counseling about the risks of breast cancer and BRCA1/2 mutations. Methods: A prospective, longitudinal study was conducted from October 2002 to February 2004 of women who received genetic counseling. The women completed a survey before their counseling and a telephone interview in the week after the counseling. Main outcome measures included change from precounseling in risk perception and accuracy of postcounseling risk perception (relative to actual risk information communicated). Results: A total of 108 women agreed to participate in the study. The women's postcounseling risk perceptions were significantly lower than their precounseling risk perceptions (breast cancer: 17%, P <.001; mutation: 13%, P <.001) but were significantly higher than the actual risk information communicated (breast cancer: 19%, P <.001; mutation: 24%, P <.001). Accuracy of breast cancer risk perception but not mutation risk perception was associated with precounseling worry (P=.04), even after adjusting for trait anxiety (P=.01). Conclusions: This research demonstrates patients' resistance to risk information. Inappropriately high risk perception derived from a risk communication with a health care provider can lead patients to make different, and potentially worse, medical decisions than they would with an accurate risk perception and to be unnecessarily distressed about their risk. C1 Dana Farber Canc Inst, Ctr Community Based Res, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Christiana Hosp, Dept Obstet & Gynecol, Newark, DE USA. RP Gurmankin, AD (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Dept Med Oncol, 44 Binney St,Smith 253, Boston, MA 02115 USA. EM adg11@cornell.edu NR 61 TC 52 Z9 52 U1 1 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 14 PY 2005 VL 165 IS 5 BP 523 EP 529 DI 10.1001/archinte.165.5.523 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 906FD UT WOS:000227625000006 PM 15767527 ER PT J AU Miller, KK Grinspoon, SK Ciampa, J Hier, J Herzog, D Klibanski, A AF Miller, KK Grinspoon, SK Ciampa, J Hier, J Herzog, D Klibanski, A TI Medical findings in outpatients with anorexia nervosa SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID X-RAY ABSORPTIOMETRY; EATING-DISORDERS; OSTEOPENIA; WOMEN; COMPLICATIONS; HYPOKALEMIA; POPULATION; PREVALENCE; MORTALITY; DENSITY AB Background: Approximately 0.5% to 1% of college-aged women have anorexia nervosa and most of them live in the community. However, few clinical data exist regarding community-dwelling women with anorexia nervosa, The objective of this study was to determine the prevalences of common medical findings for these women. Methods: Cross-sectional, community-based study of 214 women with anorexia nervosa as defined by the Diagnostic and Statistical Manual of Merital Disorders, Fourth Edition (DSM-IV). Participants were recruited through advertisements and community-based referrals to a study investigating skeletal health in outpatients with anorexia nervosa. Results: The prevalences of medical findings among the 214 participants were as follows: anemia, 38.6%; leukocytopenia, 34.4%; hyponatremia, 19.7%; hypokalemia, 19.7%; bradycardia, 41.3%; hypotension, 16.1%; hypothermia,,22.4%; elevation of alanine amino transferase concentration, 12.2%; osteopenia, 51.7%; osteoporosis, 34.6%; and primary amenorrhea, 14.8%. Moreover, 30% of the women reported histories of bone fractures. Except for leukocytopenia (P=.01), bone loss (P=.04), and bradycardia (P=.01), the probability of specific medical findings could not be predicted by the degree of undernutrition. Conclusions: These results demonstrate a high prevalence of medical findings in community-dwelling women with anorexia nervosa. Therefore, women with anorexia nervosa should be carefully followed up with regular physical examinations and laboratory assessments. In addition, low weight, particularly in conjunction with the abnormalities reported, should prompt the consideration of a diagnosis of anorexia nervosa. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM kkmiller@partners.org FU NCRR NIH HHS [M01 RR 01066-24S1, M01 RR 01066]; NIDDK NIH HHS [R01 DK 52625, R03 DK 59297] NR 33 TC 120 Z9 123 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 14 PY 2005 VL 165 IS 5 BP 561 EP 566 DI 10.1001/archinte.165.5.561 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 906FD UT WOS:000227625000012 PM 15767533 ER PT J AU Jia, XQ Kobler, J Clifton, RJ Jiao, T Zeitels, SM Langer, R AF Jia, XQ Kobler, J Clifton, RJ Jiao, T Zeitels, SM Langer, R TI Synthesis and characterization of hyaluronic acid-based hydrogels for vocal fold regeneration SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voic Rehabil, Boston, MA 02114 USA. Brown Univ, Div Engn, Providence, RI 02912 USA. EM xinqiao@mit.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 029-CARB BP U258 EP U258 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177701447 ER PT J AU Manley, PW Breitenstein, W Bruggen, J Cowan-Jacob, SW Furet, P Griffin, JD Mestan, J Meyer, T Weisberg, E AF Manley, PW Breitenstein, W Bruggen, J Cowan-Jacob, SW Furet, P Griffin, JD Mestan, J Meyer, T Weisberg, E TI Structural biology guided optimization of tyrosine kinase inhibitors: AMN107 a selective and potent Bcr-Abl inhibitor. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Novartis Inst BioMed Res, CH-4057 Basel, Switzerland. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 309-MEDI BP U163 EP U163 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600308 ER PT J AU McCarthy, JR Perez, JM Weissleder, R AF McCarthy, JR Perez, JM Weissleder, R TI PLGA encapsulated porphyrin nanoparticles as activateable photodynamic therapy and imaging agents. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Harvard Univ, Sch Med, Ctr Mol Imaging Res, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM jason_mccarthy@hms.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 171-ORGN BP U352 EP U352 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066601276 ER PT J AU Stroh, M Zimmer, JP Duda, D Levchenko, T Cohen, K Brown, E Scadden, D Torchilin, VP Bawendi, MG Fukumura, D Jain, R AF Stroh, M Zimmer, JP Duda, D Levchenko, T Cohen, K Brown, E Scadden, D Torchilin, VP Bawendi, MG Fukumura, D Jain, R TI Quantum dots provide customizable fluorescence for tumor pathophysiology and drug delivery studies. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 343-BIOT BP U232 EP U233 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177701325 ER PT J AU Partridge, AH Wong, JS Knudsen, K Gelman, R Sampson, E Gadd, M Bishop, KL Harris, JR Winer, EP AF Partridge, AH Wong, JS Knudsen, K Gelman, R Sampson, E Gadd, M Bishop, KL Harris, JR Winer, EP TI Offering participants results of a clinical trial: sharing results of a negative study SO LANCET LA English DT Article AB In general, patients are not given information about the results of trials in which they have participated. We aimed to assess the process and effect of providing clinical trial participants with results of a negative study. We offered results to 135 participants in a phase II trial of breast excision alone for women with ductal carcinoma in situ, which was stopped early because of an early high rate of local recurrence. 85 (90%) of 94 respondents chose to receive results; these women were more educated (57 [67%] of 85 college graduates) than those who chose not to (two [22%] of nine, p=0.006). Most participants reported positive feelings about being offered results and about clinical trials in general. These preliminary findings from sharing clinical trial results are encouraging. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Med & Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. RP Partridge, AH (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Med & Radiat Oncol, 44 Binney St,D1210, Boston, MA 02115 USA. EM ahpartridge@partners.org NR 5 TC 52 Z9 52 U1 0 U2 3 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAR 12 PY 2005 VL 365 IS 9463 BP 963 EP 964 DI 10.1016/S0140-6736(05)71085-0 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 905HS UT WOS:000227559800029 PM 15766998 ER PT J AU Quinn, J Kulhanek, D Nowlin, J Jones, R Pratico, D Rokach, J Stackman, R AF Quinn, J Kulhanek, D Nowlin, J Jones, R Pratico, D Rokach, J Stackman, R TI Chronic melatonin therapy fails to alter amyloid burden or oxidative damage in old Tg2576 mice: Implications for clinical trials SO BRAIN RESEARCH LA English DT Article DE Alzheimer's disease; beta amyloid; melatonin ID ALZHEIMERS-DISEASE; NEUROBLASTOMA-CELLS; ANIMAL-MODEL; ANTIOXIDANT; STRESS; INFLAMMATION; PATHOLOGY; PROTECTS; CORTEX; ACID AB Melatonin has been proposed as a treatment for Alzheimer's disease based on the demonstration of antioxidant and "anti-amyloid' effects in vitro and in vivo. Chronic melatonin therapy in old, amyloid plaque-bearing transgenic mice was studied. Tg2576 mice started melatonin treatment at 14 months of age. After 4 months of treatment, there were no differences between untreated and melatonin-treated mice in cortical levels of soluble, formic acid extracted, or histologically detectable beta amyloid (A), nor in brain levels of lipid peroxidation product (total 8,12-isoprostane F-2 alpha-VI), despite marked elevations in plasma melatonin. We conclude that melatonin fails to produce antiamyloid or antioxidant effects when initiated after the age of amyloid plaque deposition. These findings diminish the possibility that melatonin will be useful for the treatment of established Alzheimer's disease. (c) 2005 Elsevier B.V. All rights reserved. C1 Portland Vet Affairs Med Ctr, Dept Neurol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. Univ Penn, Ctr Expt Therapeut, Dept Pharmacol, Philadelphia, PA 19104 USA. Florida Inst Technol, Melbourne, FL 32901 USA. Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. RP Quinn, J (reprint author), Portland Vet Affairs Med Ctr, Dept Neurol, P3 R&D,US Vet Hosp Rd, Portland, OR 97239 USA. EM quinnj@ohsu.edu OI Stackman Jr, Robert/0000-0002-5950-046X FU NCCIH NIH HHS [AT00066] NR 17 TC 49 Z9 50 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 10 PY 2005 VL 1037 IS 1-2 BP 209 EP 213 DI 10.1016/j.brainres.2005.01.023 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 914TT UT WOS:000228251400027 PM 15777772 ER PT J AU Gori, F Demay, MB AF Gori, F Demay, MB TI The effects of BIG-3 on osteoblast differentiation are not dependent upon endogenously produced BMPs SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE BIG-3; MC3T3-E1 cells; osteoblast; BMP-2; noggin; Smad-1 ID BONE MORPHOGENETIC PROTEINS; WD-40 REPEAT PROTEIN; GROWTH-FACTOR-BETA; TRANSCRIPTION FACTOR; SIGNALING PATHWAYS; REGULATORS; SMADS; TRANSDUCTION; RECEPTORS; KINASE AB BMPs play an important role in both intramembranous and endochondral ossification. BIG-3, BMP-2-induced gene 3 kb, encodes a WD-40 repeat protein that accelerates the program of osteoblastic differentiation in vitro. To examine the potential interactions between BIG-3 and the BMP-2 pathway during osteoblastic differentiation, MC3T3-E1 cells stably transfected with BIG-3 (MC3T3E1-BIG-3), or with the empty vector (MC3T3E1-EV), were treated with noggin. Noggin treatment of pooled MC3T3E1-EV clones inhibited the differentiation-dependent increase in AP activity observed in the untreated MC3T3E1-EV clones but did not affect the increase in AP activity in the MC3T3E1-BIG-3 clones. Noggin treatment decreased the expression of Runx2 and type I collagen mRNAs and impaired mineralized matrix formation in MC3T3E1-EV clones but not in MC3T3E1-BIG-3 clones. To determine whether the actions of BIG-3 on osteoblast differentiation converged upon the BMP pathway or involved an alternate signaling pathway, Smad1 phosphorylation was examined. Basal phosphorylation of Smad1 was not altered in the MC3T3E1-BIG-3 clones. However, these clones did not exhibit the noggin-dependent decrease in phosphoSmad1 observed in the MC3T3E1-EV clones, nor did it decrease nuclear localization of phosphoSmad1. These observations suggest that BIG-3 accelerates osteoblast differentiation in MC3T3-E1 cells by inducing phosphorylation and nuclear translocation of Smad1 independently of endogenously produced BMPs. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Demay, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. EM demay@helix.mgh.harvard.edu FU NIDCR NIH HHS [1 F32 DE-05754]; NIDDK NIH HHS [DK36597] NR 28 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495, UNITED STATES SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAR 10 PY 2005 VL 304 IS 1 BP 287 EP 292 DI 10.1016/j.yexcr.2004.11.008 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 899EO UT WOS:000227127900025 PM 15707593 ER PT J AU Harris, JR AF Harris, JR TI Radiation therapy for invasive breast cancer: Not just for local control SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID COMPARING RADICAL-MASTECTOMY; POSTOPERATIVE RADIOTHERAPY; CLINICAL-TRIAL; MORTALITY C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. RP Harris, JR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. NR 15 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2005 VL 23 IS 8 BP 1607 EP 1608 DI 10.1200/JCO.2005.11.048 PG 2 WC Oncology SC Oncology GA 905RL UT WOS:000227587200006 PM 15755963 ER PT J AU Winer, EP AF Winer, EP TI Optimizing endocrine therapy for breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID TAMOXIFEN C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 9 TC 19 Z9 19 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2005 VL 23 IS 8 BP 1609 EP 1610 DI 10.1200/JCO.2005.01.005 PG 2 WC Oncology SC Oncology GA 905RL UT WOS:000227587200007 PM 15755964 ER PT J AU Dellapasqua, S Colleoni, M Gelber, RD Goldhirsch, A AF Dellapasqua, S Colleoni, M Gelber, RD Goldhirsch, A TI Adjuvant endocrine therapy for premenopausal women with early breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID RANDOMIZED CLINICAL-TRIAL; OVARIAN ABLATION; POSTMENOPAUSAL WOMEN; CMF CHEMOTHERAPY; TAMOXIFEN RESISTANCE; AROMATASE INHIBITORS; RECEPTOR; CYCLOPHOSPHAMIDE; GOSERELIN; METHOTREXATE C1 European Inst Oncol, Div Med Oncol, Dept Med, I-20141 Milan, Italy. Int Breast Canc Study Grp Coordinating Ctr, Bern, Switzerland. Oncol Inst So Switzerland, Bellinzona, Switzerland. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Int Breast Canc Study Grp Stat Ctr, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. RP Goldhirsch, A (reprint author), European Inst Oncol, Div Med Oncol, Dept Med, Via Ripamonti 435, I-20141 Milan, Italy. EM aron.goldhirsch@ibcsg.org NR 98 TC 43 Z9 44 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2005 VL 23 IS 8 BP 1736 EP 1750 DI 10.1200/JCO.2005.11.050 PG 15 WC Oncology SC Oncology GA 905RL UT WOS:000227587200025 PM 15755982 ER PT J AU Strasser-Weippl, K Goss, PE AF Strasser-Weippl, K Goss, PE TI Advances in adjuvant hormonal therapy for postmenopausal women SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID ADVANCED BREAST-CANCER; AROMATASE INHIBITOR LETROZOLE; BONE-MINERAL DENSITY; ONCOLOGY-TECHNOLOGY-ASSESSMENT; TAMOXIFEN-STIMULATED GROWTH; PLASMA ESTROGEN-LEVELS; RANDOMIZED-TRIAL; MEGESTROL-ACETATE; ENDOCRINE THERAPY; DOUBLE-BLIND C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. Wilhelminen Hosp, Dept Med & Med Oncol 1, Vienna, Austria. RP Goss, PE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, 55 Fruit St,Cox Bldg,Room 640, Boston, MA 02114 USA. EM pgoss@partners.org NR 87 TC 38 Z9 39 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2005 VL 23 IS 8 BP 1751 EP 1759 DI 10.1200/JCO.2005.11.038 PG 9 WC Oncology SC Oncology GA 905RL UT WOS:000227587200026 PM 15755983 ER PT J AU Bais, HP Prithiviraj, B Jha, AK Ausubel, FM Vivanco, JM AF Bais, HP Prithiviraj, B Jha, AK Ausubel, FM Vivanco, JM TI Mediation of pathogen resistance by exudation of antimicrobials from roots SO NATURE LA English DT Article ID PSEUDOMONAS-SYRINGAE STRAINS; PV. TOMATO DC3000; ARABIDOPSIS-THALIANA; DISEASE RESISTANCE; AVIRULENCE GENE; IDENTIFICATION; PLANTS; PHASEOLICOLA; INVASION; BIOLOGY AB Most plant species are resistant to most potential pathogens. It is not known why most plant - microbe interactions do not lead to disease, although recent work indicates that this basic disease resistance is multi-factorial(1,2). Here we show that the exudation of root-derived antimicrobial metabolites by Arabidopsis thaliana confers tissue-specific resistance to a wide range of bacterial pathogens. However, a Pseudomonas syringae strain that is both at least partly resistant to these compounds and capable of blocking their synthesis/exudation is able to infect the roots and cause disease. We also show that the ability of this P. syringae strain to block antimicrobial exudation is dependent on the type III secretory system. C1 Colorado State Univ, Dept Hort & Landscape Architecture, Ft Collins, CO 80523 USA. Colorado State Univ, Ctr Rhizosphere Biol, Ft Collins, CO 80523 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Colorado State Univ, Dept Hort & Landscape Architecture, Ft Collins, CO 80523 USA. EM ausubel@molbio.mgh.harvard.edu; j.vivanco@colostate.edu RI Rechsteiner, Cynthia/C-5894-2011 NR 30 TC 81 Z9 90 U1 4 U2 45 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 10 PY 2005 VL 434 IS 7030 BP 217 EP 221 DI 10.1038/nature03356 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 904JU UT WOS:000227494500046 PM 15759001 ER PT J AU Dluhy, RG Maher, MM Harris, NL Grinspoon, SK Wu, CL AF Dluhy, RG Maher, MM Harris, NL Grinspoon, SK Wu, CL TI A 59-year-old woman with an incidentally discovered adrenal nodule - Functional adrenal cortical adenoma. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DEPENDENT CUSHINGS-SYNDROME; HORMONE-RECEPTORS; SUPPRESSION; DIAGNOSIS; FEATURES; THERAPY; TUMORS; ACTH C1 Brigham & Womens Hosp, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Dluhy, RG (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. NR 21 TC 5 Z9 5 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 10 PY 2005 VL 352 IS 10 BP 1025 EP 1032 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 904JC UT WOS:000227491200013 PM 15758014 ER PT J AU Werner, RM Asch, DA AF Werner, RM Asch, DA TI The unintended consequences of publicly reporting quality information SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NEW-YORK-STATE; BYPASS GRAFT-SURGERY; CARDIAC-SURGERY; OF-CARE; MEDICARE BENEFICIARIES; IMPROVEMENT EFFORTS; PERFORMANCE REPORTS; HEALTH-CARE; HOSPITAL PERFORMANCE; MORTALITY HOSPITALS AB Health care report cards publicly report information about physician, hospital, and health plan quality in an attempt to improve that quality. Reporting quality information publicly is presumed to motivate quality improvement through 2 main mechanisms. First, public quality information allows patients, referring physicians, and health care purchasers to preferentially select high-quality physicians. Second, public report cards may motivate physicians to compete on quality and, by providing feedback and by identifying areas for quality improvement initiatives, help physicians to do so. Despite these plausible mechanisms of quality improvement, the value of publicly reporting quality information is largely undemonstrated and public reporting may have unintended and negative consequences on health care. These unintended consequences include causing physicians to avoid sick patients in an attempt to improve their quality ranking, encouraging physicians to achieve "target rates" for health care interventions even when it may be inappropriate among some patients, and discounting patient preferences and clinical judgment. Public reporting of quality information promotes a spirit of openness that may be valuable for enhancing trust of the health professions, but its ability to improve health remains undemonstrated, and public reporting may inadvertently reduce, rather than improve, quality. Given these limitations, it may be necessary to reassess the role of public quality reporting in quality improvement. C1 Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equit Res & Promot, Philadelphia, PA 19104 USA. RP Werner, RM (reprint author), Univ Penn, Div Gen Internal Med, 1208 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rwerner@wharton.upenn.edu FU AHRQ HHS [F32-HS-14644-01, 2-T32-HS-00009] NR 61 TC 322 Z9 326 U1 3 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 9 PY 2005 VL 293 IS 10 BP 1239 EP 1244 DI 10.1001/jama.293.10.1239 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 904LB UT WOS:000227498400024 PM 15755946 ER PT J AU Ichida, JK Zou, K Horhota, A Yu, B McLaughlin, LW Szostak, JW AF Ichida, JK Zou, K Horhota, A Yu, B McLaughlin, LW Szostak, JW TI An in vitro selection system for TNA SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEIC-ACID STRUCTURE; CHEMICAL ETIOLOGY; DNA-POLYMERASES; RECOGNITION; TEMPLATE C1 Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Boston Coll, Dept Chem, Chestnut Hill, MA 02467 USA. Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Bioorgan & Nat Prod Chem, Shanghai 200032, Peoples R China. RP Szostak, JW (reprint author), Howard Hughes Med Inst, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM53936, R01 GM053936] NR 12 TC 52 Z9 52 U1 2 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 9 PY 2005 VL 127 IS 9 BP 2802 EP 2803 DI 10.1021/ja045364w PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 904ET UT WOS:000227479600004 PM 15740086 ER PT J AU Deschamps, AM Yarbrough, WM Squires, CE Allen, RA McClister, DM Dowdy, KB McLean, JE Mingoia, JT Sample, JA Mukherjee, R Spinale, FG AF Deschamps, AM Yarbrough, WM Squires, CE Allen, RA McClister, DM Dowdy, KB McLean, JE Mingoia, JT Sample, JA Mukherjee, R Spinale, FG TI Trafficking of the membrane type-1 matrix metalloproteinase in ischemia and reperfusion - Relation to interstitial membrane type-1 matrix metalloproteinase activity SO CIRCULATION LA English DT Article DE ischemia; metalloproteinases; myocytes; remodeling; reperfusion ID ACUTE MYOCARDIAL-INFARCTION; TISSUE INHIBITOR; CELL-SURFACE; GELATINASE-A; ACTIVATION; MT1-MMP; EXPRESSION; COLLAGENASE; ENDOCYTOSIS; MECHANISMS AB Background - The matrix metalloproteinases ( MMPs) contribute to regional remodeling after prolonged periods of ischemia and reperfusion (I/ R), but specific MMP types activated during this process remain poorly understood. A novel class, the membrane-type MMPs (MT- MMPs), has been identified in the myocardium, but activity of these MMP types has not been assessed in vivo, particularly during I/R. Methods and Results - Pigs ( 30 kg, n = 8) were instrumented with microdialysis catheters to measure MT1-MMP activity in both ischemic and nonischemic (remote) myocardium. A validated MT1-MMP fluorogenic substrate was infused through the microdialysis system, and changes in fluorescence were reflective of MT1-MMP activity at steady state, during ischemia (90 minutes), and during reperfusion (120 minutes). At peak ischemia, MT1-MMP activity was increased by > 40 % in the ischemic region, with no change in the remote region, which persisted with reperfusion (P < 0.05). After I/R, MT1-MMP abundance was increased by > 50 % (P < 0.05). Differential centrifugation revealed that the endosomal fraction (which contains subcellular organelles) within the ischemic myocardium was associated with a > 135 % increase in MT1-MMP (P < 0.05). Furthermore, in an isolated left ventricular myocyte model of I/ R, hypoxia ( simulated ischemia) induced a > 70 % increase in MT1-MMP abundance in myocytes, and confocal microscopy revealed MT1-MMP internalization during this time period and reemergence to the membrane with reperfusion. Conclusions - These unique results demonstrate that a specific MMP type, MT1-MMP, is increased in abundance and activity with I/R and is likely attributed, at least in part, to changes in intracellular trafficking. C1 Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29403 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Room 625,Strom Thurmond Res Bldg,114 Doughty St, Charleston, SC 29403 USA. EM wilburnm@musc.edi OI Deschamps, Anne/0000-0001-7415-1408 FU NHLBI NIH HHS [HL-07260, HL-45024, HL-97012, HL59165, P01-HL-48788] NR 45 TC 48 Z9 50 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 8 PY 2005 VL 111 IS 9 BP 1166 EP 1174 DI 10.1161/01.CIR.0000157149.71297.3A PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 904BH UT WOS:000227469600013 PM 15723986 ER PT J AU Cury, RC Abbara, S Sandoval, LJD Houser, S Brady, TJ Palacios, IF AF Cury, RC Abbara, S Sandoval, LJD Houser, S Brady, TJ Palacios, IF TI Visualization of endomyocardial fibrosis by delayed-enhancement magnetic resonance imaging SO CIRCULATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Cury, RC (reprint author), Massachusetts Gen Hosp, Dept Radiol, 100 Charles River Plaza,Ste 400, Boston, MA 02114 USA. EM rcury@partners.org NR 0 TC 18 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 8 PY 2005 VL 111 IS 9 BP E115 EP E117 DI 10.1161/01.CIR.0000157399.96408.36 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 904BH UT WOS:000227469600019 PM 15753221 ER PT J AU Ray, SS Nowak, RJ Brown, RH Lansbury, PT AF Ray, SS Nowak, RJ Brown, RH Lansbury, PT TI Small-molecule-mediated stabilization of familial amyotrophic lateral sclerosis-linked superoxide dismutase mutants against unfolding and aggregation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE drug discovery; in silico screening; docking; thermopeutics; thermodynamics ID AMYLOID FIBRIL INHIBITORS; MOTOR-NEURON DISEASE; DISULFIDE REDUCTION; TRANSTHYRETIN; STABILITY; INSIGHTS; PACKING; QUATERNARY; COMPLEXES; DOCKING AB Familial annyotrophic lateral sclerosis (FALS) is a fatal motor neuron disease that is caused by mutations in the gene encoding superoxide dismutase-type 1 (SOD1). The affected regions of the FALS brain are characterized by aggregated SOD1, and the mutations that destabilize SOD1 appear to promote its aggregation in vitro. Because dissociation of the native SOD1 dinner is required for its in vitro aggregation, we initiated an in silico, screening program to find drug-like molecules that would stabilize the SOD1 dimer. A potential binding site for such molecules at the SOD1 dinner interface was identified, and its importance was validated by mutagenesis. About 1.5 million molecules from commercial data-bases were docked at the dinner interface. Of the 100 molecules with the highest predicted binding affinity, 15 significantly inhibited in vitro aggregation and denaturation of A4V, a FALS-linked variant of SOD1. In the presence of several of these molecules, A4V and other FALS-linked SOD1 mutants such as G93A and G85R behaved similarly to wild-type SOD1, suggesting that these compounds could be leads toward effective therapeutics against FALS. C1 Harvard Univ, Sch Med, Harvard Ctr Neurodegenerat & Repair, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Ctr Aging Genet & Neurodgenerat, Charlestown, MA 02129 USA. RP Lansbury, PT (reprint author), Harvard Univ, Sch Med, Harvard Ctr Neurodegenerat & Repair, Boston, MA 02115 USA. EM sray@rics.bwh.harvard.edu; plansbury@rics.bwh.harvard.edu FU PHS HHS [NIH 085476] NR 35 TC 79 Z9 80 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 8 PY 2005 VL 102 IS 10 BP 3639 EP 3644 DI 10.1073/pnas.0408277102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 904XY UT WOS:000227533100023 PM 15738401 ER PT J AU Luo, BH Carman, CV Takagi, J Springer, TA AF Luo, BH Carman, CV Takagi, J Springer, TA TI Disrupting integrin transmembrane domain heterodimerization increases ligand binding affinity, not valency or clustering SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FIBRINOGEN RECEPTOR; ALPHA-IIB; ACTIVATION; ALPHA(IIB)BETA(3); CONFORMATION; CELLS; ALPHA-IIB-BETA-3; DIMERIZATION; SPECIFICITY; EXPRESSION AB Residues important in the interaction between the 23-residue transmembrane (TM) domains of the integrin alpha(IIb)- and beta(3)-subunits were identified by mutating each non-Leu residue to Leu. Leu substitutions of alpha(IIb) at G972, G976, and T981, and Of beta(3) at 1693 and G708, increased ligand binding. Substitutions with other amino acids at alpha(IIb)G972 and beta(3)G708 could also increase ligand binding. The results are consistent with and extend the helical interface between the integrin alpha- and beta-subunit TM domains previously defined by cysteine scanning and disulfide bond formation. We differentiated between affinity- and valency-based modes of activation by TM domain mutations. The mutant alpha(IIb) W967C forms disulfide-linked alpha(IIb)-Subunits within an (alpha(IIb))beta(3))(2) tetramer. This tetramer behaved as an ideal model for the valency mode of regulation, because it exhibited significantly increased binding to multivalent but not monovalent ligands and basally retained the bent conformation. By contrast, the activating Leu mutants showed increased binding to the monovalent, ligand-mimetic PAC-1 Fab and increased exposure of ligand-induced binding site (LIBS) epitopes, suggesting that they partially adopt an extended conformation. Furthermore, the previously described beta(3)G708N mutation in Chinese hamster ovary cells enhanced ligand binding affinity, not valency, and did not alter cell-surface clustering as defined by confocal microscopy. Our studies provide evidence that disrupting the integrin heterodimeric TM helix-helix interface activates ligand binding mainly by increasing the monomeric affinity for ligand, but not the receptor valency, i.e., clustering. C1 Harvard Univ, Sch Med, Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Osaka Univ, Inst Prot Res, Lab Prot Synth & Express, Suita, Osaka 5650871, Japan. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu RI Carman, Christopher/L-8108-2016 OI Carman, Christopher/0000-0001-7358-2548 FU NHLBI NIH HHS [HL 48675, P01 HL048675] NR 37 TC 111 Z9 113 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 8 PY 2005 VL 102 IS 10 BP 3679 EP 3684 DI 10.1073/pnas.0409440102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 904XY UT WOS:000227533100030 PM 15738420 ER PT J AU Morrell, CN Matsushita, K Chiles, K Scharpf, RB Yamakuchi, M Mason, RJA Bergmeier, W Mankowski, JL Baldwin, WM Faraday, N Lowenstein, CJ AF Morrell, CN Matsushita, K Chiles, K Scharpf, RB Yamakuchi, M Mason, RJA Bergmeier, W Mankowski, JL Baldwin, WM Faraday, N Lowenstein, CJ TI Regulation of platelet granule exocytosis by S-nitrosylation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE alpha-granules; nitric oxide ID SENSITIVE FUSION PROTEIN; CGMP-INDEPENDENT MECHANISMS; ENDOGENOUS NITRIC-OXIDE; VASCULAR ENDOTHELIUM; MOLECULAR-MECHANISMS; VESICULAR TRANSPORT; CONTRACTING FACTORS; GUANYLATE-CYCLASE; MEMBRANE-FUSION; AGGREGATION AB Nitric oxide (NO) regulates platelet activation by cGMP-dependent mechanisms and by mechanisms that are not completely defined. Platelet activation includes exocytosis of platelet granules, releasing mediators that regulate interactions between platelets, leukocytes, and endothelial cells. Exocytosis is mediated in part by N-ethylmaleimide-sensitive factor (NSF), an ATPase that disassembles complexes of soluble NSF attachment protein receptors. We now demonstrate that NO inhibits exocytosis of dense granules, lysosomal granules, and a-granules from human platelets by S-nitrosylation of NSF. Platelets lacking endothelial NO synthase show increased rolling on venules, increased thrombosis in arterioles, and increased exocytosis in vivo. Regulation of exocytosis is thus a mechanism by which NO regulates thrombosis. C1 Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Comparat Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Anesthesiol, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Lowenstein, CJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, 950 Ross Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. EM clowenst@jhmi.edu FU NCRR NIH HHS [RR 07002, T32 RR007002]; NHLBI NIH HHS [HL 074945, R01 HL 074061, R01 HL 63706, R01 HL063706, R01 HL074061, K08 HL074945, P01 HL 56091, P01 HL 65608, P01 HL056091, P01 HL065608] NR 56 TC 89 Z9 93 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 8 PY 2005 VL 102 IS 10 BP 3782 EP 3787 DI 10.1073/pnas.0408310102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 904XY UT WOS:000227533100048 PM 15738422 ER PT J AU Engelman, JA Janne, PA Mermel, C Pearlberg, J Mukohara, T Fleet, C Cichowski, K Johnson, BE Cantley, LC AF Engelman, JA Janne, PA Mermel, C Pearlberg, J Mukohara, T Fleet, C Cichowski, K Johnson, BE Cantley, LC TI ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Akt; EGF receptor ID EPIDERMAL-GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; FACTOR-RECEPTOR; ZD1839 IRESSA; PHOSPHATIDYLINOSITOL 3-KINASE; WIDE PREDICTION; EGFR MUTATIONS; TUMOR-CELLS; PATHWAYS; TRIAL AB Therapies that target the EGF receptor (EGFR), such as gefitinib (IRESSA), are effective in a subset of patients with advanced non-small cell lung cancer (NSCLC). The differences in intracellular signaling networks between gefitinib-sensitive and -resistant NSCLCs remain poorly understood. In this study, we observe that gefitinib reduces phospho-Akt levels only in NSCLC cell lines in which it inhibits growth. To elucidate the mechanism underlying this observation, we compared immunoprecipitates of phosphoinositide 3-kinase (PI3K) between gefitinib-sensitive and -resistant NSCLC cell lines. We observe that PI3K associates with ErbB-3 exclusively in gefitinib-sensitive NSCLC cell lines. Gefitinib dissociates this complex, thereby linking EGFR inhibition to decreased Akt activity. In contrast, gefitinib-resistant cells do not use ErbB-3 to activate the PI3K/Akt pathway. in fact, abundant ErbB-3 expression is detected only in gefitinib-sensitive NSCLC cell lines. Two gefitinib-sensitive NSCLC cell lines with endogenous distinct activating EGFR mutations (L858R and De1747-749), frequently observed in NSCLC patients who respond to gefitinib, also use ErbB-3 to couple to PI3K. Down-regulation of ErbB-3 by means of short hairpin RNA leads to decreased phospho-Akt levels in the gefitinib-sensitive NSCLC cell lines, Calu-3 (WT. EGFR) and H3255 (L858R EGFR), but has no effect on Akt activation in the gefitinib-resistant cell lines, A549 and H522. We conclude that ErbB-3 is used to couple EGFR to the PI3K/Akt pathway in gefitinib-sensitive NSCLC cell lines harboring WT and mutant EGFRs. C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. RP Cantley, LC (reprint author), Harvard Inst Med, 77 Ave Louis Pasteur,Room 1022, Boston, MA 02115 USA. EM lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [1K12 CA 87723-01, 5P01 CA 089021, 5T32 CA 09172-30, K12 CA087723, P01 CA089021, P20 CA 90578-02, P20 CA090578, T32 CA009172]; NIGMS NIH HHS [R01 GM041890, GM 41890, R37 GM041890] NR 27 TC 366 Z9 383 U1 1 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 8 PY 2005 VL 102 IS 10 BP 3788 EP 3793 DI 10.1073/pnas.0409773102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 904XY UT WOS:000227533100049 PM 15731348 ER PT J AU Devor, A Ulbert, I Dunn, AK Narayanan, SN Jones, SR Andermann, ML Boas, DA Dale, AM AF Devor, A Ulbert, I Dunn, AK Narayanan, SN Jones, SR Andermann, ML Boas, DA Dale, AM TI Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE barrel cortex; blood oxygenation; intrinsic signals; optical imaging ID RAT BARREL CORTEX; VOLTAGE-SENSITIVE DYES; CEREBRAL-BLOOD-FLOW; SOMATOSENSORY CORTEX; INTRINSIC SIGNALS; SYNAPTIC ACTIVITY; HEMOGLOBIN CONCENTRATION; SENSORY STIMULATION; NEURAL ACTIVITY; BRAIN ACTIVITY AB Accurate interpretation of functional MRI,(fMRI) signals requires knowledge of the relationship between the hemodynamic response and the neuronal activity that underlies it. Here we address the question of coupling between pre- and postsynaptic neuronal activity and the hemodynamic response in rodent somatosensory (Barrel) cortex in response to single-whisker deflection. Using full-field multiwavelength optical imaging of hemoglobin oxygenation and electrophysiological recordings of spiking activity and local field potentials, we demonstrate that a point hemodynamic measure is influenced by neuronal activity across multiple cortical columns. We demonstrate that the hemodynamic response is a spatiotemporal convolution of the neuronal activation. Therefore, positive hemodynamic response in one cortical column might be explained by neuronal activity not only in that column but also in the neighboring columns. Thus, attempts at characterizing the neurovascular relationship based on point measurements of electrophysiology and hemodynamics may yield inconsistent results, depending on the spatial extent of neuronal activation. The finding that the hemodynamic signal observed at a given location is a function of electrophysiological activity over a broad spatial region helps explain a previously observed increase of local vascular response beyond the saturation of local neuronal activity. We also demonstrate that the oxy- and total-hemoglobin hemodynamic responses can be well approximated by space.-time separable functions with an antagonistic center-surround spatial pattern extending over several millimeters. The surround "negative" hemodynamic activity did not correspond to observable changes in neuronal activity. The complex spatial integration of the hemodynamic response should be considered when interpreting fMRl data. C1 Harvard Med Sch, Massachusetts Gen Hosp NMR Ctr, Charlestown, MA 02129 USA. Harvard Med Sch, Program Biophys, Charlestown, MA 02129 USA. Hungarian Acad Sci, Inst Psychol, H-1068 Budapest, Hungary. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. RP Devor, A (reprint author), Harvard Med Sch, Massachusetts Gen Hosp NMR Ctr, Charlestown, MA 02129 USA. EM adevor@nmr.mgh.harvard.edu RI Ulbert, Istvan/F-2213-2010; Dale, Anders/A-5180-2010; Dunn, Andrew/I-9527-2014 FU NCRR NIH HHS [P41 RR 14075, P41 RR014075]; NIBIB NIH HHS [R01 EB 00790, R01 EB000790]; NINDS NIH HHS [NS 44623, R01 NS044623] NR 55 TC 129 Z9 134 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 8 PY 2005 VL 102 IS 10 BP 3822 EP 3827 DI 10.1073/pnas.0407789102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 904XY UT WOS:000227533100055 PM 15734797 ER PT J AU Birdsall, HH Porter, WJ Trial, JA Rossen, RD AF Birdsall, HH Porter, WJ Trial, JA Rossen, RD TI Generation of regulatory cells by 110 kD fibronectin fragment SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1414 EP A1414 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903061 ER PT J AU Bowser, R Ranganathan, S Ganchev, P Gopalakrishnan, V Cudkowicz, M Brown, RH AF Bowser, R Ranganathan, S Ganchev, P Gopalakrishnan, V Cudkowicz, M Brown, RH TI Diagnostic biomarkers for amyotrophic lateral sclerosis (ALS) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA. Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA USA. Massachusetts Gen Hosp East, Day Neuromuscular Res Lab, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1511 EP A1511 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903510 ER PT J AU Chang, HC Tan, KM Le, Y Witte, T Ouyang, J AF Chang, HC Tan, KM Le, Y Witte, T Ouyang, J TI Cd8ab has two distinct binding modes for its interaction with peptide-MHC class I complexes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Witte, Torsten/B-5783-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1411 EP A1411 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903048 ER PT J AU Feske, S Prakriya, M Lewis, RS Rao, A AF Feske, S Prakriya, M Lewis, RS Rao, A TI Defect in CRAC Ca2+ channel function associated with altered K+ channel gating properties in T cells from immunodeficient patients SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Harvard Univ, Sch Med, CBR Inst, Boston, MA 02115 USA. Stanford Univ, Beckman Ctr, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1163 EP A1163 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610901212 ER PT J AU Houser, SL Tseng, YL Kuwaki, K Dor, FJMF Shirmzu, A Sachs, DH Cooper, DKC AF Houser, SL Tseng, YL Kuwaki, K Dor, FJMF Shirmzu, A Sachs, DH Cooper, DKC TI Cardiac xenograft vasculopathy in a pig-to-baboon model SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Transplantat Biol Res Ctr, Boston, MA 02129 USA. Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15261 USA. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1523 EP A1523 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903568 ER PT J AU Huang, MT Mason, JC Gerwin, N Ridley, AJ Haskard, DO Randi, AM AF Huang, MT Mason, JC Gerwin, N Ridley, AJ Haskard, DO Randi, AM TI Intercellular adhesion molecule (ICAM)-2 mediates angiogenesis via homophilic interaction SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Expt Therapeut, Int Union Physiol Sci C1 Univ London Imperial Coll Sci Technol & Med, BHF Cardiovasc Med, London W12 0NN, England. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. UCL Royal Free & Univ Coll, Sch Med, Ludwig Inst Canc Res, London W1W 7BS, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1714 EP A1714 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610904777 ER PT J AU Jones, RC Jacobson, M Capen, D AF Jones, RC Jacobson, M Capen, D TI Quantitative analysis of PDGF-AA/PDGF-R alpha and interstitial fibroblasts recruited as perivascular progenitor smooth muscle cells (mural cells) in adult pulmonary hypertension (PH): imaging microvessel wall structure and regulation of PDGF signalin SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1507 EP A1507 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903494 ER PT J AU Jones, RE Moes, N Zwickey, H Bourdette, D Cunningham, C Oken, B AF Jones, RE Moes, N Zwickey, H Bourdette, D Cunningham, C Oken, B TI Conditioned therapeutic response in EAE SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Portland, OR 97239 USA. Natl Coll Naturopath Med, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1441 EP A1442 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903192 ER PT J AU Krogsgaard, M Li, QJ Sumen, C Huppa, JB Huse, M Davis, MM AF Krogsgaard, M Li, QJ Sumen, C Huppa, JB Huse, M Davis, MM TI The role of agonist-self heterodimers of peptide-MHC and CD4 in T cell activation and sensitivity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA. Stanford Univ, HHMI, Stanford, CA 94305 USA. Harvard Univ, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1430 EP A1430 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903138 ER PT J AU Link, JM Rich, C Vandenbark, AA AF Link, JM Rich, C Vandenbark, AA TI RTL effects on myelin specific T cells in vivo: relationship between myelin-specific T cells in peripheral blood and EAE SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Portland Vet Affairs Med Ctr, R&D 31, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1442 EP A1443 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903197 ER PT J AU Mascarenhas, MM Garg, HG Hales, CA Quinn, DA AF Mascarenhas, MM Garg, HG Hales, CA Quinn, DA TI Hyaluronan (HA), CD44 and toll-like receptors (TLR) in ventilator-induced lung injury (VILI) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1605 EP A1605 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610904273 ER PT J AU Ochoa, CD Al-Ansari, E Mascarenhas, MM Yu, LY Hales, CA Quinn, DA AF Ochoa, CD Al-Ansari, E Mascarenhas, MM Yu, LY Hales, CA Quinn, DA TI Thrombospondin-1 in hypoxic vascular remodeling SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1331 EP A1331 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610902331 ER PT J AU Prabhala, RH Neri, P Tassone, P Shammas, M Anderson, K Munshi, N AF Prabhala, RH Neri, P Tassone, P Shammas, M Anderson, K Munshi, N TI Lack of regulation by CD4+CD25+cells and TLR-mediated responses in myeloma SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Harvard Univ, Sch Med, Boston, MA 02132 USA. DFCI, HMS, Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1404 EP A1404 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903017 ER PT J AU Rossen, RD Trial, JA Rubio, JA Siwak, EB Hamill, RI Rodriguez-Barradas, MC Breaux, K Birdsall, HH DeBakey, ME AF Rossen, RD Trial, JA Rubio, JA Siwak, EB Hamill, RI Rodriguez-Barradas, MC Breaux, K Birdsall, HH DeBakey, ME TI Predicting susceptibility to secondary infection in HIV-1 infected people SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1436 EP A1436 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903166 ER PT J AU Rumawas, ME McKeown, NM Meigs, JB Wilson, PWF Jacques, PF AF Rumawas, ME McKeown, NM Meigs, JB Wilson, PWF Jacques, PF TI Magnesium intake is favorable associated with improved insulin sensitivity in the Framingham Offspring cohort SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Tufts Univ, JM USDA HNRC, Boston, MA 02111 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Gen Clin Res Ctr, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1464 EP A1464 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903297 ER PT J AU Schutzer, WE Reed, JF Mader, SL AF Schutzer, WE Reed, JF Mader, SL TI Decline in caveolin-1 expression and scaffolding of G protein receptor kinase-2 with age in Fischer 344 aortic vascular smooth muscle SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Portland VA Med Ctr, Res Serv, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1301 EP A1301 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610902198 ER PT J AU Stone, JR Talusan, P Bedri, S Kattapuram, T AF Stone, JR Talusan, P Bedri, S Kattapuram, T TI Variations in vascular intimal proteoglycans and site-specific susceptibility to atherosclerosis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1044 EP A1044 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900335 ER PT J AU Weber, DA Dao, CT Laur, O Jensen, PE AF Weber, DA Dao, CT Laur, O Jensen, PE TI Analysis of the structural basis for DM function SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 MIT, Sch Med, Cambridge, MA 02139 USA. Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Blood Syst Res Inst, San Francisco, CA 94118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1431 EP A1431 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903143 ER PT J AU Yelick, PC Albertson, RC AF Yelick, PC Albertson, RC TI Independent roles revealed for Fgf8 signaling in left-right patterning of the visceral organs and craniofacial skeleton SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Harvard Univ, Sch Dent Med, Forsyth Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1362 EP A1363 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610902485 ER PT J AU Zavala-Ruiz, Z Strug, I Walker, BD Norris, PJ Stern, LJ AF Zavala-Ruiz, Z Strug, I Walker, BD Norris, PJ Stern, LJ TI A hairpin turn in a HIV-gag-derived peptide bound to HLA-DR1 orients peptide residues outside the binding groove for T cell recognition SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 MIT, Cambridge, MA 02139 USA. Univ Massachusetts, Sch Med, Worcester, MA 01003 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Blood Syst Res Inst, San Francisco, CA 94118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1431 EP A1431 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903144 ER PT J AU Lim, GW Wang, SX Mao, JR AF Lim, GW Wang, SX Mao, JR TI CAMP and protein kinase A contribute to the downregulation of spinal glutamate transporters after chronic morphine SO NEUROSCIENCE LETTERS LA English DT Article DE tolerance; opioid; glutamate transporter; cyclic AMP; protein kinase A ID RECEPTOR ANTAGONIST; BETA-ARRESTIN; CELL-DEATH; TOLERANCE; DEPENDENCE; EXPRESSION; NEURONS; MK-801; RATS; PAIN AB Our previous study has shown that spinal glutamate transporters (GTs) are downregulated following chronic morphine administration; however, how spinal GTs are regulated in this process remains unclear. Here we show that the downregulation of spinal GTs (EAAC1 and GLT-1) induced by a 6-day intrathecal morphine (10 mug, twice daily) treatment regimen was prevented by co-administration of morphine with 2',5'-dideoxyadenosine (ddA, 1 mug, a broad adenylyl cyclase inhibitor) or H89 (10 mug, a selective protein kinase A inhibitor). When co-administered with morphine, ddA or H89 also effectively attenuated the development of morphine tolerance in the same rats, while ddA or H89 alone did not affect the baseline nociceptive response. These results indicate that the downregulation of spinal GTs following chronic morphine is at least in part mediated through the intracellular cyclic AMP and protein kinase A pathway, suggesting that this cellular mechanism of GT regulation may be contributory to the development of morphine tolerance in rats. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pain Ctr,Dept Anesthesia & Crit Care,Pain Res Grp, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pain Ctr,Dept Anesthesia & Crit Care,Pain Res Grp, Boston, MA 02114 USA. EM jmao@partners.org FU NIDA NIH HHS [R01 DA08835]; NINDS NIH HHS [NS42661, NS45681] NR 35 TC 22 Z9 31 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 7 PY 2005 VL 376 IS 1 BP 9 EP 13 DI 10.1016/j.neulet.2004.11.016 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 898UI UT WOS:000227101300003 PM 15694265 ER PT J AU Paganetti, H Jiang, H Trofimov, A AF Paganetti, H Jiang, H Trofimov, A TI 4D Monte Carlo simulation of proton beam scanning: modelling of variations in time and space to study the interplay between scanning pattern and time-dependent patient geometry SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Workshop on Current Topics in Monte Carlo Treatment Planning CY MAY 03-05, 2004 CL McGill Univ, Montreal Gen Hosp, Montreal, CANADA SP Natl Canc Inst Canada, Canadian Inst Hlth Res, Inst Canc Res, Res Grants Off, McGill Univ, Post Grad Student Soc, Inst Phys Publishing HO McGill Univ, Montreal Gen Hosp ID DOSE CALCULATIONS; PARTICLE RADIOTHERAPY; INTENSITY MODULATION; ORGAN MOTION; LUNG-TUMORS; THERAPY; GEANT4; RANGE AB When dosimetric effects in time-dependent geometries are studied, usually either the results of individual three-dimensional (3D) calculations are combined or probability-based approaches are applied. These methods may become cumbersome and time-consuming if high time resolution is required or if the geometry is complex. Furthermore, it is difficult to study double-dynamic systems, e.g., to investigate the influence of time-dependent beam delivery (i.e., magnetically moving beam spots in proton beam scanning) on the dose deposition in a moving target. We recently introduced the technique of 4D Monte Carlo dose calculation to model continuously changing geometries. In intensity modulated proton therapy, dose is delivered by individual pristine Bragg curves. Dose spots are positioned in the patient by varying magnetic field and beam energy. If the movement of these dose spots occurs during significant respiratory motion, interplay effects can take place. Because of the inhomogeneity of individual subfields, the consequences of motion can be more severe than in conventional proton therapy. We demonstrate how the technique of 4D Monte Carlo can be used to study interplay effects in proton beam scanning. Time-dependent beam delivery to a changing patient geometry is simulated in a single 4D dose calculation. Interplay effects between respiratory motion and beam scanning speed are demonstrated. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Paganetti, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. EM hpaganetti@partners.org FU NCI NIH HHS [CA 21239] NR 29 TC 46 Z9 47 U1 1 U2 9 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAR 7 PY 2005 VL 50 IS 5 SI SI BP 983 EP 990 DI 10.1088/0031-9155/50/5/020 PG 8 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 909UT UT WOS:000227886900021 PM 15798270 ER PT J AU Shelburne, SA Visnegarwala, F Darcourt, J Graviss, EA Giordano, TP White, AC Hamill, RJ AF Shelburne, SA Visnegarwala, F Darcourt, J Graviss, EA Giordano, TP White, AC Hamill, RJ TI Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy SO AIDS LA English DT Article DE HIV; opportunistic infections; HAART; immune reconstitution inflammatory syndrome; incidence; risk factors ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HIV-INFECTED PATIENTS; RESTORATION DISEASE; CRYPTOCOCCUS-NEOFORMANS; PROTEASE-INHIBITOR; UNITED-STATES; TUBERCULOSIS; PATIENT; AIDS; INITIATION AB Background: There is little systematic information regarding the immune reconstitution inflammatory syndrome (IRIS). Objective: To determine the incidence, risk factors, and long-term outcome of IRIS in HIV-infected patients receiving highly active antiretroviral therapy (HAART) who were coinfected with one of three common opportunistic pathogens. Design: A retrospective cohort identified through a city-wide prospective surveillance program. Methods: A retrospective chart review was performed for 180 HIV-infected patients who received HAART and were coinfected with Mycobacterium tuberculosis, Mycobacterium avium complex, or Cryptococcus neoformans between 1997 and 2000. Medical records were reviewed for baseline demographics, receipt and type of HAART, response to antiretroviral therapy, development of IRIS, and long-term outcome. Results: In this cohort, 31.7% of patients who received HAART developed IRIS. Patients with IRIS were more likely to have initiated HAART nearer to the time of diagnosis of their opportunistic infection (P < 0.001), to have been antiretroviral naive at time of diagnosis of their opportunistic infection (P < 0.001), and to have a more rapid initial fall in HIV-1 RNA level in response to HAART (P < 0.001). Conclusions: IRIS is common among HIV-infected persons coinfected with M. tuberculosis, M. avium complex, or C. neoformans. Antiretroviral drug-naive patients who start HAART in close proximity to the diagnosis of an opportunistic infection and have a rapid decline in HIV-1 RNA level should be monitored for development of this disorder. (c) 2005 Lippincott Williams & Wilkins. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Infect Dis Sect, Houston, TX USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Michael E De Bakey VA Med Ctr, Houston, TX USA. RP Hamill, RJ (reprint author), Vet Affairs Med Ctr, Sect Infect Dis 111G, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM richard.hamill@med.va.gov OI White, A Clinton/0000-0002-9668-4632 FU NIAID NIH HHS [T32-AI055413]; NIMH NIH HHS [K23-MH067505] NR 35 TC 353 Z9 369 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 4 PY 2005 VL 19 IS 4 BP 399 EP 406 DI 10.1097/01.aids.0000161769.06158.8a PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 912XO UT WOS:000228113400005 PM 15750393 ER PT J AU Jang, BC Jung, TY Paik, JH Kwon, YK Shin, SW Kim, SP Ha, JS Suh, MH Suh, SI AF Jang, BC Jung, TY Paik, JH Kwon, YK Shin, SW Kim, SP Ha, JS Suh, MH Suh, SI TI Tetradecanoyl phorbol acetate induces expression of Toll-like receptor 2 in U937 cells: involvement of PKC, ERK, and NF-kappa B SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE TPA; TLR2; PKC; ERKs; NF-kappa B ID KINASE C-BETA; PROTEIN-KINASE; MAP KINASE; EPITHELIAL-CELLS; GENE-EXPRESSION; ACTIVATION; LIPOPOLYSACCHARIDE; PATHWAYS; INNATE; DIFFERENTIATION AB Toll-like receptors (TLRs) have been identified recently as crucial signaling receptors mediating the innate immune recognition. Though induction of TLR2 or TLR4 by 12-O-tetradecanoyl phorbol 13-acetate (TPA) in leukemia cells has been reported, however, the mechanism by which TPA up-regulates TLR2 or TLR4 remains poorly understood. In this study, we investigated the effect of TPA on induction of TLR2 in U937 cells. TPA markedly induced TLR2 mRNA and protein expressions. TLR2 expression in response to TPA was attenuated by pretreatments with GF109203X and Go6976 (inhibitors of protein kinase C (PKC)) and PD98059 (an inhibitor of extracellular signal-regulated kinases (ERKs)), but not SB203580 (an inhibitor of p38s) and SP600125 (an inhibitor of c-Jun N-terminal kinases), suggesting involvement of PKC and ERKs in this response. Moreover, TPA-induced PKC activation was linked to generation of reactive oxygen species, which were dispensable for TLR2 expression in U937 cells. Pretreatments with GF109203X blocked TPA-induced phosphorylation of ERKs, suggesting activation of ERKs by PKC. In addition, TPA induced nuclear factor-kappaB (NF-kappaB) activation, which was shown by increased nuclear translocation of p65 NF-kappaB and degradation of IkappaB-alpha, a NF-kappaB inhibitory protein. Importantly, TPA-induced TLR2 expression was inhibited by blockage of NF-kappaB activation using NF-kappaB inhibitors, including MG132 and BAY11-7085. Specifically, TPA-induced nuclear translocation of NF-kappaB was effectively attenuated by GF109203X and PD98059, suggesting PKC and ERK regulation of NF-kappaB nuclear localization in response to TPA. Together, these results suggest that TPA-induced TLR2 expression in U937 cells may be at least in part mediated through activation of PKC and ERKs as well as NF-kappaB transcription factor, and that cross-talk between PKC or ERKs and NF-kappaB may exist. (C) 2005 Elsevier Inc. All rights reserved. C1 Keimyung Univ, Sch Med, Chron Dis Res Ctr, Taegu 700712, South Korea. Keimyung Univ, Sch Med, Inst Med Sci, Taegu 700712, South Korea. Daegu Haany Univ, Coll Oriental Med, Dept Oriental Med, Taegu 706060, South Korea. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med & Genet, Boston, MA 02115 USA. RP Suh, SI (reprint author), Keimyung Univ, Sch Med, Chron Dis Res Ctr, 194 DongSan Dong, Taegu 700712, South Korea. EM seong@dsmc.or.kr OI Ha, Jung Sook/0000-0002-6475-4886 NR 29 TC 11 Z9 11 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 4 PY 2005 VL 328 IS 1 BP 70 EP 77 DI 10.1016/j.bbrc.2004.12.144 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 894NU UT WOS:000226799600012 PM 15670752 ER PT J AU ABou-Khamis, TA Dewald, O Zymek, P Leucker, T Ren, GF Rollins, B Entman, M Frangogiannis, N AF ABou-Khamis, TA Dewald, O Zymek, P Leucker, T Ren, GF Rollins, B Entman, M Frangogiannis, N TI C-C Chemokines in healing myocardial infarcts: studies using MCP-1/CCL2-/- and MIP-1[alpha]/CCL3 mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Baylor Coll Med, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Dewald, Oliver/A-3126-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A491 EP A491 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610703343 ER PT J AU Barber, DL Wherry, EJ Masopust, D Greenwald, RJ Sharpe, AH Freeman, GJ Ahmed, R AF Barber, DL Wherry, EJ Masopust, D Greenwald, RJ Sharpe, AH Freeman, GJ Ahmed, R TI PD-L1 blockade restores function to CD8 T cells during chronic viral infection SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA. Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. Harvard Univ, Dept Pathol, Div Immunol Res, Brigham & Womens Hosp,Med Sch, Boston, MA 02115 USA. Harvard Univ, Dept Med, Dana Farber Canc Inst, Dept Adult Oncol,Med Sch, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A893 EP A893 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610706296 ER PT J AU Bardwell, PD Shimizu, I Buchli, JC Sykes, M AF Bardwell, PD Shimizu, I Buchli, JC Sykes, M TI Successful induction of mixed chimerism and tolerance with non-myeloablative conditioning in mice presensitized with fully mismatched skin grafts SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RI Bardwell, Philip/H-2219-2014 OI Bardwell, Philip/0000-0002-3835-255X NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A331 EP A331 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610702249 ER PT J AU Chahal, MS Huynh, P Knoepp, SM Xie, YH Meier, KE AF Chahal, MS Huynh, P Knoepp, SM Xie, YH Meier, KE TI Role for phospholipase D2 in tumorigenesis in EL4 lymphoma cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Washington State Univ, Grad Program Pharmacol Toxicol, Pullman, WA 99164 USA. Washington State Univ, Dept Pharmaceut Sci, Pullman, WA 99164 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A523 EP A523 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610703493 ER PT J AU Gadjeva, MG Tomczak, MF Zhang, M Wang, Y Dull, K Erdman, S Rogers, A Fox, J Carroll, M Horwitz, B AF Gadjeva, MG Tomczak, MF Zhang, M Wang, Y Dull, K Erdman, S Rogers, A Fox, J Carroll, M Horwitz, B TI Inhibiting LPS-induced vascular collapse: a key role for NF kappa B (p50,p65) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A373 EP A373 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610702443 ER PT J AU Gray, M Zhou, HZ Swanson, R Simonis, U Ma, XK Cecchini, G AF Gray, M Zhou, HZ Swanson, R Simonis, U Ma, XK Cecchini, G TI Mitochondrial respiratory complex I function contributes to cardioprotection caused by inhibition or disruption of PARP-1 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Univ Calif San Francisco, Div Cardiol, San Francisco Gen Hosp, San Francisco, CA 94110 USA. Univ Calif San Francisco, San Francisco VA Med Ctr, Neurol Serv, San Francisco, CA 94121 USA. San Francisco State Univ, Dept Chem & Biochem, San Francisco, CA 94132 USA. Univ Calif San Francisco, Div Mol Biol, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A259 EP A260 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610701569 ER PT J AU Herman, AE Park, R Mathis, D Benoist, C AF Herman, AE Park, R Mathis, D Benoist, C TI Evolution of T regulatory cell gene expression from the peripheral immune system to an autoimmune lesion SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Genom Inst Novartis Res Fdn, San Diego, CA 92121 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A339 EP A340 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610702287 ER PT J AU Hsu, HC Yang, PA Wu, Q Zhou, JL Wu, YL Freeman, BA Mountz, JD AF Hsu, HC Yang, PA Wu, Q Zhou, JL Wu, YL Freeman, BA Mountz, JD TI Nitrotyrosine-modified proteins as target autoantigens for lupus nephritis in BXD2 mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Univ Alabama, Ctr Free Rad Biol, Birmingham, AL 35294 USA. Birmingham VAMC, Birmingham, AL 35233 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A884 EP A884 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610706257 ER PT J AU Iweala, OI McBee, ME Schauer, DB Nagler-Anderson, C AF Iweala, OI McBee, ME Schauer, DB Nagler-Anderson, C TI The influence of a Th1 polarizing bacterial infection on the response to dietary antigen SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A4 EP A4 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610700016 ER PT J AU Jones, RE Kitzerow, N Moes, N Estrada, M Bourdette, D Whitham, R Vandenbark, A Offner, H AF Jones, RE Kitzerow, N Moes, N Estrada, M Bourdette, D Whitham, R Vandenbark, A Offner, H TI Bone marrow-derived CNS APC and EAE susceptibility influenced by gender SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A349 EP A349 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610702331 ER PT J AU Kong, TQ Eltzschig, HK Karlhausen, J Colgan, SP Shelley, CS AF Kong, TQ Eltzschig, HK Karlhausen, J Colgan, SP Shelley, CS TI Leukocyte adhesion during hypoxia is mediated by HIF-1L dependent induction of beta 2 integrin gene expression SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Expt Therapeut, Int Union Physiol Sci C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Hosp Tubingen, Dept Anesthesia, D-72076 Tubingen, Germany. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A340 EP A340 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610702291 ER PT J AU Kronenberg, HM AF Kronenberg, HM TI PTHrP regulates chondrocyte proliferation and differentiation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A768 EP A768 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610705378 ER PT J AU Lathers, DMR Cigal, ML Sutton, KK Young, MR AF Lathers, DMR Cigal, ML Sutton, KK Young, MR TI Squamous cell carcinoma-derived factors selectively recruit T-cell subpopulations SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A39 EP A39 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610700184 ER PT J AU LeGuern, C Altman, E Sachs, DH Germana, S AF LeGuern, C Altman, E Sachs, DH Germana, S TI Regulatory tolerance to MHC class I-disparate allografts correlates with T-reg cell activation by self class II/peptide complexes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, TBRC, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A332 EP A332 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610702252 ER PT J AU Ma, QF Chen, CL Broom, D Li, Z Liu, Y de Nooij, J Jessell, T Woolf, C AF Ma, QF Chen, CL Broom, D Li, Z Liu, Y de Nooij, J Jessell, T Woolf, C TI Runx1 determines the phenotype of primary sensory neurons mediating thermal and neuropathic pain SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH 03755 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A764 EP A764 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610705356 ER PT J AU Mempel, TR Pittet, M Khazaie, K Weissleder, R von Boehmer, H von Andrian, UH AF Mempel, TR Pittet, M Khazaie, K Weissleder, R von Boehmer, H von Andrian, UH TI Antigen-specific CD4+CD25+ T cells selectively suppress the acquisition of lytic activity, but not the migratory or antigen recognition capacity of CD8 T cells in lymph nodes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A930 EP A930 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610706471 ER PT J AU Mernitz, H Smith, DE Zhu, AX Wang, XD AF Mernitz, H Smith, DE Zhu, AX Wang, XD TI Effects of 9-cis retinoic acid supplementation on COX-2 and RAR-beta levels and tumor formation in the lungs of NNK-induced A/J mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Tufts Univ, Nutr & Canc Biol Lab, Comparat Biol Unit, Jm USDA,Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A78 EP A78 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610700359 ER PT J AU Mitoma, J Gauguet, JM Kawashima, H Petryniak, B Lowe, JB von Andrian, UH Fukuda, M AF Mitoma, J Gauguet, JM Kawashima, H Petryniak, B Lowe, JB von Andrian, UH Fukuda, M TI Extended core 1 O-glycans in lymphocyte trafficking: analysis of mice deficient in core 1 extension enzyme, beta1,3-N-acetylglucosaminyltransferase-3 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Burnham Inst, Glycobiol Program, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A871 EP A871 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610706194 ER PT J AU Montfort, MJ Bouwer, HGA Wagner, CR Hinrichs, DJ AF Montfort, MJ Bouwer, HGA Wagner, CR Hinrichs, DJ TI CD4+ CD25+ regulatory T cells control the upper limit of peptide-specific CD8+ T-cell expansion following secondary L-monocytogenes infection SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Oregon Hlth Sci Univ, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. Earle A Chiles Res Inst, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A395 EP A396 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610702547 ER PT J AU Mora, JR Cheng, G Picarella, D Briskin, M Buchanan, N von Andrian, UH AF Mora, JR Cheng, G Picarella, D Briskin, M Buchanan, N von Andrian, UH TI Reciprocal and dynamic control of T cell homing by dendritic cells from gut and peripheral lymphoid tissues SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Millennium Pharmaceut, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A927 EP A927 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610706457 ER PT J AU Nelson, AG Million, M Chaudhuri, G Tache, Y AF Nelson, AG Million, M Chaudhuri, G Tache, Y TI Effects of estrogen on stress related alterations in colonic motor function in rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Univ Calif Los Angeles, Los Angeles, CA 90095 USA. VA Greater LA Healthcare, Ctr Neurovisceral Sci & Womens Hlth, CURE, Digest Dis Res Ctr, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A98 EP A98 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610700450 ER PT J AU Orson, FM Kinsey, BM Densmore, CL Mbawuike, IN Wyde, PR AF Orson, FM Kinsey, BM Densmore, CL Mbawuike, IN Wyde, PR TI Protection against fatal influenza infection by aerosol genetic immunization in mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Expt Therapeut, Int Union Physiol Sci C1 Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A896 EP A896 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610706310 ER PT J AU Popescu, G Badizadegan, K Dasari, RR Feld, MS AF Popescu, G Badizadegan, K Dasari, RR Feld, MS TI Imaging erythrocyte dynamic subdomains by Fourier phase Microscopy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A684 EP A684 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610704625 ER PT J AU Stone, JR Kattapuram, T Maki, JL AF Stone, JR Kattapuram, T Maki, JL TI Regulation of hnRNP-C function by physiologic levels of hydrogen peroxide and protein kinase CK1 alpha SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A819 EP A819 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610705620 ER PT J AU Tung, CH AF Tung, CH TI In vivo imaging of enzymes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A217 EP A217 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610701363 ER PT J AU Umetsu, S Lee, WL McIntire, JJ Downey, L Sanjanwala, B Akbari, O Berry, G Nagumo, H Freeman, G Umetsu, DT DeKruyff, RH AF Umetsu, S Lee, WL McIntire, JJ Downey, L Sanjanwala, B Akbari, O Berry, G Nagumo, H Freeman, G Umetsu, DT DeKruyff, RH TI Costimulation by TIM-1 induces T cell activation and inhibits the development of peripheral tolerance SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Stanford Univ, Stanford, CA 94305 USA. Northwestern Univ, Chicago, IL 60611 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Jones, Jennifer/C-8691-2015 OI Jones, Jennifer/0000-0002-9488-7719 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A905 EP A905 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610706352 ER PT J AU Wilhelm, CJ Johnson, RA Eshleman, AJ Janowsky, A AF Wilhelm, CJ Johnson, RA Eshleman, AJ Janowsky, A TI Methamphetamine: one curious transporter substrate SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Oregon Hlth Sci Univ, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A513 EP A513 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610703448 ER PT J AU Yang, G Rajadurai, A Tsao, HS AF Yang, G Rajadurai, A Tsao, HS TI Recurrent patterns of dual RB and P53 pathway inactivation in melanoma SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Massachusetts Gen Hosp, Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A482 EP A482 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610703301 ER PT J AU Zhang, M Takahashi, K Alicot, EM Kessler, B Ezekowitz, RAB Moore, FD Carrroll, MC AF Zhang, M Takahashi, K Alicot, EM Kessler, B Ezekowitz, RAB Moore, FD Carrroll, MC TI The role of mannose-binding lectin in natural IgM mediated ischemia/reperfusion injury SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Expt Therapeut, Int Union Physiol Sci C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. DecImmune Therapeut, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A321 EP A321 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610702202 ER PT J AU Zhang, M Alicot, EM Chiu I Verna, N Vorup-Jensen, T Kessler, B Shimaoka, M Chan, R Friend, D Michael, LH Entman, ML Moore, FD Carroll, MC AF Zhang, M Alicot, EM Chiu, I Verna, N Vorup-Jensen, T Kessler, B Shimaoka, M Chan, R Friend, D Michael, LH Entman, ML Moore, FD Carroll, MC TI Identification of the target self-antigens in ischemia/reperfusion injury SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Expt Therapeut, Int Union Physiol Sci C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. DecImmune Therapeut Inc, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Baylor Coll Med, DeBakey Heart Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A321 EP A321 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610702203 ER PT J AU Nagy, AK Kane, DJ Tran, CM Farley, RA Faller, LD AF Nagy, AK Kane, DJ Tran, CM Farley, RA Faller, LD TI Evidence calcium pump binds magnesium before inorganic phosphate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SARCOPLASMIC-RETICULUM ATPASE; ADENOSINE-TRIPHOSPHATASE; O-18 EXCHANGE; INDEPENDENT PHOSPHORYLATION; CONFORMATIONAL CHANGE; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; MECHANISM; ENZYME; ION AB Calcium pump-catalyzed O-18 exchange between inorganic phosphate and water was studied to test the hypothesis that all P-type pumps bind Mg2+ before P-i and validate utilization of the rate equation for ordered binding to interpret differences between site-directed mutants and wild-type enzyme. The results were remarkably similar to those obtained earlier with sodium pump ( Kasho, V. N., Stengelin, M., Smirnova, I. N., and Faller, L. D. ( 1997) Biochemistry 36, 8045 - 8052). The equation for ordered binding of Mg2+ before P-i fit the data best with only a slight chance ( 0.6%) of P-i binding to apoenzyme. Therefore, P-i is the substrate, and Mg2+ is an obligatory cofactor. The intrinsic Mg2+ dissociation constant from metalloenzyme ( K-M = 3.5 +/- 0.3 mM) was experimentally indistinguishable from the sodium pump value. However, the half-maximal concentration for P-i binding to metalloenzyme ( K'(P) = 6.3 +/- 0.6 mM) was significantly higher ( similar to 6-fold), and the probability of calcium pump forming phosphoenzyme from bound P-i ( P-c = 0.04 +/- 0.03) was significantly lower ( similar to 6-fold) than for the sodium pump. From estimates of the rate constants for phosphorylation and dephosphorylation, the calcium pump appears to catalyze phosphoryl group transfer less efficiently than the sodium pump. Ordered binding of Mg2+ before P-i implies that both calcium pump and sodium pump form a ternary enzyme(.)metal(.)phosphate complex, consistent with molecular structures of other haloacid dehalogenase superfamily members that were crystallized with Mg2+ and phosphate, or a phosphate analogue, bound. C1 Vet Adm Greater Los Angeles Healthcare Syst, CURE, Los Angeles, CA 90073 USA. Univ So Calif, Sch Med, Dept Physiol & Biochem, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA. Univ Calif Los Angeles, Sch Med, CURE, Digest Dis Res Ctr,Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90095 USA. RP Vet Adm Greater Los Angeles Healthcare Syst, CURE, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM lfaller@ucla.edu FU NIDDK NIH HHS [DK52802] NR 44 TC 3 Z9 3 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 4 PY 2005 VL 280 IS 9 BP 7435 EP 7443 DI 10.1074/jbc.M412319200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 902ZR UT WOS:000227395700004 PM 15591322 ER PT J AU Yasukawa, T Tokunaga, E Ota, H Sugita, H Martyn, JAJ Kaneki, M AF Yasukawa, T Tokunaga, E Ota, H Sugita, H Martyn, JAJ Kaneki, M TI S-nitrosylation-dependent inactivation of Akt/protein kinase B in insulin resistance SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NITRIC-OXIDE SYNTHASE; CALCIUM-RELEASE CHANNEL; SKELETAL-MUSCLE; GLUCOSE-TRANSPORT; SIGNAL-TRANSDUCTION; NITROSATIVE STRESS; MICE LACKING; ACTIVATION; CELLS; GENE AB Inducible nitric-oxide synthase ( iNOS) has been implicated in many human diseases including insulin resistance. However, how iNOS causes or exacerbates insulin resistance remains largely unknown. Protein S-nitrosylation is now recognized as a prototype of a redox-dependent, cGMP-independent signaling component that mediates a variety of actions of nitric oxide ( NO). Here we describe the mechanism of inactivation of Akt/protein kinase B ( PKB) in NO donor-treated cells and diabetic ( db/db) mice. NO donors induced S-nitrosylation and inactivation of Akt/PKB in vitro and in intact cells. The inhibitory effects of NO donor were independent of phosphatidylinositol 3-kinase and cGMP. In contrast, the concomitant presence of oxidative stress accelerated S-nitrosylation and inactivation of Akt/PKB. In vitro denitrosylation with reducing agent reactivated recombinant and cellular Akt/PKB from NO donortreated cells. Mutated Akt1/PKBalpha( C224S), in which cysteine 224 was substituted by serine, was resistant to NO donor-induced S-nitrosylation and inactivation, indicating that cysteine 224 is a major S-nitrosylation acceptor site. In addition, S-nitrosylation of Akt/PKB was increased in skeletal muscle of diabetic ( db/db) mice compared with wild-type mice. These data suggest that S-nitrosylation-mediated inactivation may contribute to the pathogenesis of iNOS- and/or oxidative stress-involved insulin resistance. C1 Harvard Univ, Sch Med, Shriners Hosp Children, Massachusetts Gen Hosp,Dept Anesthesia & Crit Car, Boston, MA 02114 USA. RP Kaneki, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 149 13th St,Rm 6604, Charlestown, MA 02129 USA. EM mkaneki@helix.mgh.harvard.edu FU NIDDK NIH HHS [R01DK058127]; NIGMS NIH HHS [R01 GM055082, GM21700, R01GM061411, R01GM055082, R01GM031569] NR 60 TC 146 Z9 151 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 4 PY 2005 VL 280 IS 9 BP 7511 EP 7518 DI 10.1074/jbc.M411871200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 902ZR UT WOS:000227395700013 PM 15632167 ER PT J AU Beaulieu, V Da Silva, N Pastor-Soler, N Brown, CR Smith, PJS Brown, D Breton, S AF Beaulieu, V Da Silva, N Pastor-Soler, N Brown, CR Smith, PJS Brown, D Breton, S TI Modulation of the actin cytoskeleton via gelsolin regulates vacuolar H+-ATPase recycling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLARIZED EPITHELIAL-CELLS; MALE REPRODUCTIVE-TRACT; DOMAIN-BINDING-PROTEIN; F-ACTIN; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; INTERCALATED CELLS; ADENYLYL-CYCLASE; CHROMAFFIN CELLS; COLLECTING DUCT; TERMINAL DOMAIN AB The role of the actin cytoskeleton in regulating membrane protein trafficking is complex and depends on the cell type and protein being examined. Using the epididymis as a model system in which luminal acidification is crucial for sperm maturation and storage, we now report that modulation of the actin cytoskeleton by the calcium- activated actin- capping and - severing protein gelsolin plays a key role in regulating vacuolar H+ ATPase ( V- ATPase) recycling. Epididymal clear cells contain abundant V- ATPase in their apical pole, and an increase in their cell- surface V- ATPase expression correlates with an increase in luminal proton secretion. We have shown that apical membrane accumulation of VATPase is triggered by an elevation in cAMP following activation of bicarbonate- regulated soluble adenylyl cyclase in response to alkaline luminal pH ( Pastor- Soler, N., Beaulieu, V., Litvin, T. N., Da Silva, N., Chen, Y., Brown, D., Buck, J., Levin, L. R., and Breton, S. ( 2003) J. Biol. Chem. 278, 49523 - 49529). Here, we show that clear cells express high levels of gelsolin, indicating a potential role in the functional activity of these cells. When jasplakinolide was used to overcome the severing action of gelsolin by polymerizing actin, complete inhibition of the alkaline pH- and cAMP- induced apical membrane accumulation of V- ATPase was observed. Conversely, when gelsolin- mediated actin filament elongation was inhibited using a 10- residue peptide ( PBP10) derived from the phosphatidylinositol 4,5- bisphosphatebinding region ( phosphoinositide- binding domain 2) of gelsolin, significant V- ATPase apical membrane mobilization was induced, even at acidic luminal pH. In contrast, the calcium chelator 1,2- bis( 2- aminophenoxy) ethaneN, N, N', N'- tetraacetic acid tetrakis( acetoxymethyl ester) and the phospholipase C inhibitor U- 73122 inhibited the alkaline pH- induced V- ATPase apical accumulation. Thus, maintenance of the actin cytoskeleton in a depolymerized state by gelsolin facilitates calcium- dependent apical accumulation of V- ATPase in response to luminal pH alkalinization. Gelsolin is present in other cell types that express the V- ATPase in their plasma membrane and recycling vesicles, including kidney intercalated cells and osteoclasts. Therefore, modulation of the actin cortex by this severing and capping protein may represent a common mechanism by which these cells regulate their rate of proton secretion. C1 Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Marine Biol Lab, BioCurrents Res Ctr, Woods Hole, MA 02543 USA. RP Breton, S (reprint author), Massachusetts Gen Hosp E, Program Membrane Biol, 149 13th St, Charlestown, MA 02129 USA. EM sbreton@partners.org FU NCRR NIH HHS [P41-RR001395]; NICHD NIH HHS [KO8-HD45524, HD08684, HD40793]; NIDDK NIH HHS [DK38452, DK42956, DK43351, DK57521] NR 92 TC 66 Z9 69 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 4 PY 2005 VL 280 IS 9 BP 8452 EP 8463 DI 10.1074/jbc.M412750200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 902ZR UT WOS:000227395700122 PM 15591047 ER PT J AU Gonzalez, E Kulkarni, H Bolivar, H Mangano, A Sanchez, R Catano, G Nibbs, RJ Freedman, BI Quinones, MP Bamshad, MJ Murthy, KK Rovin, BH Bradley, W Clark, RA Anderson, SA O'Connell, RJ Agan, BK Ahuja, SS Bologna, R Sen, L Dolan, MJ Ahuja, SK AF Gonzalez, E Kulkarni, H Bolivar, H Mangano, A Sanchez, R Catano, G Nibbs, RJ Freedman, BI Quinones, MP Bamshad, MJ Murthy, KK Rovin, BH Bradley, W Clark, RA Anderson, SA O'Connell, RJ Agan, BK Ahuja, SS Bologna, R Sen, L Dolan, MJ Ahuja, SK TI The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DISEASE PROGRESSION; BETA-CHEMOKINES; IN-VITRO; MACROPHAGE; INFECTION; CCR5; LYMPHOCYTES; PROTECTION; EVOLUTION AB Segmental duplications in the human genome are selectively enriched for genes involved in immunity, although the phenotypic consequences for host defense are unknown. We show that there are significant interindividual and interpopulation differences in the copy number of a segmental duplication encompassing the gene encoding CCL3L1 (MIP-1alphaP), a potent human immunodeficiency virus-1 (HIV-1)-suppressive chemokine and ligand for the HIV coreceptor CCR5. Possession of a CCL3L1 copy number lower than the population average is associated with markedly enhanced HIV/acquired immunodeficiency syndrome (AIDS) susceptibility. This susceptibility is even greater in individuals who also possess disease-accelerating CCR5 genotypes. This relationship between CCL3L1 dose and altered HIV/AIDS susceptibility points to a central role for CCL3L1 in HIV/AIDS pathogenesis and indicates that differences in the dose of immune response genes may constitute a genetic basis for variable responses to infectious diseases. C1 Univ Texas, Hlth Sci Ctr, Vet Adm Res Ctr AIDS & HIV1 Infect, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Consejo Nacl Invest Cient & Tecn, Lab Biol Celular & Retrovirus, RA-1245 Buenos Aires, DF, Argentina. Hosp Pediat JP Garrahan, Serv Infectol, RA-1245 Buenos Aires, DF, Argentina. Cancer Res UK Beatson Labs, Glasgow G61 1BD, Lanark, Scotland. Wake Forest Univ, Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA. Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA. Univ Utah, Dept Pediat, Salt Lake City, UT 84112 USA. SW Fdn Biomed Res, San Antonio, TX 78227 USA. Ohio State Univ, Div Nephrol, Columbus, OH 43210 USA. Wilford Hall USAF Med Ctr, Infect Dis Serv, Lackland AFB, TX 78236 USA. Wilford Hall USAF Med Ctr, Tri Serv AIDS Clin Consortium, Lackland AFB, TX 78236 USA. Wilford Hall USAF Med Ctr, Henry M Jackson Fdn, Lackland AFB, TX 78236 USA. Def Inst Med Operat, Brooks AFB, TX 78235 USA. RP Ahuja, SK (reprint author), Univ Texas, Hlth Sci Ctr, Vet Adm Res Ctr AIDS & HIV1 Infect, S Texas Vet Hlth Care Syst, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM matthew.dolan@brooks.af.mil; ahujas@uthscsa.edu OI Agan, Brian/0000-0002-5114-1669; Nibbs, Robert/0000-0002-8150-0044 FU NIAID NIH HHS [AI046326, AI043279]; NIMH NIH HHS [MH069270] NR 21 TC 781 Z9 830 U1 6 U2 41 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 MAR 4 PY 2005 VL 307 IS 5714 BP 1434 EP 1440 DI 10.1126/science.1101160 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 904MT UT WOS:000227503100037 PM 15637236 ER PT J AU Rodgers, JT Lerin, C Haas, W Gygi, SP Spiegelman, BM Puigserver, P AF Rodgers, JT Lerin, C Haas, W Gygi, SP Spiegelman, BM Puigserver, P TI Nutrient control of glucose homeostasis through a complex of PGC-1 alpha and SIRT1 SO NATURE LA English DT Article ID HEPATIC GLUCONEOGENESIS; TRANSCRIPTION FACTORS; COACTIVATOR PGC-1; REDOX STATE; PPAR-GAMMA; LIFE-SPAN; DEACETYLASE; METABOLISM; LIVER; MICE AB Homeostatic mechanisms in mammals respond to hormones and nutrients to maintain blood glucose levels within a narrow range. Caloric restriction causes many changes in glucose metabolism and extends lifespan; however, how this metabolism is connected to the ageing process is largely unknown. We show here that the Sir2 homologue, SIRT1 - which modulates ageing in several species(1-3) - controls the gluconeogenic/glycolytic pathways in liver in response to fasting signals through the transcriptional coactivator PGC-1alpha. A nutrient signalling response that is mediated by pyruvate induces SIRT1 protein in liver during fasting. We find that once SIRT1 is induced, it interacts with and deacetylates PGC-1alpha at specific lysine residues in an NAD(+)-dependent manner. SIRT1 induces gluconeogenic genes and hepatic glucose output through PGC-1alpha, but does not regulate the effects of PGC-1alpha on mitochondrial genes. In addition, SIRT1 modulates the effects of PGC-1alpha repression of glycolytic genes in response to fasting and pyruvate. Thus, we have identified a molecular mechanism whereby SIRT1 functions in glucose homeostasis as a modulator of PGC-1alpha. These findings have strong implications for the basic pathways of energy homeostasis, diabetes and lifespan. C1 Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Puigserver, P (reprint author), Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA. EM ppuigse1@bs.jhmi.edu NR 22 TC 1522 Z9 1596 U1 26 U2 153 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 3 PY 2005 VL 434 IS 7029 BP 113 EP 118 DI 10.1038/nature03354 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 902ED UT WOS:000227334600054 PM 15744310 ER PT J AU Bertram, L Hiltunen, M Parkinson, M Ingelsson, M Lange, C Ramasamy, K Mullin, K Menon, R Sampson, AJ Hsiao, MY Elliott, KJ Velicelebi, G Moscarillo, T Hyman, BT Wagner, SL Becker, KD Blacker, D Tanzi, RE AF Bertram, L Hiltunen, M Parkinson, M Ingelsson, M Lange, C Ramasamy, K Mullin, K Menon, R Sampson, AJ Hsiao, MY Elliott, KJ Velicelebi, G Moscarillo, T Hyman, BT Wagner, SL Becker, KD Blacker, D Tanzi, RE TI Family-based association between Alzheimer's disease and variants in UBQLN1 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID APOLIPOPROTEIN-E; LINKAGE; PROTEIN; ALLELE; TESTS; ONSET; UBIQUILIN; AGE; UBIQUITINATION; ACCUMULATION AB BACKGROUND Recent analyses suggest that the known Alzheimer's disease genes account for less than half the genetic variance in this disease. The gene encoding ubiquilin 1 (UBQLN1) is one of several candidate genes for Alzheimer's disease located near a well-established linkage peak on chromosome 9q22. METHODS We evaluated 19 single-nucleotide polymorphisms in three genes within the chromosome 9q linkage region in 437 multiplex families with Alzheimer's disease from the National Institute of Mental Health (NIMH) sample (1439 subjects). We then tested the single-nucleotide polymorphisms showing a positive result in an independently identified set of 217 sibships discordant for Alzheimer's disease (Consortium on Alzheimer's Genetics [CAG] sample; 489 subjects) and assessed the functional effect of an implicated single-nucleotide polymorphism in brain tissue from 25 patients with Alzheimer's disease and 17 controls. RESULTS In the NIMH sample, we observed a significant association between Alzheimer's disease and various single-nucleotide polymorphisms in UBQLN1. We confirmed these associations in the CAG sample. The risk-conferring haplotype in both samples was defined by a single intronic single-nucleotide polymorphism located downstream of exon 8. The risk allele was associated with a dose-dependent increase in an alternatively spliced UBQLN1 (lacking exon 8) transcript in RNA extracted from brain samples of patients with Alzheimer's disease. CONCLUSIONS Our findings suggest that genetic variants in UBQLN1 on chromosome 9q22 substantially increase the risk of Alzheimer's disease, possibly by influencing alternative splicing of this gene in the brain. C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Charlestown, MA USA. Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Alzheimer Dis Res Unit, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Gerontol Res Unit, Charlestown, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Neurogenetics, La Jolla, CA USA. RP Tanzi, RE (reprint author), MGH E, MIND, Genet & Aging Res Unit, 114 16th St, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu NR 30 TC 163 Z9 169 U1 2 U2 9 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 3 PY 2005 VL 352 IS 9 BP 884 EP 894 DI 10.1056/NEJMoa042765 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 901VQ UT WOS:000227310700007 PM 15745979 ER PT J AU Dahm-Daphi, J Hubbe, P Horvath, F El-Awady, RA Bouffard, KE Powell, SN Willers, H AF Dahm-Daphi, J Hubbe, P Horvath, F El-Awady, RA Bouffard, KE Powell, SN Willers, H TI Nonhomologous end-joining of site-specic but not of radiation-induced DNA double-strand breaks is reduced in the presence of wild-type p53 SO ONCOGENE LA English DT Article DE p53; double-strand break; nonhomologous end-joining; radiation; I-SceI ID HUMAN TUMOR-CELLS; HOMOLOGOUS RECOMBINATION; CELLULAR RADIOSENSITIVITY; CHROMOSOMAL-ABERRATIONS; EXONUCLEASE ACTIVITY; POTENTIAL MECHANISM; GENOMIC STABILITY; MAMMALIAN-CELLS; IN-VITRO; REPAIR AB Nonhomologous end-joining (NHEJ) of DNA double-strand breaks (DSBs) entails two principal mechanisms: modi. cation of DNA ends prior to ligation (error-prone rejoining) or precise ligation without modi. cation if the DNA ends are complementary (error-free repair). Error-prone rejoining is mutagenic, because it can lead to destruction of coding sequence or to chromosomal aberrations, and therefore must be tightly regulated. Previous studies on the role of the p53 tumor suppressor in the regulation of NHEJ have yielded conflicting results, but a rigorous analysis of NHEJ proficiency and fidelity in a purely chromosomal context has not been carried out. To this end, we created novel repair plasmid substrates that integrate into the genome. DSBs generated by the I-SceI endonuclease within these substrates were repaired by either error-prone rejoining or precise ligation. We found that the expression of wild-type p53 inhibited any repair-associated DNA sequence deletion, including a more than 250-fold inhibition of error-prone rejoining events compared to p53-null cells, while any promoting effect of p53 on precise ligation could not be directly evaluated. The role of p53 in NHEJ appeared to involve a direct transactivation-independent mechanism, possibly restricting DNA end-modi. cation by blocking the annealing of single strands along flanking stretches of microhomology. The inhibition of error-prone rejoining by p53 did not apply to the rejoining of DSBs induced by ionizing radiation. In conclusion, our data suggest that p53 restricts the mutagenic effects of NHEJ without compromising repair proficiency or cell survival, thereby maintaining genomic stability. C1 Univ Hamburg, Hosp Eppendorf, Dept Radiotherapy & Radiat Oncol, Expt Radiat Oncol Lab, D-20246 Hamburg, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Lab Mol & Cellular Radiat Biol, Charlestown, MA 02129 USA. RP Dahm-Daphi, J (reprint author), Univ Klinikum Hamburg Eppendorf, Klin Strahlentherapie & Radioonkol, Martinstr 52, D-20246 Hamburg, Germany. EM dahm@uke.uni-hamburg.de FU NCI NIH HHS [R01 CA58985] NR 54 TC 42 Z9 46 U1 1 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 MAR 3 PY 2005 VL 24 IS 10 BP 1663 EP 1672 DI 10.1038/sj.onc.1208394 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 902HI UT WOS:000227345100002 PM 15688024 ER PT J AU Lechpammer, M Xu, XJ Ellis, FH Bhattacharaya, N Shapiro, GI Loda, M AF Lechpammer, M Xu, XJ Ellis, FH Bhattacharaya, N Shapiro, GI Loda, M TI Flavopiridol reduces malignant transformation of the esophageal mucosa in p27 knockout mice SO ONCOGENE LA English DT Article DE Barrett's esophagus; Barrett's associated adenocarcinoma; p27; flavopiridol; mouse model ID DEPENDENT KINASE INHIBITOR; BARRETTS-ESOPHAGUS; CYCLIN D1; ADENOCARCINOMA; CANCER; APOPTOSIS; CELLS; TRIAL; CHEMOPREVENTION; NEOPLASMS AB The cyclin-dependent kinase (cdk) inhibitor p27 preferentially inactivates cdk complexes required for progression through the G1/S transition. Loss of p27 is associated with aggressive behavior in a variety of tumors, including Barrett's associated adenocarcinoma (BAA). We have previously shown that gastroduodenal-esophageal reflux (GDER) together with N-methyl-N-benzylnitrosamine (MBN) induces Barrett's esophagus (BE) and malignant transformation of the esophageal mucosa in mice. This process is enhanced in a p27 null background. Here, we show that chronic flavopiridol administration sharply reduced the prevalence of BE in GDER/MBN-treated p27 knockout mice when compared to animals treated with diluent only (7 vs 26%, P = 0.0079). Similarly, flavopiridol reduced the prevalence of BAA (11 vs 32%, P = 0.0098) and overall cancer prevalence (15 vs 60%, P < 0.0001). In addition, appropriate molecular targeting by flavopiridol in tumor cells was confirmed by downregulation of cyclin D1, a known target of this pan-cdk inhibitor. The results of this study represent the experimental basis for chemoprevention with cdk inhibitors in human BE and BAA. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiothorac Surg, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Loda, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, D740 44 Binney St, Boston, MA 02115 USA. EM massimo_loda@dfci.harvard.edu FU NCI NIH HHS [P20 CA90578, R01 CA90687, P01 CA89021, P50 CA90381] NR 26 TC 17 Z9 17 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 3 PY 2005 VL 24 IS 10 BP 1683 EP 1688 DI 10.1038/sj.onc.1208375 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 902HI UT WOS:000227345100004 PM 15674336 ER PT J AU Muss, HB Woolf, S Berry, D Cirrincione, C Weiss, RB Budman, D Wood, WC Henderson, IC Hudis, C Winer, E Cohen, H Wheeler, J Norton, L AF Muss, HB Woolf, S Berry, D Cirrincione, C Weiss, RB Budman, D Wood, WC Henderson, IC Hudis, C Winer, E Cohen, H Wheeler, J Norton, L CA Canc Leukemia Grp B TI Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LEUKEMIA GROUP-B; RANDOMIZED-TRIALS; ELDERLY-PATIENTS; DOSE-INTENSITY; CYCLOPHOSPHAMIDE; METHOTREXATE; TOXICITY; AGE; FLUOROURACIL; THERAPY AB Context Adjuvant chemotherapy improves survival for patients with local-regional breast cancer, but healthy older patients at high risk of recurrence are frequently not offered adjuvant chemotherapy, and the benefit of adjuvant chemotherapy in older patients is uncertain. Objective To compare the benefits and toxic effects of adjuvant chemotherapy among breast cancer patients in age groups of 50 years or younger, 51 to 64 years, and 65 years or older. Design and Setting Retrospective review of data from 4 randomized trials that accrued patients from academic and community medical centers between 1975 and 1999. Median follow-up for all patients was 9.6 years. All trials randomized patients to different regimens, doses, schedules, and durations of chemotherapy and all had a treatment arm with doses or schedules that were regarded to be "high" and potentially more toxic. Patients A total of 6487 women with lymph node-positive breast cancer; 542 (8%) patients were 65 years or older and 159 (2 %) were 70 years or older. Main Outcome Measure Comparison of disease-free survival, overall survival, and treatment-related mortality among different age groups. Results Multivariate analysis showed that smaller tumor size, fewer positive lymph nodes, more chemotherapy, and tamoxifen use were all significantly (P<.001) related to longer disease-free and overall survival. There was no association between age and disease-free survival. Overall survival was significantly (P<.001) worse for patients aged 65 or older because of death from causes other than breast cancer. Thirty-three deaths (0.5% of all patients) were attributed to treatment, and older women had higher treatment-related mortality. Older women and younger women derived Similar reductions in breast cancer mortality and recurrence from regimens containing more chemotherapy. Conclusion Age alone should not be a contraindication to the use of optimal chemotherapy regimens in older women who are in good general health. C1 Univ Vermont, Vermont Canc Ctr, Fletcher Allen Hlth Care, Burlington, VT 05401 USA. Canc & Leukemia Grp B Stat Ctr, Durham, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Vet Adm Med Ctr, Durham, NC USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NYU, N Shore Univ Hosp, Manhasset, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Emory Univ, Sch Med, Atlanta, GA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Muss, HB (reprint author), Univ Vermont, Vermont Canc Ctr, Fletcher Allen Hlth Care, UHC Campus,St Joseph 3400,1 S Prospect St, Burlington, VT 05401 USA. EM hyman.muss@uvm.edu FU NCI NIH HHS [CA32102, CA02599, CA03927, CA04326, CA04457, CA07968, CA08025, CA11028, CA11789, CA12011, CA12046, CA12449, CA16450, CA21060, CA21115, CA25224, CA26806, CA31809, CA31946, CA31983, CA32291, CA33601, CA35091, CA35279, CA35421, CA37135, CA41287, CA45374, CA45389, CA45418, CA45564, CA45808, CA47515, CA47545, CA47555, CA47559, CA47577, CA47642, CA52784, CA54697, CA60138, CA60247, CA71323, CA74811, CA77298, CA77406, CA77440, CA77597, CA77651] NR 31 TC 220 Z9 225 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 2 PY 2005 VL 293 IS 9 BP 1073 EP 1081 DI 10.1001/jama.293.9.1073 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 901LY UT WOS:000227285200017 PM 15741529 ER PT J AU Sellers, WR Meyerson, M AF Sellers, WR Meyerson, M TI EGFR gene mutations: A call for global x global views of cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID RECEPTOR INTRON-1 POLYMORPHISM; AVIAN ERYTHROBLASTOSIS VIRUS; ACUTE PROMYELOCYTIC LEUKEMIA; LUNG-CANCER; BREAST-CANCER; GEFITINIB; RESPONSIVENESS; FREQUENCY; ONCOGENES C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Broad Inst, Cambridge, MA USA. MIT, Cambridge, MA 02139 USA. RP Sellers, WR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM William_Sellers@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 NR 19 TC 22 Z9 23 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 2 PY 2005 VL 97 IS 5 BP 326 EP 328 DI 10.1093/jnci/dji079 PG 3 WC Oncology SC Oncology GA 902JY UT WOS:000227352800001 PM 15741561 ER PT J AU Singh, AK Sagar, P AF Singh, AK Sagar, P TI Gangrenous cholecystitis: prediction with CT imaging SO ABDOMINAL IMAGING LA English DT Article DE gangrenous cholecystitis; acute cholecystitis; gallbladder; mucosal enhancement ID COMPUTED-TOMOGRAPHY; GALLBLADDER; PERFORATION; DIAGNOSIS AB The aim of this study is to determine the usefulness of different patterns of gallbladder mucosal enhancement on contrast-enhanced computed tomography (CT) for differentiating between gangrenous and uncomplicated acute cholecystitis. This retrospective evaluation involved 56 patients with histopathologically proved acute cholecystitis (32 with gangrenous and 24 with uncomplicated acute cholecystitis) who had preoperative contrast-enhanced CT imaging. CT in 38 patients showed a gallbladder mucosal enhancement pattern that could be categorized into continuous, discontinuous, and/or irregular categories. In the other 18 patients, the mucosal enhancement pattern could not be classified due to lack of mucosal enhancement or inadequate mucosal enhancement. On contrast-enhanced CT evaluation, continuous and discontinuous and/or irregular mucosal enhancement patterns were seen in 20 and 18 patients, respectively. Among the 20 patients with continuous mucosal enhancement, 17 had uncomplicated acute cholecystitis. Seventeen of the 18 patients with discontinuous and/or irregular mucosal enhancement had gangrenous cholecystitis. The sensitivity and positive predictive value (PPV) of discontinuous and/or irregular mucosal enhancement in the diagnosis of gangrenous cholecystitis were 30.3% and 94.4% (17 of 18), respectively. The sensitivity and PPV of continuous mucosal enhancement in the diagnosis of uncomplicated acute cholecystitis were 30.3% and 85.5% (17 of 20), respectively. There was a statistically significant difference (p=0.0005) between the PPV of discontinuous and/or irregular (94.4%) and that of continuous (15%) mucosal enhancement for predicting gangrenous cholecystitis. The pattern of gallbladder mucosal enhancement on CT can be used as a reliable criterion for distinguishing acute, uncomplicated cholecystitis from gangrenous cholecystitis. C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Singh, AK (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. EM pallaviajay@hotmail.com NR 16 TC 21 Z9 25 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD MAR-APR PY 2005 VL 30 IS 2 BP 218 EP 221 DI 10.1007/s00261-004-0217-0 PG 4 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 911YR UT WOS:000228044800012 PM 15812680 ER PT J AU Herman, JB AF Herman, JB TI The awarding experience SO ACADEMIC PSYCHIATRY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Psychiat, Clin Serv, Boston, MA 02114 USA. RP Herman, JB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Clin Serv, Bulfinch 355,Fruit St, Boston, MA 02114 USA. EM herman@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD SPR PY 2005 VL 29 IS 1 BP 19 EP 20 DI 10.1176/appi.ap.29.1.19 PG 2 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 902KS UT WOS:000227355600005 PM 15772399 ER EF