FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Miralbell, R Fitzgerald, TJ Laurie, F Kessel, S Glicksman, A Friedman, HS Urie, M Kepner, JL Zhou, TN Chen, ZJ Barnes, P Kun, L Tarbell, NJ AF Miralbell, R Fitzgerald, TJ Laurie, F Kessel, S Glicksman, A Friedman, HS Urie, M Kepner, JL Zhou, TN Chen, ZJ Barnes, P Kun, L Tarbell, NJ TI Radiotherapy in pediatric medulloblastoma: Quality assessment of Pediatric Oncology Group Trial 9031 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE medulloblastoma; quality assurance; Pediatric Oncology Group; radiotherapy ID POSTERIOR-FOSSA; PATTERNS; CHEMOTHERAPY; FAILURE; RELAPSE; SOCIETY; IMPACT AB Purpose: To evaluate the potential influence of radiotherapy quality on survival in high-risk pediatric medulloblastoma patients. Methods and Materials: Trial 9031 of the Pediatric Oncology Group (POG) aimed to study the relative benefit of cisplatin and etoposide randomization of high-risk patients with medulloblastoma to preradiotherapy vs. postradiotherapy treatment. Two-hundred and ten patients were treated according to protocol guidelines and were eligible for the present analysis. Treatment volume (whole brain, spine, posterior fossa, and primary tumor bed) and dose prescription deviations were assessed for each patient. An analysis of first site of failure was undertaken. Event-free and overall survival rates were calculated. A log-rank test was used to determine the significance of potential survival differences between patients with and without major deviations in the radiotherapy procedure. Results: Of 160 patients who were fully evaluable for all treatment quality parameters, 91 (57%) had 1 or more major deviations in their treatment schedule. Major deviations by treatment site were brain (26%), spinal (7%), posterior fossa (40%), and primary tumor bed (17%). Major treatment volume or total dose deviations did not significantly influence overall and event-free survival. Conclusions: Despite major treatment deviations in more than half of fully evaluable patients, underdosage or treatment volume misses were not associated with a worse event-free or overall survival. (c) 2006 Elsevier Inc. C1 Univ Hosp Geneva, Div Radiooncol, Dept Radiat Oncol, CH-1211 Geneva 14, Switzerland. Qual Assurance Review Comm, Providence, RI USA. Duke Univ, South Hosp, Pediat Neurooncol Div, Durham, NC USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Childrens Oncol Grp, Operat Ctr, Arcadia, CA USA. Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. St Jude Childrens Hosp, Dept Radiat Oncol, Memphis, TN 38105 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Miralbell, R (reprint author), Univ Hosp Geneva, Div Radiooncol, Dept Radiat Oncol, CH-1211 Geneva 14, Switzerland. EM Raymond.Miralbell@hcuge.ch FU NCI NIH HHS [CA 29511] NR 14 TC 23 Z9 23 U1 0 U2 1 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 2006 VL 64 IS 5 BP 1325 EP 1330 DI 10.1016/j.ijrobp.2005.11.002 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 028HG UT WOS:000236477200005 PM 16413699 ER PT J AU Fitzek, MM Linggood, RM Adams, J Munzenrider, JE AF Fitzek, MM Linggood, RM Adams, J Munzenrider, JE TI Combined proton and photon irradiation for craniopharyngioma: Long-term results of the early cohort of patients treated at Harvard Cyclotron Laboratory and Massachusetts General Hospital SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE craniopharyngioma; protons; radiotherapy; three-dimensional treatment planning ID RELATIVE BIOLOGICAL EFFECTIVENESS; RADIATION-THERAPY; RADIOTHERAPY; EXPERIENCE; SURGERY; MANAGEMENT; CHILDREN; BEAMS; RBE AB Purpose: We report the results of the early cohort of patients treated for craniopharyngioma with combined proton-photon irradiation at the Massachusetts General Hospital and the Harvard Cyclotron Laboratory. Methods and Materials: Between 1981 and 1988, 15 patients with craniopharyngioma were treated in part or entirely with fractionated 160 MeV proton beam therapy. The group consisted of 5 children (median age, 15.9 years) and 10 adults (median age, 36.2 years). Median dose prescribed to the tumor was 56.9 cobalt Gray equivalent (CGE; 1 proton Gray = 1.1 CGE). The median proton component was 26.9 CGE. Patients were treated after documented recurrence after initial surgery (it = 6) or after subtotal resection or biopsy (n = 9). None had had prior radiation therapy. Results: Median observation period of surviving patients (n = 11) was 13.1 years from radiotherapy. One patient was lost to follow-up with tumor control after 5.2 years. Actuarial 10-year survival rate was 72%. Four patients have died 5-9.1 years after treatment, two from local failure. Actuarial 5- and 10-year local control rates were 93% and 85%, respectively. The functional status of the living adult patients is unaltered from their preradiotherapy status; all of them continued leading normal or near normal working lives. None of the patients treated as a child had experienced recurrence of tumor. One child shows learning difficulties and slight retardation, comparable to his preradiotherapy status. The others have professional achievements within the normal range. Conclusion: Results in terms of survival and local control are comparable with other contemporary series. Although no formal neuropsychological testing was performed, the surrogate measures of lifestyle and professional accomplishments appear to be satisfactory. (c) 2006 Elsevier Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Tufts Univ, New England Med Ctr, Sch Med, Radiat Oncol Ctr, Boston, MA 02111 USA. Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Sch Med, Boston, MA 02115 USA. RP Munzenrider, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM jmunzenrider@partners.org FU NCI NIH HHS [P01 CA 21239] NR 26 TC 47 Z9 47 U1 0 U2 1 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 2006 VL 64 IS 5 BP 1348 EP 1354 DI 10.1016/j.ijrobp.2005.09.034 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 028HG UT WOS:000236477200008 PM 16580494 ER PT J AU Schreibmann, E Chen, GTY Xing, L AF Schreibmann, E Chen, GTY Xing, L TI Image interpolation in 4D CT using a BSpline deformable registration model SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE four-dimensional computed tomography; deformable registration; image-guided radiotherapy; delineation; respiratory motion ID 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; FREE-FORM DEFORMATIONS; FRACTION ORGAN MOTION; NONRIGID REGISTRATION; LUNG-TUMORS; MR-IMAGES; RADIOTHERAPY; ARTIFACTS; MOVEMENT; PROSTATE AB Purpose: To develop a method for deriving the phase-binned four-dimensional computed tomography (4D CT) image sets through interpolation of the images acquired at some known phases. Methods and Materials: Four-dimensional computed tomography data sets for 3 patients were acquired. For each patient, the correlation between inhale and exhale phases was studied and quantified using a BSpline deformable model. Images at an arbitrary phase were deduced by an interpolation of the deformation coefficients. The accuracy of the proposed scheme was assessed by comparing marker trajectories and by checkerboard/difference display of the interpolated and acquired images. Results: The images at intermediate phases could be derived by an interpolation of the deformation field. An analysis of marker movements indicated that 3 mm accuracy is achievable by the interpolation. The subtraction of image analysis indicated a similar level of success. The proposed technique was useful also for automatically mapping the organ contours in a known phase to other phases, and for designing patient-specific margins in the presence of respiratory motion. Finally, the technique led to a 90% reduction in the acquired data, because in the BSpline model, a lattice of only a few thousand values is sufficient to describe a CT data set of 25 million pixels. Conclusions: Organ deformation can be well modeled by using a BSpline model. The proposed technique may offer useful means for radiation dose reduction, binning artifacts removal, and disk storage improvement in 4D imaging. (c) 2006 Elsevier Inc. C1 Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Xing, L (reprint author), Stanford Univ, Sch Med, Dept Radiat Oncol, 875 Blake Wilbur Dr, Stanford, CA 94305 USA. EM lei@reyes.stanford.edu FU NCI NIH HHS [1 R01 CA98523-01] NR 46 TC 70 Z9 77 U1 0 U2 5 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 2006 VL 64 IS 5 BP 1537 EP 1550 DI 10.1016/j.ijrobp.2005.11.018 PG 14 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 028HG UT WOS:000236477200032 PM 16503382 ER PT J AU Engelsman, M Rietzel, E Kooy, HM AF Engelsman, M Rietzel, E Kooy, HM TI Four-dimensional proton treatment planning for lung tumors SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 24-28, 2005 CL Seattle, WA SP Amer Assoc Physicists Med DE four-dimensional computed tomography; proton; treatment planning; lung ID RESPIRATORY MOTION; ONLINE COMPENSATION; BEAM RADIOTHERAPY; TARGET MOTION; CANCER; THERAPY; RADIATION; CT AB Purpose: In proton radiotherapy, respiration-induced variations in density lead to changes in radiologic path lengths and will possibly result in geometric misses. We compared different treatment planning strategies for lung tumors that compensate for respiratory motion. Methods and Materials: Particle-specific treatment planning margins were applied to standard helical computed tomography (CT) scans as well as to "representative" CT scans. Margins were incorporated beam specific laterally by aperture widening and longitudinally by compensator smearing. Furthermore, treatment plans using full time-resolved 4D-computed tomography data were generated. Results: Four-dimensional treatment planning guaranteed target coverage throughout a respiratory cycle. Use of a standard helical CT data set resulted in underclosing the target volume to 36% or the prescribed dose. For CT data representing average target positions, coverage call be expected but not guaranteed. In comparison to this strategy, 4D planning decreased the mean lung dose by tip to 16% and the lung volume receiving 20 Gy (prescribed target dose 72 Gy) by up to 15%. Conclusion: When the three planning strategies are compared., only 4D proton treatment planning guarantees delivery of the prescribed dose throughout a respiratory cycle. Furthermore, the 4D planning approach results in equal or reduced dose to critical structures; even the ipsilateral lung is spared. (c) 2006 Elsevier Inc. C1 Maastro Clin, NL-6419 PC Heerlen, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Biophys Abt, Gesell Schwerionenforsch, Darmstadt, Germany. RP Engelsman, M (reprint author), Maastro Clin, Henri Dunantstr 5, NL-6419 PC Heerlen, Netherlands. EM martijn.engelsman@maastro.nl FU NCI NIH HHS [5 P01 CA21239-24] NR 24 TC 80 Z9 83 U1 0 U2 11 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 2006 VL 64 IS 5 BP 1589 EP 1595 DI 10.1016/j.ijrobp.2005.12.026 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 028HG UT WOS:000236477200037 PM 16580508 ER PT J AU Amstalden, EMI Carvalho, RB Pacheco, EMB Oliveira, A Stragea-Neto, L Rosenberg, AE AF Amstalden, EMI Carvalho, RB Pacheco, EMB Oliveira, A Stragea-Neto, L Rosenberg, AE TI Chondromatous hamartoma of the chest wall: Description of 3 new cases and literature review SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Review DE chondromatous hamartoma; mesenchymal hamartoma; rib; chest wall; tumor; infancy ID NASAL CHONDROMESENCHYMAL HAMARTOMA; INFANTILE CARTILAGINOUS HAMARTOMA; MESENCHYMAL HAMARTOMA; INFANCY; SECONDARY; CHILDREN; RIB; MANAGEMENT AB Chondromatous hamartoma of the chest wall is art extremely rare, benign lesion that usually occurs in early infancy. It typically arises in the rib cage and produces a large mass. It is composed of a varying admixture of hyaline cartilage that has features resembling growth plate cartilage, fascicles of spindle cells, woven bone, and hemorrhagic cysts. Treatment consists mainly of surgical excision, which is usually curative. We present 3 new cases, which demonstrated interesting findings, including multicentricity, involvement of the sternum, and local recurrence, and we discuss these findings in the context of a literature review. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Univ Estadual Campinas, Dept Pathol, Campinas, SP, Brazil. Univ Estadual Campinas, Dept Radiol, Campinas, SP, Brazil. Univ Estadual Campinas, Dept Pediat Surg, Campinas, SP, Brazil. RP Rosenberg, AE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 55 Fruit St,WRN 210, Boston, MA 02114 USA. NR 34 TC 9 Z9 13 U1 0 U2 2 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD APR PY 2006 VL 14 IS 2 BP 119 EP 126 DI 10.1177/106689690601400203 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 044WC UT WOS:000237702800003 PM 16703172 ER PT J AU Casini, G Rickman, DW Brecha, NC AF Casini, G Rickman, DW Brecha, NC TI Expression of the gamma-aminobutyric acid (GABA) plasma membrane transporter-1 in monkey and human retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID INHIBITORY SYNAPTIC POTENTIALS; DECARBOXYLASE MESSENGER-RNA; GAD-LIKE IMMUNOREACTIVITY; RAT HIPPOCAMPAL SLICE; IN-SITU HYBRIDIZATION; GLUTAMIC-ACID; CEREBRAL-CORTEX; RABBIT RETINA; PRIMATE RETINA; AMACRINE CELLS AB PURPOSE. To determine the expression pattern of the predominant gamma-aminobutyric acid (GNBA) plasma membrane transporter GAT-1 in Old World monkey (Macaca mulatta) and human retina. METHODS. GAT-I was localized in retinal sections by using immunohistochemical techniques with fluorescence and confocal microscopy. Double-labeling studies were performed with the GAT-I antibody using antibodies to GABA, vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase (TH), and the bipolar cell marker Mab115A10. RESULTS. The pattern of GAT-1 immunostaining was similar in human and monkey retinas. Numerous small immunoreactive somata were in the inner nuclear layer (INL) and were present rarely in the inner plexiform layer (IPL) of all retinal regions. Medium GAT-1 somata were in the ganglion cell layer in the parafoveal and peripheral retinal regions. GAT-1 fibers were densely distributed throughout the IPL. Varicose processes, originating from both the IPL and somata in the INL, arborized in the outer plexiform layer (OPL), forming 4 sparse network in all retinal regions, except the fovea. Sparsely occurring GAT-1 processes were in the nerve fiber layer in parafoveal regions and near the optic nerve head but not in the optic nerve. In the INL, 99% of the GAT-1 somata contained GABA, and 66% of the GABA immunoreactive somata expressed GAT-1. GAT-1 immunoreactivity was in all VIP-containing cells, but it was absent in TH-immunoreactive amacrine cells and in Mab115A10 immunoreactive bipolar cells. CONCLUSIONS. GAT-1 in primate retinas is expressed by amacrine and displaced amacrine cells. The predominant expression of GAT-1 in the inner retina is consistent with the idea that GABA transporters influence neurotransmission and thus participate in visual information processing in the retina. C1 Univ Tuscia, Dipartimento Sci Ambientali, I-01100 Viterbo, Italy. Duke Univ, Dept Ophthalmol, Durham, NC USA. Duke Univ, Dept Neurobiol, Durham, NC USA. Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Neurobiol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Casini, G (reprint author), Univ Tuscia, Dipartimento Sci Ambientali, Largo Univ D, I-01100 Viterbo, Italy. EM gcasini@unitus.it FU NEI NIH HHS [EY04067, EY15573, R01 EY004067-26, R01 EY015573-02, R56 EY004067, R01 EY004067, R01 EY015573]; NIDDK NIH HHS [P30 DK041301, DK41301] NR 88 TC 14 Z9 16 U1 0 U2 2 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 2006 VL 47 IS 4 BP 1682 EP 1690 DI 10.1167/iovs.05-1117 PG 9 WC Ophthalmology SC Ophthalmology GA 029KI UT WOS:000236560800056 PM 16565409 ER PT J AU Sarawate, CA Patel, PA Schumacher, HR Yang, WY Brewer, KK Bakst, AW AF Sarawate, CA Patel, PA Schumacher, HR Yang, WY Brewer, KK Bakst, AW TI Serum urate levels and gout flares - Analysis from managed care data SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE gout; retrospective; serum urate ID HYPERURICEMIA AB Background: The desired serum urate level (SUA) for prevention of gout attacks is widely recommended to be in the subsaturating range, < 6.0 mg/dL. Objectives: The objectives of this study were to evaluate attainment of this target SUA among gout patients on allopurinol in a naturalistic setting and to assess its impact on gout flare risk. Methods: This was a retrospective, observational study in a southeastern U.S. managed care organization of approximately 2.2 million members. The first gout claim/prescription within the intake period (January 1, 2000-December 31, 2002) was the index date. Included patients had >= 2 visits with gout International Classification of Diseases, 9th Revision code (274.xx) or >= 1 pharmacy script(s) for allopurinol, colchicine, probenecid, or sulfinpyrazone. Excluded patients were < 18 years and/or did not have a 1-year continuous eligibility pre-/postindex date. Gout flares were defined by office/emergency room visit with gout or joint pain code(s) and >= 1 of the following within 7 days of the visit: intraarticular aspiration/injection, joint fluid microscopy, or pharmacy claim for nonsteroidal anti inflammatory drug, colchicine, corticosteroid, or ACTH. Multivariable regression analyses were conducted to evaluate gout flare risk/rate and association with target SUA. Results: Approximately 40% of 5942 gout patients identified used allopurinol postindex. Among allopurinol users with pre-/postindex SUA data (n = 162), mean SUA was lowered from 8.7 mg/dL to 7.1 mg/dL; reduction was significant (P < 0.001). Among allopurinol users who did not have SUA < 6.0 mg/dL preindex (n = 147), only 25% reached target levels during postindex. Despite pharmacotherapy, patients with nontarget levels were 59% more likely to flare than those at target. Allopurinol users who were not at target were 75% more likely to flare. Conclusion: The failure of allopurinol users to achieve target SUA levels of < 6.0 mg/dL may be attributed to lack of awareness of optimal SUA, allopurinol dosing, compliance, and efficacy. Patients who did not achieve target SUA were at increased flare risk. C1 HealthCore Inc, Analyt Hlth Outcomes Res, Wilmington, DE 19801 USA. Pharmaceut Prod Inc, Lake Forest, IL USA. Univ Penn, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Sarawate, CA (reprint author), HealthCore Inc, Analyt Hlth Outcomes Res, 800 Delaware Ave,5th Floor, Wilmington, DE 19801 USA. EM csartwate@healthcore.com NR 9 TC 107 Z9 108 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD APR PY 2006 VL 12 IS 2 BP 61 EP 65 DI 10.1097/01.rhu.0000209882.50228.9f PG 5 WC Rheumatology SC Rheumatology GA 035VC UT WOS:000237028800003 PM 16601538 ER PT J AU Maguen, S Litz, BT AF Maguen, S Litz, BT TI Predictors of morale in US peacekeepers SO JOURNAL OF APPLIED SOCIAL PSYCHOLOGY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; COHESION; DISINTEGRATION; SOMALIA; EVENTS; FEMALE AB In this prospective study, we examined pre- and postmission predictors of morale in U.S. military peacekeepers deployed to Kosovo. After controlling for dentographic and military characteristics, current general life stressors, unit cohesion, and reports of patriotism and nationalism were predictive of predeployment morale. We also found that positive military experiences, general overseas military stressors, and postdeployment unit cohesion were significant predictors of postdeployment morale after controlling for demographic and military characteristics and predeployment morale, cohesion, and patriotism/nationalism. The results suggest the need to broaden our understanding of the factors that may assist and motivate soldiers during demanding peacekeeping operations and the factors that may mitigate the impact of stressful demands and associated mission-related strain. C1 Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, P7SD Program 116 P, 4150 Clement St, San Francisco, CA 94121 USA. EM Shira.Maguen@va.gov RI Dopko, Rae/J-7437-2015 NR 22 TC 14 Z9 14 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0021-9029 J9 J APPL SOC PSYCHOL JI J. Appl. Soc. Psychol. PD APR PY 2006 VL 36 IS 4 BP 820 EP 836 PG 17 WC Psychology, Social SC Psychology GA 035WK UT WOS:000237032200002 ER PT J AU Chinman, M Young, AS Hassell, J Davidson, L AF Chinman, M Young, AS Hassell, J Davidson, L TI Toward the implementation of mental health consumer provider services SO JOURNAL OF BEHAVIORAL HEALTH SERVICES & RESEARCH LA English DT Review ID SELF-HELP GROUPS; ONE-YEAR OUTCOMES; QUALITY-OF-CARE; CASE-MANAGEMENT; RANDOMIZED TRIAL; CONCEPTUAL-FRAMEWORK; FOCUS GROUPS; ILLNESS; SCHIZOPHRENIA; COMMUNITY AB Encouraged by the New Freedom Commission, mental health systems such as the Veteran Administration (VA) are now becoming more recovery-oriented. Consumer providers (CPs)-those with serious mental illness who are further along in recovery who provide services to others with similar mental health problems-are viewed as a key part of this change. However, organizational change theories suggest that careful consideration of implementation issues is critical when disseminating new and sometimes controversial services into existing organizations. Therefore, to guide the dissemination of CP set-vices, the literature on the effectiveness of CPs was reviewed, and interviews, focus groups, and a brief survey of 110 administrators, providers, and patients were conducted at three large VA clinics in Southern California. Questions focused on their perceptions of feasibility and acceptability of CP services. Using literature and study findings, an organizational change framework and other strategies to overcome potential implementation challenges of CP set-vices are suggested. C1 W LA VA Healthcare Ctr, MIRECC, VISN 22, Hlth Serv Unit, Los Angeles, CA 90073 USA. Yale Univ, Sch Med, Dept Psychiat, Yale Program Recovery & Community Hlth, New Haven, CT 06511 USA. RP Chinman, M (reprint author), W Los Angeles VA MIRECC, Hlth Serv Unit, 11301 Wilshire Blvd,210A, Los Angeles, CA 90073 USA. EM chinman@rand.org; ayoung@ucla.edu; jhassell@alliant.edu RI Young, Alexander/A-1523-2009 OI Young, Alexander/0000-0002-9367-9213 NR 119 TC 49 Z9 50 U1 2 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1094-3412 J9 J BEHAV HEALTH SER R JI J. Behav. Health Serv. Res. PD APR PY 2006 VL 33 IS 2 BP 176 EP 195 DI 10.1007/s11414-006-9009-3 PG 20 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 041PG UT WOS:000237467500004 PM 16645906 ER PT J AU Bhattacharyya, T Bouchard, KA Phadke, A Meigs, JB Kassarjian, A Salamipour, A AF Bhattacharyya, T Bouchard, KA Phadke, A Meigs, JB Kassarjian, A Salamipour, A TI The accuracy of computed tomography for the diagnosis of tibial nonunion SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID FRACTURES; OUTCOMES AB Background: When a patient is seen with a possible tibial nonunion and equivocal findings on plain radiographs, the surgeon may choose to obtain a computed tomography scan to better delineate the bone anatomy. However, the sensitivity and specificity of computed tomography in this setting is not known. We investigated the accuracy of computed tomography for detecting nonunion in this clinical situation. Methods: Thirty-five patients with equivocal findings on plain radiographs underwent computed tomography scanning. The patients were first seen at an average of 9.7 months after the injury and had undergone a mean of 2.6 prior operations. A so-called gold standard of union or nonunion was determined by either surgical findings (for twenty-five patients who were operatively treated) or six months of clinical observation (for ten patients who had nonoperative treatment). Computed tomography scans were assessed by two radiologists and one orthopaedic surgeon who were blinded to the clinical outcome. Results: Computed tomography scans displayed very good diagnostic accuracy. Intraobserver agreement was high (intraclass correlation coefficient = 0.89), the sensitivity for detecting nonunion was 100%, and the overall accuracy was 89.9%. Computed tomography was limited by a low specificity of 62%, as three patients who were diagnosed as having tibial nonunion with computed tomography underwent surgery and were found to have a healed fracture. Conclusions: Computed tomography displays very good accuracy in the evaluation of tibial fracture-healing. However, it is limited by low specificity and may sometimes misrepresent a healed fracture as a nonunion. Surgeons must be aware of this pitfall in order to accurately determine which patients need surgical intervention. Level of Evidence: Diagnostic Level I. See Instructions to Authors for a complete description of levels of evidence. C1 Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, Boston, MA 02118 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, Boston, MA 02118 USA. RP Bhattacharyya, T (reprint author), Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, 55 Fruit St,Yawkey 3600, Boston, MA 02118 USA. NR 9 TC 25 Z9 27 U1 0 U2 4 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD APR PY 2006 VL 88A IS 4 BP 692 EP 697 DI 10.2106/JBJS.E.00232 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 029KF UT WOS:000236560500002 PM 16595457 ER PT J AU Bozic, KJ Morshed, S Silverstein, MD Rubash, HE Kahn, JG AF Bozic, KJ Morshed, S Silverstein, MD Rubash, HE Kahn, JG TI Use of cost-effectiveness analysis to evaluate new technologies in orthopaedics - The case of alternative bearing surfaces in total hip arthroplasty SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID CROSS-LINKED POLYETHYLENE; FOLLOW-UP; LOW WEAR; REPLACEMENT; RATES; MORTALITY; REGISTER; OUTCOMES; YOUNGER; MODEL AB Background: Alternative bearing surfaces offer the potential to reduce wear and improve implant longevity following total hip arthroplasty. However, these technologies are associated with higher costs, the potential for unintended consequences, and uncertain benefits in terms of long-term survival of the implants. The purpose of this study was to evaluate the cost-effectiveness of the use of alternative bearings in total hip arthroplasty. Methods: A decision-analysis model was constructed to estimate the cost-effectiveness of the use of alternative bearings for patients undergoing total hip arthroplasty. Model inputs, including costs, clinical outcome probabilities, and health utility values, were derived from a review of the literature. Sensitivity analyses were performed to evaluate the impact of patient age at the time of surgery, implant costs, and reductions in revision rates on the cost-effectiveness of alternate bearing surfaces. Results: In a population of fifty-year-old patients, use of an alternative bearing with an incremental cost of $2000 would be cost-saving over the individual's lifetime if it were associated with at least a 19% reduction in the twenty-year implant failure rate when compared with the failure rate for a conventional bearing. In a population of patients over the age of sixty-three years, the same implant would be associated with higher lifetime costs than would a conventional bearing, regardless of the presumed reduction in the revision rate. Conversely, an alternative bearing that adds only $500 to the cost of a conventional total hip arthroplasty could be cost-saving in a population of patients over the age of sixty-five years, even if it were associated with only a modest reduction in the revision rate. In a population of patients over the age of seventy-five years, no alternative bearing would be associated with lifetime cost-savings, regardless of the cost or the presumed reduction in the revision rate. Conclusions: The cost-effectiveness of alternative bearings is highly dependent on the age of the patient at the time of surgery, the cost of the implant, and the associated reduction in the probability of revision relative to that associated with conventional bearings. Our findings provide a quantitative rationale for requiring greater evidence of effectiveness in reducing the probability of implant failure when more costly alternative bearings are being considered, particularly for older patients. Level of Evidence: Decision analysis, Level I. See Instructions to Authors for a complete description of levels of evidence. C1 Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX 75206 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. RP Bozic, KJ (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 500 Parnassus,MU 320W, San Francisco, CA 94143 USA. EM bozick@orthosurg.ucsf.edu NR 55 TC 46 Z9 47 U1 1 U2 2 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD APR PY 2006 VL 88A IS 4 BP 706 EP 714 DI 10.2106/JBJS.E.00614 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 029KF UT WOS:000236560500004 PM 16595459 ER PT J AU Mithoefer, K Lhowe, DW Vrahas, MS Altman, DT Erens, V Altman, GT AF Mithoefer, K Lhowe, DW Vrahas, MS Altman, DT Erens, V Altman, GT TI Functional outcome after acute compartment syndrome of the thigh SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID FEMORAL-SHAFT FRACTURES; SKELETAL-MUSCLE; LOWER LEG; PRESSURE; DIAGNOSIS; ISCHEMIA; FASCIOTOMY; INJURY; MICROCIRCULATION; MECHANISMS AB Background: Acute compartment syndrome of the thigh is an uncommon condition that is associated with a high rate of morbidity. Because of its rarity, limited information is available on the long-term functional outcome for patients with this condition and the factors that affect the clinical result. Methods: Eighteen patients with acute compartment syndrome of the thigh were evaluated at an average of sixty-two months after treatment. Functional outcome was evaluated by means of physical examination, isokinetic thigh-muscle testing, and validated functional outcome scores. Results: Long-term functional deficits were present in eight patients, and only five patients had full recovery of thigh-muscle strength. The persistent dysfunction was reflected in worse overall functional outcome scores. High injury severity scores, ipsilateral femoral fracture, prolonged intervals to decompression, the presence of myonecrosis at the time of fasciotomy, and an age of more than thirty years were associated with increased long-term functional deficits, persistent thigh-muscle weakness, and worse functional outcome scores. Conclusions: Acute compartment syndrome of the thigh is often associated with considerable long-term morbidity. Several factors can affect the functional outcome, and knowledge of these factors can help in the development of a more effective clinical management strategy to reduce long-term morbidity. Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence. C1 Brigham & Womens Hosp, Harvard Vanguard Othopaed & Sports Med, Wellesley, MA 02481 USA. Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Mithoefer, K (reprint author), Brigham & Womens Hosp, Harvard Vanguard Othopaed & Sports Med, 230 Worcester St, Wellesley, MA 02481 USA. EM kmithoefer@partners.org NR 50 TC 87 Z9 91 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD APR PY 2006 VL 88A IS 4 BP 729 EP 737 DI 10.2106/JBJS.E.00336 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 029KF UT WOS:000236560500007 PM 16595462 ER PT J AU Ratcliffe, MB AF Ratcliffe, MB TI The treatment of ischemic heart failure with surgical ventricular restoration (SVR): New evidence of benefit SO JOURNAL OF CARDIAC FAILURE LA English DT Editorial Material ID FINITE-ELEMENT MODEL; VOLUME REDUCTION SURGERY; ENDOVENTRICULAR PATCH PLASTY; MYOCARDIAL-INFARCTION; MITRAL REGURGITATION; ANEURYSM; DYSFUNCTION; SURVIVAL; SIZE; ENLARGEMENT C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. Dept Vet Affairs Med Ctr, San Francisco, CA USA. RP Ratcliffe, MB (reprint author), San Francisco Vet Affairs Med Ctr, Div Surg Serv 112D, 4150 Clement St, San Francisco, CA 94121 USA. FU NHLBI NIH HHS [R01-HL-63348] NR 38 TC 2 Z9 2 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 2006 VL 12 IS 3 BP 195 EP 198 DI 10.1016/j.cardfail.2006.01.007 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 039KV UT WOS:000237305400005 PM 16624684 ER PT J AU Sethi, M Grigore, AM Davison, JK AF Sethi, M Grigore, AM Davison, JK TI Pro: It is safe to proceed with thoracoabdominal surgery after encountering a bloody tap during fluid catheter placement SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE cerebrospinal fluid drainage; bloody tap; spinal hematoma; thoracoabdominal aortic aneurysm; spinal cord protection; cancellation of surgery ID AORTIC-ANEURYSM REPAIR; ACUTE-RENAL-FAILURE; DRAINAGE; PARAPLEGIA; HYPOTHERMIA; OPERATIONS; POTENTIALS; ADJUNCTS; EFFICACY; BYPASS C1 St Lukes Episcopal Hosp, Texas Heart Inst, Baylor Coll Med, Div Cardiovasc Anesthesiol, Houston, TX 77225 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Grigore, AM (reprint author), St Lukes Episcopal Hosp, Texas Heart Inst, Baylor Coll Med, Div Cardiovasc Anesthesiol, MC 1-226,POB 20345, Houston, TX 77225 USA. EM agrigore@heart.thi.tmc.edu NR 21 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD APR PY 2006 VL 20 IS 2 BP 269 EP 272 DI 10.1053/j.jvca.2005.12.013 PG 4 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 036LG UT WOS:000237072000027 PM 16616675 ER PT J AU Adams, MS Alston, TA AF Adams, MS Alston, TA TI A duplicate inferior vena cava? SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE echocardiography; inferior vena cava ID MIRROR-IMAGE; ARTERY; COLOR C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Cardiac Anesthesia Gr, Boston, MA 02114 USA. RP Alston, TA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Cardiac Anesthesia Gr, 55 Fruit St, Boston, MA 02114 USA. EM talston@partners.org NR 4 TC 2 Z9 2 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD APR PY 2006 VL 20 IS 2 BP 284 EP 285 DI 10.1053/j.jvca.2005.09.010 PG 2 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 036LG UT WOS:000237072000031 PM 16616679 ER PT J AU Durvasula, RS Myers, HF Mason, K Hinkin, C AF Durvasula, RS Myers, HF Mason, K Hinkin, C TI Relationship between alcohol use/abuse, HIV infection and neuropsychological performance in African American men SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; INTRAVENOUS-DRUG-USERS; AIDS DEMENTIA COMPLEX; ABUSE; MEMORY; BRAIN; CONSUMPTION; COGNITION; COFACTOR; DISEASE AB This study examines the impact of alcohol use and HIV infection on neuropsychological performance in a sample of 497 community-resident African American men. HIV serostatus and alcohol use ( during the past 12 months) exerted an interactive effect on psychomotor speed, reaction time, and motor speed, and in general, HIV infected heavy drinkers evidenced significantly poorer performance than other HIV positive subjects. Main effects for HIV serostatus were noted for reaction time, with seronegative men performing better than seropositives. This study examines a sample of men who continue to show increases in HIV infection, however, sample specific issues such as comorbid substance use, past histories of head injury, and lack of data on alcohol abuse and dependence require caution in definitively attributing the findings solely to alcohol and HIV. However, these findings suggest that relatively recent heavy alcohol use may represent a potential risk factor for more rapid or pronounced cognitive decline in HIV positive individuals, and that these patterns may be even more pronounced in persons with comorbid substance use. C1 Calif State Univ Los Angeles, Dept Psychol, Los Angeles, CA 90032 USA. Charles R Drew Univ Med & Sci, Res Ctr Ethn Hlth & Behav, Los Angeles, CA 90059 USA. Charles R Drew Univ Med & Sci, Dept Psychiat, Los Angeles, CA 90059 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Calif State Univ Dominguez Hills, Dept Psychol, Carson, CA 90747 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Durvasula, RS (reprint author), Calif State Univ Los Angeles, Dept Psychol, King Hall,5151 State Univ Dr, Los Angeles, CA 90032 USA. EM rdurvas@calstatela.edu FU NIAAA NIH HHS [R21 AA011912-02, U24AA-11899, AA11912, U24 AA011899-04, U24 AA011899]; NIDA NIH HHS [DA06597] NR 62 TC 19 Z9 20 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD APR PY 2006 VL 28 IS 3 BP 383 EP 404 DI 10.1080/13803390590935408 PG 22 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 025RP UT WOS:000236284900008 PM 16618627 ER PT J AU Castellon, SA Hardy, DJ Hinkin, CH Satz, P Stenquist, PK Van Gorp, WG Myers, HF Moore, L AF Castellon, SA Hardy, DJ Hinkin, CH Satz, P Stenquist, PK Van Gorp, WG Myers, HF Moore, L TI Components of depression in HIV-1 infection: Their differential relationship to neurocognitive performance SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS DEMENTIA COMPLEX; BASE-LINE ASSESSMENT; NEUROPSYCHOLOGICAL PERFORMANCE; PSYCHIATRIC-DISORDERS; HOMOSEXUAL MEN; PSYCHOLOGICAL DISTRESS; NEUROPSYCHIATRIC AIDS; SOMATIC SYMPTOMS; BISEXUAL MEN AB Both depression and neurocognitive compromise are commonly observed among persons infected with the Human Immunodeficiency Virus (HIV). To date, the majority of studies have failed to find a consistent relationship between mood and cognition among HIV-seropositive (HIV+) individuals, suggesting that these constructs are independent of one another. However, depression is a multi-dimensional syndrome and its measurement often utilizes multi-factorial instruments containing cognitive, affective, somatic, and motivational components. The degree to which various symptoms or dimensions of depression might be related to neuropsychological performance in HIV-1 infection is not typically explored and was a main objective of the current study. A sample of 247 HIV+ persons completed both a comprehensive neurocognitive battery and the Beck Depression Inventory (BDI) as part of a standard clinical evaluation at a major community hospital. To examine the dimensionality of the BDI, a principal components analysis was conducted which suggested a three-factor solution comprised of factors representing Self-Reproach (SR), Mood-Motivation Disturbance ( MM), and Somatic Disturbance (SOM). The relationship between each of these three factors and neurocognitive performance was examined using both regression and analysis of variance techniques. These analyses showed the MM factor, more so than either the SR or SOM factors, to be associated with several aspects of neurocognitive performance, including verbal memory, executive functioning, and motor speed. These findings suggest that certain items on depression rating scales may be more indicative of central nervous system (CNS) involvement than others. The association between disturbance in mood and motivation and neurocognitive compromise may suggest that each are sequelae of disease specific mechanisms. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Cornell Univ, Weill Med Coll, Ithaca, NY USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Castellon, SA (reprint author), 760 Westwood Plaza,C8-747, Los Angeles, CA 90024 USA. EM scastell@ucla.edu FU NIMH NIH HHS [R01 MH058552, R01 MH058552-05, R01MH58552, T32 MH019535-18, T32MH19535, T32 MH019535] NR 95 TC 32 Z9 34 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD APR PY 2006 VL 28 IS 3 BP 420 EP 437 DI 10.1080/13803390590935444 PG 18 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 025RP UT WOS:000236284900010 PM 16618629 ER PT J AU Dzik, WH AF Dzik, WH TI The NHLBI clinical trials network in transfusion medicine and hemostasis: An overview SO JOURNAL OF CLINICAL APHERESIS LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the American-Society-for-Apheresis CY MAY 23-26, 2006 CL Las Vegas, NV SP Amer Soc Apheres AB Transfusion Medicine is a broad discipline that affects the health care of patients from many medical disciplines. Despite the large impact of transfusion therapies on the management of patients with a variety of diseases, there are few clinical trials that evaluate the indications or the effectiveness of transfusion therapies. To respond to this need for better clinical data, the National Heart Lung and Blood Institute of the National Institutes of Health established a clinical trials network in Transfusion Medicine and Hemostasis. Following a competitive selection process, 17 university medical centers and a data coordinating center joined together to collaboratively address clinical questions in transfusion medicine and hemostasis. The activities, organization, and scope of the network is described below. Examples of clinical trials currently in the network "pipeline" are briefly summarized as an overview to more detailed presentations given elsewhere in this symposium. C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Dzik, WH (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, J-224,55 Fruit St, Boston, MA 02114 USA. EM sdzik@partners.org NR 0 TC 10 Z9 10 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2459 J9 J CLIN APHERESIS JI J. Clin. Apheresis PD APR PY 2006 VL 21 IS 1 SI SI BP 57 EP 59 DI 10.1002/jca.20092 PG 3 WC Hematology SC Hematology GA 036TS UT WOS:000237099200003 PM 16619228 ER PT J AU Sowers, MR Jannausch, M McConnell, D Little, R Greendale, GA Finkelstein, JS Neer, RM Johnston, J Ettinger, B AF Sowers, MR Jannausch, M McConnell, D Little, R Greendale, GA Finkelstein, JS Neer, RM Johnston, J Ettinger, B TI Hormone predictors of bone mineral density changes during the menopausal transition SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PERIMENOPAUSAL WOMEN; POSTMENOPAUSAL WOMEN; SEX STEROIDS; PHYSICAL-ACTIVITY; TURNOVER MARKERS; FEMORAL-NECK; PREMENOPAUSAL; MASS; OSTEOPOROSIS; OOPHORECTOMY AB Objective and Context: Our objective was to examine predictability of reproductive hormone concentrations for bone mineral density (BMD) loss during the menopausal transition. Design: We conducted a longitudinal (five annual examinations), multiple-site (n = 5) cohort study, the Study of Women's Health Across the Nation (SWAN). Participants: Participants included, at baseline, 2311 premenopausal or early perimenopausal African-American, Caucasian, Chinese, and Japanese women. Main Outcome Measures: We assessed annual dual-energy x-ray absorptiometry lumbar spine and total hip BMD measures, with endogenous estradiol (E2), FSH, androgens, and self-reported menstrual bleeding patterns. Results: Over the 4-yr period, lumbar spine BMD loss was 5.6% in natural postmenopause, 3.9% in surgical postmenopause, or 3.2% in late perimenopause. Baseline FSH concentrations, subsequent FSH levels, and their interaction predicted 4-yr BMD loss. If baseline FSH was less than 25 mIU/ml, higher follow-up FSH (>70 mIU/ml) predicted a 4-yr spine BMD loss of -0.05 g/cm(2). If baseline FSH values were more than 35-45 mIU/ml, lower follow-up FSH (i.e. 40-50 mIU/ml) predicted a -0.05 g/cm(2) 4-yr spine BMD loss. Charts show amounts of predicted BMD losses with combinations of baseline FSH values and FSH levels over time. E2 concentrations less than 35 pg/ml were associated with lower BMD, but annual E2 measures and changes did not predict BMD loss. Testosterone, free androgen index, and dehydroepiandrosterone sulfate concentrations were not significantly associated with BMD loss. Conclusions: Spine and hip BMD losses during the menopause transition were most strongly related to the interaction between initial FSH levels and longitudinal FSH changes and not to E2 or androgen levels or changes. C1 Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48104 USA. Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48104 USA. Univ Calif Los Angeles, Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA 15261 USA. Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. RP Sowers, MR (reprint author), Univ Michigan, Sch Publ Hlth, Dept Epidemiol, 339 E Liberty St,Suite 310, Ann Arbor, MI 48104 USA. EM mfsowers@umich.edu RI Little, Roderick/H-2440-2011 FU NIA NIH HHS [AG 012531, AG 012535, AG 012539, AG 012546, AG 012553, AG 012495, AG 012505, AG 012554]; NINR NIH HHS [NR 004061] NR 39 TC 110 Z9 116 U1 0 U2 1 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 2006 VL 91 IS 4 BP 1261 EP 1267 DI 10.1210/jc.2005-1836 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 029YW UT WOS:000236601300014 PM 16403818 ER PT J AU Smith, MR Lee, H Nathan, DM AF Smith, MR Lee, H Nathan, DM TI Insulin sensitivity during combined androgen blockade for prostate cancer SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID C-REACTIVE PROTEIN; LEAN BODY-MASS; DEPRIVATION THERAPY; ARTERIAL STIFFNESS; GLUCOSE-TOLERANCE; HEART-DISEASE; RESISTANCE; OBESITY; MEN; HYPERINSULINEMIA AB Context: GnRH agonists markedly increase fat mass in men with prostate cancer, but little is known about the effects of treatment on insulin sensitivity. Objective: The objective of the study was to assess the effects of short-term GnRH agonist treatment on insulin sensitivity. Design: This was a prospective 12-wk study. Setting: The study was conducted at a general clinical research center. Patients or Other Participants: We studied 25 men with locally advanced or recurrent prostate cancer, no radiographic evidence of metastases, no history of diabetes mellitus, and no evidence of diabetes mellitus at baseline visit. Intervention: Leuprolide depot and bicalutamide were used in the study. Main Outcome Measures: Oral glucose tolerance tests and body composition assessment by dual-energy x-ray absorptiometry were performed at baseline and wk 12. The primary study outcome was change in insulin sensitivity index. Results: Mean (+/- SE) percentage fat body mass increased by 4.3 +/- 1.3% from baseline to wk 12 (P = 0.002). Insulin sensitivity index decreased by 12.9 +/- 7.6% (P = 0.02). Insulin sensitivity by homeostatic model assessment decreased by 12.8 +/- 5.9% (P = 0.02). Fasting plasma insulin levels increased by 25.9 +/- 9.3% (P = 0.04). Mean glycosylated hemoglobin also increased significantly (P < 0.001). Conclusions: Short-term treatment with leuprolide and bicalutamide significantly increased fat mass and decreased insulin sensitivity in men with prostate cancer. These observations suggest that GnRH agonists may increase the risk of diabetes mellitus and cardiovascular disease in older men. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mallinckrodt Gen Clin Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU NCI NIH HHS [P50 CA 90381]; NCRR NIH HHS [M01 RR 01066] NR 23 TC 255 Z9 263 U1 2 U2 4 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 2006 VL 91 IS 4 BP 1305 EP 1308 DI 10.1210/jc.2005-2507 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 029YW UT WOS:000236601300020 PM 16434464 ER PT J AU Pagan, YL Srouji, SS Jimenez, Y Emerson, A Gill, S Hall, JE AF Pagan, YL Srouji, SS Jimenez, Y Emerson, A Gill, S Hall, JE TI Inverse relationship between luteinizing hormone and body mass index in polycystic ovarian syndrome: Investigation of hypothalamic and pituitary contributions SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; SERUM LEPTIN LEVELS; FREE ALPHA-SUBUNIT; INSULIN-RESISTANCE; STEROID-SECRETION; PULSE-GENERATOR; LH-SECRETION; NORMAL WOMEN; OBESE WOMEN AB Context: Patients with polycystic ovarian syndrome (PCOS) have increased LH relative to FSH, but LH is modified by body mass index (BMI). Objective: The objective of the study was to determine whether the impact of BMI on neuroendocrine dysregulation in PCOS is mediated at the hypothalamic or pituitary level. Participants/Interventions/Setting: Twenty-four women with PCOS across a spectrum of BMIs underwent frequent blood sampling, iv administration of GnRH (75 ng/kg), and sc administration of the NAL-GLU GnRH antagonist (5 mu g/kg) in the General Clinical Research Center at an academic hospital. Main Outcome Measures: LH pulse frequency and LH response to submaximal GnRH receptor blockade were used as measures of hypothalamic function; LH response to GnRH was used as a measure of pituitary responsiveness. Results: BMI was negatively correlated with mean LH, LH/FSH, and LH pulse amplitude. There was no effect of BMI on LH pulse frequency. Percent inhibition of LH was decreased in PCOS, compared with normal women (53.9 +/- 1.5 vs. 63.1 +/- 4.1, respectively; P < 0.01), suggesting an increase in the amount of endogenous GnRH, but was not influenced by BMI. Pituitary responsiveness to GnRH was inversely correlated with BMI (peak LH, R = -0.475, P < 0.02; and LH area under the curve R = -0.412, P < 0.02). Conclusions: LH pulse frequency and quantity of GnRH are increased in PCOS, but there is no influence of BMI on either marker of hypothalamic function. The pituitary response to a weight-based dose of GnRH is inversely related to BMI in PCOS. These studies suggest that the effect of BMI on LH is mediated at a pituitary and not a hypothalamic level in PCOS. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Ctr Reprod Med, Boston, MA 02115 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX-5,55 Fruit St, Boston, MA 02114 USA. EM jehall@partners.org FU NCRR NIH HHS [M01 RR 01066]; NICHD NIH HHS [K24 HD 01290] NR 60 TC 56 Z9 57 U1 0 U2 1 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 2006 VL 91 IS 4 BP 1309 EP 1316 DI 10.1210/jc.2005-2099 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 029YW UT WOS:000236601300021 PM 16434454 ER PT J AU Fang, P Kofoed, EM Little, BM Wang, XD Ross, RJM Frank, SJ Hwa, V Rosenfeld, RG AF Fang, P Kofoed, EM Little, BM Wang, XD Ross, RJM Frank, SJ Hwa, V Rosenfeld, RG TI A mutant signal transducer and activator of transcription 5b, associated with growth hormone insensitivity and insulin-like growth factor-I deficiency, cannot function as a signal transducer or transcription factor SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PERIPHERAL T-CELLS; GENE-TRANSCRIPTION; STAT5 ACTIVATION; C-SRC; RECEPTOR; DNA; EXPRESSION; PROLACTIN; MUTATION; KINASES AB Context: A natural missense mutation in the signal transducer and activator of transcription ( STAT) 5b gene was recently identified in association with a female patient presenting with severe growth failure and immune dysfunction. The mutation results in an alanine to proline substitution at residue 630 (A630P) in the src-homology-2 domain, a region essential for docking of STATs to phospho-tyrosines on activated receptors, STAT dimerization, and stabilization of phospho-STAT-DNA interactions. Objective: The purpose of this study was to explore the molecular mechanisms underlying the GH insensitivity and IGF-I deficiency caused by the A630P-mutated STAT5b. Results: In reconstitution experiments using HEK293 cells, both GH and interferon-gamma were unable to activate mutant STAT5b ( A630P), as demonstrated by lack of immunodetectable phospho-tyrosyl-STAT5b A630P) and inability to drive luciferase reporter activity. However, the Src family of nonreceptor kinases [ constitutively active v-src and epithelial growth factor-induced c-src] tyrosine-phosphorylated STAT5b(A630P). The v-src-induced phospho-STAT5b(A630P) translocated to the nucleus but, unlike wild-type Stat5b, was unable to bind DNA. Conclusions: The A630P mutation disrupts the src-homology-2 architecture such that: 1) mutant STAT5b most likely cannot dock to phospho-tyrosines on ligand-activated receptors; and 2) stable interactions with DNA are prevented. Because STAT5b ( A630P) is an inefficient signal transducer and transcription factor, the detrimental impact on signaling pathways important for normal growth and immunity explains, in part, the complex clinical phenotype of GH insensitivity and immune dysfunction. C1 Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97239 USA. Univ Sheffield, Div Clin Sci, Sheffield S5 7AU, S Yorkshire, England. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. Univ Alabama, Dept Physiol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. Lucile Packard Fdn Childrens Hlth, Palo Alto, CA 94304 USA. Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. RP Hwa, V (reprint author), Oregon Hlth & Sci Univ, Dept Pediat, NRC5,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM hwav@ohsu.edu RI Ross, Richard/B-2672-2012 OI Ross, Richard/0000-0001-9222-9678 FU NCI NIH HHS [CA 58110]; NIDDK NIH HHS [DK 46395] NR 33 TC 19 Z9 21 U1 0 U2 1 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 2006 VL 91 IS 4 BP 1526 EP 1534 DI 10.1210/jc.2005-2558 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 029YW UT WOS:000236601300055 PM 16464942 ER PT J AU O'Connell, TD Swigart, PM Rodrigo, MC Ishizaka, S Joho, S Turnbull, L Tecott, LH Baker, AJ Foster, E Grossman, W Simpson, PC AF O'Connell, TD Swigart, PM Rodrigo, MC Ishizaka, S Joho, S Turnbull, L Tecott, LH Baker, AJ Foster, E Grossman, W Simpson, PC TI alpha(1)-adrenergic receptors prevent a maladaptive cardiac response to pressure overload SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LIPID-LOWERING TREATMENT; HEART-ATTACK TRIAL; VENTRICULAR EJECTION FRACTIONS; ATRIAL-NATRIURETIC-PEPTIDE; IN-VIVO; STIMULATED HYPERTROPHY; PLASMA NOREPINEPHRINE; MESSENGER-RNAS; BLOOD-PRESSURE; KNOCKOUT MOUSE AB An alpha(1)-adrenergic receptor (alpha(1)-AR) antagonist increased heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), but it is unknown whether this adverse result was due to alpha(1)-AR inhibition or a nonspecific drug effect. We studied cardiac pressure overload in mice with double KO of the 2 main alpha(1)-AR subtypes in the heart, alpha(1A) (Adra1a) and alpha(1B) (Adra1b). At 2 weeks after transverse aortic constriction (TAC), KO mouse survival was only 60% of WT, and surviving KO mice had lower ejection fractions and larger end-diastolic volumes than WT mice. Mechanistically, final heart weight and myocyte cross-sectional area were the same after TAC in KO and WT mice. However, KO hearts after TAC had increased interstitial fibrosis, increased apoptosis, and failed induction of the fetal hypertrophic genes. Before TAC, isolated KO myocytes were more susceptible to apoptosis after oxidative and beta-AR stimulation, and beta-ARs were desensitized. Thus, alpha(1)-AR deletion worsens dilated cardiomyopathy after pressure overload, by multiple mechanisms, indicating that alpha(1)-signaling is required for cardiac adaptation. These results suggest that the adverse cardiac effects of alpha(1)-antagonists in clinical trials are due to loss of alpha(1)-signaling in myocytes, emphasizing concern about clinical use of alpha(1)-antagonists, and point to a revised perspective on sympathetic activation in heart failure. C1 San Francisco Vet Affairs Med Ctr, Div Cardiol, San Francisco, CA USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA USA. Univ Calif San Francisco, Dept Med, Div Cardiol, San Francisco, CA USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Simpson, PC (reprint author), San Francisco Vet Affairs Med Ctr, Div Cardiol, San Francisco, CA USA. EM paul.simpson@ucsf.edu RI Turnbull, Lynne/A-2605-2012; O'Connell, Timothy/D-5048-2013 OI Turnbull, Lynne/0000-0002-9255-9033; FU NHLBI NIH HHS [R01 HL031113, T32 HL007731, T32HL07731] NR 86 TC 84 Z9 87 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 2006 VL 116 IS 4 BP 1005 EP 1015 DI 10.1172/JCI22811 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 029IP UT WOS:000236556100022 PM 16585965 ER PT J AU Richards, WG Zellos, L Bueno, R Jaklitsch, MT Janne, PA Chirieac, LR Yeap, BY Dekkers, RJ Hartigan, PM Capalbo, L Suarbaker, DJ AF Richards, WG Zellos, L Bueno, R Jaklitsch, MT Janne, PA Chirieac, LR Yeap, BY Dekkers, RJ Hartigan, PM Capalbo, L Suarbaker, DJ TI Phase I to II study of pleurectomy/decortication and intraoperative intracavitary hyperthermic cisplatin lavage for mesothelioma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol ID MALIGNANT PLEURAL MESOTHELIOMA; PERITONEAL CARCINOMATOSIS; INTRAPERITONEAL CHEMOTHERAPY; SYSTEMIC CHEMOTHERAPY; CYTOREDUCTIVE SURGERY; PERFUSION; CANCER; SURVIVAL; FEASIBILITY; THIOSULFATE AB Purpose To evaluate morbidity, mortality, maximum-tolerated dose (MTD), and outcome of intraoperative intracavitary hyperthermic cisplatin lavage in patients undergoing pleurectomy for malignant pleural mesothelioma (MPM). Patients and Methods Sixty-one patients were prospectively registered. Forty-four resectable patients with MPM underwent pleurectomy, followed by a 1-hour lavage of the resection cavity with dose-escalated cisplatin (50, 100, 150, 175, 200, 225, and 250 mg/m(2)) at 42 degrees C and then intravenous sodium thiosulfate (16 g/m(2) over 6 hours). Survival estimates were compared using the log-rank test and proportional hazards regression. Results Median age was 71 years (range, 50 to 82 years), Twenty-four patients had epithelial tumors, and 20 had sarcomatous or mixed histology. Postoperative mortality was 11% (five of 44 patients). Dose-limiting renal toxicity occurred at 250 mg/m(2), establishing the MTD at 225 mg/m(2). Other morbidity included atrial fibrillation (14 of 44 patients, 32%) and deep venous thrombosis (four of 44 patients, 9%). Median survival time of all registered patients was 9 months, and the median survival time of resected patients was 13 months. Survival estimates differed significantly for resectable patients exposed to low doses (50 to 150 mg/m(2); n = 9; median, 6 months) versus high doses (175 to 250 mg/m(2); n = 35; median, 18 months) of hyperthermic cisplatin (P =.0019); recurrence-free interval also differed significantly (4 v 9 months, respectively; P <.0001). Low dose level (relative risk = 3.418) and nonepithelial histology (relative risk = 2.336) were independent risk factors for poor survival. Twenty patients with epithelial tumors who underwent high-dose cisplatin lavage had a 26-month median survival time. Conclusion Pleurectomy and high-dose intraoperative intracavitary hyperthermic cisplatin lavage is feasible in this patient population with restricted surgical options. An apparent dose-related survival benefit warrants further study. C1 Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Suarbaker, DJ (reprint author), Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. EM d.sugarbaker@partners.org NR 27 TC 91 Z9 92 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 2006 VL 24 IS 10 BP 1561 EP 1567 DI 10.1200/JCO.2005.04.6813 PG 7 WC Oncology SC Oncology GA 030UK UT WOS:000236660200013 PM 16575008 ER PT J AU Perlis, RH Welge, JA Vornik, LA Hirschfeld, RMA Keck, PE AF Perlis, RH Welge, JA Vornik, LA Hirschfeld, RMA Keck, PE TI Atypical antipsychotics in the treatment of mania: A meta-analysis of randomized, placebo-controlled trials SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the New-Clinical-Drug-Evaluation-Unit CY JUN 01-04, 2004 CL Phoenix, AZ SP New Clin Drug Evaluat Unit, NIMH ID ACUTE BIPOLAR MANIA; DOUBLE-BLIND; RISPERIDONE MONOTHERAPY; OLANZAPINE; EFFICACY; 3-WEEK; PSYCHOPHARMACOLOGY; HALOPERIDOL; COMBINATION; MULTICENTER AB Background: Randomized, controlled trials have demonstrated efficacy for atypical antipsychotics in the treatment of mania in bipolar disorder, either as monotherapy or adjunctive treatment. However, there are no published comparisons of individual atypical antipsychotics for mania. Data Sources and Study Selection: We conducted a systematic review and meta-analysis of randomized, placebo-controlled monotherapy and adjunctive therapy trials of atypical antipsychotics for acute bipolar mania. Studies published through 2004 were identified using searches of PubMed/MEDLINE with the search terms mania, placebo, and each of the atypical antipsychotics, limited to randomized, controlled clinical trials; review of abstracts from the 2003 meetings of the American College of Neuropsychiatry, American Psychiatric Association, and International Conference on Bipolar Disorder; and consultations with study investigators and representatives of pharmaceutical companies that market atypical antipsychotics. Data Extraction: Analyses were performed on the changes in Young Mania Rating Scale or Mania Rating Scale total scores from baseline to endpoint, using last observation carried forward and computing the difference in change scores between each drug and its corresponding placebo arm. A random-effects model with fixed drug effects was used to combine the studies and make comparisons of the antipsychotics to each other and to placebo. Data Synthesis: Data from 12 placebo-controlled monotherapy and 6 placebo-controlled adjunctive therapy trials involving a total of 4304 subjects (including 1750 placebo-treated subjects) with bipolar mania were obtained. Aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone all demonstrated significant efficacy in monotherapy (i.e., all confidence intervals exclude zero). However, after adjusting for multiple comparisons, pairwise comparisons of individual effects identified no significant differences in efficacy among antipsychotics. Magnitude of improvement was similar whether the antipsychotic was utilized as monotherapy or adjunctive therapy. Conclusions: The 5 newer atypical antipsychotics were all superior to placebo in the treatment of bipolar mania. For monotherapy and add-on therapy, cross-trial comparisons suggest that differences in acute efficacy between the drugs, if any, are likely to be small. C1 Massachusetts Gen Hosp, Harvard Bipolar Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH USA. Univ Texas, Med Branch, Dept Psychiat & Behav Sci, Galveston, TX 77555 USA. Univ Cincinnati, Coll Med, Psychopharmacol Res Program, Dept Psychiat, Cincinnati, OH 45221 USA. Cincinnati Vet Affairs Med Ctr, Gen Clin Res Ctr, Cincinnati, OH USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Harvard Bipolar Res Program, 15 Parkma St,WACC 812, Boston, MA 02114 USA. EM rperlis@partners.org FU NIMH NIH HHS [K23MH067060] NR 35 TC 135 Z9 138 U1 0 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2006 VL 67 IS 4 BP 509 EP 516 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 043PR UT WOS:000237614100001 PM 16669715 ER PT J AU Tondo, L Albert, MJ Baldessarini, RJ AF Tondo, L Albert, MJ Baldessarini, RJ TI Suicide rates in relation to health care access in the United States: An ecological study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID BIPOLAR DISORDER; GENERAL-PRACTITIONERS; MAINTENANCE TREATMENT; CONSENSUS STATEMENT; MAJOR DEPRESSION; MENTAL-ILLNESS; MOOD DISORDERS; MANAGED CARE; RISK-FACTORS; PREVENTION AB Objective: We tested the hypothesis that suicide rates in the United States are associated with indicators of access to health care services. Method: With an ecological study design, we compared age-adjusted suicide rates for men and women with demographic, socioeconomic, and other indices of access to health care, by state (N = 51, including the District of Columbia). The most recently available information from the National Statistics Reports at the U.S. Census Bureau, the U.S. Centers for Disease Control and Prevention National Center for Health Statistics, and the American Board of Medical Specialties was used. Data on suicide are from 2001; other measures were matched for the closest available year, except that state-based data on psychiatrists and physicians are from 2004. Results: Positive bivariate associations with state suicide rates (all p <= .005) are ranked as follows: mate sex, Native American ethnicity, and higher proportion of uninsured residents. Negative bivariate associations (all p <= .002) are ranked as follows: higher population density, higher annual per capita income, higher population density of psychiatrists, higher population density of physicians, higher federal aid for mental health, and higher proportion of African Americans. All factors were associated with state suicide rates in expected directions. In multivariate models of associations between suicide rates and indices of access to health care, the state rate of federal aid for mental health was the strongest indicator, followed by the rate of uninsured persons and population density of psychiatrists and physicians and by population density. Discussion: Such aggregate analyses cannot specify risk indices for individual persons. Nevertheless, the methods employed detected several factors with well-established associations with suicide. They also yielded strong correlations of state-based suicide rates with proposed indicators of access to health care. The findings support the view that clinical intervention is a crucial element in the prevention of suicide. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorders, Belmont, MA USA. Univ Cagliari, Dept Psychol, Cagliari, Italy. Lucio Bini Mood Disorders Ctr, Cagliari, Italy. Lucio Bini Mood Disorders Ctr, Rome, Italy. RP Tondo, L (reprint author), McLean Hosp, N Belknap 318A,115 Mill St, Belmont, MA 02478 USA. EM ltondo@mclean.harvard.edu NR 74 TC 66 Z9 66 U1 2 U2 9 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2006 VL 67 IS 4 BP 517 EP 523 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 043PR UT WOS:000237614100002 PM 16669716 ER PT J AU Biederman, J Faraone, SV Spencer, TJ Mick, E Monuteaux, MC Aleardi, M AF Biederman, J Faraone, SV Spencer, TJ Mick, E Monuteaux, MC Aleardi, M TI Functional impairments in adults with self-reports of diagnosed ADHD: A controlled study of 1001 adults in the community SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; STRIATAL DOPAMINE TRANSPORTER; YOUNG-ADULTS; FOLLOW-UP; PSYCHIATRIC STATUS; CHILDHOOD-ONSET; DOUBLE-BLIND; COLLEGE-STUDENTS; METHYLPHENIDATE AB Objective: The objective of this study was to evaluate functional impairments in a nonreferred sample of adults identifying themselves as having been diagnosed with attention-deficit/hyperactivity disorder (ADHD) by a clinician in their community. Method: We completed a survey in April and May 2003 of a community sample of 500 adults who reported having received a diagnosis of ADHD in the community and 501 gender- and age-matched comparisons from a national sample representative of the U.S. population. Results: Adults with self-reports of diagnosed ADHD in the community were significantly less likely to have graduated high school (83% vs. 93% of controls; p <= .001) or obtain a college degree (19% vs. 26%; p < .01), were less likely to be currently employed (52% vs. 72%; p <= .001), and had significantly more mean job changes over 10 years (5.4 vs. 3.4 jobs; p <= .001). They also were significantly more likely to have been arrested (37% vs. 18% of controls; p <= .001) or divorced (28% vs. 15%; p <= .001) and were significantly less satisfied (p <= .001) with their family, social, and professional lives. Conclusion: Adults who reported having received a diagnosis of ADHD in the community had significant impairment in multiple domains of functioning compared with age- and gender-matched controls without this diagnosis, highly consistent with findings derived from carefully diagnosed referred samples. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, YAW-6A-6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 79 TC 254 Z9 256 U1 3 U2 16 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 2006 VL 67 IS 4 BP 524 EP 540 PG 18 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 043PR UT WOS:000237614100003 PM 16669717 ER PT J AU Fried, R Petty, CR Surman, CB Reimer, B Aleardi, M Martin, JM Coughlin, JF Biederman, J AF Fried, R Petty, CR Surman, CB Reimer, B Aleardi, M Martin, JM Coughlin, JF Biederman, J TI Characterizing impaired driving in adults with attention-deficit/hyperactivity disorder: A controlled study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; YOUNG-ADULTS; FOLLOW-UP; OUTCOMES; DIFFICULTIES; ADOLESCENCE; COMORBIDITY; IMPAIRMENTS; VIOLATIONS; BEHAVIORS AB Objective: We sought to confirm previously documented findings that individuals with attention-deficit/hyperactivity disorder (ADHD) demonstrate impaired driving behavior when compared with controls. Method: Subjects were adults with (N = 26) and without (N = 23) DSM-lV ADHD ascertained through clinical referrals to an adult ADHD program and through advertisements in the local media. Driving behavior was assessed using the Manchester Driving Behavior Questionnaire (DBQ) and 10 questions from a driving history questionnaire. Neuropsychological testing and structured interviews were also administered to all subjects. Results: Substantially more ADHD subjects had been in an accident on the highway (35% vs. 9%, p = .03) or had been rear-ended (50% vs. 17%, p = .02) compared with controls. Analysis of the DBQ findings showed that ADHD subjects had significantly higher mean +/- SD scores than control subjects on the total DBQ (34.1 +/- 15.2 vs. 18.0 +/- 8.6, p < .001) and in all 3 subscales of the DBQ: errors (9.3 +/- 5.4 vs. 4.6 +/- 3.5, p < .001), lapses (12.4 +/- 6.2 vs. 6.1 +/- 3.5, p < .001), and violations (12.4 +/- 5.2 vs. 7.4 +/- 4.1, p < .001). Using the score that separated ADHD from control drivers on the DBQ as a cutoff, ADHD drivers at high risk for poor driving outcomes had more severe rates of comorbidity and exhibited more impaired scores on neuropsychological testing. Conclusions: Our results confirm and extend previous work documenting impaired driving behavior in subjects with ADHD. Results also suggest that ADHD individuals at high risk for poor driving behavior might be distinguishable from other ADHD individuals on DBQ scores, neuropsychological deficits, and patterns of comorbidities. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Dept, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. MIT, AgeLab, Cambridge, MA 02139 USA. RP Fried, R (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Dept, 15 Parkman St,Warren 705, Boston, MA 02114 USA. EM rfried@partners.org RI Reimer, Bryan/G-6431-2010; Louza, Mario/H-8540-2013 OI Reimer, Bryan/0000-0003-4850-8738; Louza, Mario/0000-0003-1359-4111 NR 33 TC 33 Z9 33 U1 0 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2006 VL 67 IS 4 BP 567 EP 574 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 043PR UT WOS:000237614100007 PM 16669721 ER PT J AU Biederman, J Mick, E Faraone, S Hammerness, P Surman, C Harpold, T Dougherty, M Aleardi, M Spencer, T AF Biederman, J Mick, E Faraone, S Hammerness, P Surman, C Harpold, T Dougherty, M Aleardi, M Spencer, T TI A double-blind comparison of galantamine hydrogen bromide and placebo in adults with attention-deficit/hyperactivity disorder - A pilot study SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; ALZHEIMERS-DISEASE; MEMORY; NICOTINE; SMOKING AB Background: Galantamine hydrogen bromide (HBr) is a competitive and reversible inhibitor of acetylcholinesterase. Because of its cholinergic nicotinic mechanism of action, galantamine HBr was hypothesized to have therapeutic activity in the treatment of attention-deficit/hyperactivity disorder (ADHD). Method: We conducted a 12-week, double-blind, placebo-controlled, randomized clinical trial using daily doses of up to 24mg/d of galantamine HBr in the treatment of adults who met full Diagnostic and Statistical Manual of Alental Disorders, Fourth Edition criteria for ADHD with childhood-onset and persistent adult symptoms. All analyses were intention to treat with the last observation carried forward for subjects who did not complete the full study schedule. Results: The mean daily doses at week 12 were 19.8 6.4 mg for galantarnine HBr and 21.8 +/- 4.6 mg for placebo (P = 0.3). There was no statistically or clinically significant greater reduction in ADHD symptoms in subjects treated with galantamine HBr relative to those receiving placebo (P = 0.5). Using last observation carried forward, 4 (22%), of 18 patients receiving galantamine HBr were considered responders (much or very much improved on the Clinical Global Impression Improvement Scale and at least a 30% reduction on the ADHD Investigator Symptom Report Scale compared with 11% [2/18] on placebo; P = 0.4). Conclusion: These results do not support the clinical utility of galantamine HBr in the treatment of ADHD at the doses used in this pilot study. C1 Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Pediat Psychopharmacol Unit, Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. SUNY Upstate Med Univ, Dept Med Genet & Child & Adolescent Psychiat Res, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Pediat Psychopharmacol Unit, Clin & Res Program, YAW 6A 6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 14 TC 16 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 2006 VL 26 IS 2 BP 163 EP 166 DI 10.1097/01.jcp.0000204139.20417.8a PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 029JW UT WOS:000236559600009 PM 16633145 ER PT J AU Niederman, R Leitch, J AF Niederman, R Leitch, J TI "Know what" and "know how": Knowledge creation in clinical practice SO JOURNAL OF DENTAL RESEARCH LA English DT Editorial Material DE knowledge translation; knowledge creation ID CARE RESEARCH NETWORKS; CARIES C1 Forsyth Inst, Dsm Forsyth Ctr Evidence Based Dent, Boston, MA 02114 USA. Boston Univ, Goldman Sch Dent Med, Boston, MA 02114 USA. Inst Healthcare Improvement, Cambridge, MA 02138 USA. Univ Glasgow, Sch Dent, Glasgow G2 3JZ, Lanark, Scotland. RP Niederman, R (reprint author), Forsyth Inst, Dsm Forsyth Ctr Evidence Based Dent, 140 Fenway, Boston, MA 02114 USA. EM rniederman@forsyth.org OI niederman, richard/0000-0001-6674-1774 NR 12 TC 17 Z9 17 U1 1 U2 2 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD APR PY 2006 VL 85 IS 4 BP 296 EP 297 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 029WP UT WOS:000236595400004 PM 16567547 ER PT J AU Krall, EA Sosa, CA Garcia, C Nunn, ME Caplan, DJ Garcia, RI AF Krall, EA Sosa, CA Garcia, C Nunn, ME Caplan, DJ Garcia, RI TI Cigarette smoking increases the risk of root canal treatment SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE smoking; tobacco; endodontics; root canal treatment ID C-REACTIVE PROTEIN; LEUKOCYTE COUNT; TOOTH LOSS; BONE LOSS; ASSOCIATION; DISEASE; SMOKERS; INFLAMMATION; POPULATION; MARKERS AB Few studies have investigated smoking as a risk factor for root canal treatment. We studied the effect of smoking on the incidence of root canal treatment, controlling for recognized risk factors, in 811 dentate male participants in the VA Dental Longitudinal Study. Participants were not VA patients. Follow-up ranged from 2 to 28 years. Root canal treatment was verified on radiographs and evaluated with proportional hazards regression models. Compared with never-smokers, current cigarette smokers were 1.7 times as likely to have root canal treatment ( p < 0.001), but cigar and/or pipe use was not significantly associated with root canal treatment. The risk among cigarette smokers increased with more years of exposure and decreased with length of abstinence. These findings suggest that there is a dose-response relationship between cigarette smoking and the risk of root canal treatment. C1 Boston Univ, Goldman Sch Dent Med, VA Boston Healthcare Syst, VA Dent Longitudinal Study, Boston, MA 02118 USA. Boston Univ, Goldman Sch Dent Med, Dept Hlth Policy & Hlth Serv, Boston, MA 02118 USA. Univ N Carolina, Sch Dent, Dept Dent Ecol, Chapel Hill, NC 27515 USA. Univ Puerto Rico, Sch Dent, San Juan, PR 00936 USA. RP Krall, EA (reprint author), Boston Univ, Goldman Sch Dent Med, VA Boston Healthcare Syst, VA Dent Longitudinal Study, 715 Albany St,560,Room 338, Boston, MA 02118 USA. EM kralle@bu.edu FU NCRR NIH HHS [M01 RR000533, M01 RR 000533]; NIDA NIH HHS [R01 DA10073]; NIDCR NIH HHS [K24 DE000419, K24 DE00419, R01 DE 013807, R01 DE013807-01A1, R15 DE12644, T35 DE007268, T35 DE07268] NR 27 TC 14 Z9 14 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD APR PY 2006 VL 85 IS 4 BP 313 EP 317 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 029WP UT WOS:000236595400007 PM 16567550 ER PT J AU Tanner, ACR Paster, BJ Lu, SC Kanasi, E Kent, R Van Dyke, T Sonis, ST AF Tanner, ACR Paster, BJ Lu, SC Kanasi, E Kent, R Van Dyke, T Sonis, ST TI Subgingival and tongue microbiota during early periodontitis SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE microbiology; tongue; subgingival; health; early periodontitis ID PORPHYROMONAS-GINGIVALIS; BACTEROIDES-FORSYTHUS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; PREVOTELLA-INTERMEDIA; MOLECULAR ANALYSIS; PLAQUE; PREVALENCE; BACTERIA; IDENTIFICATION; ADOLESCENTS AB Periodontal infections have a microbial etiology. Association of species with early disease would be useful in determining which microbes initiate periodontitis. We hypothesized that the microbiota of subgingival and tongue samples would differ between early periodontitis and health. A cross-sectional evaluation of 141 healthy and early periodontitis adults was performed with the use of oligonucleotide probes and PCR. Most species differed in associations with sample sites; most subgingival species were associated with subgingival samples. Few species were detected more frequently in early periodontitis by DNA probes. Porphyromonas gingivalis and Tannerella forsythia ( Tannerella forsythensis) were associated with early periodontitis by direct PCR. In conclusion, the microbiota of tongue samples was less sensitive than that of subgingival samples in detecting periodontal species, and there was overlap in species detected in health and early periodontitis. Detection of periodontal pathogens in early periodontitis suggests an etiology similar to that of more advanced disease. 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, Div Oral Med, 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, M01 RR001032, RR-00533, RR-01032]; NIDCR NIH HHS [DE-09513, DE-11443, R01 DE009513, R01 DE011443] NR 30 TC 51 Z9 55 U1 0 U2 3 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD APR PY 2006 VL 85 IS 4 BP 318 EP 323 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 029WP UT WOS:000236595400008 PM 16567551 ER PT J AU Gidwani, PP Opitz, GM Perrin, JM AF Gidwani, PP Opitz, GM Perrin, JM TI Mothers' views on hyperactivity: A cross-cultural perspective SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE attention deficit hyperactivity disorder; Hispanic Americans; Latino American; parent report; mental health disparities; mental health care barriers ID CHILDREN; PARENTS; INSURANCE; DISORDER; BEHAVIOR; ISSUES; ACCESS; ADHD; CARE AB To examine cultural variation in mothers' perceptions of hyperactive behaviors in school-age boys, we surveyed 135 mothers in 3 ethnic groups: Puerto Rican, Central and South American, and Anglo. Mothers read or heard 8 taped vignettes of boys with behaviors related to DSM-IV hyperactivity criteria. In 50% of the vignettes, Spanish-responding mothers were less likely to consider the boys' behaviors expected than were the English-responding mothers. In 62.5% of the vignettes, Latina mothers expressed more interest in discussing behaviors with their physicians than did the Anglo mothers, and in 62.5% of the vignettes, Spanish-responding mothers expressed more interest in discussing behaviors with their physicians than did the English-responding mothers. We found no association of the 2 scores by the bicultural scale. Mothers' perception of hyperactivity boys varies both with ethnicity and language of response. Latina mothers, especially Spanish-responding mothers, seem interested in discussing children's behavior with physicians. C1 Childrens Hosp & Med Ctr, Ctr Child Hlth Outcomes, San Diego, CA 92123 USA. MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. RP Gidwani, PP (reprint author), Childrens Hosp & Med Ctr, Ctr Child Hlth Outcomes, 3020 Childrens Way,MC 5053, San Diego, CA 92123 USA. EM pgidwani@chsd.org FU AHRQ HHS [T32 HS00063] NR 19 TC 7 Z9 7 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD APR PY 2006 VL 27 IS 2 BP 121 EP 126 DI 10.1097/00004703-200604000-00006 PG 6 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 043OE UT WOS:000237609900006 PM 16682875 ER PT J AU Levine, M Nikkanen, H Nadel, ES Brown, DFM AF Levine, M Nikkanen, H Nadel, ES Brown, DFM TI Weakness and mental status change SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID SALICYLATE INTOXICATION; TINNITUS C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA 02115 USA. Childrens Hosp, Div Toxicol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 13 TC 2 Z9 2 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 2006 VL 30 IS 3 BP 341 EP 344 DI 10.1016/j.jemermed.2005.12.015 PG 4 WC Emergency Medicine SC Emergency Medicine GA 034GQ UT WOS:000236917500017 PM 16677990 ER PT J AU Fung, CH Tsai, J Lulejian, A Patterson, E Asch, S AF Fung, C. H. Tsai, J. Lulejian, A. Patterson, E. Asch, S. TI A national survey of clinical reminder use and barriers to clinical reminder use in an integrated healthcare system SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, David Geffen Sch Med, RAND VA Greater Los Angeles Healthcare Syst, Santa Monica, CA USA. VA Greater Los Angeles Syst, Los Angeles, CA USA. Columbia Univ, New York, NY USA. Ohio State Univ, Columbus, OH 43210 USA. Vet Adm Greater W Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 3 EP 3 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000008 ER PT J AU Hess, R McTigue, K Bryce, CL Fitzgerald, K Zickmund, S Sacco, D Olshansky, E Fischer, GS AF Hess, R. McTigue, K. Bryce, C. L. Fitzgerald, K. Zickmund, S. Sacco, D. Olshansky, E. Fischer, G. S. TI A pamphlet's just a pamphlet SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 4 EP 4 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000012 ER PT J AU Gelber, RP Kurth, T Manson, JE Buring, JE Gaziano, J AF Gelber, R. P. Kurth, T. Manson, J. E. Buring, J. E. Gaziano, J. TI A prospective study of body mass index and mortality in men SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Harvard Med Sch, VA Boston Healthcare Syst, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston Healthcare Syst, Boston, MA 02115 USA. RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 5 EP 5 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000016 ER PT J AU Hsiao, A Wong, M Goldstein, MS Becerra, L Wenger, NS Cheng, E AF Hsiao, A. Wong, M. Goldstein, M. S. Becerra, L. Wenger, N. S. Cheng, E. TI Acculturation and access to conventional care are not related to complementary and alternative medicine use among Asian American subgroups SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Irvine, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Greater Los Angeles Vet Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 8 EP 8 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000025 ER PT J AU Rodriguez, KL Barnato, AE Gambino, FJ Arnold, RM AF Rodriguez, K. L. Barnato, A. E. Gambino, F. J. Arnold, R. M. TI Acute care hospital provider utilization and perceptions of palliative care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 8 EP 8 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000026 ER PT J AU Barrett, TW Mori, M De Boer, D AF Barrett, T. W. Mori, M. De Boer, D. TI Association of perioperative statins and beta-blockers with long term mortality after vascular surgery SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 18 EP 18 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000063 ER PT J AU Aujesky, D Stone, RA Sartorius, J Obrosky, DS Fine, MJ Ibrahim, SA AF Aujesky, D. Stone, R. A. Sartorius, J. Obrosky, D. S. Fine, M. J. Ibrahim, S. A. TI Black patients with pulmonary embolism have a higher 30-day mortality than white patients SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Lausanne, Lausanne, Switzerland. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 22 EP 22 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000077 ER PT J AU Singh, H Thomas, EJ Petersen, LA AF Singh, H. Thomas, E. J. Petersen, L. A. TI Can computerized screening detect diagnostic errors in primary care? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Univ Texas Hlth Sci Ctr, Houston, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 23 EP 24 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000083 ER PT J AU Houston, TK Heudebert, GR Kiefe, CI Willett, LL Palonen, KP Allison, JJ AF Houston, T. K. Heudebert, G. R. Kiefe, C. I. Willett, L. L. Palonen, K. P. Allison, J. J. TI Can residents audit their own performance accurately? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL USA. RI Houston, Thomas/F-2469-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 24 EP 24 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000085 ER PT J AU Taylor, BB Marcantonio, ER Phillips, RS Davis, R Bates, DW Weingart, SN AF Taylor, B. B. Marcantonio, E. R. Phillips, R. S. Davis, R. Bates, D. W. Weingart, S. N. TI Do medical inpatients who report poor service quality experience more errors and adverse events? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 37 EP 37 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000134 ER PT J AU Spencer, AL Bost, JE McNeil, MA AF Spencer, A. L. Bost, J. E. McNeil, M. A. TI Do women's health residency tracks make a difference?. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, VA Pittsburgh Hlthcare Syst, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 38 EP 39 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000138 ER PT J AU Bolen, S Samuels, A Yeh, J Marinopoulos, SS McGuire, MJ Abuid, M Brancati, FL AF Bolen, S. Samuels, A. Yeh, J. Marinopoulos, S. S. McGuire, M. J. Abuid, M. Brancati, F. L. TI Does addition of a cardiologist impact intensification of antihypertensive medications by primary care providers? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. XLHlth, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Marinopoulos, Spyridon/C-4541-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 39 EP 40 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000142 ER PT J AU Bean-Mayberry, B Brucker, NJ Bayliss, N Xu, X Crick, E Mor, M Yano, E Fine, MJ AF Bean-Mayberry, B. Brucker, N. J. Bayliss, N. Xu, X. Crick, E. Mor, M. Yano, E. Fine, M. J. TI Effect of gender and race on receipt of pneumococcal and influenza immunizations in VA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 44 EP 44 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000158 ER PT J AU Frank, D Debenedetti, A Volk, RJ Williams, E Kivlahan, DR Bradley, K AF Frank, D. Debenedetti, A. Volk, R. J. Williams, E. Kivlahan, D. R. Bradley, K. TI Effectiveness of AUDIT-C as a screening test for alcohol misuse in three racial/ethnic groups SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 45 EP 46 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000162 ER PT J AU Mohanty, SA Diamant, AL Gelberg, L Anglin, D Perez, LR Asch, SM AF Mohanty, S. A. Diamant, A. L. Gelberg, L. Anglin, D. Perez, L. R. Asch, S. M. TI Effectiveness of community health workers in facilitating insurance enrollment among patients in a public sector emergency department. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 46 EP 46 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000164 ER PT J AU Dowell, D Schwartz, MD Blustein, J Dubovsky, A Gourevitch, MN AF Dowell, D. Schwartz, M. D. Blustein, J. Dubovsky, A. Gourevitch, M. N. TI Effects of medication cost-sharing on LDL cholesterol in elderly patients with diabetes or vascular disease attending an urban clinic from 1999-2004 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 NYU, New York, NY USA. US Dept Vet Affairs, New York, NY USA. NYU, Wagner Grad Sch, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 47 EP 48 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000169 ER PT J AU Volpp, KG Konetzka, RT Sochalski, J Zhu, J AF Volpp, K. G. Konetzka, R. T. Sochalski, J. Zhu, J. TI Effects of hospital price competition on quality of care for 4 high-mortality conditions SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Chicago, Chicago, IL 60637 USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 47 EP 47 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000166 ER PT J AU Grossman, E Aronson, MD Phillips, RS Weingart, SN AF Grossman, E. Aronson, M. D. Phillips, R. S. Weingart, S. N. TI Evaluating a "fail-safe'' system to follow up abnormal mammograms in primary care. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 53 EP 53 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000188 ER PT J AU Kronman, AC Orlander, JD Paasche-Orlow, M Lew, R AF Kronman, A. C. Orlander, J. D. Paasche-Orlow, M. Lew, R. TI Factors associated with disclosure of errors among residents. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Med Ctr, Boston, MA USA. VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Med Ctr, Newton, MA USA. Boston VA Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 55 EP 55 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000196 ER PT J AU Kaboli, PJ Barrett, TW Vazirani, S Osterberg, L Auerbach, AD AF Kaboli, P. J. Barrett, T. W. Vazirani, S. Osterberg, L. Auerbach, A. D. TI Growth of hospitalists in the Veterans Administration (VA) health-care system: 1997-2005. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Iowa City VAMC, Iowa City, IA USA. Univ Iowa, Iowa City, IA USA. Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. Greater Los Angeles VAMC, Los Angeles, CA USA. Stanford Univ, Palo Alto VA Med Ctr, Palo Alto, CA 94304 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 62 EP 62 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000219 ER PT J AU Nicolaidis, C Gregg, J Galian, H McFarland, B Curry, M Gerrity, M AF Nicolaidis, C. Gregg, J. Galian, H. McFarland, B. Curry, M. Gerrity, M. TI Health care beliefs and needs of depressed women with a history of intimate partner violence. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 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 SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 62 EP 62 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000220 ER PT J AU Polsky, D Lave, JR Jha, A Pauly, MV Chen, Z Cen, L Klusaritz, H Volpp, K AF Polsky, D. Lave, J. R. Jha, A. Pauly, M. V. Chen, Z. Cen, L. Klusaritz, H. Volpp, K. TI Is lower hospital mortality among blacks unique to the veterans administration? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VAMC, CHERP, Philadelphia, PA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Harvard Univ, Boston, MA 02115 USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. VA Med Ctr, CHERP, Philadelphia, PA USA. Univ Penn, VAMC, CHERP, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 77 EP 77 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000273 ER PT J AU Petersen, LA Woodard, L Urech, T Daw, C Sookanan, S AF Petersen, L. A. Woodard, L. Urech, T. Daw, C. Sookanan, S. TI Is pay for performance effective in improving the quality of health care? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 78 EP 78 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000275 ER PT J AU Eisenman, D Cordasco, K Asch, SM Golden, J Glik, D AF Eisenman, D. Cordasco, K. Asch, S. M. Golden, J. Glik, D. TI Leveraging social networks for protecting vulnerable communities' health during disasters SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. W Los Angeles VA, RAND, Los Angeles, CA USA. W Los Angeles VA, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 80 EP 80 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000284 ER PT J AU Simpson, SA Nacke, EP Long, JA AF Simpson, S. A. Nacke, E. P. Long, J. A. TI Medical education at a student-run health clinic SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Philadelphia VA CHERP, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 85 EP 85 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000300 ER PT J AU Simpson, SA Long, JA AF Simpson, S. A. Long, J. A. TI Medical student-run health clinics - A growing trend in community activism and medical education SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Philadelphia VA CHERP, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 85 EP 86 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000301 ER PT J AU Gonzales, R Camargo, CA MacKenzie, TD McCulloch, CE Maselli, J Kersey, AS Levin, SK Metlay, JP AF Gonzales, R. Camargo, C. A. MacKenzie, T. D. McCulloch, C. E. Maselli, J. Kersey, A. S. Levin, S. K. Metlay, J. P. TI Patient satisfaction with emergency department care is not associated with antibiotic treatment for acute respiratory tract infections SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 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 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 97 EP 97 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000345 ER PT J AU MacKenzie, TD Gonzales, R Levin, SK Maselli, J Camargo, CA Kersey, AS Metlay, JP AF MacKenzie, T. D. Gonzales, R. Levin, S. K. Maselli, J. Camargo, C. A., Jr. Kersey, A. S. Metlay, J. P. TI Patterns of use and acceptability of a bilingual interactive computer kiosk designed to teach patients about appropriate antibiotic use for acute respiratory tract infections SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Denver Hlth & Hosp Author, Denver, CO USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dept Vet Affairs, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 98 EP 98 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000349 ER PT J AU Keating, NL Landrum, M Rogers, S Baum, S Virnig, B Huskamp, HA Earle, C Kahn, KL AF Keating, N. L. Landrum, M. Rogers, S. Baum, S. Virnig, B. Huskamp, H. A. Earle, C. Kahn, K. L. TI Physician factors associated with discussions about end-of-life care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Alabama, Birmingham, AL USA. Univ Minnesota, Minneapolis, MN 55455 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 101 EP 101 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000360 ER PT J AU Kahn, KL Keating, NL Landrum, MB Ayanian, JZ Boer, R Klabunde, CN Catalano, PJ AF Kahn, K. L. Keating, N. L. Landrum, M. B. Ayanian, J. Z. Boer, R. Klabunde, C. N. Catalano, P. J. TI Physicians involved in the care of patients with recently diagnosed lung and colorectal cancer SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 RAND Corp, Santa Monica, CA USA. Harvard Univ, Boston, MA 02115 USA. Natl Inst Hlth, Washington, DC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 102 EP 102 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000364 ER PT J AU Steinman, MA Landefeld, CS Rosenthal, GE Bertenthal, D Sen, S Kaboli, P AF Steinman, M. A. Landefeld, C. S. Rosenthal, G. E. Bertenthal, D. Sen, S. Kaboli, P. TI Polypharmacy and prescribing quality in elders SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Iowa, Iowa City, IA 52242 USA. Iowa City VAMC, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 103 EP 104 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000368 ER PT J AU Donohue, JM Fischer, MA Huskamp, HA Weissman, J AF Donohue, J. M. Fischer, M. A. Huskamp, H. A. Weissman, J. TI Potential savings associated with consumer reports best buy drugs program SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 104 EP 104 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000371 ER PT J AU Hsu, DJ Obrosky, D Stone, RA Crick, E Fine, MJ AF Hsu, D. J. Obrosky, D. Stone, R. A. Crick, E. Fine, M. J. TI Predictors of timely initiation of antibiotic therapy for patients hospitalized with pneumonia SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healtcare Syst, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 106 EP 106 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000379 ER PT J AU Pirraglia, PA Murthy, V Weilburg, JB AF Pirraglia, P. A. Murthy, V. Weilburg, J. B. TI Primary care physician attributions for why patients did not receive adequate antidepressant treatment SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Providence VA Med Ctr, Providence, RI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 109 EP 109 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000389 ER PT J AU Trinacty, CM Adams, AS Soumerai, SB Zhang, F Meigs, JB Piette, JD Ross-Degnan, D AF Trinacty, C. M. Adams, A. S. Soumerai, S. B. Zhang, F. Meigs, J. B. Piette, J. D. Ross-Degnan, D. TI Racial differences in long-term adherence to glucose self-monitoring among patients initiating diabetes medications in an HMO SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care, Boston, MA USA. Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. Univ Michigan, Hlth Care Syst, HSR&D VA Ann Arbor Hlth Care Syst, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 118 EP 118 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000420 ER PT J AU Metlay, JP Camargo, CA MacKenzie, T McCulloch, CE Maselli, J Levin, SK Kersey, AS Gonzales, R AF Metlay, J. P. Camargo, C. A., Jr. MacKenzie, T. McCulloch, C. E. Maselli, J. Levin, S. K. Kersey, A. S. Gonzales, R. TI Randomized trial of a multidimensional educational intervention to improve antibiotic use for adults with acute respiratory tract infections managed in the emergency department SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VAMC, Philadelphia, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Denver Hlth & Hosp Authority, Denver, CO USA. Univ Calif San Francisco, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 119 EP 120 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000426 ER PT J AU Rosenfeld, KE Lorenz, K Steckart, M Riopelle, D Wagner, G AF Rosenfeld, K. E. Lorenz, K. Steckart, M. Riopelle, D. Wagner, G. TI Relationships among patient perception of prognosis, treatment and documented and communicated care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 123 EP 123 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000440 ER PT J AU Binswanger, I Stern, MF Deyo, RA Heagerty, PJ Cheadle, A Elmore, JG Koepsell, TD AF Binswanger, I. Stern, M. F. Deyo, R. A. Heagerty, P. J. Cheadle, A. Elmore, J. G. Koepsell, T. D. TI Release from prison: A high-risk time for death? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Vet Affairs Puget Sound, Seattle, WA 98195 USA. State Washington Dept Corrections, Olympia, WA USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98195 USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 124 EP 124 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000442 ER PT J AU Weissmann, PF Branch, WT Gracey, CF Haidet, PM Frankel, RM AF Weissmann, P. F. Branch, W. T. Gracey, C. F. Haidet, P. M. Frankel, R. M. TI Role modeling humanistic behavior: Learning bedside manner from the experts SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Minnesota, Minneapolis, MN 55455 USA. Emory Healthcare, Atlanta, GA USA. Univ Rochester, Rochester, NY 14627 USA. Houston Vet Affairs Med Ctr, Houston, TX USA. Indiana Univ Purdue Univ, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 127 EP 127 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000454 ER PT J AU Higashi, T Adams, JL Wenger, NS McGlynn, E Chiang, L Asch, S Kerr, EA Reuben, DB Fung, C Shekelle, PG AF Higashi, T. Adams, J. L. Wenger, N. S. McGlynn, E. Chiang, L. Asch, S. Kerr, E. A. Reuben, D. B. Fung, C. Shekelle, P. G. TI Sicker, more complex patients get better, not worse, quality of care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Kyoto Univ, Dept Epidemiol & Healthcare Res, Kyoto, Japan. RAND Corp, Santa Monica, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 130 EP 131 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000466 ER PT J AU Long, JA Armstrong, K Chang, VW Chen, Z Metlay, JP AF Long, J. A. Armstrong, K. Chang, V. W. Chen, Z. Metlay, J. P. TI Social capital, race, and glucose control SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Philadelphia VA CHERP, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 131 EP 131 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000469 ER PT J AU Farwell, WR Sesso, HD Lew, RA Scranton, RE Gaziano, JM AF Farwell, W. R. Sesso, H. D. Lew, R. A. Scranton, R. E. Gaziano, J. M. TI The association between statins and cancer prevention in the physicians' health study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Boston Healthcare Syst, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 136 EP 136 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000485 ER PT J AU Shacter, HE Long, JA AF Shacter, H. E. Long, J. A. TI The effect of state policy on access to emergency contraception SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA CHERP, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 141 EP 141 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000502 ER PT J AU Cordasco, KM Eisenman, D Asch, S Golden, J Glik, D AF Cordasco, K. M. Eisenman, D. Asch, S. Golden, J. Glik, D. TI "They blew the levee'': Distrust among hurricane Katrina evacuees SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. Vet Adm Greater W Los Angeles Healthcare Syst, Los Angeles, CA USA. W Los Angeles VA, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 150 EP 150 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000536 ER PT J AU Wheeler, S Maynard, C Bowen, J AF Wheeler, S. Maynard, C. Bowen, J. TI Women Veterans and outcomes after acute myocardial infarction SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Dept Vet Affairs, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 165 EP 166 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000591 ER PT J AU Kleinman, MK Lazarus, CJ Ahmadi, R Freund, K Pregler, JP Seaver, MR AF Kleinman, M. K. Lazarus, C. J. Ahmadi, R. Freund, K. Pregler, J. P. Seaver, M. R. TI The Heart Truth: An education website for health professionals SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Illinois, Chicago, IL 60680 USA. Chicago Med Sch, Chicago, IL USA. Yale Univ, Derby, CT USA. Boston Univ, Boston, MA 02215 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. VA Boston Healthcare Syst, Jamaica Plain, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 167 EP 167 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000597 ER PT J AU Draganescu, M Kapo, J Egan, K Seng, L Streim, J AF Draganescu, M. Kapo, J. Egan, K. Seng, L. Streim, J. TI "Hello,doc... tell me this is not true!'' Or how to teach death notification over the phone SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Philadelphia VAMC, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 173 EP 174 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000618 ER PT J AU Poon, EG Blumenfeld, B Hamann, C Graydon-Baker, E Turchin, A Baker, G McCarthy, P Poikonen, J Schnipper, JL Hallisey, RK Smith, S McCormack, C Paterno, M Coley, CM Karson, A Chueh, HC Van Putten, C Millar, SG Clapp, M Bhan, I Meyer, GS Gandhi, TK Broverman, C AF Poon, E. G. Blumenfeld, B. Hamann, C. Graydon-Baker, E. Turchin, A. Baker, G. McCarthy, P. Poikonen, J. Schnipper, J. L. Hallisey, R. K. Smith, S. McCormack, C. Paterno, M. Coley, C. M. Karson, A. Chueh, H. C. Van Putten, C. Millar, S. G. Clapp, M. Bhan, I. Meyer, G. S. Gandhi, T. K. Broverman, C. TI Design and implementation of an electronic application to support multi-disciplinary medication reconciliation efforts at two academic medical centers SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Partners Healthcare Syst, Wellesley, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 192 EP 192 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000682 ER PT J AU Tabibian, PA Fung, C AF Tabibian, P. A. Fung, C. TI Emergence of community acquired methicillin-resistant staphyloccocus aureus (CA-MRSA) pneumonia in healthy individuals. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 234 EP 235 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000836 ER PT J AU Tabibian, PA Chahal, P AF Tabibian, P. A. Chahal, P. TI HIV/AIDS infections among the elderly: A need for implementing new screening and educational measures. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 242 EP 243 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000864 ER PT J AU Armstrong, K Rose, A Peters, N Long, JA McMurphy, S Shea, JA AF Armstrong, K Rose, A Peters, N Long, JA McMurphy, S Shea, JA TI Distrust of the health care system and self-reported health in the United States SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE distrust; health status ID RATED HEALTH; PATIENTS TRUST; MEDICAL-PROFESSION; AFRICAN-AMERICAN; PATIENT TRUST; PHYSICIANS; MORTALITY; SATISFACTION; SCALE; INSTITUTIONS AB Despite theoretical concerns that health care related distrust may lead to poor health outcomes by interfering with effective health care, little is currently known about the prevalence or outcomes of distrust of the health care system in the United States. To investigate the association between distrust of the health care system and self-reported health status among the general population in the United States. Random-digit-dialing telephone survey. Nine hundred and sixty-one adult residents of the continental U.S. Distrust of the health care system and self-reported health status. Distrust of the health care system is relatively high in the United States, with between 20% and 80% of respondents reporting distrust for each item on the Health Care System Distrust scale and a median scale score of 31 (potential range from 10 to 50). Distrust of the health care system is strongly associated with self-reported fair/poor health (odds ratio [OR] 1.40%, 95% confidence interval [CI] 1.12 to 1.75 for each standard deviation increase in distrust), even after adjusting for sociodemographic characteristics, access to health care and trust in primary physicians. In contrast, low trust in one's primary physician is much lower (only 10% to 20% of respondents reported distrust for each item) and is not associated with health status. Distrust of the health care system is relatively high in the general population in the United States and is strongly associated with worse self-reported health. Further studies are needed to assess the direction of this association and the mechanisms involved. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. RP Armstrong, K (reprint author), 1204 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM karmstro@mail.med.upenn.edu FU PHS HHS [R01 2689-01] NR 46 TC 54 Z9 54 U1 2 U2 11 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 2006 VL 21 IS 4 BP 292 EP 297 DI 10.1111/j.1525-1497.2006.00396.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 036ZT UT WOS:000237117200002 PM 16686803 ER PT J AU Shrank, WH Fox, SA Kirk, A Ettner, SL Cantrell, CH Glassman, P Asch, SM AF Shrank, WH Fox, SA Kirk, A Ettner, SL Cantrell, CH Glassman, P Asch, SM TI The effect of pharmacy benefit design on patient-physician communication about costs SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE pharmacy benefit design; prescription drugs; doctor patient communication; incentive-based ID CARE; INCENTIVES; DRUGS AB Incentive-based formularies have been widely instituted to control the rising costs of prescription drugs. To work properly, such formularies depend on patients to be aware of financial incentives and communicate their cost preferences with prescribing physicians. The impact of financial incentives on patient awareness of and communication about those costs is unknown. To evaluate the relationship between enrollment in incentive-based pharmacy benefit plans and awareness of out-of-pocket costs and rates of communication about out-of-pocket costs. A matched telephone survey of patients and their primary care physicians. Los Angeles County. One thousand nine hundred and seventeen patients aged 53 to 82 (73% response rate). Patient-reported pharmacy benefit design, knowledge of out-of-pocket costs, and discussion of out-of-pocket costs with physicians. Sixty-two percent of patients who had prescription drug coverage and were aware of their pharmacy benefit design reported being enrolled in incentive-based plans. The majority of these (54%) were "never" or only "sometimes" aware of their out-of-pocket cost requirements at the time of the physician visit. After controlling for numerous physician and patient level variables, we found that patients enrolled in pharmacy benefit designs requiring no copayments were more likely to report they "never" discuss out-of-pocket costs with physicians compared with patients enrolled in incentive-based pharmacy benefit designs (81% vs 67%, P = .001) and patients with no prescription drug insurance (57%, P < .001). Incentive-based pharmacy benefit plans and lack of insurance are associated with increased rates of discussions about out-of-pocket costs. Nonetheless, most incentive-based enrollees are unaware of out-of-pocket costs when prescriptions are written and never discuss out-of-pocket costs with their physicians, likely mitigating the effectiveness of financial incentives to guide decision making. Considering that out-of-pocket costs are associated with adherence to medical therapy, interventions to improve patient access to out-of-pocket cost information and the frequency of patient-physician discussions about costs are needed. C1 Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND Hlth, Santa Monica, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Ctr Community Partnerships Hlth Promot, Los Angeles, CA USA. RP Shrank, WH (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM wshrank@partners.org FU NCI NIH HHS [R01 CA 74322] NR 23 TC 30 Z9 30 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 2006 VL 21 IS 4 BP 334 EP 339 DI 10.1111/j.1525-1497.2006.00402.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 036ZT UT WOS:000237117200009 PM 16686808 ER PT J AU Davis, KS Magruder, KM Lin, Y Powell, CK Clancy, DE AF Davis, KS Magruder, KM Lin, Y Powell, CK Clancy, DE TI Brief report: Trainee provider perceptions of group visits SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE group visits; health care delivery system; provider perceptions ID CARE; PHYSICIANS; SATISFACTION; QUALITY AB To evaluate the effect of observing group visits on trainees' perceptions of group visits as a method of health care delivery. Thirty-two trainees assigned to month-long rotations at an academic Internal Medicine Primary Care Clinic serving underinsured patients were recruited to observe between 1 and 4 group visits. Prior to observation of their first, and subsequent to observation of their last group visit, each trainee completed the Patient-Physician Orientation Scale (PPOS), a validated survey evaluating their tendencies toward being patient-centered or provider-centered. Additionally, they completed a Group Visit Questionnaire (GVQ) evaluating their perceptions of group visits as a method of health care delivery. Trainee gender, type, and level of training were similarly represented across the study population of trainees. While there were no significant differences noted on pre- and postobservation PPOS scores, the postobservation GVQs scores were significantly improved after observing at least one group visit (P < .0001). Trainees' perceptions of group visits as a method of health care delivery improved significantly after observation of at least 1 group as measured by the GVQ. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Hlth Care Res, Charleston, SC USA. Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Davis, KS (reprint author), McClennan Banks Ambulat Care Ctr, Adult Primary Care Ctr Adm Serv, 326 Calhoun St,POB 250104, Charleston, SC 29425 USA. EM davisks@musc.edu FU AHRQ HHS [5 P01 HS10871, P01 HS010871] NR 8 TC 3 Z9 3 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 2006 VL 21 IS 4 BP 357 EP 359 DI 10.1111/j.1525-1497.2006.00350.x PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 036ZT UT WOS:000237117200013 PM 16686812 ER PT J AU Ashkenazy, R Abrahamson, MJ AF Ashkenazy, R Abrahamson, MJ TI Medicare coverage for patients with diabetes - A national plan with individual consequences SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE medicare; diabetes; prescription drug plan ID HEALTH; PREVALENCE; SENIORS; BURDEN AB The prevalence of diabetes in the U.S. Medicare population is growing at an alarming rate. From 1980 to 2004, the number of people aged 65 or older with diagnosed diabetes increased from 2.3 million to 5.8 million. According to the Centers for Medicare and Medicaid (CMS), 32% of Medicare spending is attributed to the diabetes population. Since its inception, Medicare has expanded medical coverage of monitoring devices, screening tests and visits, educational efforts, and preventive medical services for its diabetic enrollees. However, oral antidiabetic agents and insulin were excluded from reimbursement. In 2003, Congress passed the Medicare Modernization Act that includes a drug benefit to be administered either through Medicare Advantage drug plans or privately sponsored prescription drug plans for implementation in January 2006. In this article we highlight key patient and drug plan characteristics and resources that providers may focus upon to assist their patients choose a coverage plan. Using a case example, we illustrate the variable financial impact the adoption of Medicare part D may have on beneficiaries with diabetes due to their economic status. We further discuss the potential consequences the legislation will have on diabetic patients enrolled in Medicare, their providers, prescribing strategies, and the diabetes market. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Ashkenazy, R (reprint author), 19 Netherlands Rd,Apt 2, Brookline, MA 02445 USA. EM rebecca_ashkenazy@yahoo.com NR 23 TC 11 Z9 14 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 2006 VL 21 IS 4 BP 386 EP 392 DI 10.1111/j.1525-1497.2006.00403.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 036ZT UT WOS:000237117200020 PM 16686819 ER PT J AU Drobetz, H Bryant, AL Pokorny, T Spitaler, R Leixnering, M Jupiter, JB AF Drobetz, H Bryant, AL Pokorny, T Spitaler, R Leixnering, M Jupiter, JB TI Volar fixed-angle plating of distal radius extension fractures: influence of plate position on secondary loss of reduction - A biomechanic study in a cadaveric model SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE fixed angle; distal radius fracture; volar locking compression plate; radial shortening; subchondral ID DORSALLY DISPLACED FRACTURES; PHOSPHATE BONE-CEMENT; INTRAARTICULAR FRACTURES; SURGICAL-TREATMENT; RADIOULNAR JOINT; FIXATION; END; COMPRESSION; STRENGTH; THERAPY AB Purpose: Treatment of extension fractures of the distal radius with volar fixed-angle plates has become increasingly popular in the past 2 years. It has been observed clinically that placement of the distal screws as close as possible to the subchondral zone is crucial to maintain radial length after surgery. The purposes of this study were (1) to evaluate radial shortening after plating with regard to plate position and (2) to evaluate whether plate position has an influence on the strength and rigidity of the plate-screw construct. Methods: An extra-articular fracture (AO classification, A3) was created in 7 pairs of fresh-frozen human cadaver radiuses. The radiuses then were plated with a volar distal radius locking compression plate. Seven plates were applied subchondrally; 7 plates were applied 4.5 mm to 7.5 mm proximal to the subchondral zone. The specimens were loaded with 800-N loads for 2,000 cycles to evaluate radial shortening in the 2 groups. Each specimen then was loaded to failure. Results: Radial shortening was significantly greater when the distal screws were placed proximal to the subchondral zone. The amount of shortening after cyclic loading correlated significantly with the distance the distal screws were placed from the subchondral zone. Rigidity of the plate systems was significantly higher in radiuses in which the distal screws were placed close to the subchondral zone. Conclusions: To maintain radial length after volar fixed-angle plating, placement of the distal screws as subchondral as possible is essential. The subchondral plate-screw-bone constructs showed significantly greater rigidity, indicating higher resistance to postoperative loads and displacement forces. C1 Neunkirchen Gen Hosp, Dept Trauma Surg, A-2620 Neunkirchen, Austria. Univ Melbourne, Ctr Hlth Exercise & Sports Med, Parkville, Vic 3052, Australia. AUVA, Trauma Ctr Lorenz Boehler, Vienna, Austria. Ludwig Boltzmann Inst Clin & Expt Traumatol, Vienna, Austria. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand Serv, Boston, MA 02115 USA. RP Drobetz, H (reprint author), Neunkirchen Gen Hosp, Dept Trauma Surg, A-2620 Neunkirchen, Austria. EM drobetz@sportchirurgie.at NR 37 TC 62 Z9 64 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD APR PY 2006 VL 31A IS 4 BP 615 EP 622 DI 10.1016/j.jhsa.2006.01.011 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 036JX UT WOS:000237068500017 PM 16632057 ER PT J AU Cantor, H Boyse, EA AF Cantor, H. Boyse, E. A. TI Functional subclasses of T lymphocytes bearing different Ly antigens I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B LYMPHOCYTES; H-2 COMPLEX; ALLOANTIGENS; KILLER; REGION; MOUSE; POPULATIONS; IDENTITY; IMMUNITY; INVITRO AB T lymphocytes mediate many immunologic functions. For example, they generate cytotoxic responses to alloantigens (1, 2), exert helper (3) and suppressor (4) effects on the production of antibody, and initiate graft-vs.-host responses (5). We do not know whether this diversity of function reflects a functional heterogeneity of T lymphocytes existing before antigen stimulation. If this were the case, then the response of a T-cell clone to stimulation by antigen would be limited to the particular immune function for which it had already been programmed during the differentiation of that T cell. Alternatively, antigen stimulation of a single T cell may induce the formation of progeny that can mediate the complete range of T-dependent responses. These alternatives are illustrated in Fig. 1. One can pose the question in this way: is it possible to separate subclasses of T cells from nonimmune animals that are already determined to express, respectively, helper activity or cytotoxic activity before they encounter antigen? A direct approach to this question could be based upon the use of alloantisera that would define cell surface components expressed selectively on one or another T-cell subclass. Genes coding for such components would most likely be expressed exclusively in T cells. Shiku and his colleagues observed that effector killer cells, ie. cells that have already responded to antigen, express a distinctive profile of Ly antigens (10). In the study reported here, we have extended the use of the Ly systems to attack the fundamental question posed above, namely whether or not the generation of functional T-cell diversity precedes the encounter with antigen. We find that subclasses of peripheral T cells with different immunological functions and biological characteristics, distinguishable by expression of different Ly alloantigens, pre-exist in mice that have not been immunized. This indicates that diversification of T-cell function, resulting in cells committed to express either helper or killer activity, is a differentiative process that has taken place before T cells meet antigen and that these diverse effector cells are derived from different maturational lines of T cells. C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Sidney Farber Canc Ctr, Div Tumor Immunol, Boston, MA 02115 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 IS 7 BP 3861 EP 3874 PG 14 WC Immunology SC Immunology GA 059YY UT WOS:000238769300006 ER PT J AU Bihl, F Frahm, N Di Giammarino, L Sidney, J John, M Yusim, K Woodberry, T Sango, K Hewitt, HS Henry, L Linde, CH Chisholm, JV Zaman, TM Pae, E Mallal, S Walker, BD Sette, A Korber, BT Heckerman, D Brander, C AF Bihl, Florian Frahm, Nicole Di Giammarino, Loriana Sidney, John John, Mina Yusim, Karina Woodberry, Tonia Sango, Kaori Hewitt, Hannah S. Henry, Leah Linde, Caitlyn H. Chisholm, John V., III Zaman, Tauheed M. Pae, Eunice Mallal, Simon Walker, Bruce D. Sette, Alessandro Korber, Bette T. Heckerman, David Brander, Christian TI Impact of HLA-B alleles, epitope binding affinity, functional avidity, and viral coinfection on the immunodominance of virus-specific CTL responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; EPSTEIN-BARR-VIRUS; LYMPHOCYTE RESPONSES; SUBDOMINANT EPITOPES; DNA IMMUNIZATION; TRANSGENIC MICE; VACCINE DESIGN; HIV-INFECTION; MEMORY AB Immunodominance is variably used to describe either the most frequently detectable response among tested individuals or the strongest response within a single individual, yet factors determining either inter- or intraindividual immunodominance are still poorly understood. More than 90 individuals were tested against 184 HIV- and 92 EBV-derived, previously defined CTL epitopes. The data show that HLA-B-restricted epitopes were significantly more frequently recognized than HLA-A- or HLA-C-restricted epitopes. HLA-B-restricted epitopes also induced responses of higher magnitude than did either HLA-A- or HLA-C-restricted epitopes, although this comparison only reached statistical significance for EBV epitopes. For both viruses, the magnitude and frequency of recognition were correlated with each other, but not with the epitope binding affinity to the restricting HLA allele. The presence or absence of HIV coinfection did not impact EBV epitope immunodominance patterns significantly. Peptide titration studies showed that the magnitude of responses was associated with high functional avidity, requiring low concentration of cognate peptide to respond in in vitro assays. The data support the important role of HLA-B alleles in antiviral immunity and afford a better understanding of the factors contributing to inter- and intraindividual immunodominance. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA. Murdoch Univ, Perth, WA, Australia. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Menzies Sch Hlth Res, Darwin, NT, Australia. Fenway Community Hlth Ctr, Boston, MA 02115 USA. Microsoft Res, Redmond, WA 98052 USA. RP Brander, C (reprint author), Massachusetts Gen Hosp E, Partners AIDS Res Ctr, 5th Floor,Room 5239,149 13th St, Charlestown, MA 02129 USA. EM cbrander@partners.org OI Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [N01-AI-15422, R21-AI-05542102] NR 48 TC 111 Z9 111 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 IS 7 BP 4094 EP 4101 PG 8 WC Immunology SC Immunology GA 059YY UT WOS:000238769300034 PM 16547245 ER PT J AU Ranjbar, S Rajsbaum, R Goldfeld, AE AF Ranjbar, Shahin Rajsbaum, Ricardo Goldfeld, Anne E. TI Transactivator of transcription from HIV type 1 subtype E selectively inhibits TNF gene expression via interference with chromatin remodeling of the TNF locus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NF-KAPPA-B; CREB-BINDING-PROTEIN; LONG TERMINAL REPEAT; TAT PROTEIN; ALPHA GENE; SWISS-MODEL; STRUCTURAL CHARACTERIZATION; HISTONE ACETYLTRANSFERASE; CYNOMOLGUS MONKEYS AB The transactivator of transcription (Tat) protein is essential for efficient HIV type 1 (HIV-1) replication and is involved in the transcriptional regulation of the host immune response gene, TNF. In this study, we demonstrate that Tat proteins from representative HIV-1 subtype E isolates, but not from subtypes B or C, selectively inhibit TNF gene transcription and protein production in CD4(+) Jurkat T cells. Strikingly, we show that this repression is due to a tryptophan at residue 32 of Tat E and is secondary to interference with recruitment of the histone acetyltransferase P/CAF to the TNF promoter and with chromatin remodeling of the TNF locus. This study presents a novel mechanism by which HIV-1 manipulates a host immune response gene that is important in its own replication. Moreover, these results demonstrate a new mechanism by which the TNF gene is regulated via chromatin remodeling secondary to viral infection. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Goldfeld, AE (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM goldfeld@cbr.med.harvard.edu RI Rajsbaum, Ricardo/F-2046-2014 FU NIAID NIH HHS [AI60433]; NIGMS NIH HHS [GM056492] NR 57 TC 20 Z9 21 U1 1 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 APR 1 PY 2006 VL 176 IS 7 BP 4182 EP 4190 PG 9 WC Immunology SC Immunology GA 059YY UT WOS:000238769300044 PM 16547255 ER PT J AU Nicholson, MJ Moradi, B Seth, NP Xing, XC Cuny, GD Stein, RL Wucherpfennig, KW AF Nicholson, Melissa J. Moradi, Babak Seth, Nilufer P. Xing, Xuechao Cuny, Gregory D. Stein, Ross L. Wucherpfennig, Kai W. TI Small molecules that enhance the catalytic efficiency of HLA-DM SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MYELIN BASIC-PROTEIN; CLASS-II PROTEINS; T-CELL EPITOPES; INVARIANT-CHAIN; PEPTIDE BINDING; FLUORESCENCE POLARIZATION; ANTIGEN PRESENTATION; CRYSTAL-STRUCTURE; MHC MOLECULES AB HLA-DM (DM) plays a critical role in Ag presentation to CD4 T-cells by catalyzing the exchange of peptides bound to MHC class II molecules. Large lateral surfaces involved in the DM:HLA-DR (DR) interaction have been defined, but the mechanism of catalysis is not understood. In this study, we describe four small molecules that accelerate DM-catalyzed peptide exchange. Mechanistic studies demonstrate that these small molecules substantially enhance the catalytic efficiency of DM, indicating that they make the transition state of the DM:DR/peptide complex energetically more favorable. These compounds fall into two functional classes: two compounds are active only in the presence of DM, and binding data for one show a direct interaction with DM. The remaining two compounds have partial activity in the absence of DM, suggesting that they may act at the interface between DM and DR/peptide. A hydrophobic ridge in the DM beta 1 domain was implicated in the catalysis of peptide exchange because the activity of three of these enhancers was substantially reduced by point mutations in this area. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. HCNR, Lab Drug Discovery Neurodegenerat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM Kai_Wucherpfennig@dfci.harvard.edu FU NIAID NIH HHS [R01 AI057493]; NIDDK NIH HHS [K01 DK068383]; NINDS NIH HHS [R01 NS044914] NR 39 TC 36 Z9 37 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 IS 7 BP 4208 EP 4220 PG 13 WC Immunology SC Immunology GA 059YY UT WOS:000238769300047 PM 16547258 ER PT J AU Cario, E Golenbock, DT Visintin, A Runzi, M Gerken, G Podolsky, DK AF Cario, Elke Golenbock, Douglas T. Visintin, Alberto Ruenzi, Michael Gerken, Guido Podolsky, Daniel K. TI Trypsin-sensitive modulation of intestinal epithelial MD-2 as mechanism of lipopolysaccharide tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTOR-4; PROTEASE-ACTIVATED RECEPTOR-2; INFLAMMATORY-BOWEL-DISEASE; NF-KAPPA-B; ENDOPLASMIC-RETICULUM; SIGNAL-TRANSDUCTION; BACTERIAL LIGANDS; GENE-EXPRESSION; QUALITY-CONTROL; CELLS AB Intestinal epithelial cells (IEC) are constantly exposed to both high concentrations of the bacterial ligand LPS and the serine protease trypsin. MD-2, which contains multiple trypsin cleavage sites, is an essential accessory glycoprotein required for LPS recognition and signaling through TLR4. The aim of this study was to characterize the expression and subcellular distribution of intestinal epithelial MD-2 and to delineate potential functional interactions with trypsin and then alteration in inflammatory bowel disease (IBD). Although MD-2 protein expression was minimal in primary IEC of normal colonic or ileal mucosa, expression was significantly increased in IEC from patients with active IBD colitis, but not in ileal areas from patients with severe Crohn's disease. Endogenous MD-2 was predominantly retained in the calnexin-calreticulin cycle of the endoplasmic reticulum; only a small fraction was exported to the Golgi. MD-2 expression correlated inversely with trypsin activity. Biochemical evidence and in vitro experiments demonstrated that trypsin exposure resulted in extensive proteolysis of endogenous and soluble MD-2 protein, but not of TLR4 in IEC, and was associated with desensitization of IEC to LPS. In conclusion, the present study suggests that endoplasmic reticulum-associated MD-2 expression in IBD may be altered by ileal protease in inflammation, leading to impaired LPS recognition and hyporesponsiveness through MD-2 proteolysis in IEC, thus implying a physiologic mechanism that helps maintain LPS tolerance in the intestine. C1 Univ Hosp Essen, Div Gastroenterol & Hepatol, Inst Grp 1, D-45147 Essen, Germany. Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA. S Essen Hosp, Div Gastroenterol & Metab, Essen, Germany. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Cario, E (reprint author), Univ Hosp Essen, Div Gastroenterol & Hepatol, Inst Grp 1, Virchowstr 171, D-45147 Essen, Germany. EM eike.cario@uni-essen.de FU NIDDK NIH HHS [DK43351, R01 DK060049, DK60049] NR 55 TC 31 Z9 33 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 IS 7 BP 4258 EP 4266 PG 9 WC Immunology SC Immunology GA 059YY UT WOS:000238769300052 PM 16547263 ER PT J AU Paintlia, AS Paintlia, MK Singh, I Singh, AK AF Paintlia, Ajaib S. Paintlia, Manjeet K. Singh, Inderjit Singh, Avtar K. TI IL-4-induced peroxisome proliferator-activated receptor gamma activation inhibits NF-kappa B trans activation in central nervous system (CNS) glial cells and protects oligodendrocyte progenitors under neuroinflammatory disease conditions: Implication for CNS-demyelinating diseases SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; NITRIC-OXIDE SYNTHASE; MULTIPLE-SCLEROSIS; T-CELL; GENE-EXPRESSION; EXTRACELLULAR DOMAIN; IMMUNE-DEVIATION; INTERFERON-GAMMA; ANIMAL-MODEL AB Th2 phenotype cytokine, IL-4, plays an important role in the regulation of Th1 cell responses and spontaneous remission of inflammatory CNS demyelinating diseases such as multiple sclerosis (MS). In this study we demonstrate IL-4-induced down-regulation of inducible NO synthase (iNOS) expression and survival of differentiating oligodendrocyte progenitors (OPs) in proinflammatory cytokine (Cyt-Mix)-treated CNS glial cells, which is a condition similar to that observed in the brain of a patient with MS. IL-4 treatment of Cyt-Mix-treated CNS glial cells significantly decreased iNOS expression/NO release with a parallel increase in survival of differentiating OPs. IL-4 effects were concentration-dependent and could be reversed by anti-IL-4R Abs. The use of inhibitors for Akt, p38 MAPK, and peroxisome proliferator-activated receptor gamma (PPAR-gamma) antagonist revealed that inhibition of Cyt-Mix-induced MOS expression and survival of differentiating OPs by IL-4 is via PPAR-gamma activation. There was a coordinate increase in the expression of both PPAR-gamma and its natural ligand-producing enzyme 12/15-lipoxygenase (12/15-LOX) in IL-4-treated cells. Next, EMSA, immunoblots, and transient cotransfection studies with reporter plasmids (pNF-kappa B-Luc and pTK-PPREx3-Luc) and 12/15-LOX small interfering RNA revealed that IL-4-induced PPAR-gamma activation antagonizes NF-kappa B transactivation in Cyt-Mix-treated astrocytes. In support of this finding, similarly treated 12/15-LOX-/- CNS glial cells further corroborated the result. Furthermore, there was reversal of IL-4 inductive effects in the brain of LPS-challenged 12/15-LOX-/mice when compared with LPS-challenged wild-type mice. Together, these data for the first time demonstrate the inhibition of Cyt-Mix-induced NF-kappa B transactivation in CNS glial cells by IL-4 via PPAR-gamma activation, hence its implication for the protection of differentiating OPs during MS and other CNS demyelinating diseases. C1 Med Univ S Carolina, Childrens Res Inst, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29425 USA. RP Singh, AK (reprint author), Med Univ S Carolina, Childrens Res Inst, Dept Pediat, 504-D,173 Ashley Ave, Charleston, SC 29425 USA. EM singhi@musc.edu OI Paintlia, Ajaib/0000-0003-4525-5333 FU NCRR NIH HHS [C06-RR015455, C06-RR018823]; NIA NIH HHS [AG-025307]; NINDS NIH HHS [NS-22576, NS-37766, NS-34741, NS-40810] NR 61 TC 41 Z9 42 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 IS 7 BP 4385 EP 4398 PG 14 WC Immunology SC Immunology GA 059YY UT WOS:000238769300066 PM 16547277 ER PT J AU Ansel, KM Heissmeyer, V Dararutana-Lapan, A Monticelli, S Rao, A AF Ansel, K. Mark Heissmeyer, Vigo Dararutana-Lapan, Ariya Monticelli, Silvia Rao, Anjana TI Murine Eri-1 regulates siRNA and miRNA expression and RNAi function in activated T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. GSF Inst Mol Immunol, D-81377 Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S294 EP S294 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102361 ER PT J AU Barrington, RA Schneider, T Verschoor, A Ma, MH Carroll, MC AF Barrington, Robert A. Schneider, Thomas Verschoor, Admar Ma, Minghe Carroll, Michael C. TI Uncoupling of CD21 and CD19 disrupts B cell regulation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Merrimack Pharmaceut, Cambridge, MA 02142 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S190 EP S190 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101376 ER PT J AU Berland, R Kari, E Fernandez, L Kearney, J Wortis, H Imanishi-Kari, T AF Berland, Robert Kari, Elena Fernandez, Luiz Kearney, John Wortis, Henry Imanishi-Kari, Thereza TI Loss of tolerance of anergic self-reactive B lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Tufts Univ, Sch Med, Boston, MA 02111 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA 02129 USA. Univ Alabama, Wallace Tumor Inst, Birmingham, AL 35294 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S190 EP S190 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101375 ER PT J AU Chang, HC Tan, KM Ouyang, J Parisini, E Liu, JH Le, Y Wang, XS Reinherz, EL Wang, JH AF Chang, Hsiu-Ching Tan, Kemin Ouyang, Jing Parisini, Emilio Liu, Jin-huan Le, Yi Wang, Xiasong Reinherz, Ellis L. Wang, Jia-huai TI Structural and mutational analyses of a CD8ab heterodimer and comparison with the CD8aa homodimer SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S52 EP S52 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100240 ER PT J AU Chang, HC Tan, KM Hsu, YM AF Chang, Hsiu-Ching Tan, Kemin Hsu, Yen-Ming TI CD8ab has two distinct binding modes of interaction with peptide-MHC class I. alpha beta SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Biogen Idec Inc, Mol Discovery Dept, Cambridge, MA 02142 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S52 EP S52 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100241 ER PT J AU Chen, YG Wilson, SB Leiter, E Serreze, D AF Chen, Yi-Guang Wilson, S. Brian Leiter, Edward Serreze, David TI CD38 is required for peripheral survival of tolerogenic CD4(+) iNKT cells in NOD mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Jackson Lab, Bar Harbor, ME 04609 USA. Massachusetts Gen Hosp, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S138 EP S138 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101137 ER PT J AU Cherayil, B Harrington, L Antony, R Shi, HN AF Cherayil, Bobby Harrington, Lynne Antony, Reuben Shi, Haining TI An important role for IFN gamma in acute Salmonella-induced enteritis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S106 EP S106 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100489 ER PT J AU Clayton, LK Touma, M Antonini, V Bobenchik, AM Bobenchik, A Osborn, SL Grusby, MJ Keskin, DB Connolly, JE Reinherz, EL AF Clayton, Linda Kathleen Touma, Maki Antonini, Valeria Bobenchik, April M. Bobenchik, April Osborn, Stephanie L. Grusby, Michael J. Keskin, Derin B. Connolly, John E. Reinherz, Ellis L. TI Targeted disruption of I kappa BNS alters T cell activation and cytokine production SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Baylor Inst Immunol Res, Dallas, TX 75204 USA. RI Connolly, John/B-8099-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S197 EP S197 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101408 ER PT J AU Eastcott, JW Taubman, MA AF Eastcott, Jean W. Taubman, Martin A. TI Lymph node NK and CD8+ T cell populations in athymic rats remain in the same proportion, with increasing age, as in euthymic rats SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Forsyth Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S295 EP S295 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102370 ER PT J AU Freyschmidt, EJ Mathias, C Laouar, A Narasimhaswamy, M Weih, F Chatila, T AF Freyschmidt, Eva-Jasmin Mathias, Clinton Laouar, Amale Narasimhaswamy, Manjunath Weih, Falk Chatila, Talal TI Eczema-prone RelB(-/-) and FoxP3(-) mice display defective immune responses and impaired viral clearance following vaccinia infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Childrens Hosp, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. IBM Corp, D-07745 Jena, Germany. Univ Calif Los Angeles, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S85 EP S86 PG 2 WC Immunology SC Immunology GA 060YD UT WOS:000238837100395 ER PT J AU Gauduin, MC Yu, Y Piatak, M Lifson, JD Desrosiers, RC Johnson, RP AF Gauduin, Marie-Claire Yu, Y. Piatak, M. Lifson, J. D. Desrosiers, R. C. Johnson, R. P. TI Induction of a virus-specific effector memory CD4+T cell response by attenuated SIV infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. NCI, SAIC, Frederick, MD 21702 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S92 EP S93 PG 2 WC Immunology SC Immunology GA 060YD UT WOS:000238837100427 ER PT J AU Germana, S LeGuern, C AF Germana, Sharon LeGuern, Christian TI Suppression of T cell activation by CD4+, CD25+ regulatory T cells is MHC class II restricted SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Biol Lab,TBRC, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S217 EP S217 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102004 ER PT J AU Grabie, N Love, V Freeman, G Sharpe, A Lichtman, A AF Grabie, Nir Love, Victoria Freeman, Gordon Sharpe, Arlene Lichtman, Andrew TI IFN-gamma-inducible PD-L1 protects the heart from CTL-mediated injury SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S187 EP S187 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101360 ER PT J AU Haining, WN Ebert, B Subramanian, A Kaech, S Ahmed, R Nadler, L Wherry, EJ Golub, T AF Haining, W. Nicholas Ebert, Benjamin Subramanian, Aravind Kaech, Susan Ahmed, Rafi Nadler, Lee Wherry, E. John Golub, Todd TI Memory T cells in mice and humans share a common molecular program of differentiation regardless of phenotype, lineage or species SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. MIT, Cambridge, MA 02141 USA. Yale Univ, New Haven, CT 06520 USA. Emory Univ, Atlanta, GA 30322 USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S303 EP S303 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102408 ER PT J AU Han, XZ LaRosa, KB Kawai, T Taubman, MA AF Han, Xiaozhe LaRosa, Karen B. Kawai, Toshihisa Taubman, Martin A. TI Evolutionary implications of bacterial genomic DNA-elicited protective immune response SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Forsyth Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S68 EP S68 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100315 ER PT J AU Henrickson, S Mempel, TR Mazo, IB von Andrian, UH AF Henrickson, Sarah Mempel, Thorsten R. Mazo, Irina B. von Andrian, Ulrich H. TI Dynamic interactions in T-cell priming modulated by altered peptide SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S173 EP S173 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101294 ER PT J AU Holers, VM Thurman, JM Kraus, D Wood, A Carroll, M Arend, WP Banda, N AF Holers, V. Michael Thurman, Joshua M. Kraus, Dannian Wood, Allyson Carroll, Michael Arend, William P. Banda, Nirmal TI Alternative complement pathway activation is essential in the passive transfer model of collagen-induced arthritis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Colorado, Hlth Sci Ctr, Div Rheumatol, Denver, CO 80262 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S151 EP S151 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101194 ER PT J AU Hsu, HC Yang, P Wu, Q Wu, YL Chen, J Accavitti-Loper, MAV Mountz, JD AF Hsu, Hui-Chen Yang, PingAr Wu, Qi Wu, Yalei Chen, Jian Accavitti-Loper, Mary Ann V. Mountz, John D. TI Over-expression of activation-induced cytidine deaminase in BXD2 B cells requires stimulation by BXD2 CD4 T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Alabama, Birmingham, AL 35294 USA. Birmingham VAMC, Birmingham, AL 35294 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S153 EP S153 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101203 ER PT J AU Jayasekera, JP Shen, CH Chen, JZ Carroll, MC AF Jayasekera, Jerome P. Shen, Ching-Hung Chen, Jianzhu Carroll, Michael C. TI Diminished CD8+ T cell response to influenza virus infection in the absence of C3 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 CBR Inst Biomed Res, Boston, MA 02115 USA. MIT, Canc Res Ctr, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S79 EP S79 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100363 ER PT J AU Keir, ME Liang, SC Guleria, IC Latchman, YE Qipo, A Albacker, LA Koulmanda, M Freeman, GJ Sayegh, MH Sharpe, AH AF Keir, Mary E. Liang, Spencer C. Guleria, Indira C. Latchman, Yvette E. Qipo, Andi Albacker, Lee A. Koulmanda, Maria Freeman, Gordon J. Sayegh, Mohamed H. Sharpe, Arlene H. TI Parenchymal expression of PD-L1 mediates peripheral T cell tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Childrens Hosp, HMS, BWH, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Dana Farber Canc Inst, HMS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S280 EP S280 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102294 ER PT J AU Keskin, DB Reche, PA Hussey, RE Ancuta, P Gabuzda, DH Reinherz, EL AF Keskin, Derin Benerci Reche, Pedro A. Hussey, Rebecca E. Ancuta, Petronela Gabuzda, Dana H. Reinherz, Ellis L. TI Elicitation of cytotoxic T lymphocytes directed against conserved HIV-1 epitopes from naive individuals SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Reche, Pedro/B-1881-2013 OI Reche, Pedro/0000-0003-3966-5838 NR 0 TC 0 Z9 0 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 APR 1 PY 2006 VL 176 SU S BP S93 EP S93 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100428 ER PT J AU Kim, M Qiao, ZS Yu, J Zoeteweij, P Glenn, GM Montefiori, D Reinherz, EL AF Kim, Mikyung Qiao, Zhisong Yu, Jessica Zoeteweij, Paul Glenn, Gregory M. Montefiori, David Reinherz, Ellis L. TI Immunogenicity of recombinant human immunodeficiency virus-like particles presenting gp41 derivatives in a pre-fusion state SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Dana Farber Canc Inst, Boston, MA 02115 USA. IOMAI, Gaithersburg, MD 20878 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S93 EP S93 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100429 ER PT J AU Kim, ST Takeuchi, K Sun, ZYJ Touma, M Wagner, G Reinherz, EL AF Kim, Sun Taek Takeuchi, Koh Sun, Zhen-Yu J. Touma, Maki Wagner, Gerhard Reinherz, Ellis L. TI Differential recognition of CD3 epsilon gamma and CD3 epsilon delta heterodimers in the alpha beta TCR complex by two anti-CD3 mAbs, 145-2C11 and 17A2 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RI Takeuchi, Koh/B-4971-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S206 EP S206 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101452 ER PT J AU Konopa, JL Lathers, DMR Young, MRI AF Konopa, Jennifer Lynn Lathers, Deanne M. R. Young, M. Rita I. TI Tumor secreted factors induce normal endothelial cells to inhibit immune cell function SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Med Univ S Carolina, Charleston, SC 29403 USA. Ralph Johnson VA Med Ctr, Res Serv, Charleston, SC 29401 USA. MUSC, STB 502, Dept Med, Charleston, SC 29401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S276 EP S276 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102278 ER PT J AU Krueger, A von Boehmer, H AF Krueger, Andreas von Boehmer, Harald TI Identification of a novel T cell progenitor from peripheral blood SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Krueger, Andreas/B-9427-2009 OI Krueger, Andreas/0000-0001-7873-7334 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S308 EP S308 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102431 ER PT J AU Luckey, CJ Bhattacharya, D Goldrath, AW Weissman, IL Benoist, C Mathis, D AF Luckey, Chance John Bhattacharya, Deepta Goldrath, Ananda W. Weissman, Irving L. Benoist, Christophe Mathis, Diane TI Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Harvard Univ, Stem Cell Inst, Joslin Diabet Ctr, Boston, MA 02215 USA. Stanford Univ, SOM, Inst Stem Cell Biol, Stanford, CA 94305 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S298 EP S299 PG 2 WC Immunology SC Immunology GA 060YD UT WOS:000238837102385 ER PT J AU Macklin, MD Zuleger, CL Breunig, A Newton, MA Albertini, MR AF Macklin, Michael D. Zuleger, Cindy L. Breunig, Adam Newton, Michael A. Albertini, Mark R. TI Analysis of T-cell receptor genes in wild-type and 6-thioguanine-resistant T-cells from melanoma patients SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Wisconsin, Ctr Comprehens Canc, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53792 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S271 EP S271 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102256 ER PT J AU Maillard, M Cotta-de-Almedia, V Nagler-Anderson, C Michetti, P Snapper, SB AF Maillard, Michel Cotta-de-Almedia, V. Nagler-Anderson, C. Michetti, P. Snapper, S. B. TI WASP-deficiency in mice leads to global regulatory T cell dysfunction with IL-2 and IL-10 deficiency SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Lausanne Hosp, Div Gastro Hepat, Lausanne, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S137 EP S137 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101133 ER PT J AU Meelu, P Cotta-De-Almeida, V Westerberg, L Rosen, M Vandenberghe, P Klein, C Snapper, SB AF Meelu, Parool Cotta-de-Almeida, V. Westerberg, L. Rosen, M. Vandenberghe, P. Klein, C. Snapper, S. B. TI Analyzing the function of constitutively activated WASP in hematopoietic cells employing a transplanation model SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Hannover Med Sch, D-3000 Hannover, Germany. SW Univ Texas, Dallas, TX 75390 USA. Univ Hosp Leuven, CHG, Louvain, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S318 EP S318 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102481 ER PT J AU Mizoguchi, E Hachiya, Y Kawada, M AF Mizoguchi, Emiko Hachiya, Yuriko Kawada, Mayunni TI Chitinase 3-like-1 (Chi3L1) potentially exacerbates acute and chronic colitis by enhancing intracellular bacterial adhesion and invasion in colonic epithelial cells. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S225 EP S225 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102039 ER PT J AU Mora, JR Iwata, M Eksteen, B Song, SY Senman, B Adams, DH von Andrian, UH AF Mora, J. Rodrigo Iwata, Makoto Eksteen, Bertus Song, Si-Young Senman, Balimkiz Adams, David H. von Andrian, Ulrich H. TI Dynamic control of lymphocyte homing by dendritic cells and retinoids. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Harvard Univ, Sch Med, CBRI, Boston, MA 02115 USA. Tokushima Bunri Univ, Tokushima 7708514, Japan. Univ Birmingham, Queen Elizabeth Hosp, Birmingham B15 2TH, W Midlands, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S44 EP S44 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100203 ER PT J AU Moseman, A Jayasekera, JP Carroll, MC AF Moseman, Ashley Jayasekera, Jerome P. Carroll, Michael C. TI Complement and natural antibody mediate influenza virus neutralization SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S79 EP S79 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100364 ER PT J AU Nath, N Prasad, R Giri, S Singh, AK Singh, I AF Nath, Narender Prasad, Ratna Giri, Shailendra Singh, Avtar K. Singh, Inderjit TI T-bet is essential for the progression of experimental autoimmune encephalomyelitis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S250 EP S250 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102156 ER PT J AU Oble, DA Seliem, RM Hasserjian, R Lauwers, GY AF Oble, Darryl Alan Seliem, Rania M. Hasserjian, Robert Lauwers, Gregory Y. TI Anti-CTLA-4 induced pathological changes of the gastrointestinal tract SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S278 EP S278 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102285 ER PT J AU Prasad, R Giri, S Nath, N Singh, I Singh, AK AF Prasad, Rama Giri, Shailendra Nath, Narender Singh, Inderjit Singh, Avtar K. TI GSNO attenuates EAE disease by S-nitrosylation mediated modulation of endothelial-monocyte interactions SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S2 EP S2 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100009 ER PT J AU Rogers, KA Matathia, S Khan, W Karim, MM Ahmed, S Hibberd, P Calderwood, S Ryan, E Ward, H AF Rogers, Kathleen A. Matathia, Sarah Khan, Wasif Karim, Mohammad M. Ahmed, Sabeena Hibberd, Patricia Calderwood, Stephen Ryan, Edward Ward, Honorine TI Comparison of serum IgG responses to Cryptosporidium hominis and C parvum antigens in Bangladeshi children with cryptosporidiosis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 T NEMC, Boston, MA 02111 USA. ICDDR B, Dhaka, Bangladesh. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S68 EP S68 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100313 ER PT J AU Roozendaal, R Verschoor, A Mempel, TR Schneider, TJ Martinez-Pomares, L Gordon, S von Andrian, U Carroll, MC AF Roozendaal, Ramon Verschoor, Admar Mempel, Thorsten R. Schneider, Thomas J. Martinez-Pomares, Luisa Gordon, Siamon von Andrian, Uli Carroll, Michael C. TI Cells bearing a ligand for the cysteine rich region of the mannose receptor mediate Ag transport to follicular dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Biomed Res Inst, CBR, Boston, MA 02115 USA. Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S60 EP S60 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100276 ER PT J AU Sasaki, Y Schmidt-Supprian, M Rajewsky, K AF Sasaki, Yoshiteru Schmidt-Supprian, Marc Rajewsky, Klaus TI Constitutive activation of both the canonical and the alternative NF-kB pathway rescues B cells from BAFF-R deficiency and induces B cell hyperplasia in a dose dependent manner SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S196 EP S196 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101404 ER PT J AU Scott, JE Freyschmidt, EJ El-Khal, A Laouar, A Narasimhaswamy, M Oettgen, H Geha, R AF Scott, Jordan Eliot Freyschmidt, Eva-Jasmin El-Khal, Abdala Laouar, Amale Narasimhaswamy, Manjunath Oettgen, Hans Geha, Raif TI Establishing a murine model of Eczema Vaccinatum SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Childrens Hosp, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S287 EP S287 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102329 ER PT J AU Shen, LL Jin, YP Zhang, Q Sharpe, AH Freeman, GJ Dana, R AF shen, linling Jin, Yiping Zhang, Qiang Sharpe, Arlene H. Freeman, Gordon J. Dana, Reza TI The expression of PD-L1 in cornea and its regulatory role SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, NRB HIM, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S232 EP S232 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102071 ER PT J AU Shimomurs, Y Ogawa, A Sugimoto, K Kawada, M Mizoguchi, E Bhan, AK Mizoguchi, A AF Shimomurs, Yasuyo Ogawa, Atsuhiro Sugimoto, Ken Kawada, Mayumi Mizoguchi, Emiko Bhan, Ain K. Mizoguchi, Atsushi TI Inducible intestinal B cell development pathway under inflammatory condition SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S229 EP S229 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102057 ER PT J AU Shirane, K Hokama, A Ogawa, A Sugimoto, K Shimomura, Y Yoshida, M Blumberg, R Mizoguchi, A AF Shirane, Katsunori Hokama, Akira Ogawa, Atsuhiro Sugimoto, Ken Shimomura, Yasuyo Yoshida, Masaru Blumberg, Richard Mizoguchi, Atsushi TI Inflammation-induced glycan modification allows galectin-4 to bind CD4+T cells to stimulate their IL-6 production SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S225 EP S225 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102041 ER PT J AU Smith, DW Prioult, G Nagler, C AF Smith, Donald W. Prioult, Guenolee Nagler, Cathryn TI Innate immune signaling via MyD88 does not govern tolerance and immunity to orally administered antigens SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S229 EP S229 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102060 ER PT J AU Sugimoto, K Ogawa, A Shimomura, Y Nagaishi, T Mizoguchi, E Blumberg, RS Mizoguchi, AC Bhan, AK AF Sugimoto, Ken Ogawa, Atsuhiro Shimomura, Yasuyo Nagaishi, Takashi Mizoguchi, Emiko Blumberg, Richard S. Mizoguchi, Atsushi C. Bhan, Atul K. TI Dependence of intestinal granuloma formation on a unique F4/80(+) dendritic cell-like subset SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S228 EP S228 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102055 ER PT J AU Sugimoto, K Ogawa, A Shimomura, Y Mizoguchi, A Bhan, AK AF Sugimoto, Ken Ogawa, Atsuhiro Shimomura, Yasuyo Mizoguchi, Atsushi Bhan, Atul K. TI IL-12p35-producing B cells regulate Th2-mediated chronic colitis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S226 EP S226 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102043 ER PT J AU Sundrud, M Wu, Y Borde, M Heissmeyer, V Feuerer, M Lapan, AD Ziegler, SF Mathis, D Benoist, C Chen, L Rao, AJ AF Sundrud, Mark Wu, Yongqing Borde, Madhuri Heissmeyer, Vigo Feuerer, Markus Lapan, Ariya D. Ziegler, Steven F. Mathis, Diane Benoist, Christophe Chen, Lin Rao, Anjana TI FOXP3 controls T regulatory function through cooperation with NFAT SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. CBR, Inst Biomed Res, Boston, MA 02115 USA. Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. Brigham & Womens Hosp, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Washington, Benaroya Res Inst Virginia Mason, Seattle, WA 98101 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S238 EP S238 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102101 ER PT J AU Taqueti, V Grabie, N Colvin, R Jarolim, P Luster, A Glimcher, L Lichtman, A AF Taqueti, Viviany Grabie, Nir Colvin, Richard Jarolim, Peter Luster, Andrew Glimcher, Laurie Lichtman, Andrew TI T-bet-dependent CXCR3 expression is required for cardiac migration of pathogenic cytotoxic T lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S39 EP S39 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100178 ER PT J AU Thompson, BD Jin, YZ Birnbaumer, L Kochevar, IE Wu, MX AF Thompson, Brian D. Jin, Yongzhu Birnbaumer, Lutz Kochevar, Irene E. Wu, Mei X. TI Antagonism between G alpha i2 and G alpha i3 in CXCR3-mediated signaling SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S25 EP S26 PG 2 WC Immunology SC Immunology GA 060YD UT WOS:000238837100118 ER PT J AU Tonomura, N Wang, SM Sykes, M Yang, YG AF Tonomura, Noriko Wang, Shumei Sykes, Megan Yang, Yong-Guang TI Antigen-specific human T cell and antibody responses in a humanized mouse model SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S169 EP S169 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101276 ER PT J AU Touma, M Chang, HC Sasada, T Clayton, LK Reinherz, EL AF Touma, Maki Chang, Hsiu-Ching Sasada, Tetsuro Clayton, Linda K. Reinherz, Ellis L. TI The TCR C beta FG loop regulates alpha beta T cell development by enhancing negative selection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S313 EP S313 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102457 ER PT J AU Wang, J Mountz, JD Chen, J Wu, Q Yang, PA Hsu, HC AF Wang, John Mountz, John D. Chen, Jian Wu, Qi Yang, PingAr Hsu, Hui-Chen TI Autoantigen responsible for augmenting activated IL-17 producing T-cell in BXD2 autoinamune mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Alabama, Birmingham, AL 35294 USA. Birmingham VAMC, Birmingham, AL 35294 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S160 EP S161 PG 2 WC Immunology SC Immunology GA 060YD UT WOS:000238837101237 ER PT J AU Wu, MX Jin, YZ AF Wu, Mei X. Jin, Yong Z. TI Identification of a Smad phosphatase up regulated in absence of Gai2 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S224 EP S224 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102037 ER PT J AU Yang, HL Reinherz, E AF Yang, Hailin Reinherz, Ellis TI CD2BP1 modulates CD2-dependent T cell activation via linkage to protein tyrosine phosphatase (PTP)-PEST SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S207 EP S207 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101454 ER PT J AU You, YY Carter, RH AF You, Yuying Carter, Robert H. TI The role of CD19 in the development of the marginal zone SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Alabama, Birmingham, AL 35294 USA. Birmingham VAMC, Birmingham, AL 35233 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S162 EP S162 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101245 ER PT J AU Zhong, WM Lugovskoy, AA Wagner, G Reinherz, EL AF Zhong, Weimin Lugovskoy, Alexey A. Wagner, Gerhard Reinherz, Ellis L. TI Molecular and structural features of a TCR V alpha repertoire in response to an immunodominant CTL epitope of influenza A virus SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, BCMP Dept, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S121 EP S121 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101058 ER PT J AU David, WS Simpson, TL Cotton, AJ AF David, WS Simpson, TL Cotton, AJ TI Taking charge - A pilot curriculum of self-defense and personal safety training for female veterans with PTSD because of military sexual trauma SO JOURNAL OF INTERPERSONAL VIOLENCE LA English DT Article DE posttraumatic stress disorder; women veterans; personal safety; self-defense ID WOMEN; EFFICACY; AGGRESSION; ASSAULT; STRESS AB The authors describe an overview of the pilot project Taking Charge, a 36-hour comprehensive behavioral intervention involving psychoeducation, personal safety, and self-defense training for 12 female veterans with posttraumatic stress disorder (PTSD) from military sexual trauma. Self-defense training can incorporate the benefits of repeated exposure while teaching proactive cognitive and behavioral responses to the feared stimuli, and thus facilitate emotional and physical rescripting of and mastery over the trauma. Results up to 6 months follow-up indicate significant reductions in behavioral avoidance, PTSD hyperarousal, and depression, with significant increases in interpersonal, activity, and self-defense self-efficacy. The authors propose that this therapeutic self-defense curriculum provides an enhanced exposure therapy paradigm that may be a potent therapeutic tool in the treatment of PTSD. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP David, WS (reprint author), VA Puget Sound Hlth Care Syst, 116-MHC,1660 S Columbian Way, Seattle, WA 98108 USA. EM wendy.david@med.va.gov NR 20 TC 16 Z9 16 U1 1 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0886-2605 J9 J INTERPERS VIOLENCE JI J. Interpers. Violence PD APR PY 2006 VL 21 IS 4 BP 555 EP 565 DI 10.1177/0886260505285723 PG 11 WC Criminology & Penology; Family Studies; Psychology, Applied SC Criminology & Penology; Family Studies; Psychology GA 023EL UT WOS:000236108400007 PM 16501219 ER PT J AU Meeran, SM Mantena, SK Elmets, CA Katiyar, SK AF Meeran, S. M. Mantena, S. K. Elmets, C. A. Katiyar, S. K. TI Interleukin-12-deficient mice are at greater risk for the development of UV radiation-induced skin cancers SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 91 BP 16 EP 16 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500092 ER PT J AU Cha, X Naylor, T Bansal, A Lu, H Seykora, J Weber, B Fakharzadeh, S AF Cha, X. Naylor, T. Bansal, A. Lu, H. Seykora, J. Weber, B. Fakharzadeh, S. TI Identification of putative basal cell carcinoma genes by array-based comparative genomic hybridization SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 112 BP 19 EP 19 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500114 ER PT J AU Chamlin, S Cella, D Lai, J Williams, M Frieden, I Mancini, A Chren, M AF Chamlin, S. Cella, D. Lai, J. Williams, M. Frieden, I. Mancini, A. Chren, M. TI Childhood Atopic Dermatitis Index (CADIS): reliability, discriminative and concurrent validity, and responsiveness SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Childrens Mem Hosp, Div Pediat Dermatol, Chicago, IL USA. Evanston NW Healthcare, Ctr Outcomes Res & Educ, Evanston, IL USA. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 287 BP 48 EP 48 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500285 ER PT J AU Delfino, M Wittenberg, E Taylor, C Qureshi, A AF Delfino, M. Wittenberg, E. Taylor, C. Qureshi, A. TI Willingness-To-Pay stated preferences for eight health-related quality of life domains in psoriasis patients SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 313 BP 53 EP 53 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500313 ER PT J AU Freeman, S Barzilai, DA Freiman, A Collier, A Muller, S Kimball, A Dellavalle, R AF Freeman, S. Barzilai, D. A. Freiman, A. Collier, A. Muller, S. Kimball, A. Dellavalle, R. TI Senior US dermatology resident perspectives on training and workforce issues SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Denver Dept Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Brown Univ, Providence, RI 02912 USA. McGill Univ, Montreal, PQ H3A 2T5, Canada. Univ Nevada, Las Vegas, NV 89154 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 316 BP 53 EP 53 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500317 ER PT J AU Chren, M Sahay, A Bertenthal, D Sen, S AF Chren, M. Sahay, A. Bertenthal, D. Sen, S. TI Patient-reported outcomes of nonmelanoma skin cancer treated in different practice settings SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VAMC, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 329 BP 55 EP 55 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500327 ER PT J AU Ciocon, DH Horn, EJ Kimball, AB AF Ciocon, D. H. Horn, E. J. Kimball, A. B. TI Quality of life among patients with psoriasis and psoriatic arthritis and patients with psoriasis only SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Brigham & Womens Hosp, Clin Unit Res Trials Skin, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Natl Psoriasis Fdn, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 326 BP 55 EP 55 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500328 ER PT J AU Li, W Fedesco, M Fan, J Cheng, J Bandyopadhay, B Li, Y Feilds, J Han, Y Chen, M Woodley, D AF Li, W. Fedesco, M. Fan, J. Cheng, J. Bandyopadhay, B. Li, Y. Feilds, J. Han, Y. Chen, M. Woodley, D. TI Heat shock protein-90: an abundant extracellular molecule in epidermis and a potent stimulus of keratinocyte re-epithelialization SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Univ So Calif, Los Angeles, CA USA. Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 524 BP 88 EP 88 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500525 ER PT J AU Katiyar, SK Mantena, SK Meeran, SM Elmets, CA AF Katiyar, S. K. Mantena, S. K. Meeran, S. M. Elmets, C. A. TI (-)-Epigallocatechin-3-gallate from green tea prevents photocarcinogenesis in mice through augmentation of repair of UV-damaged DNA via interleukin-12-dependent mechanisms SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 788 BP 132 EP 132 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500785 ER PT J AU Boswell, SA Ongusaha, P Lee, SW AF Boswell, S. A. Ongusaha, P. Lee, S. W. TI The role of RhoE in the UVB response of human keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 819 BP 137 EP 137 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500813 ER PT J AU Valencia, A Kochevar, IE AF Valencia, A. Kochevar, I. E. TI A Nox1-containing isoform of NADPH oxidase is the major source of UVA-induced reactive oxygen species in human keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 820 BP 137 EP 137 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500816 ER PT J AU Gasbarre, C Khachemoune, A Sato, N Moore, B Keevey, S Hasan, T Maytin, E AF Gasbarre, C. Khachemoune, A. Sato, N. Moore, B. Keevey, S. Hasan, T. Maytin, E. TI Vitamin D and its analogs modulate photosensitizer production in 5-aminolevulinic acid (ALA) treated psoriasis plaques and epidermal organotypic cultures. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Cleveland Clin, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 842 BP 141 EP 141 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500839 ER PT J AU Beigneux, AP Vergnes, L Qiao, X Quatela, S Davis, R Watkins, SM Coleman, RA Walzem, RL Philips, M Reue, K Young, SG AF Beigneux, AP Vergnes, L Qiao, X Quatela, S Davis, R Watkins, SM Coleman, RA Walzem, RL Philips, M Reue, K Young, SG TI Agpat6 - a novel lipid biosynthetic gene required for triacylglycerol production in mammary epithelium SO JOURNAL OF LIPID RESEARCH LA English DT Article DE acyltransferase; transacylase; milk fat ID LYSOPHOSPHATIDIC ACID ACYLTRANSFERASE; DIACYLGLYCEROL ACYLTRANSFERASE; INSERTIONAL MUTATIONS; ENDOPLASMIC-RETICULUM; GLYCEROL 3-PHOSPHATE; BARTH SYNDROME; CLONING; MOUSE; CELLS; LIVER AB In analyzing the sequence tags for mutant mouse embryonic stem (ES) cell lines in BayGenomics (a mouse gene-trapping resource), we identified a novel gene, 1-acylglycerol-3-phosphate O-acyltransferase (Agpat6), with sequence similarities to previously characterized glycerolipid acyltransferases. Agpat6's closest family member is another novel gene that we have provisionally designated Agpat8. Both Agpat6 and Agpat8 are conserved from plants, nematodes, and flies to mammals. AGPAT6, which is predicted to contain multiple membrane-spanning helices, is found exclusively within the endoplasmic reticulum (ER) in mammalian cells. To gain insights into the in vivo importance of Agpat6, we used the Agpat6 ES cell line from BayGenomics to create Agpat6-deficient ( gpat6(-/-)) mice. Agpat6(-/-) mice lacked full-length Agpat6 transcripts, as judged by northern blots. One of the most striking phenotypes of Agpat6(-/-) mice was a defect in lactation. Pups nursed by Agpat6(-/-) mothers die perinatally. Normally, Agpat6 is expressed at high levels in the mammary epithelium of breast tissue, but not in the surrounding adipose tissue. Histological studies revealed that the aveoli and ducts of Agpat6(-/-) lactating mammary glands were underdeveloped, and there was a dramatic decrease in the size and number of lipid droplets within mammary epithelial cells and ducts. Also, the milk from Agpat6(-/-) mice was markedly depleted in diacylglycerols and triacylglycerols. Thus, we identified a novel glycerolipid acyltransferase of the ER, AGPAT6, which is crucial for the production of milk fat by the mammary gland. - Beigneux, A. P., L. Vergnes, X. Qiao, S. Quatela, R. Davis, S. M. Watkins, R. A. Coleman, R. L. Walzem, M. Philips, K. Reue, and S. G. Young. Agpat6 - a novel lipid biosynthetic gene required for triacylglycerol production in mammary epithelium. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med & Human Genet, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. NYU, Sch Med, Dept Med Cell Biol & Pharmacol, New York, NY 10016 USA. Lipom Technol, W Sacramento, CA 95691 USA. Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. RP Beigneux, AP (reprint author), Univ Calif Los Angeles, Div Cardiol, Dept Internal Med, Los Angeles, CA 90095 USA. EM abeigneux@mednet.ucla.edu FU NHLBI NIH HHS [U01 HL066621, UO1 HL-66621, R01 HL094732] NR 33 TC 67 Z9 70 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD APR PY 2006 VL 47 IS 4 BP 734 EP 744 DI 10.1194/jlr.M50056-JLR200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 024VF UT WOS:000236223700006 PM 16449762 ER PT J AU Vergnes, L Beigneux, AP Davis, R Watkins, SM Young, SG Reue, K AF Vergnes, L Beigneux, AP Davis, R Watkins, SM Young, SG Reue, K TI Agpat6 deficiency causes subdermal lipodystrophy and resistance to obesity SO JOURNAL OF LIPID RESEARCH LA English DT Article DE acyltransferase; gene-trap; adipose tissue.; energy expenditure; 1-acylglycerol-3-phosphate; O-acyltransferase ID LYSOPHOSPHATIDIC ACID ACYLTRANSFERASE; CONGENITAL GENERALIZED LIPODYSTROPHY; TRIGLYCERIDE SYNTHESIS; MICE; GENE; CLONING; MOUSE; EXPRESSION; LIPIN; ABNORMALITIES AB Triglyceride synthesis in most mammalian tissues involves the sequential addition of fatty acids to a glycerol backbone, with unique enzymes required to catalyze each acylation step. Acylation at the sn-2 position requires 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) activity. To date, seven Agpat genes have been identified based on activity and/or sequence similarity, but their physiological functions have not been well established. We have generated a mouse model deficient in AGPAT6, which is normally expressed at high levels in brown adipose tissue ( BAT), white adipose tissue (WAT), and liver. Agpat6-deficient mice exhibit a 25% reduction in body weight and resistance to both diet-induced and genetically induced obesity. The reduced body weight is associated with increased energy expenditure, reduced triglyceride accumulation in BAT and WAT, reduced white adipocyte size, and lack of adipose tissue in the subdermal region. In addition, the fatty acid composition of triacylglycerol, diacylglycerol, and phospholipid is altered, with proportionally greater polyunsaturated fatty acids at the expense of monounsaturated fatty acids. Thus, Agpat6 plays a unique role in determining triglyceride content and composition in adipose tissue and liver that cannot be compensated by other members of the Agpat family. - Vergnes, L., A. P. Beigneux, R. Davis, S. M. Watkins, S. G. Young, and K. Reue. Agpat6 deficiency causes subdermal lipodystrophy and resistance to obesity. 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 Human Genet, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Cardiol, Dept Internal Med, Los Angeles, CA 90095 USA. Lipom Technol, W Sacramento, CA 95691 USA. RP Reue, K (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. EM reuek@ucla.edu FU NHLBI NIH HHS [R01 HL094732-01, R01 HL094732-01S1, R01 HL094732-03, R01 HL094732, U01 HL066621, U01 HL-66621, R01 HL094732-02] NR 29 TC 68 Z9 71 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD APR PY 2006 VL 47 IS 4 BP 745 EP 754 DI 10.1194/jlr.M500553-JLR200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 024VF UT WOS:000236223700007 PM 16436371 ER PT J AU Nichols, FC Riep, B Mun, J Morton, MD Kawai, T Dewhirst, FE Smith, MB AF Nichols, FC Riep, B Mun, J Morton, MD Kawai, T Dewhirst, FE Smith, MB TI Structures and biological activities of novel phosphatidylethanolamine lipids of Porphyromonas gingivalis SO JOURNAL OF LIPID RESEARCH LA English DT Article DE interleukin 1 beta; prostaglandin E-2; gingival fibroblast; long-chain base; gas chromatography-mass spectrometry; electrospray tandem mass spectrometry ID OUTER-MEMBRANE VESICLES; EPITHELIAL-CELLS; PERIODONTAL-DISEASE; MASS-SPECTROMETRY; ORAL EPITHELIUM; PHOSPHOLIPIDS; FIMBRIAE; EXTRACTION; SEPARATION; SECRETION AB The Gram-negative periodontal pathogen Porphyromonas gingivalis synthesizes several classes of novel phosphorylated complex lipids, including the recently characterized phosphorylated dihydroceramides. These sphingolipids promote the interleukin-1 ( IL-1)-mediated secretion of inflammatory mediators from fibroblasts, including prostaglandin E-2 and 6-keto prostaglandin F-2 alpha, and alter gingival fibroblast morphology in culture. This report demonstrates that one additional class of phosphorylated complex lipids of P. gingivalis promotes IL-1-mediated secretory responses and morphological changes in cultured fibroblasts. Structural characterization identified the new phospholipid class as 1,2-diacyl phosphatidylethanolamine, which substituted predominantly with isobranched C-15:0 and C-13:0 fatty acids. The isobranched fatty acids, rather than unbranched fatty acids, and the phosphoethanolamine head group were identified as the essential structural elements required for the promotion of IL-1-mediated secretory responses. These structural components are also observed in specific phosphorylated sphingolipids of P. gingivalis and likely contribute to the biological activity of these substances, in addition to the phosphatidylethanolamine lipids described in this report. C1 Univ Connecticut, Sch Dent Med, Dept Periodontol, Farmington, CT 06030 USA. Charite Univ Med, Dept Periodontol & Synopt Dent, D-13353 Berlin, Germany. Univ Connecticut, Dept Chem, Storrs, CT 06269 USA. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Nichols, FC (reprint author), Univ Connecticut, Sch Dent Med, Dept Periodontol, Farmington, CT 06030 USA. EM nichols@nso.uchc.edu NR 30 TC 16 Z9 17 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD APR PY 2006 VL 47 IS 4 BP 844 EP 853 DI 10.1194/jlr.M500542-JLR200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 024VF UT WOS:000236223700018 PM 16439807 ER PT J AU D'Arceuil, HE Duggan, M He, JL Pryor, J de Crespigny, A AF D'Arceuil, HE Duggan, M He, JL Pryor, J de Crespigny, A TI Middle cerebral artery occlusion in Macaca fascicularis: acute and chronic stroke evolution SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE animal care; evolution; hemorrhage; herniation; MCAo; stroke ID ISCHEMIA; INFARCTION; PRIMATE; MODEL AB Background An intravascular stroke model designed for magnetic resonance imaging was developed in Macaca fascicularis (M. fascicularis) to characterize serial stroke lesion evolution. This model produces a range of stroke lesion sizes which closely mimics human stroke evolution. This paper describes the care of animals undergoing this stroke procedure, the range of outcomes we experienced and the cause of mortality in this model. Methods Anesthesia was induced with atropine and ketamine and maintained with isoflurane or propofol. Non-invasive blood pressure, oxygen saturation, heart rate, respiration rate, temperature and end tidal CO2 were monitored continuously. The stroke was created by occluding a distal branch of the middle cerebral artery. During catheter placement animals were heparinized and vasospasm was minimized using verapamil. Results Anesthetic induction and maintenance were smooth. Animals with small strokes showed very rapid recovery, were able to ambulate and self-feed within 2 hours of recovery. Animals with strokes of >= 4% of the hemispheric volume required lengthy observation during recovery and parenteral nutrition. Large strokes resulted in significant brain edema, herniation and brainstem compression. Conclusions Intracerebral hemorrhage and or subarachnoid hemorrhage coupled with a stroke of any size was acutely fatal. In the absence of an effective acute stroke therapy, the spectrum of outcomes seen in our primate model is very similar to that observed in human stroke patients. C1 Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Sect, NMR Ctr, Hillsborough 02129, North Ireland. Massachusetts Gen Hosp, Dept Comparat Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP D'Arceuil, HE (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Sect, NMR Ctr, Rm 2301,Bldg 149,13th St, Hillsborough 02129, North Ireland. EM helen@nmr.mgh.harvard.edu FU NINDS NIH HHS [1R01NS41285] NR 14 TC 15 Z9 16 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD APR PY 2006 VL 35 IS 2 BP 78 EP 86 DI 10.1111/j.1600-0684.2006.00147.x PG 9 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 019MW UT WOS:000235842000003 PM 16556294 ER PT J AU Hiroki, M Kajimura, N Uema, T Ogawa, K Nishikawa, M Kato, M Watanabe, T Nakajima, T Takano, H Imabayashi, E Ohnishi, T Takayama, Y Matsuda, H Uchiyama, M Okawa, M Takahashi, K Fukuyama, H AF Hiroki, M Kajimura, N Uema, T Ogawa, K Nishikawa, M Kato, M Watanabe, T Nakajima, T Takano, H Imabayashi, E Ohnishi, T Takayama, Y Matsuda, H Uchiyama, M Okawa, M Takahashi, K Fukuyama, H TI Effect of benzodiazepine hypnotic triazolam on relationship of blood pressure and PaCO2 to cerebral blood flow during human non-rapid eye movement sleep SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; SYMPATHETIC-NERVE ACTIVITY; WHITE-MATTER; SUBSTANTIA INNOMINATA; PREFRONTAL CORTEX; ANOXIC INJURY; RAT; MIDAZOLAM; BRAIN; (H2O)-O-15 AB We sought to clarify the effect of short-acting benzodiazepine hypnotic on the relationship of arterial blood pressure and arterial partial pressure of carbon dioxide (PaCO2) to regional cerebral blood flow (rCBF) during human non-rapid-eye-movement (non-REM) sleep. Nine young normal volunteers were treated in a randomized, crossover design with triazolam or placebo and underwent positron emission tomography at night. During wakefulness and stage 2 and slow wave ( stages 3 and 4) sleep, we measured mean arterial blood pressure ( MAP), PaCO2, and absolute CBF. With triazolam compared to placebo, MAP reduced gradually. During stage 2 sleep, PaCO2 increased and whole-brain mean CBF decreased. With triazolam, relative rCBF of the left orbital basal forebrain decreased more during stage 2 than slow wave sleep, whereas absolute CBF of the occipital cortex and cerebral white matter remained constant. During triazolam-induced stage 2 sleep, absolute CBF of the cerebral white matter correlated more strongly to both MAP and PaCO2 than during placebo sleep and also correlated more strongly to both MAP and PaCO2 than absolute CBF of the occipital cortex. In the frontal white matter, during triazolam-induced stage 2 sleep compared to wakefulness, absolute CBF was significantly better correlated to MAP, but not to PaCO2. During triazolam-induced stage 2, the cerebral white matter may receive a modulated CBF regulation having the strengthened relationship of PaCO2 to CBF and, more locally, the frontal white matter may depend precariously on CBF regulation. C1 Shiga Univ Med Sci, Dept Psychiat, Shiga, Japan. NIMH, Dept Psychiat, NCNP, Chiba, Japan. Teikyo Univ, Sch Med, Dept Psychiat, Kanagawa, Japan. Osaka Prefectural Gen Hosp, Dept Psychiat, Osaka, Japan. Natl Ctr Hosp Mental Nervous & Muscular Disorders, Natl Ctr Neurol & Psychiat, Dept Psychiat, Tokyo, Japan. Natl Ctr Hosp Mental Nervous & Muscular Disorders, Natl Ctr Neurol & Psychiat, Dept Anesthesiol, Tokyo, Japan. Natl Ctr Hosp Mental Nervous & Muscular Disorders, Natl Ctr Neurol & Psychiat, Dept Radiol, Tokyo, Japan. Kyoto Univ, Grad Sch Med, Human Brain Res Ctr, Kyoto, Japan. RP Hiroki, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Martinos NMR Ctr, Bldg 149,13th St,Mailcode 149-2301, Charlestown, MA 02129 USA. EM CYI01752@nifty.com NR 43 TC 0 Z9 0 U1 1 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 2006 VL 95 IS 4 BP 2293 EP 2303 DI 10.1152/jn.00114.2005 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 023UQ UT WOS:000236152100025 PM 16251267 ER PT J AU Starr, PA Turner, RS Rau, G Lindsey, N Heath, S Volz, M Ostrem, JL Marks, WJ AF Starr, PA Turner, RS Rau, G Lindsey, N Heath, S Volz, M Ostrem, JL Marks, WJ TI Microelectrode-guided implantation of deep brain stimulators into the globus pallidus internus for dystonia: techniques, electrode locations, and outcomes SO JOURNAL OF NEUROSURGERY LA English DT Article DE deep brain stimulation; dystonia; globus pallidus internus; microelectrode recording ID PRIMARY GENERALIZED DYSTONIA; PARKINSONS-DISEASE; CERVICAL DYSTONIA; BASAL GANGLIA; ELECTRICAL-STIMULATION; INTRATHECAL BACLOFEN; SUBTHALAMIC NUCLEUS; SECONDARY DYSTONIA; TECHNICAL APPROACH; NEURONAL-ACTIVITY AB Object. Deep brain stimulation (DBS) of the globus pallidus internus (GPI) is a promising new procedure for the treatment of dystonia. The authors describe their technical approach for placing electrodes into the GPI in awake patients with dystonia, including methodology for electrophysiological mapping of the GPI in the dystonic state, clinical outcomes and complications, and the location of electrodes associated with optimal benefit. Methods. Twenty-three adult and pediatric patients with various forms of dystonia were included in this study. Baseline neurological status and DBS-related improvement in motor function were measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The implantation of DBS leads was performed using magnetic resonance (MR) imaging-based stereotaxy, single-cell microelectrode recording, and intraoperative test stimulation to determine thresholds for stimulation-induced adverse effects. Electrode locations were measured on computationally reformatted postoperative MR images according to a prospective protocol. Conclusions. Physiologically guided implantation of DBS electrodes in patients with dystonia was technically feasible in the awake state in most patients, and the morbidity rate was low. Spontaneous discharge rates of GPI neurons in dystonia were similar to those of globus pallidus extemus neurons, such that the two nuclei must be distinguished by neuronal discharge patterns rather than rates. Active electrode locations associated with robust improvement (> 70% decrease in BFMDRS score) were located near the intercommissural plane, at a mean distance from the pallidocapsular border of 3.6 mm. C1 Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, PADRECC, San Francisco, CA USA. RP Starr, PA (reprint author), Univ Calif San Francisco, Dept Neurosurg, 505 Parnassus,779 Moffitt, San Francisco, CA 94143 USA. EM starrp@itsa.ucsf.edu FU NINDS NIH HHS [R01 NS039146, R01 NS039146-01] NR 53 TC 102 Z9 105 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD APR PY 2006 VL 104 IS 4 BP 488 EP 501 DI 10.3171/jns.2006.104.4.488 PG 14 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 029VM UT WOS:000236592500007 PM 16619651 ER PT J AU Rauch, SL Dougherty, DD Malone, D Rezai, A Friehs, G Fischman, AJ Alpert, NM Haber, SN Stypulkowski, PH Rise, MT Rasmussen, SA Greenberg, BD AF Rauch, SL Dougherty, DD Malone, D Rezai, A Friehs, G Fischman, AJ Alpert, NM Haber, SN Stypulkowski, PH Rise, MT Rasmussen, SA Greenberg, BD TI A functional neuroimaging investigation of deep brain stimulation in patients with obsessive-compulsive disorder SO JOURNAL OF NEUROSURGERY LA English DT Article DE anxiety disorder; orbitofrontal cortex; striatum; internal capsule; positron emission tomography; neurosurgery ID TONICALLY ACTIVE NEURONS; GLUCOSE METABOLIC-RATE; SYMPTOM PROVOCATION; MONKEY STRIATUM; PREDICTORS; PET; PHARMACOTHERAPY; MECHANISMS; DEPRESSION; RESPONSES AB Object. Deep brain stimulation (DBS) of the ventral [anterior internal] capsule/ventral striatum (VCNS) is under investigation as an alternative to anterior capsulotomy for severe obsessive-compulsive disorder (OCD). In neuroimaing studies of patients with OCD, dysfunction in the orbitofrontal and anterior cingulate cortex, striatum, and thalamus has been identified; and modulation of activity in this circuit has been observed following, successful nonsurgical treatment. The purpose of the current study was to test hypotheses regarding changes in regional cerebral blood flow (rCBF) during acute DBS at the VC/VS target in patients with OCD who were participating in a clinical DBS trial. Methods. Six patients enrolled in a DBS trial for OCD underwent positron emission tomography to measure rCBF; the rCBF measured during acute DBS at high frequency was then compared with those measured during DBS at low frequency and off (control) conditions. On the basis of neuroanatomical knowledge about the VCNS and neuroimaging data on OCD, the authors predicted that acute DBS at this target would result in modulation of activity within the implicated frontal-basal ganglia-thalamic circuit. Data were analyzed using statistical parametric mapping. In a comparison of acute high-frequency DBS with control conditions, the authors found significant activation of the orbitofrontal cortex, anterior cingulate cortex, striatum, globus pallidus, and thalamus. Conclusions. Acute DBS at the VCNS target is associated with activation of the circuitry implicated in OCD. Further studies will be necessary to replicate these findings and to determine the neural effects associated with chronic VCNS DBS. Moreover, additional data are needed to investigate whether pretreatment imaging profiles can be used to predict a patient's subsequent clinical response to chronic DBS. C1 Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neurosci Res & Neurotherapeut, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Cleveland Clin, Dept Psychiat, Cleveland, OH 44106 USA. Cleveland Clin, Dept Neurosurg, Cleveland, OH 44106 USA. Brown Univ, Sch Med, Dept Neurosurg, Providence, RI 02912 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Rochester, Sch Med, Dept Pharmacol & Physiol, Rochester, NY USA. Medtron Neurol, Minneapolis, MN USA. Butler Hosp, Dept Psychiat & Behav Sci, Providence, RI 02906 USA. RP Rauch, SL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neurosci Res & Neurotherapeut, Bldg 149,13th St,CNY-2, Charlestown, MA 02129 USA. EM rauch@psych.mgh.harvard.edu FU Intramural NIH HHS NR 43 TC 133 Z9 134 U1 3 U2 13 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 2006 VL 104 IS 4 BP 558 EP 565 DI 10.3171/jns.2006.104.4.558 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 029VM UT WOS:000236592500016 PM 16619660 ER PT J AU Chen, MF Westmoreland, S Ryzhova, EV Martin-Garcia, J Soldan, SS Lackner, A Gonzalez-Scarano, F AF Chen, MF Westmoreland, S Ryzhova, EV Martin-Garcia, J Soldan, SS Lackner, A Gonzalez-Scarano, F TI Simian immunodeficiency virus envelope compartmentalizes in brain regions independent of neuropathology SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE CD4-independence; CNS compartmentalization; gp160; SIV ID CENTRAL-NERVOUS-SYSTEM; AIDS DEMENTIA COMPLEX; DYNAMICS IN-VIVO; NEUTRALIZATION SENSITIVITY; HIV-1 INFECTION; MACROPHAGE TROPISM; CD4 INDEPENDENCE; DRUG-RESISTANCE; RHESUS MACAQUES; GENETIC DRIFT AB Simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) gp160s obtained from the brain are often genetically distinct from those isolated from other organs, suggesting the presence of brain-specific selective pressures or founder effects that result in the compartmentalization of viral quasispecies. Whereas HIV has also been found to compartmentalize within different regions of the brain, the extent of brain-regional compartmentalization of SIV in rhesus macaques has not been characterized. Furthermore, much is still unknown about whether phenotypic differences exist in envelopes from different brain regions. To address these questions, env DNA sequences were amplified from four SIVmac239-infected macaques and subjected to phylogenetic and phenetic analysis. The authors demonstrated that sequences from different areas of the brain form distinct clades, and that the long-term progressing macaques demonstrated a greater degree of regional compartmentalization compared to the rapidly progressing macaques. In addition, regional compartmentalization occurred regardless of the presence of giant-cell encephalitis. Nucleotide substitution rates at synonymous and nonsynonymous sites (ds:dn rates) indicated that positive selection varied among envelopes from different brain regions. In one macaque, envelopes from some but not all brain regions acquired changes in a conserved CD4-binding motif GGGDPE at amino acids 382 to 387. Furthermore, gp160s with the mutation G383E were able to mediate cell-to-cell fusion in a CD4-independent manner and were more susceptible to fusion inhibition by pooled plasma from infected macaques. Reversion of this mutation by site-directed mutagenesis resulted in reduction of CD4-independence and resistance to fusion inhibition in cell fusion assays. These studies demonstrate that SIV evolution within the brain results in a heterogeneous viral population with different phenotypes among different regions. C1 Univ Penn, Dept Neurol, Sch Med, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Ctr Comparat Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tulane Natl Primate Res Ctr, New Orleans, LA USA. RP Gonzalez-Scarano, F (reprint author), Univ Penn, Dept Neurol, Sch Med, 3 W Gates,3400 Spruce St, Philadelphia, PA 19104 USA. EM scarano@mail.med.upenn.edu RI Martin-Garcia, Julio/A-5666-2009 OI Martin-Garcia, Julio/0000-0001-5450-5029 FU NIMH NIH HHS [MH-067734]; NINDS NIH HHS [NS-27405] NR 65 TC 15 Z9 16 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD APR PY 2006 VL 12 IS 2 BP 73 EP 89 DI 10.1080/13550280600654565 PG 17 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 057AJ UT WOS:000238566500001 PM 16798669 ER PT J AU Wuthrich, C Kesari, S Kim, WK Williams, K Gelman, R Elmeric, D De Girolami, U Joseph, JT Hedley-Whyte, T Koralnik, IJ AF Wuthrich, C Kesari, S Kim, WK Williams, K Gelman, R Elmeric, D De Girolami, U Joseph, JT Hedley-Whyte, T Koralnik, IJ TI Characterization of lymphocytic infiltrates in progressive multifocal leukoencephalopathy: Co-localization of CD8(+) T cells with JCV-infected glial cells SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE CNS; demyelination; HIV; immune response; PML ID PROLONGED SURVIVAL; VIRUS EPITOPE; NATALIZUMAB; ASSOCIATION; DISEASE; THERAPY; BRAIN AB We characterized inflammatory infiltrates in archival brain biopsy and autopsy samples from 26 HIV+ and 20 HIV- patients with progressive multifocal leukoencephalopathy (PML). The predominant inflammatory cells were CD8(+) T lymphocytes. We defined CD8(+) T cell distribution with regard to JCV-infected glial cells, PML lesions and the extent of demyelination. In most samples from either HIV+ and HIV- patients, we found positive correlations between the parenchymal CD8(+) T cells and JCV-infected glial cells and conversely, negative correlations between the perivascular CD8(+) T cells and JCV-infected glial cells in the surrounding brain. Most of these correlations remained significant after accounting for the degree of demyelination and location of the cells relative to lesions. Moreover, high numbers of CD8(+) T cells were found within and at the border of active PML lesions. These results suggest that CD8(+) T cells are primarily associated with JCV-infected glial cells in most PML cases and that an active ongoing recruitment of CD8(+) T cells and possibly viral antigen-specific retention could occur. These observations are discussed in the context of the recent evidence of PML in multiple sclerosis and Crohn's patients treated with natalizumab, underscoring the role of CD8(+) T lymphocytes in continued immunosurveillance of the CNS. C1 Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Koralnik, IJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, Res E,213 C,330 Brookline Ave, Boston, MA 02215 USA. EM ikoralni@bidmc.harvard.edu RI Kesari, Santosh/E-8461-2013 FU NIMH NIH HHS [R24MH59724]; NINDS NIH HHS [NS037654, NS040237, R0 NS047029, R01 NS041198, R24NS045491] NR 21 TC 49 Z9 51 U1 1 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD APR PY 2006 VL 12 IS 2 BP 116 EP 128 DI 10.1080/13550280600716604 PG 13 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 057AJ UT WOS:000238566500005 PM 16798673 ER PT J AU Churchill, MJ Gorry, PR Cowley, D Lal, L Sonza, S Purcell, DFJ Thompson, KA Gabuzda, D McArthur, JC Pardo, CA Wesselingh, SL AF Churchill, MJ Gorry, PR Cowley, D Lal, L Sonza, S Purcell, DFJ Thompson, KA Gabuzda, D McArthur, JC Pardo, CA Wesselingh, SL TI Use of laser capture microdissection to detect integrated HIV-1 DNA in macrophages and astrocytes from autopsy brain tissues SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE astrocyte; HIV-1; HIVD; HIVE; macrophage; provirus ID IMMUNODEFICIENCY-VIRUS TYPE-1; DEMENTIA; NEUROPATHOGENESIS; INFECTION; AIDS AB The importance of astrocytes as a reservoir of human immunodeficiency virus type 1 (HIV-1) in the brain remains elusive. By combining immunohistochemistry, laser capture microdissection, and triple-nested Alu -PCR, we demonstrate integrated HIV-1 in astrocytes and macrophages isolated directly from autopsy brain tissues of HIV-1-infected subjects. The ability of HIV-1 to integrate in terminally differentiated astrocytes suggests a permanent reservoir of provirus in brain that will impact the development and likely success of strategies aimed at eradicating HIV-1. C1 Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic 3004, Australia. Monash Univ, Dept Med, Melbourne, Vic 3004, Australia. Monash Univ, Dept Microbiol, Melbourne, Vic 3004, Australia. Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD USA. RP Gorry, PR (reprint author), Macfarlane Burnet Inst Med Res & Publ Hlth, 85 Commercial Rd, Melbourne, Vic 3004, Australia. EM gorry@burnet.edu.au RI Purcell, Damian/G-5068-2011 FU NIAID NIH HHS [R21-AI054207]; NIDA NIH HHS [K08 DA016160, K08 DA016160-04, K08-DA16160]; NINDS NIH HHS [NS049465, NS44807, R01-NS37277] NR 17 TC 55 Z9 55 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD APR PY 2006 VL 12 IS 2 BP 146 EP 152 DI 10.1080/13550280600748946 PG 7 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 057AJ UT WOS:000238566500008 PM 16798676 ER PT J AU Boyce, PD Kim, JY Weissman, DN Hunt, J Christiani, DC AF Boyce, PD Kim, JY Weissman, DN Hunt, J Christiani, DC TI pH increase observed in exhaled breath condensate from welding fume exposure SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CYSTIC-FIBROSIS; CHILDREN; ASTHMA AB Objectives: We sought to investigate changes in exhaled breath condensate (EBC) pH in healthly workers exposed to welding fumes. Methods: Fourteen exposed participants (median age 39 years, 5 smokers) and 8 nonexposed controls (median age 44 Years, 1 smoker) were monitored at an apprentice welding school. Exposure to fine particulate matter less than 2.5 mu m (PM2.5) was assessed using cyclone samplers. EBC samples were collected at baseline and at the end of the work-shift. EBC samples were deaerated using argon and pH values were measured using standard pH microelectrodes. Results: Mean +/- SEM PM2.5 levels were 1.17 +/- 0.18 mg/m(3) for exposed subjects and 0.03 +/- 0.01 mg/m(3) for controls. Baseline median (range) EBC pH values for the control and exposed group were similar (P = 0.86), 7.21 (4.91 to 8.26), and 7.39(4,85 to 7.79), respectively. The exposed subjects had a small-but-marginally significant (P = 0.07) pre- to post-work shift increase in pH of 0.28, whereas the control group showed a minimal increase of only 0.03 (P = 0.56). Compared with the control group, the exposed group had a median cross-shift pH increase of 0.25 (P = 0.49). Conclusions: The aerosolized fine particulate matter contained in metal fumes may be associated with an acute increase in EBC pH values. Further study is necessary to investigate the acute rise in EBC pH after acute exposure to welding fume. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit,Dept Med, Boston, MA 02115 USA. US EPA, Natl Ctr Environm Assessment, Res Triangle Pk, NC 27711 USA. NIOSH, Div Resp Dis Studies, Morgantown, WV 26505 USA. Univ Virginia, Div Pediat Resp Med, Charlottesville, VA USA. RP Boyce, PD (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. EM paulboyce@post.harvard.edu FU NCI NIH HHS [CA94715]; NHLBI NIH HHS [T32 HL07874]; NIEHS NIH HHS [ES00002, ES09860, T32 ES07069] NR 15 TC 15 Z9 16 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD APR PY 2006 VL 48 IS 4 BP 353 EP 356 DI 10.1097/01.jom.0000205988.50907.d8 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 033GZ UT WOS:000236836400002 PM 16607188 ER PT J AU Suggs, JF Li, GA Park, SE Sultan, PG Rubash, HE Freiberg, AA AF Suggs, JF Li, GA Park, SE Sultan, PG Rubash, HE Freiberg, AA TI Knee biomechanics after UKA and its relation to the ACL - A robotic investigation SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE knee biomechanics; UKA; ACL ID ANTERIOR CRUCIATE LIGAMENT; 10-YEAR FOLLOW-UP; JOINT KINEMATICS; IN-VITRO; UNICOMPARTMENTAL ARTHROPLASTY; MUSCLE LOADS; OSTEOARTHRITIS; CARTILAGE; FLEXION; FORCES AB Unicompartmental knee arthroplasty (UKA) has regained popularity in recent years. However, limited data exist on how UKA affects knee biomechanics. The role of the anterior cruciate ligament (ACL) after fixed bearing UKA remains controversial. In this study, a robotic testing system was used to apply a quadriceps/hamstrings load to cadaveric knee specimens in the intact state, after medial UKA, and after transection of the ACL in UKA. The load was applied to the knee from full extension to 120 degrees of flexion in 30 degrees increments. UKA generally did not affect anterior-posterior (AP) femoral position, but did cause external tibial rotation and variations in varus-valgus rotation compared to the intact knee. ACL transection after UKA shifted the femur posteriorly compared to the intact and UKA knees and increased internal tibial rotation compared to the UKA knee at low flexion. The AP motion of the articular contact position in the implant was increased after ACL transection. These data might help explain the mechanism of tibial component loosening and provide insight into further investigations of polyethylene wear in UKA. Based on the kinematic data, the ACL should be functional to provide patients the greatest opportunity for long-term success after medial UKA. (c) 2006 Orthopaedic Research Society. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, GA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org NR 30 TC 26 Z9 26 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD APR PY 2006 VL 24 IS 4 BP 588 EP 594 DI 10.1002/jor.20082 PG 7 WC Orthopedics SC Orthopedics GA 031CW UT WOS:000236682700002 PM 16514655 ER PT J AU Surkan, PJ Kreicbergs, U Valdimarsdottir, U Nyberg, U Onelov, E Dickman, PW Steineck, G AF Surkan, PJ Kreicbergs, U Valdimarsdottir, U Nyberg, U Onelov, E Dickman, PW Steineck, G TI Perceptions of inadequate health care and feelings of guilt in parents after the death of a child to a malignancy: A population-based long-term follow-up SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID BEREAVED PARENTS; CANCER-PATIENTS; OF-LIFE; DEPRESSION; NATIONWIDE; LEUKEMIA; DIFFICULTIES; SYMPTOMS; QUALITY; ANXIETY AB Background: Parental feelings of guilt can be a serious problem after the death of a child to a malignancy. This study identified predictors of feelings of guilt in parents during the year after a child's death. Methods: The Swedish Cause of Death Register and Swedish Cancer Register were used to identify all parents in Sweden who had a child who died of a malignancy between 1992-1997. Results: Among parents not reporting recent depression, those who were not confident that their child would immediately receive help from the staff in the hospital while he or she was sick with a malignancy (compared to those who felt partly or entirely sure, relative risk [RR] 4.0; 95% confidence interval [CI] 2.1-7.6), were at increased risk for reporting daily or weekly feelings of guilt in the year after the child's death. Parents who perceived that the staff in the pediatric cancer ward were incompetent were at increased risk (compared to parents reporting partial or total competence, RR 3.7; 95% CI 1.6-8.6). Compared to parents reporting that their children had moderate or much access, those who felt their children had little or no access to pain relief, dietary advice, anxiety relief, and relief of other psychological symptoms beside anxiety were at more than two times greater risk for reporting feelings of guilt. Conclusions: Bereaved parents' perceptions of inadequate health care were associated with subsequent feelings of guilt during the year following their child's death due to a malignancy. C1 Karolinska Hosp, Karolinska Inst, Dept Pathol & Oncol, Div Clin Canc Epidemiol, SE-17176 Stockholm, Sweden. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Karolinska Hosp, Karolinska Inst, Dept Woman & Child Hlth, Childhood Canc Res Unit, SE-17176 Stockholm, Sweden. Karolinska Inst, St Gorans Hosp, Dept Clin Neurosci, Stockholm, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Sahlgrenska Acad, Div Clin Canc Epidemiol, Gothenburg, Sweden. Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA. RP Surkan, PJ (reprint author), Karolinska Hosp, Karolinska Inst, Dept Pathol & Oncol, Div Clin Canc Epidemiol, Z5-U1, SE-17176 Stockholm, Sweden. EM psurkan@hsph.harvard.edu RI Dickman, Paul/B-4572-2013 OI Dickman, Paul/0000-0002-5788-3380 NR 35 TC 24 Z9 24 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD APR PY 2006 VL 9 IS 2 BP 317 EP 331 DI 10.1089/jpm.2006.9.317 PG 15 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 045XV UT WOS:000237776900025 PM 16629562 ER PT J AU Oliva, E Sarrio, D Brachtel, EF Sanchez-Estevez, C Soslow, RA Moreno-Bueno, G Palacios, J AF Oliva, E Sarrio, D Brachtel, EF Sanchez-Estevez, C Soslow, RA Moreno-Bueno, G Palacios, J TI High frequency of beta-catenin mutations in borderline endometrioid tumours of the ovary SO JOURNAL OF PATHOLOGY LA English DT Article DE ovary; borderline endometrioid tumour; endometrioid carcinoma; beta-catenin mutation; PTEN; KRAS ID MICROSATELLITE INSTABILITY; MALIGNANT-TRANSFORMATION; MOLECULAR ALTERATIONS; GENETIC ALTERATIONS; EXPRESSION PATTERN; EPITHELIAL TUMORS; K-RAS; CANCER; CARCINOMAS; BRCA1 AB Some low-grade endometrioid carcinomas arise from a background of endometrioid tumours of borderline malignancy. To determine the molecular mechanisms involved in the initiation of endometrioid carcinoma, the present study investigated whether the genetic alterations reported in these tumours (mutations in PTEN, KRAS, and beta-catenin genes, and microsatellite instability) are already present in endometrioid tumours of borderline malignancy. Eight endometrioid tumours of borderline malignancy were studied. By immunohistochemistry, beta-catenin was expressed in the nuclei of all tumours, suggesting the presence of stabilizing beta-catenin mutations. By mutational analysis, five different beta-catenin mutations were found in seven of eight cases (90%), affecting codons 32, 33, and 37. In contrast, only one tumour harboured a PTEN mutation, which affected codon 130. Neither KRAS mutations nor microsatellite instability was detected. A review of the literature indicated that beta-catenin mutations are characteristic of well-differentiated endometrioid carcinomas, since they were present in nearly 60% of grade I but in less of 3% of grade III tumours. In conclusion, the present study identifies beta-catenin mutation as a nearly constant molecular alteration in borderline endometrioid tumours, whereas PTEN and KRAS mutations and microsatellite instability are very infrequent. The findings in the present study, and previously reported data, strongly suggest that beta-catenin mutation is an early event in endometrioid ovarian carcinogenesis, and that it is involved in the development of low-grade endometrioid tumours. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 CNIO, Programa Patol Mol, Lab Breast & Gynaecol Canc, Madrid 28029, Spain. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Palacios, J (reprint author), CNIO, Programa Patol Mol, Lab Breast & Gynaecol Canc, C Melchor Fernandez Almagro 3, Madrid 28029, Spain. EM jpalacios@cnio.es RI Moreno-Bueno, Gema/K-9354-2016; OI Moreno-Bueno, Gema/0000-0002-5030-6687; Soslow, Robert/0000-0002-7269-5898 NR 30 TC 38 Z9 41 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD APR PY 2006 VL 208 IS 5 BP 708 EP 713 DI 10.1002/path.1923 PG 6 WC Oncology; Pathology SC Oncology; Pathology GA 028HT UT WOS:000236478500012 PM 16429393 ER PT J AU Belkind-Gerson, J Graeme-Cook, F Winter, H AF Belkind-Gerson, J Graeme-Cook, F Winter, H TI Enteric nervous system disease and recovery, plasticity, and regeneration SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Editorial Material ID INTESTINAL NEURONAL DYSPLASIA; NITRIC-OXIDE SYNTHASE; IRRITABLE-BOWEL-SYNDROME; CREST-DERIVED CELLS; NEURAL STEM-CELLS; FETAL-RAT GUT; HIRSCHSPRUNGS-DISEASE; MAST-CELLS; IN-VITRO; GASTROINTESTINAL-TRACT C1 Inst Nacl Salud Pul, Ctr Invest Sobre Enfermedades Cronicas, Cuernavaca 62508, Morelos, Mexico. Harvard Univ, Sch Med, Dept Pediat Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Belkind-Gerson, J (reprint author), Inst Nacl Salud Pul, Ctr Invest Sobre Enfermedades Cronicas, Av Univ 655,Col Sta Maria Ahuacatitlan, Cuernavaca 62508, Morelos, Mexico. EM cuernavacajaime@yahoo.com NR 85 TC 6 Z9 7 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD APR PY 2006 VL 42 IS 4 BP 343 EP 350 DI 10.1097/01.mpg.0000218696.58487.5b PG 8 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 037PI UT WOS:000237158800001 PM 16641570 ER PT J AU Sandler, ES Homans, A Mandell, L Amylon, M Wall, DA Devidas, M Buchanan, GR Lipton, JM Billett, AL AF Sandler, ES Homans, A Mandell, L Amylon, M Wall, DA Devidas, M Buchanan, GR Lipton, JM Billett, AL TI Hematopoietic stem cell transplantation after first marrow relapse of non-T, non-B acute lymphoblastic leukemia - A Pediatric Oncology Group pilot feasibility study SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE acute lymphoblastic leukemia; hematopoietic stem cell transplant; immunotoxin ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; TERM-FOLLOW-UP; 2ND REMISSION; UNRELATED DONORS; 1ST REMISSION; CHILDREN; CHEMOTHERAPY; CYCLOSPORINE; EXPERIENCE AB Background: Relapsed acute lymphoblastic leukemia (ALL) in children is associated with a poor outcome, especially for those patients whose relapse occurs during the first 36 months after diagnosis. The best therapy for these patients is not known. This study was designed to evaluate the feasibility of enrolling children with recurrent ALL in the standardisation treatment protocol that included receipt of a hematopoietic stem cell transplant (HSCT). Procedure: Eligible patients with a bone marrow relapse of non-T, non-B ALL underwent a common induction and consolidation followed by receipt of either an allogeneic HSCT from a human leukocyte antigen (HLA)-identical sibling or an autologous HSCT purged with B-4 blocked ricin. A common conditioning regimen was used for all patients. Results: Twenty-eight patients from eight institutions were enrolled. Fourteen patients did not receive a transplant during the study because of toxicity (4), relapse (1), inadequate purging (1), and parental or physician preference for an alternative donor transplant (8). Six patients received allogeneic HSCTs. Five of them have remained in remission for a median of 78 months. Eight patients received autologous HSCTs purged with B4-blocked ricin. Four have remained in remission for a median of 94 months. Of the nine patients who received alternative donor transplants, only two remain in remission. Conclusion: We conclude that well designed and controlled prospective studies are necessary to define the role of HSCTs in children with recurrent ALL. In order to be successful, such studies must have the full support of participating centres. Autologous HSC transplantation may not have a role in the treatment of relapsed ALL, but further studies are needed. C1 Nemours Childrens Clin, Dept Hematol Oncol, Jacksonville, FL 32207 USA. Univ Vermont, Burlington, VT 05405 USA. Mt Sinai Med Ctr, Cleveland, OH 44106 USA. Stanford Univ, Stanford, CA 94305 USA. St Louis Univ, St Louis, MO 63103 USA. Univ Florida, Gainesville, FL 32611 USA. Univ Texas, SW Med Ctr Dallas, Dallas, TX 75230 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sandler, ES (reprint author), Nemours Childrens Clin, Dept Hematol Oncol, 807 Childrens Way, Jacksonville, FL 32207 USA. EM esandler@nemours.org NR 31 TC 8 Z9 8 U1 0 U2 1 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 2006 VL 28 IS 4 BP 210 EP 215 DI 10.1097/01.mph.0000212902.84146.81 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 042NS UT WOS:000237535600004 PM 16679917 ER PT J AU Gaissert, HA Grillo, HC AF Gaissert, HA Grillo, HC TI Complications of the tracheal diverticulum after division of congenital tracheoesophageal fistula SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE tracheal diverticulum; recurrent tracheoesophageal fistula ID ESOPHAGEAL ATRESIA AB In 3 patients, recurrent respiratory symptoms after neonatal repair of congenital tracheoesophageal fistula (Gross type C in 2, D in 1) were associated with a large tracheal remnant of the fistula termed diverticulum. Symptoms resolved after resection of the diverticulum in 1 child with airway obstruction and 1 adult with recurrent tracheoesophageal fistula. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gaissert, HA (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. EM hgaissert@partners.org NR 8 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD APR PY 2006 VL 41 IS 4 BP 842 EP 844 DI 10.1016/j.jpedsurg.2005.12.038 PG 3 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 035QG UT WOS:000237015800057 PM 16567205 ER PT J AU Harada, Y Han, X Yamashita, K Kawai, T Eastcott, JW Smith, DJ Taubman, MA AF Harada, Y Han, X Yamashita, K Kawai, T Eastcott, JW Smith, DJ Taubman, MA TI Effect of adoptive transfer of antigen-specific B cells on periodontal bone resorption SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE Actinobacillus actinomycetemcomitans; antibody; antibody-secreting cells; B lymphocytes; bone resorption; periodontal disease ID T-HELPER CELLS; PORPHYROMONAS-GINGIVALIS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; AUTOIMMUNE ENCEPHALOMYELITIS; OSTEOCLAST DIFFERENTIATION; IMMUNE CHARACTERISTICS; ANTAGONISTS INHIBIT; HOST RESPONSES; ALVEOLAR BONE; DISEASE AB Background and Objectives: Host immune responses to periodontal pathogens have been considered to contribute to the alveolar bone destruction in periodontitis. However, the role of B lymphocytes in the pathogenesis of periodontal bone loss is not clear. Methods: We examined the effect of adoptive transfer of antigen-specific B cells from rat spleens on experimental periodontal bone resorption. Donor rats were immunized intraperitoneally (i.p.) with formalin-killed Actinobacillus actinomycetemeomitans. Antigen-specific B cells were prepared from splenocytes by first binding CD43(+) cells to Petri dishes coated with anti-CD43 antibody to remove T cells, and non-binding cells were passed through a nylon wool column to deplete accessory cells. The retained cells were then collected and bound to A. actinomycetemcomitans-coated Petri dishes for enrichment of A. actinomycetemcomitans-binding B cells (AAB). A. actinomycetemcomitans non-binding B cells (ANB) and B cells from non-immunized donor rats (NIB) were also collected from these procedures. Each type of B cell was injected into a group of recipient rats that were then orally infected with live A. actinomycetemcomitans. Results: At termination, the antibody levels to A. actinomycetemcomitans in serum and gingival wash fluids were significantly higher in the recipients transferred with AAB when compared to the recipients transferred with ANB or NIB. A markedly elevated number of antibody-forming cells were observed in the spleens of the recipients transferred with AAB, and these recipient rats also exhibited significantly increased bone resorption when compared to the other groups. Conclusions: It is suggested that B cells can contribute to periodontal bone resorption and that antigen-triggering of B cells is required for the bone resorption. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. RP Taubman, MA (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. EM mtaubman@forysyth.org FU NIDCR NIH HHS [R01 DE003420, DE-03420] NR 43 TC 9 Z9 9 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD APR PY 2006 VL 41 IS 2 BP 101 EP 107 DI 10.1111/j.1600-0765.2005.00839.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 023EH UT WOS:000236108000003 PM 16499712 ER PT J AU Dygert, JH Thatte, HS Kumbhani, DJ Najjar, SF Treanor, PR Khuri, SF AF Dygert, JH Thatte, HS Kumbhani, DJ Najjar, SF Treanor, PR Khuri, SF TI Intracoronary shunt-induced endothelial cell damage in porcine heart SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE coronary artery; endothelium; nitric oxide; off-pump bypass surgery ID CORONARY-ARTERY-BYPASS; INTERNAL-MAMMARY-ARTERY; HUMAN BEATING HEART; OFF-PUMP; GAS INSUFFLATION; SAPHENOUS-VEIN; SURGERY; INJURY; GRAFT; OCCLUSION AB Background. Injury to and dysfunction of the endothelium can compromise the patency of coronary arteries and lead to impaired perfusion of the heart. Such injury can occur after the application of an intravascular shunt and/or a snare to a coronary artery during bypass surgery. In this study, multiphoton microscopy was used to assess the integrity of endothelium in porcine coronary arteries subjected to shunting and snaring during off-pump coronary artery bypass grafting (OPCAB). Materials and methods. In open chest porcine, the left anterior descending artery was manipulated in different regions using snare and shunt to simulate OPCAB. Sections of left anterior descending artery were labeled with fluorescent dyes to evaluate the viability of the endothelium. The structural integrity of the endothelium was evaluated by calcein- and ethidium homodimer-mediated fluorescence. Endothelial functional viability was assessed by measuring cellular esterase activity, calcium mobilization, and endothelial nitric oxide synthase-mediated generation of nitric oxide using fluorescence dyes and multiphoton microscopy. Results. Substantial endothelial damage was observed in shunted region of the coronary arteries. In contrast, endothelium remained structurally viable in regions that were snared, similar to control regions of the coronary arteries that were not manipulated. Esterase activity, calcium mobilization, and nitric oxide generation was greater in the control and snared regions of the coronary arteries in comparison to the shunted region. Conclusions. The use of intracoronary shunts led to structural damage and attenuation of endothelial function in porcine coronary arteries, whereas snared vessels maintained their viability and integrity, similar to the control sections. The routine use of shunts in OPCABG may lead to endothelial damage and possibly to long-term graft failure. (C) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst,Dept Surg, Boston, MA 02132 USA. RP Khuri, SF (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst,Dept Surg, MC 112,1400 VFW Pkwy, Boston, MA 02132 USA. EM shukri.khuri@med.va.gov NR 25 TC 17 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD APR PY 2006 VL 131 IS 2 BP 168 EP 174 DI 10.1016/j.jss.2005.10.026 PG 7 WC Surgery SC Surgery GA 025HW UT WOS:000236257200002 PM 16412472 ER PT J AU Wilens, TE Gignac, M Swezey, A Monuteaux, MC Biederman, J AF Wilens, TE Gignac, M Swezey, A Monuteaux, MC Biederman, J TI Characteristics of adolescents and young adults with ADHD who divert or misuse their prescribed medications SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; stimulant; abuse liability; diversion ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; SUBSTANCE-ABUSING ADOLESCENTS; INTRANASAL ABUSE; METHYLPHENIDATE ABUSE; ORAL METHYLPHENIDATE; COCAINE DEPENDENCE; CONTROLLED-TRIAL; STIMULANT USE; HUMAN BRAIN AB Objective: Little is known about the risks and characteristics of attention-deficit/hyperactivity disorder (ADHD) patients who misuse or divert their stimulant medications. As part of a 10-year longitudinal study of youths with ADHD, the authors evaluated medication diversion or misuse at the last follow-up period. Method: Structured psychiatric interviews for diagnosis and a self-report questionnaire regarding medication use in medicated subjects with ADHD compared with controls without ADHD receiving psychotropics for non-ADHD treatment were employed. Results: Of 98 subjects receiving psychotropic medications (mean age of 20.8 +/- 5 years), 55 (56%) were ADHD subjects and 43 (44%) were controls receiving medications for other purposes. The authors found that 11% of the ADHD group reported selling their medications compared with no subjects in the control group (z = 0.00, p < .05). An additional 22% of the ADHD group reported misusing their medications compared with 5% of the control subjects (z = 1.7 p = .09) and that those with conduct or substance use disorders accounted for the misuse and diversion. A minority of subjects reported escalating their doses and concomitant use with alcohol and drugs. Conclusions: The data indicate that the majority of ADHD individuals, particularly those without conduct or substance use disorders, use their medications appropriately. The authors' findings also highlight the need to monitor medication use in ADHD individuals with conduct and/or substance use disorders and to carefully select agents with a low likelihood of diversion or misuse in this group. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Montreal, Inst Philippe Pinel, Montreal, PQ H3C 3J7, Canada. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, YAW 6A,32 Fruit St, Boston, MA 02114 USA. EM twilens@partners.org FU NIDA NIH HHS [R01 DA14419, K24 DA016264] NR 34 TC 120 Z9 121 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 2006 VL 45 IS 4 BP 408 EP 414 DI 10.1097/01.chi.0000199027.68828.b3 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 027NC UT WOS:000236421300007 PM 16601645 ER PT J AU Shanbhag, AS AF Shanbhag, AS TI Use of bisphosphonates to improve the durability of total joint replacements SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Article ID TOTAL HIP-ARTHROPLASTY; NITROGEN-CONTAINING BISPHOSPHONATES; PERIPROSTHETIC BONE LOSS; MOLECULAR-WEIGHT POLYETHYLENE; PARTICLE-INDUCED OSTEOLYSIS; HUMAN OSTEOBLASTIC CELLS; IN-VITRO; RAT MODEL; OSTEOPOROTIC WOMEN; MEVALONATE PATHWAY AB Total joint arthroplasty is very effective for improving the quality of life of patients with end-stage arthritis. Despite advances in materials, surgical technique, and rehabilitation regimens, joint replacements are still fraught with complications leading to their premature failure. Aseptic loosening and osteolysis are the primary causes of implant failure. Other reasons include early migration of components leading to instability, lack of ingrowth into implant porosities, and bone loss caused by stress shielding. Pharmaceutical agents used for preventing and managing postmenopausal osteoporosis leg, bisphosphonates may in the future play an important role in improving the long-term duration of joint arthroplasties. Early findings indicate that bisphosphonates upregulate bone morphogenetic protein-2 production and stimulate new bone formation. Because of their anabolic effect on osteoblasts, bisphosphonates have the potential to enhance bone ingrowth into implant porosities, prevent bone resorption under adverse conditions, and dramatically extend the long-term durability of joint arthroplasties. The long-term effects of bisphosphonate use on the mechanical properties of bone have not been adequately investigated. Along with improvements in implant design and material properties, bisphosphonates and other pharmaceutical agents may, in the near future, be part of the growing armamentarium that provides more durable joint arthroplasties. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Shanbhag, AS (reprint author), Massachusetts Gen Hosp, Biomat Lab, GRJ 1115,55 Fruit St, Boston, MA 02114 USA. FU NIAMS NIH HHS [AR47465A03] NR 67 TC 33 Z9 41 U1 0 U2 1 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD APR PY 2006 VL 14 IS 4 BP 215 EP 225 PG 11 WC Orthopedics SC Orthopedics GA 053XD UT WOS:000238338500003 PM 16585363 ER PT J AU Bush, RL Johnson, ML Collins, TC Henderson, WG Khuri, SF Yu, HJ Lin, PH Lumsden, AB Ashton, CM AF Bush, RL Johnson, ML Collins, TC Henderson, WG Khuri, SF Yu, HJ Lin, PH Lumsden, AB Ashton, CM TI Open versus endovascular abdominal aortic aneurysm repair in VA hospitals SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID QUALITY-OF-LIFE; OPEN SURGICAL REPAIR; RANDOMIZED CONTROLLED-TRIAL; LOGISTIC-REGRESSION MODELS; MYOCARDIAL-INFARCTION; AAA REPAIR; PERIOPERATIVE MORTALITY; VETERANS HEALTH; STENT GRAFT; RISK AB BACKGROUND: Endovascular abdominal aortic aneurysm repair (EVAR), when compared with conventional open surgical repair, has been shown to reduce perioperative morbidity and mortality. We performed a retrospective cohort Study with prospectively collected data from the Department of Veterans Affairs to examine outcomes after elective aneurysm repair. STUDY DESIGN: We studied 30-day mortality, 1-year survival,and postoperative complications in 1,904 patients who underwent elective abdominal aortic aneurysm repair (EVAR n = 717 [37.7%]; open n = 1,187 [62.3%]) at 123 Department of Veterans Affairs hospitals between May 1, 2001 and September 30, 2003. We investigated the influence of patient, operative, and hospital variables on outcomes. RESULTS: Patients undergoing EVAR had significantly lower 30-day (3.1% versus 5.6%, p = 0.01) and 1-year mortality rates (8.7% versus 12.1%, p = 0.018) than patients having open repair. EVAR was associated with I decrease in 30-day postoperative mortality (adjusted odds ratio[OR] = 0.59; 95% CI = 0.36, 0.99; p = 0.04). The risk of perioperative complications was much less after EVAR (15.5% versus 27.7%; p < 0.001; unadjusted OR 0.48; 95% CI = 0.38, 0.61; P < 0.001). Patients operated on at low volume hospitals (25% of entire cohort) were more likely to have had open repair (31.3% compared with 15.9% EVAR; p < 0.001) and a nearly two-fold increase in adjusted 30-day mortality risk (OR = 1.9; 95% CI = 1.19, 2.98; p = 0.006). CONCLUSIONS: In routine daily practice, veterans who undergo elective EVAR have substantially lower perioperative mortality and morbidity rates compared with patients having open repair. The benefits of a minimally invasive approach were readily apparent in this cohort, but we recommend using caution in choosing EVAR for all elective abdominal aortic aneurysm repairs until longer-term data on device durability are available. C1 Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston Ctr Qual Care & Utlizat Studies, Micheal E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Univ Colorado, Hlth Outcomes Program, Denver, CO 80202 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Bush, RL (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, 1709 Dryden,Suite 1568, Houston, TX 77030 USA. NR 42 TC 47 Z9 49 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 2006 VL 202 IS 4 BP 577 EP 587 DI 10.1016/j.jamcollsurg.2006.01.005 PG 11 WC Surgery SC Surgery GA 028HE UT WOS:000236476900002 PM 16571424 ER PT J AU Datto, CJ Thompson, R Knott, K Katz, IR AF Datto, CJ Thompson, R Knott, K Katz, IR TI Older adult report of change in depressive symptoms as a treatment decision tool SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE primary care; older adult; depression; treatment decision-making ID MEMORY-CONCENTRATION TEST; MENTAL-HEALTH-SERVICES; PRIMARY-CARE PATIENTS; RANDOMIZED-TRIAL; PERSPECTIVE; DISORDERS; DISEASE; SAMPLE; STATE AB OBJECTIVES: To evaluate patient reports of changes in depressive symptoms as information that can be used in treatment decision-making. DESIGN: Longitudinal cohort study. SETTING: The Prevention of Suicide in Primary Care Elderly: Collaborative Trial and the Primary Care Research in Substance Abuse and Mental Health for the Elderly trial, multisite studies investigating the effect of depression interventions on outcomes in primary care. PARTICIPANTS: Fifty-six patients aged 60 and older. MEASUREMENTS: Patient demographics were collected from patient reports. Symptoms of depression were measured using the Centers for Epidemiologic Studies Depression Scale (CES-D) and Hamilton Depression Scale (HAM-D). Changes in depressive symptoms were also measured using the Clinical Global Impressions of Change (CGI-C) as rated by patients in ongoing treatment. RESULTS: Patient ratings of CGI-C were significantly correlated with percentage improvement on the HAM-D as rated by the depression care manager (correlation coefficient (r)=0.44, P <.001) and percentage improvement on the CES-D (r=0.38, P=.005). The patient report of at least "much improved" predicted at least 50% treatment response based on HAM-D scale scores, with a sensitivity of 87.5% and a specificity of 74.2%. CONCLUSION: These findings suggest that patients are able to accurately report their degree of improvement in depressive symptoms. Patient report of at least "much improved" can be used as an estimate of at least 50% depression treatment response. In an era of increasingly fragmented clinical care, these findings demonstrate that older adult primary care patients can accurately self-report overall change in depressive symptoms. When results of repeated depression instruments are not available, patient report of depression treatment response can be used to inform depression treatment decision-making. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. JPA, Res & Training Inst, Chicago, IL USA. RP Datto, CJ (reprint author), 3535 Market St,Room 3055, Philadelphia, PA 19104 USA. EM cdatto@mail.med.upenn.edu RI Thompson, Richard/G-5408-2011 OI Thompson, Richard/0000-0003-0127-513X FU CMHS SAMHSA HHS [1UD1SM53033]; NIMH NIH HHS [5P30MH52129, P30-MH066270] NR 19 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 BP 627 EP 631 DI 10.1111/j.1532-5415.2006.00660.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 029SQ UT WOS:000236585100009 PM 16686873 ER PT J AU Williams, BA Lindquist, K Sudore, RL Strupp, HM Willmott, DJ Walter, LC AF Williams, BA Lindquist, K Sudore, RL Strupp, HM Willmott, DJ Walter, LC TI Being old and doing time: Functional impairment and adverse experiences of geriatric female prisoners SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE prisoners; geriatrics; activities of daily living; women ID HEALTH LITERACY; INMATES; RISK; CARE; PERFORMANCE; LIMITATIONS; PREVALENCE; DISABILITY; MORTALITY; DISEASE AB The number of older prisoners is increasing exponentially. For example, the number of geriatric female prisoners in California has increased 350% in the past decade. Despite an increasing population of geriatric female prisoners, the degree of functional impairment in this population is unknown. Therefore, the goals of this study were to describe the prevalence and nature of functional impairment in geriatric female prisoners in California and to identify aspects of the prison environment that may exacerbate functional impairments. Questionnaires were analyzed from 120 geriatric women in California state prisons. Functional impairment was defined as impairment in activities of daily living (ADLs) or in prison ADLs (PADLs), including dropping to the floor for alarms, standing for count, getting to meals, hearing orders, and climbing onto the top bunk. The mean age of participants was 62; 16% were dependent in one ADL, and 69% reported one PADL impairment. Increasing severity of functional impairment was associated with worse health status and more adverse prison experiences. For example, fall rates ranged from 33% in women without impairment to 57% with PADL impairment to 63% with ADL dependence (P=.02). Several prison environmental stressors were identified that likely exacerbate functional impairment. For example, 29% of geriatric women were assigned to a top bunk. Geriatric female prisoners report high rates of functional impairment. ADL and PADL impairment were associated with worse health status and adverse prison experiences. Therefore, the evaluation of functional impairment in geriatric female prisoners needs to consider the unique demands of the prison environment. C1 Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Legal Serv Prisoners Childrens, San Francisco, CA USA. RP Williams, BA (reprint author), 4150 Clement St,Box 181-G, San Francisco, CA 94121 USA. EM brie.williams@ucsf.edu FU NIA NIH HHS [T32-AG00212] NR 27 TC 25 Z9 25 U1 2 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 BP 702 EP 707 DI 10.1111/j.1532-5415.2006.00662.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 029SQ UT WOS:000236585100022 PM 16686886 ER PT J AU Berlowitz, D Hickey, E Czarnowski, E Saliba, D AF Berlowitz, D Hickey, E Czarnowski, E Saliba, D TI Can administrative data identify active diagnoses for the minimum data set? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Bedford VA Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, VA USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA 02215 USA. VA Greater Los Angeles Hlth Care Syst, Ctr Study Healthcare Provider Behav, 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S91 EP S91 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300264 ER PT J AU Fish, D Roberge, B Cury, A Chuang, S AF Fish, D Roberge, B Cury, A Chuang, S TI A pilot study of the prevalence and comorbidities of depressive symptoms in elders with heart failure SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Univ New England, Coll Osteopath Med, Biddeford, ME USA. Massachusetts Gen Hosp, Dept Nursing, Boston, MA 02114 USA. Massachusetts Gen Hosp, Geriatr Med Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S57 EP S57 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300164 ER PT J AU Ganz, DA Wenger, NS Roth, CP Kamberg, CJ Chang, JT MacLean, CH Young, RT Solomon, DH Higashi, T Min, L Reuben, DB Shekelle, PG AF Ganz, DA Wenger, NS Roth, CP Kamberg, CJ Chang, JT MacLean, CH Young, RT Solomon, DH Higashi, T Min, L Reuben, DB Shekelle, PG TI The effect of the ACOVE-2 quality improvement initiative on the quality of other aspects of health care: The law of unintended consequences? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RAND Hlth, Santa Monica, CA USA. Kyoto Univ, Kyoto, Japan. 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S42 EP S42 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300119 ER PT J AU O'Neill, SM Lorenz, KA Ettner, SL AF O'Neill, SM Lorenz, KA Ettner, SL TI Are rural hospices financially disadvantaged? Evidence from California. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S181 EP S181 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300529 ER PT J AU Raducha-Grace, L Kwoh, C AF Raducha-Grace, L Kwoh, C TI The knee pain map: Pain localization in knee osteoarthritis. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S103 EP S103 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300299 ER PT J AU Ruzicka, SA Sanchez-Reilly, SE AF Ruzicka, SA Sanchez-Reilly, SE TI Exploring the role of the spiritual dimension in chronic pain assessment among older adults. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Univ Texas, Hlth Sci Ctr, Dept Geriatr Med, Sch Nursing,Med Sch, San Antonio, TX USA. S Texas Vet Hlth Care Syst, GRECC, 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S32 EP S32 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300090 ER PT J AU Shaw, A Boal, J Penrod, J Hochman, T Ornstein, K DeCherrie, L AF Shaw, A Boal, J Penrod, J Hochman, T Ornstein, K DeCherrie, L TI Risk factors for hospitalization in the first year of enrollment in 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 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Mt Sinai Sch Med, Sch Med, New York, NY USA. Mt Sinai Sch Med, Brookdale Dept Geriatr, New York, NY USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. Bronx Vet Adm Med Ctr, GRECC, Bronx, NY 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S186 EP S186 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300543 ER PT J AU Sims, RV Ahmed, A Baker-Sawyer, P Allman, RM AF Sims, RV Ahmed, A Baker-Sawyer, P Allman, RM TI Diabetes predicts driving cessation in community dwelling older drivers: A propensity score analysis. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Birmingham VAMC, Birmingham, AL USA. Univ Alabama, Birmingham, AL 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S84 EP S84 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300244 ER PT J AU Stone, C Sanchez-Reilly, SE Gore, T AF Stone, C Sanchez-Reilly, SE Gore, T TI Cognitive assessment at the end of life: Is it being done? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, GRECC, 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S32 EP S32 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300091 ER PT J AU Wielert, CA Jaffe, EJ AF Wielert, CA Jaffe, EJ TI Integration of chaplain residents into a palliative care interdisciplinary team. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Univ Pittsburgh, Pittsburgh, PA 15260 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S98 EP S98 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300284 ER PT J AU Xie, Z Dong, Y Maeda, U Alfille, P Culley, DJ Crosby, G Tanzi, RE AF Xie, Z Dong, Y Maeda, U Alfille, P Culley, DJ Crosby, G Tanzi, RE TI Anesthetic isoflurane induces apoptosis and increases Abeta levels in H4 human neuroglioma cells overexpressing APP. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Massachusetts Gen Hosp, Genet & Aging Res Unit, MassGen Inst Neurogenerat Dis, Dept Neurol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S7 EP S7 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300019 ER PT J AU Whelan, JS Dvorkin, L AF Whelan, JS Dvorkin, L TI Plants from many healing landscapes: gathering information and teaching clinicians about the cultural use of medicinal herbs SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID ALTERNATIVE MEDICINE; COMPLEMENTARY; CARE C1 Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. Massachusetts Coll Pharm & Hlth Sci, Boston, MA 02115 USA. RP Whelan, JS (reprint author), Massachusetts Gen Hosp, Treadwell Lib, 55 Fruit St, Boston, MA 02114 USA. EM jcwhelan@partners.org; Lana.dvorkin@bos.mcphs.edu NR 18 TC 2 Z9 2 U1 1 U2 3 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD APR PY 2006 VL 94 IS 2 BP 223 EP 226 PG 4 WC Information Science & Library Science SC Information Science & Library Science GA 058BS UT WOS:000238639800016 PM 16636716 ER PT J AU Ahmed, S Antman, EM Murphy, SA Giugliano, RP Cannon, CP White, H Morrow, DA Braunwald, E AF Ahmed, S Antman, EM Murphy, SA Giugliano, RP Cannon, CP White, H Morrow, DA Braunwald, E TI Poor outcomes after fibrinolytic therapy for ST-segment elevation myocardial infarction: Impact of age (A meta-analysis of a decade of trials) SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE elderly; fibrinolysis; myocardial infarction; meta-analysis ID TISSUE-PLASMINOGEN-ACTIVATOR; INTRAVENOUS THROMBOLYTIC THERAPY; PRIMARY CORONARY ANGIOPLASTY; IN-HOSPITAL MORTALITY; RANDOMIZED-TRIAL; ELDERLY-PATIENTS; INTRACRANIAL HEMORRHAGE; UNFRACTIONATED HEPARIN; REPERFUSION THERAPY; OLDER PATIENTS AB Background: Fibrinolysis for ST-segment elevation myocardial infarction (STEMI) reduces mortality, but its relative efficacy and risks are age-dependent. We aimed to quantify the outcomes of fibrinolysis and adjunctive antithrombin therapy for STEMI stratified by age. Methods: We performed a meta-analysis of 11 published ( 1992 - 2001) randomized clinical trials of fibrinolysis in STEMI ( sample size >= 3000, no age limit, no placebo-controlled arms) identified by MEDLINE through June 2005. Event rates and odds ratios ( OR) in elderly vs. younger patients were calculated for mortality, intracranial hemorrhage (ICH) and total stroke (CVA). Elderly patients were defined as >= 75 years ( GUSTO I, TIMI 9B, GUSTO III, COBALT, ASSENT-2, InTIME-II TIMI-17, ASSENT-3, GUSTO V, and HERO-2), except when defined as > 65 or >= 70 years by the study ( INJECT and ISIS-3). Results: Elderly ( n = 24 531) vs. younger ( n = 123 568) patients had increased rates of mortality (19.7% vs. 5.5%), ICH (1.4% vs. 0.5%) andCVA(3.5 vs. 1.2%) by 30 - 35 days; the excess risk for these events was substantial ( OR mortality 4.37, 95% CI 4.16 - 4.58; ICH 2.83, 2.47 - 3.24; CVA 2.92, 2.62 - 3.25; p< 0.001 for all). Conclusions: Despite established mortality reductions with fibrinolysis for STEMI, elderly compared with younger patients, still have a three to four fold increased risk of mortality and adverse events when treated with fibrinolysis and antithrombin therapy in the modern era. These robust estimates of the anticipated rates for mortality, ICH, and CVA can be used as benchmarks to monitor the efficacy and safety of therapies in ongoing and newly completed clinical trials. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand. RP Antman, EM (reprint author), 350 Longwood Ave,1st Floor, Boston, MA 02215 USA. EM eantman@rics.bwh.harvard.edu RI bashzar, salman/R-5748-2016 NR 43 TC 18 Z9 20 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD APR PY 2006 VL 21 IS 2 BP 119 EP 129 DI 10.1007/s11239-006-5485-9 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 034UA UT WOS:000236954900001 PM 16622607 ER PT J AU Chen, HZ Alam, HB Querol, RILC Rhee, P Li, YQ Koustova, E AF Chen, HZ Alam, HB Querol, RILC Rhee, P Li, YQ Koustova, E TI Identification of expression patterns associated with hemorrhage and resuscitation: Integrated approach to data analysis SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 64th Annual Meeting of the American-Association-for-the-Surgery-of-Trauma CY SEP 22, 2005 CL Atlanta, GA SP Amer Assoc Surg Trauma DE genes; hemorrhage; shock; resuscitation; Ringer's solutions; ketones; pyruvate; lactate; hetastarch; hypertonic saline; lung; liver; spleen; cDNA; cellular injury; functional genomics ID GENE-EXPRESSION; MICROARRAY DATA; RAL GTPASES; SHOCK; APOPTOSIS; BIOLOGY; DNA AB Background: Although transcriptional profiling is a well-established technique, its application to systematic studying of various biological phenomena is still limited because of problems with highvolume data analysis and interpretation. This research project's objective was to create a comprehensive summary of changes in gene expression after hemorrhagic shock (HS), reliant and impartial of multiple variables, such as resuscitation treatments, organ analyzed, and time after impact. Methods: Rat model of severe (40% total blood loss) HS was employed. Hemorrhagic shock was treated with 6 different resuscitation strategies: (1) racemic lactated Ringer's (DL-LR); (2) L-lactated Ringer's (L-LR); (3) ketone Ringer's (KR); (4) pyruvate Ringer's (PR); (5) 6% hetastarch (Hex); (6) 7.5% hypertonic saline (HTS). Nonresuscitated and nonhemorrhaged rats served as controls. Ketone and pyruvate Ringer solutions were identical to the lactated Ringer's solution except for equimolar substitution of lactate with beta 3-hydroxybutyrate and sodium pyruvate, respectively. Total RNA from liver, lung, and spleen was isolated immediately (0 hour) and 24 hour postresuscitation. Each organ, time point and treatment was profiled using individual cDNA array (1,200 genes), to produce 183 separate data riles. Methods of analysis included one-way and unbalanced factorial ANOVA, Sokal-Michener average linkage clustering and contextual mapping. Results. Unresuscitated HS produced the highest number (56) of upregulated expressions in spleen and lungs. HEX and HTS affected mostly pulmonary genes (22 and 9). Fourteen genes changed in response to combination of all three factors: treatment, organ, and time. Eighteen genes were identified as treatment-specific. Fifteen genes adjusted expression 24 hour post-treatment. The largest number of genes with altered expression (168) responded differently in all three organs. In this study 15 gene clusters were pinpointed. Contextual mapping identified novel and confirmed known pathways contributing to hemorrhage/resuscitation. Conclusions. We have reliably identified genes and pathways that are affected by HS and are responsive to resuscitation. Gene expression in various organs is affected differentially by HS, which can be further modulated by the choice of resuscitation strategy. C1 Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD USA. RP Alam, HB (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org NR 26 TC 19 Z9 20 U1 1 U2 2 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 2006 VL 60 IS 4 BP 701 EP 723 DI 10.1097/01.ta.0000203699.91475.f6 PG 23 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 033RY UT WOS:000236868100003 PM 16612289 ER PT J AU Inaba, K Munera, F McKenney, M Schulman, C de Moya, M Rivas, L Pearce, A Cohn, S AF Inaba, K Munera, F McKenney, M Schulman, C de Moya, M Rivas, L Pearce, A Cohn, S TI Visceral torso computed tomography for clearance of the thoracolumbar spine in trauma: A review of the literature SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Review DE computed tomography; X-ray evaluations; thoracic vertebrae; lumbar vertebrae; retrospective studies ID LUMBAR FRACTURES; BLUNT TRAUMA; CT; DIAGNOSIS; RADIOLOGY; INJURIES AB Background. Accurate screening of the thoracolumbar spine (TLS) remains problematic in the care of trauma patients. The current standard of care for TLS screening is not clearly defined. In trauma patients undergoing computed tomography (CT) of the chest and or abdomen, compelling supportive evidence for reformatting and reusing this CT data to clear the thoracolumbar spine has accumulated over the last 3 years. The objective of this review was to identify and review all published studies comparing reformatted CT to traditional plain radiography for TLS clearance. Methods. A Medline search for all English language articles published on this subject since 1980 identified seven studies. Each was classified according to the levels of evidence classification of the Agency for Health Care Policy and Research. The methodology of each study was reviewed for the CT protocol, utilization of radiologist blinding and whether historical dictated reports or de novo image readings were used for comparison. The sensitivity and specificity of each study and the gold standard utilized in its calculation was noted. Where available, detailed information regarding the missed injuries and their clinical relevance was abstracted for each study. Results: All evaluated studies demonstrated superior sensitivity and inter-observer variability for reformatted CT compared with plain radiographic screening. CT was also more accurate in localizing, classifying, and delineating the age, bony intrusion, and soft-tissue damage associated with the fracture. For studies with time-motion components, a protocol utilizing CT clearance was not only more accurate but faster and more economical. Screening with reformatted visceral CT data required no additional scan time or radiation exposure. Conclusion: The evidence to date demonstrates the superior sensitivity of reformatted visceral CT for detecting thoracolumbar spine injury. With no further patient movement, radiation exposure, cost, or time, trauma patients undergoing visceral CT can have their thoracolumbar spine promptly evaluated. Further prospective evaluation of the CT protocols to optimize visualization of both the viscera and the bone is warranted. C1 Univ So Calif, Los Angeles Cty Med Ctr, Div Trauma & Crit Care, Los Angeles, CA 90033 USA. Jackson Mem Hosp, Div Trauma & Crit Care, Ryder Trauma Ctr, Miami, FL 33136 USA. Jackson Mem Hosp, Div Emergency Radiol, Ryder Trauma Ctr, Miami, FL 33136 USA. Massachusetts Gen Hosp, Div Trauma Emergeny Surg Surg Crit Care, Boston, MA 02114 USA. Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78284 USA. RP Inaba, K (reprint author), Univ So Calif, Los Angeles Cty Med Ctr, Div Trauma & Surg Crit Care, 1200 N State St,Room 10-750, Los Angeles, CA 90033 USA. EM kinaba@surgery.usc.edu NR 19 TC 20 Z9 20 U1 0 U2 0 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 2006 VL 60 IS 4 BP 915 EP 920 DI 10.1097/01.ta.0000196926.79065.6e PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 033RY UT WOS:000236868100049 PM 16612322 ER PT J AU Sonis, J Triffleman, E King, DW King, LA AF Sonis, J Triffleman, E King, DW King, LA TI Special section: Innovations in trauma research methods SO JOURNAL OF TRAUMATIC STRESS LA English DT Editorial Material ID TERRORIST ATTACKS; SEPTEMBER-11 C1 Univ N Carolina, Sch Med, Dept Social Med, Chapel Hill, NC 27599 USA. Boston Univ, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Sonis, J (reprint author), Univ N Carolina, Sch Med, Dept Social Med, Wing D,CB 7240, Chapel Hill, NC 27599 USA. EM jsonis@med.unc.edu FU NIMH NIH HHS [5 R13 MH068798-04] NR 11 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 2006 VL 19 IS 2 BP 169 EP 171 DI 10.1002/jts.20111 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 038KB UT WOS:000237217300001 PM 16612818 ER PT J AU King, DW King, LA McArdle, JJ Grimm, K Jones, RT Ollendick, TH AF King, DW King, LA McArdle, JJ Grimm, K Jones, RT Ollendick, TH TI Characterizing time in longitudinal trauma research SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 1st Annual Conference on Innovations in Trauma Research Methods (CITRM) CY NOV, 2004 CL New Orleans, LA ID POSTTRAUMATIC-STRESS-DISORDER; GAIN SCORES OBSOLETE; GULF-WAR VETERANS; COMPONENTS; RECOVERY; SYMPTOMS; VALIDITY; ISSUES; MODELS AB Despite the proliferation of longitudinal trauma research, careful attention to timing of assessments is often lacking. Patterns in timing of assessments, alternative time structures, and the treatment of time as an outcome are discussed and illustrated using trauma data. C1 Boston Univ, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. Univ So Calif, Los Angeles, CA 90089 USA. Univ Virginia, Charlottesville, VA 22903 USA. Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA. RP King, DW (reprint author), Natl Ctr Posttraumat Stress Disorder, 116B-5,150 S Huntington Ave, Boston, MA 02130 USA. EM danking@bu.edu FU NIMH NIH HHS [R01 MH068626-02] NR 33 TC 19 Z9 19 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 2006 VL 19 IS 2 BP 205 EP 215 DI 10.1002/jts.20112 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 038KB UT WOS:000237217300005 PM 16612827 ER PT J AU Freedland, SJ Kane, CJ Amling, CL Aronson, WJ Presti, JC Terris, MK AF Freedland, SJ Kane, CJ Amling, CL Aronson, WJ Presti, JC Terris, MK CA SEARCH Database Study Grp TI Delay of radical prostatectomy and risk of biochemical progression in men with low risk prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prostatectomy; biopsy; prostate-specific antigen ID RADIATION-THERAPY; SEARCH DATABASE; RECURRENCE; PSA; PREDICTOR; MORTALITY; ANTIGEN; BIOPSY; IMPACT AB Purpose: Men newly diagnosed with prostate cancer are faced with multiple treatment options. Understanding these options and their associated side effects, and making a decision often requires time, resulting in a delay before receiving treatment. This is particularly pertinent in men with low risk disease who may be considered candidates for watchful waiting and, thus, may not experience strong pressure to undergo treatment promptly. Whether delays and especially prolonged delays, eg greater than 180 days, before RP negatively impact the disease outcome is unclear. Materials and Methods: We examined the association between time from diagnosis to surgery, and pathological features of the RP specimen and risk of biochemical progression in 895 men with low risk prostate cancer (prostate specific antigen less than 10 ng/ml and biopsy Gleason sum 6 or less) treated with RP between 1988 and 2004 in the Shared-Equal Access Regional Cancer Hospital Database using logistic regression and Cox proportional hazards, respectively. Results: Time from biopsy to surgery was not significantly related to high grade disease in the RP specimen, positive surgical margins or extraprostatic extension (all p-trend > 0.05). After adjustment for multiple clinical covariates a longer time from biopsy to surgery was significantly associated with an increased risk of biochemical progression (p-trend = 0.002). However, this increased risk of progression was only apparent in men with delays greater than 180 days (median 263, vs 90 or fewer days RR 2.73, 95% CI 1.51 to 4.94). Conclusions: Our data suggest that patients with low risk prostate cancer can be reassured that immediate treatment is not necessary. Whether long delays (greater than 180 days) decrease the likelihood of curability in some patients requires further study. C1 Duke Univ, Med Ctr, Dept Surg & Pathol, Div Urol Surg, Durham, NC 27719 USA. Johns Hopkins Sch Med, Dept Urol, Baltimore, MD USA. Univ Calif San Francisco, Sch Med, Vet Adm Med Ctr, Urol Sect,Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. San Diego Naval Hosp, Dept Urol, San Diego, CA USA. Univ Calif Los Angeles, Sch Med, Vet Adm Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90024 USA. Vet Adm Med Ctr, Dept Surg, Urol Sect, Palo Alto, CA 94304 USA. Univ Alabama, Dept Urol, Birmingham, AL USA. Med Coll Georgia, Vet Adm Med Ctr, Dept Surg, Augusta, GA 30912 USA. Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. RP Freedland, SJ (reprint author), Duke Univ, Med Ctr, Dept Surg & Pathol, Div Urol Surg, Box 3850, Durham, NC 27719 USA. EM steve.freedland@duke.edu FU NCI NIH HHS [P50 CA92131-01A1, R01CA100938] NR 15 TC 45 Z9 47 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2006 VL 175 IS 4 BP 1298 EP 1302 DI 10.1016/S0022-5437(05)00646-4 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 022EX UT WOS:000236038900030 PM 16515984 ER PT J AU San Francisco, IF Regan, MM DeWolf, WC Olumi, AF AF San Francisco, IF Regan, MM DeWolf, WC Olumi, AF TI Low age adjusted free testosterone levels correlate with poorly differentiated prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; neoplasm recurrence; local; hypogonadism; testosterone ID LOW SERUM TESTOSTERONE; PLASMA-HORMONE LEVELS; RADICAL PROSTATECTOMY; NORMAL MEN; ANDROGEN; RESECTION; IMPACT AB Purpose: We determined the relationship between age adjusted free T, and stage, grade and the biochemical-free survival rate in patients with surgically treated prostate cancer. Materials and Methods: A retrospective cohort study was done between 1995 and 2001 in 333 patients treated for clinically localized prostate cancer with radical retropubic prostatectomy by a single surgeon at our institution. The study cohort consisted of 279 patients (84%) who had free T levels available. Free T was assessed by single cutoff value of 1.5 ng/dl or less, as suggested by the assay manufacturer, or by age adjusted free T. The relationship of low free T as a single cutoff value and age adjusted reference ranges with clinical and pathological measures of disease progression were assessed using the Fisher exact and Wilcoxon rank sum tests with the outcome assessed by the log rank test. Results: Using the assay manufacturer suggested single cutoff value of 1.5 ng/dl or less to define low free T 57% of patients with prostate cancer in the cohort were categorized as hypogonadal. However, using age adjusted free T reference ranges only 2.5% of patients with prostate cancer were categorized as hypogonadal, which is more logical and representative of clinically significant hypogonadism in the general population. Poorly differentiated prostate cancer was associated with low free T when measured by a single cutoff value of 1.5 ng/dl or less, or by age adjusted free T (p = 0.017 and 0.04, respectively). Conclusions: Low age adjusted free T as well as single cutoff free T correlates with poorly differentiated prostate cancer in surgically treated patients. C1 Beth Israel Deaconess Med Ctr, Div Urol Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Olumi, AF (reprint author), Beth Israel Deaconess Med Ctr, Div Urol Surg, Boston, MA 02215 USA. EM aolumi@bidmc.harvard.edu NR 19 TC 26 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2006 VL 175 IS 4 BP 1341 EP 1345 DI 10.1016/S0022(05)00680-4 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 022EX UT WOS:000236038900041 PM 16515994 ER PT J AU Shrikhande, G Khaodhiar, L Scali, S Lima, C Hubbard, M Dudley, K Ganda, O Ferran, C Veves, A AF Shrikhande, G Khaodhiar, L Scali, S Lima, C Hubbard, M Dudley, K Ganda, O Ferran, C Veves, A TI Valsartan improves resting skin blood flow in type 2 diabetic patients and reduces poly(adenosine diphosphate-ribose) polymerase activation SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID ENDOTHELIAL FUNCTION; POLY(ADP-RIBOSE) POLYMERASE; NITRIC-OXIDE; MEDIATED VASODILATION; HYPERTENSIVE PATIENTS; ACE-INHIBITION; RECEPTOR; DYSFUNCTION; ATHEROSCLEROSIS; AMLODIPINE AB Objective: To examine the effect of a 12-week daily treatment with 160 mg of valsartan, an angiotensin II receptor blocker, on the microcirculation and macrocirculation of type 2 diabetic patients (T2DM) and healthy subjects. Methods. This was a prospective, randomized, double-blind, placebo-controlled crossover study. Thirteen T2DM with no severe complications and 13 healthy subjects completed the trial. Results. Treatment with valsartan in T2DM improved the resting forearm skin blood flow and increased the resting brachial artery diameter but had no effects on arterial blood pressure, large vessel vascular reactivity, or carotid intima-media thickness. Resting skin blood flow increased by 60% (2%-90%; median and 25th-75th percentiles) during valsartan treatment and by only 2% (-22% to 27%) during placebo treatment (P <.05). No changes were observed in the nondiabetic subjects. Immunostaining studies of forearm skin biopsy samples from T2DM and healthy subjects showed that valsartan reduced poly(adenosine diphosphate-ribose) polymerase (PARP) activity in 50% (6/12) of the subjects. PARP activity remained unchanged in placebo-treated subjects (P <.02). In addition, valsartan treatment increased CD31 staining in 33% (4/12) of the subjects, whereas no change was noted in sequential skin biopsy samples of placebo-treated subjects (P =.057). Valsartan had no effect on the biochemical markers of endothelial cell activation and other cytokines, including CAMs, interleukin 6, tumor necrosis factor alpha, C-reactive protein, adiponectin, and plasma activator inhibitor 1. Conclusions. Valsartan increases the resting skin blood flow in T2DM, likely through reduction of PARP activity. C1 Harvard Univ, Microcirculat Lab, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Immunobiol Res Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Vasc Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Veves, A (reprint author), Harvard Univ, Microcirculat Lab, Sch Med, Beth Israel Deaconess Med Ctr, Palmer 317,W Campus,1 Deaconess Rd, Boston, MA 02215 USA. EM aveves@caregroup.harvard.edu FU NCRR NIH HHS [RR 01032] NR 32 TC 12 Z9 13 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD APR PY 2006 VL 43 IS 4 BP 760 EP 770 DI 10.1016/j.jvs.2005.12.059 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 031OO UT WOS:000236714100021 PM 16616233 ER PT J AU Brau, N Bini, EJ Currie, S Shen, H Schmidt, WN King, PD Ho, SB Cheung, RC Hu, KQ Anand, BS Simon, FR Aytaman, A Johnson, DP Awad, JA Ahmad, J Mendenhall, CL Pedrosa, MC Moseley, RH Hagedorn, CH Waters, B Chang, KM Morgan, TR Rossi, SJ Jeffers, LJ Wright, TL AF Brau, N Bini, EJ Currie, S Shen, H Schmidt, WN King, PD Ho, SB Cheung, RC Hu, KQ Anand, BS Simon, FR Aytaman, A Johnson, DP Awad, JA Ahmad, J Mendenhall, CL Pedrosa, MC Moseley, RH Hagedorn, CH Waters, B Chang, KM Morgan, TR Rossi, SJ Jeffers, LJ Wright, TL CA VA-HCV-001 Study Grp TI Black patients with chronic hepatitis C have a lower sustained viral response rate than non-Blacks with genotype 1, but the same with genotypes 2/3, and this is not explained by more frequent dose reductions of interferon and ribavirin SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE community-based practice; dose reduction; hepatitis C; racial differences; therapy ID AFRICAN-AMERICANS; PLUS RIBAVIRIN; PEGINTERFERON ALPHA-2A; INITIAL TREATMENT; RANDOMIZED-TRIAL; VIRUS-INFECTION; US VETERANS; THERAPY; COMBINATION AB In previous hepatitis C virus (HCV) treatment studies, Black patients not only had a lower sustained viral response (SVR) rate to interferon and ribavirin (RBV) than non-Black patients but also a higher frequency of HCV genotype 1 (GT-1) infection. The aim of this community-based study was to determine whether Black patients have a lower SVR rate independent of genotype. We prospectively enrolled 785 patients (24.8% Black, 71.5% White, 3.7% others) who received interferon alpha-2b 3 MU three times weekly + RBV 1000-1200 mg/day for 24 weeks (GT-2/3) or 48 weeks (GT-1). Black patients were more commonly infected with GT-1 (86.8%vs 64.8%, P < 0.001) and less frequently had an SVR compared with non-Black patients (8.4%vs 21.6%, P < 0.001). Within GT-1, Black patients had a lower SVR rate than non-Black patients (6.1%vs 14.1%, P = 0.004) but not within GT-2/3 (50.0%vs 36.5%, P = 0.47). Black patients had lower baseline haemoglobin levels (14.8 vs 15.3 g/dL, P < 0.001) and neutrophil counts (2900 vs 4100/mm(3), P < 0.001) and required more frequent dose reductions of RBV (29.8%vs 18.5%, P < 0.001) and interferon (4.7%vs 1.6%, P = 0.012). However, dose reductions were not associated with lower SVR rates while early treatment discontinuations were (2.9%vs 25.7%, P < 0.001). Independent predictors of SVR were GT-1 [odds ratio (OR) 0.33; 95% confidence interval (CI) 0.20-0.55; P < 0.001], Black race (OR 0.45; 95% CI 0.22-0.93; P = 0.030), and advanced fibrosis, stages 3 + 4 (OR 0.53; 95% CI 0.31-0.92; P = 0.023). In conclusion, Black patients infected with HCV GT-1 (but not GT-2/3) have a lower SVR rate than non-Black patients. This is not explained by their lower baseline haemoglobin levels and neutrophil counts that lead to higher rates of ribavirin and interferon dose reductions. C1 Bronx Vet Adm Med Ctr, Infect Dis Sect 111F, Bronx, NY 10468 USA. Vet Affairs Med Ctr, New York, NY USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Vet Affairs Med Ctr, Iowa City, IA 52242 USA. Vet Affairs Med Ctr, Columbia, MO USA. Vet Affairs Med Ctr, Minneapolis, MN 55417 USA. Vet Affairs Med Ctr, Palo Alto, CA 94304 USA. Vet Affairs Med Ctr, Loma Linda, CA USA. Vet Affairs Med Ctr, Houston, TX 77030 USA. Vet Affairs Med Ctr, Denver, CO USA. Vet Affairs Med Ctr, Brooklyn, NY USA. Vet Affairs Med Ctr, Bay Pines, FL USA. Vet Affairs Med Ctr, Nashville, TN 37212 USA. Vet Affairs Med Ctr, Pittsburgh, PA USA. Vet Affairs Med Ctr, Cincinnati, OH 45267 USA. Vet Affairs Med Ctr, Boston, MA USA. Vet Affairs Med Ctr, Ann Arbor, MI USA. Vet Affairs Med Ctr, Atlanta, GA 30033 USA. Vet Affairs Med Ctr, Memphis, TN USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Vet Affairs Med Ctr, Long Beach, CA USA. Vet Affairs Med Ctr, Miami, FL 33125 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Brau, N (reprint author), Bronx Vet Adm Med Ctr, Infect Dis Sect 111F, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM norbert.brau@med.va.gov NR 20 TC 30 Z9 30 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD APR PY 2006 VL 13 IS 4 BP 242 EP 249 DI 10.1111/j.1365-2893.2005.00682.x PG 8 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 022OJ UT WOS:000236065100005 PM 16611190 ER PT J AU Martinez-Picado, J Prado, JG Fry, EE Pfafferott, K Leslie, A Chetty, S Thobakgale, C Honeyborne, I Crawford, H Matthews, P Pillay, T Rousseau, C Mullins, JI Brander, C Walker, BD Stuart, DI Kiepiela, P Goulder, P AF Martinez-Picado, J Prado, JG Fry, EE Pfafferott, K Leslie, A Chetty, S Thobakgale, C Honeyborne, I Crawford, H Matthews, P Pillay, T Rousseau, C Mullins, JI Brander, C Walker, BD Stuart, DI Kiepiela, P Goulder, P TI Fitness cost of escape mutations in p24 Gag in association with control of human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID T-LYMPHOCYTE ESCAPE; VIRAL ESCAPE; HIV-1 GAG; CRYSTAL-STRUCTURE; CAPSID PROTEIN; IN-VIVO; INFECTION; REVERSION; HLA; SUBSTITUTIONS AB Mutational escape by human immunodeficiency virus (HIV) from cytotoxic T-lymphocyte (CTL) recognition is a major challenge for vaccine design. However, recent studies suggest that CTL escape may carry a sufficient cost to viral replicative capacity to facilitate subsequent immune control of a now attenuated virus. In order to examine how limitations can be imposed on viral escape, the epitope TSTLQEQIGW (TW10 [Gag residues 240 to 249]), presented by two HLA alleles associated with effective control of HIV, HLA-B*57 and -B*5801, was investigated. The in vitro experiments described here demonstrate that the dominant TW10 escape mutation, T242N, reduces viral replicative capacity. Structural analysis reveals that T242 plays a critical role in defining the start point and in stabilizing helix 6 within p24 Gag, ensuring that escape occurs at a significant cost. A very similar role is played by Thr-180, which is also an escape residue, but within a second p24 Gag epitope associated with immune control. Analysis of HIV type I gag in 206 B*57/5801-positive subjects reveals three principle alternative TW10-associated variants, and each is strongly linked to concomitant additional variants within p24 Gag, suggesting that functional constraints operate against their occurrence alone. The extreme conservation of p24 Gag and the predictable nature of escape variation resulting from these tight functional constraints indicate that p24 Gag may be a critical immunogen in vaccine design and suggest novel vaccination strategies to limit viral escape options from such epitopes. C1 Univ Hosp Germans Trias Pujol, IrsiCaixa Fdn, Barcelona, Spain. Univ Oxford, Henry Wellcome Bldg Gen Med, Div Struct Biol, Oxford OX3 7BN, England. Peter Medawar Bldg Pathogen Res, Dept Paediat, Nuffield Dept Med, Oxford OX1 3SY, England. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. Univ Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4001 Durban, South Africa. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. RP Goulder, P (reprint author), Peter Medawar Bldg,S Pk Rd, Oxford OX1 3SY, England. EM philip.goulder@ndm.ox.ac.uk RI Martinez-Picado, Javier/G-5507-2012; OI Martinez-Picado, Javier/0000-0002-4916-2129; Brander, Christian/0000-0002-0548-5778; Matthews, Philippa/0000-0002-4036-4269 FU Medical Research Council [G0500365, G0501777]; NIAID NIH HHS [P30 AI027757]; PHS HHS [A146995-01A1, N01-A1-15422]; Wellcome Trust NR 34 TC 321 Z9 327 U1 4 U2 14 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 2006 VL 80 IS 7 BP 3617 EP 3623 DI 10.1128/JVI.80.7.3617-3623.2006 PG 7 WC Virology SC Virology GA 025ZB UT WOS:000236305200049 PM 16537629 ER PT J AU Gray, L Churchill, MJ Keane, N Sterjovski, J Ellett, AM Purcell, DFJ Poumbourios, P Kol, C Wang, B Saksena, NK Wesselingh, SL Price, P French, M Gabuzda, D Gorry, PR AF Gray, L Churchill, MJ Keane, N Sterjovski, J Ellett, AM Purcell, DFJ Poumbourios, P Kol, C Wang, B Saksena, NK Wesselingh, SL Price, P French, M Gabuzda, D Gorry, PR TI Genetic and functional analysis of R5X4 human immunodeficiency virus type 1 envelope glycoproteins derived from two individuals homozygous for the CCR5 Delta 32 allele SO JOURNAL OF VIROLOGY LA English DT Article ID CHEMOKINE RECEPTOR GENE; FUSION INHIBITOR T-20; HIV-1 INFECTION; CELL-LINE; DISEASE PROGRESSION; PRIMARY MACROPHAGES; DELETION ALLELE; SMALL-MOLECULE; DIVERSE HUMAN; TROPIC HIV-1 AB We characterized human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) isolated from two HIV-1-infected CCR5 Delta 32 homozygotes. Envs from both subjects used CCR5 and CXCR4 for entry into transfected cells. Most R5X4 Envs were lymphocyte-tropic and used CXCR4 exclusively for entry into peripheral blood mononuclear cells (PBMC), but a subset was dually lymphocyte- and macrophage-tropic and used either CCR5 or CXCR4 for entry into PBMC and monocyte-derived macrophages. The persistence of CCR5-using HIV-1 in two CCR5 Delta 32 homozygotes suggests the conserved CCR5 binding domain of Env is highly stable and provides new mechanistic insights important for HIV-1 transmission and persistence. C1 Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic 3001, Australia. Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia. Royal Perth Hosp, Dept Clin Immunol & Biochem Genet, Perth, WA, Australia. Univ Western Australia, Sch Surg & Pathol, Perth, WA 6009, Australia. Monash Univ, Dept Med, Melbourne, Vic 3004, Australia. Westmead Millennium Inst, Westmead, NSW, Australia. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gorry, PR (reprint author), Macfarlane Burnet Inst Med Res & Publ Hlth, GPO Box 2284, Melbourne, Vic 3001, Australia. EM gorry@burnet.edu.au RI Purcell, Damian/G-5068-2011 FU NIAID NIH HHS [AI054207-01-A1, R21 AI054207]; NINDS NIH HHS [NS37277, R01 NS037277] NR 54 TC 41 Z9 41 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 2006 VL 80 IS 7 BP 3684 EP 3691 DI 10.1128/JVI.80.7.3684-3691.2006 PG 8 WC Virology SC Virology GA 025ZB UT WOS:000236305200060 PM 16537640 ER PT J AU Rivailler, P Kaur, A Johnson, RP Wang, F AF Rivailler, P Kaur, A Johnson, RP Wang, F TI Genomic sequence of rhesus cytomegalovirus 180.92: Insights into the coding potential of rhesus cytomegalovirus SO JOURNAL OF VIROLOGY LA English DT Article ID SIMIAN-IMMUNODEFICIENCY VIRUS; GENES; MACAQUES; STRAINS; PATHOGENESIS; INFECTION AB A pathogenic isolate of rhesus cytomegalovirus (rhCMV 180.92) was cloned, sequenced, and annotated. Comparisons with the published rhCMV 68.1 genome revealed 8 open reading frames (ORFs) in isolate 180.92 that are absent in 68.1, 10 ORFs in 68.1 that are absent in 180.92, and 34 additional ORFs that were not previously annotated. Most of the differences appear to be due to genetic rearrangements in both isolates from a region that is frequently altered in human CMV (hCMV) during in vitro passage. These results indicate that the rhCMV ORF repertoire is larger than previously recognized. Like hCMV, understanding of the complete coding capacity of rhCMV is complicated by genomic instability and may require comparisons with additional isolates in vitro and in vivo. C1 Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Immunol, New England Primate Res Ctr, Southborough, MA 01772 USA. Harvard Univ, Sch Med, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Wang, F (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. EM fwang@rics.bwh.harvard.edu FU NCI NIH HHS [CA68051, R01 CA068051]; NCRR NIH HHS [P51 RR000168, P51RR00168]; NIAID NIH HHS [AI43890, P30 AI042851, P30 AI42851, R01 AI043890] NR 19 TC 47 Z9 49 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 2006 VL 80 IS 8 BP 4179 EP 4182 DI 10.1128/JVI.80.8.4179-4182.2006 PG 4 WC Virology SC Virology GA 031DZ UT WOS:000236685600049 PM 16571834 ER PT J AU Chang, H Dittmer, DP Shin, YC Hong, Y Jung, JU AF Chang, H Dittmer, DP Shin, YC Hong, Y Jung, JU TI Role of notch signal transduction in Kaposi's sarcoma-associated herpesvirus gene expression (vol 79, pg 14371, 2005) SO JOURNAL OF VIROLOGY LA English DT Correction C1 Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA. Harvard Univ, Sch Med, New England Primate Res Ctr, Div Tumor Virol, Southborough, MA 01772 USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Chang, H (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA. NR 1 TC 0 Z9 0 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 2006 VL 80 IS 8 BP 4203 EP 4203 DI 10.1128/JVI.80.8.4203.2006 PG 1 WC Virology SC Virology GA 031DZ UT WOS:000236685600055 ER PT J AU Blackwell, T Yaffe, K Ancoli-Israel, S Scheider, JL Cauley, JA Hillier, TA Fink, HA Stone, KL AF Blackwell, T Yaffe, K Ancoli-Israel, S Scheider, JL Cauley, JA Hillier, TA Fink, HA Stone, KL CA Study Osteoporotic Fractures Grp TI Poor sleep is associated with impaired cognitive function in older women: The Study of Osteoporotic Fractures SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID JAPANESE-AMERICAN MEN; ALZHEIMERS-DISEASE; APNEA SYNDROME; BONE MASS; HEALTH; COMPLAINTS; DEMENTIA; INSOMNIA; PERFORMANCE; DYSFUNCTION AB Background. The association between objectively measured sleep and cognition among community-dwelling elderly persons remains understudied. This observational, cross-sectional analysis examined this association. Methods. Results are from 2932 women (mean age 83.5 years) in the Study of Osteoporotic Fractures between 2002 and 2004. Cognitive function was measured by Mini-Mental State Examination (MMSE) and Trail Making B Test (Trails B). Cognitive impairment was defined as MMSE < 26 or Trails B > 278 seconds. Sleep parameters measured objectively using actigraphy included total sleep time, sleep efficiency, sleep latency, wake after sleep onset (WASO), and total nap time. Results. There were 305 women (10.6%) with MMSE < 26 and 257 women (9.3%) with Trails B > 278 seconds. Compared with women with sleep efficiency >= 70%, those with < 70% had a higher risk of cognitive impairment (MMSE < 26 multivariate odds ratio [MOR] = 1.61; 95% confidence interval [CI], 1.20-2.16; Trails B > 278 MOR = 1.96; 95% CI, 1.43-2.67). Higher sleep latency was associated with higher risk of cognitive impairment (per half hour: MMSE < 26 MOR = 1.23; 95% CI, 1.13-1.33; Trails B > 278 MOR = 1.13; 95% CI, 1.04-1.24), as was higher WASO (per half hour: MMSE < 26 MOR = 1.15; 95% CI, 1.06-1.23: Trails B > 278 MOR = 1.24; 95% CI, 1.15-1.34). Women who napped >= 2 hours per day had a higher risk (MMSE < 26 MOR = 1.42; 95% CI, 1.05-1.93; Trails B > 278 MOR = 1.74; 95% CI, 1.26-2.40). There was no significant relationship for total sleep time. Conclusion. Objectively measured disturbed sleep was consistently related to poorer cognition. whereas total sleep time was not. This finding may suggest that it is disturbance of sleep rather than quantity that affects cognition. C1 SF Coordinating Ctr, San Francisco, CA 94107 USA. Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. VA Med Ctr, Geriatr Res Educ & Clin Ctr, Minneapolis, MN USA. VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. RP Blackwell, T (reprint author), SF Coordinating Ctr, 185 Berry St,Lobby 4,Suite 5700, San Francisco, CA 94107 USA. EM tblackwell@sfcc-cpmc.net RI Fink, Howard/F-3933-2012; Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [AG05394, AG05407, AG08415, R01 AG021918, R01 AG026720]; NIAMS NIH HHS [AR35582, AR35583, AR35584] NR 44 TC 149 Z9 150 U1 4 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 2006 VL 61 IS 4 BP 405 EP 410 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 035OI UT WOS:000237010500014 PM 16611709 ER PT J AU Aljarrah, K Sharp, GC Neicu, T Jiang, SB AF Aljarrah, K Sharp, GC Neicu, T Jiang, SB TI Determination of the initial beam parameters in Monte Carlo linac simulation SO MEDICAL PHYSICS LA English DT Article DE Monte Carlo; treatment planning; commissioning; linac simulation ID HIGH-ENERGY PHOTON; ELECTRON-BEAMS; DOSE DISTRIBUTIONS; RADIATION-THERAPY; OUTPUT FACTORS; ACCELERATORS; SPECTRA; BACKSCATTER; INCIDENT; FLUENCE AB For Monte Carlo linac simulations and patient dose calculations, it is important to accurately determine the phase space parameters of the initial electron beam incident on the target. These parameters, such as mean energy and radial intensity distribution, have traditionally been determined by matching the calculated dose distributions with the measured dose distributions through a trial and error process. This process is very time consuming and requires a lot of Monte Carlo simulation experience and computational resources. In this paper, we propose an easy, efficient, and accurate method for the determination of the initial beam parameters. We hypothesize that (1) for one type of linacs, the geometry and material of major components of the treatment head are the same; the only difference is the phase space parameters of the initial electron beam incident on the target, and (2) most linacs belong to a limited number of linac types. For each type of linacs, Monte Carlo treatment planning system (MC-TPS) vendors simulate the treatment head and calculate the three-dimensional (3D) dose distribution in water phantom for a grid of initial beam energies and radii. The simulation results (phase space files and dose distribution files) are then stored in a data library. When a MC-TPS user tries to model their linac which belongs to the same type, a standard set of measured dose data is submitted and compared with the calculated dose distributions to determine the optimal combination of initial beam energy and radius. We have applied this method to the 6 MV beam of a Varian 21EX linac. The linac was simulated using EGSNRC/BEAM code and the dose in water phantom was calculated using EGSNRC/DOSXYZ. We have also studied issues related to the proposed method. Several common cost functions were tested for comparing measured and calculated dose distributions, including chi(2) mean absolute error, dose difference at the penumbra edge point, slope of the dose difference of the lateral profile, and the newly proposed K-alpha factor (defined as the fraction of the voxels with absolute dose difference less than alpha%). It was found that the use of the slope of the lateral profile difference or the difference of the penumbra edge points may lead to inaccurate determination of the initial beam parameters. We also found that in general the cost function value is very sensitive to the simulation statistical uncertainty, and there is a tradeoff between uncertainty and specificity. Due to the existence of statistical uncertainty in simulated dose distributions, it is practically impossible to determine the best energy/radius combination; we have to accept a group of energy/radius combinations. We have also investigated the minimum required data set for accurate determination of the initial beam parameters. We found that the percent depth dose curves along or only a lateral profile at certain depth for a large field size is not sufficient and the minimum data set should include several lateral profiles at various depths as well as the central axis percent depth dose curve for a large field size. (c) 2006 American Association of Physicists in Medicine. C1 Univ Massachusetts, Dept Phys, Lowell, MA 01854 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jiang, SB (reprint author), Univ Massachusetts, Dept Phys, Lowell, MA 01854 USA. EM jiang.steve@mgh.harvard.edu NR 28 TC 14 Z9 16 U1 0 U2 6 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 2006 VL 33 IS 4 BP 850 EP 858 DI 10.1118/1.2168433 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 035YS UT WOS:000237038300006 PM 16696460 ER PT J AU Gong, X Glick, SJ Liu, B Vedula, AA Thacker, S AF Gong, X Glick, SJ Liu, B Vedula, AA Thacker, S TI A computer simulation study comparing lesion detection accuracy with digital mammography, breast tomosynthesis, and cone-beam CT breast imaging SO MEDICAL PHYSICS LA English DT Article DE mammography; tomosynthysis; breast imaging; cone-beam CT; flat-panel imager; ROC observer study ID FLAT-PANEL IMAGER; GEOMETRIC CALIBRATION; DISPLACED CENTER; TOMOGRAPHY; COEFFICIENTS; PERFORMANCE; ALGORITHM; RADIATION; ROTATION; SCATTER AB Although conventional mammography is currently the best modality to detect early breast cancer, it is limited in that the recorded image represents the superposition of a three-dimensional (3D) object onto a 2D plane. Recently, two promising approaches for 3D volumetric breast imaging have been proposed, breast tomosynthesis (BT) and CT breast imaging (CTBI). To investigate possible improvements in lesion detection accuracy with either breast tomosynthesis or CT breast imaging as compared to digital mammography (DM), a computer simulation study was conducted using simulated lesions embedded into a structured 3D breast model. The computer simulation realistically modeled x-ray transport through a breast model, as well as the signal and noise propagation through a CsI based flat-panel imager. Polyenergetic x-ray spectra of Mo/Mo 28 kVp for digital mammography, Mo/Rh 28 kVp for BT, and W/Ce 50 kVp for CTBI were modeled. For the CTBI simulation, the intensity of the x-ray spectra for each projection view was determined so as to provide a total average glandular dose of 4 mGy, which is approximately equivalent to that given in conventional two-view screening mammography. The same total dose was modeled for both the DM and BT simulations. Irregular lesions were simulated by using a stochastic growth algorithm providing lesions with an effective diameter of 5 mm. Breast tissue was simulated by generating an ensemble of backgrounds with a power law spectrum, with the composition of 50% fibroglandular and 50% adipose tissue. To evaluate lesion detection accuracy, a receiver operating characteristic (ROC) study was performed with five observers reading an ensemble of images for each case. The average area under the ROC curves (A) was 0.76 for DM, 0.93 for BT, and 0.94 for CTBI. Results indicated that for the same dose, a 5 mm lesion embedded in a structured breast phantom was detected by the two volumetric breast imaging systems, BT and CTBI, with statistically significant higher confidence than with planar digital mammography, while the difference in lesion detection between BT and CTBI was not statistically significant. (c) 2006 American Association of Physicists in Medicine. C1 Rush Univ, Med Ctr, Chicago, IL 60612 USA. Rush Univ, Med Ctr, Dept Radiat Oncol, Chicago, IL 60612 USA. Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gong, X (reprint author), Rush Univ, Med Ctr, 1653 W Congress Pkwy, Chicago, IL 60612 USA. EM xing_gong@rush.edu FU NCRR NIH HHS [RR016689]; NIBIB NIH HHS [EB02133] NR 56 TC 98 Z9 102 U1 0 U2 13 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 2006 VL 33 IS 4 BP 1041 EP 1052 DI 10.1118/1.2174127 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 035YS UT WOS:000237038300027 PM 16696481 ER PT J AU Bennett, GG Wolin, KY Puleo, E Emmons, KM AF Bennett, GG Wolin, KY Puleo, E Emmons, KM TI Pedometer-determined physical activity among multiethnic low-income housing residents SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE race/ethnicity; exercise; socioeconomic status; minority; pedometers ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; ACTIVITY PARTICIPATION; AMBULATORY ACTIVITY; MOTION SENSORS; PUBLIC-HEALTH; WORKING-CLASS; SOCIAL-CLASS; ADULTS; WOMEN AB Purpose: We sought to characterize pedometer-determined physical activity among a predominantly racial and ethnic minority sample of adults residing in low-income housing. Methods: Data were collected from 433 participants at baseline in a randomized colon cancer prevention intervention trial conducted within low-income housing communities. Using random effects models to control for clustering within housing sites, we examined variation in daily steps by several sociodemographic characteristics. Results: Participants recorded a mean of 5326 (+/- 3871 SD) daily steps over a 5-d sampling period. Significantly lower levels of pedometer-determined physical activity were found among older-aged participants (P < 0.0001), women (P = 0.02), those who were overweight and obese (P = 0.03), those reporting no weekly exercise (P = 0.04), as well as among nonworking individuals (P < 0.0001). No significant differences were found by education or income. In multivariable analyses, age, gender, body mass index, and employment status remained significantly associated with steps. Conclusions: These findings suggest a high prevalence of physical inactivity among low-income housing residents. These data, derived from a well-characterized sample, provide useful estimates for the investigation of pedometers as measures of total accumulated physical activity among lower-income, racial and ethnic minority populations. C1 Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Northwestern Univ, Feiberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Univ Massachusetts, Dept Publ Hlth Biostat & Epidemiol Concentrat, Amherst, MA 01003 USA. RP Bennett, GG (reprint author), 44 Binney St,SM256, Boston, MA 02115 USA. EM gbennett@hsph.harvard.edu RI Wolin, Kathleen/I-2154-2014 OI Wolin, Kathleen/0000-0001-7950-9042 FU NCI NIH HHS [R01 CA098864-01A1, 5R01CA098864-02, R01 CA098864-02, R01 CA098864, R01 CA098864-05, R01 CA098864-04S1, R01 CA098864-03, R01 CA098864-02S1, 5R01CA098864-02S1, R01 CA098864-04, R01 CA098864-03S1] NR 29 TC 43 Z9 43 U1 5 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD APR PY 2006 VL 38 IS 4 BP 768 EP 773 DI 10.1249/01.mss.0000210200.873283f PG 6 WC Sport Sciences SC Sport Sciences GA 032WE UT WOS:000236806100023 PM 16679995 ER PT J AU Zhou, HQ Spicuglia, S Hsieh, JJD Mitsiou, DJ Hoiby, T Veenstra, GJC Korsmeyer, SJ Stunnenberg, HG AF Zhou, HQ Spicuglia, S Hsieh, JJD Mitsiou, DJ Hoiby, T Veenstra, GJC Korsmeyer, SJ Stunnenberg, HG TI Uncleaved TFIIA is a substrate for taspase 1 and active in transcription SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID YEAST TFIIA/TBP/DNA COMPLEX; TATA-BINDING PROTEIN; PROTEOLYTIC CLEAVAGE; CRYSTAL-STRUCTURE; XENOPUS EMBRYOS; IN-VIVO; TBP; ACTIVATION; BASAL; MLL AB In higher eukaryotes, the large subunit of the general transcription factor TFIIA is encoded by the single TFIIA alpha beta gene and posttranslationally cleaved into alpha and beta subunits. The molecular mechanisms and biological significance of this proteolytic process have remained obscure. Here, we show that TFIIA is a substrate of taspase 1 as reported for the trithorax group mixed-lineage leukemia protein. We demonstrate that recombinant taspase 1 cleaves TFIIA in vitro. Transfected taspase 1 enhances cleavage of TFIIA, and RNA interference knockdown of endogenous taspase 1 diminishes cleavage of TFIIA in vivo. In taspase 1(-/-) MEF cells, only uncleaved TFIIA is detected. In Xenopus laevis embryos, knockdown of TFIIA results in phenotype and expression defects. Both defects can be rescued by expression of an uncleavable TFIIA mutant. Our study shows that uncleaved TFIIA is transcriptionally active and that cleavage of TFIIA does not serve to render TFIIA competent for transcription. We propose that cleavage fine tunes the transcription regulation of a subset of genes during differentiation and development. C1 Radboud Univ Dept Mol Biol, NCMLS 191, NL-6500 HB Nijmegen, Netherlands. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Natl Hellen Res Fdn, Inst Biol Res & Biotechnol, Mol Endocrinol Program, Athens 11635, Greece. RP Stunnenberg, HG (reprint author), Radboud Univ Dept Mol Biol, NCMLS 191, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM h.stunnenberg@ncmls.ru.nl RI Zhou, Huiqing/B-1721-2013; Veenstra, Gert Jan C./D-4963-2012; Stunnenberg, Hendrik/D-6875-2012; Spicuglia, Salvatore/L-2268-2016 OI Zhou, Huiqing/0000-0002-2434-3986; Veenstra, Gert Jan C./0000-0002-7787-4940; Spicuglia, Salvatore/0000-0002-8101-7108 NR 29 TC 37 Z9 38 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2006 VL 26 IS 7 BP 2728 EP 2735 DI 10.1128/MCB.26.7.2728-2735.2006 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 026BR UT WOS:000236312200023 PM 16537915 ER PT J AU Antonini, D Rossi, B Han, R Minichiello, A Di Palma, T Corrado, M Banfi, S Zannini, M Brissette, JL Missero, C AF Antonini, D Rossi, B Han, R Minichiello, A Di Palma, T Corrado, M Banfi, S Zannini, M Brissette, JL Missero, C TI An autoregulatory loop directs the tissue-specific expression of p63 through a long-range evolutionarily conserved enhancer SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR AP-2; HAY-WELLS-SYNDROME; GENE-EXPRESSION; P53 HOMOLOG; DIFFERENTIAL REGULATION; HUMAN KERATINOCYTES; DIRECT TARGET; MOUSE; DELTA-NP63-ALPHA; MUTATIONS AB p63, a p53 family member, is essential for the development of various stratified epithelia and is one of the earliest markers of many ectodermal structures, including the epidermis, oral mucosa, apical ectodermal ridge, and mammary gland. Genetic regulatory mechanisms controlling p63 spatial expression during development have not yet been defined. Using a genomic approach, we identified an evolutionarily conserved cis-regulatory element, located 160 kb downstream of the first p63 exon, which functions as a keratinocyte-specific enhancer and is sufficient to recapitulate expression of the endogenous gene during mouse embryogenesis. Dissection of the p63 enhancer activity revealed a positive autoregulatory loop in which the p63 proteins directly bind to and are essential regulators of the enhancer. Accordingly, transactivating p63 isoforms induce endogenous p63 expression in cells that do not normally express this gene, whereas dominant negative isoforms suppress p63 expression in keratinocytes. In addition the transcription factor AP-2 also binds to the enhancer and cooperates with p63 to induce its activity. These results demonstrate that a long-range autoregulatory loop is involved in the regulation of p63 expression during embryonic development and in adult cells. C1 Telethon Inst Genet & Med, I-80131 Naples, Italy. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Naples Federico II, CNR, Ist Endocrinol & Oncol Sperimentale, Dipartimento Biol & Patol Cellulare & Mol, I-80131 Naples, Italy. RP Missero, C (reprint author), Via Pietro Castellino 111, I-80131 Naples, Italy. EM missero@tigem.it RI Zannini, Mariastella/I-1735-2012; OI Han, Rong/0000-0002-5766-8277; BANFI, Sandro/0000-0002-6541-8833; Missero, Caterina/0000-0003-0905-5123 FU NIAMS NIH HHS [R01 AR045284, AR 45284]; Telethon [TGM03P14, TGM06S01] NR 42 TC 47 Z9 47 U1 1 U2 5 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 2006 VL 26 IS 8 BP 3308 EP 3318 DI 10.1128/MCB.26.8.3308-3318.2006 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 030TM UT WOS:000236657600039 PM 16581802 ER PT J AU Meeran, SM Mantena, SK Meleth, S Elmets, CA Katiyar, SK AF Meeran, SM Mantena, SK Meleth, S Elmets, CA Katiyar, SK TI Interleukin-12-deficient mice are at greater risk of UV radiation-induced skin tumors and malignant transformation of papillomas to carcinomas SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID GREEN TEA POLYPHENOLS; IFN-GAMMA PRODUCTION; ULTRAVIOLET-RADIATION; INDUCED IMMUNOSUPPRESSION; CONTACT HYPERSENSITIVITY; DNA-REPAIR; IN-VIVO; IMMUNE SUPPRESSION; PYRIMIDINE DIMERS; SUNBURN CELL AB Solar UV radiation-induced immunosuppression is a risk factor for nonmelanoma skin cancer. Interleukin (IL)-12 has been shown to possess antitumor activity and inhibit the immunosuppresive effects of UV radiation in mice. In this study, we generated IL-12 knockout (KO) mice on a C3H/HeN background to characterize the role of IL-12 in photocarcinogenesis. After exposure of the mice to UVB (180 mJ/cm(2)) radiation thrice a week for 35 weeks, the development of UV induced tumors was more rapid and the tumor multiplicity and tumor size were significantly higher in IL-12 KO mice than their wild-type (WT) counterparts (P < 0.05-0.001). Moreover, the malignant transformation of UVB-induced papillomas to carcinomas was higher in IL-12 KO mice in terms of carcinoma incidence (55%, P < 0.001), carcinoma multiplicity (77%, P < 0.001), and carcinoma size (81%, P < 0.001). As IL-12 has the ability to repair UV-induced DNA damage, we determined this effect in our in vivo IL-12 KO mouse model. We found that UVB-induced DNA damage in the form of cyclobutane pyrimidine dimers was removed or repaired more rapidly in WT mice than IL-12 KO mice. Similarly, the UVB-induced sunburn cell formation is primarily a consequence of DNA damage. It was observed that UVB-induced sunburn cells were repaired rapidly in WT mice compared with IL-12 KO mice. The rapid removal or repair of UV-induced cyclobutane pyrimidine dimers or sunburn cells will result in reduced risk of photocarcinogenesis. Taken together, our data show that IL-12 deficiency is associated with the greater risk of photocarcinogenesis in mice, and this may be due to reduction in damaged DNA repair ability. C1 Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. Univ Alabama, Skin Dis Res Ctr, Birmingham, AL 35294 USA. Univ Alabama, Biostat & Bioinformat Unit, Birmingham, AL 35294 USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557,POB 202, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU NCCIH NIH HHS [1 R01 AT002536]; NIAMS NIH HHS [AR050984-01] NR 43 TC 37 Z9 37 U1 1 U2 1 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 2006 VL 5 IS 4 BP 825 EP 832 DI 10.1158/1535-7163.MCT-06-0003 PG 8 WC Oncology SC Oncology GA 041LU UT WOS:000237458500005 PM 16648552 ER PT J AU Chirnomas, D Taniguchi, T de la Vega, M Vaidya, AP Vasserman, M Hartman, AR Kennedy, R Foster, R Mahoney, J Seiden, MV D'Andrea, AD AF Chirnomas, D Taniguchi, T de la Vega, M Vaidya, AP Vasserman, M Hartman, AR Kennedy, R Foster, R Mahoney, J Seiden, MV D'Andrea, AD TI Chemosensitization to cisplatin by inhibitors of the Fanconi anemia/BRCA pathway SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID DNA-DAMAGE RESPONSE; I CLINICAL-TRIAL; PANCREATIC-CANCER; OVARIAN-CANCER; BRCA PATHWAY; POLYMERASE BETA; BREAST-CANCER; CURCUMIN; FANCD2; PHASE AB Cisplatin resistance occurs, at least in part, through the function of the Fanconi anemia (FA)/BRCA pathway, a DNA-damage response pathway required for repair of cisplatin cross-links. In the current study, we designed a cell-based screening strategy to identify small-molecule inhibitors of the FA/BRCA pathway with the hypothesis that such molecules could restore sensitivity to platinum agents. We identified four inhibitors, including three protein kinase inhibitors (wortmannin, H-9, and alsterpaullone) and one natural compound (curcumin) that inhibit the FA/BRCA pathway. We show that curcumin, a compound that is generally regarded as safe, inhibits the monoubiquitination of the FANCD2 protein as predicted by the screen and consequently sensitizes ovarian and breast tumor cell lines to cisplatin through apoptotic cell death. We believe that this study shows an efficient, high-throughput method for identifying new compounds that may sensitize cancer cells to DNA-damaging chemotherapy. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Boston Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Div Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hamatol Oncol, Boston, MA 02114 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu RI Kennedy, Richard/J-3489-2012 OI Kennedy, Richard/0000-0003-4737-6163 FU NCI NIH HHS [P50 CA105009-01]; NHLBI NIH HHS [P01HL54785, R01HL52725]; NIDDK NIH HHS [R01 DK43889]; PHS HHS [P0150654] NR 61 TC 110 Z9 115 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 2006 VL 5 IS 4 BP 952 EP 961 DI 10.1158/1535-7163.MCT-05-0493 PG 10 WC Oncology SC Oncology GA 041LU UT WOS:000237458500019 PM 16648566 ER PT J AU Song, CS Echchgadda, I Seo, YK Oh, T Kim, S Kim, SA Cho, SW Shi, LH Chatterjee, B AF Song, CS Echchgadda, I Seo, YK Oh, T Kim, S Kim, SA Cho, SW Shi, LH Chatterjee, B TI An essential role of the CAAT/enhancer binding protein-alpha in the vitamin D-induced expression of the human steroid/bile acid-sulfotransferase (SULT2A1) SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HUMAN CYTOSOLIC SULFOTRANSFERASES; X-RECEPTOR PXR; DEHYDROEPIANDROSTERONE-SULFOTRANSFERASE; BILE-ACIDS; HYDROXYSTEROID SULFOTRANSFERASE; GENE-EXPRESSION; TRANSCRIPTIONAL REGULATION; MOLECULAR-CLONING; LIVER; INDUCTION AB The vitamin D receptor (VDR) regulates steroid and drug metabolism by inducing the genes encoding phase I and phase II enzymes. SULT2A1 is a liver- and intestine-expressed sulfo-conjugating enzyme that converts the alcohol-OH of neutral steroids, bile acids, and drugs to water-soluble sulfated metabolites. 1 alpha, 25-Dihydroxyvitamin D-3 [1,25-(OH)(2) D-3] induces SULT2A1 gene transcription after the recruitment of VDR to the vitamin D-responsive chromatin region of SULT2A1. A composite element in human SULT2A1 directs the 1,25-(OH)(2) D-3-mediated induction of natural and heterologous promoters. This element combines a VDR/retinoid X receptor-alpha-binding site [vitamin D response element ( VDRE)], which is an imperfect inverted repeat 2 of AGCTCA, and a CAAT/enhancer binding protein (C/EBP)-binding site located 9 bp downstream to VDRE. The binding sites were identified by EMSA, antibody supershift, and deoxyribonuclease I footprinting. C/EBP-alpha at the composite element plays an essential role in the VDR regulation of SULT2A1, because 1) induction was lost for promoters with inactivating mutations at the VDRE or C/EBP element; 2) SULT2A1 induction by 1,25( OH)(2) D-3 in C/ EBP-alpha-deficient cells required the expression of cotransfected C/EBP-alpha; and 3) C/EBP-beta did not substitute for C/EBP-alpha in this regulation. VDR and C/EBP-alpha were recruited concurrently to the composite element along with the coactivators p300, steroid receptor coactivator 1 (SRC-1), and SRC-2, but not SRC-3. VDR and C/EBP-alpha associated endogenously as a DNA-dependent, coimmunoprecipitable complex, which was detected at a markedly higher level in 1,25( OH)(2) D-3-treated cells. These results provide the first example of the essential role of the interaction in cis between C/EBP-alpha and VDR in directing 1,25( OH)(2) D-3-induced expression of a VDR target gene. C1 Univ Texas, Hlth Sci Ctr, Inst Biotechnol, Dept Mol Med, San Antonio, TX 78245 USA. Audie L Murphy Mem Vet Affairs Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Chatterjee, B (reprint author), Univ Texas, Hlth Sci Ctr, Inst Biotechnol, Dept Mol Med, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM chatterjee@uthscsa.edu FU NIA NIH HHS [AG-10486] NR 46 TC 28 Z9 30 U1 0 U2 1 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 2006 VL 20 IS 4 BP 795 EP 808 DI 10.1210/me.2005-0428 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 025UZ UT WOS:000236293700008 PM 16357103 ER PT J AU Dean, T Linglart, A Mahon, MJ Bastepe, M Juppner, H Potts, JT Gardella, TJ AF Dean, T Linglart, A Mahon, MJ Bastepe, M Juppner, H Potts, JT Gardella, TJ TI Mechanisms of ligand binding to the parathyroid hormone (PTH)/PTH-related protein receptor: Selectivity of a modified PTH(1-15) Radioligand for G alpha(S)-coupled receptor conformations SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PHOTOAFFINITY CROSS-LINKING; N-TERMINAL REGION; PEPTIDE RECEPTOR; AMINO-TERMINUS; PTH/PTHRP RECEPTOR; NONPEPTIDE ANTAGONISTS; CALCITONIN RECEPTOR; COUPLED RECEPTORS; SECRETIN RECEPTOR; ADENYLATE-CYCLASE AB Mechanisms of ligand binding to the PTH/PTHrP receptor (PTHR) were explored using PTH fragment analogs as radioligands in binding assays. In particular, the modified amino-terminal fragment analog, I-125-[Aib(1,3), Nle(8), Gln(10), homoarginine(11), Ala(12), Trp(14), Tyr(15)] rPTH(1 - 15) NH2, I-125-[Aib(1,3), M] PTH(1 - 15), was used as a radioligand that we hypothesized to bind solely to the juxtamembrane (J) portion of the PTHR containing the extracellular loops and transmembrane helices. We also employed I-125- PTH(1-34) as a radioligand that binds to both the amino-terminal extracellular (N) and J domains of the PTHR. Binding was examined in membranes derived from cells expressing either wild-type or mutant PTHRs. We found that the binding of I-125[ Aib(1,3), M] PTH(1 - 15) to the wild-type PTHR was strongly (similar to 90%) inhibited by guanosine 5'-O-(3-thio) triphosphate (GTP gamma S), whereas the binding of I-125- PTH( 1 - 34) was only mildly ( similar to 25%) inhibited by GTP gamma S. Of these two radioligands, only I-125[ Aib(1,3), M] PTH( 1 - 15) bound to PTHR-delNt, which lacks most of the receptor's N domain, and again this binding was strongly inhibited by GTP gamma S. Binding of I-125-[Aib(1,3), M] PTH(1 - 15) to the constitutively active receptor, PTHR-H223R, was only mildly ( similar to 20%) inhibited by GTP gamma S, as was the binding of I-125- PTH(1 - 34). In membranes prepared from cells lacking G alpha(s) via knockout mutation of Gnas, no binding of I-125-[Aib(1,3), M] PTH(1 - 15) was observed, but binding of I-125-[Aib(1,3), M] PTH( 1 - 15) was recovered by virally transducing the cells to heterologously express G alpha(s). I-125-PTH( 1 - 34) bound to the membranes with or without G alpha(s). The overall findings confirm the hypothesis that I-125-[ Aib(1,3), M] PTH( 1 - 15) binds solely to the J domain of the PTHR. They further show that this binding is strongly dependent on coupling of the receptor to G alpha(s)-containing heterotrimeric G proteins, whereas the binding of I-125- PTH( 1 - 34) can occur in the absence of such coupling. Thus, I-125-[ Aib(1,3), M] PTH( 1 - 15) appears to function as a selective probe of G alpha(s)-coupled, active-state PTHR conformations. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Gardella, TJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM gardella@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK-11794, P01 DK011794, P01 DK011794-41, P30 DK040561, P30 DK040561-11] NR 55 TC 43 Z9 44 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 2006 VL 20 IS 4 BP 931 EP 943 DI 10.1210/me.2005-0349 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 025UZ UT WOS:000236293700019 PM 16339275 ER PT J AU Sun, EY Josephson, L Weissleder, R AF Sun, Eric Yi Josephson, Lee Weissleder, Ralph TI "Clickable" nanoparticles for targeted imaging SO MOLECULAR IMAGING LA English DT Article DE nanoparticles; MR imaging; optical imaging ID IN-SITU; PROSTATE-CANCER; CHEMISTRY; CYCLOADDITION; DISCOVERY AB Nanomaterials functionalized with targeting ligands are increasingly recognized as useful materials for molecular imaging and drug delivery. Here we describe the development and validation of azide-alkyne reactions ("click chemistry") for the rapid, site-specific modification of nanoparticles with small molecules. The facile preparation of stable nanoparticles bearing azido or alkyne groups capable of reaction with their corresponding counterpart functionalized small molecules is demonstrated. The Cu(I)-catalyzed cycloaddition of azides and alkynes is shown to be a highly efficient and selective method for point functionalization of magnetic nanoparticles. Derivatized nanoparticles bearing biotin, fluorochrome, or steroid moieties are stable for several months. Nanoparticle click chemistry will be useful for other nanomaterials, design of novel sensors, and drug delivery vehicles. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5403, Charlestown, MA 02129 USA. EM weissleder@helix.mgh.harvard.edu NR 22 TC 67 Z9 67 U1 2 U2 23 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1535-3508 J9 MOL IMAGING JI Mol. Imaging PD APR-JUN PY 2006 VL 5 IS 2 BP 122 EP 128 DI 10.2310/7290.2006.00013 PG 7 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA 067EZ UT WOS:000239285900009 PM 16954026 ER PT J AU Moran, ST Cariappa, A Liu, HY Boboila, C Shi, HN Holland, PM Peschon, JJ Pillai, S AF Moran, ST Cariappa, A Liu, HY Boboila, C Shi, HN Holland, PM Peschon, JJ Pillai, S TI Protein kinase C-associated kinase is not required for the development of peripheral B lymphocyte populations SO MOLECULAR IMMUNOLOGY LA English DT Article DE protein kinase C; PKC-associated kinase; RIP4; B lymphocyte development ID NF-KAPPA-B; BRUTONS TYROSINE KINASE; CELL DEVELOPMENT; MARGINAL ZONE; PHOSPHOLIPASE C-GAMMA-2; IMMUNE-RESPONSES; T-CELL; ACTIVATION; RECEPTOR; FAMILY AB Protein kinase C-associated kinase (PKK; DIK/RIP4) is an ankyrin-repeat containing serine/threonine receptor-interacting protein (RIP)-family kinase that can activate NF kappa B, and is required for keratinocyte development. In earlier studies, the expression of a catalytically inactive mutant of PKK in the B cell lineage resulted in a marked decrease in peripheral B cells in the spleen and a severe reduction of B-1 B cells. Here we explore the consequences of a null mutation in PKK with respect to the generation of peripheral B cell lineages and the activation of NF kappa B. We show that PKK is not required for the production of B cells in the bone marrow or for the development and maintenance of all mature B lymphocyte populations. We also show that PKK is not required for the activation of NF kappa B downstream of the BCR, CD40, or TLR-4 in B cells. Taken together, these data demonstrate that the loss of this RIP-family kinase does not compromise B lymphocyte development and maintenance, but leaves open the possibility that PKK may have a redundant role in these processes. (c) 2005 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. Amgen Inc, Seattle, WA 98101 USA. RP Pillai, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM pillai@helix.mgh.harvard.edu FU NCI NIH HHS [CA102793]; NIAID NIH HHS [AI054917, AI033507] NR 42 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD APR PY 2006 VL 43 IS 10 BP 1694 EP 1699 DI 10.1016/j.molimm.2005.09.009 PG 6 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 027XZ UT WOS:000236450900021 PM 16256200 ER PT J AU Butler, SM Nelson, EJ Chowdhury, N Faruque, SM Calderwood, SB Camilli, A AF Butler, SM Nelson, EJ Chowdhury, N Faruque, SM Calderwood, SB Camilli, A TI Cholera stool bacteria repress chemotaxis to increase infectivity SO MOLECULAR MICROBIOLOGY LA English DT Article ID VIBRIO-CHOLERAE; ESCHERICHIA-COLI; SIGNAL-TRANSDUCTION; MYXOCOCCUS-XANTHUS; INTESTINAL-MUCOSA; MOTILE BACTERIA; PSEUDOMONAS-AERUGINOSA; TWITCHING MOTILITY; SENSORY ADAPTATION; GENE FUSIONS AB Factors that enhance the transmission of pathogens are poorly understood. We show that Vibrio cholerae shed in human 'rice-water' stools have a 10-fold lower oral infectious dose in an animal model than in vitro grown V. cholerae, which may aid in transmission during outbreaks. Furthermore, we identify a bacterial factor contributing to this enhanced infectivity: The achievement of a transient motile but chemotaxis-defective state upon shedding from humans. Rice-water stool V. cholerae have reduced levels of CheW-1, which is essential for chemotaxis, and were consequently shown to have a chemotaxis defect when tested in capillary assays. Through mutational analyses, such a state is known to enhance the infectivity of V. cholerae. This is the first report of a pathogen altering its chemotactic state in response to human infection in order to enhance its transmission. C1 Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. Howard Hughes Med Inst, Boston, MA 02111 USA. Int Ctr Diarrhoeal Dis Res, Dhaka 1212, Bangladesh. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Camilli, A (reprint author), Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, 136 Harrison Ave, Boston, MA 02111 USA. EM andrew.camilli@tufts.edu FU NIAID NIH HHS [AI55058, R01 AI055058, R01 AI055058-05]; NIDDK NIH HHS [P30 DK34928, P30 DK034928] NR 45 TC 42 Z9 45 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD APR PY 2006 VL 60 IS 2 BP 417 EP 426 DI 10.1111/j.1365-2958.2006.05096.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 026GZ UT WOS:000236328700014 PM 16573690 ER PT J AU Kay, DM Zabetian, CP Factor, SA Nutt, JG Samii, A Griffith, A Bird, TD Kramer, P Higgins, DS Payami, H AF Kay, DM Zabetian, CP Factor, SA Nutt, JG Samii, A Griffith, A Bird, TD Kramer, P Higgins, DS Payami, H TI Parkinson's disease and LRRK2: Frequency of a common mutation in US movement disorder clinics SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; LRRK2 G2019S mutation; genotype-phenotype correlation; family history; age at onset; geography ID AUTOSOMAL-DOMINANT PARKINSONISM; G2019S MUTATION; GENE; IDENTIFICATION AB The G2019S mutation in the LRRK2 gene is reportedly a common cause of familial Parkinson's disease (PD) and may also have a significant role in nonfamilial PD. The objective of this study was to assess mutation carrier frequency in PD patients from movement disorder clinics in the United States, stratified by family history, age at onset, and geography, to determine carrier frequency in a large and well-characterized control Population; to examine segregation Of mutation in families of patients; and to correlate genotype with clinical phenotype. One thousand four hundred twenty-five unrelated PD patients from movement disorder clinics in Oregon, Washington, and New York and 1,647 unrelated controls were Studied. The G2019S mutation was detected using a TaqMan assay and verified by sequencing. Eighteen of 1.425 patients and one of 1.647 controls had the mutation. Carrier frequency (+/- 2SE) in patients was 0.013 +/- 0.006 overall, 0.030 +/- 0.019 in familial PD, 0.007 +/- 0.005 in nonfamilial PD, 0.016 +/- 0.013 in early-onset PD. and 0.012 +/- 0.007 in late-onset PD. Geographic differences were insignificant. Age at onset of mutation carriers, ranged from 28 to 71 years. Mutation carriers were clinically indistinguishable from idiopathic PD. LRRK2 G2019S is the single most common pathogenic mutation linked to neurodegenerative disease to date. (C) 2006 Movement Disorder Society. C1 New York State Dept Hlth, Wadsworth Ctr, Genom Inst, Albany, NY 12201 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. Albany Med Ctr, Parkinsons Dis & Movement Disorder Clin, Albany, NY USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. Evergreen Hosp, Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. RP Payami, H (reprint author), New York State Dept Hlth, Wadsworth Ctr, Genom Inst, POB 22002, Albany, NY 12201 USA. EM hpayami@wadsworth.org OI Zabetian, Cyrus/0000-0002-7739-4306; Kay, Denise/0000-0002-9928-2698 FU NIA NIH HHS [AG08017]; NINDS NIH HHS [K08-NS44138, NS R01-36960] NR 18 TC 55 Z9 58 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD APR PY 2006 VL 21 IS 4 BP 519 EP 523 DI 10.1002/mds.20751 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 036UV UT WOS:000237102300013 PM 16250030 ER PT J AU Lai, LX Kang, JX Li, RF Wang, JD Witt, WT Yong, HY Hao, YH Wax, DM Murphy, CN Rieke, A Samuel, M Linville, ML Korte, SW Evans, RW Starzl, TE Prather, RS Dai, YF AF Lai, LX Kang, JX Li, RF Wang, JD Witt, WT Yong, HY Hao, YH Wax, DM Murphy, CN Rieke, A Samuel, M Linville, ML Korte, SW Evans, RW Starzl, TE Prather, RS Dai, YF TI Generation of cloned transgenic pigs rich in omega-3 fatty acids SO NATURE BIOTECHNOLOGY LA English DT Article AB Meat products are generally low in omega-3 (n-3) fatty acids, which are beneficial to human health. We describe the generation of cloned pigs that express a humanized Caenorhabditis elegans gene, fat-1, encoding an n-3 fatty acid desaturase. The hfat-1 transgenic pigs produce high levels of n-3 fatty acids from n-6 analogs, and their tissues have a significantly reduced ratio of n-6/n-3 fatty acids (P < 0.001). C1 Univ Pittsburgh, Dept Surg, Thomas Starzl Transplantat Inst, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Epidemiol, GSPH, Pittsburgh, PA 15261 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65211 USA. Univ Missouri, Div Anim Sci, Columbia, MO 65211 USA. Univ Missouri, Natl Swine Resource & Res Ctr, Columbia, MO 65211 USA. Univ Missouri, Off Anim Resources, Columbia, MO 65211 USA. RP Dai, YF (reprint author), Univ Pittsburgh, Dept Surg, Thomas Starzl Transplantat Inst, Pittsburgh, PA 15261 USA. EM pratherr@missouri.edu; daiy@upmc.edu RI Lai, Liangxue/H-4545-2011; OI Prather, Randall/0000-0002-6012-4035 FU NCI NIH HHS [CA79553]; NCRR NIH HHS [R01 RR013438, U42 RR018877]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-11, R01 DK064207, R01 DK064207-01, R01DK64207] NR 7 TC 182 Z9 241 U1 6 U2 36 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD APR PY 2006 VL 24 IS 4 BP 435 EP 436 DI 10.1038/nbt1198 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 032HU UT WOS:000236766300026 PM 16565727 ER PT J AU Huang, TT Nijman, SMB Mirchandani, KD Galardy, PJ Cohn, MA Haas, W Gygi, SP Ploegh, HL Bernards, R D'Andrea, AD AF Huang, TT Nijman, SMB Mirchandani, KD Galardy, PJ Cohn, MA Haas, W Gygi, SP Ploegh, HL Bernards, R D'Andrea, AD TI Regulation of monoubiquitinated PCNA by DUB autocleavage SO NATURE CELL BIOLOGY LA English DT Article ID DNA-POLYMERASE-ETA; FANCONI-ANEMIA PATHWAY; DEUBIQUITINATING ENZYMES; TRANSLESION SYNTHESIS; DAMAGE RESPONSE; KAPPA-B; UBIQUITIN; FIDELITY; FAMILY; FANCD2 AB Monoubiquitination is a reversible post-translational protein modification that has an important regulatory function in many biological processes, including DNA repair. Deubiquitinating enzymes (DUBs) are proteases that are negative regulators of monoubiquitination, but little is known about their regulation and contribution to the control of conjugated-substrate levels. Here, we show that the DUB ubiquitin specific protease 1 (USP1) deubiquitinates the DNA replication processivity factor, PCNA, as a safeguard against error-prone translesion synthesis (TLS) of DNA. Ultraviolet (UV) irradiation inactivates USP1 through an autocleavage event, thus enabling monoubiquitinated PCNA to accumulate and to activate TLS. Significantly, the site of USP1 cleavage is immediately after a conserved internal ubiquitin-like diglycine (Gly - Gly) motif. This mechanism is reminiscent of the processing of precursors of ubiquitin and ubiquitin-like modifiers by DUBs. Our results define a regulatory mechanism for protein ubiquitination that involves the signal-induced degradation of an inhibitory DUB. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Netherlands Canc Inst, Div Mol Carcinogenesis, Amsterdam, Netherlands. Netherlands Canc Inst, Ctr Biomed Genet, Amsterdam, Netherlands. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu OI Cohn, Martin/0000-0002-2988-3009; Bernards, Rene/0000-0001-8677-3423 NR 39 TC 262 Z9 268 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD APR PY 2006 VL 8 IS 4 BP 339 EP U13 DI 10.1038/ncb1378 PG 13 WC Cell Biology SC Cell Biology GA 029KA UT WOS:000236560000012 PM 16531995 ER PT J AU Greenway, MJ Andersen, PM Russ, C Ennis, S Cashman, S Donaghy, C Patterson, V Swingler, R Kieran, D Prehn, J Morrison, KE Green, A Acharya, KR Brown, RH Hardiman, O AF Greenway, MJ Andersen, PM Russ, C Ennis, S Cashman, S Donaghy, C Patterson, V Swingler, R Kieran, D Prehn, J Morrison, KE Green, A Acharya, KR Brown, RH Hardiman, O TI ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis SO NATURE GENETICS LA English DT Article ID SITE-DIRECTED MUTAGENESIS; HUMAN ANGIOGENIN; VEGF; ALS; DEGENERATION; DELIVERY; PROTEIN; CELLS; MODEL AB We recently identified angiogenin (ANG) as a candidate susceptibility gene for amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by adult-onset loss of motor neurons. We now report the finding of seven missense mutations in 15 individuals, of whom four had familial ALS and 11 apparently 'sporadic' ALS. Our findings provide further evidence that variations in hypoxia-inducible genes have an important role in motor neuron degeneration. C1 Royal Coll Surgeons Ireland, Dept Clin Neurol Sci, Dublin 2, Ireland. Our Ladys Hosp Sick Children, Natl Ctr Med Genet, Dublin, Ireland. Umea Univ, Dept Neurol, S-90187 Umea, Sweden. Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Boston, MA 02114 USA. Univ Coll Dublin, Sch Med & Med Sci, Conway Inst, Dublin, Ireland. Royal Victoria Hosp, Dept Neurol, Belfast BT12 6BA, Antrim, North Ireland. Univ Dundee, Ninewells Hosp, Dept Neurol, Dundee, Scotland. Royal Coll Surgeons Ireland, Dept Physiol, Dublin 2, Ireland. Univ Birmingham, Dept Clin Neurosci, Birmingham, W Midlands, England. Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England. Beaumont Hosp, Dept Neurol, Dublin 9, Ireland. RP Greenway, MJ (reprint author), Royal Coll Surgeons Ireland, Dept Clin Neurol Sci, Dublin 2, Ireland. EM mattgreenway@rcsi.ie; ohard@iol.ie RI Prehn, Jochen/A-3928-2010; OI Prehn, Jochen/0000-0003-3479-7794; Hardiman, Orla/0000-0003-2610-1291 FU Wellcome Trust [067288] NR 15 TC 373 Z9 394 U1 4 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2006 VL 38 IS 4 BP 411 EP 413 DI 10.1038/ng1742 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 026LN UT WOS:000236340500011 PM 16501576 ER PT J AU Adams, GB Scadden, DT AF Adams, GB Scadden, DT TI The hematopoietic stem cell in its place SO NATURE IMMUNOLOGY LA English DT Review ID COLONY-STIMULATING FACTOR; BONE-MARROW; DROSOPHILA OVARY; SELF-RENEWAL; CAENORHABDITIS-ELEGANS; PROGENITOR CELLS; NICHE; GERMLINE; OSTEOPONTIN; MICE AB A signature characteristic of stem cells is their ability to self-renew, affording a theoretically limitless ability to produce daughter cells and their descendents. This near-timeless dimension of stem cell function is not free of the constraints of place. The idea that highly specialized `microenvironmental' cues participate in the regulation of stem cells has evidence in classic embryology and more recently in adult stem cells through the use of model organisms. There is now ample evidence that an anatomically defined, specifically constituted place represents the niche for hematopoietic and other tissue-specific stem cells. This review provides a conceptual framework and detailed account of the hematopoietic stem cell niche as defined at present. The components are assembling into a more complex view of the niche and may now be amenable to examination as a system and possibly to alteration to affect outcomes in immune regeneration. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. EM scadden.david@mgh.harvard.edu FU NHLBI NIH HHS [HL081030, HL44851] NR 41 TC 281 Z9 293 U1 3 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2006 VL 7 IS 4 BP 333 EP 337 DI 10.1038/ni1331 PG 5 WC Immunology SC Immunology GA 024BX UT WOS:000236171000003 PM 16550195 ER PT J AU Yoshida, T Ng, SYM Zuniga-Pflucker, JC Georgopoulos, K AF Yoshida, T Ng, SYM Zuniga-Pflucker, JC Georgopoulos, K TI Early hematopoietic lineage restrictions directed by Ikaros SO NATURE IMMUNOLOGY LA English DT Article ID COMMON LYMPHOID PROGENITORS; T-CELL DEVELOPMENT; STEM-CELLS; BONE-MARROW; TRANSCRIPTIONAL REGULATION; GENE LEADS; IDENTIFICATION; COMMITMENT; DEFECTS; MICE AB Ikaros is expressed in early hematopoietic progenitors and is required for lymphoid differentiation. In the absence of Ikaros, there is a lack of markers defining fate restriction along lympho-myeloid pathways, but it is unclear whether formation of specific progenitors or expression of their markers is affected. Here we use a reporter based on Ikaros regulatory elements to separate early progenitors in wild-type and Ikaros-null mice. We found previously undetected Ikaros-null lympho-myeloid progenitors lacking the receptor tyrosine kinase Flt3 that were capable of myeloid but not lymphoid differentiation. In contrast, lack of Ikaros in the common myeloid progenitor resulted in increased formation of erythro-megakaryocytes at the expense of myeloid progenitors. Using this approach, we identify previously unknown pivotal functions for Ikaros in distinct fate 'decisions' in the early hematopoietic hierarchy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Univ Toronto, Sunnybrook & Womens Coll Hlth Sci Ctr, Dept Immunol, Toronto, ON M4N 3M5, Canada. RP Georgopoulos, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM katia.georgopoulos@cbrc2.mgh.harvard.edu RI Zuniga-Pflucker, Juan/H-1295-2012; OI Zuniga-Pflucker, Juan Carlos/0000-0003-2538-3178 FU NIAID NIH HHS [R01 AI042254-10, 5R37 R01 AI33062, 5T32 AI07529, R01 AI033062, R01 AI042254, R37 AI033062, R37 AI033062-09A1] NR 43 TC 166 Z9 171 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2006 VL 7 IS 4 BP 382 EP 391 DI 10.1038/ni1314 PG 10 WC Immunology SC Immunology GA 024BX UT WOS:000236171000012 PM 16518393 ER PT J AU Zhao, BQ Wang, S Kim, HY Storrie, H Rosen, BR Mooney, DJ Wang, XY Lo, EH AF Zhao, BQ Wang, S Kim, HY Storrie, H Rosen, BR Mooney, DJ Wang, XY Lo, EH TI Role of matrix metalloproteinases in delayed cortical responses after stroke SO NATURE MEDICINE LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; BLOOD-BRAIN-BARRIER; PLASMINOGEN ACTIVATOR; MATRIX-METALLOPROTEINASE-9; ANGIOGENESIS; INDUCTION; RECOVERY; REGENERATION; PROTEOLYSIS; EXPRESSION AB Matrix metalloproteinases ( MMPs) are zinc-endopeptidases with multifactorial actions in central nervous system (CNS) physiology and pathology(1). Accumulating data suggest that MMPs have a deleterious role in stroke. By degrading neurovascular matrix, MMPs promote injury of the blood-brain barrier, edema and hemorrhage(2-4). By disrupting cell-matrix signaling and homeostasis, MMPs trigger brain cell death(5,6). Hence, there is a movement toward the development of MMP inhibitors for acute stroke therapy. But MMPs may have a different role during delayed phases after stroke. Because MMPs modulate brain matrix, they may mediate beneficial plasticity and remodeling during stroke recovery. Here, we show that MMPs participate in delayed cortical responses after focal cerebral ischemia in rats. MMP-9 is upregulated in peri-infarct cortex at 7-14 days after stroke and is colocalized with markers of neurovascular remodeling. Treatment with MMP inhibitors at 7 days after stroke suppresses neurovascular remodeling, increases ischemic brain injury and impairs functional recovery at 14 days. MMP processing of bioavailable VEGF may be involved because inhibition of MMPs reduces endogenous VEGF signals, whereas additional treatment with exogenous VEGF prevents MMP inhibitor-induced worsening of infarction. These data suggest that, contrary to MMP inhibitor therapies for acute stroke, strategies that modulate MMPs may be needed for promoting stroke recovery. C1 Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. Massachusetts Gen Hosp, Aninthoula Martinos Ctr Biomed Imaging, MGH E 2, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Div Engn & Appl Sci, Cambridge, MA 02138 USA. RP Lo, EH (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, MGH E 149-2401, Charlestown, MA 02129 USA. EM Lo@helix.mgh.harvard.edu FU NIBIB NIH HHS [R01-EB02066]; NINDS NIH HHS [P50-NS10828, R01-NS37074, R01-NS40529, R01-NS48422]; PHS HHS [R01-EBO2066] NR 30 TC 370 Z9 395 U1 1 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2006 VL 12 IS 4 BP 441 EP 445 DI 10.1038/nm1387 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 029RE UT WOS:000236581300033 PM 16565723 ER PT J AU Wang, GG Calvo, KR Pasillas, MP Sykes, DB Hacker, H Kamps, MP AF Wang, GG Calvo, KR Pasillas, MP Sykes, DB Hacker, H Kamps, MP TI Quantitative production of macrophages or neutrophils ex vivo using conditional Hoxb8 SO NATURE METHODS LA English DT Article ID STEM-CELL EXPANSION; NF-KAPPA-B; MYELOID-LEUKEMIA; C-MYC; V-MYB; DIFFERENTIATION; GENES; HOXA9; HEMATOPOIESIS; TRANSCRIPTION AB Differentiation mechanisms and inflammatory functions of neutrophils; and macrophages are usually studied by genetic and biochemical approaches that require costly breeding and time-consuming purification to obtain phagocytes for functional analysis. Because Hox oncoproteins enforce self-renewal of factor-dependent myeloid progenitors, we queried whether estrogen-regulated Hoxb8 (ER-Hoxb8) could immortalize macrophage or neutrophil progenitors that would execute normal differentiation and normal innate immune function upon ER-Hoxb8 inactivation. Here we describe methods to derive unlimited quantities of mouse macrophages or neutrophils by immortalizing their respective progenitors with ER-Hoxb8 using different cytokines to target expansion of different committed progenitors. ER-Hoxb8 neutrophils and macrophages are functionally superior to those produced by many other ex vivo differentiation models, have strong inflammatory responses and can be derived easily from embryonic day 13 (e13) fetal Liver of mice exhibiting embryonic-lethal phenotypes. Using knockout or small interfering RNA (siRNA) technologies, this ER-Hoxb8 phagocyte maturation system represents a rapid analytical toot for studying macrophage and neutrophil biology. C1 Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Mol Pathol Grad Program, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Biomed Sci Grad Program, La Jolla, CA 92093 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA. RP Kamps, MP (reprint author), Univ Calif San Diego, Sch Med, Dept Pathol, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM mkamps@ucsd.edu RI Calvo, Katherine/A-8109-2009; Haecker, Hans/F-6826-2013; Wang, G Greg/L-6666-2014; OI Wang, G Greg/0000-0002-7210-9940; Calvo, Katherine/0000-0002-0771-4191 FU NCI NIH HHS [CA56876] NR 30 TC 86 Z9 86 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD APR PY 2006 VL 3 IS 4 BP 287 EP 293 DI 10.1038/NMETH865 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 028PX UT WOS:000236501400016 PM 16554834 ER PT J AU Williams, ZM Eskandar, EN AF Williams, ZM Eskandar, EN TI Selective enhancement of associative learning by microstimulation of the anterior caudate SO NATURE NEUROSCIENCE LA English DT Article ID BASAL GANGLIA; NEURONAL-ACTIVITY; PRIMATE STRIATUM; MONKEY STRIATUM; DOPAMINE; REPRESENTATIONS; ORGANIZATION; STIMULATION; EXPECTATION; SIGNAL AB Primates have the remarkable ability to rapidly adjust or modify associations between visual cues and specific motor responses. Whereas little is known as to how such adjustments in behavioral policy are implemented, recent learning models suggest that the anterior striatum is optimally positioned to have a role in this process. We recorded from single units and delivered microstimulation in the striatum of rhesus monkeys performing an associative learning task. Caudate activity during reinforcement was closely correlated with the rate of learning and peaked during the steepest portion of the learning curve when new associations were being acquired. Moreover, delivering microstimulation in the caudate during the reinforcement period significantly increased the rate of learning without altering the monkeys' ultimate performance. These findings suggest that the caudate is responsible for implementing selective adjustments to the 'associative weights' between sensory cues and motor responses during learning, thus enhancing the likelihood of selecting profitable actions. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH HMS Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02114 USA. RP Eskandar, EN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH HMS Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02114 USA. EM eeskandar@partners.org NR 29 TC 138 Z9 138 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD APR PY 2006 VL 9 IS 4 BP 562 EP 568 DI 10.1038/nn1662 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 026BC UT WOS:000236310700024 PM 16501567 ER PT J AU Trehin, R Figueiredo, JL Pittet, MJ Weissleder, R Josephson, L Mahmood, U AF Trehin, Rachel Figueiredo, Jose-Luiz Pittet, Mikael J. Weissleder, Ralph Josephson, Lee Mahmood, Umar TI Fluorescent nanoparticle uptake for brain tumor visualization SO NEOPLASIA LA English DT Article DE brain tumor; optical imaging; nanoparticle; fluorescence; MRI ID SUPERPARAMAGNETIC IRON-OXIDE; EXPERIMENTAL RAT GLIOMA; MALIGNANT GLIOMAS; IN-VIVO; EXPERIMENTAL-MODEL; C6 GLIOMA; MR; RESECTION; DELINEATION; INVASION AB Accurate delineation of tumor margins is vital to the successful surgical resection of brain tumors. We have previously developed a multimodal nanoparticle CLIO-Cy5.5, which is detectable by both magnetic resonance imaging and fluorescence, to assist in intraoperatively visualizing tumor boundaries. Here we examined the accuracy of tumor margin determination of orthotopic tumors implanted in hosts with differing immune responses to the tumor. Using a nonuser-based signal intensity method applied to fluorescent micrographs of 9L gliosarcoma green fluorescent protein (GFP) tumors, mean overestimations of 2 and 24 Mm were obtained using Cy5.5 fluorescence, compared to the true tumor margin determined by GFP fluorescence, in nude mice and rats, respectively. To resolve which cells internalized the nanoparticle and to quantitate degree of uptake, tumors were disaggregated and cells were analyzed by flow cytometry and fluorescence microscopy. Nanoparticle uptake was seen in both CD11b(+) cells (representing activated microglia and macrophages) and tumor cells in both animal models by both methods. CD11b+ cells were predominantly found at the tumor margin in both hosts, but were more pronounced at the margin in the rat model. Additional metastatic (CT26 colon) and primary (Gli36 glioma) brain tumor models likewise demonstrated that the nanoparticle was internalized both by tumor cells and by host cells. Together, these observations suggest that fluorescent nanoparticles provide an accurate method of tumor margin estimation based on a combination of tumor cell and host cell uptake for primary and metastatic tumors in animal model systems and offer potential for clinical translation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Mahmood, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Bldg 149,13th St,5408, Charlestown, MA 02129 USA. EM mahmood@helix.mgh.harvard.edu FU NIBIB NIH HHS [EB001872, R01 EB001872]; PHS HHS [P50 C 86355] NR 42 TC 68 Z9 71 U1 5 U2 26 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD APR PY 2006 VL 8 IS 4 BP 302 EP 311 DI 10.1593/neo.05751 PG 10 WC Oncology SC Oncology GA 067DW UT WOS:000239282900007 PM 16756722 ER PT J AU Jara, A von Hoveling, A Jara, X Burgos, ME Valdivieso, A Mezzano, S Felsenfeld, AJ AF Jara, A von Hoveling, A Jara, X Burgos, ME Valdivieso, A Mezzano, S Felsenfeld, AJ TI Effect of endothelin receptor antagonist on parathyroid gland growth, PTH values and cell proliferation in azotemic rats SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE bosentan; dietary phosphorus; endothelin; parathyroid hyperplasia ID SECONDARY HYPERPARATHYROIDISM; RENAL-FAILURE; PHOSPHORUS; P21(WAF1); SECRETION; HORMONE AB Background. A variety of stimuli are involved in the pathogenesis of parathyroid gland hyperplasia in renal failure. Recently, it was shown that blocking the signal from the endothelin-1 (ET-1) receptor (ETAR/ETBR) by a non-selective receptor antagonist, bosentan, reduced parathyroid cell proliferation, parathyroid gland hyperplasia and parathyroid hormone (PTH) levels in normal rats on a calcium deficient diet. Our goal was to determine whether in 5/6 nephrectomized (NPX) rats with developing or established hyperparathyroidism, the endothelin receptor blocker, bosentan, reduced the increase in parathyroid cell proliferation, parathyroid gland hyperplasia and PTH values. Methods. High (HPD, 1.2%) or normal phosphorus diets (PD) (NPD, 0.6%) were given to 5/6 NPX rats for 15 days (NPX15). In each dietary group, one-half the rats were given bosentan (B) i.p. 100 mg/kg/day. The four groups of rats were: (1) NPX15-1.2% P; (2) NPX15-1.2% P+B; (3) NPX15-0.6% P; and (4) NPX15-0.6% P+B. In a second study in which hyperparathyroidism was already established in 5/6 NPX rats fed a HPD for 15 days, rats were divided into two groups in which one group was maintained on a HPD and the other group was changed to very low PD (VLPD, < 0.05%) for an additional 15 days. In each dietary group, one-half the rats were given bosentan i.p. 100 mg/kg-day. The four groups of rats were: (1) NPX30-1.2% P; (2) NPX30-1.2% P+B; (3) NPX30-0.05% P and (4) NPX30-0.05% P+B. Parathyroid cell proliferation was measured by proliferating cell nuclear antigen (PCNA) staining and ET-1 expression by immunohistochemical techniques. Results. In the study of developing hyperparathyroidism, bosentan reduced ET-1 expression in the parathyroid glands of rats on the NPD and HPD (P < 0.05). But only in rats on the NPD did bosentan result in a reduced increase in parathyroid gland weight (P < 0.05). In the study of established hyperparathyroidism, in which 5/6 NPX rats were given a HPD for 15 days, bosentan started on day 15 reduced (P < 0.05) ET-1 expression in rats maintained for 15 additional days on the HPD or the VLPD. On the VLPD, parathyroid gland weight was less (P < 0.05) than that in rats on the HPD sacrificed at 15 or 30 days. Bosentan did not reduce parathyroid cell proliferation or parathyroid gland weight in rats maintained on the HPD or further reduce these parameters beyond that obtained with dietary phosphorus restriction. PTH values were lowest in the VLPD group, intermediate in the NPD group, and highest in the HPD group, but in none of the three groups did bosentan decrease PTH values. Conclusions. In azotemic rats with developing hyperparathyroidism, bosentan resulted in a reduced increase in parathyroid gland weight when dietary phosphorus content was normal. Despite a reduction in ET-1 expression in rats on a HPD with developing or established hyperparathyroidism, bosentan did not reduce the increase in parathyroid cell proliferation, parathyroid gland growth or PTH values. Thus, ET-1 blockade with bosentan did not prevent parathyroid gland growth in the azotemic rat. C1 Pontificia Univ Catolica Chile, Dept Nephrol, Santiago, Chile. Univ Austral Chile, Div Nephrol, Valdivia, Chile. W Los Angeles VA Med Ctr, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Jara, A (reprint author), Pontificia Univ Catolica Chile, Dept Nephrol, Lira 85, Santiago, Chile. EM ajara@med.puc.cl NR 17 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD APR PY 2006 VL 21 IS 4 BP 917 EP 923 DI 10.1093/ndt/gfk006 PG 7 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 025GS UT WOS:000236254000015 PM 16431896 ER PT J AU Prados, MD Lamborn, K Yung, WKA Jaeckle, K Robins, HI Mehta, M Fine, HA Wen, PY Cloughesy, T Chang, S Nicholas, MK Schiff, D Greenberg, H Junck, L Fink, K Hess, K Kuhn, J AF Prados, MD Lamborn, K Yung, WKA Jaeckle, K Robins, HI Mehta, M Fine, HA Wen, PY Cloughesy, T Chang, S Nicholas, MK Schiff, D Greenberg, H Junck, L Fink, K Hess, K Kuhn, J TI A phase 2 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: A North American Brain Tumor Consortium study SO NEURO-ONCOLOGY LA English DT Article DE clinical trial; irinotecan; phase 2; recurrent malignant glioma ID CHEMOTHERAPY; GLIOBLASTOMA; METABOLITE; ADULTS AB The purpose of this study was to determine the response to CPT-11 administered every three weeks to adults with progressive malignant glioma, treated with or without enzyme-inducing antiepileptic drug (EIAED) therapy, at the recommended phase 2 dose determined from a previous phase 1 study. Adult patients age 18 or older with a KPS of 60 or higher who had measurable recurrent grade III anaplastic glioma (AG) or grade IV glioblastoma multiforme (GBM) were eligible. No more than one prior chemotherapy was allowed, either as adjuvant therapy or for recurrent disease. The CPT-11 dose was 350 mg/m(2) i.v. every three weeks in patients not on EIAED and 750 mg/m(2) in patients on EIAED therapy. Patients with stable or responding disease could be treated until tumor progression or a total of 12 months of therapy. The primary end point of the study was to determine whether CPT-11. could significantly delay tumor progress on, using the rate of six-month progression-free survival (PFS-6). The trial was sized to be able to discriminate between a 15% and 35% rate for the GBM group alone and between a 20% and 40% rate for the entire cohort. There were 51 eligible patients, including 38 GBM and 13 AG patients, enrolled. The median age was 52 and 42 years, respectively. PFS-6 for the entire cohort was 1.7.6%. PFS-6 was 15.7% (95% confidence interval [CI], 0.07-0.31) for the GBM patients and 23% (95% CI, 0.07-0.52) for AG patients. Toxicity for the group included diarrhea and myelosuppression. We conclude that the recommended phase 2 dose of CPT-11 for patients with or without EIAED was ineffective on this schedule, in this patient population. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Wisconsin, Med Ctr, Madison, WI 53792 USA. Natl Inst Hlth, Bethesda, MD 20892 USA. Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA 90095 USA. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA 22908 USA. Univ Michigan, Ctr Med, Ann Arbor, MI 48109 USA. Univ Texas, SW Med Ctr, Dallas, TX 75390 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. RP Prados, MD (reprint author), Univ Calif San Francisco, 400 Parnassus Ave,Room A808, San Francisco, CA 94143 USA. EM pradosm@neurosurg.ucsf.edu OI mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [CA 62399, U01 CA062399] NR 12 TC 126 Z9 129 U1 0 U2 5 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2006 VL 8 IS 2 BP 189 EP 193 DI 10.1215/15228517-2005-010 PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 031MG UT WOS:000236708100012 PM 16533878 ER PT J AU Hutton, M Lewis, J Zehr, C McGowan, E Dickson, DW Eriksen, J Petrucelli, L Hyman, B Hsiao-Ashe, K AF Hutton, M Lewis, J Zehr, C McGowan, E Dickson, DW Eriksen, J Petrucelli, L Hyman, B Hsiao-Ashe, K TI Neurodegeneration and functional deficits in mouse models of tauopathy SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy CY APR 19-22, 2006 CL Geneva, SWITZERLAND C1 Mayo Clin, Coll Med, Jacksonville, FL 32224 USA. Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, Charlestown, MA USA. EM hutton.michael@mayo.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD APR PY 2006 VL 27 SU 1 MA 43 BP S10 EP S11 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 024PJ UT WOS:000236208100044 ER PT J AU Tanzi, RE AF Tanzi, RE TI Identifying the genetic causes of Alzheimer disease SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy CY APR 19-22, 2006 CL Geneva, SWITZERLAND C1 Harvard Univ, Sch Med, Genet & Aging Res Unit, Massachusetts Gen Hosp, Charlestown, MA USA. EM tanzi@helix.mgh.harvard.edu NR 2 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD APR PY 2006 VL 27 SU 1 MA 88 BP S20 EP S21 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 024PJ UT WOS:000236208100089 ER PT J AU Hewett, JW Zeng, J Niland, BP Bragg, DC Breakefield, XO AF Hewett, JW Zeng, J Niland, BP Bragg, DC Breakefield, XO TI Dystonia-causing mutant torsinA inhibits cell adhesion and neurite extension through interference with cytoskeletal dynamics SO NEUROBIOLOGY OF DISEASE LA English DT Article DE intermediate filaments; dystonia; DYT1; vimentin; fibroblasts; cell adhesion; neurite extension ID MICE LACKING VIMENTIN; HEREDITARY SPASTIC PARAPLEGIA; EARLY-ONSET DYSTONIA; DELTA-E-TORSINA; INTERMEDIATE-FILAMENTS; NUCLEAR-ENVELOPE; DYT1 DYSTONIA; LEWY BODIES; PC12 CELLS; NEURODEGENERATIVE DISEASES AB Early onset torsion dystonia is a movement disorder inherited as an autosomal dominant syndrome with reduced penetrance. Symptoms appear to result from altered neuronal circuitry within the brain with no evidence of neuronal loss. Most cases are caused by loss of a glutamic acid residue in the AAA+ chaperone protein, torsinA, encoded in the DYT1 gene. In this study, torsinA was found to move in conjunction with vimentin in three cell culture paradigms-recovery, from microtubule depolymerization, expression of a dominant-negative form of kinesin light chain and respreading after trypsinization. Co-immune precipitation studies revealed association between vimentin and torsinA in a complex including other cytoskeletal elements, actin and tubulin, as well as two proteins previously shown to interact with torsinA-the motor protein, kinesin light chain 1, and the nuclear envelope protein, LAP1. Morphologic and functional differences related to vimentin were noted in primary fibroblasts from patients carrying this DYT1 mutation as compared with controls, including an increased perinuclear concentration of vimentin and a delayed rate of adhesion to the substratum. Overexpression of mutant torsinA inhibited neurite extension in human neuroblastoma cells, with torsinA and vimentin immunoreactivity enriched in the perinuclear region and in cytoplasmic inclusions. Collectively, these studies suggest that mutant torsinA interferes with cytoskeletal events involving vimentin, possibly by restricting movement of these particles/filaments, and hence may affect development of neuronal pathways in the brain. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp E, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, Mol Neurogenet Unit, 13th St,Bldg 149,6th Floor, Charlestown, MA 02129 USA. EM breakefield@hms.harvard.edu FU NINDS NIH HHS [NS 37409, NS28384] NR 100 TC 65 Z9 68 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD APR PY 2006 VL 22 IS 1 BP 98 EP 111 DI 10.1016/j.nbd.2005.10.012 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 029WN UT WOS:000236595200011 PM 16361107 ER PT J AU Alpert, NM Reilhac, A Chio, TC Selesnick, I AF Alpert, NM Reilhac, A Chio, TC Selesnick, I TI Optimization of dynamic measurement of receptor kinetics by wavelet denoising SO NEUROIMAGE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; IMAGE-RECONSTRUCTION; COMPLEX WAVELETS; PET; DECOMPOSITION; TRANSFORM; DOMAIN AB The most important technical limitation affecting dynamic measurements with PET is low signal-to-noise ratio (SNR). Several reports have suggested that wavelet processing of receptor kinetic data in the human brain can improve the SNR of parametric images of binding potential (1111). However, it is difficult to full), assess these reports because objective standards have not been developed to measure the tradeoff between accuracy (e.g. degradation of resolution) and precision. This paper employs a realistic simulation method that includes all major elements affecting image formation. The simulation was used to derive an ensemble of dynamic PET ligand (C-11-raclopride) experiments that was subjected to wavelet processing. A method for optimizing wavelet denoising is presented and used to analyze the simulated experiments. Using optimized wavelet denoising, SNR of the four-dimensional PET data increased by about a factor of two and SNR of three-dimensional BP maps increased by about a factor of 1.5. Analysis of the difference between the processed and unprocessed means for the 4D concentration data showed that more than 80% of voxels in the ensemble mean of the wavelet processed data deviated by less than 3%. These results show that a 1.5x increase in SNR can be achieved with little degradation of resolution. This corresponds to injecting about twice the radioactivity, a maneuver that is not possible in human studies without saturating the PET camera and/or exposing the subject to more than permitted radioactivity. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02129 USA. McConnell Brain Imaging Ctr, Montreal Neurol Inst, Montreal, PQ, Canada. Polytech Univ, Dept Elect & Comp Engn, Brooklyn, NY 11201 USA. RP Massachusetts Gen Hosp, Div Nucl Med, 50 Fruit St, Boston, MA 02129 USA. EM alpert@pet.mgh.harvard.edu OI Selesnick, Ivan/0000-0002-4939-3971 NR 29 TC 24 Z9 24 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD APR 1 PY 2006 VL 30 IS 2 BP 444 EP 451 DI 10.1016/j.neuroimage.2005.09.031 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 031CR UT WOS:000236682200010 PM 16257238 ER PT J AU Lieu, SN Million, M Oh, DS Waschek, JA Tache, Y Pisegna, JR Germano, PM AF Lieu, SN Million, M Oh, DS Waschek, JA Tache, Y Pisegna, JR Germano, PM TI PACAP and its receptor, PAC1 exert a protective effect in preventing dextran sulfate sodium (DSS)-induced colitis SO NEUROPEPTIDES LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Dept Gastroenterol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD APR PY 2006 VL 40 IS 2 BP 153 EP 154 PG 2 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 046WU UT WOS:000237842600047 ER PT J AU Lieu, SN Oh, DS Lambrecht, N Yakubov, I Sachs, G Pisegna, JR Germano, PM AF Lieu, SN Oh, DS Lambrecht, N Yakubov, I Sachs, G Pisegna, JR Germano, PM TI PACAP activation of secretory and proliferative signaling pathways in BON cells is mediated through PKA, calmodulin and Ras SO NEUROPEPTIDES LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, CURE, Digest Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Pathol, David Geffen Sch Med, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD APR PY 2006 VL 40 IS 2 BP 154 EP 154 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 046WU UT WOS:000237842600048 ER PT J AU Vortherms, TA Nguyen, CH Bastepe, M Juppner, H Watts, VJ AF Vortherms, TA Nguyen, CH Bastepe, M Juppner, H Watts, VJ TI D-2 dopamine receptor-induced sensitization of adenylyl cyclase type 1 is G alpha(s) independent SO NEUROPHARMACOLOGY LA English DT Article DE D-2 dopamine receptor; heterologous sensitization; superactivation; G(i)-coupled receptor; Ca2+; drug abuse ID HETEROLOGOUS SENSITIZATION; G-ALPHA(I/O)-COUPLED RECEPTORS; WHOLE CELLS; G(S ALPHA); RAT-BRAIN; STIMULATION; ACTIVATION; PHOSPHORYLATION; G(S-ALPHA); TOLERANCE AB Acute activation of D, dopamine receptors inhibits adenylyl cyclase (EC 4.6.1.1), whereas persistent activation of these inhibitory receptors results in a compensatory increase in cyclic AMP accumulation. This sensitization of adenylyl cyclase is thought to involve enhanced G alpha(S)-adenylyl cyclase interactions; however, the absolute requirement of Ga-S has not been determined. The present study used a Ga-S-deficient cell line to examine directly the role of Ga-S in D-2 dopamine receptor-induced sensitization of recombinant adenylyl cyclase type 1 (AC 1) and 5 (AC5). In acute experiments, quinpirole activation of the D-2 dopamine receptor inhibited AC I and AC5 activity, indicating that the acute regulatory properties of AC I and AC5 were retained in the absence of G alpha(S), Subsequent experiments revealed that short-term (2 h) activation of the D, dopamine receptor resulted in significantly enhanced forskolin-stimulated AC I activity in the absence of Gas, whereas sensitization of forskolin-stimulated AC5 activity appeared to require Ga-S The Ga-S-independent sensitization of AC I was explored further using AC1-selective activation protocols (A23187 and CCE) following short- and long-term agonist treatment. These studies revealed that persistent activation of D, dopamine receptors sensitized AC1 activity to Ca2+ stimulation in cells devoid of endogenous Gas and demonstrate directly that sensitization of AC1 is G alpha(S)-independent. (c) 2005 Elsevier Ltd. All rights reserved. C1 Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Watts, VJ (reprint author), Purdue Univ, Dept Med Chem & Mol Pharmacol, 575 Stadium Mall Dr,RHPH 210, W Lafayette, IN 47907 USA. EM wattsv@pharmacy.purdue.edu RI Watts, Val/A-4633-2012 FU NIDDK NIH HHS [DK062973]; NIMH NIH HHS [MH60397] NR 38 TC 9 Z9 9 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD APR PY 2006 VL 50 IS 5 BP 576 EP 584 DI 10.1016/j.neuropharm.2005.11.004 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 034FL UT WOS:000236914300007 PM 16376953 ER PT J AU Ledezma, CJ Hoh, BL Carter, BS Pryor, JC Putman, CM Ogilvy, CS AF Ledezma, CJ Hoh, BL Carter, BS Pryor, JC Putman, CM Ogilvy, CS TI Complications of cerebral arteriovenous malformation embolization: Multivariate analysis of predictive factors SO NEUROSURGERY LA English DT Article DE arteriovenous malformations; cerebral arteriovenous malformations; complication; embolization; endovascular; multivariate; outcome; Spetzler-Martin grade ID N-BUTYL CYANOACRYLATE; PREOPERATIVE EMBOLIZATION; MULTIMODALITY TREATMENT; ENDOVASCULAR TREATMENT; HEMORRHAGIC COMPLICATIONS; SURGICAL RESECTION; BASAL GANGLIA; BRAIN; EXPERIENCE; MANAGEMENT AB OBJECTIVE: Embolization is an important therapeutic modality in the multidisciplinary management of arteriovenous malformations (AVM); however, prior series have reported a wide variability in overall complication rates caused by embolization (10-50% neurological deficit, 1-4% mortality). In this study, we reviewed our experience with AVM embolization and analyzed factors that might predict complications and clinical outcomes after AVM embolization. METHODS: We analyzed our combined neurovascular unit's results with AVM embolization from 1993 to 2004 for the following outcomes measures: 1) clinically significant complications, 2) technical complications without clinical sequelae, 3) discharge Glasgow Outcome Scale score, and 4) death. To determine embolization efficacy, we analyzed perioperative blood transfusion and rate of AVM obliteration. Univariate and multivariate analyses were performed for patient age, sex, history of rupture, history of seizure, associated aneurysms, AVM size, deep venous drainage, eloquent location, Spetzler-Martin grade, number of embolization stages, number of pedicles embolized, and primary treatment modality. RESULTS: Over an 11 year period, 295 embolization procedures (761 pedicles embolized) were performed in 168 patients with embolization as the primary treatment modality (n = 16) or as an adjunct to surgery (n = 124) or radiosurgery (n = 28). There were a total of 27 complications in this series, of which 11 were clinically significant (6.5% of patients, 3.7% per procedure), and 16 were technical complications (9.5% of patients, 5.4% per procedure). Excellent or good outcomes (Glasgow Outcome Scale >= 4) were observed in 152 (90.5%) patients. Unfavorable outcomes (Glasgow Outcome Scale 1-3) as a direct result of embolization were both 3.0% at discharge and at follow-up, with a 1.2% embolization-related mortality. In the 124 surgical patients, 96.8% had complete AVM obliteration after initial resection, and 31% received perioperative transfusion (mean 1.4 units packed red blood cells per surgical patient). Predictors of unfavorable outcome caused by embolization by univariate analysis were deep venous drainage (P < 0.05), Spetzler-Martin Grade III to V (P < 0.05), and periprocedural hemorrhage (P < 0.0001) and by multivariate analysis were Spetzler-Martin III to V (odds ratio 10.6, P = 0.03) and periprocedural hemorrhage (odds ratio 17, P = 0.004). CONCLUSION: In a single-center, retrospective, nonrandomized study, 90.5% of patients had excellent or good outcomes after AVM embolization, with a complication rate lower than previously reported. Spetzler-Martin grade III to V and periprocedural hemorrhage were the most important predictive factors in determining outcome after embolization. C1 Univ So Calif, Keck Sch Med, Dept Neurol Surg, Los Angeles, CA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Ogilvy, CS (reprint author), Massachusetts Gen Hosp, Brain Aneurysm AVM Ctr, 55 Fruit St,VBK-710, Boston, MA 02114 USA. EM cogilvy@partners.org NR 50 TC 76 Z9 84 U1 0 U2 0 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 2006 VL 58 IS 4 BP 602 EP 610 DI 10.1227/01.NEU.0000204103.91793.77 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 036BZ UT WOS:000237047200010 PM 16575323 ER PT J AU Verhey, LJ Chen, CC Chapman, P Loeffler, J Curry, WT AF Verhey, Lynn J. Chen, Clark C. Chapman, Paul Loeffler, Jay Curry, William T. TI Single-fraction stereotactic radiosurgery for intracranial targets SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID PROTON-BEAM RADIOSURGERY; RELATIVE BIOLOGICAL EFFECTIVENESS; SKULL BASE MENINGIOMAS; LINEAR-ACCELERATOR; ARTERIOVENOUS-MALFORMATIONS; NEUROSURGICAL TOOL; RADIOTHERAPY; RADIATION; THERAPY; IRRADIATION AB Stereotactic radiosurgery (SRS) is a technique for treating intracranial lesions with a high dose of ionizing radiation, usually in a single session, using a stereotactic apparatus for accurate localization and patient immobilization. This article describes several modalities of SRS and some of its applications, particularly for intracranial lesions. C1 Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Verhey, LJ (reprint author), Univ Calif San Francisco, Dept Radiat Oncol, 513 Parnassus Ave, San Francisco, CA 94143 USA. EM lverhey@radonc.ucsf.edu NR 69 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD APR PY 2006 VL 17 IS 2 BP 79 EP + DI 10.1016/j.nec.2006.04.004 PG 20 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 064YI UT WOS:000239126200003 PM 16793501 ER PT J AU Flickinger, JC Barker, FG AF Flickinger, John C. Barker, Fred G., II TI Clinical results: Radiosurgery and radiotherapy of cranial nerve schwannomas SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID FRACTIONATED STEREOTACTIC RADIOTHERAPY; GAMMA-KNIFE SURGERY; UNILATERAL ACOUSTIC NEUROMAS; VESTIBULAR SCHWANNOMA; NONACOUSTIC SCHWANNOMAS; HEARING PRESERVATION; SINGLE-INSTITUTION; MANAGEMENT; IRRADIATION AB Stereotactic radiosurgery and fractionated radiotherapy are two attractive low-morbidity alternatives to surgical resection for managing cranial nerve schwannomas. Treatment outcomes from these radiation treatment approaches are well documented with long-term outcome studies from multiple institutions. Differences in outcome between these two modalities are difficult to define clearly. The low morbidity and high long-term tumor control rates with radiation treatment have made it the choice of many patients who opt for active initial management for small- or medium-sized cranial nerve schwannomas. C1 Univ Pittsburgh, Med Ctr,Sch Med, Joint Ctr Radiat Oncol, Dept Radiat Oncol, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Neurosurg, Dept Surg, Boston, MA 02114 USA. RP Flickinger, JC (reprint author), Univ Pittsburgh, Med Ctr,Sch Med, Joint Ctr Radiat Oncol, Dept Radiat Oncol, 200 Lothrop St, Pittsburgh, PA 15213 USA. EM flickingerjc@upmc.edu OI Flickinger, John/0000-0001-6900-1384 NR 28 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1042-3680 EI 1558-1349 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD APR PY 2006 VL 17 IS 2 BP 121 EP + DI 10.1016/j.nec.2006.02.004 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 064YI UT WOS:000239126200006 PM 16793504 ER PT J AU Emfietzoglou, D Paganetti, H Papamichael, G Pathak, A AF Emfietzoglou, D Paganetti, H Papamichael, G Pathak, A TI Monte Carlo calculation of nanoscale dosimetric distributions of MeV proton tracks with secondary electron transport SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS LA English DT Article; Proceedings Paper CT 6th International Symposium on Swift Heavy Ions in Matter CY MAY 28-31, 2005 CL Aschaffenburg, GERMANY DE Monte Carlo; microdosimetry; protons; water ID LOW-ENERGY ELECTRONS; LIQUID WATER; SUBEXCITATION ELECTRONS; SOLID WATER; THERMALIZATION AB Our MC4 Monte Carlo code which simulates in an event-by-event mode the electronic losses and slowing down process of protons and all their secondary electrons in water is used to obtain dosimetric distributions of interest to the biophysical modelling of proton beams at the submicron scale. Energy loss scattering models constructed from the oscillator strength formalism of Bethe as well as Ritchie's dielectric approach have been implemented in order to explore the influence of non-linear density effects induced by the liquid-like cellular environment. We present results on energy deposition and its straggling for nanometer spherical volumes relevant to DNA- and chromatin-size targets. The influence of the impact geometry and the size of the volume are examined. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Hyderabad, Sch Phys, Hyderabad 500046, Andhra Pradesh, India. Univ Ioannina, Sch Med, Dept Med Phys, GR-45110 Ioannina, Greece. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Natl Tech Univ Athens, Dept Mech Engn, Athens 15710, Greece. RP Pathak, A (reprint author), Univ Hyderabad, Sch Phys, Hyderabad 500046, Andhra Pradesh, India. EM appsp@uohyd.ernet.in RI Emfietzoglou, Dimitris/G-7168-2012 NR 22 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-583X J9 NUCL INSTRUM METH B JI Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms PD APR PY 2006 VL 245 IS 1 BP 80 EP 84 DI 10.1016/j.nimb.2005.11.083 PG 5 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical; Physics, Nuclear SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 025SZ UT WOS:000236288500018 ER PT J AU Sisterson, JM Chadwick, MB AF Sisterson, JM Chadwick, MB TI Cross section measurements for neutron-induced reactions in Ti, Fe and Ni at several neutron energies ranging from 70.7 to 151.6 MeV SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS LA English DT Article DE spallation reactions; quasi-monoenergetic neutron beams; cross section measurements ID COSMOGENIC NUCLIDES; EXCITATION-FUNCTIONS; NOBLE-GASES; RADIONUCLIDES; CHONDRITE; COPPER; MODEL; CO-59; IRON AB Cross sections for neutron-induced reactions producing relatively short-lived radionuclides were measured in natural targets of Ti, Fe and Ni using quasi-monoenergetic neutron beams at several different neutron energies between 70.7 and 151.6 MeV. Comparisons of these new measurements were made with energy integrated cross section measurements and reported data measured at low neutron energies Lis well as with MC-ALICE calculations. These cross section measurements are part of a systematic study to measure relevant cross sections needed to better understand cosmic ray interactions with extraterrestrial materials. (c) 2005 Elsevier B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. Los Alamos Natl Lab, Adv Simulat & Comp, Los Alamos, NM 87544 USA. RP Sisterson, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM jsisterson@partners.org NR 36 TC 8 Z9 8 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-583X J9 NUCL INSTRUM METH B JI Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms PD APR PY 2006 VL 245 IS 2 BP 371 EP 378 DI 10.1016/j.nimb.2005.12.002 PG 8 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical; Physics, Nuclear SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 028PO UT WOS:000236500500005 ER PT J AU Seddon, JM Gensler, G Klein, ML Milton, RC AF Seddon, JM Gensler, G Klein, ML Milton, RC TI C-reactive protein and homocysteine are associated with dietary and behavioral risk factors for age-related macular degeneration SO NUTRITION LA English DT Article DE age-related macular degeneration; biomarkers; C-reactive protein; homocysteine; diet; lutein/zeaxanthin; fish intake; body mass index; smoking ID ADULTS AB Objective: We investigated whether age-related macular degeneration risk factors are associated with high-sensitivity C-reactive protein (CRP) and homocysteine (HCY), systemic biomarkers for cardiovascular disease. Methods: Subjects with a range of age-related macular maculopathies or no maculopathy at two centers in the United States were evaluated. Risk factors and biomarkers were assessed by questionnaire, direct measurement, or analyses of blood specimens. Results: Higher levels of serum antioxidants vitamin C and lutein/zeaxanthin and higher fish intake were associated with lower serum CRP levels, whereas serum vitamin E, smoking, and increased body mass index were associated with increased CRP. Serum vitamin E, serum a-carotene, and dietary intake of antioxidants and vitamin 86 were associated with lower levels of plasma HCY, whereas hypertension was associated with increased HCY. Conclusions: C-reactive protein and HCY levels are related to traditional dietary and behavioral factors associated with age-related macular degeneration. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Epidemiol Unit,Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EMMES Corp, Rockville, MD USA. Devers Eye Inst, Portland, OR USA. Casey Eye Inst, Portland, OR USA. RP Seddon, JM (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Epidemiol Unit,Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. EM jseddon@earthlink.net FU NEI NIH HHS [N01EY02117, N01EY02126] NR 10 TC 34 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD APR PY 2006 VL 22 IS 4 BP 441 EP 443 DI 10.1016/j.nut.2005.12.004 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 027FC UT WOS:000236398500015 PM 16530626 ER PT J AU Subak, LL Brown, JS Kraus, SR Brubaker, L Lin, F Richter, HE Bradley, CS Grady, D AF Subak, Leslee L. Brown, Jeanette S. Kraus, Stephen R. Brubaker, Linda Lin, Feng Richter, Holly E. Bradley, Catherine S. Grady, Deborah CA DAISy Grp TI The "costs" of urinary incontinence for women SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the American-Urogynecologic-Society CY SEP 15-17, 2005 CL Atlanta, GA SP Amer Urogynecol Soc ID WILLINGNESS-TO-PAY; QUALITY-OF-LIFE; URGE INCONTINENCE; INSTRUMENT; INDEX; CARE AB OBJECTIVE: To estimate costs of routine care for female urinary incontinence, health-related quality of life, and willingness to pay for incontinence improvement. METHODS: In a cross-sectional study at 5 U.S. sites, 293 incontinent women quantified supplies, laundry, and dry cleaning specifically for incontinence. Costs were calculated by multiplying resources used by national resource costs and presented in 2005 United States dollars ($2005). Health-related quality of life was estimated with the Health Utilities index. Participants estimated willingness to pay for 25-100% improvement in incontinence. Potential predictors of these outcomes were examined using multivariable linear regression. RESULTS: Mean age was 56 +/- 11 years; participants were racially diverse and had a broad range of incontinence severity. Nearly 90% reported incontinence-related costs. Median weekly cost (25%, 75% interquartile range) increased from $0.37 ($0, 4) for slight to $10.98 ($4, 21) for very severe incontinence. Costs increased with incontinence severity (P < .001). Costs were 2.4-fold higher for African American compared with white women (P < .001) and 65% higher for women with urge compared with those having stress incontinence (P < .001). More frequent incontinence was associated with lower Health Utilities Index score (mean 0.90 +/- 0.11 for weekly and 0.81 +/- 0.21 for daily incontinence; P = .02). Women were willing to pay a mean of $70 +/- $64 per month for complete resolution of incontinence, and willingness to pay increased with income and greater expected benefit. CONCLUSION: Women with severe urinary incontinence pay $900 annually for incontinence routine care, and incontinence is associated with a significant decrement in health-related quality of life. Effective incontinence treatment may decrease costs and improve quality of life. C1 Univ Calif San Francisco, Mt Zion Womens Hlth Clin Res Ctr, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94115 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Loyola Univ, Maywood, IL 60153 USA. Univ Alabama, Birmingham, AL USA. Univ Iowa, Iowa City, IA 52242 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. San Francisco Vet Affiars Med Ctr, San Francisco, CA USA. RP Subak, LL (reprint author), Univ Calif San Francisco, Mt Zion Womens Hlth Clin Res Ctr, Dept Obstet Gynecol & Reprod Sci, 1635 Diuvisadero St,Suite 600, San Francisco, CA 94115 USA. EM subakl@obgyn.ucsf.edu FU NIDDK NIH HHS [P50 DK064538] NR 29 TC 63 Z9 66 U1 1 U2 5 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 2006 VL 107 IS 4 BP 908 EP 916 DI 10.1097/01.AOG.0000206213.48334.09 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 095GM UT WOS:000241296200025 PM 16582131 ER PT J AU Paredes, I Ahmed, M Foster, CS AF Paredes, I Ahmed, M Foster, CS TI Immunomodulatory therapy for Vogt-Koyanagi-Harada patients as first-line therapy SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE Vogt-Koyanagi-Harada disease (VKH); immunomodulatory therapy (IMT); corticosteroids ID NONINFECTIOUS UVEITIS; DISEASE; ASSOCIATION; HLA; ANTIGENS AB Purpose: To report on the use of immunomodulatory therapy (IMT) in a group of patients with Vogt-Koyanagi-Harada disease (VKH) and to compare the outcomes with those of another group of patients with VKH who were treated for prolonged periods with corticosteroids. Methods: Treatment regimens and their respective outcomes ( visual acuity) were compared for the following groups: prolonged steroid with or without delayed addition of IMT ( Group 1) and relatively prompt IMT with or without steroid ( Group 2). Results: The average duration of follow-up in Group 1 was 28.9 months and in Group 2 23.4 months. In Group 1, visual acuity deteriorated in three of the five patients (60%) and improved in one (20%). The fifth patient showed improvement in visual acuity in one eye, but decreased visual acuity in the other eye. In Group 2, seven of the eight patients showed improvement in their visual acuities (87.5%); visual acuity deteriorated in one patient (12.5%). Conclusions: The results suggest that IMT as first-line therapy for VKH is associated with a superior visual outcome when compared to steroid as monotherapy or with delayed addition of IMT. C1 Harvard Univ, Sch Med, Massachusetts Eye Res & Surg Inst, Ocular Immunol & Uveitis Fdn, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Foster, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Eye Res & Surg Inst, Ocular Immunol & Uveitis Fdn, 165 Cambridge St,100 Charles Plaza, Boston, MA 02114 USA. EM fosters@uveitis.org NR 34 TC 30 Z9 35 U1 0 U2 0 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 PY 2006 VL 14 IS 2 BP 87 EP 90 DI 10.1080/09273940500536766 PG 4 WC Ophthalmology SC Ophthalmology GA 038SK UT WOS:000237243700003 PM 16597537 ER PT J AU Canellos, GP AF Canellos, George P. TI Introduction to a special series of unique entities within the spectrum of large-cell lymphoma SO ONCOLOGIST LA English DT Editorial Material ID DIFFUSE; PREDICTION; EXPRESSION; SURVIVAL C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Canellos, GP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St 1B14, Boston, MA 02115 USA. EM george_canellos@dfci.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD APR PY 2006 VL 11 IS 4 BP 374 EP 374 DI 10.1634/theoncologist.11-4-374 PG 1 WC Oncology SC Oncology GA 085TK UT WOS:000240627100006 PM 16614232 ER PT J AU Ferry, JA AF Ferry, Judith A. TI Burkitt's lymphoma: Clinicopathologic features and differential diagnosis SO ONCOLOGIST LA English DT Article DE Burkitt's lymphoma; immunophenotype; c-myc; outcome; differential diagnosis ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; FOLLICULAR LYMPHOMA; GRANULOMATOUS REACTION; CHILDREN; LEUKEMIA; AIDS; PATHOGENESIS; CYTOGENETICS; MORPHOLOGY AB Burkitt's lymphoma is a highly aggressive lymphoma identified and described in the last century by Denis Burkitt in Africa, in areas endemic for malaria. Since its description in African children, it has been recognized outside areas with endemic malaria, frequently also in children as well as among individuals with an underlying immunodeficiency. Since its initial designation as Burkitt's lymphoma, this type of lymphoma and lymphomas closely resembling it have received a variety of names in different classifications of lymphomas and leukemias: undifferentiated lymphoma, Burkitt's and nonBurkitt's type in the modified Rappaport Classification, malignant lymphoma, small non-cleaved cell, Burkitt's type in the Working Formulation, Burkitt's lymphoma and high-grade B-cell lymphoma, Burkitt-like in the REAL Classification, and acute lymphoblastic leukemia, L3 type in the FAB Classification. With the publication of the WHO Classification of Haematopoietic and Lymphoid Tumors, the nomenclature of this lymphoma has come full circle, and it is once again known simply as Burkitt's lymphoma. In recent years, efforts have focused on improving therapy for this rapidly proliferating neoplasm while minimizing, to the extent possible, treatment-associated toxicity. These efforts have led to the development of high-intensity, short-duration combination chemotherapy that has proven extremely effective for a high proportion of Burkitt's lymphoma patients. The differential diagnosis of Burkitt's lymphoma is broad, and precise diagnosis based on histologic, immunophenotypic, and genetic features remains the critical first step in planning appropriate therapy. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ferry, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA. EM jferry@partners.org NR 39 TC 118 Z9 131 U1 1 U2 11 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD APR PY 2006 VL 11 IS 4 BP 375 EP 383 DI 10.1634/theoncologist.11-4-375 PG 9 WC Oncology SC Oncology GA 085TK UT WOS:000240627100007 PM 16614233 ER PT J AU Abramson, JS AF Abramson, Jeremy S. TI T-cell/histiocyte-rich B-cell lymphoma: Biology, diagnosis, and management SO ONCOLOGIST LA English DT Article DE DLBCL; lymphoma; tumor-infiltrating lymphocytes; nodular lymphocyte-predominant Hodgkin's lymphoma; Hodgkin's disease ID PREDOMINANT HODGKINS-DISEASE; DISTINCT CLINICOPATHOLOGICAL ENTITY; 3-WEEKLY CHOP CHEMOTHERAPY; DIFFERENTIAL-DIAGNOSIS; AGGRESSIVE LYMPHOMAS; FOLLICULAR LYMPHOMA; ELDERLY-PATIENTS; HISTIOCYTE-RICH; YOUNG-PATIENTS; SURVIVAL AB T-cell/histiocyte-rich B-cell lymphoma (T/HRBCL) is an uncommon morphologic variant of diffuse large B-cell lymphoma (DLBCL). Pathologically, it is distinguished by < 10% malignant B cells amid a majority population of reactive T lymphocytes and histiocytes. Diagnosis of this entity is occasionally difficult, as it may appear similar to other lymphoid diseases, such as nodular lymphocyte-predominant Hodgkin's lymphoma and classic Hodgkin's lymphoma. Accurate diagnosis therefore rests with careful immunohistochemical analysis of the tumor cells and the inflammatory microenvironment. Clinically, T/HRBCL occurs in younger patients, predominantly affects men, and involves the liver, spleen, and bone marrow with greater frequency than traditional DLBCL. Despite the unique clinical features and robust host inflammatory response, T/HRBCL follows a natural history similar to those of other DLBCLs and responds similarly to therapy. Recent gene expression analysis demonstrates that a productive relationship with the host immune response may extend beyond this small DLBCL variant to include as many as one third of all DLBCLs. At present, T/HRBCL should be treated similarly to other stage-matched DLBCLs, though future therapies will likely be targeted at the relationship of the tumor cells with their inflammatory microenvironment. C1 Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Abramson, JS (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jeremy_abramson@dfci.harvard.edu NR 53 TC 40 Z9 41 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD APR PY 2006 VL 11 IS 4 BP 384 EP 392 DI 10.1634/theoncologist.11-4-384 PG 9 WC Oncology SC Oncology GA 085TK UT WOS:000240627100008 PM 16614234 ER PT J AU Duska, LR AF Duska, LR TI Fertility-preserving options for cervical cancer - The Plante/Roy article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID RADICAL TRACHELECTOMY C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Duska, LR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD APR PY 2006 VL 20 IS 5 BP 492 EP 493 PG 2 WC Oncology SC Oncology GA 052FE UT WOS:000238216200008 ER PT J AU Brown, KS Kane, MA AF Brown, KS Kane, MA TI Chemoprevention of squamous cell carcinoma of the oral cavity SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID GROWTH-FACTOR RECEPTOR; 2ND PRIMARY TUMORS; NECK-CANCER PATIENTS; BETA-CAROTENE; RETINOIC ACID; VITAMIN-A; 13-CIS-RETINOIC ACID; PHARYNGEAL CANCER; RANDOMIZED-TRIAL; LUNG-CANCER AB The potential for chemoprevention of squamous cell carcinoma of the oral cavity has long been recognized. Its easily identifiable precursor lesions and the failure of local therapies to prevent progression of these lesions to cancer has fueled much of the interest in identifying an effective chemopreventive compound. Early optimism regarding retinoids has been tempered by concerns about toxicity and lack of long-term efficacy. Although several other compounds have been studied, none as yet have been shown to be safe and effective in large studies. Agents that target specific molecular carcinogenic pathways have shown promise. Chemoprevention of this disease remains an active area of investigation. C1 Denver Hlth Med Ctr, Denver, CO 80204 USA. Univ Colorado, Hlth Sci Ctr, Div Hematol & Oncol, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Div Med Oncol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Brown, KS (reprint author), Denver Hlth Med Ctr, 660 Bannock St,MC 4000, Denver, CO 80204 USA. EM kevin.brown@dhha.org NR 81 TC 7 Z9 7 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD APR PY 2006 VL 39 IS 2 BP 349 EP + DI 10.1016/j.otc.2005.11.010 PG 16 WC Otorhinolaryngology SC Otorhinolaryngology GA 036JA UT WOS:000237066200009 PM 16580916 ER PT J AU Teitell, MA Mikkola, HKA AF Teitell, MA Mikkola, HKA TI Transcriptional activators, repressors, and epigenetic modifiers controlling hematopoietic stem cell development SO PEDIATRIC RESEARCH LA English DT Review ID YOLK-SAC; LEUKEMIA GENE; SELF-RENEWAL; ADULT HEMATOPOIESIS; MOUSE EMBRYO; MICE LACKING; DIFFERENTIATION; PROLIFERATION; MAINTENANCE; EXPANSION AB Hematopoietic stein cells (HSCs) are pluripotent cells that give rise to all of the circulating blood cell types. Their unique ability to self-renew while generating differentiated daughter cells permits HSCS to sustain blood cell production throughout life. In mammals, the pool of HSCs shifts from early sites in the aorta-gonad-mesonephros region and the placenta to the fetal liver and Ultimately bone marrow. During the past decade, a map of transcriptional activators and repressors that regulate gene expression ill HSCs, their precursors and their progeny, at distinct stages of development has been drafted. These factors control a program that first establishes the pool of HSCs in the fetus, and later guides decisions between quiescence, self-renewal, and lineage commitment with progressive differentiation to maintain homeostasis. Continuing studies of the regulatory mechanisms that control HSC gene expression followed by the identification of specific loci that are activated of silenced during the life of an HSC will help to further elucidate longstanding issues in HSC decisions to self-renew or to differentiate, and to define the origins of and connections between distinct HSC pools and their precursors. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Calif NanoSyst Inst, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Stem Cell Biol & Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Teitell, MA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, 10833 Conte Ave, Los Angeles, CA 90095 USA. EM mteitell@ucla.edu FU NCI NIH HHS [CA107300, CA90571]; NIDDK NIH HHS [DK069659]; NIGMS NIH HHS [GM073981] NR 63 TC 23 Z9 24 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2006 VL 59 IS 4 BP 33R EP 39R DI 10.1203/01.pdr.0000205155.26315.c7 PN 2 PG 7 WC Pediatrics SC Pediatrics GA 026RK UT WOS:000236359600006 PM 16549546 ER PT J AU Misra, M Prabhakaran, R Miller, KK Tsai, P Lin, A Lee, N Herzog, DB Klibanski, A AF Misra, M Prabhakaran, R Miller, KK Tsai, P Lin, A Lee, N Herzog, DB Klibanski, A TI Role of cortisol in menstrual recovery in adolescent girls with anorexia nervosa SO PEDIATRIC RESEARCH LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; LEPTIN RECEPTOR GENE; HYPOTHALAMIC AMENORRHEA; SECRETORY DYNAMICS; BODY-COMPOSITION; BONE METABOLISM; SERUM LEPTIN; WOMEN; WEIGHT; MUTATION AB Neuroendocrine abnormalities in anorexia nervosa (AN) include hypercortisolemia, hypogonadism, and hypoleptinemia, and neuroendocrine predictors of menstrual recovery are unclear. Preliminary data suggest that increases in fat mass may better predict menstrual recovery than leptin. High doses of cortisol decrease luteinizing hormone (LH) pulse frequency, and cortisol predicts regional fat distribution. We hypothesized that an increase in fat mass and decrease in cortisol Would predict menstrual recovery in adolescents with AN. Thirty-three AN girls 12-18 y old and 33 controls were studied prospectively for I y. Body composition [dual energy x-ray absorptiometry (DXA)], leptin, and urinary cortisol (UFC) were measured at 0, 6, and 12 mo. Serum cortisol was measured overnight (every 30 min) in 18 AN subjects and 17 controls. AN subjects had higher UFC/cr.m(2) and cortisol area under curve (AUC), and lower leptin levels than controls. Leptin increased significantly with recovery. When menses-recovered AN subjects were compared with AN subjects not recovering menses and controls, menses-recovered AN Subjects had higher baseline cortisol levels and greater increases in leptin than controls and greater increases in fat mass than AN subjects not recovering menses and controls (adjusted for multiple comparisons). In a logistic regression model, increasing fat mass, but not leptin, predicted menstrual recovery. Baseline cortisol level strongly predicted increases in the percentage of body fat. We demonstrate that 1) high baseline cortisol level predicts increases in body fat and 2) increases in body fat predict menses recovery in AN. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org FU NCRR NIH HHS [K23 RR018851, M01-RR-01066]; NIDDK NIH HHS [DK 062249] NR 32 TC 47 Z9 47 U1 1 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2006 VL 59 IS 4 BP 598 EP 603 DI 10.1203/01.pdr.0000203097.64918.63 PN 1 PG 6 WC Pediatrics SC Pediatrics GA 026RG UT WOS:000236359200021 PM 16549537 ER PT J AU Jalmsell, L Kreicbergs, U Onelov, E Steineck, G Henter, JI AF Jalmsell, L Kreicbergs, U Onelov, E Steineck, G Henter, JI TI Symptoms affecting children with malignancies during the last month of life: A nationwide follow-up SO PEDIATRICS LA English DT Article DE cancer; children; age; symptoms ID PALLIATIVE CARE; CANCER; DEATH; END AB OBJECTIVE. In a population-based nationwide survey, we aimed to study symptoms in children with malignancies during the last month of their lives. Understanding which symptoms affect children in the terminal phase of disease is crucial to improve palliative care. METHODS. We attempted to contact all parents in Sweden who had lost a child to cancer during a 6-year period. The parents were asked, through an anonymous postal questionnaire, about symptoms that affected the child's sense of well-being during the last month of life. RESULTS. Information was supplied by 449 (80%) of 561 eligible parents. The symptoms most frequently reported with high or moderate impact on the child's well-being were: physical fatigue (86%), reduced mobility (76%), pain (73%), and decreased appetite (71%). Irrespective of the specific malignancy, physical fatigue was the most frequently reported symptom, and pain was among the 3 most frequently reported. Children who died at 9 to 15 years of age were reported to be moderately or severely affected, by a number of symptoms, significantly more often than other children. The gender of the reporting parent had no significant bearing on any of the symptoms reported. CONCLUSIONS. The most frequently reported symptoms in children with malignancies to be aware of and possibly address during the terminal phase are physical fatigue, reduced mobility, pain, and decreased appetite. Children aged 9 to 15 years are reported to be moderately or severely affected by more symptoms than children in other age groups. Mothers and fathers report a similar prevalence of symptoms. C1 Karolinska Inst, Karolinska Hosp, Dept Woman & Child Hlth, Childhood Canc Res Unit, S-10401 Stockholm, Sweden. Karolinska Inst, Karolinska Hosp, Dept Oncol & Pathol, Div Clin Canc Epidemiol, S-10401 Stockholm, Sweden. Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA. Dept Sahlgrenska Acad, Div Clin Canc Epidemiol, Gothenburg, Sweden. RP Jalmsell, L (reprint author), Karolinska Univ Hosp, Childhood Canc Res Unit, Q6-05, SE-17176 Stockholm, Sweden. EM Li.Jalmsell@ki.se OI Steineck, Gunnar/0000-0002-0787-3969 NR 20 TC 76 Z9 78 U1 0 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 2006 VL 117 IS 4 BP 1314 EP 1320 DI 10.1542/peds.2005-1479 PG 7 WC Pediatrics SC Pediatrics GA 029EA UT WOS:000236540500065 PM 16585329 ER PT J AU Brown, SD Truog, RD Johnson, JA Ecker, JL AF Brown, SD Truog, RD Johnson, JA Ecker, JL TI Do differences in the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists positions on the ethics of maternal-fetal interventions reflect subtly divergent professional sensitivities to pregnant women and fetuses? SO PEDIATRICS LA English DT Article DE ethics; perinatal medicine; pregnancy; professional attitudes; prenatal care ID COUNSELING FOLLOWING DIAGNOSIS; PERINATAL MANAGEMENT; PRENATAL-DIAGNOSIS; ABNORMALITY; GENETICISTS; ATTITUDES AB As therapeutic interventions that are designed for the direct benefit of the fetus have evolved, pediatric specialists along with obstetricians have become increasingly engaged in the management of pregnancies that are complicated by fetal disorders. Do the 2 groups of medical specialists hold differing "world views" on the nature of the maternal - fetal relationship that could have an impact on decision-making? A direct comparison of the positions of the ethics committees of the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists concerning maternal - fetal conflicts and fetal therapy reveals subtle but telling differences. Compared with the American College of Obstetricians and Gynecologists policy, the American Academy of Pediatrics statement accords somewhat less weight to maternal decision-making and is more tolerant of overriding maternal refusal of interventions that are recommended for fetal benefit. In doing so, it may oblige pregnant patients to assume greater risk and tolerate diminished autonomy. We urge leaders from both disciplines to meet and seek consensus so that a common approach and language can guide treatment of the patients whom we share. C1 Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Div Crit Care Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Med Eth, Boston, MA 02115 USA. Childrens Hosp, Off Eth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet Serv, Boston, MA 02114 USA. RP Brown, SD (reprint author), Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM Stephen.brown@childrens.harvard.edu NR 20 TC 13 Z9 13 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2006 VL 117 IS 4 BP 1382 EP 1387 DI 10.1542/peds.2005-2724 PG 6 WC Pediatrics SC Pediatrics GA 029EA UT WOS:000236540500072 PM 16585336 ER PT J AU Geller, AC Brooks, DR Colditz, GA Koh, HK Frazier, AL AF Geller, AC Brooks, DR Colditz, GA Koh, HK Frazier, AL TI Sun protection practices among offspring of women with personal or family history of skin cancer SO PEDIATRICS LA English DT Article DE melanoma; skin cancer; family history; children; parents; sun protection; sunscreen ID BASAL-CELL CARCINOMA; RISK-FACTORS; US YOUTH; ADOLESCENTS; PREVENTION; EXPOSURE; MELANOMA; PREVALENCE; BEHAVIORS; SUNSCREEN AB OBJECTIVE. Family history of skin cancer is an important determinant of skin cancer risk for offspring. No previous study of the effect of personal or family history of skin cancer on the sun protection behaviors of the offspring has been published. METHODS. A retrospective study was conducted of the sun protection behaviors of the adolescent participants in the Growing Up Today Study (GUTS), who were offspring of mothers from the Nurses Health Study II. Adolescents' surveys were matched with their mothers' reports of a personal or family history of skin cancer and compared with adolescents whose mothers did not report a personal or family history of skin cancer. The outcome measures were (1) occurrence of frequent sunburns during the past summer, (2) use of a tanning bed during the past year, and (3) routine use of sunscreen. Frequent sunburns were defined as the report of >= 3 sunburns during the past summer. We compared those who reported having used a tanning bed in the past year at least once with those who reported no tanning bed use in the past year. Routine use of sunscreen was defined as a respondent who replied that he or she "always" or "often" used sunscreen with sun protection factor of 15 or more when he or she was outside for >15 minutes on a sunny day during the past summer. General estimating equations were used to calculate odds ratios and 95% confidence intervals adjusted for gender, age, color of untanned skin, and number of friends who were tanned. We also conducted an additional analysis restricted to children whose mothers had received a diagnosis of skin cancer in which we assessed sun protection behaviors according to the child's age and mother's age at the time of the mother's diagnosis and the number of years that had passed since the diagnosis of the mother's skin cancer. RESULTS. In 1999, 9943 children reported their sun protection behaviors; 8697 of their mothers had not received a diagnosis of skin cancer or reported a family history of melanoma, 463 participants' mothers had received a diagnosis of skin cancer, and 783 participants' mothers reported a family history of melanoma. Between 1989 and 1999, 371 mothers of GUTS participants received a diagnosis of skin cancer: melanoma (n = 44), squamous cell (n = 39), and basal cell cancer n = 311); 23 mothers received a diagnosis of > 1 type of skin cancer. Because GUTS includes siblings from the same family, the 371 mothers with skin cancer had 463 offspring in GUTS. Offspring of mothers with skin cancer were slightly more likely to report frequent sunburns in the past year compared with those with neither maternal diagnosis nor family history (39% vs 36%). Tanning bed use was not significantly different among those with either a maternal diagnosis of skin cancer or family history of melanoma as compared with nonaffected adolescents (8% vs 9% vs 10%). Sunscreen use among offspring of mothers with skin cancer was higher than among those whose mothers had a family history of melanoma or mothers with no personal history of skin cancer (42% vs 33% vs 34%). Tan-promoting attitudes were also similar across all groups. Only 25% thought that a natural skin color was most attractive, and on average, 25% in each group agreed that it was worth burning to get a tan. Children of mothers who had received a diagnosis > 2 years in the past were less likely to use sunscreen, more likely to sunburn, and more likely to use tanning beds than children of mothers with a more recent diagnosis, although the results did not reach statistical significance. CONCLUSION. Frequent sunburns, suboptimal sunscreen use, and high rates of tanning bed use are commonplace even among the children of health professionals who are at risk for developing skin cancer themselves as a result of personal or family history. With new information on family risk, pediatricians can use the potential of a teachable moment to ensure optimal sun protection for children who are at risk. C1 Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Div Publ Hlth Practice, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Geller, AC (reprint author), Boston Univ, Sch Med, Dept Dermatol, 720 Harrison Ave,DOB801A, Boston, MA 02118 USA. EM ageller@bu.edu RI Colditz, Graham/A-3963-2009; OI Colditz, Graham/0000-0002-7307-0291; Brooks, Daniel/0000-0001-6220-6889 FU NCI NIH HHS [P50CA93683-04] NR 24 TC 24 Z9 24 U1 0 U2 5 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 2006 VL 117 IS 4 BP E688 EP E694 DI 10.1542/peds.2005-1734 PG 7 WC Pediatrics SC Pediatrics GA 029EA UT WOS:000236540500011 PM 16585282 ER PT J AU Winickoff, JP Tanski, SE McMillen, RC Hipple, BJ Friebely, J Healey, EA AF Winickoff, JP Tanski, SE McMillen, RC Hipple, BJ Friebely, J Healey, EA TI A national survey of the acceptability of quitlines to help parents quit smoking SO PEDIATRICS LA English DT Article DE smoking; tobacco; pediatrics; family practice; parent; smoking cessation; secondhand smoke; environmental tobacco smoke; tobacco control; quitline; telephone counseling ID ENVIRONMENTAL TOBACCO-SMOKE; ADOLESCENT SMOKING; CESSATION INTERVENTION; NICOTINE REPLACEMENT; ADVISING PARENTS; STOP SMOKING; PRIMARY-CARE; CHILDREN; PEDIATRICIANS; WOMEN AB OBJECTIVE. Provision of telephone smoking cessation counseling can increase the rate of quitting smoking. The US Public Health Service recently helped to establish a free national quitline enrollment service. No previous surveys have assessed the acceptability to parents of enrollment in quitline counseling in the context of their child's health care visits. Therefore, the objective of this study was to assess acceptability to parents of enrollment in quitline counseling and to compare that with the reported rate of actually being enrolled in any smoking cessation counseling outside the office in the context of the child's health care visit. METHODS. Data were collected by a national random-digit-dial telephone survey of households from September to November 2004. The sample is weighted by race and gender on the basis of the current US Census to be representative of the US population. RESULTS. Of 3615 eligible respondents contacted, 3011 (83.3%) completed surveys; 958 (31.8%) who completed the survey were parents with children under the age of 18 years. Of these parents, 187 (19.7%) were self-identified smokers. Of the parents who smoked, 113 (64.2%) said that they would accept enrollment in a telephone cessation program if the child's doctor offered it to them. In contrast, of the 122 smoking parents who accompanied their child to the doctor in the past year, only 11 (9%) had any counseling recommended to them, and only 1 (0.8%) was actually enrolled. These results did not vary by parent age, gender, race, or child age. CONCLUSIONS. When interacting with parents who smoke, child health care providers have low rates of referring and enrolling parents in any services related to smoking. Enrollment in quitlines would be acceptable to the majority of parents in the context of their child's health care visit. Tobacco control efforts in the child health care setting should include implementation of office systems that can facilitate enrollment of parental smokers in telephone quitlines. C1 Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Univ Rochester, AAP, Ctr Child Hlth Res, Rochester, NY USA. Univ Rochester, Strong Childrens Res Ctr, Rochester, NY USA. Mississippi State Univ, Social Sci Res Ctr, Mississippi State, 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 A 01]; PHS HHS [4 D1A RH 00005-01-01] NR 51 TC 20 Z9 20 U1 3 U2 4 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 2006 VL 117 IS 4 BP E695 EP E700 DI 10.1542/peds.2005-1946 PG 6 WC Pediatrics SC Pediatrics GA 029EA UT WOS:000236540500012 PM 16585283 ER PT J AU Naeser, MA AF Naeser, MA TI Photobiomodulation of pain in carpal tunnel syndrome: Review of seven laser therapy studies SO PHOTOMEDICINE AND LASER SURGERY LA English DT Review ID LOW-LEVEL LASER; NERVE-STIMULATION; QUESTIONNAIRE; ACUPUNCTURE; MANAGEMENT; TRIAL; HAND AB In this review, seven studies using photoradiation to treat carpal tunnel syndrome (CTS) are discussed: two controlled studies that observed real laser to have a better effect than sham laser, to treat CTS; three open-protocol studies that observed real laser to have a beneficial effect to treat CTS; and two studies that did not observe real laser to have a better effect than a control condition, to treat CTS. In the five studies that observed beneficial effect from real laser, higher laser dosages (9 joules, 12-30 Joules, 32 J/cm(2), 225 J/cm(2)) were used at the primary treatment sites (median nerve at the wrist, or cervical neck area), than dosages in the two studies where real laser was not observed to have a better effect than a control condition (1.8 Joules or 6 J/cm2). The average success rate across the first five studies was 84% (SD, 8.9; total hands =171). The average pain duration prior to successful photoradiation was 2 years. Photoradiation is a promising new, conservative treatment for mild/moderate CTS cases (motor latency < 7 msec; needle EMG, normal). It is cost-effective compared to current treatments. C1 VA BOston Healthcare Syst, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Naeser, MA (reprint author), VA BOston Healthcare Syst, 12-A,150 So Huntington Ave, Boston, MA 02130 USA. EM mnaeser@bu.edu NR 47 TC 19 Z9 19 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-5418 J9 PHOTOMED LASER SURG JI Photomed. Laser Surg. PD APR PY 2006 VL 24 IS 2 BP 101 EP 110 DI 10.1089/pho.2006.24.101 PG 10 WC Surgery SC Surgery GA 047EN UT WOS:000237862700001 PM 16706688 ER PT J AU Saffarian, S Qian, H Collier, I Elson, E Goldberg, G AF Saffarian, S Qian, H Collier, I Elson, E Goldberg, G TI Powering a burnt bridges Brownian ratchet: A model for an extracellular motor driven by proteolysis of collagen SO PHYSICAL REVIEW E LA English DT Article ID SKIN FIBROBLAST COLLAGENASE; MOLECULAR MOTORS; I COLLAGEN; GROWING MICROTUBULES; CELL-SURFACE; MATRIX; ACTIVATION; TRANSPORT; MT1-MMP; FORCE AB Biased diffusion of collagenase on collagen fibrils may represent the first observed adenosine triphosphate-independent extracellular molecular motor. The magnitude of force generated by the enzyme remains unclear. We propose a propulsion mechanism based on a burnt bridges Brownian ratchet model with a varying degree of coupling of the free energy from collagen proteolysis to the enzyme motion. When constrained by experimental observations, our model predicts 0.1 pN stall force for individual collagenase molecules. A dimer, surprisingly, can generate a force in the range of 5 pN, suggesting that the motor can be of biological significance. C1 Harvard Univ, Sch Med, Dept Cell Biol, CBR, Boston, MA 02115 USA. Univ Washington, Dept Appl Math, Seattle, WA 98195 USA. Washington Univ, Dept Dermatol, St Louis, MO 63110 USA. Washington Univ, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. RP Saffarian, S (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, CBR, 200 Longwood Ave, Boston, MA 02115 USA. NR 29 TC 25 Z9 25 U1 0 U2 5 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD APR PY 2006 VL 73 IS 4 AR 041909 DI 10.1103/PhysRevE.73.041909 PN 1 PG 5 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 037KU UT WOS:000237146400066 PM 16711838 ER PT J AU Donovan, A Roy, CN Andrews, NC AF Donovan, A Roy, CN Andrews, NC TI The ins and outs of iron homeostasis SO PHYSIOLOGY LA English DT Review ID ERYTHROID 5-AMINOLEVULINATE SYNTHASE; AUTOSOMAL-DOMINANT HEMOCHROMATOSIS; ANTIMICROBIAL PEPTIDE HEPCIDIN; TRANSFERRIN-BOUND IRON; MESSENGER-RNA; ERYTHROPOIETIC PROTOPORPHYRIA; REGULATORY PROTEIN-2; HEREDITARY HEMOCHROMATOSIS; JUVENILE HEMOCHROMATOSIS; SIDEROBLASTIC ANEMIA AB Iron is an essential element that is toxic when it accumulates in excess. Intricate regulatory mechanisms have evolved to maintain iron homeostasis within cells and between different tissues of complex organisms. This review discusses the proteins involved in iron transport and storage and their regulation in health and disease. C1 Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Donovan, A (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM nancy_andrews@hms.harvard.edu OI Andrews, Nancy/0000-0003-0243-4462 NR 107 TC 43 Z9 50 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1548-9213 J9 PHYSIOLOGY JI Physiology PD APR PY 2006 VL 21 BP 115 EP 123 DI 10.1152/physiol.00052.2005 PG 9 WC Physiology SC Physiology GA 033BT UT WOS:000236822000005 PM 16565477 ER PT J AU Kumar, P Lee, SK Shankar, P Manjunath, N AF Kumar, Priti Lee, Sang Kyung Shankar, Premlata Manjunath, N. TI A single siRNA suppresses fatal encephalitis induced by two different flaviviruses SO PLOS MEDICINE LA English DT Article ID WEST-NILE-VIRUS; RNA INTERFERENCE; JAPANESE ENCEPHALITIS; MAMMALIAN-CELLS; GENE-EXPRESSION; BRAIN CANCER; MOUSE-BRAIN; INHIBITION; REPLICATION; INFECTION AB Background Japanese encephalitis virus (JEV) and West Nile virus (WNV) are neurotropic flaviviruses that can cause acute encephalitis with a high fatality rate. Currently there is no effective treatment for these infections. Methods and Findings We tested RNA interference (RNAi)-based intervention to suppress lethal JE and WN encephalitis in mice. To induce RNAi, we used either lentivirally expressed short hairpin RNA (shRNA) or synthetic short interfering RNA (siRNA). As target, we selected the cd loop-coding sequence in domain 11 of the viral Envelope protein, which is highly conserved among all flaviviruses because of its essential role in membrane fusion. Using as a target a species-specific sequence in the cd loop that is conserved only among the different strains of either JEV or WNV, we could achieve specific protection against the corresponding virus. However, by targeting a cross-species conserved sequence within the cd loop, we were able to protect mice against encephalitis induced by both viruses. A single intracranial administration of lentivirally delivered shRNA or lipid-complexed siRNA before viral challenge or siRNA treatment after viral challenge was sufficient for protection against lethal encephalitis. Conclusions RNAi-based intervention affords near complete protection from both JEV- and WNV-induced encephalitis in mice. Our results show, to our knowledge for the first time, that SiRNA can be used as a broad-spectrum antiviral agent for treating encephalitis caused by multiple related viruses. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Hanyang Univ, Dept Bioengn, Seoul 133791, South Korea. RP Shankar, P (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM shankar@cbr.med.harvard.edu; swamy@cbr.med.harvard.edu RI Kumar, Priti/C-5699-2009; OI Kumar, Priti/0000-0002-6901-5601 FU NIAID NIH HHS [U19 AI056900, U19 AI 056900] NR 41 TC 113 Z9 124 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD APR PY 2006 VL 3 IS 4 BP 505 EP 514 AR e96 DI 10.1371/journal.pmed.0030096 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 042RX UT WOS:000237548200019 PM 16464133 ER PT J AU Wolin, KY Colditz, G Stoddarde, AM Emmons, KM Sorensen, G AF Wolin, KY Colditz, G Stoddarde, AM Emmons, KM Sorensen, G TI Acculturation and physical activity in a working class multiethnic population SO PREVENTIVE MEDICINE LA English DT Article DE acculturation; physical activity; immigrant ID MEXICAN-AMERICANS; CANCER PREVENTION; ACTIVITY QUESTIONNAIRE; HEALTHY DIRECTIONS; LEISURE-TIME; BEHAVIORS; HISPANICS; ADULTS; SCALE; REPRODUCIBILITY AB Background. Determinants of physical activity in minority populations remain under-explored. Acculturation is one proposed mechanism for the disparities that exist between racial and ethnic groups in health outcomes. Methods. This cross-sectional study evaluated the relation of language acculturation and generation in the US since migration with leisure-time and occupational activity. A low-income, multiethnic urban population was recruited from Massachusetts small businesses (SB) (n = 1725) and health centers (HC) (n = 2205). Baseline data were collected between May 2000 and February 2002. Results. Individuals with low acculturation reported leisure-time activity 3-5 MET hours/week lower than those who were highly acculturated (P < 0.05). Generation predicted leisure-time activity only in SB participants. In the HC, least acculturated participants reported occupational activity 10-12 MET hours/week higher than highly acculturated participants. In SB men, acculturation was inversely associated with occupational activity; in SB women, language acculturation was positively associated with occupational activity. Generation was not predictive of occupational activity. Conclusion. Language acculturation and generation were positively associated with leisure-time activity. Language acculturation is also associated with occupational activity. Acculturation is important to consider when designing public health interventions. (c) 2006 Elsevier Inc. All rights reserved. C1 Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. New England Res Inst, Watertown, MA 02472 USA. RP Wolin, KY (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1102, Chicago, IL 60611 USA. EM kwolin@northwestern.edu RI Colditz, Graham/A-3963-2009; Wolin, Kathleen/I-2154-2014 OI Colditz, Graham/0000-0002-7307-0291; Wolin, Kathleen/0000-0001-7950-9042 FU NCI NIH HHS [P01 CA 75308, P01 CA075308, R25 CA100600, T32 CA009001, 5T32 CA09001-28, T32 CA009001-28]; NIAID NIH HHS [R25 CA 100600-01AI] NR 37 TC 50 Z9 50 U1 4 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD APR PY 2006 VL 42 IS 4 BP 266 EP 272 DI 10.1016/j.ypmed.2006.01.005 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 037MO UT WOS:000237151200004 PM 16481031 ER PT J AU Xue, P Ci, HL Chen, W Li, YP AF Xue, P Ci, HL Chen, W Li, YP TI Molecular cloning and expression analysis of a novel E1 like gene UBAL in mouse and chicken SO PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS LA Chinese DT Article DE ubiquitin-like proteins; ubiquitin-activating enzyme like protein; cloning; expression profile ID UBIQUITIN; ASYMMETRY; PROTEIN; SYSTEM; HEX AB According the EST sequence contained a UBA-NAD binding domain, a novel gene UBAL (ubiquitin-activating enzyme like protein) was cloning both in mouse and chicken by the homology scanning and EST splicing methods. UBAL contains the conserved domain I of Uba1, ATP binding motif and putative active site Cys. The expression profile of mUBAL was detected in most of the tissues of the 11 investigated tissues, especially in kidney, testis, brain and heart. Whole-mount in situ hybridization with the coding region of mUBAL showed that expression of mUBAL was presented in the early streak stage of mouse embryo and migrated anterior with anterior visceral endoderm (AVE) and then in the telencephalon. The gUBAL expression was also found in the brain of HH14, HH16 and HH18 chick embryos. The conserved structures and expression patterns of UBAL suggested that UBAL may play important roles in the developing brain of embryo and adult tissues as El like enzyme. C1 Beijing Normal Univ, Coll Life Sci, Biomed Res Inst, Beijing 100875, Peoples R China. Chinese Acad Sci, Inst Biophys, Prot Platform, Beijing 100101, Peoples R China. Zhejiang Cell Biomed Res Coll, Hangzhou 310006, Peoples R China. Harvard Univ, Sch Dent Med, Forsyth Inst, Boston, MA 02115 USA. RP Li, YP (reprint author), Beijing Normal Univ, Coll Life Sci, Biomed Res Inst, Beijing 100875, Peoples R China. EM YPLi@forsyth.org NR 14 TC 0 Z9 0 U1 0 U2 0 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1000-3282 J9 PROG BIOCHEM BIOPHYS JI Prog. Biochem. Biophys. PD APR PY 2006 VL 33 IS 4 BP 382 EP 387 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 036CZ UT WOS:000237049800012 ER PT J AU Teicholz, JG AF Teicholz, Judith Guss TI Enactment as therapeutic hand grenade: How bursts of emotional honesty can get a stuck treatment moving again: Discussion of Holly Levenkron's paper SO PSYCHOANALYTIC INQUIRY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat & Psychol, Cambridge, MA 02138 USA. RP Teicholz, JG (reprint author), 127 Mt Auburn St, Cambridge, MA 02138 USA. EM judy_teicholz@yahoo.com NR 19 TC 1 Z9 1 U1 0 U2 0 PU ANALYTIC PRESS PI HILLSDALE PA 101 WEST STREET, HILLSDALE, NJ 07642 USA SN 0735-1690 J9 PSYCHOANAL INQ JI Psychoanal. Inq. PD APR-MAY PY 2006 VL 26 IS 2 BP 263 EP 278 PG 16 WC Psychology, Psychoanalysis SC Psychology GA 081BE UT WOS:000240291400009 ER PT J AU Rifai, MA Moles, JK Lehman, LP Van der Linden, BJ AF Rifai, MA Moles, JK Lehman, LP Van der Linden, BJ TI Hepatitis C screening and treatment outcomes in patients with substance use/dependence disorders SO PSYCHOSOMATICS LA English DT Article ID ADDICTION SEVERITY INDEX; NONINJECTING DRUG-USERS; UNITED-STATES VETERANS; SERVICES TASK-FORCE; VIRUS-INFECTION; ALCOHOL-CONSUMPTION; DEPENDENT PATIENTS; LIVER-CIRRHOSIS; PLUS RIBAVIRIN; PREVALENCE AB The authors evaluated the association between hepatitis C virus ( HCV) seropositivity status and substance use treatment outcomes in an alcohol- and substance-dependent population undergoing rehabilitation. The second aim was to assess the impact of early screening for HCV infection and substance use treatment on HCV treatment outcomes. HCV-antibody testing of 338 patients attending a substance-use residential program was performed. HCV antibody status, lifetime comorbid psychiatric diagnoses, program completion rates, and 6-month abstinence rates after program discharge were assessed. HCV treatment outcomes were followed in patients who remained abstinent 6 months after completion of substance-use treatment. Almost one-fourth ( 23.1%) of patients were HCV antibody-positive. HCV-seropositive patients were more likely to complete the 28-day program and more likely to remain abstinent at 6 months after program discharge. HCV seropositive status was the strongest predictor for the likelihood of completing the program, and remaining abstinent for 6 months afterward. Patients with HCV who completed a substance-use treatment program were more likely to receive HCV treatment than substance-dependent patients with HCV who never attended a substance-use treatment program. Detecting HCV infection in the structured setting of substance-use treatment is ideal to initiate management of this infection, and it has a positive influence on the outcomes of both substance-use treatment and HCV treatment. C1 Univ Virginia, Sch Med, Salem, VA USA. Vet Affairs Med Ctr, Salem, VA USA. RP Rifai, MA (reprint author), Portland VA Med Ctr, NW Hepatitis C Res Ctr, POB 1034,P3MHADM, Portland, OR 97239 USA. EM AlyRifai@aol.com NR 44 TC 22 Z9 22 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD APR PY 2006 VL 47 IS 2 BP 112 EP 121 DI 10.1176/appi.psy.47.2.112 PG 10 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 017BR UT WOS:000235669600003 PM 16508022 ER PT J AU Mrus, JM Schackman, BR Wu, AW Freedberg, KA Tsevat, J Yi, MS Zackin, R AF Mrus, JM Schackman, BR Wu, AW Freedberg, KA Tsevat, J Yi, MS Zackin, R TI Variations in self-rated health among patients with HIV infection SO QUALITY OF LIFE RESEARCH LA English DT Article DE AIDS; clinical trials; HIV; quality of life ID QUALITY-OF-LIFE; HUMAN-IMMUNODEFICIENCY-VIRUS; COST-EFFECTIVENESS; ANTIRETROVIRAL THERAPY; RACIAL-DIFFERENCES; UNITED-STATES; CLINICAL-TRIAL; MENTAL-HEALTH; DISEASE; MORTALITY AB Purpose:To assess how patients with HIV who are enrolled in a clinical trials cohort rate their health and to compare their ratings with those of patients with HIV from 2 other cohorts: the HIV Cost and Services Utilization Study (HCSUS), and Adult AIDS Clinical Trials Group protocol 320 (ACTG 320). Methods: We analyzed baseline information for the 1649 subjects enrolled in the Adult AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT) study prior to March 2002 who had self-rated health data available. We compared those results with results from 2 other groups: HCSUS, the only nationally representative sample of people in care for HIV in the U.S., which conducted baseline interviews in 1996 and 1997, and ACTG 320, a randomized, double-blinded, placebo-controlled trial comparing a 3-drug antiretroviral regimen with a 2-drug combination, which enrolled subjects in the same general time frame as HCSUS. We used t tests, Pearson correlations, and linear regression to determine factors associated with self-rated health and z scores to compare results between cohorts. Results: The mean (SD) rating scale value on a 0-100 scale for ALLRT participants was 79.8 (16.8). Values were significantly lower for subjects who were older, had a history of injection drug use, had lower CD4 cell counts, or were beginning salvage antiretroviral therapy. Subjects in ALLRT reported significantly better self-rated health at baseline than those in HCSUS or ACTG 320 (11-12% higher rating scale values in ALLRT; p < 0.05). When cohort differences were accounted for through regression and stratification, the differences in scores between subjects in ALLRT and HCSUS increased and the differences in scores between subjects in ALLRT and ACTG 320 diminished. Conclusions: Self-rated health varied significantly by age, CD4 count, injection drug use history, and salvage therapy status. Differences in self-rated health for clinical trials and non-clinical trials samples appear to be substantial and should be considered when applying trial results to clinical populations. C1 Cincinnati VA Med Ctr, Hlth Serv Res & Dev, Cincinnati, OH USA. Univ Cincinnati, Med Ctr, Dept Internal Med, Cincinnati, OH USA. Univ Cincinnati, Med Ctr, Inst Study Hlth, Cincinnati, OH USA. Cornell Univ, Weill Med Coll, Dept Publ Hlth, Ithaca, NY 14853 USA. Johns Hopkins Univ, Dept Hlth Policy & Management, Baltimore, MD USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. RP Mrus, JM (reprint author), GlaxoSmithKline Inc, Infect Dis Med Dev Ctr, POB 13398, Res Triangle Pk, NC 27709 USA. EM joseph.m.mrus@gsk.com FU NCCIH NIH HHS [K24-AT001676, K24 AT001676]; NIAID NIH HHS [K24-AI062476, U01 AI027668, U01 AI025897, P30 AI060354, U01-AI25897, U01-AI27668, K24 AI062476, U01-AI46386, U01 AI046386, R01-AI42006, U01-AI38855, U01 AI038858, U01-AI42006, R01 AI042006, U01 AI038855, P30-AI060354, U01-AI38858]; NICHD NIH HHS [K23 HD044556, K23-HD044556]; NIDA NIH HHS [K01 DA017179, K01-DA017179] NR 46 TC 7 Z9 7 U1 0 U2 1 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 2006 VL 15 IS 3 BP 503 EP 514 DI 10.1007/s11136-005-1946-4 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 023BN UT WOS:000236100300020 PM 16547789 ER PT J AU Thrall, JH AF Thrall, JH TI Leadership and organizational development: Lessons from the USS Constitution and the age of fighting sail SO RADIOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, M2-FND 216,Box 9657,14 Fruit St, Boston, MA 02114 USA. EM thrall.james@mgh.harvard.edu NR 25 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2006 VL 239 IS 1 BP 5 EP 9 DI 10.1148/radiol.2391051895 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 030XQ UT WOS:000236669100003 PM 16567478 ER PT J AU Zalis, ME Perumpillichira, JJ Magee, C Kohlberg, G Hahn, PF AF Zalis, ME Perumpillichira, JJ Magee, C Kohlberg, G Hahn, PF TI Tagging-based, electronically cleansed CT colonography: Evaluation of patient comfort and image readability SO RADIOLOGY LA English DT Article ID COLORECTAL-CANCER; CONVENTIONAL COLONOSCOPY; NEOPLASIA AB Purpose: To prospectively compare the homogeneity, adequancy, and patient acceptance of nonionic iodine-based regimens with those of a barium-based regimen for computed tomographic (CT) colonography with electronic subtraction cleansing. Materials and Methods: After institutional review board approval and informed consent wee obtained, 68 subjects (41 men (60%) men, 27 (40%) women : mean age, 60 years +/- 6 [standard deviation]) with average or moderate risk factors for development of colorectal carcinoma were recruited and placed into three groups. Group 1 (n = 25) ingested 150-mL aliquots of 2% barium sulfate suspension with meals and snacks for 48 hours prior to imaging. without other diet modification or a cathartic. Group 2 (n = 21) ingested 10-mL aliguots of nonionic iodinated contrast material (iopromide) with a concentration of 300 mg per millimeter with meals and snacks fro 2 days before imaging without diet modification or a cathartic. Group 3 (n = 22) ingested nonionic iodinated contrastmaterial (iohexol) with a concentration of 300 mg per milliliter with meals and snacks for 2 days before imaging and ingested 64g of colonography was also performed on 10 control subjects who ingested polyethylene glycol electrolyte solution prior to imaging . Subjective and numerical measures of bowel preparation quality, homogeneity, and patient comfort among the noncathartic and cathartic cohorts were compared with nonparametric analysis of variance, the Fisher exact test, and the F test, as appropriate. The study was HPIAA compliant. Results: Study subjects who recieved tagging preperations reported significantly improved discomfort scores when compared with those of the control subjects (P < .05 each comparison). There was no significant difference in discomfort scores among groups 1,2 and 3. For each reader, scores of subtracted image readability were highest for group 3. Dichotomized rates of preperation "success" were also greatest for group 3. Conclusion: In this series, the patient discomfort scores were significantly improvedwith tagging preparations for CT colonography. Nonionic iodinated contrast material in conjunction with hypoerosmotic laxative (magnesium citrate) was associated with the best subjective and numerical indices of readability. (c) RSNA, 2006 C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Zalis, ME (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. EM mzalis@mgh.harvard.edu FU NCI NIH HHS [1K22 CA 098422-01A1] NR 20 TC 72 Z9 73 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 2006 VL 239 IS 1 BP 149 EP 159 DI 10.1148/radiol.2383041308 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 030XQ UT WOS:000236669100019 PM 16567485 ER PT J AU Caruso, PA Watkins, LM Suwansaard, P Yamamoto, M Durand, ML Romo, LV Rincon, SP Curtin, HD AF Caruso, PA Watkins, LM Suwansaard, P Yamamoto, M Durand, ML Romo, LV Rincon, SP Curtin, HD TI Odontogenic orbital inflammation: Clinical and CT findings - Initial observations SO RADIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; CELLULITIS AB To retrospectively review computed tomographic (CT) and clinical findings in patients with odontogenic orbital infection. Materials and Approval front the institutional review board was obtained Methods: for chart. and scan review. and informed consent was waived for this HIPAA-compliant study. Five patients. two male and three female (median age. 37 years; age range, 13-55 years), who had odontogenic orbital cellulitis underwent clinical evalutation, CT scanning. and treatment. CT findings, including periapical lucency suggesting abscess, shins opacification, and the route of spread of infection, were analyzed in each patient. Imaging, clinical, find surgical findings, including the initial clinical diagnosis and the presence of a periapical abscess fit surgery, and at pathologic examination. were compared. Results: Periapical lucency and Sinus opacification were seen in all patients. The route or infection spread was through either the premalar soft tissues or the maxillary sinuses. The odontogenic origin of the orbital infection was not clinically suspected in ally patients. Correct diagnosis was later made at CT in all patients. Four patients had periapical abscesses at pathologic analysis, and the fifth patient had apical periodontitis at clinical analysis and granuloma at pathologic analysis. Dental surgery was required in each or the five patients for resolution of infection; four patients underwent extraction of the infected tooth, and one patient underwent. incision and drainage of a periapical abscess. Conclusion: Abnormal periapical lucency, widening or the periodontal ligament space, and the presence of a subperiosteal abscess suggested an odontogenic origin of orbital infection. (c) RSNA, 2006. C1 Harvard Univ, Sch Med, Dept Radiol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Phramongkutklao Hosp, Dept Radiol, Bangkok, Thailand. Phramongkutklao Med Sch, Bangkok, Thailand. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. RP Caruso, PA (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM paul_caruso@meei.harvard.edu NR 14 TC 14 Z9 18 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2006 VL 239 IS 1 BP 187 EP 194 DI 10.1148/radiol.2391041243 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 030XQ UT WOS:000236669100024 PM 16567486 ER PT J AU Benner, T Wisco, JJ van der Kouwe, AJW Fischl, B Vangel, MG Hochberg, FH Sorensen, AG AF Benner, T Wisco, JJ van der Kouwe, AJW Fischl, B Vangel, MG Hochberg, FH Sorensen, AG TI Comparison of manual and automatic section positioning of brain MR images SO RADIOLOGY LA English DT Article ID MULTIPLE-SCLEROSIS; LESION VOLUME; REGISTRATION; ERROR; SEGMENTATION; VARIABILITY; RELIABILITY; SERIAL; LOAD AB The study protocol was approved by the institutional review board and was in full compliance with HIPAA guidelines. Informed consent, was obtained from all patients. The purpose of this study was to prospectively compare intra- and intersubject variability of manual versus antomatic magnetic resonance (MR) imaging section prescription. In two examinations, T2-weighted series were acquired with both methods. All intrasubject and three of six intersubject section prescription variances were significantly higher for manual prescription (P <.01). Root mean square errors confirmed better coregistration of the automated approach (P <.001). Automatic section prescription leads to improved reproducibility of imaging orientations for intra- and intersubject series in clinical practice. (c) RSNA, 2006. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr,Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr,Gen Clin Res Ctr, Charlestown, MA 02129 USA. MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. RP Benner, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr,Dept Radiol, 149 13th St,Rm 2301, Charlestown, MA 02129 USA. EM thomas.benner@nmr.mgh.harvard.edu FU NCI NIH HHS [5T32 CA 09502]; NCRR NIH HHS [P41 RR 14075, R01 RR 16594-01A1, U24 RR 021382]; NIBIB NIH HHS [R01 EB 001550, R21 EB 02530] NR 25 TC 31 Z9 31 U1 0 U2 3 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 2006 VL 239 IS 1 BP 246 EP 254 DI 10.1148/radiol.2391050221 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 030XQ UT WOS:000236669100032 PM 16507753 ER PT J AU Schulte-Hermann, R Wogan, GN Berry, C Brown, NA Czeizel, A Giavini, E Holmes, LB Kroes, R Nau, H Neubert, D Oesch, F Ott, T Pelkonen, O Robert-Gnansia, E Sullivan, FM AF Schulte-Hermann, R Wogan, GN Berry, C Brown, NA Czeizel, A Giavini, E Holmes, LB Kroes, R Nau, H Neubert, D Oesch, F Ott, T Pelkonen, O Robert-Gnansia, E Sullivan, FM TI Analysis of reproductive toxicity and classification of glufosinate-ammonium SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Review DE glufosinate-ammonium; reproductive effects; toxicology; regulatory; European Commission ID UNADENYLYLATED GLUTAMINE-SYNTHETASE; DOSE-RESPONSE RELATIONSHIPS; AMINO-ACIDS; MOUSE EMBRYOS; USE INFORMATION; SALMONELLA-TYPHIMURIUM; ALKYLATING-AGENTS; RISK ASSESSMENT; RHESUS-MONKEYS; PREGNANT RATS AB Conclusion regarding classification of glufosmate-ammonium. Science Partners' Evaluation Group (Evaluation Group) has conducted an independent analysis of the herbicide glufosinate-ammonium (GA) relative to its potential to cause reproductive toxicity in humans. Further, the Evaluation Group has evaluated the implementation of Annex 6 of Commission Directive 2001/59/EC (28th ATP of Council Directive 67/548/EEC) and Council Directive 91/414/EEC, with respect to classification of chemicals posing potential reproductive hazards. After consideration of all information available to us relevant to the potential of glufosinate-ammonium (GA) to cause reproductive toxicity, the Science Partners Evaluation Group concludes that no classification of GA is justified. The following form the basis of this conclusion. There are no human data to suggest that GA causes reproductive toxicity in women or in their conceptus. The issue concerning possible reproductive hazard to humans is raised solely on the basis of positive animal test results that show GA to cause preimplantation or implantation losses in rats. Specifically: a. Daily treatment with GA had no detectable effect on the earliest stages of the reproductive sequence including gametogenesis, ovulation, mating and conception; b. Treatment with GA interfered with rat gestation before and at the stage when the conceptus implants into the uterus. This effect occurred at doses of 360 ppm in the feed (corresponding to daily doses of 27.8 mg/kg bw) and above; and c. After implantation, no further effect of GA on prenatal and post-natal development was recognized. Previous concerns that GA might be toxic to embryonic stages after implantation were not supported by the data. Abortions and stillbirth seen were associated with, and regarded as secondary to, maternal toxicity. There was no evidence suggesting the induction of malformations in the offspring. The mechanism underlying this adverse effect in experimental laboratory animals is identified-inhibition of glutamine synthetase. Glutamine is essential to the viability of the embryo. The embryo is dependent on a maternal source of the amino acid. For embryo lethality to occur, a significant reduction of maternal glutamine is required. Such reduction in maternal glutamine depends on a significant inhibition of glutamine synthetase by GA. This can only occur when the mother is exposed to very high levels of GA. Specifically: a. The reproductive toxicity of GA is confined to very short, early stages of reproduction, during which the conceptus is dependent on maternal glutamine; and b. In order for the effect to occur, significant reduction in maternal blood glutamine level is required, which in turn depends on a significant inhibition of glutamine synthetase, induced by high levels of GA in the maternal system. There is no evidence for accumulation of GA in the mammalian organism beyond a factor of two and no evidence for its metabolic toxification. To raise a concern in humans, women would have to be exposed to GA during the very limited time frame of preimplantation or implantation and the exposure would have to be to the exceedingly high levels necessary to alter the maternal metabolism and, correspondingly, result in glutamine levels in maternal tissue and blood plasma being drastically reduced. There is no basis to suggest that such exposures would occur under conditions of normal handling and use. Specifically: a. Under conditions of normal handling and use, operators would never be exposed to GA levels that could potentially inhibit glutamine synthetase to the extent that this inhibition could impair preimplantation or implantation. b. All acceptable exposure measurements and predictive calculations confirm this conclusion, and in fact demonstrate that reasonably foreseeable exposure of workers would be to levels significantly below the AOEL. c. The evidence is also clear that there is no reproductive toxicity hazard to workers upon reentry tosprayed fields, bystanders, consumers or toddlers. The safety margin compared to the NOAEL in animal studies is sufficiently large to assure protection of the health of workers using GA as well as bystanders, consumers, and toddlers. Pursuant to Annex 6 of Commission Directive 2001/59/EC (28th ATP of Council Directive 67/548/EEC), to justify a classification of category 2 there must be sufficient evidence to produce a strong presumption that human exposure to the substance may result in impaired fertility in humans. It is the conclusion of the Science Partners Evaluation Group that there is no reasonable evidence to suggest a strong presumption of impairment. To the contrary, there is clear evidence demonstrating a strong presumption that exposure to GA would not cause the adverse effect demonstrated in rats. Pursuant to Annex 6 of Commission Directive 2001/59/EC (28th ATP of Council Directive 67/548/EEC), to justify a classification of category 3, there must be sufficient evidence to provide a strong suspicion of impaired fertility in humans. There is no basis to conclude that the animal data demonstrating impaired preimplantation or implantation has any relevance to humans in that the effect found in rats only occurs at levels which would never be experienced by workers under conditions of normal handling and use or by bystanders, consumers, or toddlers. C1 Med Univ Vienna, Div Toxicol & Prevent, Vienna, Austria. Sci Partners LLC, Cambridge, MA USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. Queen Mary Univ London, Dept Pathol, London, England. St Georges Univ London, Div Basic Med Sci, London, England. Fdn Community Control Hereditary Dis, Budapest, Hungary. Univ Milan, Inst Biol, I-20122 Milan, Italy. Harvard Univ, Dept Pediat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Genet, Perinatal Diagnost Unit, Genet & Teratol Unit, Boston, MA 02114 USA. Sch Vet Med, Dept Food Toxicol, Hannover, Germany. Dept Clin Pharmacol & Toxicol, Berlin, Germany. Johannes Gutenberg Univ Mainz, Inst Toxicol, D-6500 Mainz, Germany. Univ Oulu, Dept Pharmacol & Toxicol, Oulu, Finland. Inst Europeen Genomutat, Lyon, France. RP Wogan, GN (reprint author), Sci Partners, 245 1st St,Suite 1800, Cambridge, MA 02142 USA. EM geraldwogan@sciencepartners.com NR 140 TC 6 Z9 7 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD APR PY 2006 VL 44 IS 3 SU 1 BP S1 EP S76 PG 76 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 034DC UT WOS:000236904200001 PM 16510221 ER PT J AU Hess, DR Peters, JI AF Hess, DR Peters, JI TI Respiratory care of patients with "other" conditions SO RESPIRATORY CARE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, Div Pulm Dis Crit Care Med, San Antonio, TX USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESPIR CARE JI Respir. Care PD APR PY 2006 VL 51 IS 4 BP 355 EP 356 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 031SI UT WOS:000236723900001 ER PT J AU Hospenthal, MAC AF Hospenthal, MAC TI Diagnosis and management of idiopathic pulmonary fibrosis: Implications for respiratory care SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT 21st Annual New Horizons Symposium CY DEC 04, 2005 CL San Antonio, TX DE interstitial; lung diseases; pulmonary fibrosis; pulmonary function testing; fibrosing alveolitis; lung biopsy; management ID INTERSTITIAL LUNG-DISEASES; HAMMAN-RICH SYNDROME; PATHOGENESIS; ACCURACY; PNEUMONIA; BIOPSY; EPIDEMIOLOGY; ALVEOLITIS; THERAPY; SMOKING AB Although poorly understood, idiopathic pulmonary fibrosis is the most common of the idiopathic interstitial lung diseases. Its etiology is unknown, but how this fibrotic process develops in the lung has been studied over the last 60 years. It is a relatively rare disease, afflicting those 50-70 years of age, slightly more common among men than women, without racial predilection. The most common complaint is progressive shortness of breath. Pulmonary function testing reveals a restrictive ventilatory defect with a diminished diffusion capacity. The lungs demonstrate fibrotic and cystic areas interspersed with normal lung on radiographic and pathologic examination. No definitive medical treatment is available, although most patients are given trials of corticosteroids, alone or in combination with cytotoxic agents. On average, patients survive 2-4 years after diagnosis. Lung transplantation has been the only therapy shown to improve survival of those with idiopathic pulmonary fibrosis. C1 Univ Texas, Hlth Sci Ctr, Div Pulm & Crit Care Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Hospenthal, MAC (reprint author), Audie Murphy Mem Vet Affairs Hosp, 7400 Merton Minter Blvd,111E, San Antonio, TX 78229 USA. EM hospenthal@uthscsa.edu NR 55 TC 4 Z9 5 U1 0 U2 2 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESPIR CARE JI Respir. Care PD APR PY 2006 VL 51 IS 4 BP 382 EP 391 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 031SI UT WOS:000236723900004 PM 16563193 ER PT J AU Levine, SM Angel, LF AF Levine, SM Angel, LF TI The patient who has undergone lung transplantation: Implications for respiratory care SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT 21st Annual New Horizons Symposium CY DEC 04, 2005 CL San Antonio, TX DE lung transplantation; postoperative; rejection; obliterative bronchiolitis; post-operative management; patient assessment ID BRONCHIOLITIS-OBLITERANS-SYNDROME; ISHLT WORKING GROUP; HIGH-RESOLUTION CT; PRIMARY GRAFT FAILURE; INHALED NITRIC-OXIDE; QUALITY-OF-LIFE; HEART-LUNG; RISK-FACTORS; PULMONARY TRANSPLANTATION; INVASIVE ASPERGILLOSIS AB Lung transplantation is now performed in patients with end-stage pulmonary parenchymal or vascular lung disease. The process of evaluating a patient for transplantation, managing the patient during the peri-operative period, and caring for the patient following transplantation is complex. Lung-transplant recipients are prone to unique complications of lung transplantation, as well as general complications of an immunosuppressed host. This article reviews the indications for, expected outcomes of, and management of complications that can develop following lung transplantation. Respiratory therapists play an instrumental role in assisting in the management of this group of patients in the pretransplant and post-transplant periods, and in their long-term management. C1 Univ Texas, Hlth Sci Ctr, Div Pulm & Crit Care Med, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Cardiothorac Surg, San Antonio, TX 78229 USA. RP Levine, SM (reprint author), Univ Texas, Hlth Sci Ctr, Div Pulm & Crit Care Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM levines@uthscsa.edu NR 112 TC 0 Z9 0 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESPIR CARE JI Respir. Care PD APR PY 2006 VL 51 IS 4 BP 392 EP 402 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 031SI UT WOS:000236723900005 PM 16563192 ER PT J AU Chan, RVP Lee, TC Chaganti, RK Cestari, DM Kim, MT Lee, S AF Chan, R. V. Paul Lee, Thomas C. Chaganti, R. Krishna Cestari, Dean M. Kim, Marshall T. Lee, Sangwoo TI Macular star associated with Behcet disease SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE Behcet disease; macular star; uveitis ID OPTIC DISK EDEMA; DIAGNOSIS C1 Cornell Univ, New York Presbyterian Hosp, Retina Serv, Weill Med Coll, New York, NY 10021 USA. Hosp Special Surg, Rheumatol Serv, New York, NY 10021 USA. New York Hosp, Ophthalmol Serv, Flushing, NY USA. RP Chan, RVP (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 12th Floor,243 Charles St, Boston, MA 02114 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD APR PY 2006 VL 26 IS 4 BP 468 EP 470 PG 3 WC Ophthalmology SC Ophthalmology GA 100QX UT WOS:000241684800014 PM 16603968 ER PT J AU Menke, MN Kim, EC Bula, DV Bertram, KM Arroyo, JG AF Menke, Marcel N. Kim, Eva C. Bula, Deisy V. Bertram, Kurt M. Arroyo, Jorge G. TI The question of macular hole: Avulsed epiretinal membrane shadowing artifact in optical coherence tomography testing SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE epiretinal membrane; imaging artifacts; macular hole; optical coherence tomography C1 Beth Israel Deaconess Med Ctr, Div Ophthalmol, Retina Serv, Boston, MA 02215 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Schepens Retina Assoc Fdn, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Arroyo, JG (reprint author), Beth Israel Deaconess Med Ctr, Div Ophthalmol, Retina Serv, Shapiro 5th Floor,330 Brookline Ave, Boston, MA 02215 USA. EM jarroyo@bidmc.harvard.edu NR 5 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD APR PY 2006 VL 26 IS 4 BP 473 EP 475 DI 10.1097/00006982-200604000-00017 PG 3 WC Ophthalmology SC Ophthalmology GA 100QX UT WOS:000241684800017 PM 16603971 ER PT J AU Yang, WH Yu, JH Gulick, T Bloch, KD Bloch, DB AF Yang, WH Yu, JH Gulick, T Bloch, KD Bloch, DB TI RNA-associated protein 55 (RAP55) localizes to mRNA processing bodies and stress granules SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE mRNA processing body; stress granule; mRNA decay; autoantigen ID PROTEIN COMPLEX; CELL-CYCLE; GW BODIES; P-BODIES; SITES; STABILITY; COMPONENT; ELEGANS; GW182; DECAY AB The mRNA processing body (P-body) is a cellular structure that has an important role in mRNA degradation. P-bodies have also been implicated in RNAi-mediated post-transcriptional gene silencing. The objective of this study was to identify and characterize novel components of the mammalian P-body. Approximately 5% of patients with the autoimmune disease primary biliary cirrhosis have antibodies directed against this structure. Serum from one of these patients was used to identify a cDNA encoding RAP55, a 463-amino acid protein. RAP55 colocalized with previously identified P-body components DCP1a and Ge-1. RAP55 contains an N-terminal Sm-like domain and two C-terminal RGG-rich domains separated by an FDF motif. The two RGG domains and the FDF domain were necessary and sufficient to target the protein to P-bodies. A fragment of RAP55 consisting of the FDF and the second RGG domains did not localize to P-bodies, but was able to displace other P-body components from this structure. After cells were subjected to arsenite-induced stress, RAP55 was detected in TIA-containing stress granules. The second RGG domain was necessary and sufficient for stress granule localization. siRNA-mediated knock-down of RAP55 resulted in loss of P-bodies, suggesting that RAP55 acts prior to the 5'-decapping step in mRNA degradation. The results of this study show that RAP55 is a component of P-bodies in cells at rest and localizes in stress granules in arsenite-treated cells. RAP55 may serve to shuttle mRNAs between P-bodies and stress granules. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr Gen Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bloch, DB (reprint author), Massachusetts Gen Hosp E, CNY 8302,149 13th St, Charlestown, MA 02129 USA. EM bloch@helix.mgh.harvard.edu FU NHLBI NIH HHS [HL070896, HL074352, R01 HL070896, R01 HL074352]; NIDDK NIH HHS [DK051179] NR 30 TC 90 Z9 96 U1 1 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD APR PY 2006 VL 12 IS 4 BP 547 EP 554 DI 10.1261/rna.2302706 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 031JH UT WOS:000236700200003 PM 16484376 ER PT J AU Carothers, JM Davis, JH Chou, JJ Szostak, JW AF Carothers, JM Davis, JH Chou, JJ Szostak, JW TI Solution structure of an informationally complex high-affinity RNA aptamer to GTP SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE aptamer; NMR; affinity; in vitro selection; information; complexity ID RESIDUAL DIPOLAR COUPLINGS; NUCLEIC-ACID APTAMERS; BINDING RNA; MOLECULAR DISCRIMINATION; LIGAND-BINDING; NMR; RIBOZYME; RECOGNITION; ATP; MACROMOLECULES AB Higher-affinity RNA aptamers to GTP are more informationally complex than lower-affinity aptamers. Analog binding studies have shown that the additional information needed to improve affinity does not specify more interactions with the ligand. In light of those observations, we would like to understand the structural characteristics that enable complex aptamers to bind their ligands with higher affinity. Here we present the solution structure of the 41-nt Class I GTP aptamer (K(d) = 75 nM) as determined by NMR. The backbone of the aptamer forms a reverse-S that shapes the binding pocket. The ligand nucleobase stacks between purine platforms and makes hydrogen bonds with the edge of another base. Interestingly, the local modes of interaction for the Class I aptamer and an RNA aptamer that binds ATP with a K(d)of 6 mu M are very much alike. The aptamers exhibit nearly identical levels of binding specificity and fraction of ligand sequestered from the solvent (81% - 85%). However, the GTP aptamer is more informationally complex (similar to 45 vs. 35 bits) and has a larger recognition bulge (15 vs. 12 nucleotides) with many more stabilizing base - base interactions. Because the aptamers have similar modes of ligand binding, we conclude that the stabilizing structural elements in the Class I aptamer are responsible for much of the difference in Kd. These results are consistent with the hypothesis that increasing the number of intra-RNA interactions, rather than adding specific contacts to the ligand, is the simplest way to improve binding affinity. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Simches Res Ctr 7215, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu RI Chou, James/N-9840-2013 FU NIGMS NIH HHS [F32 GM017438, GM17438, GM53936, R01 GM053936] NR 52 TC 41 Z9 42 U1 2 U2 22 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD APR PY 2006 VL 12 IS 4 BP 567 EP 579 DI 10.1261/rna.2251306 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 031JH UT WOS:000236700200006 PM 16510427 ER PT J AU Sim, K DeWitt, I Ditman, T Zalesak, M Greenhouse, I Goff, D Weiss, AP Heckers, S AF Sim, K DeWitt, I Ditman, T Zalesak, M Greenhouse, I Goff, D Weiss, AP Heckers, S TI Hippocampal and parahippocampal volumes in schizophrenia: A structural MRI study SO SCHIZOPHRENIA BULLETIN LA English DT Article DE medial temporal lobe; entorhinal; perirhinal; parahippocampal; region; functional ID MEDIAL TEMPORAL-LOBE; ENTORHINAL CORTEX; RECOGNITION MEMORY; ALZHEIMERS-DISEASE; BRAIN MORPHOLOGY; GYRUS; REDUCTION; REGION; PATHOLOGY; ANTERIOR AB Smaller medial temporal lobe volume is a frequent finding in studies of patients with schizophrenia, but the relative contributions of the hippocampus and three surrounding cortical regions (entorhinal cortex, perirhinal cortex, and parahippocampal cortex) are poorly understood. We tested the hypothesis that the volumes of medial temporal lobe regions are selectively changed in schizophrenia. We studied 19 male patients with schizophrenia and 19 age-matched male control subjects. Hippocampal and cortical volumes were estimated using a three-dimensional morphometric protocol for the analysis of high-resolution structural magnetic resonance images, and repeated measures ANOVA was used to test for region-specific differences. Patients had smaller overall medial temporal lobe volumes compared to controls. The volume difference was not specific for either region or hemisphere. The finding of smaller medial temporal lobe volumes in the absence of regional specificity has important implications for studying the functional role of the hippocampus and surrounding cortical regions in schizophrenia. C1 Harvard Univ, Sch Med, McLean Hosp, Schizophrenia & Bipolar Disorders Program, Belmont, MA 02478 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Woodbridge Hosp, Inst Mental Hlth, Singapore, Singapore. RP Sim, K (reprint author), Harvard Univ, Sch Med, McLean Hosp, Schizophrenia & Bipolar Disorders Program, Mill St, Belmont, MA 02478 USA. EM ksim@mclean.harvard.edu RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 FU NIMH NIH HHS [R01 MH070560] NR 81 TC 39 Z9 40 U1 1 U2 7 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 2006 VL 32 IS 2 BP 332 EP 340 DI 10.1093/schbul/sbj030 PG 9 WC Psychiatry SC Psychiatry GA 023DV UT WOS:000236106600027 PM 16319377 ER PT J AU Lee, SH Wynn, JK Green, MF Kim, H Lee, KJ Nam, M Park, JK Chung, YC AF Lee, SH Wynn, JK Green, MF Kim, H Lee, KJ Nam, M Park, JK Chung, YC TI Quantitative EEG and low resolution electromagnetic tomography (LORETA) imaging of patients with persistent auditory hallucinations SO SCHIZOPHRENIA RESEARCH LA English DT Article DE auditory hallucination; schizophrenia; gamma and beta frequency oscillation; qEEG; LORETA ID CHRONIC-SCHIZOPHRENIA; CORTEX; BRAIN; SYNCHRONIZATION; OSCILLATIONS; GAMMA; NEUROANATOMY; POTENTIALS; INCREASES; VOICES AB Electrophysiological studies have demonstrated gamma and beta frequency oscillations in response to auditory stimuli. The purpose of this study was to test whether auditory hallucinations (AH) in schizophrenia patients reflect abnormalities in gamma and beta frequency oscillations and to investigate source. generators of these abnormalities. This theory was tested using quantitative electroencephalography (qEEG) and low-resolution electromagnetic tomography (LORETA) source imaging. Twenty-five schizophrenia patients with treatment refractory AH, lasting for at least 2 years, and 23 schizophrenia patients with non-AH (N-AH) in the past 2 years were recruited for the study. Spectral analysis of the qEEG and source imaging of frequency bands of artifact-free 30 s epochs were examined during rest. AH patients showed significantly increased beta I and beta 2 frequency amplitude compared with N-AH patients. Gamma and beta (2 and 3) frequencies were significantly correlated in AH but not in N-AH patients. Source imaging revealed significantly increased beta (I and 2) activity in the left inferior parietal lobule and the left medial frontal gyrus in AH versus N-AH patients. These results imply that AH is reflecting increased beta frequency oscillations with neural generators localized in speech-related areas. (c) 2006 Elsevier B.V. All rights reserved. C1 Inje Univ, Coll Med, Ilsanpaik Hosp, Dept Psychiat, Goyang 411706, South Korea. Univ Calif Los Angeles, Psychiat & Behav Sci, Los Angeles, CA USA. VA Greater Los Angles Healthcare Syst, Los Angeles, CA USA. RP Lee, SH (reprint author), Inje Univ, Coll Med, Ilsanpaik Hosp, Dept Psychiat, 2240 Daehwa Dong, Goyang 411706, South Korea. EM lshpss@hailmail.net RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 NR 37 TC 46 Z9 47 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2006 VL 83 IS 2-3 BP 111 EP 119 DI 10.1016/j.schres.2005.11.025 PG 9 WC Psychiatry SC Psychiatry GA 035OW UT WOS:000237012200001 PM 16524699 ER PT J AU Makris, N Goldstein, JM Kennedy, D Hodge, SM Caviness, VS Faraone, SV Tsuang, MT Seidman, LJ AF Makris, N Goldstein, JM Kennedy, D Hodge, SM Caviness, VS Faraone, SV Tsuang, MT Seidman, LJ TI Decreased volume of left and total anterior insular lobule in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Review DE schizophrenia; MRI; insula ID FUNCTIONAL MAGNETIC-RESONANCE; OLD-WORLD MONKEY; POSTERIOR PARIETAL CORTEX; 1ST EPISODE SCHIZOPHRENIA; ENTORHINAL AREA 28; ADULT HUMAN BRAIN; RHESUS-MONKEY; TEMPORAL-LOBE; HIPPOCAMPAL VOLUME; INTERHEMISPHERIC PROJECTIONS AB The insula is anatomically situated to be critically involved in many bio-behavioral functions impaired in schizophrenia. Furthermore, its total volume has been shown to be reduced in schizophrenia. In the present study, we tested the hypothesis that in schizophrenia it is the anterior insular lobule (aINS(lbl)) rather than the posterior insular lobule (pINS(lbl)) that is smaller, given that limbic system abnormalities are central in schizophrenia and that the affiliations of the limbic system are principally with the anterior insular lobule. We used T1-weighted high resolution magnetic resonance imaging (MRI) to measure the cortical volume of the left and right anterior and posterior insular subdivisions. The subjects included a sample of healthy community controls (N=40) and chronic patients with DSM-III-R schizophrenia (N=41). We correlated insula volumes with positive and negative symptoms. We found that the total aINS(lbl), and the left aINS(lbl) in particular, were significantly volumetrically smaller in schizophrenia compared to controls, and significantly correlated with bizarre behavior. Given that the anterior insular lobule offers anatomic features that allow for MRI-based morphometric analysis, namely its central and circular sulci, this brain structure provides a useful model to test hypotheses regarding genotype-phenotype relationships in schizophrenia using the anterior insular lobule as a candidate endophenotype. (c) 2005 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Morphometr Anal,Athinoula A Martinos Ctr,Dept, Charlestown, MA 02129 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02124 USA. Harvard Univ, Sch Med, Dept Psychiat, Beth Israel Deaconess Med Ctr,Div Publ Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02120 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02120 USA. Brigham & Womens Hosp, Div Womens Hlth, Boston, MA USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Univ Calif San Diego, Dept Psychiat, Inst Behav Genom, La Jolla, CA 90293 USA. San Diego VA Healthcare Syst, La Jolla, CA 90293 USA. Harvard Univ, Sch Med, Dept Psychiat, Brockton W Roxbury VA Med Ctr, Brockton, MA 02401 USA. SUNY Upstate Med Univ, New York Genet Res Program, Syracuse, NY 13210 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. RP Makris, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Morphometr Anal,Athinoula A Martinos Ctr,Dept, Bldg 149,13th St, Charlestown, MA 02129 USA. EM nikos@cma.mgh.harvard.edu RI Kennedy, David/H-3627-2012; OI Faraone, Stephen/0000-0002-9217-3982 FU NCRR NIH HHS [P41RR14075]; NIMH NIH HHS [MH 43518, MH 46318, R01 MH 56956] NR 122 TC 106 Z9 109 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2006 VL 83 IS 2-3 BP 155 EP 171 DI 10.1016/j.schres.2005.11.020 PG 17 WC Psychiatry SC Psychiatry GA 035OW UT WOS:000237012200005 PM 16448806 ER PT J AU Holt, DJ Titone, D Long, LS Goff, DC Cather, C Rauch, SL Judge, A Kuperberg, GR AF Holt, DJ Titone, D Long, LS Goff, DC Cather, C Rauch, SL Judge, A Kuperberg, GR TI The misattribution of salience in delusional patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat DE schizophrenia; delusion; emotion; salience; word; language ID PERSECUTORY DELUSIONS; FACIAL EXPRESSIONS; THOUGHT-DISORDER; COGNITIVE MODEL; PERCEPTION; PSYCHOSIS; CONTEXT; THREAT; WORDS; IDEATION AB Introduction: Delusions may arise from abnormalities in emotional perception. In this study, we tested the hypothesis that delusional schizophrenia patients are more likely than non-delusional schizophrenia patients and healthy participants to assign affective meanings to neutral stimuli. Methods: Unpleasant, pleasant, and neutral words were randomly presented to three subject groups-patients with schizophrenia with prominent delusions, patients with schizophrenia without delusions, and healthy participants. Participants performed three tasks: one in which they decided whether a letter string was a word or a non-word (lexical decision) and two affective classification tasks in which they judged whether words were 1) neutral or unpleasant, or 2) neutral or pleasant. Results: While there were no significant between-group differences in lexical decision performance, patients with delusions showed selective performance deficits in both affective classification tasks. First, delusional patients were significantly more likely than non-delusional patients and healthy participants to classify words as unpleasant. Second, delusional patients took significantly longer than both other groups to correctly classify neutral words in both affective classification tasks. Conclusions: Taken together, these findings suggest that delusions are associated with the explicit misattribution of salience to neutral stimuli. (c) 2006 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. McGill Univ, Dept Psychol, Montreal, PQ, Canada. Harvard Univ, Cambridge, MA 02138 USA. Tufts Univ, Dept Psychol, Medford, MA USA. RP Holt, DJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,13th St, Charlestown, MA 02129 USA. EM dholt@partners.org FU NIMH NIH HHS [R01 MH07163] NR 45 TC 41 Z9 41 U1 5 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2006 VL 83 IS 2-3 BP 247 EP 256 DI 10.1016/j.schres.2005.12.858 PG 10 WC Psychiatry SC Psychiatry GA 035OW UT WOS:000237012200015 PM 16540291 ER PT J AU Khazaie, K von Boehmer, H AF Khazaie, K von Boehmer, H TI The impact of CD4(+)CD25(+) Treg on tumor specific CD8(+) T cell cytotoxicity and cancer SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE tumor; Treg; cytotoxicity; TGF-beta; inflammation ID IMMUNOLOGICAL SELF-TOLERANCE; GROWTH-FACTOR-BETA; IN-VIVO; EFFECTOR FUNCTION; CROSS-PRESENTATION; BONE-MARROW; CLONAL DELETION; SOLID TUMORS; PERIPHERAL TOLERANCE; AUTOIMMUNE-DISEASE AB There is sufficient evidence to suggest that tumor growth elicits specific immune responses, including CD8(+) and CD4(+) T cell responses that may delay tumor growth and could potentially be harnessed to eradicate cancer. Nevertheless the frequent outcome of cancer is lethality associated with uncontrolled growth and dissemination of tumor cells. The failure of the immune response may be naturally programmed and related to a specific subpopulation of CD4(+)CD25(+) regulatory T cells, whose function is to protect us against autoimmunity. Recent investigations have shed light on the in vivo behavior and functions of these cells. It is becoming evident that a major impact of these cells is on the ctolytic action of specific CD8(+) T cells that target the tumor. Inhibition of cytotoxicity is dependent on TGF-beta signaling by the effector cells. Thus, targeting immune regulation may provide a promising approach to the immune therapy of cancer. This approach however could also have unexpected deleterious consequences, as surprising new observations indicate that regulatory T cells can also delay tumor growth by independent mechanisms that relate to their cross talk with the innate immune response to cancer. (c) 2005 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dept Canc Immunol & Aids, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Khazaie, K (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & Aids, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Khashayarsha_khazaie@dfci.harvard.edu; Harald_Von_Boehmer@dfci.harvard.edu FU NCI NIH HHS [R33 CA 97728-02, 1R01 CA 104547-01A1]; NIAID NIH HHS [R37 AI 53102] NR 155 TC 70 Z9 93 U1 3 U2 13 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD APR PY 2006 VL 16 IS 2 BP 124 EP 136 DI 10.1016/j.semcancer.2005.11.006 PG 13 WC Oncology SC Oncology GA 026MR UT WOS:000236343500006 PM 16443370 ER PT J AU Zorn, E AF Zorn, E TI CD4+CD25+regulatory T cells in human hematopoietic cell transplantation SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE allogeneic HCT; CD4+CD25+T-reg; FOXP3; GVHD; immune reconstitution ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; TRANSCRIPTION FACTOR FOXP3; REGULATORY CELLS; SUPPRESSOR FUNCTION; AUTOIMMUNE-DISEASE; PERIPHERAL-BLOOD; TGF-BETA; IN-VITRO; EXTRACORPOREAL PHOTOPHERESIS AB Naturally occurring CD4(+)CD25(+) regulatory T cells (T-reg)are differentiated T lymphocytes actively involved in the control of peripheral immunity. Over the past few years, a number of animal studies have demonstrated the critical role of these cells in the outcome of allogeneic hematopoietic stem cell transplantation (HCT). In these models T-reg can exert a potent suppressive effect on immune effector cells reactive to host antigens and prevent graft versus host disease (GVHD) while preserving the graft-versus-leukemia effect (GVL). The present review summarizes current knowledge on the role of T-reg populations in humans following allogeneic HCT. Recent investigations focusing on T-reg in transplant patients have generated conflicting results mostly due to the use of different parameters to assess T-reg. Nonetheless, these studies suggested that an imbalance between T-reg and effector cells during immune reconstitution can substantially impair regulatory mechanisms and contributes to the development of GVHD. Building on these studies, a number of therapeutic strategies are being developed to positively modulate T-reg pools in vivo and prevent or even correct GVHD. Conversely, clinical interventions can also be envisaged to decrease T-reg activity in vivo and enhance the GVL effect. These potential strategies are discussed herein. Coining years will undoubtedly yield additional knowledge on how to use T-reg subsets in vivo and successfully control and modulate immune responses in patients post-HCT. (c) 2005 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Zorn, E (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM emmanuel_zorn@dfci.harvard.edu FU NIAID NIH HHS [AI 29530] NR 73 TC 29 Z9 41 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD APR PY 2006 VL 16 IS 2 BP 150 EP 159 DI 10.1016/j.semcancer.2005.11.008 PG 10 WC Oncology SC Oncology GA 026MR UT WOS:000236343500008 PM 16431128 ER PT J AU Bluestone, JA von Boehmer, H AF Bluestone, JA von Boehmer, H TI Regulatory T cells SO SEMINARS IN IMMUNOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jbluest@diabetes.ucsf.edu; Harald_Von_Boehmer@dfci.harvard.edu NR 0 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD APR PY 2006 VL 18 IS 2 BP 77 EP 77 DI 10.1016/j.smim.2006.01.003 PG 1 WC Immunology SC Immunology GA 022FU UT WOS:000236041400001 ER PT J AU Jaeckel, E Kretschmer, K Apostolou, I von Boehmer, H AF Jaeckel, E Kretschmer, K Apostolou, I von Boehmer, H TI Instruction of Treg commitment in peripheral T cells is suited to reverse autoimmunity SO SEMINARS IN IMMUNOLOGY LA English DT Review DE Treg; Foxp3; Treg conversion; autoimmunity; diabetes; tumor immunity ID IN-VIVO; DENDRITIC CELLS; ANTIGEN; INDUCTION; TOLERANCE; DYNAMICS; PEPTIDE; FOXP3 AB In order to exploit regulatory T cells in a clinical setting it is desirable to be able to generate such cells by a variety of antigens that elicit unwanted immune responses. This goal has been achieved by targeting antigen to dendritic cells under subimmunogenic conditions which results in the conversion of naive Foxp3 negative T cells into Foxp3-expressing regulatory T cells that are indistinguishable from what has been referred to as natural Treg. Such cells have the ability to interfere with immunity at early as well as late stages of the immune response during which effector cells have already been formed. This suggests that Treg cannot only be exploited to prevent immune responses but also to interfere with already established immunity. (c) 2006 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu RI Kretschmer, Karsten/E-8174-2010 FU NIAID NIH HHS [R37AI53102] NR 23 TC 23 Z9 26 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD APR PY 2006 VL 18 IS 2 BP 89 EP 92 DI 10.1016/j.smim.2006.01.011 PG 4 WC Immunology SC Immunology GA 022FU UT WOS:000236041400003 PM 16473523 ER PT J AU Goss, PE AF Goss, PE TI Preventing relapse beyond 5 years: The MA.17 extended adjuvant trial SO SEMINARS IN ONCOLOGY LA English DT Review ID EARLY BREAST-CANCER; POSTMENOPAUSAL WOMEN; AROMATASE INHIBITORS; RANDOMIZED-TRIAL; UPDATED FINDINGS; TAMOXIFEN; LETROZOLE; THERAPY; RECURRENCE; PLACEBO C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Cox Bldg,Room 640, Boston, MA 02114 USA. EM pegoss@interlog.com NR 22 TC 17 Z9 18 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2006 VL 33 IS 2 SU 7 BP S8 EP S12 DI 10.1053/j.seminoncol.2006.03.025 PG 5 WC Oncology SC Oncology GA 050ZH UT WOS:000238129300003 PM 16730271 ER PT J AU Strecker, RE Basheer, R McKenna, JT McCarley, RW AF Strecker, RE Basheer, R McKenna, JT McCarley, RW TI Another chapter in the adenosine story SO SLEEP LA English DT Editorial Material ID BASAL FOREBRAIN; BEHAVIORAL STATE; SLEEP; WAKEFULNESS; RATS; MICRODIALYSIS; INHIBITION; NEURONS C1 Harvard Univ, Sch Med, Neurosci Lab, Brockton, MA 02301 USA. Boston VA Healthcare Syst, Boston, MA USA. RP Strecker, RE (reprint author), Harvard Univ, Sch Med, Neurosci Lab, 151-C,940 Belmont St,Bldg 46, Brockton, MA 02301 USA. EM robert_strecker@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NHLBI NIH HHS [T32 HL07901, P50 HL060292]; NIMH NIH HHS [F32 MH070156, R37 MH039683] NR 16 TC 7 Z9 7 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 1 PY 2006 VL 29 IS 4 BP 426 EP 428 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 036HD UT WOS:000237061300005 PM 16676774 ER PT J AU Lo, YL Jordan, AS Malhotra, A Wellman, A Heinzer, RC Schory, K Dover, L Fogel, RB White, DP AF Lo, YL Jordan, AS Malhotra, A Wellman, A Heinzer, RC Schory, K Dover, L Fogel, RB White, DP TI Genioglossal muscle response to CO2 stimulation during NREM sleep SO SLEEP LA English DT Article DE genioglossus; hypercapnia; sleep; upper airway; pharynx; continuous positive airway pressure; respiration ID HYPERCAPNIC VENTILATORY RESPONSE; POSITIVE AIRWAY PRESSURE; ELECTROMYOGRAM RESPONSES; NEGATIVE-PRESSURE; APNEA PATIENTS; NORMAL MEN; ACTIVATION; HUMANS; REFLEX; WAKEFULNESS AB Study Objectives: The objective was to evaluate the responsiveness of upper airway muscles to hypercapnia with and without intrapharyngeal negative pressure during non-rapid eye movement (NREM) sleep and wakefulness. Design: We assessed the genioglossal muscle response to CO2 off and on continuous positive airway pressure (CPAP) (to attenuate negative pressure) during stable NREM sleep and wakefulness in the supine position. Setting: Laboratory of the Sleep Medicine Division, Brigham and Women's Hospital. Patients or Participants: Eleven normal healthy subjects. Interventions: During wakefulness and NREM sleep, we measured genioglossal electromyography (EMG) on and off CPAP at the normal eupneic level and at levels 5 and 10 mm Hg above the awake eupneic level. Measurements and Results: We observed that CO 2 could increase upper-airway muscle activity during NREM sleep and wakefulness in the supine position with and without intrapharyngeal negative pressure. The application of nasal CPAP significantly decreased genioglossal EMG at all 3 levels of PETCO2 during NREM sleep (13.0 +/- 4.9% vs. 4.6 +/- 1.6% of maximal EMG, 14.6 +/- 5.6% vs. 7.1 +/- 2.3% of maximal EMG, and 17.3 +/- 6.3% vs, 10.2 +/- 3.1 % of maximal EMG, respectively). However, the absence of negative pressure in the upper airway did not significantly affect the slope of the pharyngeal airway dilator muscle response to hypercapnia during NREM sleep (0.72 +/- 0.30% vs. 0.79 +/- 0.27% of maximal EMG per mm Hg PCO2, respectively, off and on CPAP). Conclusions: We conclude that both chemoreceptive and negative pressure reflex inputs to this upper airway dilator muscle are still active during stable NREM sleep. C1 Chang Gang Mem Hosp, Dept Thorac Med, Taipei, Taiwan. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Sleep Med, Boston, MA USA. CHUV, Serv Pneumol, Lausanne, Switzerland. Merck & Co Inc, Resp & Allergy Div, Rahway, NJ USA. RP Lo, YL (reprint author), BIDMC, Sleep Disorders Program, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM lyulun@partners.org OI Jordan, Amy/0000-0001-8561-9766 FU NCRR NIH HHS [M01 RR001032, RR01032]; NHLBI NIH HHS [P50 HL60292, P50 HL060292, R01 HL048531, R01 HL073146, R01 HL073146-02, R01 HL48531]; NIA NIH HHS [AG024837-01, K23 AG024837, K23 AG024837-03] NR 41 TC 41 Z9 41 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 1 PY 2006 VL 29 IS 4 BP 470 EP 477 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 036HD UT WOS:000237061300011 PM 16676780 ER PT J AU Colla, J Buka, S Harrington, D Murphy, JM AF Colla, J Buka, S Harrington, D Murphy, JM TI Depression and modernization SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE cross-cultural; epidemiology; modernization; women ID PSYCHIATRIC-DISORDER; MAJOR DEPRESSION; URBAN-POPULATION; COMMUNITY; STRESS; PREVALENCE; MORBIDITY; NIGERIA; SAMPLE; WOMEN AB Background This study concerns depression among women living in developing and developed parts of the world. Using a continuum of environments conceptualized as ranging from traditional to modern, the goal is to explore the hypothesis that the prevalence of depression will be higher among those living in modern compared to traditional societies. This issue is examined among samples from West Africa and North America. Methods The subjects are 657 women who reside in four locations. An operational definition of modernization is used to place the locales as a continuum in the following order: rural Yorubaland in Nigeria, Yorubas living in urban Nigeria, rural Canada, and urban United States. Variables employed include education, religious orientation, and the role of women as mothers and workers. Depression is assessed using an algorithm based on generally acknowledged criteria. Multivariate logistic regression is used to generate point estimates and confidence intervals for prevalence odds ratios, to adjust for potential confounders, and to assess effect modification. Results The prevalence of depression was lowest among rural Nigerians and highest among urban residents in the United States. The association of depression with the proposed continuum was strongest among women under the age of 45 who had living children ( Odds Ratio: 2.1; 95% Confidence Interval: 1.6 - 2.9). Conclusions In the areas studied, a traditional way of life seems to offer protection against some of the stresses associated with modernization although it does not appear to compensate for the adversity of childlessness. Level of modernization may be a useful concept for understanding differences in rates of depression in different parts of the world. C1 Dartmouth Coll Sch Med, Dept Community & Family Med, Hanover, NH 03755 USA. Harvard Univ, Sch Publ Hlth, Dept Maternal & Child Hlth & Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat Sci, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Colla, J (reprint author), Dartmouth Coll Sch Med, Dept Community & Family Med, Strasenburg Hall, Hanover, NH 03755 USA. EM judith.colla@dartmouth.edu RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 NR 55 TC 10 Z9 12 U1 3 U2 11 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0933-7954 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD APR PY 2006 VL 41 IS 4 BP 271 EP 279 DI 10.1007/s00127-006-0032-8 PG 9 WC Psychiatry SC Psychiatry GA 027LF UT WOS:000236416400003 PM 16520885 ER PT J AU Peteet, JR AF Peteet, John R. TI Case discussion: Disease as punishment SO SOUTHERN MEDICAL JOURNAL LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Peteet, JR (reprint author), Dana Farber Canc Inst, 44 Binney St,Gossman 411, Boston, MA 02115 USA. EM jpeteet@partners.org NR 3 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD APR PY 2006 VL 99 IS 4 BP 434 EP 435 DI 10.1097/01.smj.0000208420.06456.55 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 095NR UT WOS:000241315100035 PM 16634269 ER PT J AU Wagers, AJ Weissman, IL AF Wagers, Amy J. Weissman, Irving L. TI Differential expression of alpha 2 integrin separates long-term and short-term reconstituting Lin(-/lo)Thy1.1(lo)c-kit(+)Sca-1(+) hematopoietic stem cells SO STEM CELLS LA English DT Article DE cell surface markers; integrins; hematopoietic stem cell; hematopoietic stem cell transplantation ID COLONY-STIMULATING FACTOR; ALPHA(2)BETA(1) INTEGRIN; BONE-MARROW; 3-DIMENSIONAL COLLAGEN; CYCLE PROGRESSION; PROGENITOR CELLS; CARCINOMA CELLS; MOBILIZATION; MOUSE; IDENTIFICATION AB Self-renewing, multipotent hematopoietic stem cells are highly enriched within the Lin(-)Thy1.1(lo)c-kit(+)Sca-1(+) subset of mouse bone marrow. However, heterogeneous expression within this population of certain cell surface markers raises the possibility that it may be further fractionated phenotypically and perhaps functionally. We previously identified alpha 2-integrin (CD49b) as a surface marker with heterogeneous expression on Lin(-/lo)Thy1.1(lo)c-kit(+)Sca-1(+) stem cells. To determine whether differences in alpha 2 expression were indicative of differences in stem cell function, we purified alpha 2(-) and alpha 2(hi) stem cells by fluorescence-activated cell sorting and analyzed their function in long- and short-term hematopoietic reconstitution assays. Both alpha 2(-) and alpha 2(hi) cells could give rise to mature lymphoid and myeloid cells after transplantation into lethally irradiated congenic recipients. However, alpha 2(hi) cells supported hematopoiesis for only a short time (< 4 weeks), whereas alpha 2(-) cells reproducibly yielded robust, long-term (> 20 weeks) reconstitution, suggesting that alpha 2(-) cells represent a more primitive population than do alpha 2(hi) cells. Consistent with this idea, alpha 2(-)Lin(-/) loThy1.1(lo)c-kit(+)Sca-1(+) cells exhibited an approximately sixfold decreased frequency of spleen colony-forming units (day 12) versus a2hi cells. Furthermore, bone marrow cells isolated from animals transplanted > 20 weeks previously with 20 alpha 2(-)Lin(-/lo)Thy1.1(lo)c-kit(+)Sca-1(+) cells included both alpha 2(-) and alpha 2(hi) stem cells of donor origin, indicating that alpha 2(hi) cells are likely lineal descendents of alpha 2(-) cells. Interestingly, alpha 2 integrin expression is significantly reduced on lineage-restricted oligopotent progenitors in the marrow, suggesting that high level expression of alpha 2 selectively marks a subset of primitive hematopoietic cells which retains multilineage reconstitution potential but exhibits reduced self-renewal capacity. C1 Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA. RP Wagers, AJ (reprint author), Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM amy.wagers@joslin.harvard.edu FU NCI NIH HHS [CA86065]; NHLBI NIH HHS [2 R01 HL58770] NR 33 TC 37 Z9 37 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD APR PY 2006 VL 24 IS 4 BP 1087 EP 1094 DI 10.1634/stemcells.2005-0396 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 085WY UT WOS:000240636300031 PM 16373693 ER PT J AU Taub, E Uswatte, G King, DK Morris, D Crago, JE Chatterjee, A AF Taub, E Uswatte, G King, DK Morris, D Crago, JE Chatterjee, A TI A placebo-controlled trial of constraint-induced movement therapy for upper extremity after stroke SO STROKE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Physiological-Society CY APR, 2003 CL San Diego, CA SP Amer Physiol Soc DE controlled clinical trials; rehabilitation; stroke; treatment outcome ID MOTOR FUNCTION-TEST; LEARNED NONUSE; REHABILITATION; RELIABILITY AB Background and Purpose - Constraint-Induced Movement therapy (CI therapy) is a neurorehabilitation technique developed to improve use of the more affected upper extremity after stroke. A number of studies have reported positive effects for this intervention, but an experiment with a credible placebo control group has not yet been published. Methods - We conducted a placebo-controlled trial of CI therapy in patients with mild to moderate chronic ( mean = 4.5 years after stroke) motor deficit after stroke. The CI therapy group received intensive training ( shaping) of the more affected upper extremity for 6 hours per day on 10 consecutive weekdays, restraint of the less affected extremity for a target of 90% of waking hours during the 2-week treatment period, and application of a number of other techniques designed to produce transfer to the life situation. The placebo group received a program of physical fitness, cognitive, and relaxation exercises for the same length of time and with the same amount of therapist interaction as the experimental group. Results - After CI therapy, patients showed large ( Wolf Motor Function Test) to very large improvements in the functional use of their more affected arm in their daily lives ( Motor Activity Log; P < 0.0001). The changes persisted over the 2 years tested. Placebo subjects showed no significant changes. Conclusion - The results support the efficacy of CI therapy for rehabilitating upper extremity motor function in patients with chronic stroke. C1 Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. Univ Alabama, Dept Rehabil Serv, Birmingham, AL 35294 USA. Univ Alabama, Dept Phys Therapy, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. RP Taub, E (reprint author), Univ Alabama, Dept Psychol, 1530 3rd Ave S,CPM 712, Birmingham, AL 35294 USA. EM etaub@uab.edu RI Uswatte, Gitendra/C-4913-2009 FU NICHD NIH HHS [HD34273] NR 16 TC 200 Z9 225 U1 1 U2 19 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 2006 VL 37 IS 4 BP 1045 EP 1049 DI 10.1161/01.STR.0000206463.66461.97 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 025UJ UT WOS:000236292100027 PM 16514097 ER PT J AU Hylek, EM D'Antonio, J Evans-Molina, C Shea, C Henault, LE Regan, S AF Hylek, EM D'Antonio, J Evans-Molina, C Shea, C Henault, LE Regan, S TI Translating the results of randomized trials into clinical practice - The challenge of warfarin candidacy among hospitalized elderly patients with atrial fibrillation SO STROKE LA English DT Article DE atrial fibrillation; geriatrics; warfarin ID HIGH-RISK PATIENTS; ANTITHROMBOTIC THERAPY; STROKE PREVENTION; MEDICARE BENEFICIARIES; ORAL ANTICOAGULATION; DOSE WARFARIN; SPORTIF-III; PREVALENCE; ADULTS; GUIDELINES AB Background and Purpose - Numerous studies have documented under use of warfarin particularly among elderly patients. A better understanding of the discrepancy between trials and clinical practice will help inform stroke prevention strategies in this vulnerable age group. The study objective was to prospectively assess the use of antithrombotic therapy among a contemporary cohort of patients with atrial fibrillation at the time of hospital discharge. In addition to baseline characteristics, we sought to define the physician-cited reason for not prescribing warfarin for each patient. Methods - Patients with atrial fibrillation were prospectively identified and followed to hospital discharge. Enrolled patients were >= 65 years of age, not taking warfarin on admission, and had their longitudinal care provided at our institution. Predictors of warfarin use were determined and physician- cited contraindications were compared across age groups. Results - Fifty-one percent ( n = 206) of patients were discharged on warfarin: 75% of those 65 to 69 years of age, 59% 70 to 79, 45% 80 to 89, and 24% age >= 90 years. Of the remaining 199 patients, 83% had >= 2 major risk factors for stroke, and 98% were felt to have contraindications including nearly 25% who were unable to tolerate warfarin in the past. Among patients age >= 80, falling was the most often physician- cited reason for not prescribing warfarin (41%) followed by hemorrhage (28%). Conclusion - Our findings suggest that many elderly patients at high risk for stroke may not be optimal candidates for anticoagulant therapy. There is a pressing need for alternative stroke prevention strategies for this expanding patient population. C1 Boston Univ, Sch Med, Gen Internal Med Sect, Res Unit,Dept Med, Boston, MA 02118 USA. Univ Pittsburgh, Dept Med, Div Cardiol, Pittsburgh, PA 15260 USA. Univ Virginia, Dept Med, Charlottesville, VA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Hylek, EM (reprint author), Boston Univ, Sch Med, Gen Internal Med Sect, Res Unit,Dept Med, 91 E Concord St,Suite 200, Boston, MA 02118 USA. EM ehylek@bu.edu NR 41 TC 155 Z9 161 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2006 VL 37 IS 4 BP 1075 EP 1080 DI 10.1161/01.STR.0000209239.71702.ce PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 025UJ UT WOS:000236292100033 PM 16527999 ER PT J AU Yenari, MA Xu, LJ Tang, XN Qiao, YL Giffard, RG AF Yenari, MA Xu, LJ Tang, XN Qiao, YL Giffard, RG TI Microglia potentiate damage to blood-brain barrier constituents - Improvement by minocycline in vivo and in vitro SO STROKE LA English DT Article DE blood-brain barrier; inflammation; ischemia; microglia ID CEREBRAL-ARTERY OCCLUSION; NITRIC-OXIDE SYNTHASE; ENDOTHELIAL-CELLS; MILD HYPOTHERMIA; NADPH OXIDASE; HYPOXIA REOXYGENATION; EXPERIMENTAL STROKE; CORTICAL-NEURONS; ASTROGLIAL CELLS; ISCHEMIA AB Background - Blood - brain barrier (BBB) disruption after stroke can worsen ischemic injury by increasing edema and causing hemorrhage. We determined the effect of microglia on the BBB and its primary constituents, endothelial cells (ECs) and astrocytes, after ischemia using in vivo and in vitro models. Methods and Results - Primary astrocytes, ECs, or cocultures were prepared with or without added microglia. Primary ECs were more resistant to oxygen-glucose deprivation/reperfusion than astrocytes. ECs plus astrocytes showed intermediate vulnerability. Microglia added to cocultures nearly doubled cell death. This increase was prevented by minocycline and apocynin. In vivo, minocycline reduced infarct volume and neurological deficits and markedly reduced BBB disruption and hemorrhage in mice after experimental stroke. Conclusions - Inhibition of microglial activation may protect the brain after ischemic stroke by improving BBB viability and integrity. Microglial inhibitors may prove to be an important treatment adjunct to fibrinolysis. C1 Univ Calif San Francisco, VAMC, Dept Neurol, San Francisco, CA 94121 USA. Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Yenari, MA (reprint author), Univ Calif San Francisco, VAMC, Dept Neurol, 4150 Clement St, San Francisco, CA 94121 USA. EM yenari@alum.mit.edu FU NIGMS NIH HHS [R01 GM49831]; NINDS NIH HHS [P01 NS37520, P50 NS14543, R01 NS40516] NR 41 TC 169 Z9 173 U1 3 U2 14 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 2006 VL 37 IS 4 BP 1087 EP 1093 DI 10.1161/01.STR.0000206281.77178.ac PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 025UJ UT WOS:000236292100035 PM 16497985 ER PT J AU Warshaw, AL AF Warshaw, AL TI Advocacy by and for surgeons and our patients SO SURGERY LA English DT Editorial Material ID SURGICAL QUALITY; COMPENSATION; PROGRAM; CARE C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM awarshaw@partners.org NR 11 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD APR PY 2006 VL 139 IS 4 BP 460 EP 461 DI 10.1016/j.surg.2006.01.002 PG 2 WC Surgery SC Surgery GA 036CL UT WOS:000237048400002 PM 16627053 ER PT J AU McGee, GE Warshaw, AL Harken, AH AF McGee, GE Warshaw, AL Harken, AH TI Mississippi medical liability reform experience SO SURGERY LA English DT Article C1 Forrest Gen Hosp, Trauma Surg Clin, Dept Surg, Hattiesburg, MS 39404 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ Calif San Francisco E Bay, Dept Surg, Oakland, CA USA. RP McGee, GE (reprint author), Forrest Gen Hosp, Trauma Surg Clin, Dept Surg, POB 16389, Hattiesburg, MS 39404 USA. EM GMcGee@forrestgeneral.com NR 4 TC 1 Z9 1 U1 0 U2 1 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 2006 VL 139 IS 4 BP 462 EP 465 DI 10.1016/j.surg.2005.01.016 PG 4 WC Surgery SC Surgery GA 036CL UT WOS:000237048400003 PM 16627054 ER PT J AU Joseph, AM AF Joseph, AM TI Care coordination and telehealth technology in promoting self-management among chronically ill patients SO TELEMEDICINE JOURNAL AND E-HEALTH LA English DT Article AB With an increasingly complex healthcare system, the need to coordinate the care for chronically ill patient often goes unmet. This results in increased utilization of services at significant costs. In addition, providing patients with the tools to manage their own disease processes over the long term is also lacking in the healthcare environment. The Veterans Health Administration (VHA) approached these challenges by creating a Care Coordination program using technology to promote self management for veterans. Although a relatively new program, the Veterans Integrated Services Network (VISN) 7, has shown substantial gains in both decreasing the use of high cost care, such as emergency department (ED) visits and hospitalizations, as well as improving clinical outcomes with better glycemic control for patients with diabetes and improved lipid management for all patients. C1 Dept Vet Affairs, Atlanta, GA USA. RP Joseph, AM (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. EM Amelia.joseph2@med.va.gov NR 7 TC 17 Z9 17 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED J E-HEALTH JI Telemed. J. e-Health PD APR PY 2006 VL 12 IS 2 BP 156 EP 159 DI 10.1089/tmj.2006.12.156 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 044BT UT WOS:000237647800026 PM 16620170 ER PT J AU Galea, M Tumminia, J Garback, LM AF Galea, M Tumminia, J Garback, LM TI Telerehabilitation in spinal cord injury persons: A novel approach SO TELEMEDICINE JOURNAL AND E-HEALTH LA English DT Article ID NUTRITION INTERVENTION; TELEMEDICINE AB The care of a spinal cord injury (SCI) person constitutes a great challenge for the provider: SCI persons are mobility impaired, and they are prone to develop multiple comorbidities such as diabetes mellitus, hypertension, obesity, bladder infections, wounds, and depression. Furthermore, disease manifestations can be misleading depending on the level of injury. The utilization of telemedicine to monitor patients and deliver care has opened a new horizon for SCI persons. Several telehealth programs are now in use to monitor pressure ulcers and post-discharge rehabilitation in SCI persons. To answer the need for a more comprehensive approach to the multifaceted manifestation of SCI at the James J. Peters VAMC, we have started a customized telerehabilitation program. The program monitors the most common comorbidities of SCI, it is instrumental in the reintegration of the SCI person in the community, it offers individualized in-home rehabilitation programs, it addresses safety issues, and it offers counseling, weight reduction, and maintenance plans. A team of SCI specialists - including an internist, a registered nurse, a physical therapist, a nutritionist, a psychologist, and a recreational therapist - are available for weekly meetings with the patients. The programs are tailored to the patients' needs and agreed upon by both parties. Both messaging devices and videomonitors are utilized. An interdisciplinary template is used to record assessments and plans. Preliminary results are encouraging; coordination of the team and relative poor technology are some of the obstacles we have identified. Further evaluation is necessary to determine cost effectiveness. C1 James J Peters Vet Adm Med Ctr, Spinal Cord Injury Clin, Bronx, NY 10468 USA. RP Galea, M (reprint author), James J Peters Vet Adm Med Ctr, Spinal Cord Injury Clin, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM marinella.galea@med.va.gov NR 9 TC 20 Z9 22 U1 1 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED J E-HEALTH JI Telemed. J. e-Health PD APR PY 2006 VL 12 IS 2 BP 160 EP 162 DI 10.1089/tmj.2006.12.160 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 044BT UT WOS:000237647800027 PM 16620171 ER PT J AU Sood, A Ford, ES Camargo, CA AF Sood, A Ford, ES Camargo, CA TI Association between leptin and asthma in adults SO THORAX LA English DT Article ID BODY-MASS INDEX; OBSTRUCTIVE PULMONARY-DISEASE; NEWLY-DIAGNOSED ASTHMA; C-REACTIVE PROTEIN; PHYSICAL-ACTIVITY; CHILDHOOD ASTHMA; NATIONAL-HEALTH; UNITED-STATES; ONSET ASTHMA; OBESITY AB Background: Leptin, a pro-inflammatory cytokine produced by adipose tissue, has previously been shown to be associated with asthma in children. We hypothesised that high serum leptin concentrations would also be associated with asthma in adults. Methods: The Third National Health and Nutrition Examination Survey is a cross sectional study that included fasting serum leptin concentrations and self-report of doctor diagnosed asthma. Data were analysed using multivariable logistic regression analysis. Results: Of 5876 participants, those with current asthma had a higher mean unadjusted leptin concentration than those who had never had asthma ( geometric mean ( SE) 9.2 (0.6) mu g/l v 7.6 (0.2) mu g/l; p = 0.02). After adjustment for triceps skinfold thickness and other covariates, the association between leptin and asthma appeared stronger in women than in men, and in premenopausal women than in postmenopausal women. Body mass index (BMI) was also associated with current asthma in women, but this association was not significantly affected by adjustment for leptin concentrations. Conclusions: The results of this large population based study support the hypothesis that leptin is associated with asthma in women. In addition, while BMI also is related to asthma in women, this study does not support the suggestion that leptin contributes significantly to this association. C1 So Illinois Univ, Sch Med, Div Pulm & Crit Care Med, Springfield, IL 62794 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Sood, A (reprint author), So Illinois Univ, Sch Med, Div Pulm & Crit Care Med, 701 N 1st St,Room D434,POB 19636, Springfield, IL 62794 USA. EM asood2@siumed.edu FU NIAID NIH HHS [AI-52338] NR 56 TC 123 Z9 135 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD APR PY 2006 VL 61 IS 4 BP 300 EP 305 DI 10.1136/thx.2004.031468 PG 6 WC Respiratory System SC Respiratory System GA 025GT UT WOS:000236254100007 PM 16540481 ER PT J AU Hamel, LP Nicole, MC Sritubtim, S Morency, MJ Ellis, M Ehlting, J Beaudoin, N Barbazuk, B Klessig, D Lee, J Martin, G Mundy, J Ohashi, Y Scheel, D Sheen, J Xing, T Zhang, SQ Seguin, A Ellis, BE AF Hamel, Louis-Philippe Nicole, Marie-Claude Sritubtim, Somrudee Morency, Marie-Jose Ellis, Margaret Ehlting, Juergen Beaudoin, Nathalie Barbazuk, Brad Klessig, Dan Lee, Justin Martin, Greg Mundy, John Ohashi, Yuko Scheel, Dierk Sheen, Jen Xing, Tim Zhang, Shuqun Seguin, Armand Ellis, Brian E. TI Ancient signals: comparative genomics of plant MAPK and MAPKK gene families SO TRENDS IN PLANT SCIENCE LA English DT Review ID ACTIVATED PROTEIN-KINASE; ARABIDOPSIS-THALIANA; SCAFFOLD PROTEINS; PATHWAYS; YEAST; ORGANIZATION; DUPLICATION; DIVERGENCE; EVOLUTION AB MAPK signal transduction modules play crucial roles in regulating many biological processes in plants, and their components are encoded by highly conserved genes. The recent availability of genome sequences for rice and poplar now makes it possible to examine how well the previously described Arabidopsis MAPK and MAPKK gene family structures represent the broader evolutionary situation in plants, and analysis of gene expression data for MPK and MKK genes in all three species allows further refinement of those families, based on functionality. The Arabidopsis MAPK nomenclature appears sufficiently robust to allow it to be usefully extended to other well-characterized plant systems. C1 Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z3, Canada. Nat Resources Canada, Canadian Forest Serv, Laurentian Forestry Ctr, Ste Foy, PQ G1V 4C7, Canada. Univ Sherbrooke, Dept Biol, Sherbrooke, PQ J1K 2R1, Canada. Donald Danforth Plant Sci Ctr, St Louis, MO 63132 USA. Boyce Thompson Inst Plant Res, Ithaca, NY 14853 USA. Leibnitz Inst Plant Biochem, D-06120 Halle, Germany. Inst Mol Biol & Physiol, DK-1353 Copenhagen K, Denmark. Natl Inst Agrobiol Sci, Dept Plant Physiol, Tsukuba, Ibaraki 3058602, Japan. Harvard Univ, Sch Med, Dept Mol Biol, Massachusetts Gen Hosp, Boston, MA 02114 USA. Carleton Univ, Dept Biol, Ottawa, ON K1S 5B6, Canada. Univ Missouri, Dept Biochem, Life Sci Ctr 109, Columbia, MO 65211 USA. RP Ellis, BE (reprint author), Univ British Columbia, Michael Smith Labs, 2185 East Mall, Vancouver, BC V6T 1Z3, Canada. EM bee@interchange.ubc.ca RI Martin, Gregory/F-6262-2011; Lee, Justin/B-6096-2012; mundy, john/A-2361-2013; OI Martin, Gregory/0000-0003-0044-6830; Lee, Justin/0000-0001-8269-7494; mundy, john/0000-0001-7490-4588; Beaudoin, Nathalie/0000-0001-7835-4077 NR 21 TC 203 Z9 257 U1 5 U2 49 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1360-1385 J9 TRENDS PLANT SCI JI Trends Plant Sci. PD APR PY 2006 VL 11 IS 4 BP 192 EP 198 DI 10.1016/j.tplants.2006.02.007 PG 7 WC Plant Sciences SC Plant Sciences GA 045QI UT WOS:000237756400007 PM 16537113 ER PT J AU D'Amico, AV Manola, J McMahon, E Loffredo, M Lopes, L Ching, J Albert, M Hurwitz, M Suh, WW Vivenzio, TA Beard, C AF D'Amico, AV Manola, J McMahon, E Loffredo, M Lopes, L Ching, J Albert, M Hurwitz, M Suh, WW Vivenzio, TA Beard, C TI A prospective evaluation of rectal bleeding after dose-escalated three-dimensional conformal radiation therapy using an intrarectal balloon for prostate gland localization and immobilization SO UROLOGY LA English DT Article ID RANDOMIZED-TRIAL; CANCER; RADIOTHERAPY; TOXICITY; MOTION AB Objectives. To estimate the rates of rectal bleeding after dose-escalated three-dimensional conformal radiation therapy (3D-CRT) on a prospective, Phase II study in which a modified intrarectal balloon was used for prostate gland localization and immobilization. Methods. The study cohort comprised 100 men with biopsy-proven adenocarcinoma of the prostate and at least one high-risk feature (prostate-specific antigen level greater than 10 ng/mL, Gleason score 7 or higher, or clinical or radiographic T3 disease). Treatment consisted of androgen suppression therapy and four-field 3D-CRT with an intrarectal balloon for the initial 15 treatments. Planning treatment volume dose was 75.6 Gy. The primary endpoint of time to grade 3 rectal bleeding was estimated with the Kaplan-Meier method for 57 men with a minimum follow-up of 1 year. Results. For 57 men with a median (range) follow-up of 1.8 (1.0 to 3.3) years, the median (range) volume of rectum exceeding 70 Gy was 3.7 (0.6 to 14.7) cm(3), and the 2-year estimate of grade 3 rectal bleeding rate was 10%. This rate was 100% as compared with 0 (P < 0.0001) for men who were taking warfarin (n = 3) or high-dose aspirin (n = 1) as compared with neither, respectively. All grade 3 rectal bleeding events were controlled with argon plasma coagulation. Conclusions. Dose-escalated 3D-CRT with an intrarectal balloon technique for prostate localization and immobilization produced no measurable grade 3 rectal bleeding unless the patient was taking anticoagulants. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Biostat, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Phys, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. EM adamico@lroc.harvard.edu FU NCI NIH HHS [R25 CA089017] NR 19 TC 21 Z9 21 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 2006 VL 67 IS 4 BP 780 EP 784 DI 10.1016/j.urology.2005.10.008 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 036EV UT WOS:000237054800031 PM 16584760 ER PT J AU Velmahos, GC AF Velmahos, GC TI Posttraumatic thromboprophylaxis revisited: An argument against the current methods of DVT and PE prophylaxis after injury SO WORLD JOURNAL OF SURGERY LA English DT Review ID DEEP VENOUS THROMBOSIS; MOLECULAR-WEIGHT HEPARIN; RISK TRAUMA PATIENTS; INTERMITTENT PNEUMATIC COMPRESSION; PULMONARY-EMBOLISM; VEIN THROMBOSIS; MAJOR TRAUMA; THROMBOEMBOLISM; PREVENTION; EFFICACY AB Background: Thromboprophylaxis after injury is a controversial issue. Practices and outcomes vary widely. Methods: Review of selected trauma literature on venous thromboprophylaxis after injury. Results: Multiple trauma articles suggest that the efficacy of different methods of thromboprophylaxis is unproven. Most of the practices on this issue are extrapolated from studies which were performed in non-trauma patients and therefore, may not be applicable in the unique trauma population. Conclusions: In the absence of undisputable evidence, none of the current methods of venous thromboprophylaxis after injury should be considered as standard of care. There is a need to discover new methods of thromboprophylaxis for the Trauma patient. C1 Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 38 TC 8 Z9 8 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD APR PY 2006 VL 30 IS 4 BP 483 EP 487 DI 10.1007/s00268-005-0427-9 PG 5 WC Surgery SC Surgery GA 030FC UT WOS:000236618600001 PM 16568226 ER PT J AU Nguyen, TD Kim, US Perrine, SP AF Nguyen, TD Kim, US Perrine, SP TI Novel short chain fatty acids restore chloride secretion in cystic fibrosis SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE cystic fibrosis; Delta F508-CFTR; 2,2-dimethyl-butyrate; alpha-methylhydrocinnamic acid; iodide efflux; IB3-1 airway cells; butyrate derivatives; intracellular trafficking; chloride channel; chloride conductance ID ORAL SODIUM PHENYLBUTYRATE; EPITHELIAL-CELL LINE; FETAL-HEMOGLOBIN; CFTR FUNCTION; 4-PHENYLBUTYRATE; DELTA-F508-CFTR; ACTIVATION; EXPRESSION; MUTATIONS; INDUCTION AB Phenylalanine deletion at position 508 of the cystic fibrosis transmembrane conductance regulator (Delta F508-CFTR), the most common mutation in cystic fibrosis (CF), causes a misfolded protein exhibiting partial chloride conductance and impaired trafficking to the plasma membrane. 4-Phenylbutyrate corrects defective Delta F508-CFTR trafficking in vitro, but is not clinically efficacious. From a panel of short chain fatty acid derivatives, we showed that 2,2-dimethyl-butyrate (ST20) and alpha-methylhydrocinnamic acid (ST7), exhibiting high oral bioavailability and sustained plasma levels, correct the Delta F508-CFTR defect. Pre-incubation (>= 6 h) of CF 1B3-1 airway cells with >= 1 mM ST7 or ST20 restored the ability of 100 mu M forskolin to stimulate an I-125(-) efflux. This efflux was fully inhibited by NPPB, DPC, or glibenclamide, suggesting mediation through CFTR. Partial inhibition by DIDS suggests possible contribution from an additional CI- channel regulated by CFTR. Thus, ST7 and ST20 offer treatment potential for CF caused by the Delta F508 mutation. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Boston Univ, Sch Med, Ctr Canc, Dept Pediat, Boston, MA 02118 USA. Boston Univ, Sch Med, Ctr Canc, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Ctr Canc, Dept Pharmacol, Boston, MA 02118 USA. Boston Univ, Sch Med, Ctr Canc, Dept Expt Therapeut, Boston, MA 02118 USA. RP Nguyen, TD (reprint author), Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA 98108 USA. EM T1Nguyen@u.washington.edu FU NIDDK NIH HHS [DK-52962, DK-55885] NR 22 TC 8 Z9 8 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 31 PY 2006 VL 342 IS 1 BP 245 EP 252 DI 10.1016/j.bbrc.2006.01.127 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 018VV UT WOS:000235793800033 PM 16472777 ER PT J AU Taha, TA Hannun, YA Obeid, LM AF Taha, TA Hannun, YA Obeid, LM TI Sphingosine kinase: Biochemical and cellular regulation and role in disease SO JOURNAL OF BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE angiogenesis; inflammation; sphingolipids; sphingosine kinase ID PROTEIN-COUPLED RECEPTORS; HUMAN ENDOTHELIAL-CELLS; FC-EPSILON-RI; FACTOR-INDUCED ACTIVATION; DENSITY-LIPOPROTEINS HDL; SMOOTH-MUSCLE-CELLS; BREAST-CANCER CELLS; FUNCTIONAL-CHARACTERIZATION; MOLECULAR-CLONING; HUMAN PLATELETS AB Sphingolipids have emerged as molecules whose metabolism is regulated leading to generation of bioactive products including ceramide, sphingosine, and sphingosine-I-phosphate. The balance between cellular levels of these bioactive products is increasingly recognized to be critical to cell regulation; whereby, ceramide and sphingosine cause apoptosis and growth arrest phenotypes, and sphingosine-1-phosphate mediates proliferative and angiogenic responses. Sphingosine kinase is a key enzyme in modulating the levels of these lipids and is emerging as an important and regulated enzyme. This review is geared at mechanisms of regulation of sphingosine kinase and the coming to light of its role in disease. 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), Med Univ S Carolina, Dept Med, 171 Ashley Ave, Charleston, SC 29425 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [P01 CA 97132]; NHLBI NIH HHS [HL43707]; NIGMS NIH HHS [GM62887] NR 192 TC 185 Z9 197 U1 2 U2 9 PU SPRINGER SINGAPORE PTE LTD PI SINGAPORE PA #04-01 CENCON I, 1 TANNERY RD, SINGAPORE 347719, SINGAPORE SN 1225-8687 J9 J BIOCHEM MOL BIOL JI J. Biochem. Mol. Biol. PD MAR 31 PY 2006 VL 39 IS 2 BP 113 EP 131 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 026LO UT WOS:000236340600001 PM 16584625 ER PT J AU Yan, D Li, F Hall, ML Sage, C Hu, WH Giallourakis, C Upadhyay, G Ouyang, XM Du, LL Bethea, JR Chen, ZY Yajnik, V Liu, XZ AF Yan, D Li, F Hall, ML Sage, C Hu, WH Giallourakis, C Upadhyay, G Ouyang, XM Du, LL Bethea, JR Chen, ZY Yajnik, V Liu, XZ TI An isoform of GTPase regulator DOCK4 localizes to the stereocilia in the inner ear and binds to harmonin (USH1C) SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE DOCK4; GTPase regulator; harmonin; actin bundling protein ID ACTIN-BUNDLING PROTEINS; USHER-SYNDROME; RECESSIVE DEAFNESS; RHO GTPASES; HAIR-CELLS; IN-VIVO; MOUSE; PHAGOCYTOSIS; MUTATIONS; HOMOLOG AB The driving forces for the regulation of cell morphology are the Rho family GTPases that coordinate the assembly of the actin cytoskeleton. This dynamic feature is a result of tight coupling between the cytoskeleton and signal transduction and is facilitated by actin-binding proteins (ABPs). Mutations in the actin bundling and PDZ domain-containing protein harmonin are the causes of Usher syndrome type 1C (USH1C), a syndrome of congenital deafness and progressive blindness, as well as certain forms of non-syndromic deafness. Here, we have used the yeast two-hybrid assay to isolate molecular partners of harmonin and identified DOCK4, an unconventional guanine exchange factor for the Rho family of guanosine triphosphatases (Rho GEF GTPases), as a protein interacting with harmonin. Detailed molecular analysis revealed that a novel DOCK4 isoform (DOCK4-Ex49) is expressed in the brain, eye and inner ear tissues. We have further provided evidence that the DOCK4-Ex49 binds to nucleotide free Rac as effectively as DOCK2 and DOCK4 and it is a potent Rac activator. By immunostaining using a peptide antibody specific to DOCK4-Ex49, we showed its localization in the inner ear within the hair bundles along the stereocilia (SC). Together, our data indicate a possible Rac-DOCK4-ABP harmonin-activated signaling pathway in regulating actin cytoskeleton organization in stereocilia. (c) 2006 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Univ Miami, Dept Otolaryngol, Miami, FL 33101 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Miami, Miami Project Cure Paralysis, Miami, FL 33101 USA. Univ Miami, Program Neurosci, Miami, FL 33101 USA. RP Yajnik, V (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM vyajnik@partners.org; xliu@med.miami.edu FU NIDCD NIH HHS [DC 05575]; NIDDK NIH HHS [DK 63933] NR 36 TC 15 Z9 15 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 31 PY 2006 VL 357 IS 3 BP 755 EP 764 DI 10.1016/j.jmb.2006.01.017 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 030IY UT WOS:000236629300006 PM 16464467 ER PT J AU Nishioka, NS Lauwers, GY AF Nishioka, NS Lauwers, GY TI Case 10-2006: A 66-year-old woman with Barrett's esophagus with high-grade dysplasia - Barrett's esophagus with high-grade dysplasia and intramucosal carcinoma with regression of dysplasia and regression of Barrett's esophagus after endoscopic mucosal resection and photodynamic therapy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PORFIMER SODIUM; FOLLOW-UP; CANCER; ADENOCARCINOMA; ABLATION; SURVEILLANCE; MULTICENTER; PROGRESSION; MANAGEMENT; EPITHELIUM C1 Massachusetts Gen Hosp, Gastrointestinal Unit, 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 Pathol, Cambridge, MA 02138 USA. RP Nishioka, NS (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 22 TC 3 Z9 3 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 30 PY 2006 VL 354 IS 13 BP 1403 EP 1409 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 026KO UT WOS:000236338000011 PM 16571884 ER PT J AU Lee, SR Kim, HY Rogowska, J Zhao, BQ Bhide, P Parent, JM Lo, EH AF Lee, SR Kim, HY Rogowska, J Zhao, BQ Bhide, P Parent, JM Lo, EH TI Involvement of matrix metalloproteinase in neuroblast cell migration from the subventricular zone after stroke SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neurogenesis; cerebral ischemia; extracellular matrix; stroke recovery; neural precursor; stroke ID FOCAL CEREBRAL-ISCHEMIA; TISSUE-PLASMINOGEN ACTIVATOR; BLOOD-BRAIN-BARRIER; GENE KNOCK-OUT; ADULT BRAIN; MATRIX-METALLOPROTEINASE-9; NEUROGENESIS; PROTEOLYSIS; INJURY; DEATH AB After brain injury, neuroblast cells from the subventricular zone ( SVZ) expand and migrate toward damaged tissue. The mechanisms that mediate these neurogenic and migratory responses remain to be fully dissected. Here, we show that bromodeoxyuridine-labeled and doublecortin-positive cells from the SVZ colocalize with the extracellular protease matrix metalloproteinase-9 (MMP-9) during the 2 week recovery period after transient focal cerebral ischemia in mice. Treatment with the broad spectrum MMP inhibitor GM6001 significantly decreases the migration of doublecortin-positive cells that extend from the SVZ into the striatum. These data suggest that MMPs are involved in endogenous mechanisms of neurogenic migration as the brain seeks to heal itself after injury. C1 Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02129 USA. Keimyung Univ, Dept Pharmacol, Taegu 700712, South Korea. Konkuk Univ, Dept Neurol, Seoul 143701, South Korea. McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA. Univ Michigan, Sch Med, Dept Neurol, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Lo, EH (reprint author), Massachusetts Gen Hosp E, Neuroprotect Res Lab, Boston, MA 02129 USA. EM Lo@helix.mgh.harvard.edu FU NINDS NIH HHS [R01-NS37074, P50-NS10828, R01-NS40529, R01-NS48422] NR 33 TC 175 Z9 189 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 29 PY 2006 VL 26 IS 13 BP 3491 EP 3495 DI 10.1523/JNEUROSCI.4085-05.2006 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 026SV UT WOS:000236363400014 PM 16571756 ER PT J AU Turk, BE Lee, DH Yamakoshi, Y Klingenhoff, A Reichenberger, E Wright, JT Simmer, JP Komisarof, JA Cantley, LC Bartlett, JD AF Turk, BE Lee, DH Yamakoshi, Y Klingenhoff, A Reichenberger, E Wright, JT Simmer, JP Komisarof, JA Cantley, LC Bartlett, JD TI MMP-20 is predominately a tooth-specific enzyme with a deep catalytic pocket that hydrolyzes type V collagen SO BIOCHEMISTRY LA English DT Article ID HYPOMATURATION AMELOGENESIS-IMPERFECTA; PEPTIDE SUBSTRATE SPECIFICITIES; DEVELOPING MOUSE MOLARS; MATRIX METALLOPROTEINASES; FUNCTIONAL ANTAGONISM; ODONTOGENIC-TUMORS; ENAMELYSIN MMP-20; MICE DISPLAY; EXPRESSION; GENE AB Matrix metalloproteinase-20 (MMP-20, enamelysin) has a highly restricted pattern of expression. In healthy tissues, MMP-20 is observed in the enamel organ and pulp organ of developing teeth and is present only as an activated enzyme. To identify other tissues that may express MMP-20, we performed a systematic mouse tissue expression screen. Among the non-tooth tissues assayed, MMP-20 transcripts were identified only in minute quantities within the large intestine. The murine Mmp20 promoter was cloned, sequenced, and assessed for potential tooth-specific regulatory elements. In silico analysis identified four promoter modules that were common to Mmp20 and at least two of three coregulated predominantly tooth-specific genes that encode ameloblastin, amelogenin, and enamelin. We asked if the highly restricted MMP-20 expression pattern was associated with a broad substrate specificity that might preclude its expression in other tissues. An iterative mixture-based random doedecamer peptide library screen with Edman sequencing of MMP-20 cleavage products revealed that, among MMPs previously screened. MMP-20 had unique substrate preferences. These preferences indicate that MMP-20 has a deep and wide catalytic pocket that can accommodate Substrates with large aromatic residues in the P1' position. On the basis of matrices derived from the peptide library data, we identified and then confirmed that type V collagen is an MMP-20 Substrate. Since type V collagen is not present in dental enamel but is an otherwise widely distributed collagen. and since only active MMP-20 has been observed in teeth. our data suggest that control of MMP-20 activity is primarily regulated by transcriptional means. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Yale Univ, Dept Pharmacol, New Haven, CT 06520 USA. Univ Michigan, Dent Res Lab, Ann Arbor, MI 48108 USA. Univ Connecticut, Ctr Restorat Med & Skeletal Dev, Sch Dent Med, Dept Oral Rehabil Biomat & Skeletal Dev, Farmington, CT 06030 USA. Univ N Carolina, Dept Pediat Dent, Chapel Hill, NC 27599 USA. Ctr Excellence Educ, Res Sci Inst, Vienna, VA 22124 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. Genomatix Software GmbH, D-80335 Munich, Germany. RP Bartlett, JD (reprint author), Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. EM jbartlett@forsyth.org RI Wright, John/B-5390-2013; Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCRR NIH HHS [C06RR11244]; NIDA NIH HHS [DA 13237]; NIDCR NIH HHS [DE14084, P01 DE013237, P01 DE013237-010004, P01 DE013237-020004, P01 DE013237-030004, P01 DE013237-040004, P01 DE013237-050004, R01 DE014084, R01 DE014084-01A1, R01 DE014084-02, R01 DE014084-03, R01 DE014084-04, R01 DE014084-05, R01 DE016276, R01 DE016276-01A2, R01 DE016276-02, R01 DE016276-03, R29 DE012098, R29 DE012098-03, R29 DE012098-04, R29 DE012098-05]; NIGMS NIH HHS [R01 GM056203-03, GM56203, R01 GM056203, R01 GM056203-04, R01 GM056203-05, R01 GM056203-06, R01 GM056203-07, R01 GM056203-08, R01 GM056203-09, R01 GM056203-10, R01 GM056203-11, R01 GM056203-12] NR 63 TC 28 Z9 30 U1 0 U2 3 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 28 PY 2006 VL 45 IS 12 BP 3863 EP 3874 DI 10.1021/bi0522520 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 028NT UT WOS:000236495400003 PM 16548514 ER PT J AU Chan, AT Manson, JE Albert, CM Chae, CU Rexrode, KM Curhan, GC Rimm, EB Willett, WC Fuchs, CS AF Chan, AT Manson, JE Albert, CM Chae, CU Rexrode, KM Curhan, GC Rimm, EB Willett, WC Fuchs, CS TI Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events SO CIRCULATION LA English DT Article DE acetaminophen; aspirin; cardiovascular diseases; cyclooxygenase-2 inhibitors; nonsteroidal antiinflammatory drugs ID ACUTE MYOCARDIAL-INFARCTION; NONNARCOTIC ANALGESIC USE; LOW-DOSE ASPIRIN; PRIMARY PREVENTION; CYCLO-OXYGENASE-2 INHIBITORS; CYCLOOXYGENASE-2 INHIBITORS; COX-2 INHIBITORS; RENAL-FUNCTION; US WOMEN; POPULATION AB Background - Although randomized trials of cyclooxygenase-2 (COX-2) inhibitors have shown increased cardiovascular risk, studies of nonselective, nonsteroidal antiinflammatory drugs ( NSAIDs) and acetaminophen have been inconsistent. Methods and Results - We examined the influence of NSAIDs and acetaminophen on the risk of major cardiovascular events ( nonfatal myocardial infarction, fatal coronary heart disease, nonfatal and fatal stroke) in a prospective cohort of 70 971 women, aged 44 to 69 years at baseline, free of known cardiovascular disease or cancer, who provided medication data biennially since 1990. During 12 years of follow-up, we confirmed 2041 major cardiovascular events. Women who reported occasional ( 1 to 21 d/mo) use of NSAIDs or acetaminophen did not experience a significant increase in the risk of cardiovascular events. However, after adjustment for cardiovascular risk factors, women who frequently ( >= 22 d/mo) used NSAIDs had a relative risk (RR) for a cardiovascular event of 1.44 ( 95% CI, 1.27 to 1.65) compared with nonusers, whereas those who frequently consumed acetaminophen had a RR of 1.35 ( 95% CI, 1.14 to 1.59). The elevated risk associated with frequent NSAID use was particularly evident among current smokers ( RR = 1.82; 95% CI, 1.38 to 2.42) and was absent among never smokers (P-interaction = 0.02). Moreover, we observed significant dose-response relations: Compared with nonusers, the RRs for a cardiovascular event among women who used >= 15 tablets per week were 1.86 ( 95% CI, 1.27 to 2.73) for NSAIDs and 1.68 ( 95% CI, 1.10 to 2.58) for acetaminophen. Conclusions - Use of NSAIDs or acetaminophen at high frequency or dose is associated with a significantly increased risk for major cardiovascular events, although more moderate use did not confer substantial risk. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Div Cardiol, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ 722, Boston, MA 02114 USA. EM achan@partners.org OI Rexrode, Kathryn/0000-0003-3387-8429 FU NCI NIH HHS [CA107412, CA 87969]; NHLBI NIH HHS [HL 34594] NR 57 TC 159 Z9 167 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 28 PY 2006 VL 113 IS 12 BP 1578 EP 1587 DI 10.1161/CIRCULATIONAHA.105.595793 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 025UO UT WOS:000236292600009 PM 16534006 ER PT J AU Little, WC Freeman, GL AF Little, WC Freeman, GL TI Pericardial disease SO CIRCULATION LA English DT Article DE cardiac tamponade; pericarditis; pericardium ID EFFUSIVE-CONSTRICTIVE PERICARDITIS; VENTRICULAR DIASTOLIC COLLAPSE; ACUTE MYOCARDIAL-INFARCTION; CARDIAC TROPONIN-I; RESTRICTIVE CARDIOMYOPATHY; RECURRENT PERICARDITIS; DOPPLER-ECHOCARDIOGRAPHY; ETIOLOGIC DIAGNOSIS; INTRAPERICARDIAL TREATMENT; BALLOON PERICARDIOTOMY C1 Wake Forest Univ, Bowman Gray Sch Med, Cardiol Sect, Winston Salem, NC 27157 USA. Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, Dept Physiol, San Antonio, TX USA. RP Little, WC (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Cardiol Sect, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM wlittle@wfubmc.edu NR 83 TC 135 Z9 155 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 28 PY 2006 VL 113 IS 12 BP 1622 EP 1632 DI 10.1161/CIRCULATIONAHA.105.561514 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 025UO UT WOS:000236292600014 PM 16567581 ER PT J AU Chu, BC Yuan, C Takaya, N Shewchuk, JR Clowes, AW Hatsukami, TS AF Chu, BC Yuan, C Takaya, N Shewchuk, JR Clowes, AW Hatsukami, TS TI Serial high-spatial-resolution, multisequence magnetic resonance imaging studies identify fibrous cap rupture and penetrating ulcer into carotid atherosclerotic plaque SO CIRCULATION LA English DT Editorial Material C1 Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Univ Washington, Dept Surg, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Dept Surg, Seattle, WA USA. RP Chu, BC (reprint author), Univ Washington, Dept Radiol, Box 357115,1959 NE Pacific St, Seattle, WA 98195 USA. EM chubc@u.washington.edu FU NHLBI NIH HHS [R01-HL-61851, R01-HL-073401] NR 4 TC 16 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 28 PY 2006 VL 113 IS 12 BP E660 EP E661 DI 10.1161/CIRCULATIONAHA.105.567255 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 025UO UT WOS:000236292600017 PM 16567574 ER PT J AU Mager, DL AF Mager, D. L. TI Bacteria and cancer: cause, coincidence or cure? A review SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Review ID HELICOBACTER-PYLORI INFECTION; ORAL DNA VACCINE; STREPTOCOCCUS-BOVIS BACTEREMIA; GASTRIC CARDIA ADENOCARCINOMA; DECAY-ACCELERATING FACTOR; CEA-TRANSGENIC MICE; CELL-LUNG-CANCER; ESCHERICHIA-COLI; COLORECTAL-CANCER; GALLBLADDER CANCER AB Research has found that certain bacteria are associated with human cancers. Their role, however, is still unclear. Convincing evidence links some species to carcinogenesis while others appear promising in the diagnosis, prevention or treatment of cancers. The complex relationship between bacteria and humans is demonstrated by Helicobacter pylori and Salmonella typhi infections. Research has shown that H. pylori can cause gastric cancer or MALT lymphoma in some individuals. In contrast, exposure to H. pylori appears to reduce the risk of esophageal cancer in others. Salmonella typhi infection has been associated with the development of gallbladder cancer; however S. typhi is a promising carrier of therapeutic agents for melanoma, colon and bladder cancers. Thus bacterial species and their roles in particular cancers appear to differ among different individuals. Many species, however, share an important characteristic: highly site-specific colonization. This critical factor may lead to the development of non-invasive diagnostic tests, innovative treatments and cancer vaccines. C1 Forsyth Inst, Boston, MA 02115 USA. RP Mager, DL (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM dmager@forsyth.org NR 137 TC 79 Z9 83 U1 2 U2 20 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD MAR 28 PY 2006 VL 4 AR 14 DI 10.1186/1479-5876-4-14 PG 18 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 054VW UT WOS:000238407700001 PM 16566840 ER PT J AU Morita, M Al-Chalabi, A Andersen, PM Hosler, B Sapp, P Englund, E Mitchell, JE Habgood, JJ de Belleroche, J Xi, J Brown, RH AF Morita, M Al-Chalabi, A Andersen, PM Hosler, B Sapp, P Englund, E Mitchell, JE Habgood, JJ de Belleroche, J Xi, J Brown, RH TI A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementia SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; EXTRAMOTOR INVOLVEMENT; CORTICOSPINAL TRACT; PRESENILE-DEMENTIA; SPASTIC PARALYSIS; INCLUSION-BODIES; LOBE; GENE; DEGENERATION AB Objective: To perform genetic linkage analysis in a family affected with ALS and frontotemporal dementia (FTD). Methods: The authors performed a genome-wide linkage analysis of a four-generation, 50-member Scandinavian family in which five individuals were diagnosed with ALS and nine with FTD. Linkage calculations assuming autosomal dominant inheritance of a single neurodegenerative disease manifesting as either ALS or FTD with age-dependent penetrance were performed. Further analyses for ALS alone and FTD alone were performed. A parametric logarithm of odds (lod) score of 2.0 or greater was required for further study of a potential locus and crossover (haplotype) analysis. Results: A new ALS-FTD locus was identified between markers D9s1870 and D9s1791 on human chromosome 9p21.3-p13.3. A maximum multipoint lod score of 3.00 was obtained between markers D9s1121 and D9s2154. Crossover analysis indicates this region covers approximately 21.8 cM, or 14Mb. Conclusions: A locus on chromosome 9p21.3-p13.3 is linked to ALS-FTD. C1 Massachusetts Gen Hosp, Day Neuromuscular Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Univ London Kings Coll, Inst Psychiat, Dept Neurol, London WC2R 2LS, England. Umea Univ Hosp, Dept Neurol, S-90185 Umea, Sweden. Umea Univ, Inst Clin Neurosci, Umea, Sweden. MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. Univ Lund Hosp, Dept Pathol, S-22185 Lund, Sweden. Charing Cross Hosp, Imperial Coll London, Fac Med, London, England. Orebro Univ Hosp, Dept Clin Med, Orebro, Sweden. RP Brown, RH (reprint author), Massachusetts Gen Hosp, Day Neuromuscular Lab, Boston, MA 02129 USA. EM BrownRHJr@aol.com RI Al-Chalabi, Ammar/E-5361-2010 OI Al-Chalabi, Ammar/0000-0002-4924-7712 FU NINDS NIH HHS [1PO1NS31248-02, R01NS37912] NR 51 TC 231 Z9 236 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 28 PY 2006 VL 66 IS 6 BP 839 EP 844 DI 10.1212/01.wnl.0000200048.53766.b4 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 025UL UT WOS:000236292300012 PM 16421333 ER PT J AU Loeppky, JA Caprihan, A Altobelli, SA Icenogle, MV Scotto, P Melo, MFV AF Loeppky, JA Caprihan, A Altobelli, SA Icenogle, MV Scotto, P Melo, MFV TI Validation of a two-compartment model of ventilation/perfusion distribution SO RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY LA English DT Article DE alveolar-arterial PO2 difference; arterial-alveolar PCO2 difference; chronic obstructive pulmonary disease; diffusion limitation; hypoxemia; V-A/Q models ID OBSTRUCTIVE PULMONARY-DISEASE; GAS-EXCHANGE; PERFUSION INEQUALITY; DIFFUSING-CAPACITY; EXERCISE; OXYGEN; BLOOD; LUNG; DOGS; O2 AB Ventilation (V-A) to perfusion (Q) heterogeneity (V-A/Q) analyses by a two-compartment lung model (2(C)), utilizing routine gas exchange measurements and a computer solution to account for O-2 and CO2 measurements, were compared with multiple inert gas elimination technique (MIGET) analyses and a multi-compartment (MC) model. The 2C and MC estimates of V-A/Q mismatch were obtained in 10 healthy subjects, 43 patients having chronic obstructive pulmonary disease (COPD) and in 14 dog experiments where hemodynamics and acid-base status were manipulated with gas mixtures, fluid loading and tilt-table stressors. MIGET comparisons with 2C were made on 6 patients and 32 measurements in healthy subjects before and after exercise at normoxia and altitude hypoxia. Statistically significant correlations for logarithmic standard deviations of V-A/Q distributions (SD(V-A/Q)) were obtained for all 2C comparisons, with similar values between 2C and both other methods in the 1.1-1.5 range, compatible with mild to moderate COPD. 2C tended to overestimate MC and MIGET values at low and underestimate them at high SD(VA/Q) values. SD(VA/Q) weighted by Q agreed better with MC and MIGET estimates in the normal range, whereas SD(V-A/Q) weighted by VA was closer to MC at higher values because the V-A-weighted SD(V-A/Q) is related to blood-to-gas PCO2 differences that are elevated in disease, thereby allowing better discrimination. The 2C model accurately described functional V-A/Q characteristics in 26 normal and bronchoconstricted dogs during non-steady state rebreathing and could be used to quantify the effect of reduced O-2 diffusing capacity in diseased lungs. These comparisons indicate that 2C adequately describes V-A/Q mismatch and can be useful in clinical or experimental situations where other techniques are not feasible. (c) 2005 Elsevier B. V. All rights reserved. C1 Vet Adm Med Ctr, Cardiol Sect 111B, Albuquerque, NM 87108 USA. New Mexico Resonance, Albuquerque, NM 87106 USA. Univ Naples Federico II, Dipartimento Farmacol Sperimentale, I-80131 Naples, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Loeppky, JA (reprint author), Vet Adm Med Ctr, Cardiol Sect 111B, 1501 San Pedro Dr SE, Albuquerque, NM 87108 USA. EM Loeppky@unm.edu NR 43 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9048 J9 RESP PHYSIOL NEUROBI JI Respir. Physiol. Neuro. PD MAR 28 PY 2006 VL 151 IS 1 BP 74 EP 92 DI 10.1016/j.resp.2005.06.002 PG 19 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 029YB UT WOS:000236599200005 PM 16024300 ER PT J AU Moreland, EC Volkening, LK Lawlor, MT Chalmers, KA Anderson, BJ Laffel, LMB AF Moreland, EC Volkening, LK Lawlor, MT Chalmers, KA Anderson, BJ Laffel, LMB TI Use of a blood glucose monitoring manual to enhance monitoring adherence in adults with diabetes - A randomized controlled trial SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID GLYCEMIC CONTROL; MELLITUS; COMPLICATIONS; POPULATION; BARRIERS; CARE; FREQUENCY; OUTCOMES AB Background: Frequent blood glucose (BG) monitoring is a critical component of diabetes management, yet many barriers exist to consistent monitoring. Methods: In this randomized controlled trial, we sought to determine if an educational manual, the Blood Sugar Monitoring Owner's Manual (BGMOM), could increase adherence to BG monitoring by helping patients form realistic expectations and responses to BG monitoring results. The 199 participants were recruited from a multidisciplinary diabetes clinic and had high-risk diabetes (hemoglobin A(1C) >= 8.0%); 35% had type 1 diabetes mellitus. Participants were randomized to 1 of 3 groups: BGMOM intervention (BGM+), attention control ( BG meter only [MT]), or standard care (SC). The BGM+ and MT groups received BG meters and meter education; the BGM+ group also received BGMOM booklets. The SC group received usual care. Data gathered during 6 months of follow-up included BG monitoring frequency and hemoglobin A(1C) measurement. Results: Monitoring frequency increased significantly in the BGM+ group (1.9 +/- 1.3 to 2.8 +/- 1.5 times daily, P < .001) but only slightly in the MT group (1.7 +/- 1.3 to 2.0 +/- 1.3 times daily). The BGM+ group experienced the greatest improvement in hemoglobin A(1C) level (BGM+: -0.13 +/- 1.28; MT: -0.04 +/- 1.31; SC: 0.04 +/- 1.10). Further, a higher percentage of those in the BGM+ group (61%) improved their glycemic control compared with the other groups (44%; P = .05). Finally, the BGM+ group displayed the most knowledge about the definition of hemoglobin A(1C) (P = .04) and reported the least amount of negative affect about out-of-range BG monitoring results (P =. 03). Conclusion: As an adjunct to standard diabetes education and support, a manual such as the BGMOM can help optimize BG monitoring and glycemic control. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. Joslin Diabet Ctr, Sect Behav & Mental Hlth, Boston, MA 02215 USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU NIDDK NIH HHS [T32 DK007260, T32 DK063702] NR 26 TC 38 Z9 38 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 27 PY 2006 VL 166 IS 6 BP 689 EP 695 DI 10.1001/archinte.166.6.689 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 025RH UT WOS:000236284100016 PM 16567610 ER PT J AU Schernhammer, ES Tranah, GJ Giovannucci, E Chan, AT Ma, J Colditz, GA Hunter, DJ Willett, WC Fuchs, CS AF Schernhammer, ES Tranah, GJ Giovannucci, E Chan, AT Ma, J Colditz, GA Hunter, DJ Willett, WC Fuchs, CS TI Cyclin DI A870G polymorphism and the risk of colorectal cancer and adenoma SO BRITISH JOURNAL OF CANCER LA English DT Article DE cyclin D; CCNDI; A870D; polymorphism; colorectal cancer; colorectal adenoma ID D1 GENE; BREAST-CANCER; BLADDER-CANCER; METHYLENETETRAHYDROFOLATE REDUCTASE; G870A POLYMORPHISM; CIGARETTE-SMOKING; PROSTATE-CANCER; AA GENOTYPE; ASSOCIATION; CARCINOMA AB Cyclin D1 ( CCND1) plays a key role in cell cycle control, particularly in the transition from G(1) to S phase, which is regulated by cyclin-dependent kinases. A common adenine to guanine polymorphism ( A870G) in the CCND1 gene has been associated with a longer- life protein and an increased risk of colorectal cancer and adenoma in some studies. Among subjects with hereditary nonpolyposis colorectal cancer, the A870G polymorphism has also been associated with a younger age of onset of colorectal cancer. We analysed 181 colorectal cancer cases and 475 matched controls and 524 adenoma cases and 517 matched controls within women in the Nurses' Health Study ( NHS) cohort, 171 colorectal cancer cases and 347 matched controls and 372 adenoma cases and 712 matched controls nested within men in the Health Professionals' Follow- Up Study ( HPFS) cohort, and 258 colorectal cancer cases and 415 matched controls within men in the Physicians' Health Study ( PHS) cohort to assess the risk associated with the CCND1 A870G genotype. Moreover, we assessed whether CCND1 genotype modified the effect of a sporadic ( nonsyndromic) family history of colorectal cancer as well as the effect of other dietary and lifestyle risk factors for colorectal cancer and adenoma. In all cohorts combined, the CCND1 polymorphism did not show statistically significant associations to risk of colorectal cancer ( odds ratio ( OR) for A allele carriers, 1.04; 95% confidence interval ( 95% CI), 0.82 - 1.32) or adenoma ( OR, 0.96; 95% Cl, 0.79 - 1.18). The CCND1 A870G genotype was associated with a modest, although nonsignificantly elevated risk of colorectal cancer ( OR, 1.59; 95% Cl, 0.98 - 2.57) in women. In contrast, the polymorphism was not associated with increased risk of adenoma in either men or women. Among participants with the A870G genotype, a family history of colorectal cancer conferred a substantially greater risk of colorectal cancer in the women ( P for interaction 0.06) and adenoma in the men ( P for interaction 0.02). Current postmenopausal hormone ( PMH) use was associated with a significant reduction in the risk of colorectal cancer and adenoma among women with the A870G genotype, whereas there was no effect of PMH use among those with the GG genotype. The CCND1 polymorphism appeared to confer a modest elevation in the risk of colorectal cancer among women. Moreover, the A870G genotype may enhance the protective effect of postmenopausal oestrogen use on the development of colorectal neoplasia. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. KFJ Spital, Ludwig Boltzmann Inst Appl Canc Res, Vienna, Austria. Inst Translat Res Vienna, Vienna, Austria. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Ctr Canc Prevent, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Dana Faber Canc Inst, Program Epidemiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Schernhammer, ES (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM eva.schemhammer@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA87969, CA42812, CA55075, CA58684, CA70817, CA90598, P01 CA055075, P01 CA087969, R01 CA058684, R01 CA070817, R01 CA090598] NR 44 TC 23 Z9 23 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR 27 PY 2006 VL 94 IS 6 BP 928 EP 934 DI 10.1038/sj.bjc.6603007 PG 7 WC Oncology SC Oncology GA 024BU UT WOS:000236170700023 PM 16495921 ER PT J AU Kitchens, WH Uehara, S Chase, CM Colvin, RB Russell, PS Madsen, JC AF Kitchens, WH Uehara, S Chase, CM Colvin, RB Russell, PS Madsen, JC TI The changing role of natural killer cells in solid organ rejection and tolerance SO TRANSPLANTATION LA English DT Editorial Material DE natural killer cells; organ transplantation; allograft rejection; tolerance; cardiac allograft vasculopathy ID PORCINE ENDOTHELIAL-CELLS; APOPTOSIS-INDUCING LIGAND; HUMAN NK CELLS; ALLOGRAFT-REJECTION; BONE-MARROW; DENDRITIC CELLS; IFN-GAMMA; LIVER-TRANSPLANTATION; XENOGRAFT REJECTION; HYBRID RESISTANCE AB Natural killer (NK) cells have emerged as a particular focus of interest in transplantation due to their ability to distinguish allogeneic major histocompatibility complex (MHC) antigens and their potent cytolytic effector mechanisms. Once relegated to the field of bone marrow transplantation, NK cells have recently been shown to participate in the immune response against solid organ allo- and xenografts. These new findings suggest that the role of NK cells in solid organ rejection and tolerance needs to be reexamined. C1 Massachusetts Gen Hosp, Dept Surg, Div Transplantat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Transplantat, Bul 119,55 Fruit St, Boston, MA 02114 USA. EM madsen@helix.mgh.harvard.edu FU NHLBI NIH HHS [R01 HL 071932] NR 92 TC 88 Z9 92 U1 0 U2 2 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 2006 VL 81 IS 6 BP 811 EP 817 DI 10.1097/01.tp.0000202844.33794.0e PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 027UK UT WOS:000236440900001 PM 16570001 ER PT J AU Burroughs, L Mielcarek, M Leisenring, W Sandmaier, BM Maloney, DG Baron, F Martin, PJ Flowers, MED Forman, SJ Chauncey, TR Bruno, B Storb, R AF Burroughs, L Mielcarek, M Leisenring, W Sandmaier, BM Maloney, DG Baron, F Martin, PJ Flowers, MED Forman, SJ Chauncey, TR Bruno, B Storb, R TI Extending postgrafting cyclosporine decreases the risk of severe graft-versus-host disease after nonmyeloablative hematopoietic cell transplantation SO TRANSPLANTATION LA English DT Article DE graft-versus-host disease; nonmyeloablative conditioning; allogeneic hematopoietic cell transplantation; cyclosporine ID BONE-MARROW-TRANSPLANTATION; TOTAL-BODY IRRADIATION; MATCHED RELATED DONORS; SEVERE APLASTIC-ANEMIA; TERM FOLLOW-UP; HEMATOLOGIC MALIGNANCIES; COMPARING METHOTREXATE; RANDOMIZED-TRIAL; UNRELATED DONORS; HUMAN RECIPIENTS AB Background. It is unknown whether the duration of systemic immunosuppressive treatment after allogeneic nonmyeloablative hematopoietic cell transplantation (HCT) might influence the incidence, severity, timing, and/or corticosteroid-responsiveness of graft-versus-host disease (GVHD). Methods. We retrospectively analyzed outcomes among 185 patients with hematologic malignancies who were given grafts from HLA-matched related donors following conditioning with 2 Gy total body irradiation alone or in combination with fludarabine between December 1998 and March 2003. Postgrafting immunosuppression consisted of mycophenolate mofetil (days 0-27) in combination with 3 different cyclosporine (CSP) regimens: taper from (A) days 35 to 56 (n=107), (B) days 56 to 77 (n=35), and (C) days 56 to 180 (n=43). Results. The overall incidences of grades II-IV and III-IV acute GVHD, and extensive chronic GVHD were 52%,13%, and 56%, respectively. The duration of CSP prophylaxis did not significantly influence the overall rate of acute GVHD (grade II-IV), extensive chronic GVHD, or non-relapse mortality. However, prolonged administration of CSP (group C) was associated with a significantly decreased hazard of grades III-IV acute GVHD (HR 0.2, 95% CI [0.04, 0.9]) and with an increased likelihood of discontinuing all systemic immunosuppression (HR 2.4, 95% Cl [1.1, 5.2]) when compared to the shortest course of CSP (group A). Conclusion. Longer CSP duration decreased the risk of severe GVHD and increased the likelihood of discontinuing all systemic immunosuppression after nonmyeloablative HCT with HLA-matched related grafts. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Turin, Turin, Italy. 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 [CA 18029, CA 15704, CA 78902, K12 CA 076930, P01 CA078902]; NHLBI NIH HHS [HL 36444]; NIDDK NIH HHS [DK 064715] NR 34 TC 27 Z9 27 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 2006 VL 81 IS 6 BP 818 EP 825 DI 10.1097/01.tp.0000203556.06145.5b PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 027UK UT WOS:000236440900002 PM 16570002 ER PT J AU Xu, YX Yang, YG Ohdan, H Ryan, D Harper, D Wu, C Kruger-Grey, HS Thall, AD Awwad, M Sykes, M AF Xu, YX Yang, YG Ohdan, H Ryan, D Harper, D Wu, C Kruger-Grey, HS Thall, AD Awwad, M Sykes, M TI Characterization of anti-Gal antibody-producing cells of baboons and humans SO TRANSPLANTATION LA English DT Article DE anti-Gal antibody-secreting cells; B cells; plasma cells ID NUCLEAR TRANSFER; PLASMA-CELLS; B-1 CELLS; B-CELLS; PIG; DEPLETION; EPITOPES; TRANSPLANTATION; IMMUNOTHERAPY; PERITONEAL AB Background. Anti-Gal antibodies cause hyperacute and delayed xenograft rejection in pig-to-primate transplantation. The cell populations producing anti-Gal and other natural antibodies in primates are unknown. Methods. Cells from different lymphoid compartments of naive or sensitized baboons were examined for anti-Gal and total Ig production by ELISPOT. B and plasma cells from humans and baboons were purified by FACS sorting and characterized for anti-Gal and total Ig production and cytology. Results. In naive baboons, the spleen was the major source of anti-Gal IgM-secreting cells. Two months after sensitization with porcine tissues, high frequencies of anti-Gal IgM- and IgG-secreting cells were detected in the spleen, lymph nodes, and bone marrow. Six months after antigen exposure, anti-Gal IgM- and IgG-secreting cells were preferentially localized in the bone marrow. Cells from human spleen, bone marrow, and blood were also analyzed and anti-Gal IgM-secreting cells were detected mainly in the spleen. Sorting of baboon and human cells showed that anti-Gal IgM-secreting cells were mainly splenic B cells (CD20(+), CD138(-), and Ig(+)). Although low in percentage, sorted CD20(-)CD138(+) plasma cells in spleen and bone marrow secreted large quantities of anti-Gal IgM. Most anti-Gal IgG-secreting cells were plasma cells (CD138(+)) at both early(Ig(+)) and late (Ig(-)) stages of differentiation. Conclusions. Similar to Gal knockout mice, natural anti-Gal IgM antibodies in primates are produced mainly by splenic B cells. After antigen exposure, anti-Gal IgM and IgG were secreted by both B and plasma cells. These results suggest strategies to remove xenoreactive antibody-secreting cells prior to transplantation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Immerge BioTherapeut, Cambridge, MA USA. BioTransplant Inc, Medford, MA USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E Bldg 149-5102,13th St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu FU NIAID NIH HHS [R01 AI 045897]; PHS HHS [P01 08646] NR 31 TC 9 Z9 9 U1 1 U2 1 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 2006 VL 81 IS 6 BP 940 EP 948 DI 10.1097/01.tp.0000203300.87272.a3 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 027UK UT WOS:000236440900021 PM 16570021 ER PT J AU Schwarzschild, MA AF Schwarzschild, Michael A. TI Progress on the etiology, modeling and treatment of Parkinson's disease SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Serv Neurol, Boston, MA 02129 USA. EM michaels@helix.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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 26 PY 2006 VL 231 MA 172-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125906390 ER PT J AU Moffat, J Grueneberg, DA Yang, XP Kim, SY Kloepfer, AM Hinkle, G Piqani, B Eisenhaure, TM Luo, B Grenier, JK Carpenter, AE Foo, SY Stewart, SA Stockwell, BR Hacohen, N Hahn, WC Lander, ES Sabatini, DM Root, DE AF Moffat, J Grueneberg, DA Yang, XP Kim, SY Kloepfer, AM Hinkle, G Piqani, B Eisenhaure, TM Luo, B Grenier, JK Carpenter, AE Foo, SY Stewart, SA Stockwell, BR Hacohen, N Hahn, WC Lander, ES Sabatini, DM Root, DE TI A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen SO CELL LA English DT Article ID CULTURED-MAMMALIAN-CELLS; CAENORHABDITIS-ELEGANS; INTERFERING RNAS; HUMAN KINASES; IN-VIVO; GENOME; IDENTIFICATION; APOPTOSIS; PATHWAY; COMPONENTS AB To enable arrayed or pooled loss-of-function screens in a wide range of mammalian cell types, including primary and nondividing cells, we are developing lentiviral short hairpin RNA (shRNA) libraries targeting the human and murine genomes. The libraries currently contain 104,000 vectors, targeting each of 22,000 human and mouse genes with multiple sequence-verified constructs. To test the utility of the library for arrayed screens, we developed a screen based on high-content imaging to identify genes required for mitotic progression in human cancer cells and applied it to an arrayed set of 5,000 unique shRNA-expressing lentiviruses that target 1,028 human genes. The screen identified several known and similar to 100 candidate regulators of mitotic progression and proliferation; the availability of multiple shRNAs targeting the same gene facilitated functional validation of putative hits. This work provides a widely applicable resource for loss-of-function screens, as well as a roadmap for its application to biological discovery. C1 MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02139 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. Columbia Univ, Dept Chem, Dept Sci Biol, New York, NY 10027 USA. RP Root, DE (reprint author), MIT, Broad Inst, Cambridge, MA 02139 USA. EM droot@broad.mit.edu RI Carpenter, Anne/C-4982-2008; Stewart, Sheila/C-5213-2012; Tang, Amy/L-3226-2016 OI Carpenter, Anne/0000-0003-1555-8261; Tang, Amy/0000-0002-5772-2878 FU NCI NIH HHS [CA103866, P50 CA112962, R01CA97061] NR 42 TC 878 Z9 901 U1 13 U2 66 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 24 PY 2006 VL 124 IS 6 BP 1283 EP 1298 DI 10.1016/j.cell.2006.01.040 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 038RS UT WOS:000237241400026 PM 16564017 ER PT J AU Nishio, J Gaglia, JL Turvey, SE Campbell, C Benoist, C Mathis, D AF Nishio, J Gaglia, JL Turvey, SE Campbell, C Benoist, C Mathis, D TI Islet recovery and reversal of murine type 1 diabetes in the absence of any infused spleen cell contribution SO SCIENCE LA English DT Article ID NOD MICE; IMMUNOTHERAPY; MOUSE AB A cure for type 1 diabetes will probably require the provision or elicitation of new pancreatic islet beta cells as welt as the reestablishment of immunological tolerance. A 2003 study. reported achievement of both advances in the NOD mouse model by coupling injection of Freund's complete adjuvant with infusion of allogeneic spleen cells. it was concluded that the adjuvant eliminated anti-islet autoimmunity and the donor splenocytes differentiated into insulin-producing (presumably beta) cells, culminating in islet regeneration. Here, we provide data indicating that the recovered islets were all of host origin, reflecting that the diabetic NOD mice actually retain substantial beta cell mass, which can be rejuvenated/regenerated to reverse disease upon adjuvant-dependent dampening of autoimmunity. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Stem Cell Inst, Boston, MA 02215 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu OI Gaglia, Jason/0000-0003-2904-312X; Turvey, Stuart/0000-0003-1599-1065 FU NCI NIH HHS [T32 CA09382] NR 13 TC 90 Z9 101 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 24 PY 2006 VL 311 IS 5768 BP 1775 EP 1778 DI 10.1126/science.1124004 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 024OA UT WOS:000236204300046 PM 16556845 ER PT J AU Rush, AJ Trivedi, MH Wisniewski, SR Stewart, JW Nierenberg, AA Thase, ME Ritz, L Biggs, MM Warden, D Luther, JF Shores-Wilson, K Niederehe, G Fava, M AF Rush, AJ Trivedi, MH Wisniewski, SR Stewart, JW Nierenberg, AA Thase, ME Ritz, L Biggs, MM Warden, D Luther, JF Shores-Wilson, K Niederehe, G Fava, M CA STAR D Study Team TI Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID STAR-ASTERISK-D; SEROTONIN REUPTAKE INHIBITORS; SEQUENCED TREATMENT ALTERNATIVES; RESISTANT MAJOR DEPRESSION; OPEN-LABEL TRIAL; REPORT QIDS-SR; PSYCHOMETRIC EVALUATION; TREATMENT STRATEGY; QUICK INVENTORY; RATING SCALE AB BACKGROUND After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor (SSRI), it is not known whether switching to one antidepressant is more effective than switching to another. METHODS We randomly assigned 727 adult outpatients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSRI citalopram to receive one of the following drugs for up to 14 weeks: sustained-release bupropion (239 patients) at a maximal daily dose of 400 mg, sertraline (238 patients) at a maximal daily dose of 200 mg, or extended-release venlafaxine (250 patients) at a maximal daily dose of 375 mg. The study was conducted in 18 primary and 23 psychiatric care settings. The primary outcome was symptom remission, defined by a total score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of the study. Scores on the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR-16), obtained at treatment visits, determined secondary outcomes, including remission (a score of 5 or less at exit) and response (a reduction of 50 percent or more on baseline scores). RESULTS Remission rates as assessed by the HRSD-17 and the QIDS-SR-16, respectively, were 21.3 percent and 25.5 percent for sustained-release bupropion, 17.6 percent and 26.6 percent for sertraline, and 24.8 percent and 25.0 percent for extended-release venlafaxine. QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion, 26.7 percent for sertraline, and 28.2 percent for extended-release venlafaxine. These treatments did not differ significantly with respect to outcomes, tolerability, or adverse events. CONCLUSIONS After unsuccessful treatment with an SSRI, approximately one in four patients had a remission of symptoms after switching to another antidepressant. Any one of the medications in the study provided a reasonable second-step choice for patients with depression. C1 Univ Texas, SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Coll Phys & Surg, New York, NY USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. NIMH, Bethesda, MD 20892 USA. RP Rush, AJ (reprint author), Univ Texas, SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM john.rush@utsouthwestern.edu RI Biggs, Dr. Melanie/C-1468-2010; Howland, Robert/K-6937-2015; OI Howland, Robert/0000-0002-6533-6010; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003] NR 41 TC 521 Z9 530 U1 5 U2 45 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 23 PY 2006 VL 354 IS 12 BP 1231 EP 1242 DI 10.1056/NEJMoa052963 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 023ZH UT WOS:000236164200002 PM 16554525 ER PT J AU Trivedi, MH Fava, M Wisniewski, SR Thase, ME Quitkin, F Warden, D Ritz, L Nierenberg, AA Lebowitz, BD Biggs, MM Luther, JF Shores-Wilson, K Rush, AJ AF Trivedi, MH Fava, M Wisniewski, SR Thase, ME Quitkin, F Warden, D Ritz, L Nierenberg, AA Lebowitz, BD Biggs, MM Luther, JF Shores-Wilson, K Rush, AJ CA STAR D Study Team TI Medication augmentation after the failure of SSRIs for depression SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID STAR-ASTERISK-D; SEQUENCED TREATMENT ALTERNATIVES; ALGORITHM PROJECT; RATIONALE; DISORDER AB BACKGROUND Although clinicians frequently add a second medication to an initial, ineffective antidepressant drug, no randomized controlled trial has compared the efficacy of this approach. METHODS We randomly assigned 565 adult outpatients who had nonpsychotic major depressive disorder without remission despite a mean of 11.9 weeks of citalopram therapy (mean final dose, 55 mg per day) to receive sustained-release bupropion (at a dose of up to 400 mg per day) as augmentation and 286 to receive buspirone (at a dose of up to 60 mg per day) as augmentation. The primary outcome of remission of symptoms was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of this study; scores were obtained over the telephone by raters blinded to treatment assignment. The 16-item Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR-16) was used to determine the secondary outcomes of remission (defined as a score of less than 6 at the end of this study) and response (a reduction in baseline scores of 50 percent or more). RESULTS The sustained-release bupropion group and the buspirone group had similar rates of HRSD-17 remission (29.7 percent and 30.1 percent, respectively), QIDS-SR-16 remission (39.0 percent and 32.9 percent), and QIDS-SR-16 response (31.8 percent and 26.9 percent). Sustained-release bupropion, however, was associated with a greater reduction (from baseline to the end of this study) in QIDS-SR-16 scores than was buspirone (25.3 percent vs. 17.1 percent, P<0.04), a lower QIDS-SR-16 score at the end of this study (8.0 vs. 9.1, P<0.02), and a lower dropout rate due to intolerance (12.5 percent vs. 20.6 percent, P<0.009). CONCLUSIONS Augmentation of citalopram with either sustained-release bupropion or buspirone appears to be useful in actual clinical settings. Augmentation with sustained-release bupropion does have certain advantages, including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Mood Disorder Program & Clin, Dallas, TX 75390 USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. NIMH, Bethesda, MD 20892 USA. RP Trivedi, MH (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, Mood Disorder Program & Clin, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM trivedi@utsouthwestern.edu RI Biggs, Dr. Melanie/C-1468-2010; Howland, Robert/K-6937-2015; OI Howland, Robert/0000-0002-6533-6010; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003] NR 18 TC 517 Z9 527 U1 6 U2 26 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 23 PY 2006 VL 354 IS 12 BP 1243 EP 1252 DI 10.1056/NEJMoa052964 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 023ZH UT WOS:000236164200003 PM 16554526 ER PT J AU Hurtado, RM Sahani, DV Kradin, RL Schapiro, RH Harris, NL Tseng, JF Peppercorn, AF AF Hurtado, RM Sahani, DV Kradin, RL Schapiro, RH Harris, NL Tseng, JF Peppercorn, AF TI 35-year-old woman with recurrent right-upper-quadrant pain - Hepatolithiasis and cholangitis (recurrent pyogenic cholangiohepatitis) with infection by Ascaris lumbricoides and gram-negative bacteria consistent with klebsiella species. Mildly active chronic hepatitis due to hepatitis C infection. Chronic cholecystitis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID INTRAHEPATIC STONES; BILIARY ASCARIASIS; PANCREATITIS; MANAGEMENT C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Hurtado, RM (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. NR 23 TC 4 Z9 4 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 23 PY 2006 VL 354 IS 12 BP 1295 EP 1303 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 023ZH UT WOS:000236164200010 PM 16554532 ER PT J AU Whang, W Manson, JE Hu, FB Chae, CU Rexrode, KM Willett, WC Stampfer, MJ Albert, CM AF Whang, W Manson, JE Hu, FB Chae, CU Rexrode, KM Willett, WC Stampfer, MJ Albert, CM TI Physical exertion, exercise, and sudden cardiac death in women SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-HEART-DISEASE; FACTOR INTERVENTION TRIAL; MYOCARDIAL-INFARCTION; VIGOROUS EXERCISE; RISK-FACTORS; MORTALITY; MEN; PREVENTION; FITNESS; ARREST AB Context Exercise is associated with a lower risk of cardiovascular events but may transiently increase the risk of ventricular arrhythmias. Its short-term and long-term associations with risk of sudden cardiac death among women are unclear. Objectives To compare the risk of sudden cardiac death in women during moderate to vigorous exertion with the risk of sudden cardiac death during lighter or no exertion; and to assess the long-term association between moderate to vigorous exercise and sudden cardiac death. Design, Setting, and Participants Prospective, nested case-crossover study of 288 cases of sudden cardiac death within the Nurses' Health Study (1980-2004); and a prospective cohort analysis of 69 693 participants without prior cardiovascular disease followed up from 1986-2004. Main Outcome Measure Risk of sudden cardiac death associated with moderate to vigorous exertion. Results The absolute risk of sudden cardiac death associated with moderate to vigorous exertion was exceedingly low at 1 per 36.5 million hours of exertion. In case-crossover analyses, the risk of sudden cardiac death was transiently elevated during moderate to vigorous exertion ( relative risk [RR], 2.38; 95% confidence interval [CI], 1.23-4.60; P=.01) compared with the risk during lesser or no exertion. Habitual moderate to vigorous exertion modified this transient risk (P=.005 for interaction) and the risk was no longer significantly elevated among those who exercised 2 or more hours per week. In the cohort analyses, an increasing amount of moderate to vigorous exercise was associated with a lower long-term risk of sudden cardiac death in age-adjusted and multivariable models that excluded biological intermediates (P=.006 for trend). This relationship was attenuated when biological intermediates were included (P=.06 for trend); however, the reduction in risk remained significant among women who exercised 4 or more hours per week ( adjusted RR, 0.41; 95% CI, 0.20-0.83; P=.01) compared with women who did not exercise. Conclusions These prospective data suggest that sudden cardiac death during exertion is an extremely rare event in women. Regular exercise may significantly minimize this small transient risk and may lower the overall long-term risk of sudden cardiac death. C1 Brigham & Womens Hosp, Div Prevent Med, Ctr Arrhythmia Prevent, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Cardiovasc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Channing Lab, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. RP Albert, CM (reprint author), Brigham & Womens Hosp, Div Prevent Med, Ctr Arrhythmia Prevent, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM calbert@partners.org OI Rexrode, Kathryn/0000-0003-3387-8429 FU NCI NIH HHS [CA-87969]; NHLBI NIH HHS [HL-34594, HL-03783]; NIDDK NIH HHS [P30 DK040561-11] NR 28 TC 63 Z9 65 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 22 PY 2006 VL 295 IS 12 BP 1399 EP 1403 DI 10.1001/jama.295.12.1399 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 023WU UT WOS:000236157700017 PM 16551711 ER PT J AU Chen, S Velardez, MO Warot, X Yu, ZX Miller, SJ Cros, D Corfas, G AF Chen, S Velardez, MO Warot, X Yu, ZX Miller, SJ Cros, D Corfas, G TI Neuregulin 1-erbB signaling is necessary for normal myelination and sensory function SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Schwann cell; myelin protein zero; pain; sciatic nerve; transgenic mouse; neuregulin ID 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE; GUILLAIN-BARRE-SYNDROME; MARIE-TOOTH-DISEASE; SCHWANN-CELL; SHEATH THICKNESS; NERVOUS-SYSTEM; NEUROPATHIC PAIN; NEURAL CREST; INNER-EAR; RECEPTOR AB To investigate the role of erbB signaling in the interactions between peripheral axons and myelinating Schwann cells, we generated transgenic mice expressing a dominant-negative erbB receptor in these glial cells. Mutant mice have delayed onset of myelination, thinner myelin, shorter internodal length, and smaller axonal caliber in adulthood. Consistent with the morphological defects, transgenic mice also have slower nerve conduction velocity and defects in their responses to mechanical stimulation. Molecular analysis indicates that erbB signaling may contribute to myelin formation by regulating transcription of myelin genes. Analysis of sciatic nerves showed a reduction in the levels of expression of myelin genes in mutant mice. In vitro assays revealed that neuregulin-1 (NRG1) induces expression of myelin protein zero (P0). Furthermore, we found that the effects of NRG1 on P0 expression depend on the NRG1 isoform used. When NRG1 is presented to Schwann cells in the context of cell - cell contact, type III but not type I NRG1 regulates P0 gene expression. These results suggest that disruption of the NRG1 - erbB signaling pathway could contribute to the pathogenesis of peripheral neuropathies with hypomyelination and neuropathic pain. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Univ Cincinnati, Childrens Hosp, Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA. RP Corfas, G (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Neurosci, 300 Longwood Ave, Boston, MA 02115 USA. EM gabriel.corfas@childrens.harvard.edu FU NICHD NIH HHS [P30-HD 18655]; NINDS NIH HHS [R01 NS035884, R01 NS35884] NR 55 TC 121 Z9 126 U1 1 U2 7 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 22 PY 2006 VL 26 IS 12 BP 3079 EP 3086 DI 10.1523/JNEUROSCI.3785-05.2006 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 024NM UT WOS:000236202200001 PM 16554459 ER PT J AU Hunt, PW Deeks, SG Bangsberg, DR Moss, A Sinclair, E Liegler, T Bates, M Tsao, G Lampiris, H Hoh, R Martin, JN AF Hunt, PW Deeks, SG Bangsberg, DR Moss, A Sinclair, E Liegler, T Bates, M Tsao, G Lampiris, H Hoh, R Martin, JN TI The independent effect of drug resistance on T cell activation in HIV infection SO AIDS LA English DT Article; Proceedings Paper CT 11th Conference on Retroviruses and Opportunistic Infections CY FEB 08-11, 2004 CL San Francisco, CA DE HIV; antiretroviral therapy; drug resistance; T cell activation ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; IMMUNE ACTIVATION; PROTEASE INHIBITORS; VIRAL LOAD; LYMPHOCYTE ACTIVATION; CLINICAL PROGRESSION; COMBINATION THERAPY; DISEASE PROGRESSION; VIROLOGICAL FAILURE AB Objective: Antiretroviral-treated individuals with drug-resistant HIV experience slower CD4 cell count declines than untreated individuals, independent of degree of viremia. As immune activation independently predicts disease progression, we hypothesized that patients with drug-resistant viremia would have less immune activation than patients with wild-type viremia, independent of plasma HIV RNA levels and that these differences would not be explained by a direct drug effect of protease inhibitors. Methods: Percentages of activated (CD38/HLA-DR) T cells were compared between untreated participants with wild-type viremia and anti retroviral-treated participants with drug-resistant viremia, after adjusting for plasma HIV RNA levels among other factors associated with T cell activation. Changes in T cell activation were also assessed in subjects discontinuing protease inhibitors while continuing other antiretroviral medications. Results: Twenty-one untreated participants with wild-type viremia and 70 antiretroviral-treated participants with drug-resistant viremia were evaluated. Relative to untreated participants, those with drug-resistant viremia had 29% fewer activated CD4 (P = 0.051) and CD8 (P = 0.012) T cells after adjustment for plasma HIV RNA levels among other factors. There was no evidence for an early change in T cell activation among 13 Subjects with drug-resistant viremia interrupting protease inhibitors while continuing other antiretroviral medications, but a significant increase in T cell activation with complete or partial emergence of wild-type sequences in protease. Conclusions: Anti retroviral-treated patients with drug-resistant viremia have less T cell activation than untreated patients, independent of plasma HIV RNA level. Decreased ability of drug-resistant variants to cause T cell activation likely contributes to slower CD4 cell count declines among patients with drug-resistant viremia. (C) 2006 Lippincott Williams & Wilkins. C1 Univ Calif San Francisco, Posit Hlth Program, San Francisco Gen Hosp, San Francisco, CA 94110 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. Virol Inc, San Francisco, CA USA. Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco Gen Hosp, Gen Clin Res Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Epidemiol & Prevent Intervent Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Infect Dis, San Francisco, CA 94143 USA. RP Hunt, PW (reprint author), Univ Calif San Francisco, Posit Hlth Program, San Francisco Gen Hosp, Blg 80,Ward 84,995 Potrero Ave, San Francisco, CA 94110 USA. EM phunt@php.ucsf.edu FU NCRR NIH HHS [5-MO1-RR00083-37]; NIAID NIH HHS [K23 AI 65244, P30 AI27763, R01 AI 52745]; NIMH NIH HHS [R01 MH054907, P30 MH62246, P30 MH59037, MH 54907] NR 56 TC 31 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 21 PY 2006 VL 20 IS 5 BP 691 EP 699 DI 10.1097/01.aids.0000216369.30948.18 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 027MZ UT WOS:000236421000008 PM 16514299 ER PT J AU Parimon, T Au, DH Martin, PJ Chien, JW AF Parimon, T Au, DH Martin, PJ Chien, JW TI A risk score for mortality after allogeneic hematopoietic cell transplantation SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID BONE-MARROW-TRANSPLANTATION; 2 IRRADIATION REGIMENS; RANDOMIZED-TRIAL; MYELOID-LEUKEMIA; FAILURE; VALUES; COHORT AB Background: Despite recent advances, mortality rates after allogeneic hematopoietic cell transplantation remain high and cannot be accurately predicted. Objective: To develop a reliable and valid predictor of all-cause mortality during the first 2 years after allogeneic hematopoietic cell transplantation. Design: Retrospective cohort. Setting: Tertiary hematopoietic cell transplantation center. Patients: Patients (n = 2802) who received a first hematopoietic cell transplant between 1990 and 2002 were assigned to a development group or a validation group. Measurements: Potential predictor variables were assessed with univariate and multivariable Cox proportional hazards methods to generate a prediction model. The c-statistic was calculated for 5 validation cohorts to assess model performance across early and late time periods and among patients with different diagnoses. Results: The authors constructed a 50-point Pretransplantation Assessment of Mortality (PAM) score that incorporated 8 pretransplantation clinical variables: patient age, donor type, disease risk, conditioning regimen, FEV(1), carbon monoxide diffusion capacity, serum creatinine level, and serum alanine aminotransferase concentration. The risk for death within 2 years for patients with PAM scores in the highest category was significantly higher than for those with scores in the lowest category. C-statistic values ranged from 0.69 to 0.76 for all validation cohorts. Limitations: The predictor model was not validated in an external cohort and is only useful for predicting the risk for death within the first 2 years after hematopoietic cell transplantation. Conclusions: Integrating pretransplantation clinical variables into a single score reliably predicts survival within 2 years after allogeneic hematopoietic cell transplantation. Accurate estimates of the risk for death may be useful in clinical trials and in epidemiologic studies. Such information can also be used to help physicians counsel patients regarding the expected outcomes of this potentially curative procedure. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Chien, JW (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,Suite D5-280, Seattle, WA 98109 USA. EM jchien@fhcrc.org FU NHLBI NIH HHS [K23HL69860-01] NR 18 TC 97 Z9 98 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 21 PY 2006 VL 144 IS 6 BP 407 EP 414 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 025FX UT WOS:000236251800004 PM 16549853 ER PT J AU Wiviott, SD de Lemos, JA Cannon, CP Blazing, M Murphy, SA McCabe, CH Califf, R Braunwald, E AF Wiviott, SD de Lemos, JA Cannon, CP Blazing, M Murphy, SA McCabe, CH Califf, R Braunwald, E TI A tale of two trials - A comparison of the post-acute coronary syndrome lipid-lowering trials A to Z and PROVE IT-TIMI 22 SO CIRCULATION LA English DT Article DE acute coronary syndrome; cholesterol; clinical trial; lipid lowering; statins ID RANDOMIZED CONTROLLED-TRIAL; HIGH-DOSE ATORVASTATIN; C-REACTIVE PROTEIN; TO-Z TRIAL; STATIN THERAPY; CHOLESTEROL; SIMVASTATIN; DISEASE; EFFICACY; SAFETY AB Background - The Aggrastat to Zocor (A to Z) and Pravastatin or Atorvastatin Evaluation and Infection Therapy ( PROVE IT) trials compared intensive and moderate statin therapy after acute coronary syndromes, with seemingly disparate results. We analyzed the design, implementation, and results of the two trials in an attempt to clarify the effects of early intensive statin therapy. Methods and Results - Study design, end points, and definitions were compared. In each trial, comparisons were made between intensive and moderate arms for both trials' primary end points and death/myocardial infarction. Analyses were performed over various time points: at the end of the trials, <= 4 months, and > 4 months. Subjects in A to Z had higher-risk demographics. More PROVE IT subjects were enrolled in the United States and underwent prerandomization revascularization. The low-density lipoprotein (LDL) difference was greater in A to Z than in PROVE IT early (<= 4 months) but less late. Significant C-reactive protein reduction was earlier in PROVE IT. With common end points, event rates were higher in A to Z, and early favorable separation of event curves was seen in PROVE IT but not in A to Z. Clinical end point rates and reductions were similar in both trials after 4 months. Conclusions - An early benefit was seen in PROVE IT but not in A to Z. Late-phase results were similar. Factors that may explain this disparity include the intensity of therapy in the early phase, timing, and magnitude of LDL and C-reactive protein lowering, differences in early revascularization, and the play of chance. Taken together, the results of these trials support a strategy of early intensive statin therapy coupled with revascularization when appropriate in patients after acute coronary syndrome. C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, SW Med Sch, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75235 USA. Duke Univ, Clin Res Inst, Durham, NC USA. RP Wiviott, SD (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM swiviott@partners.org NR 20 TC 53 Z9 57 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 21 PY 2006 VL 113 IS 11 BP 1406 EP 1414 DI 10.1161/CIRCULATIONAHA.105.586347 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 023MV UT WOS:000236131700009 PM 16534008 ER PT J AU Kathiresan, S Larson, MG Vasan, RS Guo, CY Gona, P Keaney, JF Wilson, PWF Newton-Cheh, C Musone, SL Camargo, AL Drake, JA Levy, D O'Donnell, CJ Hirschhorn, JN Benjamin, EJ AF Kathiresan, S Larson, MG Vasan, RS Guo, CY Gona, P Keaney, JF Wilson, PWF Newton-Cheh, C Musone, SL Camargo, AL Drake, JA Levy, D O'Donnell, CJ Hirschhorn, JN Benjamin, EJ TI Contribution of clinical correlates and 13 C-reactive protein gene polymorphisms to interindividual variability in serum C-reactive protein level SO CIRCULATION LA English DT Article DE epidemiology; inflammation; genetics; C-reactive protein; risk factors ID CORONARY-HEART-DISEASE; SINGLE-NUCLEOTIDE POLYMORPHISMS; PLASMA CRP LEVELS; LINKAGE DISEQUILIBRIUM; CARDIOVASCULAR-DISEASE; HUMAN GENOME; PROMOTER REGION; INFLAMMATION; ASSOCIATION; RISK AB Background - Serum C-reactive protein (CRP) level is a heritable complex trait that predicts incident cardiovascular disease. We investigated the clinical and genetic sources of interindividual variability in serum CRP. Methods and Results - We studied serum CRP in 3301 Framingham Heart Study (FHS) participants (mean age 61 years, 53% women). Twelve clinical covariates explained 26% of the variability in CRP level, with body mass index alone explaining 15% (P < 0.0001) of the variance. To investigate the influence of genetic variation at the CRP gene on CRP levels, we first constructed a dense linkage disequilibrium map for common single-nucleotide polymorphisms (SNPs) spanning the CRP locus (1 SNP every 850 bases, 26 kilobase [kb] genomic region). Thirteen CRP SNPs were genotyped in 1640 unrelated FHS participants with measured CRP levels. After adjustment for clinical covariates, 9 of 13 SNPs were associated with CRP level (P < 0.05). To account for correlation among SNPs, we conducted forward stepwise selection among all 13 SNPs; a triallelic SNP (rs3091244) remained associated with CRP level (stepwise P < 0.0001). The triallelic SNP (C3T3A; allele frequencies 62%, 31%, and 7%), located in the promoter sequence, explained 1.4% of total serum CRP variation; haplotypes harboring the minor T and A alleles of this SNP were associated with higher CRP level (haplotype P=0.0002 and 0.004). Conclusions - In our community-based sample, clinical variables explained 26% of the interindividual variation in CRP, whereas a common triallelic CRP SNP contributed modestly. Studies of larger samples are warranted to assess the association of genetic variation in CRP and risk of cardiovascular disease. C1 Boston Univ, Sch Med, Framington Heart Study, Framingham, MA 01702 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Med Univ S Carolina, Dept Endocrinol, Charleston, SC 29425 USA. MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Div Cardiol, Cambridge, MA USA. Harvard Univ, Childrens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med, Framington Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM emelia@bu.edu OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [2K24HL004334, HL66582, N01-HC-25195, R01HL064753, R01HL076784] NR 37 TC 147 Z9 153 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 21 PY 2006 VL 113 IS 11 BP 1415 EP 1423 DI 10.1161/CIRCULATIONAHA.105.591271 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 023MV UT WOS:000236131700010 PM 16534007 ER PT J AU Hartman, MCT Josephson, K Szostak, JW AF Hartman, MCT Josephson, K Szostak, JW TI Enzymatic aminoacylation of tRNA with unnatural amino acids SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE aminoacyl-tRNA synthetases; enzyme specificity; MALDI-TOF mass spectrometry; translation ID IN-VITRO SELECTION; PROTEIN SYNTHESIZING SYSTEMS; SITE-SPECIFIC INCORPORATION; THERMOPHILUS EF-TU; ESCHERICHIA-COLI; GENETIC-CODE; EFFICIENT INCORPORATION; METHIONINE ANALOGS; MASS-SPECTROMETRY; ACTIVE-SITE AB The biochemical flexibility of the cellular translation apparatus offers, in principle, a simple route to the synthesis of drug-like modified peptides and novel biopolymers. However, only approximate to 75 unnatural building blocks are known to be fully compatible with enzymatic tRNA acylation and subsequent ribosomal synthesis of modified pepticles. Although the translation system can reject substrate analogs at several steps along the pathway to peptide synthesis, much of the specificity resides at the level of the aminoacyl-tRNA synthetase (AARS) enzymes that are responsible for charging tRNAs with amino acids. We have developed an AARS assay based on mass spectrometry that can be used to rapidly identify unnatural monomers that can be enzymatically charged onto tRNA. By using this assay, we have found 59 previously unknown AARS substrates. These include numerous side-chain analogs with useful functional properties. Remarkably, many beta-amino acids, N-methyl amino acids, and alpha,alpha-disubstituted amino acids are also AARS substrates. These previously unidentified AARS substrates will be useful in studies of the specificity of subsequent steps in translation and may significantly expand the number of analogs that can be used for the ribosomal synthesis of modified pepticles. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Simches Res Ctr, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu NR 62 TC 65 Z9 67 U1 3 U2 26 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 21 PY 2006 VL 103 IS 12 BP 4356 EP 4361 DI 10.1073/pnas.0509219103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 026SN UT WOS:000236362600008 PM 16537388 ER PT J AU Ilany, J Bilan, PJ Kapur, S Caldwell, JS Patti, ME Marette, A Kahn, CR AF Ilany, J Bilan, PJ Kapur, S Caldwell, JS Patti, ME Marette, A Kahn, CR TI Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE diabetes mellitus; glucose transport; RGK GTPase; transgenic mouse ID TYPE-2 DIABETES-MELLITUS; SKELETAL-MUSCLE; LIPOPROTEIN-LIPASE; TRANSGENIC MICE; RHO-KINASE; PROTEIN; GTPASE; GENE; EXPRESSION; CELLS AB Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad in vivo, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter-enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose-response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Univ Laval, Quebec City, PQ G1K 7P4, Canada. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu RI Marette, Andre/E-9342-2013 FU NIDDK NIH HHS [P30 DK036836, DK 36836, DK 45935, R01 DK045935] NR 38 TC 19 Z9 19 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 21 PY 2006 VL 103 IS 12 BP 4481 EP 4486 DI 10.1073/pnas.0511246103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 026SN UT WOS:000236362600030 PM 16537411 ER PT J AU Anand, BS Verstovsek, G Cole, G AF Anand, Bhupinder S. Verstovsek, Gordana Cole, George TI Tubulovillous adenoma of anal canal: A case report SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE tubulovillous adenoma; anal canal AB Tumors arising from the anal canal are usually of epithelial origin and are mostly squamous cell carcinoma or basal cell carcinoma. We present a case of benign anal adenomas arising from the anus, an extremely rare diagnosis. A 78-year-old white man presented with rectal bleeding of several months duration. Examination revealed a 4 cm friable mass attached to the anus by. a stalk. At surgery, the mass was grasped with a Babcock forceps and was resected using electrocautery. Microscopic examination revealed a tubulovillus adenoma with no areas of high grade dysplasia or malignant transformation. The squamocolumnar junction was visible at the edges of the lesion confirming the anal origin of the tumor. We believe the tubulovillus adenoma arose from either an anal gland or its duct that opens into the anus. Although seen rarely, it is important to recognize and treat these tumors at an early stage because of their potential to transform into adenocarcinoma. (c) 2006 The WJG Press. All rights reserved. C1 Michael DeBakey Vet Adm Med Ctr, Dept Med, Houston, TX USA. Michael DeBakey Vet Adm Med Ctr, Dept Pathol, Houston, TX USA. Michael DeBakey Vet Adm Med Ctr, Dept Surg, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Anand, BS (reprint author), VA Med Ctr, Digest Dis Sect, 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. EM ana0@flash.net NR 4 TC 4 Z9 4 U1 0 U2 0 PU W J G PRESS PI BEIJING PA PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD MAR 21 PY 2006 VL 12 IS 11 BP 1780 EP 1781 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 076YZ UT WOS:000239995900021 PM 16586552 ER PT J AU Geiger, AM West, CN Nekhlyudov, L Herrinton, LJ Liu, ILA Altschuler, A Rolnick, SJ Harris, EL Greene, SM Elmore, JG Emmons, KM Fletcher, SV AF Geiger, AM West, CN Nekhlyudov, L Herrinton, LJ Liu, ILA Altschuler, A Rolnick, SJ Harris, EL Greene, SM Elmore, JG Emmons, KM Fletcher, SV TI Contentment with quality of life among breast cancer survivors with and without contralateral prophylactic mastectomy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 2nd Annual Conference of the American-Psychosocial-Oncology-Society CY JAN 27-29, 2005 CL Phoenix, AZ SP Amer Psychosocial Oncol Soc ID LONG-TERM; WOMEN; SATISFACTION; PREDICTORS; EFFICACY; REGRETS; HEALTH; IMPACT; SCALE AB Purpose To understand psychosocial outcomes after prophylactic removal of the contralateral breast in women with unilateral breast cancer. Methods We mailed surveys to women with contralateral prophylactic mastectomy after breast cancer diagnosis between 1979 and 1999 at six health care delivery systems, and to a smaller random sample of women with breast cancer without the procedure. Measures were modeled on instruments developed to assess contentment with quality of life, body image, sexual satisfaction, breast cancer concern, depression, and health perception. We examined associations between quality of life and the other domains using logistic regression. Results The response rate was 72.6%. Among 519 women who underwent contralateral prophylactic mastectomy, 86.5% were satisfied with their decision; 76.3% reported high contentment with quality of life compared with 75.4% of 61 women who did not undergo the procedure (P = .88). Among all case subjects, less contentment with quality of life was not associated with contralateral prophylactic mastectomy or demographic characteristics, but was associated with poor or fair general health perception (odds ratio [OR], 7.0; 95% CI 3.4 to 14.1); possible depression (OR, 5.4-1 95% CI, 3.1 to 9.2); dissatisfaction with appearance when dressed (OR, 3.5; 95% Cl, 2.0 to 6.0); self-consciousness about appearance (OR, 2.0; 95% CI, 1.1 to 3.7); and avoiding thoughts about breast cancer (modest: OR, 2.2; 95% CI, 1.1 to 4.5; highest: OR, 1.7; 95% CI, 0.9 to 3.2). Conclusion Most women undergoing contralateral prophylactic mastectomy report satisfaction with their decision and experience psychosocial outcomes similar to breast cancer survivors without the procedure. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Social Sci & Hlth Policy, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. Kaiser Permanente So Calif, Res & Evaluat Dept, Pasadena, CA USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Kaiser Permanente No Calif, Div Res, Oakland, CA USA. Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. HealthPartners Res Fdn, Minneapolis, MN USA. Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. Univ Washington, Ctr Hlth Studies, Grp Hlth Cooperat, Div Gen Internal Med, Seattle, WA 98195 USA. RP Geiger, AM (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Social Sci & Hlth Policy, Div Publ Hlth Sci, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA. EM ageiger@wfubmc.edu FU NCI NIH HHS [U19 CA79689, R01 CA090323] NR 33 TC 53 Z9 57 U1 1 U2 10 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 2006 VL 24 IS 9 BP 1350 EP 1356 DI 10.1200/JCO.200501.9901 PG 7 WC Oncology SC Oncology GA 028PU UT WOS:000236501100006 PM 16549829 ER PT J AU Kemeny, NE Niedzwiecki, D Hollis, DR Lenz, HJ Warren, RS Naughton, MJ Weeks, JC Sigurdson, ER Herndon, JE Zhang, CF Mayer, RJ AF Kemeny, NE Niedzwiecki, D Hollis, DR Lenz, HJ Warren, RS Naughton, MJ Weeks, JC Sigurdson, ER Herndon, JE Zhang, CF Mayer, RJ TI Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: A randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FLUOROURACIL PLUS LEUCOVORIN; LIVER METASTASES; THYMIDYLATE SYNTHASE; INTRAARTERIAL FLOXURIDINE; INTRAHEPATIC INFUSION; PROGNOSTIC FACTORS; GENE-EXPRESSION; MIXTURE-MODELS; PHASE-I; IRINOTECAN AB Purpose Hepatic metastases derive most of their blood supply from the hepatic artery; therefore, for patients with hepatic metastases from colorectal cancer, hepatic arterial infusion (HAI) of chemotherapy may improve outcome. Methods In a multi-institutional trial, 135 patients were randomly assigned to receive HAI versus systemic bolus fluorouracil and leucovorin. The primary end point was survival; secondary end points were response, recurrence, toxicity, quality of life, cost, and the influence of molecular markers. Results Overall survival was significantly longer for HAI versus systemic treatment (median, 24.4 v 20 months; P = .0034), as were response rates (47% and 24%; P = .012) and time to hepatic progression (THP; 9.8 v 7.3 months; P = .034). Time to extrahepatic progression (7.7 v 14.8 months; P = .029) was significantly shorter in the HAI group. Quality-of-life measurements showed improved physical functioning in the HAI group at the 3- and 6-month follow-up assessments. Toxicity included grade >= 3 neutropenia (2% and 45%; P < .01), stomatitis (0% and 24%; P < .01), and bilirubin elevation (18.6% and 0; P < .01) in the HAI and systemic treatment groups, respectively. A greater proportion of men versus women receiving HAI experienced biliary toxicity (37% and 15%, respectively; P = .05). For HAI patients with thymidylate synthase levels in tumor less than or >= 4, the median survival was 24 and 14 months, respectively (P = .17). Conclusion HAI therapy increased overall survival, response rate, THP, and was associated with better physical functioning compared with systemic therapy. Additional studies need to address the overall benefit and cost of new chemotherapy agents versus HAI alone or the combination of HAI with new agents. C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Canc & Leukemia Grp B Stat Ctr, Durham, NC USA. Univ So Calif, Los Angeles, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Kemeny, NE (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. EM kemenyn@mskcc.org FU NCI NIH HHS [CA03927, CA04326, CA07968, CA12046, CA12449, CA16450, CA21060, CA23318, CA27525, CA31946, CA32291, CA33601, CA60138, CA77651] NR 47 TC 191 Z9 199 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 20 PY 2006 VL 24 IS 9 BP 1395 EP 1403 DI 10.1200/JCO.2005.03.8166 PG 9 WC Oncology SC Oncology GA 028PU UT WOS:000236501100013 PM 16505413 ER PT J AU Duda, DG Cohen, KS di Tomaso, E Au, AP Klein, RJ Scadden, DT Willett, CG Jain, RK AF Duda, DG Cohen, KS di Tomaso, E Au, AP Klein, RJ Scadden, DT Willett, CG Jain, RK TI Differential CD 146 expression on circulating versus tissue endothelial cells in rectal cancer patients: Implications for circulating endothelial and progenitor cells as biomarkers for antiangiogenic therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Special Conf on Angiogenesis and Drug Delivery to Tumors CY NOV 09-13, 2005 CL Waltham, MA SP Amer Assoc Canc Res ID PERIPHERAL-BLOOD; SURROGATE MARKER; MEL-CAM; CD146; ANGIOGENESIS; BEVACIZUMAB; MUC18; IDENTIFICATION; ACTIVATION; INDICATOR AB Purpose Circulating endothelial cells (CECs) and progenitor cells are currently evaluated as potential biomarkers of antiangiogenic therapy. CD146 is considered a panendothelial-specific marker, but its utility as a CEC marker in cancer patients remains unclear. Patients and Methods We analyzed the expression of CD146 on mononuclear blood cells, primary tissue endothelial cells, and malignant and normal tissues by flow cytometric and immunohistochemical analyses. Furthermore, we measured the circulation kinetics of CD146(+) cells before, and then 3 and 12 days after vascular endothelial growth factor (VEGF) antibody blockade by bevacizumab infusion in rectal cancer patients enrolled in a phase I trial. Results In the peripheral blood of these cancer patients, over 90% of the CD146(+) cells were CD45(+) hematopoietic cells. CD146 expression was primarily detected on a subset of CD3(+)CD4(+) lymphocytes, and was undetectable on CD34(+)CD133(+)CD45(dim) progenitor cells or CD31(bright)CD45(-) viable CECs. In contradistinction, CD146 was detectable in tissues on both cellular components of tumor vessel wall: CD31(bright)CD45(-) endothelial cells and alpha-SMA(+) pericytes. Unlike viable CECs and progenitor cells, CD146(+) cell concentration in the peripheral blood of cancer patients did not decrease during VEGF blockade. Conclusion CD146 is fairly homogeneously expressed on vascular endothelium but not on viable CECs or progenitor cells. The vast majority of CD146(+) blood cells are lymphocytes, and VEGF blockade by bevacizumab did not significantly change their number in rectal cancer patients. These results underscore the need for further characterization and identification of new markers for CEC subpopulations for their development as biomarkers of antiangiogenic therapy. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. RP Duda, DG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Cox 734,100 Blossom St, Boston, MA 02114 USA. EM duda@steele.mgh.harvard.edu FU NCI NIH HHS [P01 CA080124, P01 CA080124-08, P01 CA80124, R21 CA099237, R21 CA099237-02] NR 25 TC 88 Z9 97 U1 0 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 2006 VL 24 IS 9 BP 1449 EP 1453 DI 10.1200/JCO.2005.04.2861 PG 5 WC Oncology SC Oncology GA 028PU UT WOS:000236501100021 PM 16549839 ER PT J AU Draenert, R Allen, TM Liu, Y Wrin, T Chappey, C Verrill, CL Sirera, G Eldridge, RL Lahaie, MP Ruiz, L Clotet, B Petropoulos, CJ Walker, BD Martinez-Picado, J AF Draenert, R Allen, TM Liu, Y Wrin, T Chappey, C Verrill, CL Sirera, G Eldridge, RL Lahaie, MP Ruiz, L Clotet, B Petropoulos, CJ Walker, BD Martinez-Picado, J TI Constraints on HIV-1 evolution and immunodominance revealed in monozygotic adult twins infected with the same virus SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELL RESPONSES; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; NEUTRALIZING ANTIBODY-RESPONSES; CLASS-I MOLECULE; TYPE-1 INFECTION; ESCAPE MUTATION; SEQUENCE ALIGNMENT; IMMUNE SELECTION; CTL RESPONSES; IMMUNODEFICIENCY AB The predictability of virus-host interactions and disease progression in rapidly evolving human viral infections has been difficult to assess because of host and genetic viral diversity. Here we examined adaptive HIV-specific cellular and humoral immune responses and viral evolution in adult monozygotic twins simultaneously infected with the same virus. CD4 T cell counts and viral loads followed similar trajectories over three years of follow up. The initial CD8 T cell response targeted 17 epitopes, 15 of which were identical in each twin, including two immunodominant responses. By 36 months after infection, 14 of 15 initial responses were still detectable in both, whereas all new responses were subdominant and remained so. Of four responses that declined in both twins, three demonstrated mutations at the same residue. In addition, the evolving antibody responses cross-neutralized the other twin's virus, with similar changes in the pattern of evolution in the envelope gene. These results reveal considerable concordance of adaptive cellular and humoral immune responses and HIV evolution in the same genetic environment, suggesting constraints on mutational pathways to HIV immune escape. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Monogram Biosci, San Francisco, CA 94080 USA. Hosp Univ Germans Trias & Pujol, Fundacio irsiCaixa, Badalona 08916, Spain. RP Walker, BD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst, Charlestown, MA 02129 USA. EM bwalker@partners.org; jmpicado@irsicaixa.es RI Martinez-Picado, Javier/G-5507-2012; Allen, Todd/F-5473-2011 OI Martinez-Picado, Javier/0000-0002-4916-2129; FU NIAID NIH HHS [AI054178-01, AI44656, R01 AI028568, R01 AI044656, R01 AI054178, R01 AI28568, R56 AI054178]; PHS HHS [N01-A1-15442] NR 51 TC 58 Z9 59 U1 0 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 20 PY 2006 VL 203 IS 3 BP 529 EP 539 DI 10.1084/jem.20052116 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 028WZ UT WOS:000236520800009 PM 16533886 ER PT J AU Chauhan, AK Motto, DG Lamb, CB Bergmeier, W Dockal, M Plaimauer, B Scheiflinger, F Ginsburg, D Wagner, DD AF Chauhan, AK Motto, DG Lamb, CB Bergmeier, W Dockal, M Plaimauer, B Scheiflinger, F Ginsburg, D Wagner, DD TI Systemic antithrombotic effects of ADAMTS13 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID VON-WILLEBRAND-FACTOR; THROMBOTIC THROMBOCYTOPENIC PURPURA; FACTOR-CLEAVING PROTEASE; VONWILLEBRAND-FACTOR MULTIMERS; HEMOLYTIC-UREMIC SYNDROME; P-SELECTIN; IN-VIVO; STELLATE CELLS; FACTOR-VIII; CLEAVAGE AB The metalloprotease ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I repeats 13) cleaves highly adhesive large von Willebrand factor (VWF) multimers after their release from the endothelium. ADAMTS13 deficiency is linked to a life-threatening disorder, thrombotic thrombocytopenic purpura (TTP), characterized by platelet-rich thrombi in the microvasculature. Here, we show spontaneous thrombus formation in activated microvenules of Adamts13(-/-) mice by intravital microscopy. Strikingly, we found that ADAMTS13 down-regulates both platelet adhesion to exposed subendothelium and thrombus formation in injured arterioles. An inhibitory antibody to ADAMTS13 infused in wild-type mice prolonged adhesion of platelets to endothelium and induced thrombi formation with embolization in the activated microvenules. Absence of ADAMTS13 did not promote thrombi formation in alpha IIb beta 3 integrin-inhibited blood. Recombinant ADAMTS13 reduced platelet adhesion and aggregation in histamine-activated venules and promoted thrombus dissolution in injured arterioles. Our findings reveal that ADAMTS13 has a powerful natural antithrombotic activity and recombinant ADAMTS13 could be used as an antithrombotic agent. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. BAxter Biosci, A-1220 Vienna, Austria. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM wagner@cbr.med.harvard.edu FU NHLBI NIH HHS [P01 HL057346, R01 HL041002, R01 HL039693, R01 HL39693, R37 HL041002, R37 HL41002] NR 51 TC 131 Z9 140 U1 0 U2 7 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 20 PY 2006 VL 203 IS 3 BP 767 EP 776 DI 10.1084/jem.20051732 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 028WZ UT WOS:000236520800030 PM 16533881 ER PT J AU Rasmussen, RA Ong, H Kittel, C Ruprecht, CR Ferrantelli, F Hu, SL Policano, P McKenna, J Moon, J Travis, B Ruprecht, RM AF Rasmussen, RA Ong, H Kittel, C Ruprecht, CR Ferrantelli, F Hu, SL Policano, P McKenna, J Moon, J Travis, B Ruprecht, RM TI DNA prime/protein boost immunization against HIV clade C: Safety and immunogenicity in mice SO VACCINE LA English DT Article DE HIV clade C; bimodal vaccination ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; ENVELOPE GLYCOPROTEIN; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODY; TYPE-1 INFECTION; VACCINIA VIRUS; MUCOSAL CHALLENGE; IMMUNE-RESPONSES; IN-VITRO AB The induction of both cellular and Immoral immunity is an important goal for vaccine development against HIV. As a Step towards the development of an efficacious vaccine against HIV clade C, the world's most prevalent strain, a combination DNA prime/protein boost immunization strategy was tested. A DNA expression vector was prepared encoding a codon-optimized env gene derived from a pediatric HIV clade C isolate, 1084i. Mice were immunized with HIV 1084i env-encoding DNA, then boosted with homologous 1084i gp 160. HIV 1084i Env-specific T-cell responses were induced with DNA vaccination alone, but the strongest cellular immune responses were seen after boosting with gp160. Immunization with gp160 alone induced high-titer antibodies but required two inoculations. In contrast, high-titer antibodies were seen after a single 1084i gp160 boost in DNA-primed animals. All animals given gp160 inoculations, whether DNA primed or not, developed neutralizing antibodies reactive with HIV1084i and a macaque-passaged simian/human immunodeficiency construct, SHIV-1084ip. The results demonstrate the utility of this DNA prime/protein boost approach to generate cellular immunity, as well as neutralizing antibodies, against HIV clade C env antigens. (c) 2005 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Washington, Seattle, WA 98121 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM ruth_ruprecht@dfci.harvard.edu RI Hu, Shiu-Lok/A-3196-2008; Ferrantelli, Flavia/J-7794-2016 OI Hu, Shiu-Lok/0000-0003-4336-7964; Ferrantelli, Flavia/0000-0002-0768-1078 FU NIAID NIH HHS [P01 AI48240] NR 48 TC 18 Z9 22 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 20 PY 2006 VL 24 IS 13 BP 2324 EP 2332 DI 10.1016/j.vaccine.2005.11.063 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 025IT UT WOS:000236259800013 PM 16406147 ER PT J AU Shang, AJ Zhou, DB Wang, LH Gao, Y Fan, M Wang, XY Zhou, RP Zhang, CG AF Shang, AJ Zhou, DB Wang, LH Gao, Y Fan, M Wang, XY Zhou, RP Zhang, CG TI Increased neuroglobin levels in the cerebral cortex and serum after ischemia-reperfusion insults SO BRAIN RESEARCH LA English DT Article DE ischemia-reperfusion insult; neuroglobin; biomarker; gerbils ID NEURON-SPECIFIC ENOLASE; PROTECTS NEURONS; BRAIN; HIPPOCAMPUS; EXPRESSION; INJURY; STROKE AB Neuroglobin (NGB) is a newly discovered protein localized in neurons of the central and peripheral nervous systems in vertebrates. It functions to bind, store, and facilitate the utilization of oxygen in neuronal cells. Recent studies suggest that it may modulate hypoxic and ischemic injury. The major goal of the present study is to characterize the dynamic changes of NGB protein in the brain and serum in a global forebrain ischemia-reperfusion model using gerbils. The sensitivity and validity of serum NGB as a potential biomarker for brain injury were further evaluated. Global cerebral ischemia-reperfusion models were induced by bilateral carotid occlusion for 20 min followed with 2-, 8-, 16-, 24-, 48-, or 72-h reperfusion in forty-six Mongolian gerbils. Sham-operated and operated animals were sacrificed at the designated time after reperfusion. Brains were fixed for immunocytochemical study to evaluate the time-dependent expression of NGB, and the concentration of NGB in serum was measured by enzyme-linked immunosorbent assay. Our results showed that the expression of NGB was upregulated in the cerebral cortex but significantly downregulated in the hippocampus from 2 to 72 h of reperfusion after 20 min of bilateral common carotid arteries occlusion. The concentration of NGB in serum was significantly increased at 8 h and reached a peak at 48 h of reperfusion. There is a significant correlation between NGB levels in the serum and severity of neuronal damage in the gerbil brain. In summary, the upregulation of NGB in cerebral cortex and downregulation in hippocampus after reperfusion insults in the gerbil brain are consistent with the fact that cerebral cortex is more tolerant to hypoxic or ischemic injury than the hippocampus. Moreover, the changes of NGB levels in serum may be used to monitor the extent of brain damage in ischemic brain diseases. (c) 2006 Elsevier B.V. All rights reserved. C1 Beijing Inst Radiat Med, Dept Neurobiol, Beijing 100850, Peoples R China. Gen Hosp Peoples Liberat Army, Dept Neurosurg, Beijing 100853, Peoples R China. Beijing Inst Basic Med, Dept Neurophysiol, Beijing 100850, Peoples R China. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02111 USA. Harvard Univ, Sch Med, Boston, MA 02111 USA. Rutgers State Univ, Coll Pharm, Dept Chem Biol, Piscataway, NJ 08854 USA. RP Zhang, CG (reprint author), Beijing Inst Radiat Med, Dept Neurobiol, Beijing 100850, Peoples R China. EM zhangcg@bmi.ac.cn RI Zhang, Chenggang/B-1480-2009 OI Zhang, Chenggang/0000-0002-4521-3304 FU NICHD NIH HHS [P01 HD23315] NR 15 TC 37 Z9 51 U1 0 U2 4 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 17 PY 2006 VL 1078 BP 219 EP 226 DI 10.1016/j.brainres.2006.01.064 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 035CO UT WOS:000236977800022 PM 16492379 ER PT J AU Letai, A AF Letai, A TI Growth factor withdrawal and apoptosis: The middle game SO MOLECULAR CELL LA English DT Editorial Material ID SURVIVAL; DEATH AB In this issue of Molecular Cell, Maurer et al. (2006) detail molecular events that trigger apoptosis following growth factor withdrawal, linking irreversible mitochondrial permeabilization to activation of GSK-3 and subsequent phosphorylation, ubiquitinylation, and degradation of the antiapoptotic BCL-2 family member MCL-1. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St Dana 530B, Boston, MA 02115 USA. NR 8 TC 30 Z9 31 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 17 PY 2006 VL 21 IS 6 BP 728 EP 730 DI 10.1016/j.molcel.2006.03.005 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 025KP UT WOS:000236265100002 PM 16543140 ER PT J AU Sansam, CG Roberts, CWM AF Sansam, CG Roberts, CWM TI Epigenetics and cancer - Altered chromatin remodeling via Snf5 loss leads to aberrant cell cycle regulation SO CELL CYCLE LA English DT Article DE Snf5; Ini1; Swi/Snf; epigenetics; p53; chromatin remodeling ID MALIGNANT RHABDOID TUMOR; TRANSCRIPTIONAL ACTIVATION; CHROMOSOMAL INSTABILITY; SWI/SNF COMPLEX; DNA-REPLICATION; SUPPRESSOR; MICE; TUMORIGENESIS; MUTATIONS; INI1 AB The term 'epigenetics' refers to heritable changes in gene function that occur in the absence of any change in DNA sequence. Perturbations of epigenetic gene regulation may play a critical role in the genesis of most, if not all, cancers. These alterations include changes in covalent modifications of DNA and histones as well as non covalent changes in nucleosome positioning. Covalent epigenetic modifications have been the main focus of cancer investigation, perhaps because they are more readily assayed and understood than non covalent modifications. Recently, evidence has emerged demonstrating that perturbation of complexes that remodel the structure of chromatin by mobilizing nucleosomes may have a key role in tumor suppression and oncogenic transformation. For example, Snf5 (Ini1/Baf47/Smarcb1), a core component of the Swi/Snf ATPase chromatin remodeling complex, is a potent tumor suppressor that is specifically inactivated in lethal childhood cancers. Notably, these cancers may serve as a paradigm for epigenetic cancers as, despite their extremely aggressive nature, the majority have an entirely normal karyotype with only microdeletions at the Snf5 locus. Recent investigations have shed light upon the mechanistic basis of Snf5 function by demonstrating that Snf5 and the Swi/Snf complex regulate the cell cycle and cooperate with p53 to prevent oncogenic transformation. C1 Childrens Hosp, Dept Pediat Oncol, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Roberts, CWM (reprint author), Childrens Hosp, Dept Pediat Oncol, Dana Farber Canc Inst, Div Hematol Oncol, 44 Binney St M657, Boston, MA 02115 USA. EM charles_roberts@dfci.harvard.edu NR 50 TC 40 Z9 41 U1 4 U2 7 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR 16 PY 2006 VL 5 IS 6 BP 621 EP 624 DI 10.4161/cc.5.6.2579 PG 4 WC Cell Biology SC Cell Biology GA 053CU UT WOS:000238282400018 PM 16582616 ER PT J AU Treadway, K AF Treadway, K TI Becoming a physician: Heart sounds SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Treadway, K (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 16 PY 2006 VL 354 IS 11 BP 1112 EP 1113 DI 10.1056/NEJMp058202 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 021KI UT WOS:000235981700003 PM 16540610 ER PT J AU Asch, SM Kerr, EA Keesey, J Adams, JL Setodji, CM Malik, S McGlynn, EA AF Asch, SM Kerr, EA Keesey, J Adams, JL Setodji, CM Malik, S McGlynn, EA TI Who is at greatest risk for receiving poor-quality health care? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID OF-CARE; RACIAL-DIFFERENCES; PHYSICIAN COMMUNICATION; HEART-FAILURE; UNITED-STATES; BENEFICIARIES; INSURANCE; ADULTS; BLACK AB Background: American adults frequently do not receive recommended health care. The extent to which the quality of health care varies among sociodemographic groups is unknown. Methods: We used data from medical records and telephone interviews of a random sample of people living in 12 communities to assess the quality of care received by those who had made at least one visit to a health care provider during the previous two years. We constructed aggregate scores from 439 indicators of the quality of care for 30 chronic and acute conditions and for disease prevention. We estimated the rates at which members of different sociodemographic subgroups received recommended care, with adjustment for the number of chronic and acute conditions, use of health care services, and other sociodemographic characteristics. Results: Overall, participants received 54.9 percent of recommended care. Even after adjustment, there was only moderate variation in quality-of-care scores among sociodemographic subgroups. Women had higher overall scores than men (56.6 percent vs. 52.3 percent, P<0.001), and participants below the age of 31 years had higher scores than those over the age of 64 years (57.5 percent vs. 52.1 percent, P<0.001). Blacks (57.6 percent) and Hispanics (57.5 percent) had slightly higher scores than whites (54.1 percent, P<0.001 for both comparisons). Those with annual household incomes over $50,000 had higher scores than those with incomes of less than $15,000 (56.6 percent vs. 53.1 percent, P<0.001). Conclusions: The differences among sociodemographic subgroups in the observed quality of health care are small in comparison with the gap for each subgroup between observed and desirable quality of health care. Quality-improvement programs that focus solely on reducing disparities among sociodemographic subgroups may miss larger opportunities to improve care. C1 RAND Hlth, Santa Monica, CA 90407 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. Vet Affairs Ann Arbor Hlth Care Syst, Vet Affairs Ctr Practice Management & Outcomes Re, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. Univ Calif Irvine, Dept Med, Div Cardiol, Irvine, CA 92717 USA. RP Asch, SM (reprint author), RAND Hlth, Santa Monica, CA 90407 USA. NR 32 TC 261 Z9 264 U1 1 U2 17 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 16 PY 2006 VL 354 IS 11 BP 1147 EP 1156 DI 10.1056/NEJMsa044464 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 021KI UT WOS:000235981700008 PM 16540615 ER PT J AU Podolsky, DK Gonzalez, RG Hasserjian, RP Siegel, CA Hochberg, EP AF Podolsky, DK Gonzalez, RG Hasserjian, RP Siegel, CA Hochberg, EP TI A 71-year-old woman with Crohn's disease and altered mental status - Diffuse large-B-cell lymphoma, EBV-positive, associated with iatrogenic immunosuppression. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID INFLAMMATORY-BOWEL-DISEASE; EPSTEIN-BARR-VIRUS; POPULATION-BASED COHORT; COLORECTAL-CANCER; CLONAL ANALYSIS; INCREASED RISK; AZATHIOPRINE; INFLIXIMAB; 6-MERCAPTOPURINE; DISORDERS C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 27 TC 11 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 16 PY 2006 VL 354 IS 11 BP 1178 EP 1184 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 021KI UT WOS:000235981700013 PM 16540619 ER PT J AU Gharib, SA Liles, WC Matute-Bello, G Glenny, RW Martin, TR Altemeier, WA AF Gharib, SA Liles, WC Matute-Bello, G Glenny, RW Martin, TR Altemeier, WA TI Computational identification of key biological modules and transcription factors in acute lung injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; gene network; microarray; transcription factor ID RESPIRATORY-DISTRESS-SYNDROME; MECHANICAL VENTILATION; GENE-ONTOLOGY; TIDAL VOLUMES; ACTIVATION; REGULATORS; CYP2E1; DAMAGE; CELLS; SP1 AB Rationale: Mechanical ventilation augments the acute lung injury (ALI) caused by bacterial products. The molecular pathogenesis of this synergistic interaction remains incompletely understood. Objective: We sought to develop a computational framework to systematically identify gene regulatory networks activated in ALI. Methods: We have developed a mouse model in which the combination of mechanical ventilation and intratracheal LPS produces significantly more injury to the lung than either insult alone. We used global gene ontology analysis to determine overrepresented biological modules and computational transcription factor analysis to identify putative regulatory factors involved in this model of ALI. Results: By integrating expression profiling with gene ontology and promoter analysis, we constructed a large-scale regulatory modular map of the important processes activated in ALI. This map assigned differentially expressed genes to highly overrepresented biological modules, including "defense response," "immune response," and "oxidoreductase activity." These modules were then systematically incorporated into a gene regulatory network that consisted of putative transcription factors, such as IFN-stimulated response element, IRF7, and Sp1, that may regulate critical processes involved in the pathogenesis of ALI. Conclusions: We present a novel, unbiased, and powerful computational approach to investigate the synergistic effects of mechanical ventilation and LPS in promoting ALI. Our methodology is applicable to any expression profiling experiment involving eukaryotic organisms. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Physiol, Seattle, WA 98195 USA. Univ Washington, Dept Biophys, Seattle, WA 98195 USA. Vet Affairs Puget Sound Healthcare Syst, Med Res Serv, Seattle, WA USA. RP Gharib, SA (reprint author), Box 356522,1959 NE Pacific St, Seattle, WA 98195 USA. EM sagharib@u.washington.edu FU NHLBI NIH HHS [K08 HL071020] NR 29 TC 35 Z9 38 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 15 PY 2006 VL 173 IS 6 BP 653 EP 658 DI 10.1164/rccm.200509-1473OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 024FY UT WOS:000236182100012 PM 16387799 ER PT J AU Malo, MS Mozumder, M Chen, A Mostafa, G Zhang, XB Hodin, RA AF Malo, MS Mozumder, M Chen, A Mostafa, G Zhang, XB Hodin, RA TI PFRL7: An ideal vector for eukaryotic promoter analysis SO ANALYTICAL BIOCHEMISTRY LA English DT Editorial Material ID TRANSGENE EXPRESSION; GENE-TRANSFER; PROTEIN C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hodin, RA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM rhodin@partners.org FU NIDDK NIH HHS [DK47186, DK50623] NR 9 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAR 15 PY 2006 VL 350 IS 2 BP 307 EP 309 DI 10.1016/j.ab.2005.12.018 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 023VT UT WOS:000236155000020 PM 16460660 ER PT J AU Rush, AJ Bernstein, IH Trivedi, MH Carmody, TJ Wisniewski, S Mundt, JC Shores-Wilson, K Biggs, MM Woo, A Nierenberg, AA Fava, M AF Rush, AJ Bernstein, IH Trivedi, MH Carmody, TJ Wisniewski, S Mundt, JC Shores-Wilson, K Biggs, MM Woo, A Nierenberg, AA Fava, M TI An evaluation of the quick inventory of depressive symptomatology and the Hamilton rating scale for depression: A sequenced treatment alternatives to relieve depression trial report SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Quick Inventory of Depressive Symptomatology; Inventory of Depressive Symptomatology; item response theory; Samejima graded response model; depressive symptoms ID MEDICATION ALGORITHM PROJECT; STAR-ASTERISK-D; REPORT QIDS-SR; PSYCHOMETRIC PROPERTIES; MAJOR DEPRESSION; COMMON FACTORS; IDS-SR; DISORDER; RELIABILITY; RATIONALE AB Background. Nine DSM-IV-TR criterion symptom domains are evaluated to diagnose major depressive disorder (MDD). The Quick Inventory of Depressive Symptomatology (QIDS) provides an efficient assessment of these domains and is available as a clinician rating (QIDS-C-16), a self-report (QIDS-SR16), and in an automated, interactive voice response (IVR) (QIDS-IVR16) telephone system. This report compares the performance of these three versions of the QIDS and the 17-item Hamilton Rating Scale for Depression (HRSD17). Methods: Data were acquired at baseline and exit from the first treatment step (citalopram) in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, Outpatients with nonpsychotic MDD who completed all four ratings within +/- 2 days were identified from the first 1500 STAR*D subjects. Both item response theory and classical test theory. analyses were conducted. Results: The three methods for obtaining QIDS data produced consistent findings regarding relationships between the nine symptom domains and overall depression, demonstrating interchangeability among the three methods. The HRSD17 while generally satisfactory, rarely utilized the full range of item scores, and evidence suggested multidimensional measurement properties. Conclusions: In nonpsychotic MDD outpatients without overt cognitive impairment, clinician assessment of depression severity using either the QIDS-C-16 or HRSD17 may be successfully replaced by either the self-report or lVR version of the QIDS. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Univ Texas, Dept Psychol, Arlington, TX 76019 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. Healthcare Technol Syst, Madison, WI USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. RP Rush, AJ (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM john.rush@utsouthwestern.edu RI Biggs, Dr. Melanie/C-1468-2010; OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003, MH-068852, R01 MH068852-01, R01 MH068852-02, MH68851] NR 47 TC 200 Z9 204 U1 4 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 15 PY 2006 VL 59 IS 6 BP 493 EP 501 DI 10.1016/j.biopsych.2005.08.022 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 024JJ UT WOS:000236191000002 PM 16199008 ER PT J AU Meyer-Olson, D Brady, KW Bartman, MT O'Sullivan, KM Simons, BC Conrad, JA Duncan, CB Lorey, S Siddique, A Draenert, R Addo, M Altfeld, M Rosenberg, E Allen, TM Walker, BD Kalams, SA AF Meyer-Olson, D Brady, KW Bartman, MT O'Sullivan, KM Simons, BC Conrad, JA Duncan, CB Lorey, S Siddique, A Draenert, R Addo, M Altfeld, M Rosenberg, E Allen, TM Walker, BD Kalams, SA TI Fluctuations of functionally distinct CD8(+) T-cell clonotypes demonstrate flexibility of the HIV-specific TCR repertoire SO BLOOD LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; V-BETA REPERTOIRE; LYMPHOCYTE CLONES; PRIMARY INFECTION; IMMUNE-RESPONSES; ESCAPE VARIANTS; RECEPTOR; VIREMIA; RECOGNITION AB T-cell receptor (TCR) diversity of virusspecific CD8(+) T cells likely helps prevent escape mutations in chronic viral infections. To understand the dynamics of the virus-specific T cells in more detail, we followed the evolution of the TCR repertoire specific for a dominant HLA-B*08restricted epitope in Nef (FLKEKGGL) in a cohort of subjects infected with HIV. Epitope-specific CD8+ T cells used structurally diverse TCR repertoires, with different TCRP variable regions and with high amino acid diversity within antigen recognition sites. In a longitudinal study, distinct V beta populations within the HIV-specific TCR repertoire expanded simultaneously with changes in plasma viremia, whereas other V beta populations remained stable or even decreased. Despite antigenic variation in some subjects, all subjects had the consensus sequence present during the study period. Functional analysis of distinct V beta populations revealed differences in HIV-specific IFN-gamma secretion ex vivo as well as differences in tetramer binding, indicating functional heterogeneity among these populations. This contrasts with findings in a subject on antiretroviral therapy with suppression of viremia to less than 50 copies/mL, where we observed long-term persistence of a single clonotype. Our findings illustrate the flexibility of a heterogeneous HIV-1-specific CD8(+) TCR repertoire in subjects with partial control of viremia. C1 Vanderbilt Univ, Med Ctr, Infect Dis Unit, Dept Internal Med, Nashville, TN 37232 USA. Harvard Univ, Sch Med, Partners AIDS Res Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hannover Med Sch, Abt Klin Immunol, Hannover, Germany. Vanderbilt Univ, Med Ctr, Dept Microbiol & Immunol, Nashville, TN USA. RP Kalams, SA (reprint author), Vanderbilt Univ, Med Ctr, Infect Dis Unit, Dept Internal Med, MCN A4103, Nashville, TN 37232 USA. EM spyros.a.kalams@vanderbilt.edu RI Allen, Todd/F-5473-2011 FU NIAID NIH HHS [R01 AI39966] NR 53 TC 44 Z9 47 U1 2 U2 4 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 2006 VL 107 IS 6 BP 2373 EP 2383 DI 10.1182/blood-2005-04-1636 PG 11 WC Hematology SC Hematology GA 021VO UT WOS:000236014200029 PM 16322475 ER PT J AU Yamanaka, K Clark, R Rich, B Dowgiert, R Hirahara, K Hurwitz, D Shibata, M Mirchandani, N Jones, DA Goddard, DS Eapen, S Mizutani, H Kupper, TS AF Yamanaka, K Clark, R Rich, B Dowgiert, R Hirahara, K Hurwitz, D Shibata, M Mirchandani, N Jones, DA Goddard, DS Eapen, S Mizutani, H Kupper, TS TI Skin-derived interleukin-7 contributes to the proliferation of lymphocytes in cutaneous T-cell lymphoma SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; IN-VIVO; SEZARY-SYNDROME; IL-7 PROMOTES; GROWTH-FACTOR; MEMORY CELLS; EXPRESSION; SURVIVAL; NAIVE; HOMEOSTASIS AB Cutaneous T-cell lymphomas (CTCLS) are malignancies of T cells that have a special affinity for the skin. We have previously reported that much of the T-cell receptor repertoire is altered in CTCL, and both malignant and nonmalignant clones are numerically expanded, presumably in response to T-cell trophic cytokines. We therefore examined levels of the T-cell trophic cytokines IL-2, IL-4, IL-7, IL-12, IL-13, and IL-15 in plasma in 93 CTCL patients and healthy controls. Only IL-7 levels were elevated in CTCL. We next looked at lesional skin from patients with CTCL and found elevated levels of IL-7 mRNA. Explant cultures of normal and lesional CTCL skin biopsies revealed significantly more IL-7 protein production in CTCL skin. Additionally, cultures of CTCL skin released greater numbers of T cells than normal skin; this was blocked by the addition of an IL-7 neutralizing antibody. Finally, these cultures induced proliferation of normal peripheral skin-homing T cells that were added to the cultures. These observations led us to postulate that IL-7 produced by skin cells contributes to the survival and proliferation of T cells within skin lesions and is likely the source of elevated circulating IL-7 in CTCL. C1 Brigham & Womens Hosp, Harvard Skin Dis Res Ctr, Dept Dermatol, Harvard Inst Med, Boston, MA 02115 USA. Mie Univ, Grad Sch Med, Dept Dermatol, Tsu, Mie, Japan. Dana Farber Harvard Canc Ctr, Dana Farber Canc Inst, Biostat Core Facil, Dept Biostat, Boston, MA USA. RP Kupper, TS (reprint author), Brigham & Womens Hosp, Harvard Skin Dis Res Ctr, Dept Dermatol, Harvard Inst Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM tskupper@rics.bwh.harvard.edu FU NIAMS NIH HHS [R01 AR065807] NR 46 TC 36 Z9 37 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2006 VL 107 IS 6 BP 2440 EP 2445 DI 10.1182/blood-2005-03-1139 PG 6 WC Hematology SC Hematology GA 021VO UT WOS:000236014200037 PM 16322477 ER PT J AU Richardson, PG Barlogie, B Berenson, J Singhal, S Jagannath, S Irwin, DH Rajkumar, SV Srkalovic, G Alsina, M Anderson, KC AF Richardson, PG Barlogie, B Berenson, J Singhal, S Jagannath, S Irwin, DH Rajkumar, SV Srkalovic, G Alsina, M Anderson, KC TI Extended follow-up of a phase II trial in relapsed, refractory multiple myeloma - Final time-to-event results from the SUMMIT trial SO CANCER LA English DT Article DE bortezomib; proteasome inhibitor; multiple myeloma; dexamethasone ID PROTEASOME INHIBITOR PS-341; CHEMOTHERAPEUTIC-AGENTS; BORTEZOMIB; CELLS; SENSITIVITY; THERAPY; GROWTH; MM AB BACKGROUND. Bortezomib, a first-in-class proteasome inhibitor, has shown clinical activity in relapsed, refractory multiple myeloma in a pivotal Phase 11 trial, SUMMIT. METHODS. Patients received bortezomib 1.3 mg/m(2) on Days 1, 4, 8, and 11 followed by a 10-day rest period for up to 8 cycles. Dexamethasone 20 mg on the day of and the day after bortezomib was permitted for suboptimal response. Extended treatment beyond 8 cycles was offered to patients whose physicians felt they would benefit from additional therapy. Follow-up was conducted in all patients for a median of 23 months, an additional 13 months from the original report. RESULTS. Of 202 patients enrolled in SUMMIT, 193 were evaluable for response. Seven (4%) patients achieved a complete response, 12 (6%) achieved a nearly complete response, 34 (18%) achieved a partial response, and 14 (7%) had a minimal response while on bortezomib. The updated median duration of response to bortezomib alone was 12.7 months. The median overall time to progression for all SUMMIT patients was 7 months. For responding patients, the median time to progression was 13.9 months, whereas for those with progressive disease (PD) or who were not evaluable, the median time to progression was 1.3 months. The median overall survival (OS) for all SUMMIT patients was 17.0 months. Whereas the median OS for patients with PD or who were not evaluable was 8 months, the median OS for responding patients was not reached at 23 months of follow-up. CONCLUSIONS. These data demonstrate that treatment with bortezomib results in meaningful long-term benefit for patients with relapsed and refractory myeloma. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol Hematol Malignancies, Boston, MA 02115 USA. Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. Inst Myeloma & Bone Canc Res, W Hollywood, CA USA. Feinberg Sch Med, Robert H Lurie Canc Ctr, Multiple Myeloma Program, Div Hematol & Oncol, Chicago, IL USA. St Vincents Comprehens Canc Ctr, Multiple Myeloma Serv, New York, NY USA. Alta Bates Canc Ctr, Dept Hematol, Berkeley, CA USA. Mayo Clin, Div Hematol, Rochester, MN USA. Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA. H Lee Moffitt Canc Ctr & Res Inst, Malignant Hematol Program, Tampa, FL 33612 USA. RP Richardson, PG (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol Hematol Malignancies, 44 Binney St,Dana 1B02, Boston, MA 02115 USA. EM Paul_Richardson@dfci.harvard.edu OI Rajkumar, S. Vincent/0000-0002-5862-1833 NR 15 TC 102 Z9 114 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2006 VL 106 IS 6 BP 1316 EP 1319 DI 10.1002/cncr.21740 PG 4 WC Oncology SC Oncology GA 021XP UT WOS:000236019500014 PM 16470606 ER PT J AU Stipa, F Yoon, SS Liau, KH Fong, YM Jarnagin, WR D'Angelica, M Abou-Alfa, G Blumgart, LH DeMatteo, RP AF Stipa, F Yoon, SS Liau, KH Fong, YM Jarnagin, WR D'Angelica, M Abou-Alfa, G Blumgart, LH DeMatteo, RP TI Outcome of patients with fibrolamellar hepatocellular carcinoma SO CANCER LA English DT Article DE fibrolamellar; hepatocellular carcinoma; hepatic resection; outcome ID LIVER-TRANSPLANTATION; HEPATOMA; HEPATECTOMY; DIAGNOSIS; RESECTION; FEATURES; TUMORS; CT AB BACKGROUND. Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare variant of hepatocellular carcinoma, has distinct pathologic features, and typically occurs in young patients without underlying hepatitis or cirrhosis. METHODS. Forty-one patients with the pathologic diagnosis of FL-HCC evaluated at our institution between 1986 and 2003 were identified from a prospective database. RESULTS. Median age of all patients was 27 years. None of these patients had underlying hepatitis or cirrhosis, and only 3 (7%) patients had an a-fetoprotein level > 200 ng/mL. Twenty-eight patients with primary disease underwent complete gross resection, and 13 patients were unresectable. In patients treated with resection, median tumor size was 9 cm (range, 3-17), 9 (36%) had vascular invasion, and 14 (50%) had lymph node metastases. There were no perioperative deaths. With a median follow-up of 34 months, 5-year overall survival for resected patients was 76%. However, 5-year recurrence-free survival was only 18%, and of the 9 resected patients with more than 5 years of follow-up, 7 had recurrences. Lymph node metastasis was the only significant negative prognostic factor. Seventeen (61%) patients underwent a second operation for recurrent disease. Median survival for unresected patients with FL-HCC was only 12 months, and no patient survived beyond 5 years. CONCLUSIONS. FL-HCC occurs in a distinctly different population of patients than common HCC, and patients with FL-HCC generally fare better after complete resection. These tumors have a relatively indolent tumor biology, and late recurrences are common. Repeat resections for recurrence should be considered given the lack of other effective treatment options. C1 Mem Sloan Kettering Canc Ctr, Dept Surg, Hepatobiliary Serv, New York, NY 10021 USA. San Giovanni Hosp, Dept Surg, Rome, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Surg Oncol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Med & Biostat, New York, NY 10021 USA. RP DeMatteo, RP (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, Hepatobiliary Serv, 1275 York Ave, New York, NY 10021 USA. EM dematteo@mskcc.org OI Jarnagin, William/0000-0002-1635-5768 NR 29 TC 72 Z9 79 U1 0 U2 3 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 2006 VL 106 IS 6 BP 1331 EP 1338 DI 10.1002/cncr.21703 PG 8 WC Oncology SC Oncology GA 021XP UT WOS:000236019500017 PM 16475212 ER PT J AU Alvarez, JV Greulich, H Sellers, WR Meyerson, M Frank, DA AF Alvarez, JV Greulich, H Sellers, WR Meyerson, M Frank, DA TI Signal transducer and activator of transcription 3 is required for the oncogenic effects of non-small-cell lung cancer-associated mutations of the epidermal growth factor receptor SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE KINASE; TYROSINE KINASES; GENE-EXPRESSION; SERINE PHOSPHORYLATION; EGFR MUTATIONS; GEFITINIB; STAT3; INHIBITOR; PATHWAYS; COMMON AB Somatic mutations in the epidermal growth factor receptor (EGFR) occur frequently in lung cancer and confer sensitivity to EGFR kinase inhibitors gefitinib and erlotinib. These mutations, which occur in the kinase domain of the protein, also render EGFR constitutively active and transforming. Signal transducers and activators of transcription 3 (STAT3) transduces signals from a number of oncogenic tyrosine kinases and contributes to a wide spectrum of human malignancies. Here, we show that STAT3 is activated by mutant EGFRs and is necessary for its downstream phenotypic effects. Inhibiting STAT3 function in fibroblasts abrogates transformation by mutant EGFR. In non-small-cell lung cancer cells, STAT3 activity is regulated by EGFR through modulation of STAT3 serine phosphorylation. Inhibiting STAT3 function increases apoptosis of these cells, suggesting that STAT3 is necessary for their survival. Finally, a group of genes constituting a STAT3 signature is enriched in lung tumors with EGFR mutations. Thus, STAT3 is a critical mediator of the oncogenic effects of somatic EGFR mutations and targeting STAT3 may be an effective strategy for treating tumors characterized by these mutations. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Mayer 522B,44 Binney St, Boston, MA 02115 USA. EM david_frank@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 NR 39 TC 140 Z9 151 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 2006 VL 66 IS 6 BP 3162 EP 3168 DI 10.1158/0008-5472.CAN-05-3757 PG 7 WC Oncology SC Oncology GA 022ZA UT WOS:000236093500037 PM 16540667 ER PT J AU Yang, SC Batra, RK Hillinger, S Reckamp, KL Strieter, RM Dubinett, SM Sharma, S AF Yang, SC Batra, RK Hillinger, S Reckamp, KL Strieter, RM Dubinett, SM Sharma, S TI Intrapulmonary administration of CCL21 gene-modified dendritic cells reduces tumor burden in spontaneous murine bronchoalveolar cell carcinoma SO CANCER RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; REGULATORY T-CELLS; GROWTH-FACTOR-BETA; LUNG-CANCER; IN-VIVO; ANTITUMOR RESPONSES; IMMUNITY; ANTIGEN; LYMPHOCYTES; VACCINES AB The antitumor efficiency of dendritic cells transduced with an adenovirus vector expressing secondary lymphoid chemokine (CCL21) was evaluated in a murine model of spontaneous bronchoalveolar cell carcinoma. The transgenic mice (CC-10 TAg) express the SV40 large T antigen (TAg) under the Clara cell promoter, develop bilateral, multifocal, and pulmonary adenocarcinomas, and die at 4 months as a result of progressive pulmonary tumor burden. A single intratracheal administration of CCL21 gene-modified dendritic cells (DC-AdCCL21) led to a marked reduction in tumor burden with extensive mommuclear cell infiltration of the tumors. The reduction in tumor burden was accompanied by the enhanced elaboration of type I cytokines [IFN-gamma, interleukin (IL)-12, and granulocyte macrophage colony-stimulating factor] and antiangiogenic chemokines (CXCL9 and CXCL10) but a concomitant decrease in the immunosuppressive molecules (IL-10, transforming growth factor-P, prostaglandin E-2) in the tumor microenvironment. The DC-AdCCL21 therapy group revealed a significantly greater frequency of tumor-specific T cells releasing IFN-gamma, compared with the controls. Continuous therapy with weekly intranasal delivery of DC-AdCCL21 significantly prolonged median survival by > 7 weeks in CC10 TAg mice. Both innate natural killer and specific T-cell antitumor responses significantly increased following DC-AdCCL21 therapy. Significant reduction in tumor burden in a model in which tumors develop in an organ-specific manner provides a strong rationale for further evaluation of intrapulmonary-administered DC-AdCCL21 in regulation of tumor immunity and genetic immunotherapy for lung cancer. C1 Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Ctr Hlth Sci 37 131, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Dept Med, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Mol Med Lab, Los Angeles, CA USA. Univ Zurich Hosp, CH-8091 Zurich, Switzerland. RP Sharma, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Ctr Hlth Sci 37 131, 10833 LeConte Ave, Los Angeles, CA 90095 USA. EM sharmasp@ucla.edu OI Batra, Raj K./0000-0002-1126-543X; Reckamp, Karen/0000-0002-9213-0325 FU NCI NIH HHS [P50 CA90388, R01 CA85686] NR 48 TC 47 Z9 51 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2006 VL 66 IS 6 BP 3205 EP 3213 DI 10.1158/0008-5472.CAN-05-3619 PG 9 WC Oncology SC Oncology GA 022ZA UT WOS:000236093500042 PM 16540672 ER PT J AU Fecci, PE Mitchell, DA Whitesides, JF Xie, WH Friedman, AH Archer, GE Herndon, JE Bigner, DD Dranoff, G Sampson, JH AF Fecci, PE Mitchell, DA Whitesides, JF Xie, WH Friedman, AH Archer, GE Herndon, JE Bigner, DD Dranoff, G Sampson, JH TI Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma. SO CANCER RESEARCH LA English DT Article ID PRIMARY INTRACRANIAL TUMORS; PRIMARY BRAIN-TUMORS; TGF-BETA; PERIPHERAL-BLOOD; INFILTRATING LYMPHOCYTES; CUTTING EDGE; CD4(+)CD25(+); ACTIVATION; IL-2; IMMUNOBIOLOGY AB Immunosuppression is frequently associated with malignancy and is particularly severe in patients with malignant glioma. Anergy and counterproductive shifts toward T(H)2 cytokine production are long-recognized T-cell defects in these patients whose etiology has remained elusive for > 30 years. We show here that absolute counts of both CD4(+) T cells and CD4(+)CD25(+)FOXP3(+)CD45RO(+) T cells (T-regs) are greatly diminished in patients with malignant glioma, but T-regs frequently represent an increased fraction of the remaining CD4 compartment. This increased T-reg fraction, despite reduced counts, correlates with and is sufficient to elicit the characteristic manifestations of impaired patient T-cell responsiveness in vitro. Furthermore, Treg removal eradicates T-cell proliferative defects and reverses TH2 cytokine shifts, allowing T cells from patients with malignant glioma to function in vitro at levels equivalent to those of normal, healthy controls. Such restored immune function may give license to physiologic antiglioma activity, as in vivo, T-reg depletion proves permissive for spontaneous tumor rejection in a murine model of established intracranial glioma. These findings dramatically alter our understanding of depressed cellular immune function in patients with malignant glioma and advance a role for T-regs in facilitating tumor immune evasion in the central nervous system. C1 Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Div Neurosurg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Div Neurosurg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Div Neurosurg, Durham, NC 27710 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Sampson, JH (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, 221 Sands Res Bldg, Durham, NC 27710 USA. EM samps001@mc.duke.edu FU NCI NIH HHS [1P50 CA108786, R01 CA09722]; NIGMS NIH HHS [T32 GM-07171] NR 36 TC 235 Z9 241 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2006 VL 66 IS 6 BP 3294 EP 3302 DI 10.1158/0008-5472.CAN-05-3773 PG 9 WC Oncology SC Oncology GA 022ZA UT WOS:000236093500053 PM 16540683 ER PT J AU Milan, DJ Giokas, AC Serluca, FC Peterson, RT MacRae, CA AF Milan, DJ Giokas, AC Serluca, FC Peterson, RT MacRae, CA TI Notch1b and neuregulin are required for specification of central cardiac conduction tissue SO DEVELOPMENT LA English DT Article DE notch; neuregulin; cardiac conduction system; development; zebrafish ID PURKINJE-FIBER DIFFERENTIATION; EMBRYONIC HEART; CARDIOVASCULAR-SYSTEM; IMPULSE PROPAGATION; ENDOTHELIAL-CELLS; ZEBRAFISH; GENE; EXPRESSION; INDUCTION; DISEASE AB Normal heart function is critically dependent on the timing and coordination provided by a complex network of specialized cells: the cardiac conduction system. We have employed functional assays in zebrafish to explore early steps in the patterning of the conduction system that previously have been inaccessible. We demonstrate that a ring of atrioventricular conduction tissue develops at 40 hours post-fertilization in the zebrafish heart. Analysis of the mutant cloche reveals a requirement for endocardial signals in the formation of this tissue. The differentiation of these specialized cells, unlike that of adjacent endocardial cushions and valves, is not dependent on blood flow or cardiac contraction. Finally, both neuregulin and notch1b are necessary for the development of atrioventricular conduction tissue. These results are the first demonstration of the endocardial signals required for patterning central 'slow' conduction tissue, and they reveal the operation of distinct local endocardial-myocardial interactions within the developing heart tube. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Novartis Inst Biomed Res, Cambridge, MA USA. RP Milan, DJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM dmilan@partners.org FU NHLBI NIH HHS [HL079267, HL076361, HL065962, K08 HL068711]; NIGMS NIH HHS [R21 GM075946] NR 57 TC 100 Z9 102 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR 15 PY 2006 VL 133 IS 6 BP 1125 EP 1132 DI 10.1242/dev.02279 PG 8 WC Developmental Biology SC Developmental Biology GA 031AQ UT WOS:000236676900013 PM 16481353 ER PT J AU Ueda, Y Okano, M Williams, C Chen, TP Georgopoulos, K Li, E AF Ueda, Y Okano, M Williams, C Chen, TP Georgopoulos, K Li, E TI Roles for Dnmt3b in mammalian development: a mouse model for the ICF syndrome SO DEVELOPMENT LA English DT Article DE DNA methylation; Dnmt3b; ICF syndrome; T cell; apoptosis ID DNA METHYLTRANSFERASE GENE; DE-NOVO METHYLATION; FACIAL ANOMALIES; CYTOSINE-5 METHYLTRANSFERASES; IMMUNODEFICIENCY SYNDROME; CENTROMERIC INSTABILITY; SATELLITE DNA; T-LYMPHOCYTES; FAMILY-MEMBER; IKAROS GENE AB ICF (Immunodeficiency, Centromeric instability and Facial anomalies) syndrome is a rare autosomal recessive disease caused by mutations in the DNA methyltransferase gene DNMT3B. To investigate the function of Dnmt3b in mouse development and to create animal models for ICF syndrome, we have generated three mutant alleles of Dnmt3b in mice: one carrying a deletion of the catalytic domain (null allele) and two carrying ICF-like missense mutations in the catalytic domain. The Dnmt3b null allele results in embryonic lethality from E14.5 to E16.5 with multiple tissue defects, including liver hypotrophy, ventricular septal defect and haemorrhage. By contrast, mice homozygous for the ICF mutations develop to term and some survive to adulthood. These mice show phenotypes that are reminiscent of ICF patients, including hypomethylation of repetitive sequences, low body weight, distinct cranial facial anomalies and T cell death by apoptosis. These results indicate that Dnmt3b plays an essential role at different stages of mouse development, and that ICF missense mutations cause partial loss of function. These mutant mice will be useful for further elucidation of the pathogenic and molecular mechanisms underlying ICF syndrome. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RIKEN, Ctr Dev Biol, Kobe, Hyogo 6500047, Japan. Novartis Inst Biomed Res, Epigenet Program, Cambridge, MA 02139 USA. RP Li, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM en.li@pharma.novartis.com OI Ueda, Yoshihide/0000-0003-3196-3494 FU NCI NIH HHS [CA82389]; NIGMS NIH HHS [GM52106] NR 44 TC 81 Z9 85 U1 1 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR 15 PY 2006 VL 133 IS 6 BP 1183 EP 1192 DI 10.1242/dev.02293 PG 10 WC Developmental Biology SC Developmental Biology GA 031AQ UT WOS:000236676900019 PM 16501171 ER PT J AU Shen, HX McElhinny, AS Cao, Y Gao, P Liu, JX Bronson, R Griffin, JD Wu, LZ AF Shen, HX McElhinny, AS Cao, Y Gao, P Liu, JX Bronson, R Griffin, JD Wu, LZ TI The Notch coactivator, MAML1, functions as a novel coactivator for MEF2C-mediated transcription and is required for normal myogenesis SO GENES & DEVELOPMENT LA English DT Article DE MAML1; MEF2C; Notch; muscular dystrophy; myogenesis; transcriptional coactivator ID SKELETAL-MUSCLE DIFFERENTIATION; MYOCYTE ENHANCER FACTOR-2; GENE-EXPRESSION; POSTNATAL MYOGENESIS; CELL ACTIVATION; MADS-BOX; MASTERMIND; MEF2; PROTEINS; EMBRYO AB The MAML (mastermind-like) proteins are a family of three cotranscriptional regulators that are essential for Notch signaling, a pathway critical for cell fate determination. Though the functions of MAML proteins in normal development remain unresolved, their distinct tissue distributions and differential activities in cooperating with various Notch receptors suggest that they have unique roles. Here we show that mice with a targeted disruption of the Maml1 gene have severe muscular dystrophy. In vitro, Maml1-null embryonic fibroblasts failed to undergo MyoD-induced myogenic differentiation, further suggesting that Maml1 is required for muscle development. Interestingly, overexpression of MAML1 in C2C12 cells dramatically enhanced myotube formation and increased the expression of muscle-specific genes, while RNA interference (RNAi)-mediated MAML1 knockdown abrogated differentiation. Moreover, we determined that MAML1 interacts with MEF2C (myocyte enhancer factor 2C), functioning as its potent cotranscriptional regulator. Surprisingly, however, MAML1's promyogenic effects were completely blocked upon activation of Notch signaling, which was associated with recruitment of MAML1 away from MEF2C to the Notch transcriptional complex. Our study thus reveals novel and nonredundant functions for MAML1: It acts as a coactivator for MEF2C transcription and is essential for proper muscle development. Mechanistically, MAML1 appears to mediate cross-talk between Notch and MEF2 to influence myogenic differentiation. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Univ Arizona, Dept Cell Biol & Anat, Tucson, AZ 85724 USA. Harvard Univ, Sch Med, Rodent Histopathol Core, Boston, MA 02115 USA. RP Wu, LZ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM lizi_wu@dfci.harvard.edu FU NCI NIH HHS [R01 CA036167, R01 CA097148] NR 40 TC 75 Z9 77 U1 2 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 15 PY 2006 VL 20 IS 6 BP 675 EP 688 DI 10.1101/gad.1383706 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 023XG UT WOS:000236158900007 PM 16510869 ER PT J AU Hodges, A Strand, AD Aragaki, AK Kuhn, A Sengstag, T Hughes, G Elliston, LA Hartog, C Goldstein, DR Thu, D Hollingsworth, ZR Collin, F Synek, B Holmans, PA Young, AB Wexler, NS Delorenzi, M Kooperberg, C Augood, SJ Faull, RLM Olson, JM Jones, L Luthi-Carter, R AF Hodges, A Strand, AD Aragaki, AK Kuhn, A Sengstag, T Hughes, G Elliston, LA Hartog, C Goldstein, DR Thu, D Hollingsworth, ZR Collin, F Synek, B Holmans, PA Young, AB Wexler, NS Delorenzi, M Kooperberg, C Augood, SJ Faull, RLM Olson, JM Jones, L Luthi-Carter, R TI Regional and cellular gene expression changes in human Huntington's disease brain SO HUMAN MOLECULAR GENETICS LA English DT Article ID IN-SITU HYBRIDIZATION; MOUSE MODELS; TRINUCLEOTIDE REPEAT; MICROARRAY ANALYSES; MESSENGER-RNA; POLYGLUTAMINE; RECEPTOR; CELLS; NEURODEGENERATION; DOPAMINE AB Huntington's disease (HD) pathology is well understood at a histological level but a comprehensive molecular analysis of the effect of the disease in the human brain has not previously been available. To elucidate the molecular phenotype of HD on a genome-wide scale, we compared mRNA profiles from 44 human HD brains with those from 36 unaffected controls using microarray analysis. Four brain regions were analyzed: caudate nucleus, cerebellum, prefrontal association cortex [Brodmann's area 9 (BA9)] and motor cortex [Brodmann's area 4 (BA4)]. The greatest number and magnitude of differentially expressed mRNAs were detected in the caudate nucleus, followed by motor cortex, then cerebellum. Thus, the molecular phenotype of HD generally parallels established neuropathology. Surprisingly, no mRNA changes were detected in prefrontal association cortex, thereby revealing subtleties of pathology not previously disclosed by histological methods. To establish that the observed changes were not simply the result of cell loss, we examined mRNA levels in laser-capture microdissected neurons from Grade 1 HD caudate compared to control. These analyses confirmed changes in expression seen in tissue homogenates; we thus conclude that mRNA changes are not attributable to cell loss alone. These data from bona fide HD brains comprise an important reference for hypotheses related to HD and other neurodegenerative diseases. C1 Ecole Polytech Fed Lausanne, Lab Funct Neurogemom, Stn 15, CH-1015 Lausanne, Switzerland. Univ Wales Coll Med, Dept Psychol Med, Cardiff CF14 4XN, Wales. Univ Wales Coll Med, Dept Med Genet, Cardiff CF14 4XN, Wales. Univ Cardiff Wales, Sch Biosci, Cardiff CF14 4XN, Wales. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. SIB, CH-1015 Lausanne, Switzerland. Univ Auckland, Dept Anat Radiol, Auckland 1, New Zealand. Massachusetts Gen Hosp, MIND, Charlestown, MA 02129 USA. Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA. Columbia Univ, New York, NY 10032 USA. Auckland City Hosp, Auckland, New Zealand. Hereditary Dis Fdn, Santa Monica, CA 90405 USA. RP Luthi-Carter, R (reprint author), Ecole Polytech Fed Lausanne, Lab Funct Neurogemom, Stn 15, AI 2138, CH-1015 Lausanne, Switzerland. EM ruth.luthi-carter@epfl.ch RI Hodges, Angela/C-5676-2011; turton, miranda/F-4682-2011; Holmans, Peter/F-4518-2015 OI Holmans, Peter/0000-0003-0870-9412 FU NCI NIH HHS [CA74841] NR 47 TC 338 Z9 342 U1 1 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR 15 PY 2006 VL 15 IS 6 BP 965 EP 977 DI 10.1093/hmg/ddl013 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 018NS UT WOS:000235771800014 PM 16467349 ER PT J AU Marucci, L Lane, AM Li, WJ Egan, KM Gragoudas, ES Adams, JA Collier, JM Munzenrider, JE AF Marucci, L Lane, AM Li, WJ Egan, KM Gragoudas, ES Adams, JA Collier, JM Munzenrider, JE TI Conservation treatment of the eye: Conformal proton reirradiation for recurrent uveal melanoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 04-08, 2001 CL SAN FRANCISCO, CA SP Amer Soc Therapeut Radiol & Oncol DE proton beam radiation therapy; uveal melanoma; eye; survival rate ID BEAM RADIATION-THERAPY; CHOROIDAL MELANOMA; PLAQUE RADIOTHERAPY; TUMOR-CONTROL; ENUCLEATION; SURVIVAL; IRRADIATION; COMPLICATIONS AB Purpose: To evaluate the outcomes of a second course of proton beam radiation therapy (PBRT) in patients with recurrent uveal melanoma. Methods and Materials: Thirty-one patients received a second course of PBRT. The mean interval between the first and the second PBRT course was 50.2 months (range, 8-165 months). Most patients (87%) received 70 cobalt Gray equivalent (CGE) for both courses. Visual acuity was 20/200 or better in 30 patients initially and in 22 patients at the second treatment. The mean follow-up time after the second treatment was 50 months (range, 6-164 months). Results: At the time of the last follow-up, 20 patients were classified as having no evidence of disease, defined as tumor regression or an absence of tumor progression. Nine eyes (29%) were enucleated because of local recurrence (n = 5) or intractable pain (n = 4). The 5-year eye retention rate was 55% (95% confidence interval: 25.2-77.4). Six of the 22 patients who retained the eye (27%) had useful vision (20/200 or better). Conclusions: A second course of PBRT for recurrent uveal melanoma to total doses between 118 and 140 CGE was associated with a relatively good probability of local control and a low enucleation rate. Although most patients lost vision, the majority were able to retain the reirradiated eye. Further evaluation is needed to assess metastasis-free survival of additional proton irradiation vs. enucleation after local recurrence. (C) 2006 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Tufts Univ New England Med Ctr, Biostat Unit, Boston, MA 02111 USA. RP Munzenrider, JE (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM jmunzenrider@partners.org RI Li, Wenjun/F-5634-2015 OI Li, Wenjun/0000-0001-5335-7386 NR 21 TC 14 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2006 VL 64 IS 4 BP 1018 EP 1022 DI 10.1016/j.ijrobp.2005.09.035 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 020GQ UT WOS:000235897100006 PM 16376492 ER PT J AU Taghian, AG Kozak, KR Doppke, KP Katz, A Smith, BL Gadd, M Specht, M Hughes, K Braaten, R Kachnic, LA Recht, A Powell, SN AF Taghian, AG Kozak, KR Doppke, KP Katz, A Smith, BL Gadd, M Specht, M Hughes, K Braaten, R Kachnic, LA Recht, A Powell, SN TI Initial dosimetric experience using simple three-dimensional conformal external-beam accelerated partial-breast irradiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 16-20, 2005 CL Denver, CO SP Amer Soc Therapeut Radiol & Oncol DE breast cancer; accelerated partial-breast irradiation; simple 3D conformal external-beam irradiation ID DOSE-RATE BRACHYTHERAPY; 20-YEAR FOLLOW-UP; CONSERVING SURGERY; CLINICAL-EXPERIENCE; CANCER; RADIOTHERAPY; MAMMOSITE; THERAPY; TRIAL; MASTECTOMY AB Purpose: Several accelerated partial-breast irradiation (APBI) techniques are being investigated in patients with early-stage breast cancer. We present our initial experience using three-dimensional conformal radiation therapy (3D-CRT). Methods and Materials: Sixty-one patients with tumors of 2 cm or less and negative axillary nodes were treated with 3D-CRT accelerated partial-breast irradiation (APBI) between August 2003 and March 2005. The prescribed radiation dose was 32 Gy in 4-Gy fractions given twice daily. Efforts were made to minimize the number of beams required to achieve adequate planning target volume (PTV) coverage. Results: A combination of photons and electrons was used in 85% of patients. A three-field technique that consisted of opposed, conformal tangential photons and enface electrons was employed in 43 patients (70%). Nine patients (15%) were treated with a four-field arrangement, which consisted of three photon fields and enface electrons. Mean PTV volumes that received 100%, 95%, and 90% of the prescribed dose were 93% +/- 7%, 97% +/- 4%, and 98% +/- 2%, respectively. Dose inhomogeneity exceeded 10% in only 7 patients (11%). Mean doses to the ipsilateral lung and heart were 1.8 Gy and 0.8 Gy, respectively. Conclusions: Simple 3D-CRT techniques of APBI can achieve appropriate PTV coverage while offering significant normal-tissue sparing. Therefore, this noninvasive approach may increase the availability of APBI to patients with early-stage breast cancer. (C) 2006 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Breast Pathol, Boston, MA 02114 USA. Boston Med Ctr, Dept Radiat Oncol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM ataghian@partners.org OI Hughes, Kevin/0000-0003-4084-6484 FU NCI NIH HHS [P50 CA89393] NR 29 TC 76 Z9 77 U1 0 U2 1 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 2006 VL 64 IS 4 BP 1092 EP 1099 DI 10.1016/j.ijrobp.2005.09.042 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 020GQ UT WOS:000235897100016 PM 16406392 ER PT J AU Ray, ME Thames, HD Levy, LB Horwitz, EM Kupelian, PA Martinez, AA Michalski, JM Pisansky, TM Shipley, WU Zelefsky, MJ Zietman, AL Kuban, DA AF Ray, ME Thames, HD Levy, LB Horwitz, EM Kupelian, PA Martinez, AA Michalski, JM Pisansky, TM Shipley, WU Zelefsky, MJ Zietman, AL Kuban, DA TI PSA nadir predicts biochemical and distant failures after external beam radiotherapy for prostate cancer: A multi-institutional analysis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 17-20, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol DE prostate cancer; PSA nadir; external beam radiotherapy ID DISEASE-FREE SURVIVAL; RADIATION-THERAPY; ANTIGEN NADIR; DOSE-RESPONSE; CONFORMAL RADIOTHERAPY; PRETREATMENT NOMOGRAM; LOCALIZED CARCINOMA; STAGE T1-T2; IRRADIATION; ESCALATION AB Purpose: To determine the significance of prostate-specific antigen (PSA) nadir (nPSA) and the time to nPSA (T-nPSA) in predicting biochemical or clinical disease-free survival (PSA-DFS) and distant metastasis-free survival (DMFS) in patients treated with definitive external beam radiotherapy (RT) for clinical Stage T1b-T2 prostate cancer. Methods and Materials: Nine participating institutions submitted data on 4839 patients treated between 1986 and 1995 for Stage T1b-T2cN0-NxM0 prostate cancer. All patients were treated definitively with RT alone to doses >= 60 Gy, without neoadjuvant or planned adjuvant androgen suppression. A total of 4833 patients with a median follow-up of 6.3 years met the criteria for analysis. Two endpoints were considered: (1) PSA-DFS, defined as freedom from PSA failure (American Society for Therapeutic Radiology and Oncology definition), initiation of androgen suppression after completion of RT, or documented local or distant failure; and (2) DMFS, defined as freedom from clinically apparent distant failure. In patients with failure, nPSA was defined as the lowest PSA measurement before any failure. In patients without failure, nPSA was the lowest PSA measurement during the entire follow-up period. T-nPSA was calculated from the completion of RT to the nPSA date. Results: A greater nPSA level and shorter T-nPSA were associated with decreased PSA-DFS and DMFS in all patients and in all risk categories (low [Stage T1b, T1c, or T2a, Gleason score <= 6, and PSA level <= 10 ng/mL], intermediate [Stage T1b, T1c, or T2a, Gleason score <= 6, and PSA level >10 but <= 20 ng/mL, or Stage T2b or T2c, Gleason score <= 6, and PSA level <= 20 ng/mL, or Gleason score 7 and PSA level <= 20 ng/mL], and high [Gleason score 8-10 or PSA level >20 ng/mL]), regardless of RT dose. The 8-year PSA-DFS and DMFS rate for patients with nPSA <0.5 ng/mL was 75% and 97%; nPSA >= 0.5 but <1.0 ng/mL, 52% and 96%; nPSA >= 1.0 but <2.0 ng/mL, 40% and 91%; and nPSA >= 2.0 ng/mL, 17% and 73%, respectively. The 8-year PSA-DFS and DMFS rate for patients with T-nPSA <6 months was 27% and 66%; T-nPSA >= 6 but <12 months, 31% and 85%; T-nPSA >= 12 but <24 months, 42% and 94%; and T-nPSA >= 24 months, 75% and 99%, respectively. A shorter T-nPSA was associated with decreased PSA-DFS and DMFS, regardless of the nPSA. Both nPSA and T-nPSA were significant predictors of PSA-DFS and DMFS in multivariate models incorporating clinical stage, Gleason score, initial PSA level, and RT dose. The significance of nPSA and T-nPSA was supported by landmark analysis, as well as by analysis of nPSA and T-nPSA as time-dependent covariates. A dose >= 70 Gy was associated with a lower nPSA level and longer T-nPSA in all risk categories, and a greater dose was significantly associated with greater PSA-DFS and DMFS in multivariate analysis. Regression analysis confirmed that higher clinical stage, Gleason score, and initial PSA were associated with a greater nPSA level. Conclusion: The results of this large, multi-institutional analysis of 4833 patients have provided important evidence that nPSA and T-nPSA after definitive external beam RT are not only predictive of a predominantly PSA endpoint (PSA-DFS), but are also predictive of distant metastasis in all clinical risk categories. Greater RT doses were associated with lower nPSA, longer T-nPSA, and improved PSA-DFS and DMFS. (C) 2006 Elsevier Inc. C1 Univ Michigan, Med Ctr, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biomath, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Div Radiat Oncol, Houston, TX 77030 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Cleveland Clin Fdn, Dept Radiat Oncol, Cleveland, OH 44195 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Edward Mallinckrodt Inst Radiol, Dept Radiat Oncol, St Louis, MO 63110 USA. Mayo Clin, Coll Med, Div Radiat Oncol, Rochester, MN USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. RP Ray, ME (reprint author), Univ Michigan, Med Ctr, Dept Radiat Oncol, UH-B2C490,Box 0010,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM mray@umich.edu NR 36 TC 83 Z9 85 U1 1 U2 5 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 2006 VL 64 IS 4 BP 1140 EP 1150 DI 10.1016/j.ijrobp.2005.07.006 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 020GQ UT WOS:000235897100022 PM 16198506 ER PT J AU Shipley, WU DeSilvio, M Pilepich, MV Roach, M Wolkov, HB Sause, WT Rubin, P Lawton, CA AF Shipley, WU DeSilvio, M Pilepich, MV Roach, M Wolkov, HB Sause, WT Rubin, P Lawton, CA TI Early initiation of salvage hormone therapy influences survival in patients who failed initial radiation for locally advanced prostate cancer: A secondary analysis of RTOG Protocol 86-10 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; external-beam radiotherapy; neoadjuvant hormonal therapy; salvage hormonal therapy ID ANDROGEN SUPPRESSION; ONCOLOGY GROUP; DEFINITIVE RADIOTHERAPY; DEPRIVATION; CARCINOMA; TRIAL; GOSERELIN AB Purpose: We examined overall and disease-specific survival outcomes both from the time of initial treatment and from the start of salvage hormone therapy (HT), by the extent of disease progression at the time salvage HT was started in patients treated on RTOG Protocol 86-10. Methods and Materials: With a median follow-up of 9.0 years, 247 patients (54%) had received subsequent salvage HT. The overall survival (OVS) and disease-specific survival (DSS) were compared by the extent of disease progression at the time salvage HT was started. Results: For those patients with distant metastases (DM) present at the start of salvage HT, the OVS and DSS were significantly reduced when compared with those with DM absent at the time salvage HT was started (OVS at 8 years, 31% vs. 58%; DSS at 8 years, 38% vs. 65%). A statistically significant increase in DSS was observed among the 143 patients with DM absent when patients with prostate-specific antigen (PSA) less than 20 were compared with those with PSA greater than 20 at the time salvage HT was started. Conclusions: The DSS and the OVS of the relapsed patient are decreased in those with more extensive disease at the time of salvage HT. However, because this protocol could not evaluate the effect of posttreatment PSA velocity on outcomes, which is likely a better predictor of long-term success with salvage HT, these results cannot be taken to demonstrate that early salvage HT in patients with long posttreatment PSA doubling times is necessary for longer survival. (C) 2006 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RTOG, Dept Biostat, Philadelphia, PA USA. Univ Calif Los Angeles, Med Ctr, Dept Radiat Oncol, Los Angeles, CA 90024 USA. Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. Radiat Oncol Ctr, Sacramento, CA USA. LDS Hosp, Dept Radiat Oncol, Salt Lake City, UT USA. Univ Rochester, Dept Radiat Oncol, Rochester, NY USA. Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. RP Shipley, WU (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM wshipley@partners.org FU NCI NIH HHS [CA-21661, CA-32115] NR 17 TC 35 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2006 VL 64 IS 4 BP 1162 EP 1167 DI 10.1016/j.ijrobp.2005.09.039 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 020GQ UT WOS:000235897100024 PM 16427211 ER PT J AU Zhou, XD Pogue, BW Chen, B Demidenko, E Joshi, R Hoopes, J Hasan, T AF Zhou, XD Pogue, BW Chen, B Demidenko, E Joshi, R Hoopes, J Hasan, T TI Pretreatment photosensitizer dosimetry reduces variation in tumor response SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE photodynamic therapy; photodynamic; dosimetry; heterogeneity; treatment planning ID LIGHT-DOSE DEPENDENCE; NORMAL RAT-LIVER; PHOTODYNAMIC THERAPY; IN-VIVO; ALUMINUM PHTHALOCYANINE; VASCULAR-PERMEABILITY; CLINICAL-APPLICATIONS; FLUORESCENCE; OXYGEN; TISSUE AB Purpose: To compensate for photosensitizer uptake variation in photodynamic therapy (PDT), via control of delivered light dose through photodynamic dose calculation based on online dosimetry of photosensitizer in tissue before treatment. Methods and Materials: Photosensitizer verteporfin was quantified via multiple fluorescence microprobe measurements immediately before treatment. To compensate individual PDT treatments, photodynamic doses were calculated on an individual animal basis, by matching the light delivered to provide an equal photosensitizer dose multiplied by light dose. This was completed for the lower quartile, median, and upper quartile of the photosensitizer distribution. PDT-induced tumor responses were evaluated by the tumor regrowth assay. Results: Verteporfin uptake varied considerably among tumors and within a tumor. The coefficient of variation in the surviving fraction was found significantly decreased in groups compensated to the lower quartile (CL-PDT), the median (CM-PDT), and the upper quartile (CU-PDT) of photosensitizer distribution. The CL-PDT group was significantly less effective compared with NC-PDT (Noncompensated PDT), CM-PDT, and CU-PDT treatments. No significant difference in effectiveness was observed between NC-PDT, CM-PDT, and CU-PDT treatment groups. Conclusions: This research suggests that accurate quantification of tissue photosensitizer levels and subsequent adjustment of light dose will allow for reduced subject variation and improved treatment consistency. (C) 2006 Elsevier Inc. C1 Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA USA. Dartmouth Med Sch, Dept Surg, Hanover, NH USA. Dartmouth Med Sch, Epidemiol & Biostat Sect, Hanover, NH USA. RP Pogue, BW (reprint author), Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. EM Brian.W.Pogue@Dartmouth.edu FU NCI NIH HHS [P01CA84203, R01CA109558] NR 64 TC 58 Z9 59 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2006 VL 64 IS 4 BP 1211 EP 1220 DI 10.1016/j.ijrobp.2005.11.019 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 020GQ UT WOS:000235897100032 PM 16504761 ER PT J AU Shirato, H Suzuki, K Sharp, GC Fujita, K Onimaru, R Fujino, M Kato, N Osaka, Y Kinoshita, R Taguchi, H Onodera, S Miyasaka, K AF Shirato, H Suzuki, K Sharp, GC Fujita, K Onimaru, R Fujino, M Kato, N Osaka, Y Kinoshita, R Taguchi, H Onodera, S Miyasaka, K TI Speed and amplitude of lung tumor motion precisely detected in four-dimensional setup and in real-time tumor-tracking radiotherapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE four-dimensional radiotherapy; setup; real-time tracking; four-dimensional setup ID RESPIRATORY MOTION; STEREOTACTIC RADIOTHERAPY; RADIATION-THERAPY; CT-SIMULATION; SYSTEM; CANCER; SCANS AB Background: To reduce the uncertainty of registration for lung tumors, we have developed a four-dimensional (4D) setup system using a real-time tumor-tracking radiotherapy system. Methods and Materials: During treatment planning and daily setup in the treatment room, the trajectory of the internal fiducial marker was recorded for 1 to 2 min at the rate of 30 times per second by the real-time tumor-tracking radiotherapy system. To maximize gating efficiency, the patient's position on the treatment couch was adjusted using the 4D setup system with fine on-line remote control of the treatment couch. Results: The trajectory of the marker detected in the 4D setup system was well visualized and used for daily setup. Various degrees of interfractional and intrafractional changes in the absolute amplitude and speed of the internal marker were detected. Readjustments were necessary during each treatment session, prompted by baseline shifting of the tumor position. Conclusion: The 4D setup system was shown to be useful for reducing the uncertainty of tumor motion and for increasing the efficiency of gated irradiation. Considering the interfractional and intrafractional changes in speed and amplitude detected in this study, intercepting radiotherapy is the safe and cost-effective method for 4D radiotherapy using real-time tracking technology. (C) 2006 Elsevier Inc. C1 Hokkaido Univ, Sch Med, Dept Radiol, Sapporo, Hokkaido 0608636, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Shirato, H (reprint author), Hokkaido Univ, Sch Med, Dept Radiol, North 15 West 7, Sapporo, Hokkaido 0608636, Japan. EM hshirato@radi.med.hokudai.ac.jp RI Shirato, Hiroki/A-7068-2010; Katoh, Norio/A-5488-2012; Onimaru, Rikiya/C-9805-2012; OI Onimaru, Rikiya/0000-0002-4768-2358; Suzuki, Keishiro/0000-0001-6866-7897 NR 22 TC 109 Z9 114 U1 2 U2 4 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 2006 VL 64 IS 4 BP 1229 EP 1236 DI 10.1016/j.ijrobp.2005.11.016 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 020GQ UT WOS:000235897100034 PM 16504762 ER PT J AU Bert, C Metheany, KG Doppke, KP Taghian, AG Powell, SN Chen, GTY AF Bert, C Metheany, KG Doppke, KP Taghian, AG Powell, SN Chen, GTY TI Clinical experience with a 3D surface patient setup system for alignment of partial-breast irradiation patients SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 17-20, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol DE partial-breast irradiation setup; surface imaging; radiotherapy ID CANCER RADIOTHERAPY; POSITIONING SYSTEM; RADIATION-THERAPY; VERIFICATION; CARCINOMA; PROSTATE; MOTION AB Purpose: To assess the utility of surface imaging on patient setup for accelerated partial-breast irradiation (APBI). Methods and Material: A photogrammetry system was used in parallel to APBI setup by laser and portal imaging. Surface data were acquired after laser and port-film setup for 9 patients. Surfaces were analyzed in comparison to a reference surface from the first treatment session by use of rigid transformations. The surface model after laser setup was used in a simulated photogrammetry setup procedure. In addition, breathing data were acquired by surface acquisition at a frame rate of 7 Hz. Results: Mean 3D displacement was 7.3 mm (SD, 4.4 mm) and 7.6 mm (SD, 4.2 mm) for laser and port film, respectively. Simulated setup with the photogrammetry system yielded mean displacement of 1 mm (SD, 1.2 mm). Distance analysis resulted in mean distances of 3.7 mm (SD, 4.9 mm), 4.3 mm (SD, 5.6 mm), and 1.6 mm (SD, 2.4 mm) for laser, port film, and photogrammetry, respectively. Breathing motion at isocenter was smaller than 3.7 mm, with a mean of 1.9 mm (SD, 1.1 mm). Conclusions: Surface imaging for PBI setup appears promising. Alignment of the 3D breast surface achieved by stereo-photogrammetry shows greater breast topology congruence than when patients are set up by laser or portal imaging. A correlation of breast surface and CTV must be quantitatively established. (C) 2006 Elsevier Inc. C1 Gesell Schwerionenforsch mbH, Biophys Abt, D-6100 Darmstadt, Germany. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bert, C (reprint author), GSI, Biophys, Planckstr 1, D-64291 Darmstadt, Germany. EM c.bert@gsi.de RI Bert, Christoph/C-2585-2013 OI Bert, Christoph/0000-0002-8539-6600 NR 21 TC 92 Z9 93 U1 0 U2 8 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 2006 VL 64 IS 4 BP 1265 EP 1274 DI 10.1016/j.ijrobp.2005.11.008 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 020GQ UT WOS:000235897100038 PM 16504764 ER PT J AU Aksan, A Irimia, D He, XM Toner, M AF Aksan, A Irimia, D He, XM Toner, M TI Desiccation kinetics of biopreservation solutions in microchannels SO JOURNAL OF APPLIED PHYSICS LA English DT Article ID POLYMER-SOLVENT SYSTEMS; WATER-VAPOR ABSORPTION; DIFFUSION-COEFFICIENTS; MOLECULAR-WEIGHT; VITRIFICATION; ANHYDROBIOSIS; CARBOHYDRATE; TEMPERATURE; DEPENDENCE; EXPOSURE AB A microfluidic device was utilized to measure the viscosity gradients formed in carbohydrate solutions of biological significance during desiccation and skin formation. A complementary numerical model employed the free volume theory to predict the concentration-dependent diffusion coefficients and viscosity gradients in concentrated solutions. It was established that the glassy skin formation at the gas-liquid interface played a key role in water entrapment and the formation and persistence of very steep concentration and viscosity gradients in the desiccating solutions. The results of this study highlighted an important phenomenon that should be accounted for during isothermal drying of glass-forming solutions: solutions with high glass transition temperatures, inevitably, dry heterogeneously. In the final product, there are significant spatial variations in water and solute content affecting the storage stability. (c) 2006 American Institute of Physics. C1 Univ Minnesota, Dept Mech Engn, Minneapolis, MN 55455 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Sci, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Aksan, A (reprint author), Univ Minnesota, Dept Mech Engn, Minneapolis, MN 55455 USA. EM aaksan@me.umn.edu RI Aksan, Alptekin/A-7187-2008; He, Xiaoming/C-5499-2008; Aksan, Alptekin/C-1579-2014; OI He, Xiaoming/0000-0003-0125-6086; Aksan, Alptekin/0000-0001-9891-1715; Irimia, Daniel/0000-0001-7347-2082 NR 26 TC 15 Z9 15 U1 0 U2 4 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-8979 J9 J APPL PHYS JI J. Appl. Phys. PD MAR 15 PY 2006 VL 99 IS 6 AR 064703 DI 10.1063/1.2181280 PG 9 WC Physics, Applied SC Physics GA 028CR UT WOS:000236464400078 ER PT J AU Gvilia, I Turner, A McGinty, D Szymusiak, R AF Gvilia, I Turner, A McGinty, D Szymusiak, R TI Preoptic area neurons and the homeostatic regulation of rapid eye movement sleep SO JOURNAL OF NEUROSCIENCE LA English DT Article DE sleep homeostasis; REM sleep; sleep deprivation; ventrolateral preoptic area; GABA; median preoptic nucleus ID DORSAL RAPHE NUCLEUS; SEROTONIN-CONTAINING NEURONS; WAKING DISCHARGE PATTERNS; MONOAMINERGIC CELL GROUPS; FREELY MOVING CATS; C-FOS; GABAERGIC INNERVATION; GALANINERGIC NEURONS; HYPOTHALAMIC NEURONS; PARADOXICAL SLEEP AB The median preoptic nucleus (MnPN) and the ventral lateral preoptic area (vlPOA) of the hypothalamus express sleep-related Fos immunoreactivity, and a subset of Fos-immunoreactive neurons (IRNs) in these nuclei contain glutamic acid decarboxylase (GAD), a marker of GABAergic cells. We recently showed that the numbers of Fos-positive (Fos +) and Fos + GAD-IRNs in both the MnPN and the vlPOA are positively correlated with the total amount of preceding sleep. The present study was designed to clarify whether or not activation of sleep-related neurons in the rat MnPN and vlPOA is associated with rapid eye movement (REM) sleep regulation. Expression of c-fos in MnPN and vlPOA neurons was examined under conditions of spontaneous sleep, REM sleep restriction, and REM sleep recovery after REM sleep restriction. Across all conditions, the number of Fos-IRNs was highest in REM-sleep- restricted rats displaying the highest levels of REM sleep homeostatic pressure/drive, i. e., those rats exhibiting the most frequent attempts to enter REM sleep. This finding provides the first evidence that activation of subsets of MnPN and vlPOA neurons is more strongly related to REM sleep pressure than to REM sleep amount. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA 91343 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Beritashvili Inst Physiol, GE-0160 Tbilisi, Rep of Georgia. RP Szymusiak, R (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, 16111 Plummer St, North Hills, CA 91343 USA. EM irmagvilia@hotmail.com; rszym@ucla.edu FU NHLBI NIH HHS [HL60296]; NIMH NIH HHS [MH63323] NR 35 TC 51 Z9 57 U1 0 U2 1 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 15 PY 2006 VL 26 IS 11 BP 3037 EP 3044 DI 10.1523/JNEUROSCI.4827-05.2006 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 021QU UT WOS:000236000400022 PM 16540582 ER PT J AU Bilenca, A Yun, SH Tearney, GJ Bouma, BE AF Bilenca, A Yun, SH Tearney, GJ Bouma, BE TI Numerical study of wavelength-swept semiconductor ring lasers: the role of refractive-index nonlinearities in semiconductor optical amplifiers and implications for biomedical imaging applications SO OPTICS LETTERS LA English DT Article ID PULSES AB Recent results have demonstrated unprecedented wavelength-tuning speed and repetition rate performance of semiconductor ring lasers incorporating scanning filters. However, several unique operational characteristics of these lasers have not been adequately explained, and the lack of an accurate model has hindered optimization. We numerically investigated the characteristics of these sources, using a semiconductor optical amplifier (SOA) traveling-wave Langevin model, and found good agreement with experimental measurements. In particular, we explored the role of the SOA refractive-index nonlinearities in determining the intracavity frequency-shift-broadening and the emitted power dependence on scan speed and direction. Our model predicts both continuous-wave and pulse operation and shows a universal relationship between the output power of lasers that have different cavity lengths and the filter peak frequency shift per round trip, therefore revealing the advantage of short cavities for high-speed biomedical imaging. (c) 2006 Optical Society of America C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Bilenca, A (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM abilenca@partners.org FU NCI NIH HHS [R01 CA103769, R01 CA103769-03]; NHLBI NIH HHS [R01 HL076398-05, R01 HL076398] NR 10 TC 35 Z9 35 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD MAR 15 PY 2006 VL 31 IS 6 BP 760 EP 762 DI 10.1364/OL.31.000760 PG 3 WC Optics SC Optics GA 019KG UT WOS:000235833400028 PM 16544615 ER PT J AU Sun, CH Munn, LL AF Sun, CH Munn, LL TI Influence of erythrocyte aggregation on leukocyte margination in postcapillary expansions: A lattice Boltzmann analysis SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article; Proceedings Paper CT 13th International Conference on Discrete Simulation of Fluid Dyanmics CY AUG 16-20, 2004 CL Cambridge, MA SP Tufts Univ DE erythrocyte aggregation; blood rheology; lattice Boltzmann; leukocyte margination ID PARTICULATE SUSPENSIONS; SHEAR-FLOW; ADHESION; EQUATION; VENULES; DEFORMATION; ENDOTHELIUM; MESENTERY; SURFACES; ARREST AB Leukocyte rolling on the vascular endothelium requires initial contact between the circulating leukocytes in the blood and the vessel wall. Although specific adhesion mechanisms are involved in leukocyte-endothelium interactions, adhesion patterns in vivo suggest other rheological mechanisms are involved as well. Previous studies have proposed that the abundance of leukocyte rolling in postcapillary venules is due to interactions between red blood cells and leukocytes as they enter capillary expansions as well as red blood cell (RBC) aggregation. We have established a lattice Boltzmann approach to analyze the interactions of RBC aggregates and leukocytes as they flow through a postcapillary expansion. The lattice Boltzmann technique provides the complete solution of the flow field and quantification of the particle-particle forces. Our results show that RBC aggregation strongly influences leukocyte-endothelium interactions. (c) 2005 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Munn, LL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM csun@steele.mgh.harvard.edu; lance@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 25 TC 23 Z9 23 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD MAR 15 PY 2006 VL 362 IS 1 BP 191 EP 196 DI 10.1016/j.physa.2005.09.027 PG 6 WC Physics, Multidisciplinary SC Physics GA 016OZ UT WOS:000235630900030 ER PT J AU Saidman, SL Roth, AE Sonmez, T Unver, MU Delmonico, FL AF Saidman, SL Roth, AE Sonmez, T Unver, MU Delmonico, FL TI Increasing the opportunity of live kidney donation by matching for two- and three-way exchanges SO TRANSPLANTATION LA English DT Article DE kidney; transplant; donor; exchange; paired ID SCHOOL MATCH; LIVING-DONOR; TRANSPLANTATION; PROGRAM; DESIGN; RECIPIENTS; MARKET; ALLOWS; ORGANS AB Background. To expand the opportunity for paired live donor kidney transplantation, computerized matching algorithms have been designed to identify maximal sets of compatible donor/recipient pairs from a registry of incompatible pairs submitted as candidates for transplantation. Methods. Demographic data of patients who had been evaluated for live donor kidney transplantation but found to be incompatible with their potential donor (because of ABO blood group or positive crossmatch) were submitted for computer analysis and matching. Data included ABO and H LA types of donor and recipient, %PRA and specificity of recipient alloantibody, donor/recipient relationship, and the reason the donor was incompatible. The data set used for the initial simulation included 29 patients with one donor each and 16 patients with multiple donors for a total of 45 patients and 68 donor/patient pairs. In addition, a simulation based on OPTN/SRTR data was used to further assess the practical importance of multiple exchange combinations. Results. If only exchanges involving two patient-donor pairs were allowed, a maximum of 8 patient-donor pairs in the data set could exchange kidneys. If three-way exchanges were also allowed, a maximum of I 1 pairs could exchange kidneys. Simulations with OPTN/SRTR data demonstrate that the increase in the number of potential transplants if three-way exchanges are allowed is robust, and does not depend on the particular patients in our sample. Conclusions. A computerized matching protocol can be used to identify donor/recipient pairs from a registry of incompatible pairs who can potentially enter into donor exchanges that otherwise would not readily occur. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Dept Econ, Cambridge, MA 02138 USA. Harvard Univ, Sch Business, Boston, MA 02115 USA. Boston Coll, Dept Econ, Chestnut Hill, MA USA. Univ Pittsburgh, Dept Econ, Pittsburgh, PA 15260 USA. New England Organ Bank Inc, Newton, MA USA. RP Saidman, SL (reprint author), New England Program Kidney Exchange, 1 Gateway Ctr, Boston, MA 02114 USA. EM ssaidman@partners.org NR 28 TC 76 Z9 78 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 15 PY 2006 VL 81 IS 5 BP 773 EP 782 DI 10.1097/01.tp.0000195775.77081.25 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 024XN UT WOS:000236229900020 PM 16534482 ER PT J AU Iken, K Huang, L Bekele, H Schmidt, EV Koziel, MJ AF Iken, K Huang, L Bekele, H Schmidt, EV Koziel, MJ TI Apoptosis of activated CD4+and CD8+T cells is enhanced by co-culture with hepatocytes expressing hepatitis C virus (HCV) structural proteins through FasL induction SO VIROLOGY LA English DT Article DE HCV; apoptosis; immune evasion; lymphocytes; hepatocytes; Fas-FasL; viral persistence ID CD8(+) T-CELLS; BLOOD MONONUCLEAR-CELLS; PERIPHERAL-BLOOD; IMMUNE-RESPONSE; CORE PROTEIN; TOLERANCE INDUCTION; LIVER ALLOGRAFTS; DENDRITIC CELLS; IN-VIVO; INFECTION AB A central unresolved issue in hepatitis C virus (HCV) infection is how the virus establishes chronic infection. Recent studies suggest that the liver microenvironment leads to apoptosis of activated T cells, which may be involved in the tolerance to liver allograft. Here, We report that murine hepatocytes expressing a transgene encoding the HCV structural proteins core, envelope 1 (E1) and envelope 2 (E2) enhance apoptosis of activated T cells. Unlike normal liver, which appears to selectively remove only activated CD8+ T cells, enhanced apoptosis was seen for both CD4+ and CD8+ T cells. Enhanced apoptosis of activated T lymphocytes was associated with upregulation of FasL by HCV transgenic hepatocytes and was specifically inhibited by anti-FasL blocking antibody. Increased apoptosis of activated T cells induced by HCV structural proteins could amplify the ability of the liver to down-modulate T cell responses, leading to attenuation of anti-viral responses and facilitating viral persistence. (C) 2005 Elsevier Inc. All rights reserved. C1 Beth Israel Deaconess Hosp, Div Infect Dis, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Tumor Biol Program, Charlestown, MA 02129 USA. RP Koziel, MJ (reprint author), Beth Israel Deaconess Hosp, Div Infect Dis, HIM 223A,330 Brookline Ave, Boston, MA 02115 USA. EM mkoziel@bidmc.harvard.edu FU NIAID NIH HHS [AI 50752, AI43478, R01 AI043478-03, R01 AI050752]; NIDDK NIH HHS [DK075331-4, R21 DK075331] NR 57 TC 28 Z9 30 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 15 PY 2006 VL 346 IS 2 BP 363 EP 372 DI 10.1016/j.virol.2005.11.017 PG 10 WC Virology SC Virology GA 024JR UT WOS:000236191800011 PM 16336987 ER PT J AU Vandegraaff, N Devroe, E Turlure, F Silver, PA Engelman, A AF Vandegraaff, N Devroe, E Turlure, F Silver, PA Engelman, A TI Biochemical and genetic analyses of integrase-interacting proteins lens epithelium-derived growth factor growth factor related protein 2 function and (LEDGF)/p75 and hepatoma-derived (HRP2) in preintegration complex HTV-1 replication SO VIROLOGY LA English DT Article DE LEDGF/p75; HRP2; HIV-1; integration; integrase; PIC; RNAi ID HUMAN-IMMUNODEFICIENCY-VIRUS; TO-AUTOINTEGRATION FACTOR; RETROVIRAL DNA INTEGRATION; HIV TYPE-1 INTEGRATION; VIRAL NUCLEIC-ACIDS; IN-VITRO; PRODUCTIVE INFECTION; INTERACTION DOMAIN; HUMAN GENOME; HUMAN-CELLS AB Human immunodeficiency virus type 1 (HIV-1) integrase (IN) functions in cells within the context of high molecular weight preintegration complexes (PICs). Lens epithelium-derived growth factor (LEDGF) transcriptional coactivator/p75 and hepatoma-derived growth factor related protein 2 (HRP2) tightly bind to HIV-1 IN and stimulate its integration activity in vitro. Here, we show that each recombinant host cell factor efficiently reconstitutes the in vitro activity of HIV-1 PTCs disrupted for functional integration by pre-treatment with high concentrations of salt. Mutational analysis reveals that both the IN-binding and I)NA-binding activities of LEDGF/p75 contribute to functional PIC reconstitution. We also investigate a role(s) for these proteins in HIV-1 infection by using short-interfering RNA. HIV-1 infection was essentially unaffected in HeLa-P4 cells depleted for LEDGF/p75, HRP2, or both proteins. We conclude that cells knocked-out for LEDGF/p75 and/or HRP2 will be useful genetic tools to address the roles of these host cell factors in HIV-1 replication. (C) 2005 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu FU NIAID NIH HHS [AI39394, AI60354, AI52014] NR 65 TC 72 Z9 75 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 0042-6822 J9 VIROLOGY JI Virology PD MAR 15 PY 2006 VL 346 IS 2 BP 415 EP 426 DI 10.1016/j.virol.2005.11.022 PG 12 WC Virology SC Virology GA 024JR UT WOS:000236191800017 PM 16337983 ER PT J AU Shin, JM Homerin, M Domagala, F Ficheux, H Sachs, G AF Shin, JM Homerin, M Domagala, F Ficheux, H Sachs, G TI Characterization of the inhibitory activity of tenatoprazole on the gastric H+,K+-ATPase in vitro and in vivo SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE the gastric H,K-ATPase; tenatoprazole; binding stoichiometry; inhibition of acid secretion; proton pump inhibitor; omeprazole ID PROTON PUMP INHIBITORS; PLASMA HALF-LIFE; ACID-SECRETION; INTRAGASTRIC PH; HEALTHY-VOLUNTEERS; PARIETAL-CELL; OMEPRAZOLE; VESICLES; ATPASE; ESOMEPRAZOLE AB Tenatoprazole is a prodrug of the proton pump inhibitor (PPI) class, which is converted to the active sulfenamide or sulfenic acid by acid in the secretory canaliculus of the stimulated parietal cell of the stomach. This active species binds to lurninally accessible cysteines of the gastric H+,K+-ATPase resulting in disulfide formation and acid secretion inhibition. Tenatoprazole binds at the catalytic subunit of the gastric acid pump with a stoichiometry of 2.6 nmol mg(-1) of the enzyme in vitro. In vivo, maximum binding of tenatoprazole was 2.9 nmol mg(-1) of the enzyme at 2 h after IV administration. The binding sites of tenatoprazole were in the TM5/6 region at Cys813 and Cys822 as shown by tryptic and thermolysin digestion of the ATPase labeled by tenatoprazole. Decay of tenatoprazole binding on the gastric H+,K+-ATPase consisted of two components. One was relatively fast, with a half-life 3.9 h due to reversal of binding at cysteine 813, and the other was a plateau phase corresponding to ATPase turnover reflecting binding at cysteine 822 that also results in sustained inhibition in the presence of reducing agents in vitro. The stability of inhibition and the long plasma half-life of tenatoprazole should result in prolonged inhibition of acid secretion as compared to omeprazole. Further, the bioavailability of tenatoprazole was twofold greater in the (S)-tenatoprazole sodium salt hydrate form as compared to the free form in dogs which is due to differences in the crystal structure and hydrophobic nature of the two forms. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol & Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Membrane Biol Lab, Los Angeles, CA 90073 USA. Negma Lerads, F-78771 Magny Les Hameaux, France. RP Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol & Med, Los Angeles, CA 90024 USA. EM jaishin@ucla.edu; gsachs@ucla.edu FU NIDDK NIH HHS [DK46917, DK53462, DK58333] NR 35 TC 33 Z9 36 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 EI 1873-2968 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAR 14 PY 2006 VL 71 IS 6 BP 837 EP 849 DI 10.1016/j.bcp.2005.11.030 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 017WD UT WOS:000235723100014 PM 16405921 ER PT J AU Aikawa, E Whittaker, P Farber, M Mendelson, K Padera, RF Aikawa, M Schoen, FJ AF Aikawa, E Whittaker, P Farber, M Mendelson, K Padera, RF Aikawa, M Schoen, FJ TI Human semilunar cardiac valve remodeling by activated cells from fetus to adult - Implications for postnatal adaptation, pathology, and tissue engineering SO CIRCULATION LA English DT Article DE cells; collagen; remodeling; tissue engineering; valves ID HEART-VALVES; ADHESION MOLECULES; POLARIZED-LIGHT; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; COLLAGEN; MICROSCOPE; EXPRESSION; MORPHOLOGY; PHENOTYPE AB Background - The evolution of cell phenotypes and matrix architecture in cardiac valves during fetal maturation and postnatal adaptation through senescence remains unexplored. Methods and Results - We hypothesized that valvular interstitial (VIC) and endothelial cell (VEC) phenotypes, critical for maintaining valve function, change throughout life in response to environmental stimuli. We performed quantitative histological assessment of 91 human semilunar valves obtained from fetuses at 14 to 19 and 20 to 39 weeks' gestation; neonates minutes to 30 days old; children aged 2 to 16 years; and adults. A trilaminar architecture appeared by 36 weeks of gestation but remained rudimentary compared with that of adult valves. VECs expressed an activated phenotype throughout fetal development. VIC density, proliferation, and apoptosis were significantly higher in fetal than adult valves. Pulmonary and aortic fetal VICs showed an activated myofibroblast-like phenotype (alpha-actin expression), abundant embryonic myosin, and matrix metalloproteinase-collagenases, which indicates an immature/activated phenotype engaged in matrix remodeling versus a quiescent fibroblast-like phenotype in adults. At birth, the abrupt change from fetal to neonatal circulation was associated with a greater number of alpha-actin-positive VICs in neonatal aortic versus pulmonary valves. Collagen content increased from early to late fetal stages but was subsequently unchanged, whereas elastin significantly increased postnatally. Collagen fiber color analysis revealed a progressive temporal decrease in thin fibers and a corresponding increase in thick fibers. Additionally, collagen fibers were more aligned in adult than fetal valves. Conclusions - Fetal valves possess a dynamic/adaptive structure and contain cells with an activated/immature phenotype. During postnatal life, activated cells gradually become quiescent, whereas collagen matures, which suggests a progressive, environmentally mediated adaptation. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Brigham & Womens Hosp, Cardiovasc Div, Dept Med,Med Sch, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Dept Emergency Med, Amherst, MA 01003 USA. Univ Massachusetts, Sch Med, Dept Anesthesiol, Amherst, MA 01003 USA. RP Schoen, FJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM eaikawa@partners.org; fschoen@partners.org RI Whittaker, Peter/F-1234-2011 OI Whittaker, Peter/0000-0002-5627-2166 NR 37 TC 193 Z9 198 U1 5 U2 31 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 14 PY 2006 VL 113 IS 10 BP 1344 EP 1352 DI 10.1161/CIRCULATIONAHA.105.591768 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 021GL UT WOS:000235971600013 PM 16534030 ER PT J AU Murugappan, A Coplin, WM Al-Sadat, AN McAllen, KJ Schwamm, LH Wechsler, LR Kidwell, CS Saver, JL Starkman, S Gobin, YP Duckwiler, G Krueger, M Rordorf, G Broderick, JP Tietjen, GE Levine, SR AF Murugappan, A Coplin, WM Al-Sadat, AN McAllen, KJ Schwamm, LH Wechsler, LR Kidwell, CS Saver, JL Starkman, S Gobin, YP Duckwiler, G Krueger, M Rordorf, G Broderick, JP Tietjen, GE Levine, SR TI Thrombolytic therapy of acute ischemic stroke during pregnancy SO NEUROLOGY LA English DT Article ID RISK AB The authors report eight pregnant women with acute ischemic stroke treated with thrombolysis (rt-PA [recombinant human tissue plasminogen activator] or urokinase). Seven women recovered. Two extracranial and two asymptomatic intracranial hemorrhages complicated treatment; one woman died of arterial dissection complicating angiography. Three patients had therapeutic abortions, two fetuses were miscarried, and two babies were delivered healthy. Although pregnant women may be treated safely with thrombolytics, risks and benefits to mother and fetus must be carefully weighed. C1 CUNY Mt Sinai Sch Med, Dept Neurol, Stroke Ctr, New York, NY 10029 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Emergency Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA. Wayne State Univ, Sch Med, Stroke & Neurosci Crit Care Program, Dept Neurol, Detroit, MI 48202 USA. Wayne State Univ, Sch Med, Dept Neurol Surg, Detroit, MI 48202 USA. Wayne State Univ, Sch Med, Dept Pharm Adm, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Cincinnati, Cincinnati, OH USA. Med Univ Ohio, Toledo, OH USA. RP Levine, SR (reprint author), CUNY Mt Sinai Sch Med, Dept Neurol, Stroke Ctr, Box 1137,1 Gustave L Levy Pl, New York, NY 10029 USA. EM steven.levine@mssm.edu RI Gobin, Yves/A-8008-2008; OI Schwamm, Lee/0000-0003-0592-9145; Saver, Jeffrey/0000-0001-9141-2251 FU NINDS NIH HHS [NS 38905]; PHS HHS [43992] NR 8 TC 51 Z9 54 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAR 14 PY 2006 VL 66 IS 5 BP 768 EP 770 DI 10.1212/01.wnl.0000201272.90216.15 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 021GM UT WOS:000235971700035 PM 16534124 ER PT J AU Bodner, RA Outeiro, TF Altmann, S Maxwell, MM Cho, SH Hyman, BT McLean, PJ Young, AB Housman, DE Kazantsev, AG AF Bodner, RA Outeiro, TF Altmann, S Maxwell, MM Cho, SH Hyman, BT McLean, PJ Young, AB Housman, DE Kazantsev, AG TI Pharmacological promotion of inclusion formation: A therapeutic approach for Huntington's and Parkinson's diseases SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE misfolded proteins; neuroclegenerative disease ID UBIQUITIN-PROTEASOME SYSTEM; ALPHA-SYNUCLEIN AGGREGATION; POLYGLUTAMINE PROTEINS; MOLECULAR CHAPERONES; COMMON MECHANISM; BODY FORMATION; DEGRADATION; RENATURATION; IMPAIRMENT; TOXICITY AB Misfolded proteins accumulate in many neurodegenerative diseases, including huntingtin in Huntington's disease and alpha-synuclein in Parkinson's disease. The disease-causing proteins can take various conformations and are prone to aggregate and form larger cytoplasmic or nuclear inclusions. One approach to the development of therapeutic intervention for these diseases has been to identify chemical compounds that reduce the size or number of inclusions. We have, however, identified a compound that promotes inclusion formation in cellular models of both Huntington's disease and Parkinson's disease. Of particular interest, this compound prevents huntingtin-mediated proteasome dysfunction and reduces a-synuclein-mediated toxicity. These results demonstrate that compounds that increase inclusion formation may actually lessen cellular pathology in both Huntington's and Parkinson's diseases, suggesting a therapeutic approach for neurodegenerative diseases caused by protein misfolding. C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Housman, DE (reprint author), MIT, Ctr Canc Res, Room E18-505,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM dhousman@mit.edu; orakazantsev@partners.org RI Outeiro, Tiago/C-1067-2008 OI Outeiro, Tiago/0000-0003-1679-1727 FU NINDS NIH HHS [P50 NS038372, 5P50NS38372A-06] NR 23 TC 163 Z9 170 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2006 VL 103 IS 11 BP 4246 EP 4251 DI 10.1073/pnas.0511256103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 027QE UT WOS:000236429300057 PM 16537516 ER PT J AU Zambetti, GP Horwitz, EM Schipani, E AF Zambetti, GP Horwitz, EM Schipani, E TI Skeletons in the p53 tumor suppressor closet: genetic evidence that p53 blocks bone differentiation and development SO JOURNAL OF CELL BIOLOGY LA English DT Review ID PATHWAY AB A series of in vitro tissue culture studies indicated that the p53 tumor suppressor promotes cellular differentiation, which could explain its role in preventing cancer. Quite surprisingly, however, two new in vivo studies (Lengner et al., 2006; Wang et al., 2006) provide genetic evidence that p53 blocks osteoblast differentiation and bone development. These interesting results and their biological and clinical implications are the focus of this comment. C1 St Jude Childrens Hosp, Dept Biochem, Memphis, TN 38105 USA. St Jude Childrens Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, Boston, MA 02114 USA. RP Zambetti, GP (reprint author), St Jude Childrens Hosp, Dept Biochem, Memphis, TN 38105 USA. EM gerard.zambetti@stjude.org NR 11 TC 23 Z9 25 U1 0 U2 0 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 13 PY 2006 VL 172 IS 6 BP 795 EP 797 DI 10.1083/jcb.200601114 PG 3 WC Cell Biology SC Cell Biology GA 021GO UT WOS:000235971900004 PM 16533941 ER PT J AU Kock, N Allchorne, AJ Sena-Esteves, M Woolf, CJ Breakefield, XO AF Kock, N Allchorne, AJ Sena-Esteves, M Woolf, CJ Breakefield, XO TI RNAi blocks DYT1 mutant torsinA inclusions in neurons SO NEUROSCIENCE LETTERS LA English DT Article DE RNAi; shRNA; TorsinA; DYT1 ID EARLY-ONSET DYSTONIA; PC12 CELLS; NUCLEAR-ENVELOPE; MOUSE MODEL; PROTEIN; MOTOR; GENE; NEURODEGENERATION; EXPRESSION; PHENOTYPE AB Early onset generalized dystonia is a dominantly inherited movement disorder caused by neuronal dysfunction without an apparent loss of neurons. The same single mutation (GAG deletion) causes most cases and results in loss of a glutamic acid (E) in the carboxy terminal region of torsinA (Delta 302/303). To model the neuronal involvement, adult rat primary sensory dorsal root ganglion neurons in culture were infected with lentivirus vectors expressing human wild-type or mutant torsinA. Expression of the mutant protein resulted in formation of torsinA-positive perinuclear inclusions. When the cells were co-infected with lentivirus vectors expressing the mutant torsinA message and a shRNA selectively targeting this message, inclusion formation was blocked. Vector-delivered siRNAs have the potential to decrease the adverse effects of this mutant protein in neurons without affecting wild-type protein. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Dept Neurol, Mol Neurogenet Unit, Massachusetts Gen Hosp,Sch Med, Boston, MA 02129 USA. Harvard Univ, Dept Radiol, Mol Neurogenet Unit, Massachusetts Gen Hosp,Sch Med, Boston, MA 02129 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02129 USA. Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, Boston, MA 02129 USA. RP Breakefield, XO (reprint author), Harvard Univ, Dept Neurol, Mol Neurogenet Unit, Massachusetts Gen Hosp,Sch Med, Bldg 149,13th St,Room 6101, Boston, MA 02129 USA. EM breakefield@hms.harvard.edu FU NINDS NIH HHS [NS37409, NS28384] NR 34 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 13 PY 2006 VL 395 IS 3 BP 201 EP 205 DI 10.1016/j.neulet.2005.10.098 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 016CH UT WOS:000235597800005 PM 16332410 ER PT J AU Lambrecht, NWG Yakubov, I Zer, C Sachs, G AF Lambrecht, NWG Yakubov, I Zer, C Sachs, G TI Transcriptomes of purified gastric ECL and parietal cells: identification of a novel pathway regulating acid secretion SO PHYSIOLOGICAL GENOMICS LA English DT Article DE entero-chromaffin-like cell; oligonucleotide expression microarray; transcriptome; apelin; APJ receptor ID ENTEROCHROMAFFIN-LIKE CELLS; FASTING RAT STOMACH; HUMAN APJ RECEPTOR; CIRCADIAN-RHYTHM; MOLECULAR-IDENTIFICATION; GASTROINTESTINAL-TRACT; INTRAGASTRIC ACIDITY; PEPTIDE PRECURSOR; ENERGY-BALANCE; DUODENAL-ULCER AB The gastric entero-chromaffin-like (ECL) cell plays a key regulatory role in peripheral regulation of acid secretion due to the release of histamine that stimulates acid secretion by the parietal cell. Studies in intact animals, gastric glands, and isolated cells after short-term culture have shown expression of stimulatory CCK2 and PAC1 and inhibitory SST2 and Gal1 receptors as well as histidine decarboxylase. However, the pattern of its gene expression as a neuroendocrine cell has not been explored. Comparison of gene expression by 95% pure ECL cells obtained by density gradient, elutriation, and fluorescence-assisted cell sorting with isolates of the intact fundic gastric epithelium ( i.e., "subtractive hybridization") identified a variety of additional expressed gene families characteristic of this neuroendocrine cell. These include genes 1) involved in neuropeptide synthesis and secretory vesicle exocytosis, 2) involved in control of inflammation, 3) implicated in healing of the epithelium, 4) encoding inhibitory G(i) protein-coupled receptors, 5) playing a role in neuroendocrine regulation of food intake, and 6) encoding proteins likely involved in maintenance of circadian rhythm, in addition to the ECL cell-specific genes histidine decarboxylase and monoamine transporter. Particularly, the inhibitory apelin receptor gene, APJ, was highly expressed in the ECL cell preparation. Because parietal cells express apelin, immunohistochemical and functional studies showed that there is an inhibitory feed back loop between the parietal and ECL cell during gastrin stimulation, providing evidence for a novel pathway of downregulation of acid secretion due to interaction between these two cell types. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Med, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Membrane Biol Lab, Los Angeles, CA 90073 USA. RP Lambrecht, NWG (reprint author), Wadsworth VA Hosp, Bldg 113,Rm 325A, Los Angeles, CA 90073 USA. EM nilslam@ucla.edu OI Lambrecht, Nils/0000-0002-1275-1384 FU NIDDK NIH HHS [DK-58333, DK-46917, DK-53462] NR 72 TC 38 Z9 38 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD MAR 13 PY 2006 VL 25 IS 1 BP 153 EP 165 DI 10.1152/physiolgenomics.00271.2005 PG 13 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 031RW UT WOS:000236722700016 PM 16403840 ER PT J AU Koenig, SP Kuritzkes, DR Hirsch, MS Leandre, F Mukherjee, LS Farmer, PE del Rio, C AF Koenig, SP Kuritzkes, DR Hirsch, MS Leandre, F Mukherjee, LS Farmer, PE del Rio, C TI HIV and global health - Monitoring HIV treatment in developing countries SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID RESOURCE-POOR SETTINGS; DIRECTLY OBSERVED THERAPY; ANTIRETROVIRAL THERAPY; DRUG-RESISTANCE; SCALING-UP; TUBERCULOSIS; ADHERENCE; OUTCOMES; INFECTION; MUTATIONS C1 Brigham & Womens Hosp, Div Social Med & Hlth Inequal, Boston, MA 02120 USA. Brigham & Womens Hosp, Sect Retroviral Therapeut, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Partners Hlth, Boston, MA USA. Harvard Univ, Sch Med, Dept Social Med, Program Infect Dis & Social Change, Boston, MA 02115 USA. Zanmi Lasante, HIV Programme, Cange, Haiti. Zanmi Lasante, TB Programme, Cange, Haiti. Emory Univ, Ctr AIDS Res, Atlanta, GA 30322 USA. RP Koenig, SP (reprint author), Brigham & Womens Hosp, Div Social Med & Hlth Inequal, 1620 Tremont St, Boston, MA 02120 USA. EM skoenig@partners.org RI del Rio, Carlos/B-3763-2012 OI del Rio, Carlos/0000-0002-0153-3517 FU FIC NIH HHS [1K01TW007142-01, D43 TW01042]; NCRR NIH HHS [K24 RR16482]; NIAID NIH HHS [2P30 AI50409-04A1, 5T32AI007433-13, P30 AI60354] NR 22 TC 21 Z9 22 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD MAR 11 PY 2006 VL 332 IS 7541 BP 602 EP 604 DI 10.1136/bmj.332.7541.602 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 026CN UT WOS:000236314400022 PM 16528087 ER PT J AU Kalabis, J Rosenberg, I Podolsky, DK AF Kalabis, J Rosenberg, I Podolsky, DK TI Vangl1 protein acts as a downstream effector of intestinal trefoil factor (ITF)/TFF3 signaling and regulates wound healing of intestinal epithelium SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN HOMOLOG; DISCS-LARGE; CELL; GENE; STRABISMUS; PEPTIDES; POLARITY; FAMILY; IDENTIFICATION; DROSOPHILA AB The intestinal trefoil factor (ITF/TFF3) protects intestinal epithelia from a range of insults and contributes to mucosal repair. However, the signaling events that mediate healing responses are only partially understood. To identify ITF signaling pathways, proteins that were Ser/Thr phosphorylated in response to ITF stimulation were immunoprecipitated from human colon carcinoma cell lines and identified by mass spectrometry. We demonstrated that Van Gogh-like protein 1 ( also designated Vang-like 1 or Vangl1), a protein with four transmembrane domains, was Ser/Thr phosphorylated in response to ITF stimulation. Vangl1 was present in normal human colon and all intestinal epithelial cell lines (IEC) tested. In transfected IEC, FLAG-Vangl1 was mostly present in the Nonidet P-40 soluble fraction as detected by Western blotting, corresponding to the localization of endogenous protein in cytoplasmic vesicular structures by confocal microscopy with rabbit polyclonal antihuman Vangl1 antibody (alpha-Vangl1). Vangl1 cell membrane association increased with differentiation, as demonstrated by co-localization with E-cadherin in differentiated IEC. Increased Vangl1 phosphorylation after stimulation with ITF corresponded to decreased cell membrane association with E-cadherin. Functionally, Vangl1 overexpression enhanced ITF unstimulated and stimulated wound closure of IEC, whereas siRNA directed against Vangl1 inhibited the migratory response to ITF. Vangl1 protein may serve as an effector mediating the ITF healing response of the intestinal mucosa. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM dpodolsky@partners.org FU NIDDK NIH HHS [P30DK043351, R01DK046906] NR 34 TC 29 Z9 31 U1 1 U2 7 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 10 PY 2006 VL 281 IS 10 BP 6434 EP 6441 DI 10.1074/jbc.M512905200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 022BX UT WOS:000236030800037 PM 16410243 ER PT J AU Batchelor, T Loeffler, JS AF Batchelor, T Loeffler, JS TI Primary CNS lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; NON-HODGKINS-LYMPHOMA; HIGH-DOSE METHOTREXATE; STEM-CELL RESCUE; MALIGNANT-LYMPHOMA; PHASE-II; DEFERRED RADIOTHERAPY; SALVAGE CHEMOTHERAPY; BRAIN LYMPHOMA; SURVIVAL AB Primary CNS lymphoma (PCNSL), an uncommon form of extranodal non-Hodgkin's lymphoma (NHL), has increased in incidence during the last three decades and occurs in both immunocompromised and immunocompetent hosts. PCNSL in immunocompetent patients is associated with unique diagnostic, prognostic, and therapeutic issues, and the management of this malignancy is different from that of other forms of extranodal NHL. Characteristic imaging features should be suggestive of the diagnosis, avoidance of corticosteroids, if possible, and early neurosurgical consultation for stereotactic biopsy. Because PCNSL may involve the brain, CSF, and eyes, diagnostic evaluation should include assessment of all of these regions as well as screening for possible occult systemic disease. Resection provides no therapeutic benefit and should be reserved for the rare patient with neurologic deterioration due to brain herniation. Whole-brain radiation therapy (WBRT) alone is insufficient for durable tumor control and is associated with a high risk of neurotoxicity in patients older than age 60. Neurotoxicity typically is associated with significant cognitive, motor, and autonomic dysfunction, and has a negative impact on quality of life. Chemotherapy and WBRT together improve tumor response rates and survival compared with WBRT alone. Methotrexate-based multiagent chemotherapy without WBRT is associated with similar tumor response rates and survival compared with regimens that include WBRT, although controlled trials have not been performed. The risk of neurotoxicity is lower in patients treated with chemotherapy alone. C1 Massachusetts Gen Hosp, Dept Neurol, Div Neurooncol, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Batchelor, T (reprint author), Massachusetts Gen Hosp, Dept Neurol, Div Neurooncol, Stephen E & Catherine Pappas Ctr Neurooncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM tbatchelor@partners.org NR 51 TC 162 Z9 184 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 10 PY 2006 VL 24 IS 8 BP 1281 EP 1288 DI 10.1200/JCO.2005.04.8819 PG 8 WC Oncology SC Oncology GA 024ZS UT WOS:000236235700008 PM 16525183 ER PT J AU Saldarriaga, OA Travi, BL Park, W Perez, LE Melby, PC AF Saldarriaga, OA Travi, BL Park, W Perez, LE Melby, PC TI Immunogenicity of a multicomponent DNA vaccine against visceral leishmaniasis in dogs SO VACCINE LA English DT Article DE visceral leishmaniasis; Leishmania donovani; Leishmania chagasi; vaccine; cellular immunity; interferon-gamma ID MURINE CUTANEOUS LEISHMANIASIS; CELLULAR IMMUNE-RESPONSE; CANINE KALA-AZAR; PROTECTIVE IMMUNITY; MAJOR VACCINE; DOUBLE-BLIND; IN-VIVO; ANTILEISHMANIAL ACTIVITY; CONFERS PROTECTION; ASYMPTOMATIC DOGS AB Vaccination of dogs, the domestic reservoir of Leishmania chagasi, could not only decrease the burden of canine visceral leishmaniasis (VL), but could also indirectly reduce the incidence of human VL. Intramuscular vaccination of foxhounds with a Leishmania multicomponent (10 antigen) DNA vaccine resulted in antigen-induced lymphoproliferative and IFN-gamma (but not IL-4) responses. This response was not augmented by co-administration of canine IL-12 or GM-CSF DNA adjuvants. The multicomponent DNA vaccine also induced a delayed type hypersensitivity (DTH) response to viable L. donovani promastigotes and led to a reduction of parasite burden in an in vitro intracellular infection model, and in the draining lymph node of dogs early after cutaneous challenge. Thus, the multicomponent DNA vaccine was effective in priming dogs for a parasite-specific type 1 cellular immune response, which was able to restrict parasite growth. (c) 2005 Elsevier Ltd. All rights reserved. C1 S Texas Vet Hlth Care Syst, Dept Vet Affairs Med Ctr, Res Ctr, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78285 USA. Ctr Int Entrenamiento & Invest Med, CIDEIM, Cali 5390, Colombia. RP Melby, PC (reprint author), S Texas Vet Hlth Care Syst, Dept Vet Affairs Med Ctr, Res Ctr, 7400 Merton Minter Dr,Mailstop 151, San Antonio, TX 78229 USA. EM melby@uthscsa.edu FU NIAID NIH HHS [AI48823] NR 73 TC 27 Z9 29 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 10 PY 2006 VL 24 IS 11 BP 1928 EP 1940 DI 10.1016/j.vaccine.2005.10.052 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 025IR UT WOS:000236259600025 PM 16310897 ER PT J AU Perides, G Zhuge, YZ Lin, T Stins, MF Bronson, RT Wu, JK AF Perides, G Zhuge, YZ Lin, T Stins, MF Bronson, RT Wu, JK TI The fibrinolytic system facilitates tumor cell migration across the blood-brain barrier in experimental melanoma brain metastasis SO BMC CANCER LA English DT Article ID UROKINASE PLASMINOGEN-ACTIVATOR; MICROVASCULAR ENDOTHELIAL-CELLS; BREAST-CANCER; GENE-TRANSFER; T-ANTIGEN; INHIBITOR; INVASION; RECEPTOR; VITRONECTIN; ADHESION AB Background: Patients with metastatic tumors to the brain have a very poor prognosis. Increased metastatic potential has been associated with the fibrinolytic system. We investigated the role of the fibrinolytic enzyme plasmin in tumor cell migration across brain endothelial cells and growth of brain metastases in an experimental metastatic melanoma model. Methods: Metastatic tumors to the brain were established by direct injection into the striatum or by intracarotid injection of B16F10 mouse melanoma cells in C57Bl mice. The role of plasminogen in the ability of human melanoma cells to cross a human blood-brain barrier model was studied on a transwell system. Results: Wild type mice treated with the plasmin inhibitor epsilon-aminocaproic acid ( EACA) and plg(-/-) mice developed smaller tumors and survived longer than untreated wild type mice. Tumors metastasized to the brain of wild type mice treated with EACA and plg-/- less efficiently than in untreated wild type mice. No difference was observed in the tumor growth in any of the three groups of mice. Human melanoma cells were able to cross the human blood-brain barrier model in a plasmin dependent manner. Conclusion: Plasmin facilitates the development of tumor metastasis to the brain. Inhibition of the fibrinolytic system could be considered as means to prevent tumor metastasis to the brain. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg,Div Neurosurg, Boston, MA 02115 USA. Tufts Univ, Sch Med, Tufts New England Med Ctr, Dept Surg, Boston, MA 02111 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Harvard Med, Dana Farber Harvard Canc Ctr, Boston, MA USA. Tufts Univ, Sch Med, Tufts New England Med Ctr, Dept Neurosurg, Boston, MA 02111 USA. RP Wu, JK (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg,Div Neurosurg, Boston, MA 02115 USA. EM gperides@tufts-nemc.org; yu8zheng@yahoo.com; tlin@mah.harvard.edu; mstins@jhmi.edu; roderick_bronson@hms.harvard.edu; jwu3@tufts-nemc.org NR 44 TC 17 Z9 17 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD MAR 9 PY 2006 VL 6 AR 56 DI 10.1186/1471-2407-6-56 PG 9 WC Oncology SC Oncology GA 029FQ UT WOS:000236546700001 PM 16524486 ER PT J AU Takayesu, JK Bazari, H Linshaw, M AF Takayesu, JK Bazari, H Linshaw, M TI A 47-year-old man with altered mental status and acute renal failure - Ethylene glycol intoxication SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SERUM ANION GAP; DIABETIC-KETOACIDOSIS; SODIUM FLUORESCEIN; METABOLIC-ACIDOSIS; URINE FLUORESCENCE; INGESTION; ALCOHOL; METHANOL; BICARBONATE; ANTIFREEZE C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Div Nephrol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Div Nephrol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Takayesu, JK (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 35 TC 13 Z9 13 U1 1 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 9 PY 2006 VL 354 IS 10 BP 1065 EP 1072 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 019FY UT WOS:000235822200012 PM 16525144 ER PT J AU Yosefy, C Feingold, M AF Yosefy, C Feingold, M TI Continuation of hormone replacement therapy during acute myocardial infarction after the women's health initiative study. Is it the time for change? SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Review DE hormone replacement therapy; myocardial infarction ID CORONARY-HEART-DISEASE; POSTMENOPAUSAL ESTROGEN REPLACEMENT; ESTROGEN/PROGESTIN REPLACEMENT; CARDIOVASCULAR-DISEASE; CONTROLLED TRIAL; CHEST-PAIN; TASK-FORCE; PREVENTION; LIPIDS; HYPERCHOLESTEROLEMIA AB Hormone replacement therapy (HRT) was given for many years in order to relieve menopausal symptoms and was used for as long as symptom control was necessary. The Heart and Estrogen/Progestin Replacement Study (HERS) and Women's Health Initiative (WHI) studies showed that HRT should not be given for primary or secondary prevention of coronary heart disease (CHD). However, what about those patients during acute myocardial infarction who are already taking HRT? Is the 'don't stop don't start' rule still true? A 58-year-old white female, on HRT was admitted with acute myocardial infarction (MI). We tried to answer the above questions ill light of the new information: 1) continuation of HRT during acute MI 2) HRT and cardiovascular risk factors 3) HRT and coronary revascularization 4) HRT and the prevention of acute MI Based on current evidence available from HERS and WHI trials, it is not advisable to initiate HRT in women with established CHD for the sole purpose of preventing first or recurring coronary events. A statement by the American Heart Association recommends that the decision to continue or stop HRT in women with CV disease should be based on established benefits and risks, taking patients preference into account. The WHI study did not change this policy in the acute phase. In most cases, we believe HRT should be continued for some period (our decision for 3 months long was arbitrary), and discontinued gradually. We believe that this should be the policy until we have a double-blind placebo-control data to revise. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Ben Gurion Univ Negev, Dept Cardiol, Ashqelon, Israel. Univ Boston Hosp, Dept Obstet & Gynecol, Boston, MA 02118 USA. RP Yosefy, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, 55 Fruit St,VBK 508, Boston, MA 02114 USA. EM cyosefy@partners.org NR 44 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD MAR 8 PY 2006 VL 107 IS 3 BP 293 EP 298 DI 10.1016/J.IJCARD.2005.04.002 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 024PL UT WOS:000236208300001 PM 16503250 ER PT J AU Bates, EA Victor, M Jones, AK Shi, Y Hart, AC AF Bates, EA Victor, M Jones, AK Shi, Y Hart, AC TI Differential contributions of Caenorhabditis elegans histone deacetylases to Huntingtin polyglutamine toxicity SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Huntington; polyglutamine; HDAC; polyQ; neurodegeneration; CBP ID CREB-BINDING PROTEIN; C-ELEGANS; COREPRESSOR COMPLEX; SENSORY NEURON; IN-VIVO; DISEASE; GENE; TRANSCRIPTION; INHIBITORS; EXPRESSION AB Expansion of a polyglutamine tract in the huntingtin protein causes neuronal degeneration and death in Huntington's disease patients, but the molecular mechanisms underlying polyglutamine-mediated cell death remain unclear. Previous studies suggest that expanded polyglutamine tracts alter transcription by sequestering glutamine rich transcriptional regulatory proteins, thereby perturbing their function. We tested this hypothesis in Caenorhabditis elegans neurons expressing a human huntingtin fragment with an expanded polyglutamine tract (Htn-Q150). Loss of function alleles and RNA interference (RNAi) were used to examine contributions of C. elegans cAMP response element-binding protein (CREB), CREB binding protein (CBP), and histone deacetylases (HDACs) to polyglutamine-induced neurodegeneration. Deletion of CREB (crh-1) or loss of one copy of CBP (cbp-1) enhanced polyglutamine toxicity in C. elegans neurons. Loss of function alleles and RNAi were then used to systematically reduce function of each C. elegans HDAC. Generally, knockdown of individual C. elegans HDACs enhanced Htn-Q150 toxicity, but knockdown of C. elegans hda-3 suppressed toxicity. Neuronal expression of hda-3 restored Htn-Q150 toxicity and suggested that C. elegans HDAC3 (HDA-3) acts within neurons to promote degeneration in response to Htn-Q150. Genetic epistasis experiments suggested that HDA-3 and CRH-1 (C. elegans CREB homolog) directly oppose each other in regulating transcription of genes involved in polyglutamine toxicity. hda-3 loss of function failed to suppress increased neurodegeneration in hda-1/+; Htn-Q150 animals, indicating that HDA-1 and HDA-3 have different targets with opposing effects on polyglutamine toxicity. Our results suggest that polyglutamine expansions perturb transcription of CREB/CBP targets and that specific targeting of HDACs will be useful in reducing associated neurodegeneration. C1 Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hart, AC (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, 149-7202 13th St, Charlestown, MA 02129 USA. EM hart@helix.mgh.harvard.edu FU NINDS NIH HHS [R01 NS040048-05, R01 NS040048]; PHS HHS [40048] NR 61 TC 91 Z9 109 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 8 PY 2006 VL 26 IS 10 BP 2830 EP 2838 DI 10.1523/JNEUROSCI.3344-05.2006 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 019WS UT WOS:000235868800025 PM 16525063 ER PT J AU Pierce, A deWaal, E VanRemmen, H Richardson, A Chaudhuri, A AF Pierce, A deWaal, E VanRemmen, H Richardson, A Chaudhuri, A TI A novel approach for screening the proteome for changes in protein conformation SO BIOCHEMISTRY LA English DT Article ID CREATINE-KINASE; ACTIVE-SITE; SURFACE HYDROPHOBICITY; OXIDATIVE MODIFICATION; HYDROGEN-PEROXIDE; IN-VIVO; RHODANESE; INACTIVATION; BINDING; FLUORESCENCE AB Changes in surface hydrophobicity are generally considered as a sensitive indicator for monitoring the structural alterations of proteins that are often associated with changes in function. Currently, no technique has been developed to screen a complex mixture of proteins for changes in the conformation of specific proteins. In this study, we adapted a UV photolabeling approach, using an apolar fluorescent probe, 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (BisANS), to monitor changes in surface hydrophobic domains in either purified rhodanese or skeletal muscle cytosolic proteins by urea-induced unfolding or in response to in vitro metal-catalyzed oxidation. Using two-dimensional polyacrylamide gel electrophoresis (2D PAGE), we identified two specific proteins in skeletal muscle cytosol that exhibited a marked loss of incorporation of BisANS after exposure to in vitro oxidative stress: creatine kinase (CK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We found that the activities of both enzymes were also reduced significantly in response to oxidative stress. We then determined if this method could detect changes in surface hydrophobicity in specific proteins arising from oxidative stress generated in vivo by muscle denervation. A loss in surface hydrophobic domains in CK and GAPDH was again observed as measured by the BisANS photoincorporation approach. In addition, the CK and GAPDH activity in denervated muscle was markedly reduced. These data demonstrate for the first time that this assay can screen a complex mixture of proteins for alterations in surface hydrophobic domains of individual proteins. C1 Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78284 USA. RP Chaudhuri, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Biochem, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM chaudhuria@uthscsa.edu RI Pierce, Anson/D-1079-2012 OI Pierce, Anson/0000-0002-1383-0180 FU NIA NIH HHS [R01-AG23843, P01 AG19316] NR 46 TC 24 Z9 25 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 7 PY 2006 VL 45 IS 9 BP 3077 EP 3085 DI 10.1021/bi052031i PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 018VI UT WOS:000235792500034 PM 16503663 ER PT J AU Nahrendorf, M Hu, K Frantz, S Jaffer, FA Tung, CH Hiller, KH Voll, S Nordbeck, P Sosnovik, D Gattenlohner, S Novikov, M Dickneite, G Reed, GL Jakob, P Rosenzweig, A Bauer, WR Weissleder, R Ertl, G AF Nahrendorf, M Hu, K Frantz, S Jaffer, FA Tung, CH Hiller, KH Voll, S Nordbeck, P Sosnovik, D Gattenlohner, S Novikov, M Dickneite, G Reed, GL Jakob, P Rosenzweig, A Bauer, WR Weissleder, R Ertl, G TI Factor XIII deficiency causes cardiac rupture, impairs wound healing, and aggravates cardiac remodeling in mice with myocardial infarction SO CIRCULATION LA English DT Article DE factor XIII; healing; heart failure; myocardial infarction; remodeling ID COAGULATION-FACTOR-XIII; LEFT-VENTRICULAR DYSFUNCTION; FACTOR-KAPPA-B; INFLAMMATORY RESPONSE; ISCHEMIA-REPERFUSION; BLOOD; FIBROBLASTS; EXPRESSION; COLLAGEN; FAILURE AB Background - Identification of key molecular players in myocardial healing could lead to improved therapies, reduction of scar formation, and heart failure after myocardial infarction (MI). We hypothesized that clotting factor XIII (FXIII), a transglutaminase involved in wound healing, may play an important role in MI given prior clinical and mouse model data. Methods and Results - To determine whether a truly causative relationship existed between FXIII activity and myocardial healing, we prospectively studied myocardial repair in FXIII-deficient mice. All FXIII-/- and FXIII-/- ( FXIII activity < 5% and 70%) mice died within 5 days after MI from left ventricular rupture. In contradistinction, FXIII-/- mice that received 5 days of intravenous FXIII replacement therapy had normal survival rates; however, cardiac MRI demonstrated worse left ventricular remodeling in these reconstituted FXIII-/- mice. Using a FXIII-sensitive molecular imaging agent, we found significantly greater FXIII activity in wild-type mice and FXIII-/- mice receiving supplemental FXIII than in FXIII-/- mice (P < 0.05). In FXIII-/- but not in reconstituted FXIII-/- mice, histology revealed diminished neutrophil migration into the MI. Reverse transcriptase - polymerase chain reaction studies suggested that the impaired inflammatory response in FXIII-/- mice was independent of intercellular adhesion molecule and lipopolysaccharide-induced CXC chemokine, both important for cell migration. After MI, expression of matrix metalloproteinase-9 was 650% higher and collagen-1 was 53% lower in FXIII-/- mice, establishing an imbalance in extracellular matrix turnover and providing a possible mechanism for the observed cardiac rupture in the FXIII-/- mice. Conclusions - These data suggest that FXIII has an important role in murine myocardial healing after infarction. C1 Univ Wurzburg, Med Klin, Phys Inst EP5, D-97080 Wurzburg, Germany. Univ Wurzburg, Med Klin & Poliklin 1, D-97080 Wurzburg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. ZLB Behring, Marburg, Germany. Med Coll Georgia, Dept Med, Div Cardiol, Augusta, GA 30912 USA. RP Ertl, G (reprint author), Univ Wurzburg, Med Klin, Phys Inst EP5, Josef Schneider Str 2, D-97080 Wurzburg, Germany. EM Ertl_G@medizin.uni-wuerzburg.de RI Frantz, Stefan/G-1723-2012; OI Jaffer, Farouc/0000-0001-7980-384X; Jakob, Peter/0000-0002-3481-5545; Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [R24 CA 92782, R24 CA092782]; NHLBI NIH HHS [U01 HL080731, R01 HL 078641, R01 HL058496, R01 HL078562, R01 HL078641, U01 HL 080731] NR 27 TC 96 Z9 98 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 7 PY 2006 VL 113 IS 9 BP 1196 EP 1202 DI 10.1161/CIRCULATIONAHA.105.602094 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 018ZE UT WOS:000235803400011 PM 16505171 ER PT J AU Armstrong, EJ Morrow, DA Sabatine, MS AF Armstrong, EJ Morrow, DA Sabatine, MS TI Inflammatory biomarkers in acute coronary syndromes Part IV: Matrix metalloproteinases and biomarkers of platelet activation SO CIRCULATION LA English DT Editorial Material ID PLASMA-PROTEIN-A; MYOCARDIAL-INFARCTION; P-SELECTIN; CD40; INHIBITION; REDUCTION; MECHANISM; LIGAND C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org NR 21 TC 29 Z9 32 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 7 PY 2006 VL 113 IS 9 BP E382 EP E385 DI 10.1161/CIRCULATIONAHA.105.595553 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 018ZE UT WOS:000235803400019 PM 16520416 ER PT J AU Cabral, CB Bullock, K Bischoff, D Yu, YM Tompkins, RG Kelleher, JK AF Cabral, CB Bullock, K Bischoff, D Yu, YM Tompkins, RG Kelleher, JK TI Measuring glutathione fractional synthesis in vivo with deuterated water SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Hosp Children, 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 2006 VL 20 IS 5 BP A1470 EP A1470 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326205480 ER PT J AU Cowart, LA Hui, W AF Cowart, LA Hui, W TI Sphingolipid involvement in insulin sensitivity in C2C12 myotubes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Med Univ S Carolina, Charleston, SC 29403 USA. Ralph H Johnson VA Med Ctr, 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 7 PY 2006 VL 20 IS 5 BP A1345 EP A1345 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326204414 ER PT J AU Ichinose, F Buys, E Neilan, TG Scherrer-Crosbie, M Bloch, KD AF Ichinose, F Buys, E Neilan, TG Scherrer-Crosbie, M Bloch, KD TI Myocyte-specific overexpression of NOS3 prevents endotoxin-induced myocardial dysfunction in mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, 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 7 PY 2006 VL 20 IS 5 BP A1196 EP A1197 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326203223 ER PT J AU Ingelfinger, JR AF Ingelfinger, JR TI Mechanisms of renal programming and cardiorenal endowment SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Massachusetts Gen Hosp, 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 2006 VL 20 IS 5 BP A1330 EP A1330 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326204342 ER PT J AU Kramer, HF Witczak, CA Hirshman, MF Fujii, N Jessen, N Ho, R Sakamoto, K Lienhard, GE Goodyear, LJ AF Kramer, HF Witczak, CA Hirshman, MF Fujii, N Jessen, N Ho, R Sakamoto, K Lienhard, GE Goodyear, LJ TI Rab-GAP AS160 is differentially regulated by multiple effectors of glucose transport in mouse skeletal muscle SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Dartmouth Coll, Sch Med, Hanover, NH 03755 USA. RI Jessen, Niels/E-1731-2011; Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 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 2006 VL 20 IS 5 BP A1280 EP A1280 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326204114 ER PT J AU Mercado, A Broumand, V Zandi-Nejad, K Enck, AH Mount, DB AF Mercado, A Broumand, V Zandi-Nejad, K Enck, AH Mount, DB TI A carboxy-terminal domain in KCC2 confers constitutive K+-Cl- cotransport SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. VA Boston Healthcare Syst, Div Gen Internal Med, W Roxbury, MA 02132 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 2006 VL 20 IS 5 BP A838 EP A838 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326200097 ER PT J AU Olson, TR Grinspan, ZM Cimino, C Hochman, AT Downie, SA AF Olson, TR Grinspan, ZM Cimino, C Hochman, AT Downie, SA TI Dissection as a clinical and patient-centered learning experience: Anatomy reports on the Internet (ARI) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Albert Einstein Coll Med, Bronx, NY 10461 USA. Massachuetts Gen Hosp, Boston, MA 02114 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 2006 VL 20 IS 5 BP A874 EP A875 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326200267 ER PT J AU Quinn, DA Mascarenhas, M Garg, H Hales, CA AF Quinn, DA Mascarenhas, M Garg, H Hales, CA TI Inhibition of low molecular weight hyaluronan production as treatment option for ventilator-induced lung injury SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Pulmonary & Crit Care Unit, Boston, MA 01908 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 2006 VL 20 IS 5 BP A1261 EP A1261 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326204030 ER PT J AU Verdine, GL Banerjee, A Radom, CT Spong, MC Crenshaw, CM Blainey, P Xie, SX AF Verdine, GL Banerjee, A Radom, CT Spong, MC Crenshaw, CM Blainey, P Xie, SX TI Structural snapshots of base excision DNA repair SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Harvard Univ, Dept Chem Biol & Mol, Cambridge, MA 02138 USA. Harvard Univ, Dept Cell Biol, Cambridge, MA 02138 USA. Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Harvard Univ, Dana Farber Canc Inst, Program Canc Chem Biol, Cambridge, MA 02138 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 2006 VL 20 IS 5 BP A1306 EP A1306 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326204234 ER PT J AU Vidal, M AF Vidal, M TI Interactome networks SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 2006 VL 20 IS 5 BP A1308 EP A1308 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326204242 ER PT J AU Witczak, CA Fujii, N Brandauer, J Seifert, M Nozaki, N Goodyear, LJ AF Witczak, CA Fujii, N Brandauer, J Seifert, M Nozaki, N Goodyear, LJ TI CaMKK alpha activates AMPK signaling in mouse skeletal muscle in vivo SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Kanagawa Dent Coll, Yokosuka, Kanagawa 238, Japan. RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 NR 0 TC 3 Z9 3 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 2006 VL 20 IS 5 BP A820 EP A820 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326200012 ER PT J AU Zheng, Z Rumbaut, RE Burns, AR AF Zheng, Z Rumbaut, RE Burns, AR TI Transendothelial pressure inhibits neutrophil migration across IL1-treated endothelial cells: a role for nitric oxide. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 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 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 2006 VL 20 IS 5 BP A1159 EP A1160 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326203060 ER PT J AU Giri, J McDermott, MM Greenland, P Guralnik, JM Criqui, MH Liu, K Ferrucci, L Green, D Schneider, JR Tian, L AF Giri, J McDermott, MM Greenland, P Guralnik, JM Criqui, MH Liu, K Ferrucci, L Green, D Schneider, JR Tian, L TI Statin use and functional decline in patients with and without peripheral arterial disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; CHRONIC HEART-FAILURE; ANKLE BRACHIAL INDEX; HYPERCHOLESTEROLEMIC PATIENTS; REDUCTASE INHIBITORS; INTERMITTENT CLAUDICATION; SUBSEQUENT DISABILITY; CIRCULATING MONOCYTES; TREADMILL WALKING; LONGITUDINAL DATA AB OBJECTIVES We determined whether statin use (vs. non-use) is associated with less annual decline in lower-extremity functioning in patients with and without lower-extremity peripheral arterial disease (PAD) over three-year follow-up. BACKGROUND It is unclear whether statin use is associated with less functional decline in patients with PAD. METHODS Participants included 332 men and women with an ankle brachial index (ABI) < 0.90 and 212 with ABI 0.90 to 1.50. Functional outcomes included 6-min walk distance and usual and rapid-pace 4-m walking velocity. A summary performance score combined performance in walking speed, standing balance, and time for five repeated chair rises into an ordinal score ranging from 0 to 12 (12 = best). RESULTS Adjusting for age, race, gender, comorbidities, education, health insurance, total cholesterol/high-density lipoprotein level, body mass index, pack-years of smoking, leg symptoms, immediately previous year functioning, statin use/non-use, ABI, and change in ABI, the PAD participants using statins had less annual decline in usual-pace walking velocity (0.002 vs. -0.024 m/s/year, p = 0.013), rapid-pace walking velocity (-0.006 vs. -0.042 m/s/year, p = 0.006), 6-min walk performance (-34.5 vs. -57.9 feet/year, p = 0.088), and the summary performance score (-0.152 vs. -0.376, p = 0.067) compared with non-users. These associations were attenuated slightly by additional adjustment for high-sensitivity C-reactive protein levels. Among non-PAD participants, there were no significant associations between statin use and functional decline. CONCLUSIONS The PAD patients on statins have less annual decline in lower-extremity performance than PAD patients who are not taking statins. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Calif San Diego, San Diego, CA 92103 USA. NIA, Clin Res Branch, NIH, Bethesda, MD 20892 USA. Evanston Northwestern Hosp, Evansville, IN USA. RP McDermott, MM (reprint author), 676 N St Clair,Suite 200, Chicago, IL 60611 USA. EM mdm608@northwestern.edu FU NCRR NIH HHS [RR-00048]; NHLBI NIH HHS [R01-HL58099, R01-HL64739] NR 43 TC 53 Z9 54 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 7 PY 2006 VL 47 IS 5 BP 998 EP 1004 DI 10.1016/j.jacc.2005.10.052 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 018TN UT WOS:000235787800013 PM 16516084 ER PT J AU Woo, JS Derleth, C Stratton, JR Levy, WC AF Woo, JS Derleth, C Stratton, JR Levy, WC TI The influence of age, gender, and training on exercise efficiency SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID POSTEXERCISE OXYGEN-CONSUMPTION; MAXIMAL AEROBIC CAPACITY; GAS-EXCHANGE KINETICS; HEART-FAILURE; MODERATE EXERCISE; SEDENTARY MEN; OLDER MEN; MUSCLE; YOUNG; DECLINE AB OBJECTIVES The aim of this study was to determine whether changes in oxygen efficiency occur with aging or exercise training in healthy young and older subjects. BACKGROUND Exercise capacity declines with age and improves with exercise training. Whether changes in oxygen efficiency, defined as the oxygen cost per unit work, contributes to the effects of aging or training has not yet been defined. METHODS Sixty-one healthy subjects were recruited into four groups of younger women (ages 20 to 33 years, n = 15), younger men (ages 20 to 30 years, n = 12), older women (ages 65 to 79 years, n = 16), and older men (ages 65 to 77 years, n = 18). All subjects under-went cardiopulmonary exercise testing to analyze aerobic parameters before and after three to six months of supervised aerobic exercise training. RESULTS Before training, younger subjects had a much higher exercise capacity, as shown by a 42% higher peak oxygen consumption (VO2) (ml/kg/min, p < 0.0001). This was associated with an 11% lower work VO2/W (P = 0.02) and an 8% higher efficiency than older subjects (p = 0.03). With training, older subjects displayed a larger increase in peak W/kg (+ 29% vs. +12%, p = 0.001), a larger decrease in work VO2/W (-24% vs. -2%, p < 0.0001), and a greater improvement in exercise efficiency (+30% vs. 2%, p < 0.0001) compared to the young. CONCLUSIONS Older age is associated with a decreased exercise efficiency and an increase in the oxygen cost of exercise, which contribute to a decreased exercise capacity. These age-related changes are reversed with exercise training, which improves efficiency to a greater degree in the elderly than in the young. C1 Univ Washington, Dept Internal Med, Seattle, WA 98195 USA. Univ Washington, Dept Cardiol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Cardiol, Seattle, WA USA. RP Levy, WC (reprint author), Univ Washington, Dept Internal Med, Box 356422,1959 NE Pacific St, Seattle, WA 98195 USA. EM levywc@u.washington.edu FU NIA NIH HHS [AG 15462] NR 36 TC 48 Z9 49 U1 0 U2 12 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 7 PY 2006 VL 47 IS 5 BP 1049 EP 1057 DI 10.1016/j.jacc.2005.09.066 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 018TN UT WOS:000235787800021 PM 16516092 ER PT J AU Vazquez, F Matsuoka, S Sellers, WR Yanagida, T Ueda, M Devreotes, PN AF Vazquez, F Matsuoka, S Sellers, WR Yanagida, T Ueda, M Devreotes, PN TI Tumor suppressor PTEN acts through dynamic interaction with the plasma membrane SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE single molecule; membrane binding ID CELL-MIGRATION; BINDING MOTIF; PROTEIN; PATHWAY; CHEMOTAXIS; PHOSPHORYLATION; PROGRESSION; ACTIVATION; MICROSCOPY; MECHANISM AB The tumor suppressor function of PTEN is strongly linked to its ability to dephosphorylate phosphatidylinositol-3,4,5 trisphosphate and, thereby, control cell growth, survival, and migration. However, the mechanism of action of PTEN in living cells is largely unexplored. Here we use single-molecule TIRF microscopy in living cells to reveal that the enzyme binds to the membrane for a few hundred milliseconds, sufficient to degrade several phosphaticlylinositol-3,4,5 trisphosphate molecules. Deletion of an N-terminal lipid-binding motif completely abrogates membrane interaction and in vivo function. Several mechanisms, including C-terminal tail phosphorylations, appear to hold PTEN in a constrained conformation that limits its rate of association with the membrane. The steady-state level of bound PTEN is highest at sites of retracting membrane, including the rear of highly polarized cells. The dynamic membrane association could be modulated temporally or spatially to alter PTEN activity in specific physiological situations and could have important implications for tumor suppressor function. C1 Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA. Osaka Univ, Lab Nanobiol, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA. EM pnd@jhmi.edu RI Yanagida, Toshio/D-1919-2009 FU NIGMS NIH HHS [R01-GM28007, R01 GM028007, R01 GM034933, R01-GM34933] NR 32 TC 113 Z9 115 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 7 PY 2006 VL 103 IS 10 BP 3633 EP 3638 DI 10.1073/pnas.0510570103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 024VU UT WOS:000236225300026 PM 16537447 ER PT J AU Huang, HC Kearney, JF Grusby, MJ Benoist, C Mathis, D AF Huang, HC Kearney, JF Grusby, MJ Benoist, C Mathis, D TI Induction of tolerance in arthritogenic B cells with receptors of differing affinity for self-antigen SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE arthritis; autoimmunity; B cell tolerance ID TRANSGENIC MICE; AUTOIMMUNE-DISEASE; ESCAPE TOLERANCE; ANTIBODY; ANERGY; LYMPHOCYTES; MATURATION; ARTHRITIS; DELETION; ENZYME AB Multiple mechanisms of tolerance induction limit autoimmunity, but their relative contribution for lymphocytes recognizing self-antigens of differing availability is incompletely understood. The mechanisms applied to arthritogenic B cells expressing antigen-specific B cell receptors (BCRs) with different affinities for glucose-6-phosphate isomerase (GPI) were examined in the corresponding Ig gene knock-in mice. This ubiquitously expressed and blood-borne enzyme is the target autoantigen in the K/BxN model of inflammatory arthritis and perhaps in some humans with arthritis. Negative selection of B cells expressing high-affinity anti-GPI specificities, whose surface receptors were occupied by GPI, operated mainly at the transitional B cell stages in the spleen, preventing their final differentiation and entry into follicular areas. Receptor editing contributed to the purging of cells displaying anti-GPI BCRs, and significant numbers of autoreactive cells escaped through expression of an additional Ig light (L) chain, accumulating gradually in lymphoid organs. In contrast, low-affinity anti-GPI B cells, whose surface receptors did not carry GPI, matured normally. The "escaped" dual-L-chain cells and the "ignored" low-affinity cells are the likely precursors of cells that produce pathogenic autoantibodies once T cell help is provided. These studies portray, in a single system, the range of tolerance mechanisms applied to potentially pathogenic B cells, and serve as a base for dissecting where T cell help intervenes and where therapeutic agents impinge. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp,Joslin Diabet Ctr, Dept Med,Sect Immunol & Immunogenet, Boston, MA 02215 USA. Univ Alabama, Div Dermatol & Clin Immunol, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Joslin Diabet Ctr, Dept Med,Sect Immunol & Immunogenet, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu FU NIAID NIH HHS [R01 AI14782, R01 AI014782]; NIAMS NIH HHS [R01 AR046580, R01 AR046580-06] NR 31 TC 35 Z9 35 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 7 PY 2006 VL 103 IS 10 BP 3734 EP 3739 DI 10.1073/pnas.0600214103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 024VU UT WOS:000236225300043 PM 16505356 ER PT J AU Ayyanan, A Civenni, G Ciarloni, L Morel, C Mueller, N Lefort, K Mandinova, A Raffoul, W Fiche, M Dotto, GP Brisken, C AF Ayyanan, A Civenni, G Ciarloni, L Morel, C Mueller, N Lefort, K Mandinova, A Raffoul, W Fiche, M Dotto, GP Brisken, C TI Increased Wnt signaling triggers oncogenic conversion of human breast epithelial cells by a Notch-dependent mechanism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE breast cancer; DNA damage response; medullary carcinoma ID BETA-CATENIN; PROGENITOR CELLS; UP-REGULATION; RBP-J; CANCER; EXPRESSION; TRANSFORMATION; PATHWAY; MOUSE; MICE AB Wnt and Notch signaling have long been established as strongly oncogenic in the mouse mammary gland. Aberrant expression of several Writs and other components of this pathway in human breast carcinomas has been reported, but evidence for a causative role in the human disease has been missing. Here we report that increased Wnt signaling, as achieved by ectopic expression of Wnt-1, triggers the DNA damage response (DDR) and an ensuing cascade of events resulting in tumorigenic conversion of primary human mammary epithelial cells. Wnt-1-transformed cells have high telomerase activity and compromised p53 and Rb function, grow as spheres in suspension, and in mice form tumors that closely resemble medullary carcinomas of the breast. Notch signaling is up-regulated through a mechanism involving increased expression of the Notch ligands DII1, DII3, and DII4 and is required for expression of the tumorigenic phenotype. Increased Notch signaling in primary human mammary epithelial cells is sufficient to reproduce some aspects of Wnt-induced transformation. The relevance of these findings for human breast cancer is supported by the fact that expression of Wnt-1 and Wnt-4 and of established Wnt target genes, such as Axin-2 and Lef-1, as well as the Notch ligands, such as DII3 and DII4, is up-regulated in human breast carcinomas. C1 Swiss Inst Expt Canc Res, Natl Ctr Competence Res Mol Oncol, CH-1066 Epalinges, Switzerland. Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. CHU Vaudois, CH-1011 Lausanne, Switzerland. Ecole Polytech Fed Lausanne, Sch Life Sci, CH-1015 Lausanne, Switzerland. RP Brisken, C (reprint author), Swiss Inst Expt Canc Res, Natl Ctr Competence Res Mol Oncol, 155 Chemin Boveresses, CH-1066 Epalinges, Switzerland. EM cathrin.brisken@isrec.ch OI Civenni, Gianluca/0000-0003-1921-161X NR 57 TC 171 Z9 185 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 7 PY 2006 VL 103 IS 10 BP 3799 EP 3804 DI 10.1073/pnas.0600065103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 024VU UT WOS:000236225300054 PM 16501043 ER PT J AU Oh, WY Yun, SH Vakoc, BJ Tearney, GJ Bouma, BE AF Oh, WY Yun, SH Vakoc, BJ Tearney, GJ Bouma, BE TI Ultrahigh-speed optical frequency domain imaging and application to laser ablation monitoring SO APPLIED PHYSICS LETTERS LA English DT Article ID SWEPT SEMICONDUCTOR-LASER; COHERENCE TOMOGRAPHY; REFLECTOMETRY AB We demonstrate a linear laser resonator incorporating a semiconductor optical amplifier and scanning filter for high repetition rate, broad wavelength, unidirectional scanning. The laser operates at up to 115 kHz repetition rates and demonstrates a tuning-speed-independent power of > 30 mW. We apply this laser to enable ultrahigh-speed optical frequency domain imaging of the dynamics of laser ablation of biological tissue. The imaging system acquires single longitudinal scans (A-lines) in 8.7 mu s and complete cross-sectional images comprising 575 A-lines at a rate of 200 frames per second. (c) 2006 American Institute of Physics. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Oh, WY (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR 704, Boston, MA 02114 USA. EM woh1@partners.org RI Oh, Wang-Yuhl/C-2055-2011 NR 19 TC 25 Z9 25 U1 0 U2 5 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0003-6951 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD MAR 6 PY 2006 VL 88 IS 10 AR 103902 DI 10.1063/1.2179125 PG 3 WC Physics, Applied SC Physics GA 020JV UT WOS:000235905800091 ER PT J AU Beyer, KS Lee, MF Gusella, JF Naar, AM Ramesh, V AF Beyer, KS Lee, MF Gusella, JF Naar, AM Ramesh, V TI Understanding the role of the merlin interacting protein magicin as part of the mammalian Mediator complex SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Cell Biol,Canc Ctr, 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 6 PY 2006 VL 20 IS 4 BP A79 EP A79 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500379 ER PT J AU Bhattacharjee, A Xu, B Frank, D Feldman, G Cathcart, M AF Bhattacharjee, A Xu, B Frank, D Feldman, G Cathcart, M TI Monocyte 15-lipoxygenase expression is regulated by a novel cytosolic signaling complex with PKC delta and tyrosine phosphorylated Stat3 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. US FDA, Bethesda, MD 20892 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 6 PY 2006 VL 20 IS 4 BP A635 EP A635 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206505218 ER PT J AU Brandauer, J Weiss, EP Witkowski, S Phares, DA Hagberg, JM AF Brandauer, J Weiss, EP Witkowski, S Phares, DA Hagberg, JM TI Effect of endurance exercise training on fasting and postprandial plasma adiponectin levels in older men and women SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Maryland, College Pk, MD 20742 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 6 PY 2006 VL 20 IS 4 BP A397 EP A397 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503221 ER PT J AU Coaxum, SD Gooz, M Baldys, A Garnovskaya, MN Raymond, JR AF Coaxum, SD Gooz, M Baldys, A Garnovskaya, MN Raymond, JR TI Epidermal growth factor activates Na+/H+ exchange in podocytes through a mechanism that involves janus kinase and calmodulin SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Med Univ S Carolina, Med Nephrol Div, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Med & Res Serv, 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 6 PY 2006 VL 20 IS 4 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 024OW UT WOS:000236206506265 ER PT J AU Dahiya, S Erlander, M Ma, XJ Sgroi, D AF Dahiya, S Erlander, M Ma, XJ Sgroi, D TI Stromal-epithelial gene expression profiles in human breast cancer SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Pathol, Charlestown, MA 02129 USA. Arcturus Biosci Inc, Mountain View, CA 94043 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 6 PY 2006 VL 20 IS 4 BP A222 EP A222 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501485 ER PT J AU Dong, LS Mani, M Mukhopadhyay, L Alsup, C Yeap, B Richards, W Gordon, GJ Bueno, R AF Dong, LS Mani, M Mukhopadhyay, L Alsup, C Yeap, B Richards, W Gordon, GJ Bueno, R TI Reproducibility of a gene expression ratio based prognostic test in malignant pleural mesothelioma (MPM) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen 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 6 PY 2006 VL 20 IS 4 BP A216 EP A216 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501457 ER PT J AU Fitzgerald, ML AF Fitzgerald, ML TI Purification of ABCA1 and associated binding proteins reveals the importance of beta 1-syntrophin in cholesterol efflux SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, 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 6 PY 2006 VL 20 IS 4 BP A93 EP A93 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500441 ER PT J AU Granner, DK Hall, RK Wang, XH AF Granner, DK Hall, RK Wang, XH TI Hormonal regulation of assembly of the PEPCK gene transcription complex SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Vanderbilt Univ, Med Ctr, Ctr Diabet, Nashville, TN 37232 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 6 PY 2006 VL 20 IS 4 BP A454 EP A454 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503490 ER PT J AU Harrison, SC Boll, W Cheng, YF Ehrlich, M Fotin, A Grigorieff, N Kirchbausen, T Massol, R Rapoport, I Safarian, S Sliz, P Walz, T Xing, Y AF Harrison, SC Boll, W Cheng, YF Ehrlich, M Fotin, A Grigorieff, N Kirchbausen, T Massol, R Rapoport, I Safarian, S Sliz, P Walz, T Xing, Y TI Structure and dynamics of clathrin coated vesicles SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Annual Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Expt Therapeut C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Brandeis Univ, Rosenstiel Ctr, Waltham, MA 02454 USA. Howard Hughes Med Inst, Waltham, MA 02454 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 6 PY 2006 VL 20 IS 4 BP A35 EP A35 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500166 ER PT J AU Jones, R Capen, D AF Jones, R Capen, D TI Circulating momicytic cells (MCs) and restoration of capillaries lost from the alveolar-capillary membrane SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Harvard Univ, Sch Med, Boston, MA 02115 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 6 PY 2006 VL 20 IS 4 BP A213 EP A213 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501442 ER PT J AU Lee, MF Beyer, KS Beauchamp, R Gusella, JF Ramesh, V AF Lee, MF Beyer, KS Beauchamp, R Gusella, JF Ramesh, V TI Magicin (MED28), a potential adaptor protein SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, 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 6 PY 2006 VL 20 IS 4 BP A103 EP A103 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500491 ER PT J AU Rhodes, ME Barkowski, KE Teets, BE Trice, MW Czambel, RK Rubin, RT AF Rhodes, ME Barkowski, KE Teets, BE Trice, MW Czambel, RK Rubin, RT TI Sexually diergic hypothalamic-pituitary-adrenal axis responses to single-dose nicotine alone and following continuous administration of nicotine by osmotic mini-pumps in rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 St Vincent Coll, Dept Biol, Latrobe, PA 15650 USA. ASRI, Ctr Res Neurosci, Pittsburgh, PA 15212 USA. VA Greater Los Angeles Healthcare Syst, Dept Psychiat & Mental Hlth, Los Angeles, CA 90073 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 6 PY 2006 VL 20 IS 4 BP A258 EP A258 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502138 ER PT J AU Settleman, J AF Settleman, J TI P190 RhoGAP functions in tissue morphogenesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 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 6 PY 2006 VL 20 IS 4 BP A456 EP A456 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503500 ER PT J AU Shea, MK O'Donnell, CJ Hoffman, U Price, PA Dawson-Hughes, B Booth, SL AF Shea, MK O'Donnell, CJ Hoffman, U Price, PA Dawson-Hughes, B Booth, SL TI Plasma vitamin K levels are associated with coronary calcification in older adults. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Tufts Univ, HNRCA, Calcium & Bone Lab, Boston, MA 02111 USA. NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Radiol, Boston, MA 02114 USA. Univ Calif San Diego, Div Biol, La Jolla, CA 92093 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 6 PY 2006 VL 20 IS 4 BP A134 EP A134 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501090 ER PT J AU Shrimali, RK Park, JM Irons, R Carlson, BA Hatfield, DL AF Shrimali, RK Park, JM Irons, R Carlson, BA Hatfield, DL TI Selenoproteins play a major role in immune function SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NCI, DCP, Nutr Sci Res Grp, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 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 6 PY 2006 VL 20 IS 4 BP A68 EP A68 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500327 ER PT J AU Spiegelman, BM St Pierre, J Drori, S Uldry, M Lin, J Bachoo, R AF Spiegelman, BM St Pierre, J Drori, S Uldry, M Lin, J Bachoo, R TI PGC-1 coactivators and the control of energy homeostasis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 6 PY 2006 VL 20 IS 4 BP A455 EP A455 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503492 ER PT J AU Wei, CC Zhang, SL Guo, DF Ingelfinger, JR Chan, JSD AF Wei, CC Zhang, SL Guo, DF Ingelfinger, JR Chan, JSD TI Molecular cloning of a 70-kiloDalton (kDa) nuclear protein that binds to insulin responsive element (IRE) of rat angiotensinogen (ANG) gene promoter and modulates ANG gene expression in kidney proximal tubular cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 CHUM, Hop Hotel Dieu, Res Ctr, Montreal, PQ H2X 2L3, Canada. Massachusetts Gen Hosp, 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 6 PY 2006 VL 20 IS 4 BP A766 EP A766 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206506275 ER PT J AU Yu, LY Quinn, DA Garg, HG Hales, CA AF Yu, LY Quinn, DA Garg, HG Hales, CA TI Gene expression of cyclin-dependent kinase inhibitors and effect of heparin on the expression in mice with hypoxia-induced pulmonary hypertension SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit, 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 6 PY 2006 VL 20 IS 4 BP A401 EP A401 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503239 ER PT J AU Sun, BK Deaton, AM Lee, JT AF Sun, BK Deaton, AM Lee, JT TI A transient heterochromatic state in Xist preempts X inactivation choice without RNA stabilization SO MOLECULAR CELL LA English DT Article ID MOUSE EMBRYONIC STEM; CHROMOSOME INACTIVATION; TSIX TRANSCRIPTION; INTERGENIC TRANSCRIPTION; ANTISENSE TRANSCRIPTION; METHYLATION; GENE; CELLS; CHROMATIN; LOCUS AB X chromosome inactivation (XCI) depends on a non-coding sense-antisense transcript pair, Xist and Tsix. At the onset of XCI, Xist RNA accumulates on one of two Xs, coating and silencing the chromosome in cis. The molecular basis for monoallelic Xistupregulation is not known, though evidence predominantly supports a posttranscriptional mechanism through RNA stabilization. Here, we test whether Tsix RNA destabilizes Xist RNA. Unexpectedly, we find that Xistupregulation is not based on transcript stabilization at all but is instead controlled by transcription in a sex-specif ic manner. Tsix directly regulates its transcription. On the future inactive X, Tsix downregulation induces a transient heterochromatic state in Xist, followed paradoxically by high-level Xist expression. A Tsix-deficient X chromosome adopts the heterochromatic state in pre-XCI cells. This state persists through XCI establishment and "reverts" to a euchromatic state during XCI maintenance. We have therefore identified chromatin marks that preempt and predict asymmetric Xist expression. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu OI Sun, Bryan/0000-0002-0740-0125 NR 44 TC 192 Z9 200 U1 1 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAR 3 PY 2006 VL 21 IS 5 BP 617 EP 628 DI 10.1016/j.molcel.2006.01.028 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 023OB UT WOS:000236135000004 PM 16507360 ER PT J AU Gonzales, R Camargo, CA MacKenzie, T Kersey, AS Maselli, J Levin, SK McCulloch, CE Metlay, JP AF Gonzales, R Camargo, CA MacKenzie, T Kersey, AS Maselli, J Levin, SK McCulloch, CE Metlay, JP CA IMPAACT Trial Investigators TI Antibiotic treatment of acute respiratory infections in acute care settings SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE antibiotics; acute respiratory tract infections; emergency department; physician practice patterns ID COMMUNITY-ACQUIRED PNEUMONIA; DOUBLE-BLIND TRIAL; ACUTE BRONCHITIS; GENERAL-PRACTICE; TRACT INFECTIONS; PNEUMOCOCCAL PNEUMONIA; PENICILLIN-V; SORE THROAT; ADULTS; RESISTANCE AB Objectives: To examine the patterns of antibiotic use for acute respiratory tract infections (ARIs) in acute care settings. Methods: Chart reviews were performed retrospectively on a random sample of adult ARI visits to seven Veterans Affairs (VA) and seven non-VA emergency departments (EDs) for the period of November 2003 to February 2004. Visits were limited to those discharged to home and those with primary diagnoses of antibiotic-responsive (pneumonia, acute exacerbation of chronic bronchitis, pharyngitis, sinusitis) and antibiotic-nonresponsive conditions (acute bronchitis, nonspecific upper respiratory tract infection [URI]). Results are expressed as adjusted odds ratios with 95% confidence intervals. Results: Of 2,270 ARI visits, 62% were for antibiotic-nonresponsive diagnoses. Seventy-two percent of acute bronchitis and 38% of URI visits were treated with antibiotics (p < 0.001). Stratified analyses show that antibiotic prescription rates were similar among attending-only and housestaff-associated visits for antibiotic-responsive diagnoses (p = 0.11), and acute bronchitis (76% vs. 59%; p = 0.31). However, the antibiotic prescription rate for URIs was greater for attending-only visits compared with housestaff-associated visits (48% vs. 15%; p = 0.01). Antibiotic prescription rates for total ARIs varied between sites, ranging from 42% to 89%. Patient age, gender, race and ethnicity, smoking status, comorbidities, and clinical setting (VA vs. non-VA) were not independently associated with antibiotic prescribing. Conclusions: Acute care settings are important targets for reducing inappropriate antibiotic prescribing. The mechanisms accounting for lower antibiotic prescription rates observed with housestaff-associated visits merit further study. C1 Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94118 USA. Univ Calif San Francisco, Div Gen Internal Med, Dept Med, San Francisco, CA 94118 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Denver Hlth Med Ctr, Denver, CO USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Gonzales, R (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 3333 Calif St,Box 1211, San Francisco, CA 94118 USA. EM ralphg@medicine.ucsf.edu FU AHRQ HHS [1 R01 HS013915] NR 29 TC 35 Z9 35 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAR PY 2006 VL 13 IS 3 BP 288 EP 294 DI 10.1197/j.aem.2005.10.016 PG 7 WC Emergency Medicine SC Emergency Medicine GA 022UV UT WOS:000236082500009 PM 16514122 ER PT J AU Kerfoot, BP Baker, H Jackson, TL Hulbert, WC Federman, DD Oates, RD DeWolf, WC AF Kerfoot, BP Baker, H Jackson, TL Hulbert, WC Federman, DD Oates, RD DeWolf, WC TI A multi-institutional randomized controlled trial of adjuvant web-based teaching to medical students SO ACADEMIC MEDICINE LA English DT Article ID INSTRUCTION; EDUCATION; UROLOGY; CURRICULUM; KNOWLEDGE AB Purpose To investigate the impact of an adjuvant Web-based teaching program on medical students' learning during clinical rotations. Method From April 2003 to May 2004, 351 students completing clinical rotations in surgery-urology at four U.S. medical schools were invited to volunteer for the study. Web-based teaching cases were developed covering four core urologic topics. Students were block randomized to receive Web-based teaching on two of the four topics. Before and after a designated duration at each institution (ranging one to three weeks), students completed a validated 28-item Web-based test (Cronbach's alpha = .76) covering all four topics. The test was also administered to a subset of students at one school at the conclusion of their third-year to measure long-term learning. Results Eighty-one percent of all eligible students (286/351) volunteered to participate in the study, 73% of whom (210/286) completed the Web-based program. Compared to controls, Web-based teaching significantly increased test scores in the four topics at each medical school (p < .001, mixed analysis of variance), corresponding to a Cohen's d effect size of 1.52 (95% confidence interval [CI], 1.23-1.80). Learning efficiency was increased three-fold by Web-based teaching (Cohen's d effect size 1.16; 95% CI 1.13-1.19). Students who were tested a median of 4.8 months later demonstrated significantly higher scores for Web-based teaching compared to non-Web-based teaching (p = .007, paired t-test). Limited learning was noted in the absence of Web-based teaching. Conclusions This randomized controlled trial provides Class I evidence that Web-based teaching as an adjunct to clinical experiences can significantly and durably improve medical students' learning. C1 Vet Adm Boston Healthcare Syst, Boston, MA USA. Calif State Univ Channel Isl, Camarillo, CA USA. Univ Vermont, Coll Med, Burlington, VT USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Med Ctr, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Kerfoot, BP (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,151D1A, Jamaica Plain, MA 02130 USA. EM drskerfoot@msn.com NR 24 TC 49 Z9 49 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD MAR PY 2006 VL 81 IS 3 BP 224 EP 230 DI 10.1097/00001888-200603000-00004 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 025GQ UT WOS:000236253800004 PM 16501262 ER PT J AU Kilbourne, AM Pincus, HA Schutte, K Kirchner, JAE Haas, GL Yano, EM AF Kilbourne, AM Pincus, HA Schutte, K Kirchner, JAE Haas, GL Yano, EM TI Management of mental disorders in VA primary care practices SO ADMINISTRATION AND POLICY IN MENTAL HEALTH LA English DT Article DE depression; health services organization; mental disorders; mental health services; primary care ID UNITED-STATES; DEPRESSION; QUALITY; BURDEN; SYSTEM AB The association between facility-level organizational features and management of mental health services was assessed based on a survey of directors from 219 VA primary care facilities. Overall, 26.4% of VA primary care facilities referred patients with depression, while 72.6% and 46.1% referred patients with serious mental illness and substance use disorders, respectively Staffing mix (i.e., physician extenders such as nurse practitioners) was associated with a lesser likelihood of mental health referral. Managed care (preauthorization requirement) was associated with a greater likelihood of referral for depression. VA primary care programs, while tending to refer for more serious mental illnesses, may also be using mental health specialists and physician extenders to provide mental health care within general medical settings. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. RAND Univ Pittsburgh, Hlth Inst, Pittsburgh, PA USA. VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. VA Ctr Mental Healthcare & Outcomes Res, S Cent VA Mental Illness Res Educ Clin Ctr, Little Rock, AR 72114 USA. VA Greater Los Angeles Healthcare Syst, HSR&D Ctr Excellence 152, Sepulveda Ambulatory Care Ctr & Nursing Home, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Kilbourne, AM (reprint author), VA Pittsburgh Ctr Hlth Equ Res & Promot 151C, Univ Dr C, Pittsburgh, PA 15240 USA. EM Amy.Kilbourne@med.va.gov NR 19 TC 13 Z9 13 U1 0 U2 0 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD MAR PY 2006 VL 33 IS 2 BP 208 EP 214 DI 10.1007/s10488-006-0034-6 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 043ND UT WOS:000237607000007 PM 16477518 ER PT J AU Bogart, LM Fremont, AM Young, AS Pantoja, P Chinman, M Morton, S Koegel, P Sullivan, G Kanouse, DE AF Bogart, LM Fremont, AM Young, AS Pantoja, P Chinman, M Morton, S Koegel, P Sullivan, G Kanouse, DE TI Patterns of HIV care for patients with serious mental illness SO AIDS PATIENT CARE AND STDS LA English DT Article ID UNITED-STATES; ANTIRETROVIRAL TREATMENT; INFECTED PERSONS; CASE-MANAGEMENT; RISK BEHAVIORS; PEOPLE; AIDS; THERAPY; SEROPREVALENCE; INITIATION AB Individuals with serious mental illness are at higher risk for HIV than are members of the general population. Although studies have shown that individuals with serious mental illness experience less adequate care and worse physical health outcomes than comparable patients without serious mental illness, little is known about HIV care among individuals with serious mental illness who become infected with HIV. In the present study, we describe patterns of highly active antiretroviral treatment ( HAART) use and physician monitoring received by 154 patients with serious mental illness infected with HIV. Participants were recruited from mental health agencies in Los Angeles, California. Data from 762 HIV-only patients from a separate Western U. S. probability sample were used for comparison. High proportions of serious mental illness patients with HIV in our sample appeared to be receiving adequate HIV care. Fifty-one percent of all serious mental illness patients with serious mental illness with HIV were taking HAART, and the majority received close monitoring of their CD4 counts (84%) and viral loads (82%) throughout a 1-year period. HAART use and patterns of CD4 count and viral load monitoring did not differ significantly between patients with both serious mental illness and HIV, and patients with HIV only (all p > 0.05). Specialized programs providing assistance to serious mental illness populations with HIV may be helping to narrow health care disparities as a result of having serious mental illness. C1 RAND Corp, Santa Monica, CA 90407 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Dept Vet Affairs Desert Pacific Mental Illness Re, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. VA S Cent Mental Illness Res Educ & Clin Ctr, N Little Rock, AR USA. Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. RP Bogart, LM (reprint author), RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA. EM lbogart@rand.org RI Young, Alexander/A-1523-2009 OI Young, Alexander/0000-0002-9367-9213 FU AHRQ HHS [U-01HS08578]; NIMH NIH HHS [P50 MH-54623, R01MH55936-05] NR 23 TC 13 Z9 13 U1 2 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD MAR PY 2006 VL 20 IS 3 BP 175 EP 182 DI 10.1089/apc.2006.20.175 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 029QN UT WOS:000236579600005 PM 16548714 ER PT J AU Mitchell, SH Reeves, JM Li, N Phillips, TJ AF Mitchell, SH Reeves, JM Li, N Phillips, TJ TI Delay discounting predicts behavioral sensitization to ethanol in outbred WSC mice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE impulsivity; delay discounting; behavioral sensitization; locomotion; mice ID CONDITIONED PLACE PREFERENCE; ADJUSTING-AMOUNT PROCEDURE; RECOMBINANT INBRED MICE; LOCOMOTOR-ACTIVITY; VOLUNTARY ETHANOL; CHRONIC TOLERANCE; SELF-CONTROL; ALCOHOL; IMPULSIVITY; SENSITIVITY AB Background: Alcoholic individuals discount the value of future rewards more steeply than social drinkers, which is viewed as symptomatic of higher levels of impulsivity. However, the mechanisms underlying this difference are unknown. This study examined 2 hypotheses about the relationship between discounting and ethanol's effects in mice: (1) steep discounters are less sensitive to the initial stimulant-like effects of ethanol and (2) steep discounters exhibit greater behavioral adaptation to stimulant effects with repeated ethanol exposure. Methods: An adjusting amount procedure was used to assess discounting as a function of delay in ethanol-naive genetically heterogeneous WSC mice. Mice chose between a small amount of sucrose solution delivered immediately and 19.5 mu L delivered following a delay (0, 2, 4, 8, or 12 seconds, varied between sessions). Within sessions, the amount (mu L) of immediate sucrose was adjusted until animals became indifferent between the immediate and specific delayed reward. Hyperbolic discount functions were fitted to quantify the degree of delay discounting. Then, in a within-subjects design over 13 days, mice received a pattern of daily injections of saline or ethanol, and after certain treatments their locomotor activity was assessed for 15 minutes. Results: Animals with steeper discount functions (greater impulsivity) tended to exhibit less locomotor stimulation on their initial exposure to ethanol. However, steeper discounting was positively associated with increases in locomotor activity after repeated exposure (sensitization), indicating that steep discounters showed higher levels of sensitization to the stimulating effects of ethanol. Conclusions: These results suggest 2 behavioral effects of ethanol, associated with an increased risk for alcohol abuse, that are associated with variations in delay discounting. C1 Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland Alcohol Res Ctr, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Mitchell, SH (reprint author), Oregon Hlth Sci Univ, Dept Behav Neurosci, L470,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM mitchesu@ohsu.edu OI Mitchell, Suzanne/0000-0002-0225-7200 FU NIAAA NIH HHS [P60 AA010760, P50 AA10760] NR 43 TC 38 Z9 39 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAR PY 2006 VL 30 IS 3 BP 429 EP 437 DI 10.1111/j.1530-0277.2006.00047.x PG 9 WC Substance Abuse SC Substance Abuse GA 019EB UT WOS:000235817300005 PM 16499483 ER PT J AU Taylor, AN Tio, DL Bando, JK Romeo, HE Prolo, P AF Taylor, AN Tio, DL Bando, JK Romeo, HE Prolo, P TI Differential effects of alcohol consumption and withdrawal on circadian temperature and activity rhythms in Sprague-Dawley, Lewis, and Fischer male and female rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ethanol dependence; biotelemetry; sex; inbred rat strains; corticotropin-releasing hormone ID CORTICOTROPIN-RELEASING HORMONE; SUPRACHIASMATIC NUCLEUS; LOCOMOTOR-ACTIVITY; BODY-TEMPERATURE; SEX-DIFFERENCES; TIME-SERIES; ETHANOL; RESPONSES; STRAINS; CORTICOSTERONE AB Background: Hypothalamic synthesis and secretion of corticotropin-releasing hormone (CRH), a putative mediator of various behavioral and physiological responses to ethanol (EtOH), is defective in inbred Lewis (LEW) rats in comparison with their genetically related inbred Fischer 344 (F344) and outbred Sprague-Dawley (S-D) strains. We aimed to characterize the effects of continuous EtOH consumption and withdrawal on circadian patterns of body temperature and spontaneous locomotor activity in males and females of these 3 strains. Methods: Adult LEW, F344, and S D males and randomly cycling females were fed an EtOH-containing liquid diet or the control (pair-fed or lab chow and water) diet for 14 days. Biotelemetric body temperature data for the last 3 days of EtOH diet feeding and the first 3 days of withdrawal were subjected to cosinor analysis of the circadian rhythm parameters of midline-estimating statistic of rhythm (MESOR), amplitude, and acrophase. Mean dark-phase activity during these periods was also computed. Results: In the control diet condition, the MESORs and amplitudes of LEW males were lower than those of F344 males. MESORs of rhythms of LEW females were lower than those of both F344 and S-D females. Ethanol consumption caused hypothermia with reduced MESORs and amplitudes of LEW and F344 males and amplitudes of F344 and S-D females. Upon withdrawal, MESORs of the males increased during each day as the amplitudes decreased, reflective of their initial withdrawal-induced dark-phase hypothermia, which was most pronounced in the LEW males, followed by light-phase hyperthermia. MESORs of females were not affected by withdrawal; their amplitudes were differentially affected. Acrophase of LEW males shifted from dark to light on the first day of withdrawal. All rats responded to EtOH exposure with a reduction of dark-phase spontaneous locomotor activity and an immediate increase upon withdrawal. Conclusions: Body temperature rhythms of the males were generally more affected by EtOH consumption and withdrawal than the females; within each sex, LEW and F344 rats differed significantly. The specific hormonal factors that mediate the differential temperature responses remain to be defined. C1 Univ Calif Los Angeles, Dept Neurobiol, David Geffen Sch Med, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Brain Res Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. RP Taylor, AN (reprint author), Univ Calif Los Angeles, Dept Neurobiol, David Geffen Sch Med, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM ataylor@mednet.ucla.edu FU NIAAA NIH HHS [AA09850] NR 51 TC 13 Z9 13 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAR PY 2006 VL 30 IS 3 BP 438 EP 447 DI 10.1111/j.1530-0277.2006.00048.x PG 10 WC Substance Abuse SC Substance Abuse GA 019EB UT WOS:000235817300006 PM 16499484 ER PT J AU Alhomsi, K Cluette-Brown, JE Laposata, M AF Alhomsi, K Cluette-Brown, JE Laposata, M TI Fatty acid ethyl esters in human mononuclear cells: Production by endogenous synthesis greatly exceeds the uptake of preformed ethyl esters SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE human mononuclear cells; fatty acid ethyl esters; ethyl oleate; ethanol; free fatty acids ID NONOXIDATIVE ETHANOL-METABOLISM; WHITE BLOOD-CELLS; PANCREATIC INJURY; ALCOHOL; HYDROLYSIS; SYNTHASE; MARKERS; PURIFICATION; PLATELETS; DAMAGE AB Background: Fatty acid ethyl esters (FAEE) are nonoxidative metabolites of ethanol. They are esterification products of ethanol and fatty acids. Fatty acid ethyl esters have been implicated as important mediators of ethanol-induced cytotoxicity, organ damage, and disease. In addition, they serve as specific and sensitive biomarkers for ethanol intake. Following ethanol consumption, FAEE are found in circulating blood bound to albumin or/and lipoproteins. Objectives: Using a mononuclear fraction of white blood cells (WBC) exposed to ethanol, we investigated FAEE synthesis. We then determined the amount of uptake of preformed FAEE presented to the cells and compared the amounts of FAEE within the cells that were derived from endogenous synthesis with the amount derived from uptake of exposure FAEE. We also measured the persistence of FAEE within these cells and assessed the fate of the FAEE-associated fatty acid upon FAEE hydrolysis. Methods: A mononuclear fraction of human WBC was incubated with 25, 50, or 100 mM ethanol for 0.08 to 120 minutes, and FAEE synthesis was measured by gas chromatography/mass spectrometry. In other experiments, mononuclear cells were incubated with 25, 50, and/or 100 mu M [3 H]ethyl oleate, a representative FAEE species, for 0.08-120 minutes, and FAEE uptake and hydrolysis were measured. Results: The total FAEE formed by treating the cells with 25 mM ethanol, which represents a physiologic dose achievable with excess alcohol intake, greatly exceeded the FAEE within cells derived from uptake of 100 MM ethyl oleate, which represents a supraphysiologic dose. There was hydrolysis of FAEE by human mononuclear cells, with free fatty acids as major metabolites of FAEE hydrolysis. Unlike any other cell type or homogenate studied, the only ethyl ester formed by human mononuclear cells exposed to ethanol was ethyl oleate. Conclusions: There is significant synthesis of FAEE by human mononuclear cells within seconds of exposure to physiologic doses of ethanol. The amount of FAEE in these cells derived from endogenous synthesis greatly exceeds the amount acquired by exogenous uptake. C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Northeastern Univ, Dept Biomed Sci, Boston, MA 02115 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Room 235 Gray Bldg,55 Fruit St, Boston, MA 02114 USA. EM mlaposata@partners.org NR 35 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAR PY 2006 VL 30 IS 3 BP 560 EP 566 DI 10.1111/j.1530-0277.2006.00062.x PG 7 WC Substance Abuse SC Substance Abuse GA 019EB UT WOS:000235817300020 PM 16499498 ER PT J AU Spertus, JA Peterson, E Rumsfeld, JS Jones, PG Decker, C Krumholz, H AF Spertus, JA Peterson, E Rumsfeld, JS Jones, PG Decker, C Krumholz, H CA Cardiovascular Outcomes Res Consor TI The Prospective Registry Evaluating Myocardial Infarction: Events and Recovery (PREMIER) - Evaluating the impact of myocardial infarction on patient outcomes SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; QUALITY-OF-LIFE; HEART-ASSOCIATION; AMERICAN-COLLEGE; CARDIOVASCULAR-DISEASE; ARTERY DISEASE; HEALTH-STATUS; MANAGEMENT AB Background More information on the longitudinal care and outcomes of patients after myocardial infarction (MI) is needed to further improve the quality of MI care. The PREMIER study was designed to meet this need. Methods Patients with MI were prospectively screened and enrolled from 19 US centers between January 1, 2003, and June 28, 2004. Consenting patients had detailed chart abstractions of their medical history and processes of inpatient care, supplemented with a detailed, patient-centered interview. Centralized follow-up at 1, 6, and 12 months is being conducted to quantify patients' postdischarge care and outcomes, with a focus on their health status (symptoms, function, and quality of life). In 2003, detailed chart abstractions, devoid of all personal health information, were collected for patients eligible but not enrolled in PREMIER. Results Of 10911 patients screened, 3953 were eligible and 2498 enrolled into PREMIER. Few clinically significant differences between the total MI population and those enrolled into PREMIER were observed. Adherence to accepted processes of quality care, such as aspirin and beta-blockers on admission (96% and 91%) or discharge (96% and 93%), was high. One-month follow-up rates were high, with only 9% of patients being lost to follow-up. Conclusion PREMIER is a novel registry with detailed insights into patients' sociodemographic, clinical, and health status characteristics, as well as detailed monitoring of their inpatient and outpatient processes of care. Ultimately, PREMIER will describe patients' health status outcomes and identify determinants of these outcomes as an important step toward improving MI care. C1 Mid Amer Heart Inst, Kansas City, MO 64111 USA. Univ Missouri, Kansas City, MO USA. Yale Univ, New Haven, CT USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO USA. RP Spertus, JA (reprint author), Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA. EM spertusj@umkc.edu FU AHRQ HHS [R-01 HS11282-01] NR 30 TC 80 Z9 83 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2006 VL 151 IS 3 BP 589 EP 597 DI 10.1016/j.ahj.2005.05.026 PG 17 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 026PF UT WOS:000236353900006 PM 16504619 ER PT J AU Joseph, J Rimawi, A Mehta, P Cottler-Fox, M Sinha, A Singh, BK Pacheco, R Smith, ES Mehta, JL AF Joseph, J Rimawi, A Mehta, P Cottler-Fox, M Sinha, A Singh, BK Pacheco, R Smith, ES Mehta, JL TI Safety and effectiveness of granulocyte-colony stimulating factor in mobilizing stem cells and improving cytokine profile in advanced chronic heart failure SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BLOOD; INTERLEUKIN-10; TRANSPLANTATION; MOBILIZATION; FILGRASTIM AB The objective of this study was to determine a safe and effective dose of granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells in patients with advanced heart failure and to determine its effects on the cytokine profile. Patients with advanced heart failure (n = 6) and implantable defibrillators in situ were administered G-CSF after baseline echocardiographic and laboratory evaluation, using an escalating dose schedule designed to ensure safety. The peripheral CD34+ hematopoietic stem cell count increased from 3.6 +/- 0.5/mu l to 38.7 +/- 13/mu l (p = 0.022) after 5 days of 5 mu g/kg/day G-CSF therapy. The baseline or peak white blood cell count did not predict the stem cell response. G-CSF increased plasma levels of interleukin-10. Left ventricular ejection fraction increased significantly in the 4 patients with ischemic cardiomyopathy 9 months after treatment. No major adverse effects attributable to the drug occurred during administration or 9 months of follow-up. Our results have shown that low-dose G-CSF significantly mobilized hematopoietic stem cells in advanced heart failure and improved left ventricular function in the ischemic subset of patients. G-CSF significantly increased plasma levels of the anti-inflammatory cytokine interleukin-10, without changing proinflammatory cytokine levels. In conclusion, these results indicate a novel mechanism of action for the potential therapeutic benefit of G-CSF in advanced ischemic cardiomyopathy. (C) 2006 Elsevier Inc. All rights reserved. C1 VA Boston Healthcare Syst, Dept Med, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Arkansas Med Sci, Dept Med, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Physiol & Biophys, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. RP Joseph, J (reprint author), VA Boston Healthcare Syst, Dept Med, Boston, MA USA. EM jacob.joseph@med.va.gov FU NCRR NIH HHS [2M01 RR 014288-06 041] NR 10 TC 18 Z9 18 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2006 VL 97 IS 5 BP 681 EP 684 DI 10.1016/j.amjcard.2005.09.112 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 021XW UT WOS:000236020200019 PM 16490437 ER PT J AU Norton, MC Skoog, I Toone, L Corcoran, C Tschanz, JAT Lisota, RD Hart, AD Zandi, PP Breitner, JCS Welsh-Bohmer, KA Steffens, DC AF Norton, MC Skoog, I Toone, L Corcoran, C Tschanz, JAT Lisota, RD Hart, AD Zandi, PP Breitner, JCS Welsh-Bohmer, KA Steffens, DC CA Cache County Investigators TI Three-year incidence of first-onset depressive syndrome in a population sample of older adults: The cache county study SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY MAR 01-04, 2003 CL HONOLULU, HI SP Amer Assoc Geriatr Psychiat DE depression; epidemiology ID ELDERLY POPULATION; ALZHEIMERS-DISEASE; MENTAL-DISORDERS; MAJOR DEPRESSION; PREVALENCE; COMMUNITY; AD; EPIDEMIOLOGY; ANTAGONISTS; AGE AB Objective: Estimates of incidence of late-life depression vary greatly with few studies excluding demented cases through in-depth evaluation and most studies failing to control for the effect of mortality and interval treatment. In a large population-based study, the authors examined the effect on incidence of first-onset depressive syndrome to determine whether any gender or age differences in incidence are attenuated with inclusion of these additional measures. Method: Incidence rates of depressive syndrome per 1,000 person-years are presented for 2,877 nondemented elderly ( ages 65 to 100 years) residents of Cache County, Utah. Cases are identified by direct interview methods, by inference from prescription antidepressant medicine use, and by postmortem informant interview for decedents. Results: In-person interviews yielded incidence rates of first-onset depressive disorder (any type) of 13.09 for men and 19.44 for women. Inclusion of antidepressant users increased these figures to 15.55 for men and 23.30 for women. Addition of postmortem interview data yielded rates of 20.66 for men and 26.29 for women. Individuals with no history of depression had rates for major depression of 7.88 for men and 8.75 for women; minor depression rates were 19.23 for men and 24.46 for women (p = 0.691; effect for minor depression p < 0.0001). Age did not predict incidence. Conclusions: Incidence of first-onset major depression varies with data source and prior lifetime history of depression. Gender effects apparent in interview data are attenuated when postmortem information and pharmacotherapy were considered. C1 Utah State Univ, Dept Family Consumer & Human Dev, Logan, UT 84322 USA. Utah State Univ, Dept Psychol, Logan, UT 84322 USA. Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA. Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. Gothenburg Univ, Sect Psychiat, Inst Clin Neurosci, S-41124 Gothenburg, Sweden. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. Johns Hopkins Univ, Dept Mental Hyg, Baltimore, MD 21218 USA. Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. RP Norton, MC (reprint author), Utah State Univ, Dept Family Consumer & Human Dev, 2905 Old Main Hill, Logan, UT 84322 USA. EM mnorton@cc.usu.edu RI Corcoran, Chris/F-2155-2010; Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013 FU NIA NIH HHS [R01-AG-11380] NR 30 TC 32 Z9 33 U1 2 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2006 VL 14 IS 3 BP 237 EP 245 DI 10.1097/01.JGP.0000196626.34881.42 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 016LE UT WOS:000235620900006 PM 16505128 ER PT J AU Kris, AE Cherlin, EJ Prigerson, H Carlson, MDA Johnson-Hurzeler, R Kasl, SV Bradley, EH AF Kris, AE Cherlin, EJ Prigerson, H Carlson, MDA Johnson-Hurzeler, R Kasl, SV Bradley, EH TI Length of hospice enrollment and subsequent depression in family caregivers: 13-month follow-up study SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE hospice; depression; caregiver ID TERMINAL CARE; NURSING-HOMES; MANAGEMENT; DISORDERS; SPOUSES; BURDEN; IMPACT; GRIEF; LIFE; PAIN AB Objective: Although more people are using hospice than ever before, the average length of hospice enrollment is decreasing. Little is known about the effect of hospice length of enrollment on surviving family caregivers. The authors examine the association between patient length of hospice enrollment and major depressive disorder (MDD) among the surviving primary family caregivers 13 months after the patient's death. Methods: The authors conducted a three-year longitudinal study of 175 primary family caregivers of patients with terminal cancer who consecutively enrolled in the participating hospice from October 1999 through September 2001. Interviews were conducted with the primary family caregiver when the patient first enrolled with hospice and again 13 months after the patient's death. The authors used multivariate logistic regression models to estimate caregivers' adjusted risk at 13 months postloss for MDD, assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ( SCID). Results: The effect of very short hospice length of enrollment ( three days or less) compared with longer lengths of enrollment on caregiver MDD 13 months after their loss was nonsignificant in unadjusted analyses. The adjusted risk of MDD was significantly elevated for caregivers of patients who had very short hospice enrollments (adjusted odds ratio: 8.76, 95% confidence interval: 1.09-70.19) only after adjusting for baseline MDD, caregiver gender, caregiver age, kinship relationship to patient, caregiver education, caregiver chronic conditions, and caregiver burden. The adjustment for caregiver burden resulted in the greatest increase in odds ratio for very short hospice length of enrollment on risk of caregiver MDD 13 months after the loss. Conclusions: This study identifies a potential target group of family caregivers, characterized by hospice length of enrollment and several caregiver features, who might be most in need of mental health interventions. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Connecticut Hospice, Branford, CT USA. John D Thompson Hospice Inst Educ Training & Res, Branford, CT USA. RP Bradley, EH (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St, New Haven, CT 06520 USA. EM Elizabeth.bradley@yale.edu FU NCI NIH HHS [CA106370, R01 CA106370]; NIA NIH HHS [P30AG21342]; NIMH NIH HHS [MH63892] NR 21 TC 45 Z9 46 U1 5 U2 11 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2006 VL 14 IS 3 BP 264 EP 269 DI 10.1097/01.JGP.0000194642.86116.ce PG 6 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 016LE UT WOS:000235620900009 PM 16505131 ER PT J AU Chepenik, LG Ten Have, T Oslin, D Datto, C Zubritsky, C Katz, IR AF Chepenik, LG Ten Have, T Oslin, D Datto, C Zubritsky, C Katz, IR TI A daily diary study of late-life depression SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE depressive disorders; minor depression; dysphoria; positive affect; diaries ID BEHAVIORAL HEALTH-CARE; CORTISOL SECRETION; RANDOMIZED-TRIAL; DAILY EVENTS; PRISM-E; DISORDER; MOOD; VARIABILITY; QUALITY; DISEASE AB Objective: The objective of this study was to use data from daily diaries to characterize the day-to-day variability in positive and negative affects, and the relationship between daily events and daily affects in primary care patients with late-life depression. Method: Daily diary data were obtained from primary care patients with major depression (N = 25) and other depressive disorders (N = 33); data from a two-week period were compared with those from elderly normal volunteer comparison subjects (N = 70) who participated in other studies. Results: There was significant day-to-day variability in negative affect in patients with major depression and other depressive disorders. Dysphoric days ( days with a negative affect ratings that occurred once every two weeks in normal subjects) represented 65.3% ( standard deviation [SD]: 37.1) of days in those with major depression and 50.6% (SD: 37.6) in those with other depression versus 7.7% (SD: 16.3) in normal subjects (F = 36.0, p < 0.001). The groups did not differ significantly in the number of positive and negative events reported, but the proportion of dysphoric days that occurred in association with negative events was greater in normal subjects than in those with major depression. Mixed-effects analyses demonstrated that patients with major depression had blunted positive affective responses to positive events, consistent with impairments in hedonic processes, and that patients with other depressions exhibited heightened negative affective responses to negative events, greater than those in normal subjects and patients with major depression. Conclusions: Diary methods demonstrated characteristics of late-life depression that have not been identified with assessment methods that have lower time resolution. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. RP Katz, IR (reprint author), Univ Penn, Dept Psychiat, 3535 Market St,Rm 3001, Philadelphia, PA 19104 USA. EM katzi@mail.med.upenn.edu FU NIMH NIH HHS [R01 MH58349, MH66270] NR 26 TC 12 Z9 12 U1 1 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2006 VL 14 IS 3 BP 270 EP 279 DI 10.1097/01.JGP.0000194644.63245.42 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 016LE UT WOS:000235620900010 PM 16505132 ER PT J AU Hynes, DM Stroupe, KT Kaufman, JS Reda, DJ Peterman, A Browning, MM Huo, ZP Sorbara, D AF Hynes, DM Stroupe, KT Kaufman, JS Reda, DJ Peterman, A Browning, MM Huo, ZP Sorbara, D CA ESRD Cost Study Grp TI Adherence to guidelines for ESRD anemia management SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE erythropoietin; anemia management; end-stage renal disease (ESRD); clinical guidelines; veterans ID RED-CELL APLASIA; STAGE RENAL-DISEASE; HEMODIALYSIS-PATIENTS; INTRAVENOUS EPOETIN; DIALYSIS PATIENTS; ERYTHROPOIETIN; THERAPY; IV AB Background. A costly component of end-stage renal disease care is anemia management with recombinant human erythropoietin. National Kidney Foundation clinical practice guidelines recommend that erythropoietin be administered subcutaneously, rather than intravenously, given that the target hemoglobin level can be maintained with a lower subcutaneous dose. Because reimbursement for erythropoietin differs for federal versus private-sector dialysis centers, we hypothesized different use patterns by facility type. Methods: Using data from a multisite prospective observational study of hemodialysis patients from 2001 to 2003, we examined compliance with erythropoietin administration guidelines across Veterans Affairs (VA) versus private-sector facilities and implications for erythropoietin dose, anemia management, and cost. Results: Erythropoietin was administered predominantly subcutaneously for 52% of patients in VA versus 15% in private-sector facilities (P<0.0001). Average adjusted weekly subcutaneous erythropoietin doses were 13,710 and 13,362 units at VA and private-sector facilities versus 19,453 and 21,237 units for intravenous erythropoietin (P=0.01), with corresponding hemoglobin levels of 11.55 and 12.34 g/dL (115.5 and 123.4 g/L) for subcutaneous and 11.38 and 11.91 g/dL (113.8 and 119.1 g/L) for intravenous erythropoietin (P=0.0002), respectively. Yearly erythropoietin costs per patient for subcutaneous administration were $7,129 and $6,948 at VA and private-sector facilities versus S10,116 and S11,043 for intravenous administration (P=0.01), respectively. Conclusion: We found greater guideline adherence at VA facilities compared with the private sector, with lower erythropoietin costs, although overall adherence is low. Anemia management was similar. Future research should examine how patient preferences and financial incentives impact on the wider use of subcutaneous erythropoietin administration. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Midw Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Cooperat Studies Program Coordinating Ctr, Hines, IL 60141 USA. Loyola Univ, Dept Med, Div Gen Internal Med, Maywood, IL 60153 USA. Univ Illinois, Dept Epidemiol & Biostat, Chicago, IL USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Vet Affairs Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Univ N Carolina, Dept Psychol, Charlotte, NC 28223 USA. RP Hynes, DM (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Midw Ctr Hlth Serv & Policy Res, POB 5000 151V, Hines, IL 60141 USA. EM denise.hynes@va.gov NR 19 TC 14 Z9 14 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAR PY 2006 VL 47 IS 3 BP 455 EP 461 DI 10.1053/j.ajkd.2005.11.012 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 026FV UT WOS:000236325700012 PM 16490624 ER PT J AU Gaviani, P Mullins, ME Braga, TA Hedley-Whyte, ET Halpern, EF Schaefer, PS Henson, JW AF Gaviani, P Mullins, ME Braga, TA Hedley-Whyte, ET Halpern, EF Schaefer, PS Henson, JW TI Improved detection of metastatic melanoma by T2(*)-weighted imaging SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID MALIGNANT-MELANOMA; MR AB BACKGROUND AND PURPOSE: The imaging features of metastatic melanomas are distinctive due to the presence of melanin and the propensity for hemorrhage. Both hemorrhage and melanin can produce T1-weighted hyperintensity and T2*-weighted signal intensity loss. We hypothesized that T2*-weighted images would improve detection of metastatic melanoma. METHODS: The T2* and T1 characteristics of 120 newly detected metastatic brain lesions from 31 patients with malignant melanoma were compared with those of 120 brain metastases from 23 patients with lung cancer. RESULTS: Melanoma metastases were 5 times more likely to demonstrate prominent T2*-related signal intensity loss (susceptibility effect) than were lung metastases (42% vs 8%; P < .01), and 4.5 times more likely to demonstrate T1 hyperintensity (55% vs 12%; P < .01). Patients with melanoma had lesions that were either hypointense on T2*-weighted images, hyperintense on T1 images, or both, in 71% (85/120), compared with 19% (23/120) of lung carcinoma metastases (P < .01). Melanoma lesions were 16 times more likely than lung cancer lesions to show combined T2* related signal intensity loss and T1 hyperintensity (P < .01). Remarkably, 8 melanoma lesions (7%) in 3 patients were detectable principally on the T2*-weighted sequences, whereas no lung cancer lesion was detected solely on susceptibility images. We found a direct correlation between melanin content and T1 hyperintensity but no correlation between T2* intensity and melanin. CONCLUSION: T2*-weighted images improve lesion detection in patients with melanoma metastases, and in conjunction with T1-weighted sequences, can suggest melanoma as the etiology of an intracranial mass. This sequence should be employed for evaluation of possible brain metastasis in patients without a known primary malignancy and in studies for melanoma staging. C1 Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stephen E & Cahterine Pappas Ctr Neuro Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuropathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Div Neuroradiol, Yawkey 9E,Fruit St, Boston, MA 02114 USA. NR 9 TC 30 Z9 35 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 2006 VL 27 IS 3 BP 605 EP 608 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 028SF UT WOS:000236508400030 PM 16552002 ER PT J AU Houldin, A Curtiss, CP Haylock, PJ AF Houldin, A Curtiss, CP Haylock, PJ TI Executive summary: The state of the science on nursing approaches to managing late and long-term sequelae of cancer and cancer treatment SO AMERICAN JOURNAL OF NURSING LA English DT Article ID SURVIVORSHIP; TRENDS; NATION C1 Univ Penn, Adult Oncol Nurse Practitioner Program, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Palliat Care Serv, Philadelphia, PA USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. RP Houldin, A (reprint author), Univ Penn, Adult Oncol Nurse Practitioner Program, Philadelphia, PA 19104 USA. EM houldin@nursing.upenn.edu; carol.curtiss@verizon.net; pjhaylock@indian-creek.net NR 13 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD MAR PY 2006 VL 106 IS 3 BP 54 EP 59 PG 6 WC Nursing SC Nursing GA 016JI UT WOS:000235616100027 PM 16534393 ER PT J AU Tocyap, ML Azar, N Chen, T Wiggs, J AF Tocyap, ML Azar, N Chen, T Wiggs, J TI Clinical and molecular characterization of a patient with an interstitial deletion of chromosome 12q15-q23 and peripheral corneal abnormalities SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PLANA; KERATOCAN; REGION AB PURPOSE: To describe the ocular features of a patient with an interstitial deletion of chromosome 12 and to determine the molecular boundaries of the deletion. DESIGN: Observational case report and laboratory investigation. METHODS: A patient with an interstitial deletion of chromosome 12 was clinically examined for ocular abnormalities. DNA samples were used for molecular studies to define the deletion boundaries. RESULTS: Ocular examination showed abnormalities of the anterior segment consistent with a diagnosis of cornea plana. Molecular analyses showed the deletion included the KERA gene, the SLRP (small leucine repeat protein) gene cluster, the genetic loci for autosomal-dominant (CNA1) and autosomal,recessive (CNA2) cornea Plana, and a portion of the mapped locus for high myopia (MYP3). CONCLUSIONS: These results, combined with previous genetic linkage studies, identifies a 3-cM region located between microsatellite markers D12S82 and D12S351 that is likely to contain a gene responsible for CNA1. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Wiggs, J (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu FU NEI NIH HHS [P30 EY 14104, R01 EY 09847] NR 8 TC 5 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2006 VL 141 IS 3 BP 566 EP 567 DI 10.1016/j.ajo.2005.09.024 PG 2 WC Ophthalmology SC Ophthalmology GA 022LS UT WOS:000236057900024 PM 16490510 ER PT J AU Kim, WK Alvarez, X Fisher, J Bronfin, B Westmoreland, S McLaurin, J Williams, K AF Kim, WK Alvarez, X Fisher, J Bronfin, B Westmoreland, S McLaurin, J Williams, K TI CD163 identifies perivascular macrophages in normal and viral encephalitic brains and potential precursors to perivascular macrophages in blood SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; SIMIAN IMMUNODEFICIENCY VIRUS; SCAVENGER RECEPTOR CD163; NUCLEAR ANTIGEN-EXPRESSION; MARROW-DERIVED ELEMENTS; MICROGLIAL CELLS; MONOCLONAL-ANTIBODY; HUMAN MONOCYTES; MOUSE-BRAIN; RAT-BRAIN AB Perivascular macrophages are uniquely situated at the intersection between the nervous and immune systems. Although combined myeloid marker detection differentiates perivascular from resident brain macrophages (parenchymal microglia), no single marker distinguishes perivascular macrophages in humans and mice. Here, we present the macrophage scavenger receptor CD163 as a marker for perivascular macrophages; in humans, monkeys, and mice. CD163 was primarily confined to perivascular macrophages and populations of meningeal and choroid plexus macrophages in normal brains and in brains of humans and monkeys with human immunodeficiency virus or simian immunodeficiency virus (SIV) encephalitis. Scattered microglia in SIV encephalitis lesions and multinucleated giant cells were also CD163 positive. Consistent with prior findings that perivascular macrophages are primary targets of human immunodeficiency virus and SIV, all SIN-infected cells in the brain were CD163 positive. Using fluorescent dyes that definitively and selectively label perivascular macrophages in vivo, we confirmed that dye-labeled simian perivascular macrophages were CD163 positive and able to repopulate the central nervous system within 24 hours. Flow cytometric studies demonstrated a subset of monocytes (CD163(+)CD14(+)CD16(+)) that were immunophenotypically similar to brain perivascular macrophages. These findings recognize CD163(+) blood monocytes/macrophages as a source of brain perivascular macrophages and underscore the utility of this molecule in studying the biology of perivascular macrophages and their precursors in humans, monkeys, and mice. C1 Harvard Univ, Div Viral Pathogenesis, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Tulane Univ, Div Comparat Pathol, Tulane Natl Primate Res Ctr, Covington, LA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. RP Williams, K (reprint author), Harvard Univ, Div Viral Pathogenesis, Sch Med, Beth Israel Deaconess Med Ctr, 330 Brookline Ave,RE 113, Boston, MA 02215 USA. EM Kenneth_Williams@jhms.harvard.edu FU NCRR NIH HHS [P51 RR000164, RR00150, K01 RR000150, RR00164]; NIMH NIH HHS [R24 MH059724]; NINDS NIH HHS [NS37654, R01 NS037654, R01 NS040237, NS40237]; PHS HHS [CIHR37857] NR 80 TC 103 Z9 103 U1 0 U2 7 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAR PY 2006 VL 168 IS 3 BP 822 EP 834 DI 10.2353/ajpath.2006.050215 PG 13 WC Pathology SC Pathology GA 017UV UT WOS:000235719700013 PM 16507898 ER PT J AU O'Donnell, JM Zampino, M Alpert, NM Fasano, MJ Geenen, DL Lewandowski, ED AF O'Donnell, JM Zampino, M Alpert, NM Fasano, MJ Geenen, DL Lewandowski, ED TI Accelerated triacylglycerol turnover kinetics in hearts of diabetic rats include evidence for compartmented lipid storage SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE metabolism; nuclear magnetic resonance; palmitate; triglyceride; fatty acids ID ISOLATED WORKING HEARTS; FATTY-ACID OXIDATION; SUBSTRATE UTILIZATION; CARDIAC DYSFUNCTION; METABOLISM; CARDIOMYOPATHY; MITOCHONDRIAL; TRIGLYCERIDE; ACCUMULATION; TRANSPORT AB Triacylglycerol (TAG) storage and turnover rates in the intact, beating rat heart were determined for the first time using dynamic mode C-13-NMR spectroscopy to elucidate profound differences between hearts from diabetic rats (DR, streptozotocin treatment) and normal rats (NR). The incorporation of [2,4,6,8,10,12,14,16-C-13(8)] palmitate into the TAG pool was monitored in isolated hearts perfused with physiological (0.5 mM palmitate, 5 mM glucose) and elevated substrate levels (1.2 mM palmitate, 11 mM glucose) characteristic of the diabetic condition. Surprisingly, although the normal hearts were enriched at a near-linear profile for >= 2 h before exponential characterization, exponential enrichment of TAG in diabetic hearts reached steady state after only 45 min. Consequently, TAG turnover rate was determined by fitting an exponential model to enrichment data rather than conventional two-point linear analysis. In the high-substrate group, both turnover rate (DR 820 +/- 330, NR 190 +/- 150 nmol (.) min(-1.)g(-1) dry wt; P < 0.001) and [TAG] content (DR 78 +/- 10, NR 32 +/- 4 mu mol/g dry wt; P < 0.001) were greater in the diabetic group. At lower substrate concentrations, turnover was greater in diabetics (DR 530 +/- 300, NR 160 +/- 30; P < 0.05). However, this could not be explained by simple mass action, because [ TAG] content was similar between groups [DR 34 +/- 7, NR 39 +/- 9 mu mol/g dry wt; not significant (NS)]. Consistent with exponential enrichment data, C-13 fractional enrichment of TAG was lower in diabetics (low-substrate groups: DR 4 +/- 1%, NR 10 +/- 4%, P < 0.05; high-substrate groups: DR 8 +/- 3%, NR 14 +/- 9%, NS), thereby supporting earlier speculation that TAG is compartmentalized in the diabetic heart. C1 Univ Illinois, Dept Physiol & Biophys, Program Integrat Cardiac Metab, Chicago, IL 60612 USA. Univ Illinois, Coll Med, Ctr Cardiovasc Res, Chicago, IL 60612 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Lewandowski, ED (reprint author), Univ Illinois, Dept Physiol & Biophys, Program Integrat Cardiac Metab, 835 S Wolcott Ave, Chicago, IL 60612 USA. EM dougl@uic.edu FU NHLBI NIH HHS [R01-HL-62702, R37-HL-49244] NR 42 TC 33 Z9 33 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAR PY 2006 VL 290 IS 3 BP E448 EP E455 DI 10.1152/ajpendo.00139.2005 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 010QU UT WOS:000235210000007 PM 16234271 ER PT J AU Czimmer, J Million, M Tache, Y AF Czimmer, J Million, M Tache, Y TI Urocortin 2 acts centrally to delay gastric emptying through sympathetic pathways while CRF and urocortin 1 inhibitory actions are vagal dependent in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE adrenergic receptors; vagus; corticotropin; releasing hormone receptor ID CORTICOTROPIN-RELEASING-FACTOR; DORSAL RAPHE NUCLEUS; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; C-FOS EXPRESSION; PERIPHERAL UROCORTIN; FACTOR-RECEPTOR; CONSCIOUS RATS; STRESS; BRAIN; TRANSIT AB Urocortin 2 acts centrally to delay gastric emptying through sympathetic pathways while CRF and urocortin 1 inhibitory actions are vagal dependent in rats. Am J Physiol Gastrointest Liver Physiol 290: G511-G518, 2006. First published Octobert 13, 2005; doi: 10.1152/ajpgi.00289.2005.-We characterized the influence of the selective corticotropin-releasing factor 2 (CRF2) receptor agonist human urocortin 2 (Ucn 2), injected intracisternally, on gastric emptying and its mechanism of action compared with intracisternal CRF or urocortin (Ucn 1) in conscious rats. The methylcellulose phenol red solution was gavaged 20 min after peptide injection, and gastric emptying was measured 20 min later. The intracisternal injection of Ucn 2 (0.1 and 1 mu g) and Ucn 1 (1 mu g) decreased gastric emptying to 37.8 +/- 6.9%, 23.1 +/- 8.6%, and 21.6 +/- 5.9%, respectively, compared with 58.4 +/- 3.8% after intracisternal vehicle. At lower doses, Ucn 2 (0.03 mu g) and Ucn 1 (0.1 mu g) had no effect. The CRF2 antagonist astressin(2)-B (3 mu g ic) antagonized intracisternal Ucn 2 (0.1 mu g) and CRF (0.3 mu g)-induced inhibition of gastric emptying. Vagotomy enhanced intracisternal Ucn 2 (0.1 or 1 mu g)-induced inhibition of gastric emptying compared with sham-operated group, whereas it blocked intracisternal CRF (1 mu g) inhibitory action (45.5 +/- 8.4% vs. 9.7 +/- 9.7%). Sympathetic blockade by bretylium prevented intracisternal and intracerebroventricular Ucn 2-induced delayed gastric emptying, whereas it did not influence intravenous Ucn 2-, intracisternal CRF-, and intracisternal Ucn 1-induced inhibition of gastric emptying. Prazosin abolished the intracisternal Ucn 2 inhibitory effect, whereas yohimbine and propranolol did not. None of the pretreatments modified basal gastric emptying. These data indicate that intracisternal Ucn 2 induced a central CRF2-mediated inhibition of gastric emptying involving sympathetic alpha(1)-adrenergic mechanisms independent from the vagus contrasting with the vagal-dependent inhibitory actions of CRF and Ucn 1. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CURE, Digest Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, Div Digest Dis, Dept Med, Los Angeles, CA USA. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, CURE CNS Bldg 115,Rm 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU NIDDK NIH HHS [DK-41301, R01 DK-33061] NR 50 TC 39 Z9 40 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAR PY 2006 VL 290 IS 3 BP G511 EP G518 DI 10.1152/ajpgi.00289.2005 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 011NP UT WOS:000235275500012 PM 16223946 ER PT J AU Kim, NH Rincon-Choles, H Bhandari, B Choudhury, GG Abboud, HE Gorin, Y AF Kim, NH Rincon-Choles, H Bhandari, B Choudhury, GG Abboud, HE Gorin, Y TI Redox dependence of glomerular epithelial cell hypertrophy in response to glucose SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE high glucose; angiotensin II; podocytes; reactive oxygen species; protein synthesis; hypertrophy ID SMOOTH-MUSCLE-CELLS; AKT/PROTEIN KINASE-B; ACTIVATED PROTEIN-KINASE; PROXIMAL TUBULAR CELLS; II-INDUCED ACTIVATION; ANGIOTENSIN-II; DIABETIC-NEPHROPATHY; MESANGIAL CELLS; PODOCYTE INJURY; NADPH OXIDASE AB Podocytes or glomerular epithelial cells ( GECs) are important targets of the diabetic microenvironment. Podocyte foot process effacement and widening, loss of GECs and hypertrophy are pathological features of this disease. ANG II and oxidative stress are key mediators of renal hypertrophy in diabetes. The cellular mechanisms responsible for GEC hypertrophy in diabetes are incompletely characterized. We investigated the effect of high glucose on protein synthesis and GEC hypertrophy. Exposure of GECs to high glucose dose dependently stimulated [ (3)H] leucine incorporation, but not [ (3)H] yhymidine incorporation. High glucose resulted in the activation of ERK1/2 and Akt/PKB. ERK1/2 pathway inhibitor or the dominant negative mutant of Akt/PKB inhibited high glucose-induced protein synthesis. High glucose elicited a rapid generation of reactive oxygen species ( ROS). The stimulatory effect of high glucose on ROS production, ERK1/2, and Akt/PKB activation was prevented by the antioxidants catalase, diphenylene iodonium, and N-acetylcysteine. Exposure of the cells to hydrogen peroxide mimicked the effects of high glucose. In addition, ANG II resulted in the activation of ERK1/2 and Akt/PKB and GEC hypertrophy. Moreover, high glucose and ANG II exhibited additive effects on ERK1/2 and Akt/PKB activation as well as protein synthesis. These additive responses were abolished by treatment of the cells with the antioxidants. These data demonstrate that high glucose stimulates GEC hypertrophy through a ROS-dependent activation of ERK1/2 and Akt/PKB. Enhanced ROS generation accounts for the additive effects of high glucose and ANG II, suggesting that this signaling cascade contributes to GEC injury in diabetes. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. Chonnam Natl Univ, Dept Med, Kwangju, South Korea. S Texas Vet Hlth Care Syst, Audie L Murphy Mem Vet Hosp Div, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Gorin, Y (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM gorin@uthscsa.edu OI Gorin, Yves/0000-0003-4048-6925 FU NIDDK NIH HHS [DK-33665, DK-43988, DK-50190, DK-55815, P50 DK-61597] NR 54 TC 40 Z9 41 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAR PY 2006 VL 290 IS 3 BP F741 EP F751 DI 10.1152/ajprenal.00313.2005 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 009AE UT WOS:000235082700022 PM 16234311 ER PT J AU Subramanya, AR Yang, CL Zhu, XM Ellison, DH AF Subramanya, AR Yang, CL Zhu, XM Ellison, DH TI Dominant-negative regulation of WNK1 by its kidney-specific kinase-defective isoform SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE distal nephron; thiazide-sensitive sodium-chloride cotransporter; with-no-lysine kinases; aldosterone ID EPITHELIAL SODIUM-CHANNEL; NA-CL COTRANSPORTER; BLOOD-PRESSURE; HUMAN HYPERTENSION; MOLECULAR SWITCH; TRANSPORT; GENE; HYPERKALEMIA; REABSORPTION; ALDOSTERONE AB With-no-lysine kinase-1 (WNK1) gene mutations cause familial hyperkalemic hypertension (FHHt), a Mendelian disorder of excessive renal Na(+) and K(+) retention. Through its catalytic activity, full-length kinase-sufficient WNK1 (L-WNK1) suppresses its paralog, WNK4, thereby upregulating thiazide-sensitive Na-Cl cotransporter (NCC) activity. The predominant renal WNK1 isoform, KS-WNK1, expressed exclusively and at high levels in distal nephron, is a shorter kinase-defective product; the function of KS-WNK1 must therefore be kinase independent. Here, we report a novel role for KS-WNK1 as a dominant-negative regulator of L-WNK1. Na(+) transport studies in Xenopus laevis oocytes demonstrate that KS-WNK1 downregulates NCC activity indirectly, by inhibiting L-WNK1. KS-WNK1 also associates with L-WNK1 in protein complexes in oocytes and attenuates L-WNK1 kinase activity in vitro. These observations suggest that KS-WNK1 plays an essential role in the renal molecular switch regulating Na(+) and K(+) balance; they provide insight into the kidney-specific phenotype of FHHt. C1 Oregon Hlth Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Heart Res Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Ellison, DH (reprint author), Oregon Hlth Sci Univ, Dept Med, Div Nephrol & Hypertens, PP262,3314 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM ellisond@ohsu.edu OI Ellison, David/0000-0003-2915-265X FU NIDDK NIH HHS [F32 DK 72865, R01 DK 51496] NR 29 TC 69 Z9 72 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAR PY 2006 VL 290 IS 3 BP F619 EP F624 DI 10.1152/ajprenal.00280.2005 PG 6 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 009AE UT WOS:000235082700008 PM 16204408 ER PT J AU Biener, L Reimer, RL Wakefield, M Szczypka, G Rigotti, NA Connolly, G AF Biener, L Reimer, RL Wakefield, M Szczypka, G Rigotti, NA Connolly, G TI Impact of smoking cessation aids and mass media among recent quitters SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID NICOTINE REPLACEMENT THERAPY; SMOKERS QUIT; YOUTH; INTERVENTIONS; CAMPAIGN; ADVERTISEMENTS; APPRAISAL; CONTEXT AB Background: Although studies have addressed the effectiveness of conventional smoking aids such as quit-smoking programs and pharmaceutical therapy, few studies have assessed their likely impact on cessation at the population level relative to the impact of mass media anti-tobacco advertisements. Methods: A random digit dial telephone survey of 6739 Massachusetts residents conducted in 2001-2002 yielded a subsample of 787 individuals who had quit-smoking within the past 2 years. Measures included the types of cessation aids used and perceptions of their helpfulness. Rates of population impact were estimated. Multinomial logistic regression determined the preclictoys of being helped by conventional aids, by TV advertisements only, or having no help. Results: Analyses conducted in 2004-2005 showed that advertisements were the most frequently mentioned source of help among recent quitters. Older more dependent smokers were most likely to find converitional aids helpful. Younger respondents and those who had remained abstinent for more than 6 months were most likely to report being helped by TV ads. The most helpful ads were those that depicted illness due to smoking or provided inspirational quit tips. Conclusions: Anti-tobacco media campaigns are a vital component of the National Action Plan for Tobacco Cessation. It is essential that such a campaign be implemented, both to support the National Quit Line and to provide assistance to those smokers who find no other form of aid helpful. C1 Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Massachusetts Gen Hosp, Tobacco Treatment & Res Ctr, Boston, MA USA. Canc Council Victoria, Melbourne, Vic, Australia. Univ Illinois, Inst Hlth Res & Policy, Chicago, IL USA. Harvard Sch Publ Hlth, Cambridge, MA USA. RP Biener, L (reprint author), Univ Massachusetts, Survey Res Ctr, 100 Morrissey Blvd, Boston, MA 02125 USA. EM lois.biener@umb.edu RI Wakefield, Melanie/E-5019-2012; OI Biener, Lois/0000-0002-4130-8138 FU NCI NIH HHS [CA 86257, R01 CA86273-01] NR 35 TC 47 Z9 47 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAR PY 2006 VL 30 IS 3 BP 217 EP 224 DI 10.1016/j.amepre.2005.10.026 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 016YN UT WOS:000235660700005 PM 16476637 ER PT J AU Spencer, TJ Biederman, J Ciccone, PE Madras, BK Dougherty, DD Bonab, AA Livni, E Parasrampuria, DA Fischman, AJ AF Spencer, TJ Biederman, J Ciccone, PE Madras, BK Dougherty, DD Bonab, AA Livni, E Parasrampuria, DA Fischman, AJ TI PET study examining pharmacokinetics, detection and likeability, and dopamine transporter receptor occupancy of short- and long-acting oral methylphenidate SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 12-16, 2004 CL San Juan, PR SP Vanderbilt Univ, Sch Med, Dept Psychiaty, Amer Coll Neuropsychopharmacol ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; POSITRON-EMISSION-TOMOGRAPHY; ONCE-A-DAY; COCAINE; DRUG; RELEASE; TRIAL AB Objective: The abuse potential of methylphenidate has been related to the drug's capacity to produce a rapid onset of blockade of the presynaptic dopamine transporter in the brain. An oral once-a-day osmotic controlled-release formulation of methylphenidate produces a more gradual rise in plasma methylphenidate concentration, compared with immediate-release methylphenidate. The authors hypothesized that osmotic-release methylphenidate would also produce a slower onset of blockade of the presynaptic dopamine transporter and would be associated with a lower risk for detection and likeability, compared to immediate-release methylphenidate. Method: Twelve healthy adults were randomly assigned to receive single doses of immediate-release methylphenidate or osmotic-release methylphenidate. Doses predicted to produce equivalent maximum concentration (C-max) values were selected (40 mg of immediate-release methylphenidate and 90 mg of osmotic-release methylphenidate). Plasma d-methylphenidate levels and responses to detection/likeability questionnaire items were obtained hourly for 10 hours after administration of methylphenidate on two separate occasions for each subject. Dopamine transporter receptor occupancies were measured at hours 1, 3, 5, and 7 by using a carbon-11-labeled imaging agent (Altropane) and positron emission tomography. Results: Despite similar C-max values for both formulations, osmotic-release methylphenidate was associated with a longer time to maximum concentration, longer time to maximum CNS dopamine transporter occupancy, and no detection/likeability, compared with immediate-release methylphenidate. Conclusions: The findings suggest that the abuse potential of oral methylphenidate is strongly influenced by the rate of delivery and not solely by the magnitude of plasma concentration or brain transporter occupancy. These results advance understanding of the underlying central effects of methylphenidate in humans and identify a potentially less abusable methylphenidate formulation. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. McNeil Consumer & Specialty Pharmaceut, Ft Washington, MD USA. New England Reg Primate Res Ctr, Div Neurochem, Boston, MA USA. Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Psychiat Serv, ACC-725,YAW 6900,55 Fruit St, Boston, MA 02114 USA. EM spencer@helix.mgh.harvard.edu FU NIMH NIH HHS [R01 MH-064019] NR 28 TC 122 Z9 124 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2006 VL 163 IS 3 BP 387 EP 395 DI 10.1176/appi.ajp.163.3.387 PG 9 WC Psychiatry SC Psychiatry GA 017XG UT WOS:000235726000010 PM 16513858 ER PT J AU Bowie, CR Reichenberg, A Patterson, TL Heaton, RK Harvey, PD AF Bowie, CR Reichenberg, A Patterson, TL Heaton, RK Harvey, PD TI Determinants of real-world functional performance in schizophrenia subjects: Correlations with cognition, functional capacity, and symptoms SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 12-16, 2004 CL San Juan, PR SP Vanderbilt Univ, Sch Med, Dept Psychiaty, Amer Coll Neuropsychopharmacol ID NEUROCOGNITIVE DEFICITS; MENTALLY-ILL; DISABILITY; MATRICS; TARGETS; SUPPORT; DISEASE; SKILLS; SCALE AB Objective: Impairments in adaptive life skills are a major source of disability in patients with schizophrenia. The relationship between adaptive life skills in realworld settings and performance on neuropsychological tests may be complicated by other factors that interfere with deployment of skills. Assessment of the ability to perform life skills under optimal conditions (i.e., assessment of functional capacity) has been proposed as a means to clarify these relationships. Method: The authors examined cross-sectional data from a study of the course of neuropsychological and adaptive life skills of older (age 50-85) schizophrenia patients (N=78). Functional capacity was examined with a performance-based measure (UCSD Performance-Based Skills Assessment), and case managers rated realworld adaptive functions ( i.e., interpersonal skills, work skills, and community activities). Neuropsychological performance was assessed with a comprehensive battery, while symptoms were assessed with patient self-report and clinical ratings. Results: Confirmatory path analyses were used to evaluate the effects of neuropsychological performance, functional capacity, and symptoms on the various domains of real-world functioning. Neuropsychological performance predicted functional capacity, which predicted all three domains of real-world functioning. Depression predicted interpersonal and work skills, while negative symptoms affected interpersonal skills independently of other predictors. Conclusions: Real-world adaptive life skills are predicted by neuropsychological performance, symptoms, and functional capacity. Neuropsychological performance contributes little to the prediction of real-world performance after accounting for functional capacity. In some domains, negative and depressive symptoms influenced real-world performance while not relating to functional capacity or neuropsychological performance. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. Univ Calif San Diego, Med Ctr, Dept Psychiat, San Diego, CA 92103 USA. RP Bowie, CR (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1425 Madison Ave,4th Floor,Box 1230, New York, NY 10029 USA. EM christopher.bowie@mssm.edu FU NIMH NIH HHS [MH-36692, MH-63116] NR 37 TC 312 Z9 323 U1 2 U2 21 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2006 VL 163 IS 3 BP 418 EP 425 DI 10.1176/appi.ajp.163.3.418 PG 8 WC Psychiatry SC Psychiatry GA 017XG UT WOS:000235726000014 PM 16513862 ER PT J AU Sergi, MJ Rassovsky, Y Nuechterlein, KH Green, MF AF Sergi, MJ Rassovsky, Y Nuechterlein, KH Green, MF TI Social perception as a mediator of the influence of early visual processing on functional status in schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT International-Congress-on-Schizophrenia-Research CY APR 03, 2005 CL Savannah, GA SP Int Congress Schizophrenia Res ID NEUROCOGNITIVE DEFICITS; AFFECT RECOGNITION; COGNITION; EMOTION; DISORDER; BEHAVIOR; MASKING; SCALE; MIND AB Objective: The potential of social cognition as a mediator of relations between neurocognition and functional status in schizophrenia has been suggested by correlational studies that link neurocognition to social cognition or link social cognition to functional status. The authors used structural equation modeling to test more directly whether one aspect of social cognition (social perception) mediates relations between basic visual perception and functional status in patients with schizophrenia. Method: Seventy-five outpatients with schizophrenia were administered measures of early visual processing (computerized visual masking procedures), social perception (Half Profile of Nonverbal Sensitivity), and functional status (Role Functioning Scale). Results: Structural equation modeling supported social perception as a mediator of relations between early visual processing and functional status in schizophrenia. The mediation model indicated that early visual processing is linked to functional status through social perception, thereby supporting a significant indirect relationship. The direct relationship between early visual processing and functional status was significant in a model that did not include social perception but was not significant in the mediation model that included social perception. Conclusions: Social cognition appears to be a key determinant of functional status in schizophrenia. Using a very basic measure of visual perception, the present study found that social perception mediates the influence of early visual processing on functional status in schizophrenia. C1 Calif State Univ Northridge, Dept Psychol, Northridge, CA 91330 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Sergi, MJ (reprint author), Calif State Univ Northridge, Dept Psychol, 18111 Nordhoff St, Northridge, CA 91330 USA. EM mark.sergi@csun.edu FU NIMH NIH HHS [MH-43292, MH-65707] NR 43 TC 163 Z9 167 U1 1 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2006 VL 163 IS 3 BP 448 EP 454 DI 10.1176/appi.ajp.163.3.448 PG 7 WC Psychiatry SC Psychiatry GA 017XG UT WOS:000235726000018 PM 16513866 ER PT J AU Onitsuka, T Niznikiewicz, MA Spencer, KM Frumin, M Kuroki, N Lucia, LC Shenton, ME McCarley, RW AF Onitsuka, T Niznikiewicz, MA Spencer, KM Frumin, M Kuroki, N Lucia, LC Shenton, ME McCarley, RW TI Functional and structural deficits in brain regions subserving face perception in schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID GYRUS VOLUME; RECOGNITION; EXPERTISE; OBJECTS; AREA; REDUCTION; CORTEX AB Objective: Schizophrenia impairs many cognitive functions, including face perception. Veridical face perception is critical for social interaction, including distinguishing friend from foe and familiar from unfamiliar faces. The main aim of this study was to determine whether patients with schizophrenia show less activation in neural networks related to face processing, compared with healthy subjects, and to investigate the relationships between this functional abnormality and anatomical abnormalities in the fusiform gyrus shown with magnetic resonance imaging (MRI). Method: Twenty male chronic schizophrenia patients and 16 healthy comparison subjects matched with the patients for age, gender, handedness, and parental socioeconomic status underwent high-spatial-resolution MRI. Event-related potentials elicited by images of faces, cars, and hands were recorded in a separate session. Results: Compared to the healthy subjects, the patients with schizophrenia showed bilateral N170 amplitude reduction in response to images of faces but not to images of other objects. The patients also had smaller bilateral anterior and posterior fusiform gyrus gray matter volumes, compared to the healthy subjects. In addition, right posterior fusiform gyrus volume was significantly correlated with N170 amplitude measured at the right posterior temporal electrode site in response to images of faces in the schizophrenia patients but not in the healthy comparison subjects. Conclusions: The results provide evidence for deficits in the early stages of face perception in schizophrenia. The association of these deficits with smaller fusiform gyrus volume in patients with schizophrenia, relative to healthy subjects, suggests that the fusiform gyrus is the site of a defective anatomical substrate for face processing in schizophrenia. C1 Harvard Univ, Sch Med,Lab Neurosci,Div Clin Neurosci, VA Boston Healthcare Syst, Brockton Div,Dept Psychiat 116A, Brockton, MA 02301 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Kyushu Univ, Grad Sch Med Sci, Dept Neuropsychiat, Fukuoka 812, Japan. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol,Surg Planning Lab,MRI Div, Boston, MA 02115 USA. RP McCarley, RW (reprint author), Harvard Univ, Sch Med,Lab Neurosci,Div Clin Neurosci, VA Boston Healthcare Syst, Brockton Div,Dept Psychiat 116A, 940 Belmont St, Brockton, MA 02301 USA. EM robert_mccarley@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NIMH NIH HHS [R01 MH040799, K02 MH-01110, K02 MH001110, K02 MH001110-10, R01 MH-40799, R01 MH-50747] NR 29 TC 63 Z9 66 U1 1 U2 12 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2006 VL 163 IS 3 BP 455 EP 462 DI 10.1176/appi.ajp.163.3.455 PG 8 WC Psychiatry SC Psychiatry GA 017XG UT WOS:000235726000019 PM 16513867 ER PT J AU Walder, DJ Seidman, LJ Cullen, N Su, J Tsuang, MT Goldstein, JM AF Walder, DJ Seidman, LJ Cullen, N Su, J Tsuang, MT Goldstein, JM TI Sex differences in language dysfunction in schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SUPERIOR TEMPORAL GYRUS; ADULT HUMAN BRAIN; GENDER-DIFFERENCES; PLANUM TEMPORALE; THOUGHT-DISORDER; NEUROPSYCHOLOGICAL PERFORMANCE; 1ST-EPISODE SCHIZOPHRENIA; SEMANTIC FLUENCY; VOLUME REDUCTION; MRI AB Objective: Normal sex differences in language functions are disrupted in schizophrenia. However, identification of specific language components most vulnerable in schizophrenia and how they may differ by sex remain unexamined. The current study investigated this issue in the domains of phonology, semantics, and grammar, which have been closely linked with neuroanatomic regions for which sex differences have been identified. Method: Thirty-one outpatients with DSM-III-R schizophrenia and 27 healthy subjects comparable within sex on age, handedness, parental socioeconomic status, and ethnicity were systematically ascertained from a Boston catchment area. The subjects were administered an extensive language battery in the context of a comprehensive neuropsychological battery that included measures of phonology, semantics, and grammar. Results: Male patients performed significantly worse than their healthy counterparts on all three domains, with phonology least affected. In contrast, language function was relatively preserved in the female patients, compared to their healthy counterparts, with phonology most affected. Across domains, the effect sizes in comparisons of male patients and healthy male subjects had a twofold difference, whereas the difference in effect sizes in comparisons of female patients and healthy female subjects was less in all areas. Conclusions: Findings were consistent with prior evidence of overall language dysfunction in schizophrenia and may have implications for understanding sex differences in neuroanatomic abnormalities in regions associated with phonological processing. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med,Connors Ctr Womens Hlth & Gender, Div Womens Hlth, Boston, MA 02120 USA. Harvard Univ, Brigham & Womens Hosp, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Dept Psychait,Beth Israel Deaconess Med Ctr, Boston, MA 02120 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Div Psychiat Neurosci, Boston, MA 02120 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Boston, MA 02115 USA. MIT, Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Inst Psychiat Epidemiol & Genet, Dept Epidemiol, Boston, MA 02120 USA. Univ Calif San Diego, Dept Psychiat, Inst Behav Genom, La Jolla, CA 92093 USA. RP Goldstein, JM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med,Connors Ctr Womens Hlth & Gender, Div Womens Hlth, 1 Brigham Circle,3rd Floor,1620 Tremont St, Boston, MA 02120 USA. EM jill_goldstein@hms.harvard.edu FU NIMH NIH HHS [K21 MH-00096, T32 MH-16259, R01 MH-56956] NR 82 TC 25 Z9 28 U1 2 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2006 VL 163 IS 3 BP 470 EP 477 DI 10.1176/appi.ajp.163.3.470 PG 8 WC Psychiatry SC Psychiatry GA 017XG UT WOS:000235726000021 PM 16513869 ER PT J AU Rizzo, S Kalra, M Schmidt, B Dalal, T Suess, C Flohr, T Blake, M Saini, S AF Rizzo, S Kalra, M Schmidt, B Dalal, T Suess, C Flohr, T Blake, M Saini, S TI Comparison of angular and combined automatic tube current modulation techniques with constant tube current CT of the abdomen and pelvis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE abdomen; CT technique; pelvis; radiation dose; tube current modulation ID DOSE REDUCTION; COMPUTED-TOMOGRAPHY; OPTIMIZATION AB OBJECTIVE. The objective of our study was to compare image quality and radiation dose associated with abdominopelvic CT using combined modulation, angular modulation, and constant tube current. CONCLUSION. Compared with using a constant tube current to scan the abdomen and pelvis, the use of a combined modulation technique results in a substantial reduction (42-44%) in radiation dose with acceptable image noise and diagnostic acceptability. C1 Emory Univ Hosp, Dept Radiol, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Siemens Med Solut, Forchheim, Germany. RP Kalra, M (reprint author), Emory Univ Hosp, Dept Radiol, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. EM mkalra@emory.edu NR 11 TC 110 Z9 124 U1 0 U2 6 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2006 VL 186 IS 3 BP 673 EP 679 DI 10.2214/AJR.04.1513 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 016JN UT WOS:000235616600013 PM 16498094 ER PT J AU Kiyokawa, T Young, RH Scully, RE AF Kiyokawa, T Young, RH Scully, RE TI Krukenberg tumors of the ovary - A clinicopathologic analysis of 120 cases with emphasis on their variable pathologic manifestations SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Review DE ovary; neoplasm; Krukenberg tumor ID RING CELL-CARCINOMA; METASTATIC TUMORS; GASTRIC-CARCINOMA; URINARY-BLADDER; PELVIC MASS; STOMACH; COLON; PREGNANCY; RECTUM; YOUNG AB 120 Krukenberg tumors were analyzed with emphasis on their wide microscopic spectrum and resultant problems in differential diagnosis. The patients ranged from 13 to 84 years (average, 45 years) with 43% of them under 40 years. Abdominal swelling or pain usually accounted for the clinical presentation, but 17 had abnormal vaginal bleeding, 4 had virilization, and 4 had hirsutism without virilization. Ascites was present in 43% of the cases. Sixty-three percent of the tumors were documented to be bilateral, but both ovaries were not always removed or rigorously examined microscopically. The mean diameter of the tumors was 10.4cm, and they typically had intact, bosselated external surfaces without adhesions. The sectioned surfaces were typically solid and firm to edematous to gelatinous; one third of the tumors also had cysts. Microscopic examination showed great variation from case to case and within individual neoplasms. Multiple nodules separated by normal stroma were seen in small neoplasms and focally in many larger ones. The tumors were often more cellular at their periphery and edematous to gelatinous centrally. An irregular distribution of cellular and less cellular areas often imparted a pseudolobular pattern. The cellularity of the stroma ranged from densely cellular to paucicellular; the latter regions ranged from edematous to mucoid. The overall morphology varied according to the prominence of signet-ring cells, extracellular mucin, edema, and various epithelial patterns. Signet-ring cells were numerous in most neoplasms (and by definition occupied at least 10% of the neoplasm) but were often absent or inconspicuous in significant areas of them. The signet-ring cells typically had modest but sometimes copious amounts of pale to basophilic cytoplasm; occasionally, it was eosinophilic. The signet-ring cells varied widely in their arrangement, growing singly, in clusters, forming confluent masses or pseudotubular arrays or lining part of all of a true tubule. Small glands and tubules were common, often resembling microcysts (when the lining cells were flattened) or Sertoli tubules; mucinous glands and cysts and medium-sized to large intestinal-type glands were also relatively common, particularly the latter. Extracellular mucin was often conspicuous and, when associated with scant acellular collagenous stroma, gave a distinctive appearance referred to by us as "feathery degeneration." Stromal luteinization was present in the tumors of the 8 pregnant patients and was seen in 14% of the nonpregnant patients. Unusual features that complicated the microscopic picture included diffuse sheets or other arrangements of mucin-free indifferent cells, squamous cells, clear cells, transitional cells, and corded, trabecular, and insular patterns. Vascular space invasion was common. Two thirds of the primary carcinomas were detected synchronously with, or subsequent to, detection of the Krukenberg tumor compounding the diagnostic difficulty posed by the cases. Two thirds of the primary tumors were in the stomach; other primary sites in order of frequency were appendix, colon, breast, small intestine, rectum, gallbladder, and urinary bladder. Our observations emphasize that the microscopic spectrum of the Krukenberg tumor is broader that often presented in the literature, in particular tubules, glands, and cysts often being present, and the wide pathologic differential diagnosis is discussed. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Young, RH (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. NR 110 TC 89 Z9 100 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2006 VL 30 IS 3 BP 277 EP 299 PG 23 WC Pathology; Surgery SC Pathology; Surgery GA 021DW UT WOS:000235964900001 PM 16538048 ER PT J AU de Leval, L Waltregny, D Boniver, J Young, RH Castronovo, V Oliva, E AF de Leval, L Waltregny, D Boniver, J Young, RH Castronovo, V Oliva, E TI Use of histone deacetylase 8 (HDAC8), a new marker of smooth muscle differentiation, in the classification of mesenchymal tumors of the uterus SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE histone deacetylase; HDAC8; uterus; smooth muscle tumors; endometrial stromal tumors; immunohistochemistry ID ENDOMETRIAL STROMAL SARCOMA; NORMAL HUMAN-TISSUES; H-CALDESMON; IMMUNOHISTOCHEMICAL DISTINCTION; CELLULAR LEIOMYOMA; BREAST-LESIONS; EXPRESSION; P53; CD10; ACTIN AB Uterine smooth muscle tumors (SMTs) are usually recognized on the basis of their routine morphologic features; however, their distinction from endometrial stromal tumors (ESTs), the second most common mesenchymal tumor of the uterus, is sometimes problematic. Histone deacetylases (HDACs) were originally identified as nuclear enzymes regulating histone acetylation. We have recently shown that in normal human tissues, HDAC8 is exclusively expressed in the cytoplasm of cells showing smooth muscle differentiation. In this study, we examined HDAC8 expression in SMTs and ESTs of the uterus to determine whether HDAC8 may be a useful diagnostic tool in the classification of problematic uterine mesenchymal tumors. HDAC8 immunohistochemical staining was performed in 15 leiomyomas (LMs), 9 highly cellular leiomyomas (HCLs), 8 epithelioid SMTs, 13 leiomyosarcomas (LMSs), and 17 ESTs, including 3 with sex-cord differentiation and 5 with smooth muscle differentiation. All tumors were also stained for other smooth muscle markers (desmin, h-caldesmon, smooth muscle actin [SMA], smooth muscle myosin heavy chain) and for CD 10. All LMs had moderate to strong expression of all smooth muscle markers. HDAC8 was detected in 8 of 9 HCLs and in all epithelioid SMTs (8 of 8); however, it was weak in 4 epithelioid SMTs. In contrast, desmin, h-caldesmon and smooth muscle myosin were positive in only 2 of 8, 1 of 8 and 4 of 8 epithelioid SMTs, respectively. All smooth muscle markers had similar frequency of staining in LMSs; however, HDAC8 showed overall moderate intensity compared with other smooth muscle markers, which showed stronger staining. HDAC8, h-caldesmon, and smooth muscle myosin did not stain conventional areas of ESTs or ESTs with sex-cord differentiation, whereas SMA and desmin were positive in those areas in 4 of 12 and 3 of 12 ESTs, respectively. Areas of smooth muscle differentiation in ESTs were positive for HDAC8 in all cases, but they were less constantly positive for the other smooth muscle markers. CD10 was expressed in most ESTs (14 of 17), but it was also positive in 15 of 45 SMTs. In conclusion: 1) HDAC8 seems to be a specific marker of SM differentiation because conventional ESTs and ESTs with sex-cord differentiation are negative for HDAC8, whereas areas of smooth muscle differentiation in these tumors are consistently positive; 2) HDAC8 gives similar results to those obtained with desmin, h-caldesmon, and smooth muscle myosin in both LMs and LMSs, although the staining for HDAC8 in LMSs tends to be less intense; 3) HDAC8 may be a more sensitive marker than desmin and h-caldesmon in epithelioid SMTs. Thus, HDAC8 detection may be useful in helping the differential diagnosis of uterine mesenchymal tumors. C1 Univ Liege, Dept Pathol, Liege, Belgium. Univ Liege, Metastasis Res Lab, Ctr Expt Canc Res, Liege, Belgium. Harvard Univ, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Sch Med, Boston, MA USA. RP de Leval, L (reprint author), CHU Sart Tilman, Dept Pathol, Pathol Bldg,Bat 23,Level plus-1, B-4000 Liege, Belgium. EM L.deLeval@ulg.ac.be NR 35 TC 29 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2006 VL 30 IS 3 BP 319 EP 327 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 021DW UT WOS:000235964900004 PM 16538051 ER PT J AU Colvina, RB AF Colvina, RB TI C4d in liver allografts: A sign of antibody-mediated rejection? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material ID PLASMA-CELLS; HEPATITIS-C C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Colvina, RB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. EM colvin@helix.mgh.harvard.edu NR 10 TC 21 Z9 21 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2006 VL 6 IS 3 BP 447 EP 448 DI 10.1111/j.1600-6143.2006.01245.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 010UU UT WOS:000235224200002 PM 16468952 ER PT J AU Fossey, MD Otto, MW Yates, WR Wisniewski, SR Gyulai, L Allen, MH Miklowitz, DJ Coon, KA Ostacher, MJ Neel, JL Thase, ME Sachs, GS Weiss, RD AF Fossey, MD Otto, MW Yates, WR Wisniewski, SR Gyulai, L Allen, MH Miklowitz, DJ Coon, KA Ostacher, MJ Neel, JL Thase, ME Sachs, GS Weiss, RD CA STEP-BD Investigators TI Validity of the distinction between primary and secondary substance use disorder in patients with bipolar disorder: Data from the first 1000 STEP-BD participants SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID TREATMENT ENHANCEMENT PROGRAM; MENTAL-DISORDERS; ABUSE; ILLNESS; ALCOHOL; DEPENDENCE; IMPACT; ONSET AB The validity of a primary/secondary substance use disorder ( SUD) distinction was evaluated in the first 1000 patients enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder. Patients with primary SUD (n = 116) were compared with those with secondary SUD (n = 275) on clinical course variables. Patients with secondary SUD had fewer days of euthymia, more episodes of mania and depression, and a greater history of suicide attempts. These findings were fully explained by variations in age of onset of bipolar disorder. The order of onset of SUDs was not linked to bipolar outcomes when age of onset of bipolar disorder was statistically controlled. The primary/secondary distinction for SUD is not valid when variations in the age of onset of the non-SUD are linked to course characteristics. C1 Univ Oklahoma, Coll Med, Dept Psychiat, Tulsa, OK 74135 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. Univ Penn, Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Oklahoma State Univ, Coll Osteopath Med, Tulsa, OK USA. McLean Hosp, Belmont, MA 02178 USA. RP Fossey, MD (reprint author), Univ Oklahoma, Coll Med, Dept Psychiat, 4502 E 41st St, Tulsa, OK 74135 USA. EM mark-fossey@ouhsc.edu RI Allen, Michael/A-8776-2011; OI Ostacher, Michael/0000-0003-0353-7535; Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [N01 MH80001] NR 23 TC 30 Z9 30 U1 2 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAR-APR PY 2006 VL 15 IS 2 BP 138 EP 143 DI 10.1080/10550490500528423 PG 6 WC Substance Abuse SC Substance Abuse GA 029QH UT WOS:000236579000004 PM 16595351 ER PT J AU Shah, PR Ahmad-Annuar, A Ahmadi, KR Russ, C Sapp, PC Horvitz, HR Brown, RH Goldstein, DB Fisher, EMC AF Shah, PR Ahmad-Annuar, A Ahmadi, KR Russ, C Sapp, PC Horvitz, HR Brown, RH Goldstein, DB Fisher, EMC TI No association of DYNC1H1 with sporadic ALS in a case-control study of a northern European derived population: A tagging SNP approach SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE DYNC1H1; ALS; association study; cytoplasmic dynein; tagging SNP ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; LINKAGE-DISEQUILIBRIUM; CYTOPLASMIC DYNEIN; NATURAL-SELECTION; HOMOZYGOSITY TEST; AXONAL-TRANSPORT; COMMON DISEASE; GENE; MUTATIONS AB The cytoplasmic dynein-dynactin complex has been implicated in the aetiology of motor neuron degeneration in both mouse models and human forms of motor neuron disease. We have previously shown that mutations in the cytoplasmic dynein 1 heavy chain 1 gene (Dync1h1) are causal in a mouse model of late-onset motor neuron degeneration but have found no association of the homologous sites in human DYNC1H1 with human motor neuron disease. Here we extend these analyses to investigate the DYNC1H1 genomic locus to determine if it is associated with sporadic amyotrophic lateral sclerosis (ALS) in a northern European-derived population. Among the 16 single nucleotide polymorphisms ( SNPs) we examined, just two SNPs (rs2251644 and rs941793) were sufficient to tag the majority of haplotypic variation (r(2) >= 0.85) and these were tested in a case-control association study with 266 North American sporadic ALS patients and 225 matched controls. We found no association between genetic variation at DYNC1H1 and sporadic ALS ( rs2251644; p=0.538, rs941793; p=0.204, haplotype; p=0.956). In addition we investigated patterns of diversity at DYNC1H1 in Japanese and Cameroonian populations to establish the evolutionary history for this gene and observed reduced genetic diversity in the northern Europeans suggestive of selection at this locus. C1 Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England. Inst Neurol, MRC, Prion Unit, London WC1N 3BG, England. UCL, Dept Biol, London WC1E 6BT, England. Massachusetts Gen Hosp, Day Lab Neuromuscular Res, Boston, MA 02114 USA. MIT, Dept Biochem, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Fisher, EMC (reprint author), Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London WC1N 3BG, England. EM e.fisher@prion.ucl.ac.uk RI AHMAD ANNUAR, AZLINA/B-8305-2010 NR 43 TC 2 Z9 3 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PD MAR PY 2006 VL 7 IS 1 BP 46 EP 56 DI 10.1080/14660820500397057 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 022IY UT WOS:000236050100008 PM 16546759 ER PT J AU Kling, DE Brandon, KL Sollinger, CA Cavicchio, AJ Ge, QY Kinane, TB Donahoe, PK Schnitzer, JJ AF Kling, DE Brandon, KL Sollinger, CA Cavicchio, AJ Ge, QY Kinane, TB Donahoe, PK Schnitzer, JJ TI Distribution of ERK1/2 and ERK3 during normal rat fetal lung development SO ANATOMY AND EMBRYOLOGY LA English DT Article DE mitosis; MAP kinase; cell differentiation; lung development; epithelial; mesenchymal ID TRANSCRIPTION FACTOR HFH-4; ACTIVATED PROTEIN-KINASES; BRANCHING MORPHOGENESIS; CELL-DIFFERENTIATION; MAP-KINASE; MOUSE LUNG; HISTONE H3; EXPRESSION; APOPTOSIS; MECHANISM AB The extracellular regulated kinases-1 and -2 (ERK1/2) are well-characterized mitogen-activated protein kinases (MAPK) that play critical roles in proliferation and differentiation, whereas the function(s) of MAPK ERK3 are currently unknown. To understand better the roles of these kinases in development, the temporal distribution of ERK1, -2, and -3 proteins were investigated in multiple tissues. The ERK3 protein, in contrast to ERK1/2 varied both between and within individual organs over time. To characterize this variability in greater detail, the temporal and spatial distributions of activated ERK1/2 and ERK3 during rat fetal lung development were investigated. The diphosphorylated (activated) forms of ERK1/2 (dp-ERK1/2), ERK3, and its phosphorylated form (P-ERK3) decreased from embryonic day 17 (E17) through E21 while both ERK1 and ERK2 total proteins remained unchanged, indicating that ERK1/2 and ERK3 proteins are expressed independently during fetal lung development. In addition, characterization of the distribution of these proteins by fluorescent immunohistochemistry indicated that phosphorylated ERK1/2 and total ERK1/2 were distributed throughout multiple cell types, with the phosphorylated ERK1/2 colocalizing with prophase mitotic cells. In contrast, ERK3 was restricted to the distal lung epithelium during the pseudoglandular phase (E17) but shifted to the proximal airways, particularly Clara cells during the saccular stage (E21). The P-ERK3 colocalized with the mitotic marker P-histone H3 in fetal lung and in NIH3T3 and HeLa cells, implicating a potential role for P-ERK3 in mitosis. Thus, expression of ERK1/2 and ERK3 and their phosphorylated forms are expressed independently and are temporally and spatially localized during fetal lung morphogenesis. These observations will facilitate detailed functional analysis of these kinases to assess their roles in pulmonary development and diseases. C1 Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. Cell Signaling Technol Inc, Beverly, MA 01915 USA. Harvard Univ, Massachusetts Gen Hosp, Lab Dev Immunol, Dept Pediat,Sch Med, Boston, MA USA. RP Kling, DE (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, CPZ-6-100,185 Cambridge St, Boston, MA 02114 USA. EM dkling@partners.org FU NHLBI NIH HHS [HL069684, HL062615]; NICHD NIH HHS [P01HD039942] NR 53 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-2061 J9 ANAT EMBRYOL JI Anat. Embryol. PD MAR PY 2006 VL 211 IS 2 BP 139 EP 153 DI 10.1007/s00429-005-0063-z PG 15 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 015RW UT WOS:000235569500007 PM 16374608 ER PT J AU Mashour, GA Schwamm, LH Leffert, L AF Mashour, GA Schwamm, LH Leffert, L TI Intracranial subdural hematomas and cerebral herniation after labor epidural with no evidence of dural puncture SO ANESTHESIOLOGY LA English DT Article ID SPINAL-ANESTHESIA; BLOOD PATCH; POSTPARTUM HEADACHE; HYPOTENSION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. RP Mashour, GA (reprint author), 55 Fruit St,Clin 309, Boston, MA 02114 USA. EM gmashour@partners.org OI Schwamm, Lee/0000-0003-0592-9145 NR 18 TC 11 Z9 11 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAR PY 2006 VL 104 IS 3 BP 610 EP 612 DI 10.1097/00000542-200603000-00030 PG 3 WC Anesthesiology SC Anesthesiology GA 018LS UT WOS:000235766400029 PM 16508410 ER PT J AU Dahlin, C Lynch, M Szmuilowicz, E Jackson, V AF Dahlin, C Lynch, M Szmuilowicz, E Jackson, V TI Management of symptoms other than pain SO ANESTHESIOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID ILL CANCER-PATIENTS; QUALITY-OF-LIFE; OBSTRUCTIVE PULMONARY-DISEASE; INOPERABLE BOWEL OBSTRUCTION; RANDOMIZED CONTROLLED-TRIAL; INTRACTABLE HICCUPS; DOUBLE-BLIND; NEBULIZED FUROSEMIDE; INHALED FUROSEMIDE; MEGESTROL-ACETATE AB Symptom management requires an understanding of the likely cause of the symptom in the individual patient, comprehensive assessment, and evidence-based interventions. This article explores the management strategies for common symptoms encountered in palliative care practice. Stomatitis, xerostomia, dysphagia, nausea and vomiting, anorexia, constipation, dyspnea, and fatigue are among the symptoms reviewed. C1 Dana Farber Canc Inst, Dept Pain & Palliat Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Dahlin, C (reprint author), Massachusetts Gen Hosp, Pallat Care Serv, 55 Fruit St,Founders 604, Boston, MA 02114 USA. EM cdahlin@partners.org NR 95 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8537 J9 ANESTHESIOL CLIN N A JI Anesthesiol. Clin. N. Am. PD MAR PY 2006 VL 24 IS 1 BP 39 EP + DI 10.1016/j.atc.2005.12.007 PG 23 WC Anesthesiology SC Anesthesiology GA 021DD UT WOS:000235962800005 PM 16487895 ER PT J AU Gruenewald, DA White, EJ AF Gruenewald, DA White, EJ TI The illness experience of older adults near the end of life: a systematic review SO ANESTHESIOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID QUALITY-OF-LIFE; TERMINALLY-ILL; PATIENTS PERSPECTIVES; DYING PATIENTS; ELDERLY PATIENTS; DECISION-MAKING; PEOPLES VIEWS; LUNG-CANCER; CARE; PREFERENCES AB A systematic literature review identified qualitative studies of issues important to older people near the end of their lives, to develop a model of the illness experience near the end of life based on the views of older people. Six elements were identified from 40 studies that comprise a core domain of the experience of illness while dying: burden, Suffering, hope, dignity, decision making, and control and autonomy. These elements were interwoven with three main themes: contextual factors, perceptions and concerns, and response to illness. Collectively, the core domain and the three themes comprise a model of the experience of illness near the end of life. C1 Vet Affairs Puget Sound Hlth Care Syst, Geriatr & Extended Care Serv, Palliat Care & Hosp Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA 98108 USA. Univ Washington, Sch Nursing, Seattle, WA 98195 USA. RP Gruenewald, DA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr & Extended Care Serv, Palliat Care & Hosp Serv, S-182-GEC,1660 S Columbian Way, Seattle, WA 98108 USA. EM dgruen@u.washington.edu NR 43 TC 17 Z9 17 U1 1 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8537 J9 ANESTHESIOL CLIN N A JI Anesthesiol. Clin. N. Am. PD MAR PY 2006 VL 24 IS 1 BP 163 EP + DI 10.1016/j.atc.2005.12.003 PG 19 WC Anesthesiology SC Anesthesiology GA 021DD UT WOS:000235962800011 PM 16487901 ER PT J AU Abadie, JM Bankson, DD AF Abadie, JM Bankson, DD TI Assessment of serum free light chain assays for plasma cell disorder screening in a veterans affairs population SO ANNALS OF CLINICAL AND LABORATORY SCIENCE LA English DT Article DE light chains; monoclonal gammopathy; myeloma; electrophoresis; plasma cell dyscrasia ID MULTIPLE-MYELOMA; KAPPA AB This study evaluated serum. and l free light chain (FLC) concentrations in a Veterans Affairs (VA) population. We hypothesized that our older, mostly male, population should not differ in serum FLC ranges from levels previously established for younger male and female populations and that the assay would improve our screening protocol for plasma cell dyscrasias (PCD). Serum. and l FLC were assayed in 312 consecutive serum samples collected during a 16-week period from veterans whose clinical presentation indicated a need for serum protein electrophoresis (SPEP) analysis. We reviewed our laboratory information system (LIS) files to evaluate the patients' diagnoses and treatment status in conjunction with serum FLC levels. All assays and validation studies were conducted using an immunoturbidimetric method with a Roche/Hitachi 911 modular analytical system. The intra-assay variability (CV) was < 5%, based on 13 replicate assays of 4 control samples and 1 blank sample. Of the 312 patients, the SPEP results were normal in 235 and abnormal in 77. Of the 235 patients with normal SPEP results, 37 had abnormal FLC values and 20 of these were diagnosed as PCD. Of the 77 patients with abnormal SPEP results, only 9 had diagnoses unrelated to PCD. Using the FLC assay in conjunction with retrospective reviews of medical records, we obtained an 86% detection rate of PCD. This detection rate increased to 100% when both SPEP and FLC results were considered. In conclusion, this study documents an important role for serum FLC assays in diagnosing and monitoring PCD in a VA population. Our results support previously established serum FLC reference ranges that were obtained in younger, male and female populations. Using the serum FLC results in conjunction with SPEP results improves the sensitivity and specificity for managing VA patients whose clinical presentation indicates the need to evaluate PCD. C1 Vet Affairs Puget Sound Hlth Care Syst, Pathol & Lab Med Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA. RP Abadie, JM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Pathol & Lab Med Serv, 1660 S Columbian Way S-113 Lab, Seattle, WA 98108 USA. EM judeabadie@medscape.com NR 13 TC 25 Z9 26 U1 0 U2 0 PU ASSN CLINICAL SCIENTISTS PI MIDDLEBURY PA PO BOX 1287, MIDDLEBURY, VT 05753 USA SN 0091-7370 J9 ANN CLIN LAB SCI JI Ann. Clin. Lab. Sci. PD SPR PY 2006 VL 36 IS 2 BP 157 EP 162 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 043LU UT WOS:000237603400006 PM 16682511 ER PT J AU Marill, KA deSouza, IS Nishijima, DK Stair, TO Setnik, GS Ruskin, JN AF Marill, KA deSouza, IS Nishijima, DK Stair, TO Setnik, GS Ruskin, JN TI Amiodarone is poorly effective for the acute termination of ventricular tachycardia SO ANNALS OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine (SAEM) CY MAY, 2005 CL New York, NY SP Soc Acad Emergency Med ID SHORT-TERM TREATMENT; WIDE QRS COMPLEX; INTRAVENOUS AMIODARONE; INTRAVENTRICULAR-CONDUCTION; DIFFERENTIAL-DIAGNOSIS; CLINICAL EFFICACY; ORAL AMIODARONE; HEART-DISEASE; RECURRENT; LIDOCAINE AB Study objective: It is hypothesized that intravenous (IV) amiodarone is poorly effective for the acute termination of sustained monomorphic ventricular tachycardia because of the relatively slow onset of its Vaughn-Williams class III effect to prolong myocardial depolarization and the refractory period. This study is designed to determine the effectiveness and safety of IV amiodarone for the termination of sustained monomorphic ventricular tachycardia. Methods: A retrospective case series was collected at 4 urban university-affiliated hospitals from September 1996 to April 2005 after institutional review board approval with waiver of informed consent. Emergency department (ED) patients treated with IV amiodarone for ventricular tachycardia were identified by ED treatment and hospital pharmacy billing records, International Classification of Diseases, Ninth Revision discharge codes, and ECG characteristics. All consecutive patients who received at least 150 mg amiodarone in 15 minutes or less for spontaneous sustained monomorphic ventricular tachycardia were eligible for inclusion. Sustained monomorphic ventricular tachycardia was defined as a tachycardia with uninterrupted duration or rapid recurrence despite automatic internal cardiac defibrillator therapy for at least 5 minutes before amiodarone treatment, monomorphic morphology, rate greater than 120 beats/min, QRS duration greater than 120 ms, and subsequently determined to be ventricular tachycardia by ECG criteria (eg, atrioventricular dissociation), implanted device interrogation, or formal electrophysiology study. Measured outcomes included sustained termination of ventricular tachycardia within 20 minutes of initiation of amiodarone infusion and any documented adverse effects. Rates of successful termination and adverse effects and their 95% confidence intervals (Cls) were calculated. The presence or average values of potentially confounding predictors in patients with and without ventricular tachycardia termination after amiodarone were also calculated and compared. Results: Thirty-three patients were identified and included. Five patients received electrical therapy within 20 minutes of initiation of amiodarone infusion, and the response to amiodarone was unknown. Twenty-seven of the remaining 28 patients received 150 mg amiodarone, and the rate of successful ventricular tachycardia termination was 8 of 28, 29% (95% Cl 13 to 49). Two of 33 patients, 6% (95% Cl 1 to 20), required direct current cardioversion for presyncope or hypotension temporally associated with amiodarone treatment. Conclusion: IV amiodarone, as currently administered, is relatively safe but ineffective for the acute termination of sustained ventricular tachycardia. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Mt Auburn Hosp, Cambridge, MA 02238 USA. RP Marill, KA (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Clin 115, Boston, MA 02114 USA. EM kmarill@partners.org NR 32 TC 20 Z9 21 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAR PY 2006 VL 47 IS 3 BP 217 EP 224 DI 10.1016/j.annemergemed.2005.08.022 PG 8 WC Emergency Medicine SC Emergency Medicine GA 020OP UT WOS:000235919500001 PM 16492484 ER PT J AU Valente, EM Brancat, F Silhavy, JL Castori, M March, SE Barrano, G Bertini, E Boltshauser, E Zaki, MS Abdel-Aleem, A Abdel-Salam, GMH Bellacchlo, E Battini, R Cruse, RP Dobyns, WB Krishnamoorthy, KS Lagier-Tourenne, C Magee, A Pascual-Castroviejo, I Salpietro, CD Sarco, D Dallapiccola, B Gleeson, JG AF Valente, EM Brancat, F Silhavy, JL Castori, M March, SE Barrano, G Bertini, E Boltshauser, E Zaki, MS Abdel-Aleem, A Abdel-Salam, GMH Bellacchlo, E Battini, R Cruse, RP Dobyns, WB Krishnamoorthy, KS Lagier-Tourenne, C Magee, A Pascual-Castroviejo, I Salpietro, CD Sarco, D Dallapiccola, B Gleeson, JG CA Int JSRD Stdy Grp TI AHI1 gene mutations cause specific forms of Joubert syndrome-related disorders SO ANNALS OF NEUROLOGY LA English DT Article ID LOCUS; NEPHRONOPHTHISIS; INVOLVEMENT; FAMILIES; DELETION AB Joubert syndrome (JS) is a recessively inherited developmental brain disorder with several identified causative chromosomal loci. It is characterized by hypoplasia of the cerebellar vermis and a particular midbrain-hindbrain "molar tooth" sign, a finding shared by a group of Joubert syndrome-related disorders (JSRDs), with wide phenotypic variability. The frequency of mutations in the first positionally cloned gene, AHI1, is unknown. Methods: We searched for mutations in the AHI1 gene among a cohort of 137 families with JSRD and radiographically proven molar tooth sign. Results: We identified 15 deleterious mutations in 10 families with pure JS or JS plus retinal and/or additional central nervous system abnormalities. Mutations among families with JSRD including kidney or liver involvement were not detected. Transheterozygous mutations were identified in the majority of those without history of consanguinity. Most mutations were truncating or splicing errors, with only one missense mutation in the highly conserved WD40 repeat domain that led to disease of similar severity. Interpretation AHI1 mutations are a frequent cause of disease in patients with specific forms of JSRD. C1 Ist Ricovero & Cura & Carattere Sci, CSS, Mendel Inst, Rome, Italy. G Dannunzio Univ, Dept Biol Sci, Chieti, Italy. Univ Roma La Sapienza, Dept Expt Med & Pathol, Rome, Italy. Univ Calif San Diego, Dept Neurosci, Neurogenet Lab, La Jolla, CA 92093 USA. Bambino Gesu Pediat Hosp, IRCCS, Mol Med Unit, Dept Lab Med, Rome, Italy. Childrens Univ Hosp, Dept Neurol, Zurich, Switzerland. Natl Res Ctr, Dept Clin Genet, Cairo, Egypt. Natl Res Ctr, Dept Mol Genet, Cairo, Egypt. Univ Pisa, Stella Maris Sci Inst, Div Child Neurol & Psychiat, Pisa, Italy. Texas Childrens Hosp, Clin Care Ctr, Houston, TX USA. Univ Chicago, Dept Human Genet, Div Biol Sci, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Pediat Neurol Unit, Boston, MA USA. Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France. Belfast City Hosp, Reg Genet Serv, Belfast BT9 7AD, Antrim, North Ireland. Hosp Univ La Paz, Madrid, Spain. Univ Messina, Dept Med & Surg Pediat Sci, Operat Unit Pediat Genet & Immunol, Messina, Italy. Harvard Univ, Sch Med, Dept Neurol, Childrens Hosp, Boston, MA 02115 USA. RP Gleeson, JG (reprint author), Univ Calif San Diego, LBR3A16, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM evalente@css-mendel.it RI Castori, Marco/K-1099-2016; Dallapiccola, Bruno/K-8692-2016; OI Castori, Marco/0000-0002-6069-0993; Dallapiccola, Bruno/0000-0002-5031-1013; Abdel-Salam, Ghada/0000-0003-2893-8802; Bertini, Enrico/0000-0001-9276-4590; Dobyns, William/0000-0002-7681-2844; Zaki, Maha/0000-0001-7840-0002 FU NINDS NIH HHS [R01 NS052455, NS4853] NR 18 TC 72 Z9 75 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAR PY 2006 VL 59 IS 3 BP 527 EP 534 DI 10.1002/ana.20749 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 020OU UT WOS:000235920000012 PM 16453322 ER PT J AU Treon, SP Hunter, ZR Aggarwal, A Ewen, EP Masota, S Lee, C Santos, DD Hatjiharissi, E Xu, L Leleu, X Tournilhac, O Patterson, CJ Manning, R Branagan, AR Morton, CC AF Treon, SP Hunter, ZR Aggarwal, A Ewen, EP Masota, S Lee, C Santos, DD Hatjiharissi, E Xu, L Leleu, X Tournilhac, O Patterson, CJ Manning, R Branagan, AR Morton, CC TI Characterization of familial Waldenstrom's macroglobulinemia SO ANNALS OF ONCOLOGY LA English DT Article DE Waldenstrom's macroglobulinemia; B-cell; familial clustering ID ACUTE LYMPHOBLASTIC-LEUKEMIA; B-CELL DEVELOPMENT; CHROMOSOMAL-ABNORMALITIES; LYMPHOID MALIGNANCIES; 6Q DELETIONS; LONG ARM; REGION; CLASSIFICATION; MATURATION; BROTHERS AB Background: Familial clustering of B-cell disorders among Waldenstrom's macroglobulinemia (WM) patients has been reported, though the frequency and any differences in disease manifestation for familial patients remain to be defined. Patients and methods: We therefore analyzed clinicopathological data from 257 consecutive and unrelated WM patients. Forty-eight (18.7%) patients had at least one first-degree relative with either WM (n = 13, 5.1%), or another B-cell disorder including non-Hodgkin's lymphoma (n = 9, 3.5%), myeloma (n = 8, 3.1%), chronic lymphocytic leukemia (n = 7, 2.7%), monoclonal gammopathy of unknown significance (n = 5, 1.9%), acute lymphocytic leukemia (n = 3, 1.2%) and Hodgkin's disease (n = 3, 1.2%). Patients with a familial history of WM or a plasma cell disorder (PCD) were diagnosed at a younger age and with greater bone marrow involvement. Results: Deletions in 6q represented the only recurrent structural chromosomal abnormality and were found in 13% of patients, all non-familial cases. Interphase FISH analysis demonstrated deletions in 6q21-22.1 in nearly half of patients, irrespective of familial background. Conclusions: The above results suggest a high degree of clustering for B-cell disorders among first-degree relatives of patients with WM, along with distinct clinical features at presentation based on familial disease cluster patterns. Genomic studies to delineate genetic predisposition to WM are underway. C1 Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Program Waldenstroms Macroglobulinemia, LG102,44 Binney St, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 FU NCI NIH HHS [K23 CA087977-03, P30 CA06516] NR 41 TC 80 Z9 85 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2006 VL 17 IS 3 BP 488 EP 494 DI 10.1093/annonc/mdj111 PG 7 WC Oncology SC Oncology GA 018NH UT WOS:000235770700020 PM 16357024 ER PT J AU Hahn, MS Kobler, JB Zeitels, SM Langer, R AF Hahn, MS Kobler, JB Zeitels, SM Langer, R TI Quantitative and comparative studies of the vocal fold extracellular matrix II: Collagen SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE animal model; collagen; collagen turnover; lamina propria; quantitative histology; vocal fold ID TISSUE INHIBITORS; LAMINA PROPRIA; SENESCENT EXPRESSION; FIBERS; METALLOPROTEINASES; ATHEROSCLEROSIS; SECTIONS; THERAPY; MUCOSA; LUNGS AB Objectives: This study examines the collagen content and turnover in the midmembranous vocal fold laminae propriae (LPs) of humans, dogs, pigs, and ferrets. Methods: The LP collagen levels were assessed by quantifying tissue hydroxyproline. Quantitative histology allowed evaluation of the collagen content in specific LP regions. Several collagen types and two markers of collagen turnover were examined immunohistochemically. Results: Collagen made up 43.4% +/- 2.6% of human LP total protein (TP), with men having approximately 30% higher collagen content than women (p < .024). The collagen levels in pigs (52.6% +/- 1.9% of TP) and ferrets (29.8% +/- 3.7% of TP), but not that in dogs (45.3% +/- 1.2% of TP), varied significantly from that in humans (pigs, p < .016; ferrets, p < .011). Quantitative histology indicated marked interspecies differences in total collagen distribution. Collagen types I, III, and IV were detected in the LP, and spatially complex staining patterns were observed for the two markers of collagen turnover studied. Conclusions: The collagen content of the human LP is approximately 60% to 70% of that of human dermis. Although canine LP collagen levels are most similar to those of humans, quantitative histology indicates that the collagen distribution of the human LP is best matched by the porcine LP. Collagen types I and III seem to be the dominant LP collagens. Spatial variations in collagen turnover appear to exist that may contribute to normal LP physiology. C1 Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Dept Surg, Boston, MA 02114 USA. MIT, Dept Comp Sci & Elect Engn, Boston, MA USA. MIT, Dept Chem Engn, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Dept Surg, 1 Bowdoin Square,11th Floor, Boston, MA 02114 USA. RI Hahn, Mariah/G-3998-2014 OI Hahn, Mariah/0000-0001-8794-129X NR 28 TC 61 Z9 62 U1 0 U2 8 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAR PY 2006 VL 115 IS 3 BP 225 EP 232 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 022PI UT WOS:000236067700011 PM 16572613 ER PT J AU Sung, SJ Conry, JM AF Sung, SJ Conry, JM TI Role of buprenorphine in the management of heroin addiction SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE addiction; buprenorphine; heroin; opioid ID METHADONE-MAINTENANCE INTERVENTIONS; OPIATE-DEPENDENT VOLUNTEERS; COST-EFFECTIVENESS; OPIOID DEPENDENCE; METAANALYSIS; BEHAVIOR AB OBJECTIVE: To review buprenorphine and explore its role in the treatment of heroin dependence. DATA SOURCES: Articles were identified through a search of MEDLINE (1966-February 2005) using the key terms buprenorphine, heroin, opioid, addiction, and methadone. DATA SYNTHESIS: Buprenorphine appears to provide potential advantages over methadone. Two Cochrane meta-analyses were evaluated on the use of buprenorphine in opioid dependence-one in the management of opioid dependence and the other in the management of opioid withdrawal. CONCLUSIONS: Buprenorphine offers several advantages for the treatment of heroin addiction. As maintenance treatment, buprenorphine is effective, but not more effective than methadone. In the management of opioid withdrawal, buprenorphine may be better tolerated than clonidine or methadone. C1 St Johns Univ, Coll Pharm & Allied Hlth Profess, Jamaica, NY 11439 USA. Bronx Vet Affairs Med Ctr, Dept Pharm, Bronx, NY USA. RP Conry, JM (reprint author), St Johns Univ, Coll Pharm & Allied Hlth Profess, St Alberts Hall,Rm 114,8000 Utopia Pkwy, Jamaica, NY 11439 USA. EM conryj@stjohns.edu NR 23 TC 12 Z9 12 U1 0 U2 2 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD MAR PY 2006 VL 40 IS 3 BP 501 EP 505 DI 10.1345/aph1G276 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 022JW UT WOS:000236052900017 PM 16434562 ER PT J AU Schroeder, RA Marroquin, CE Bute, BP Khuri, S Henderson, WG Kuo, PC AF Schroeder, RA Marroquin, CE Bute, BP Khuri, S Henderson, WG Kuo, PC TI Predictive indices of morbidity and mortality after liver resection SO ANNALS OF SURGERY LA English DT Article ID MELD SCORE; PUGH SCORE; CHILD-PUGH; SURVIVAL; MODEL; RISK; TRANSPLANTATION; VALIDATION; DISEASE; PATIENT AB Objective: To determine if use of Model for End-Stage Liver Disease (MELD) scores to elective resections accurately predicts short-term morbidity or mortality. Summary Background Data: MELD scores have been validated in the setting of end-stage liver disease for patients awaiting transplantation or undergoing transvenous intrahepatic portosystemic shunt procedures. Its use in predicting outcomes after elective hepatic resection has not been evaluated. Methods: Records of 587 patients who underwent elective hepatic resection and were included in the National Surgical Quality Improvement Program Database were reviewed. MELD score, CTP score, Charlson Index of Comorbidity, American Society of Anesthesiology classification, and age were evaluated for their ability to predict short-term morbidity and mortality. Morbidity was defined as the development of one or more of the following complications: pulmonary edema or embolism, myocardial infarction, stroke, renal failure or insufficiency, pneumonia, deep venous thrombosis, bleeding, deep wound infection, reoperation, or hyperbilirubinemia. The analysis was repeated with patients divided according to their procedure and their primary diagnosis. Parametric or nonparametric analyses were performed as appropriate. Also, a new index was developed by dividing the patients into a development and a validation cohort, to predict morbidity and mortality in patients undergoing elective hepatic resection. ROC curves were also constructed for each of the primary indices. Results: CTP and ASA scores were superior in predicting outcome. Also, patients undergoing resection of primary malignancies had a higher rate of mortality but no difference in morbidity. Conclusion: MELD scores should not be used to predict outcomes in the setting of elective hepatic resection. C1 Duke Univ, Sch Med, Dept Anesthesiol, Durham Vet Med Ctr,VAMC 112C, Durham, NC 27705 USA. Boston VA Healthcare Syst, Surg Serv, Boston, MA USA. Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. Dept Prevent Med & Biometr, Aurora, CO USA. RP Schroeder, RA (reprint author), Duke Univ, Sch Med, Dept Anesthesiol, Durham Vet Med Ctr,VAMC 112C, 508 Fulton St, Durham, NC 27705 USA. EM Schro016@mc.duke.edu NR 18 TC 149 Z9 162 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAR PY 2006 VL 243 IS 3 BP 373 EP 379 DI 10.1097/01.sla.0000201483.95911.08 PG 7 WC Surgery SC Surgery GA 017VE UT WOS:000235720600014 PM 16495703 ER PT J AU Lee, PS Drager, LR Stossel, TP Moore, FD Rogers, SO AF Lee, PS Drager, LR Stossel, TP Moore, FD Rogers, SO TI Relationship of plasma gelsolin levels to outcomes in critically ill surgical patients SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 100th International Conference of the American-Thoracic-Society CY MAY 21-26, 2004 CL Orlando, FL SP Amer Thorac Soc ID RESPIRATORY-DISTRESS-SYNDROME; INTENSIVE-CARE-UNIT; ACUTE LUNG INJURY; SCAVENGER SYSTEM; TRAUMA PATIENTS; APACHE-II; ACTIN; MECHANISMS; DEPRESSION; MORTALITY AB Objective: To examine the relationship between plasma gelsolin levels and mortality following surgery or trauma. Background: Few simple predictive diagnostic tests are available to predict mortality following surgery or trauma. We hypothesize that plasma concentrations of gelsolin, a protein that responds to injured tissue, might be a predictor of patient outcomes. Methods: We conducted a prospective, observational study in the surgical intensive units (ICU) at a tertiary care teaching hospital. A total of 31 patients were enrolled in the study. Chart abstraction was used to gather data about patient demographics, clinical characteristics, and clinical outcomes. Plasma gelsolin concentrations were assessed serially on day 0 through day 5. Results: Low plasma gelsolin levels were associated with increased risk of death occurring in the ICU. Plasma gelsolin levels lower than 61 mg/L predicted longer ICU stay, prolonged ventilator dependence, and increased overall in-hospital mortality. Conclusion: Plasma gelsolin is a potential prognostic biomarker for critically ill surgical patients. Plasma gelsolin replacement may have therapeutic application. C1 Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Rogers, SO (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM SROGERS@Partners.org NR 29 TC 44 Z9 54 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAR PY 2006 VL 243 IS 3 BP 399 EP 403 DI 10.1097/01.sla.0000201798.77133.55 PG 5 WC Surgery SC Surgery GA 017VE UT WOS:000235720600017 PM 16495706 ER PT J AU Yoon, SS Kim, SH Gonen, M Heffernan, NM Detwiller, KY Jarnagin, WR D'Angelica, M Blumgart, LH Tanabe, KK DeMatteo, RP AF Yoon, SS Kim, SH Gonen, M Heffernan, NM Detwiller, KY Jarnagin, WR D'Angelica, M Blumgart, LH Tanabe, KK DeMatteo, RP TI Profile of plasma angiogenic factors before and after hepatectomy for colorectal cancer liver metastases SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE colorectal cancer; liver metastases; angiogenesis; vascular endothelial growth factor; basic fibroblast growth factor; hepatocyte growth factor ID ENDOTHELIAL GROWTH-FACTOR; CLINICAL IMPLICATIONS; TUMOR ANGIOGENESIS; SURGICAL-TREATMENT; PLUS IRINOTECAN; FACTOR RECEPTOR; PHASE-II; REGENERATION; CARCINOMA; FLUOROURACIL AB Circulating angiogenic factors in patients with colorectal cancer liver metastases may promote tumor growth and contribute to liver regeneration after partial hepatectomy. We analyzed blood samples from 26 patients with colorectal cancer liver metastases before and after liver resection and used samples from 20 healthy controls as a reference. Plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and hepatocyte growth factor (HGF) were measured, and levels were correlated with recurrence. The median preoperative levels of all four factors were significantly higher and more variable in colorectal cancer liver metastasis patients than in controls. HGF and bFGF levels increased significantly 3 days and 1 month after hepatectomy, respectively, and returned to near preoperative levels at 3 months. Postoperative VEGF and EGF levels remained relatively stably increased over 3 months. After a median follow-up of 19 months, 10 patients (42%) experienced recurrence. Higher preoperative VEGF and HGF levels correlated with subsequent recurrence (P = .018 and .021, respectively), and a preoperative adjusted total value of all four factors accurately identified patients at low, moderate, and high risk of recurrence (P = .034). Patients who experienced disease recurrence also had relatively higher bFGF levels 3 months after operation (P = .035). Plasma angiogenic factors are increased in patients with colorectal cancer liver metastases and remain increased at least 3 months after partial hepatectomy. Measurement of certain factors before and after hepatic resection can predict recurrence. Targeted biological agents may counteract the tumor-promoting effects of these circulating factors on subclinical disease. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Surg Oncol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, Hepatobiliary Serv, New York, NY 10021 USA. RP Yoon, SS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Surg Oncol, Yawkey 7B-7926,55 Fruit St, Boston, MA 02114 USA. EM syoon@partners.org RI Gonen, Mithat/E-4826-2012; OI Jarnagin, William/0000-0002-1635-5768 FU NCI NIH HHS [CA94503, K12CA87723-02] NR 40 TC 45 Z9 48 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 2006 VL 13 IS 3 BP 353 EP 362 DI 10.1245/ASO.2006.03.060 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA 013ZY UT WOS:000235449700013 PM 16474912 ER PT J AU Gerard, HC Whittum-Hudson, JA Schumacher, HR Hudson, AP AF Gerard, HC Whittum-Hudson, JA Schumacher, HR Hudson, AP TI Synovial Chlamydia trachomatis up regulates expression of a panel of genes similar to that transcribed by Mycobacterium tuberculosis during persistent infection SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID DIFFERENTIAL EXPRESSION; DEVELOPMENTAL CYCLE; GENOME SEQUENCE; PNEUMONIAE; DNA; MACROPHAGES; ARTHRITIS; PRODUCTS AB Background: Synovial tissues in patients with Chlamydia associated arthritis are persistently infected by C trachomatis, an organism for which genetic manipulation is not possible. M tuberculosis also engages in persistent infection, and because this bacterium is genetically tractable many groups have been able to define transcriptional characteristics of mycobacterial growth and persistence. Objective: To investigate whether the pattern of gene expression underlying chlamydial persistence is similar to that underlying mycobacterial persistence. Methods: 194 genes in M tuberculosis that are transcriptionally up regulated to support in vivo growth and persistence of that organism have previously been identified. Each of those genes was compared with the C trachomatis genome to identify orthologues. Expression of selected chlamydial orthologues so identified was assessed by real time RT-PCR in an in vitro model of chlamydial persistence and synovial tissues from patients who were PCR positive for C trachomatis at that site. Results: 67 C trachomatis genes were identified as being orthologous to mycobacterial persistence related genes, representing 35% of the genes tested. The chlamydial orthologues fell into similar metabolic and other categories as those in M tuberculosis. Expression of a majority of selected chlamydial orthologues was strongly up regulated in an in vitro model of chlamydial persistence and in synovial tissues of relevant patients, compared with their expression during active infection. Conclusions: These observations provide new insight into the molecular genetic basis underlying chlamydial persistence, and indicate that this information can be obtained, in some instances, by extrapolating observations made in other biological systems and/or organisms. C1 Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Detroit, MI 48201 USA. Univ Penn, Dept Med, Div Rheumatol, Sch Med, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Detroit, MI 48201 USA. RP Hudson, AP (reprint author), Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Gordon H Scott Hall,540 E Canfield Ave, Detroit, MI 48201 USA. EM ahudson@med.wayne.edu FU NIAID NIH HHS [AI-44493]; NIAMS NIH HHS [AR-47186, AR-42541] NR 27 TC 16 Z9 17 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAR PY 2006 VL 65 IS 3 BP 321 EP 327 DI 10.1136/ard.2005.042226 PG 7 WC Rheumatology SC Rheumatology GA 011NQ UT WOS:000235275600008 PM 16192289 ER PT J AU Mukhopadhyay, NK Weisberg, E Gilchrist, D Bueno, R Sugarbaker, DJ Jakjitsch, MT AF Mukhopadhyay, NK Weisberg, E Gilchrist, D Bueno, R Sugarbaker, DJ Jakjitsch, MT TI Effectiveness of trichostatin a as a potential candidate for anticancer therapy in non-small-cell lung cancer SO ANNALS OF THORACIC SURGERY LA English DT Article ID HISTONE-DEACETYLASE INHIBITORS; ACUTE MYELOID-LEUKEMIA; GELSOLIN EXPRESSION; IN-VIVO; TRANSCRIPTIONAL CONTROL; ANTITUMOR-ACTIVITY; MESSENGER-RNA; DIFFERENTIATION; APOPTOSIS; AGENTS AB Background. A well-known histone deacetylase inhibitor, trichostatin A, was applied to non-small-cell lung cancer cells to determine whether inhibition of histone deacetylase leads to the production of proteins that either arrest tumor cell growth or lead to tumor cell death. Methods. Trichostatin A (0.01 to 1.0 mu mol/L) was applied to one normal lung fibroblast and four non-small-cell lung cancer lines, and its effect was determined by flow cytometry, annexin-V staining, immunoprecipitation, and Western blot analysis. Results. Trichostatin A demonstrated tenfold greater growth inhibition in all four non-small-cell lung cancer lines compared with normal controls, with a concentration producing 50% inhibition ranging from 0.01 to 0.04 mu mol/L for the tumor cell lines and 0.7 mu mol/L for the normal lung fibroblast line. Trichostatin A treatment reduced the percentage of cells in S phase (10% to 23%) and increased G(1) populations (10% to 40%) as determined by flow cytometry. Both annexin-V binding assay and upregulation of the protein, gelsolin (threefold to tenfold), demonstrated that the tumor cells were apoptotic, whereas normal cells were predominantly in cell cycle arrest. Trichostatin A increased histone H4 acetylation and expression of p21 twofold to 15-fold without significant effect on p16, p27, CDK2, and cyclin D1. Conclusions. Collectively, these data suggest that inhibition of histone deacetylation may provide a valuable approach for lung cancer treatment. We evaluated trichostatin A as a potential candidate for anticancer therapy in non-small-cell lung cancer. C1 Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Mukhopadhyay, NK (reprint author), Brigham & Womens Hosp, Div Urol, 221 Longwood Ave, Boston, MA 02115 USA. EM nmukhopadhyay@partners.org NR 48 TC 29 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAR PY 2006 VL 81 IS 3 BP 1034 EP 1042 DI 10.1016/j.athoracsur.2005.06.059 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 019NN UT WOS:000235844100041 PM 16488717 ER PT J AU Ogawa, K Nakamura, K Onishi, H Koizumi, M Sasak, T Araya, M Miyabe, Y Otani, Y Teshima, T AF Ogawa, K Nakamura, K Onishi, H Koizumi, M Sasak, T Araya, M Miyabe, Y Otani, Y Teshima, T CA Japanese Patterns Care Study Worki TI Influence of age on the pattern and outcome of external beam radiotherapy for clinically localized prostate cancer SO ANTICANCER RESEARCH LA English DT Article DE patterns of care study; prostatic carcinoma; age; elderly patients; radiation therapy ID CARE PROCESS SURVEY; LONG-TERM SURVIVAL; RADIATION-THERAPY; ELDERLY-PATIENTS; CHANGING TRENDS; JAPAN; MEN; CARCINOMA; TOXICITY; ONCOLOGY AB Background: The influence of age on the patterns and outcomes of external beam radiotherapy for clinically localized prostate cancer patients was examined. Materials and Methods: The Japanese Patterns of Care Study surveys were used to compare the processes and outcomes of radical external beam radiotherapy in 140 elderly patients (> 75 years old) and 304 younger patients (< 75 years old). Results: Although the Karnofsky performance status was significantly different between elderly and younger patients, there were no significant differences in disease characteristics such as pretreatment PSA level, differentiation, Gleason combined score and clinical T stage. There were also no significant differences in the treatment characteristics such as CT-based treatment planning, conformal therapy, total radiation doses (both a median of 66.0 Gy) and hormonal therapy usage. Moreover, no significant differences in overall survival, biochemical relapse-free survival and late toxicity rates were observed between elderly and younger patients. Conclusion: Age did not influence the disease characteristics, patterns of external beam radiotherapy, survival and late toxicities for clinically localized prostate cancer patients. Therefore, radiotherapy could represent an important treatment modality for elderly patients as well as for younger ones. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Ryukyus, Dept Radiol, Okinawa 90301, Japan. Univ Ryukyus, Dept Clin Radiol, Okinawa 90301, Japan. Univ Yamanashi, Dept Radiol, Yamanashi, Japan. Kyoto Prefectural Univ, Dept Radiol, Kyoto 606, Japan. Osaka Univ, Dept Med Phys & Engn, Suita, Osaka 565, Japan. RP Ogawa, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM kogawa@med.u-ryukyu.ac.jp NR 31 TC 12 Z9 12 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 2006 VL 26 IS 2B BP 1319 EP 1325 PG 7 WC Oncology SC Oncology GA 030ZY UT WOS:000236675100002 PM 16619540 ER PT J AU Stone, JR Yang, SP AF Stone, James R. Yang, Suping TI Hydrogen peroxide: A signaling messenger SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID SMOOTH-MUSCLE-CELLS; PROTEIN-TYROSINE PHOSPHATASES; ENTEROCOCCAL NADH PEROXIDASE; YAP1 TRANSCRIPTION FACTOR; DISULFIDE BOND FORMATION; NUCLEAR RIBONUCLEOPROTEIN C1/C2; GROWING ESCHERICHIA-COLI; HUMAN ENDOTHELIAL-CELLS; EPIDERMAL-GROWTH-FACTOR; CYSTEINE-SULFINIC ACID AB Hydrogen peroxide (H2O2) is a well-documented component of living cells. It plays important roles in host defense and oxidative biosynthetic reactions. In addition there is growing evidence that at low levels, H2O2 also functions as a signaling agent, particularly in higher organisms. This review evaluates the evidence that H2O2 functions as a signaling agent in higher organisms in light of the known biology and biochemistry of H2O2. All aerobic organisms studied to date from prokaryotes to humans appear to tightly regulate their intracellular H2O2 concentrations at relatively similar levels. Multiple biochemical strategies for rapidly reacting with these low endogenous levels of H2O2 have been elucidated from the study of peroxidases and catalases. Well-defined biochemical pathways involved in the response to exogenous H2O2 have been described in both prokaryotes and yeast. In animals and plants, regulated enzymatic systems for generating H2O2 have been described. In addition oxidation-dependent steps in signal transduction pathways are being uncovered, and evidence is accumulating regarding the nature of the specific reactive oxygen species involved in each of these pathways. Application of physiologic levels of H2O2 to mammalian cells has been shown to stimulate biological responses and to activate specific biochemical pathways in these cells. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Stone, JR (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 501B,55 Fruit St, Boston, MA 02114 USA. EM jrstone@partners.org FU NHLBI NIH HHS [HL074324] NR 242 TC 546 Z9 560 U1 8 U2 89 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD MAR-APR PY 2006 VL 8 IS 3-4 BP 243 EP 270 DI 10.1089/ars.2006.8.243 PG 28 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 042OZ UT WOS:000237539200001 PM 16677071 ER PT J AU Mele, J Van Remmen, H Vijg, J Richardson, A AF Mele, James Van Remmen, Holly Vijg, Jan Richardson, Arlan TI Characterization of transgenic mice that overexpress both copper zinc superoxide dismutase and catalase SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID CELLULAR GLUTATHIONE-PEROXIDASE; OXIDATIVE STRESS; DROSOPHILA-MELANOGASTER; MUTANT MICE; LIFE-SPAN; HYDROGEN-PEROXIDE; CU,ZN-SUPEROXIDE DISMUTASE; MEDIATED CYTOTOXICITY; ANTIOXIDANT ENZYMES; LIPID-PEROXIDATION AB Transgenic mice overexpressing both Cu/ZnSOD and catalase [Tg(SOD1/CAT)(+/o)] were used to evaluate the effects of overexpression of both genes against oxidative stress. Characterization of these transgenic mice revealed that catalase or Cu/ZnSOD activities were two- to fourfold higher in the tissues of transgenic mice compared to wild-type mice, and the activities of the other major antioxidant enzymes were not altered in the tissues of the transgenic mice. The murine embryonic fibroblasts (MEFs) from the Tg(SOD1/CAT)(+/o) and MEFs overexpressing Cu/ZnSOD were more resistant to paraquat cytotoxicity, relative to wild-type MEFs. The MEFs from Tg(SOD1/CAT)(+/o) tended to be more resistant (up to 2.25-fold) to paraquat cytotoxicity than MEFs overexpressing either Cu/ZnSOD or catalase alone. MEFs from Tg(CAT)(+/o) and Tg(SOD1/CAT)(+/o) were equally as resistant to hydrogen peroxide cytotoxicity. However, there were no significant differences in whole animal survival against either paraquat or gamma-radiation. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Barchop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Dept Geriatr Res, Educ & Clin Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. RP Richardson, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM richardsona@uthscsa.edu FU NIA NIH HHS [P01 AG19316, P01 AG20591, P03 AG13319] NR 65 TC 33 Z9 33 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD MAR-APR PY 2006 VL 8 IS 3-4 BP 628 EP 638 DI 10.1089/ars.2006.8.628 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 042OZ UT WOS:000237539200036 PM 16677106 ER PT J AU Seliem, RM Freeman, JK Steingart, RH Hasserjian, RP AF Seliem, RM Freeman, JK Steingart, RH Hasserjian, RP TI Immunophenotypic changes and clinical outcome in B-cell lymphomas treated with rituximab SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY LA English DT Article DE CD20; B-cell lymphoma; rituximab; flow cytometry; immunohistochemistry ID NON-HODGKINS-LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; MONOCLONAL-ANTIBODY THERAPY; IDEC-C2B8 RITUXIMAB; CD20 ANTIGEN; ANTI-CD20; MODULATION; EXPRESSION; TRIAL AB Rituximab is a chimeric monoclonal antibody that recognizes the CD20 antigen and is used to treat B-cell non-Hodgkin lymphoma (B-NHL). Few studies have been published examining the use of antibody panels to evaluate B-NHL treated with rituximab. The authors performed a retrospective analysis of immunophenotypic changes and clinical outcome in 18 patients with B-NHL following rituximab therapy. The intensity of CD20 expression was evaluated by flow cytometry and/or immunohistochemistry, before and after rituximab therapy; the latter samples were taken 5 to 12 months after initiating rituximab therapy (median 7 months). Nine of the 18 patients (50%) achieved complete or partial clinical remission and did not have morphologic evidence of lymphoma in the post-therapy samples. The other nine patients (50%) had persistent disease. Two patterns of CD20 expression were noted in the post-therapy samples: unchanged expression of CD20 in neoplastic cells (4/9 cases) and loss of or a significant decrease in detected CD20 expression in neoplastic cells (5/9 cases). These results show that in many cases of B-NHL persisting after rituximab therapy, CD20 expression decreases or is lost, raising the possibility of deletion or expression modulation of the CD20 gene in neoplastic cells. This study also underscores the importance of using a panel of antibodies to evaluate rituximab-treated B-NHL. C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Tufts Univ, Sch Med, Springfield, MA 01199 USA. Baystate Med Ctr, Springfield, MA 01199 USA. RP Hasserjian, RP (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, 55 Fruit St,Warren Bldg,2nd Floor, Boston, MA 02114 USA. EM rhasserjian@partners.org NR 22 TC 20 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-3345 J9 APPL IMMUNOHISTO M M JI Appl. Immunohistochem. PD MAR PY 2006 VL 14 IS 1 BP 18 EP 23 DI 10.1097/01.pai.0000145130.02931.74 PG 6 WC Anatomy & Morphology; Medical Laboratory Technology; Pathology SC Anatomy & Morphology; Medical Laboratory Technology; Pathology GA 018ME UT WOS:000235767600004 PM 16540725 ER PT J AU Scherrer-Crosbie, M AF Scherrer-Crosbie, M TI Role of echocardiography in studies of murine models of cardiac diseases SO ARCHIVES DES MALADIES DU COEUR ET DES VAISSEAUX LA English DT Article DE murine models; myocardial perfusion; echocardiography; applications studies ID LEFT-VENTRICULAR MASS; TRANSTHORACIC ECHOCARDIOGRAPHY; MYOCARDIAL-INFARCTION; DIASTOLIC FUNCTION; ANESTHETIZED MICE; DOPPLER; MOUSE; ULTRASOUND; ABNORMALITIES; DEFICIENCY AB Mice are increasingly used in cardiovascular research. Echocardiography is uniquely suited to monitor their cardiac phenotype, as it is noninvasive and can be serially obtained. The present review summarizes the parameters obtained by echocardiography and some of its applications. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. EM marielle@crosbie.com NR 29 TC 3 Z9 3 U1 0 U2 0 PU J B BAILLIERE PI PARIS PA 2, CITE PARADIS, 75010 PARIS, FRANCE SN 0003-9683 J9 ARCH MAL COEUR VAISS JI Arch. Mal. Coeur Vaiss. PD MAR PY 2006 VL 99 IS 3 BP 237 EP 241 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 032YR UT WOS:000236813300008 PM 16618027 ER PT J AU Hofmann, SG Meuret, AE Smits, JAJ Simon, NM Pollack, MH Eisenmenger, K Shiekh, M Otto, MW AF Hofmann, SG Meuret, AE Smits, JAJ Simon, NM Pollack, MH Eisenmenger, K Shiekh, M Otto, MW TI Augmentation of exposure therapy with D-cycloserine for social anxiety disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID FEAR-POTENTIATED STARTLE; PLACEBO-CONTROLLED TRIAL; BEHAVIORAL GROUP-THERAPY; GLYCINE RECEPTOR; COMMUNITY SAMPLE; CONDITIONED FEAR; PHOBIA; EXTINCTION; MEMORY; METAANALYSIS AB Context: Social anxiety disorder ( SAD) is common and debilitating. Although exposure therapy is one of the most effective forms of psychotherapy for this disorder, many patients remain symptomatic. Fear reduction in exposure therapy is similar to extinction learning, and early clinical data with specific phobias suggest that the treatment effects of exposure therapy for SAD may be enhanced with D-cycloserine, an agonist at the glutamatergic N-methyl-D-aspartate receptor. Objective: To determine whether short-term treatment with 50 mg of D-cycloserine enhances the efficacy of exposure therapy for SAD. Design: Randomized, double-blind, placebo-controlled augmentation trial examining the combination of D-cycloserine or pill placebo with exposure therapy for SAD. Setting: Patients were self-referred from the general community to 1 of 3 research clinics. Participants: Twenty-seven participants meeting DSM-IV criteria for SAD with significant public speaking anxiety. Interventions: Following a diagnostic interview and pretreatment assessment, participants received 5 therapy sessions delivered in either an individual or group therapy format. The first session provided an introduction to the treatment model and was followed by 4 sessions emphasizing exposure to increasingly challenging public speech situations with videotaped feedback of performances. One hour prior to each session, participants received single doses of D-cycloserine or placebo. Main Outcome Measures: Symptoms were assessed by patient self-report and by clinicians blind to the randomization condition before treatment, after treatment, and 1 month after the last session. Results: Participants receiving D-cycloserine in addition to exposure therapy reported significantly less social anxiety compared with patients receiving exposure therapy plus placebo. Controlled effect sizes were in the medium to large range. Conclusion: The pilot data provide preliminary support for the use of short-term dosing of D-cycloserine as an adjunctive intervention to exposure therapy for SAD. C1 Boston Univ, Dept Psychol, Boston, MA 02215 USA. Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. So Methodist Univ, Dept Psychol, Dallas, TX 75275 USA. RP Hofmann, SG (reprint author), Boston Univ, Dept Psychol, 648 Beacon St,6th Floor, Boston, MA 02215 USA. EM shofmann@bu.edu RI Smits, Jasper/A-4350-2008; Hofmann, Stefan/B-8769-2014; OI Smits, Jasper/0000-0001-7128-9807; Hofmann, Stefan/0000-0002-3548-9681; Smits, Jasper/0000-0003-1633-9693 NR 57 TC 344 Z9 348 U1 11 U2 41 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 2006 VL 63 IS 3 BP 298 EP 304 DI 10.1001/archpsyc.63.3.298 PG 7 WC Psychiatry SC Psychiatry GA 021GH UT WOS:000235971200009 PM 16520435 ER PT J AU Henson, JW AF Henson, JW TI Treatment of glioblastoma multiforme - A new standard SO ARCHIVES OF NEUROLOGY LA English DT Review ID RADIATION-THERAPY; MALIGNANT GLIOMAS; TEMOZOLOMIDE AB Glioblastoma multiforme is one of the most lethal and treatment-resistant of human tumors. Among the therapeutic triad of surgery, radiation therapy, and chemotherapy, only radiation therapy has been shown to improve survival.(1) Despite 30 years of intensive efforts to find an effective chemotherapy regimen for glioblastoma multiforme, the median survival of 12 to 15 months has not changed appreciably since the introduction of radiation therapy. C1 Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Neurol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuroradiol, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Neurol Serv, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM henson@helix.mgh.harvard.edu NR 7 TC 27 Z9 27 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2006 VL 63 IS 3 BP 337 EP 341 DI 10.1001/archneur.63.3.337 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 024ID UT WOS:000236187800004 PM 16533960 ER PT J AU Leverenz, JB Fishel, MA Peskind, ER Montine, TJ Nochlin, D Steinbart, E Raskind, MA Schellenberg, GD Bird, TD Tsuang, D AF Leverenz, JB Fishel, MA Peskind, ER Montine, TJ Nochlin, D Steinbart, E Raskind, MA Schellenberg, GD Bird, TD Tsuang, D TI Lewy body pathology in familial Alzheimer disease - Evidence for disease- and mutation-specific pathologic phenotype SO ARCHIVES OF NEUROLOGY LA English DT Article ID SPORADIC PARKINSONS-DISEASE; A-BETA DEPOSITION; ALPHA-SYNUCLEIN; NEUROFIBRILLARY CHANGES; CLINICAL-CRITERIA; APOLIPOPROTEIN-E; BODIES; DEMENTIA; PRESENILIN-1; BRAINS AB Background: The origin and significance of Lewy bodies and neurites (Lewy body pathology [LBP]) in Alzheimer disease (AD) are poorly understood. Objective: To examine LBP in the brainstem, limbic cortex, and neocortex of a large number of familial AD cases with mutations in 2 presenilin (PSEN) genes. Methods: Twenty-five familial AD cases with 9 known PSEN I mutations and 14 familial AD cases with a single PSEN 2 mutation (N1411) were examined for LBP using alpha-synuclein immunohistochemistry and sampling of multiple brainstem and cortical regions. Results: The amygdala was the most vulnerable site for LBP. In fact, virtually all (24 [96%] of 25 cases) of the PSEN 1 mutation cases had LBP in the amygdala. The PSEN 1 mutation cases also had more frequent LBP in the arnygdala and neocortex than those with the PSEN 2 mutation. However, within families with a single mutation of either PSEN I or PSEN 2, there was frequent variability of the LBP. Conclusion: These findings suggest that there are genetic influences on the presence of LBP in familial AD as demonstrated by the differences between PSEN I and PSEN 2 mutation cases. Results: The amygdala was the most vulnerable site for LBP. In fact, virtually all (24 [96%] of 25 cases) of the PSEN 1 mutation cases had LBP in the amygdala. The PSEN 1 mutation cases also had more frequent LBP in the amygdala and neocortex than those with the PSEN 2 mutation. However, within families with a single mutation of either PSEN I or PSEN 2, there was frequent variability of the LBP. Conclusion: These findings suggest that there are genetic influences on the presence of LBP in familial AD as demonstrated by the differences between PSEN I and PSEN 2 mutation cases. C1 Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Ctr, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Ctr, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Geriatr Ctr, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA USA. Univ Washington, Sch Med, Div Neuropathol, Dept Pathol, Seattle, WA USA. Univ Washington, Sch Med, Div Gerontol Geriatr, Dept Med, Seattle, WA USA. RP Leverenz, JB (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Ctr, 116MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM leverenz@u.washington.edu RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU NINDS NIH HHS [R01 NS048595] NR 45 TC 50 Z9 52 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2006 VL 63 IS 3 BP 370 EP 376 DI 10.1001/archneur.63.3.370 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 024ID UT WOS:000236187800008 PM 16533963 ER PT J AU Afshari, NA Duncan, SM Tanhehco, TY Azar, DT AF Afshari, NA Duncan, SM Tanhehco, TY Azar, DT TI Optimal size and location for corneal rotational autografts - A simplified mathematical model SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID IPSILATERAL AUTOKERATOPLASTY; KERATOPLASTY AB Objective: To calculate clinical guidelines for the optimal location and size of a rotational autokeratoplasty. Methods: The ideal graft size and trephine decentration for a rotational autograft were calculated based on scar location using geometric models. Mathematical variables were set to maximize postoperative visual acuity and for generalization of the geometric model. This model was used in a rotational autokeratoplasty of a patient with a history of a corneal scar and diplopia. An 8-mm autograft was decentered 0.5mm superiorly and rotated 180 to relocate the scar to the superior aspect of the cornea, out of the patient's vision. Results: For cases that satisfy the given variables, a graft diameter of 8-mm with a decentration of 0.5 mm balances maximization of scar removal and scar movement superiorly, with minimization of discrepancy in corneal thickness after rotation. For scars that are alpha degrees from horizontal, the graft should be rotated 180-alpha degrees. By using these calculations, the autograft in this case successfully resolved the diplopia and improved visual acuity. Conclusions: A rotational autograft can be an effective alternative to standard penetrating keratoplasty for some patients with corneal scars. We establish a mathematical model for most clinical instances of a rotational autograft, in which an 8-mm graft with a decentration of 0.5 mm best satisfies the goals of surgery. C1 Duke Univ, Med Ctr, Ctr Eye, Durham, NC 27710 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. RP Afshari, NA (reprint author), Duke Univ, Med Ctr, Ctr Eye, Box 3802, Durham, NC 27710 USA. EM afsha003@mc.duke.edu NR 18 TC 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 2006 VL 124 IS 3 BP 410 EP 413 DI 10.1001/archopht.124.3.410 PG 4 WC Ophthalmology SC Ophthalmology GA 021GI UT WOS:000235971300014 PM 16534062 ER PT J AU Hanauer, DA Wentzell, K Tovar, A Zeuhlke, J Kumar, V Laffel, LMB AF Hanauer, DA Wentzell, K Tovar, A Zeuhlke, J Kumar, V Laffel, LMB TI Parent and youth assessments of a handheld wireless device to enhance diabetes mellitus management SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Editorial Material C1 Joslin Diabet Ctr, Pediat & Adolescent Sect, Boston, MA 02115 USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Pediat & Adolescent Sect, 1 Joslin Pl, Boston, MA 02115 USA. EM lori.laffel@joslin.harvard.edu NR 6 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAR PY 2006 VL 160 IS 3 BP 321 EP 321 DI 10.1001/archpedi.160.3.321-a PG 1 WC Pediatrics SC Pediatrics GA 019XK UT WOS:000235871300015 PM 16520456 ER PT J AU Nosek, MA Hughes, RB Petersen, NJ Taylor, HB Robinson-Whelen, S Byrne, M Morgan, R AF Nosek, MA Hughes, RB Petersen, NJ Taylor, HB Robinson-Whelen, S Byrne, M Morgan, R TI Secondary conditions in a community-based sample of women with physical disabilities over a 1-year period SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE comorbidity; connective tissue diseases; disabled persons; joint diseases; multiple sclerosis; muscle weakness; nervous system; neurodegenerative diseases; neuromuscular diseases; obesity; pain; rehabilitation; rheumatic diseases; spinal cord injuries; trauma; women; women's health ID SPINAL-CORD-INJURY; INDEPENDENT LIVING CENTERS; UNITED-STATES; HEALTH; OUTCOMES; PEOPLE; GENDER; ADULTS AB Secondary conditions in a community-based sample of women with physical disabilities over a 1-year period. Arch Phys Med Rehabil 2006;87:320-7. Objective: To examine prevalence and predictors of secondary conditions in women with physical disabilities. Design: Cross-sectional. Setting: Women were recruited through private and public health clinics and various community organizations. Participants: A sample of 443 predominantly ethnic minority women with physical disabilities. Interventions: Not applicable. Main Outcome Measure: Health Conditions Checklist interference score. Results: Aggregated data over a 1-year period showed that nearly the entire sample reported interference from pain (94.5%) and fatigue (93.7%) and that at least three quarters of the sample reported problems with spasticity (85.4%), weakness (81.8%), sleep problems (80.2%), vision impairment (77.9%), and circulatory problems (77.9%). Obesity was substantially more prevalent in this sample (47.6%) than in the general population of women (34.0%). The mean number of secondary conditions per woman +/- standard deviation was 14.6 +/- 6.2 (range, 1-42), with 75% of the sample endorsing 10 or more conditions. On average, women reported experiencing 5.7 +/- 4.03 (range, 0-20) conditions that they rated as significant or chronic. A third (33.4%) of the variance in interference scores was accounted for in the regression analysis, with significant variance accounted for by race, disability type (women with joint and connective tissue disorders and women with postpolio reported the highest overall interference scores), greater functional limitations, and lower levels of general mental health. Conclusions: Secondary conditions in women with physical disabilities are substantially more problematic than reported previously in the literature. Further research is needed to determine health disparities of women with and without disabilities. Measurement issues and the clinical relevance of these findings are discussed. C1 Baylor Coll Med, Ctr Res Women Disabil, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Dept Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33152 USA. Univ Texas, Hlth Sci Ctr, Div Dev Pediat, Houston, TX USA. RP Nosek, MA (reprint author), Baylor Coll Med, Ctr Res Women Disabil, Dept Phys Med & Rehabil, 6550 Fannin,Ste 1421, Houston, TX 77030 USA. EM mnosek@bcm.tmc.edu RI Morgan, Robert/A-8577-2009 FU PHS HHS [R04/CCR618805] NR 34 TC 40 Z9 41 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2006 VL 87 IS 3 BP 320 EP 327 DI 10.1016/j.apmr.2005.11.003 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 021XZ UT WOS:000236020500003 PM 16500164 ER PT J AU Flood, KM Huang, ME Roberts, TL Pasquina, PF Nelson, VS Bryant, PR AF Flood, KM Huang, ME Roberts, TL Pasquina, PF Nelson, VS Bryant, PR TI Limb deficiency and prosthetic management. 2. Aging with limb loss SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE aging; amputation; artificial limbs; complications; outcome assessment (health care); rehabilitation ID AMPUTEE PATIENT; RISK-FACTORS; AMPUTATION; REHABILITATION; POPULATION; VETERANS; PAIN AB This self-directed learning module highlights the issues faced by people aging with limb loss. It is part of the study guide on limb deficiency and vascular rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article specifically focuses on the impact that limb loss has on health and physical function throughout the life span. Case examples are used to illustrate what effect limb loss in childhood or young adulthood has on the incidence and management of new impairments or disease processes commonly associated with aging. Overall Article Objective: To discuss the impact of early-life limb loss on the incidence and management of physiologic and functional changes associated with aging. C1 VA Pittsburgh Healthcare Syst, Phys Med & Rehabil Program, Pittsburgh, PA 15240 USA. Northwestern Univ, Feinberg Sch Med, Rehabil Inst Chicago, Dept Phys Med & Rehabil, Chicago, IL 60611 USA. George E Wahlen Dept Vet Affairs Med Ctr, Phys Med & Rehabil Serv, Salt Lake City, UT USA. Walter Reed Army Med Ctr, Phys Med & Rehabil Serv, Washington, DC 20307 USA. Univ Michigan, Sch Med, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA. Good Shepherd Rehabil Hosp, Allentown, PA USA. RP Flood, KM (reprint author), VA Pittsburgh Healthcare Syst, Phys Med & Rehabil Program, 132Y-A,Univ Dr C, Pittsburgh, PA 15240 USA. EM vze2zn62@verizon.net NR 33 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2006 VL 87 IS 3 SU 1 BP S10 EP S14 DI 10.1016/j.apmr.2005.11.023 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 024PK UT WOS:000236208200003 PM 16500188 ER PT J AU Huang, ME Nelson, VS Flood, KM Roberts, TL Bryant, PR Pasquina, PF AF Huang, ME Nelson, VS Flood, KM Roberts, TL Bryant, PR Pasquina, PF TI Limb deficiency and prosthetic management. 3. Complex limb deficiency SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE amputation; artificial limbs; burns; multiple trauma; rehabilitation ID KNEE AMPUTATION LEVEL; ELECTRICAL BURNS; UPPER EXTREMITY; REHABILITATION; INJURIES; AMPUTEE; SALVAGE; SKIN AB This self-directed learning module highlights rehabilitation and prosthetic issues associated with complex limb deficiencies. It is part of the chapter on acquired limb deficiencies in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article discusses rehabilitation and prosthetic management of patients with amputations for complex limb deficiencies secondary to trauma. Mechanisms of injury, prosthetic issues, prosthetic components, and potential problems in prosthetic fitting will be discussed. Overall Article Objective: To evaluate common problems associated with complex limb deficiency. C1 Northwestern Univ, Rehabil Inst Chicago, Feinberg Sch Med, Dept Phys Med & Rehabil, Chicago, IL 60611 USA. Univ Michigan, Sch Med, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA. Vet Affairs Pittsburgh Healthcare Syst, Phys Med & Rehabil Program, Pittsburgh, PA USA. George E Wahlen Dept Vet Affairs, Med Ctr, Phys Med & Rehabil Serv, Salt Lake City, UT USA. Good Shepherd Rehabil Hosp, Allentown, PA USA. Walter Reed Army Med Ctr, Phys Med & Rehabil Serv, Washington, DC 20307 USA. RP Huang, ME (reprint author), Northwestern Univ, Rehabil Inst Chicago, Feinberg Sch Med, Dept Phys Med & Rehabil, 345 E Super St, Chicago, IL 60611 USA. EM mhuang@ric.org NR 34 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2006 VL 87 IS 3 SU 1 BP S15 EP S20 DI 10.1016/j.apmr.2005.11.024 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 024PK UT WOS:000236208200004 PM 16500189 ER PT J AU Nelson, VS Flood, KM Bryant, PR Huang, ME Pasquina, PF Roberts, TL AF Nelson, VS Flood, KM Bryant, PR Huang, ME Pasquina, PF Roberts, TL TI Limb deficiency and prosthetic management. 1. Decision making in prosthetic prescription and management SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE amputation; artificial limbs; limb deformities, congenital; prostheses and implants; rehabilitation AB Limb deficiency and prosthetic management. 1. Decision making in prosthetic prescription and management. C1 Univ Michigan, Sch Med, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA. Vet Affairs Pittsburgh Healthcare Syst, Phys Med & Rehabil Program, Pittsburgh, PA USA. Good Shepherd Rehabil Hosp, Allentown, PA USA. Northwestern Univ, Feinberg Sch Med, Dept Phys Med & Rehabil, Chicago, IL 60611 USA. Walter Reed Army Med Ctr, Phys Med & Rehabil Serv, Washington, DC 20307 USA. George E Wahlen Dept Vet Affairs Med Ctr, Phys Med & Rehabil Serv, Salt Lake City, UT USA. RP Nelson, VS (reprint author), Dept PM&R, 325 E Eisenhower, Ann Arbor, MI 48108 USA. EM vsnelson@umich.edu NR 21 TC 16 Z9 17 U1 4 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2006 VL 87 IS 3 SU 1 BP S3 EP S9 DI 10.1016/j.apmr.2005.11.022 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 024PK UT WOS:000236208200002 PM 16500187 ER PT J AU Pasquina, PF Bryant, PR Huang, ME Roberts, TL Nelson, VS Flood, KM AF Pasquina, PF Bryant, PR Huang, ME Roberts, TL Nelson, VS Flood, KM TI Advances in amputee care SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Review DE amputation; prosthetics and implants; rehabilitation; review [publication type] ID DIFFERENT PROSTHETIC COMPONENTS; LOWER-LIMB AMPUTATIONS; TRANS-FEMORAL AMPUTEE; BELOW-KNEE AMPUTEES; QUALITY-OF-LIFE; ENERGY-EXPENDITURE; INTELLIGENT PROSTHESIS; TRANSFEMORAL AMPUTEES; HAND TRANSPLANTATION; OUTCOME MEASURE AB This self-directed learning module highlights the recent in novations in amputee care. It is part of the study guide on limb deficiency in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This focused review article describes the key elements of a successful comprehensive amputee program, the basic surgical considerations for upper- and lower-extremity amputation, and some of the more recent advances in prosthetic components. Further, an update is given on issues such as hand transplantation and the integration of robotics and artificial muscles for people with limb loss. Overall Article Objective: (a) To discuss current issues and advances in the care of patients with amputation, (b) to describe the key elements in designing a comprehensive amputee care program, and (c) to discuss surgical considerations of limb preservation and amputation levels. C1 Walter Reed Army Med Ctr, Sect 3J, Phys Med & Rehabil Serv, Washington, DC 20307 USA. Good Shepherd Rehabil Hosp, Allentown, PA USA. Northwestern Univ, Feinberg Sch Med, Dept Phys Med & Rehabil, Chicago, IL 60611 USA. George E Wahlen Dept Vet Affairs, Med Ctr, Salt Lake City, UT USA. Univ Michigan, Sch Med, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA. Vet Affairs Pittsburgh Healthcare Syst, Phys Med & Rehabil Program, Pittsburgh, PA USA. RP Pasquina, PF (reprint author), Walter Reed Army Med Ctr, Sect 3J, Phys Med & Rehabil Serv, Bldg 2,6900 Georgia Ave, Washington, DC 20307 USA. EM Paul.Pasquina@NA.AMEDD.ARMY.MIL NR 86 TC 28 Z9 30 U1 1 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2006 VL 87 IS 3 SU 1 BP S34 EP S43 DI 10.1016/j.apmr.2005.11.026 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 024PK UT WOS:000236208200006 PM 16500191 ER PT J AU Roberts, TL Pasquina, PF Nelson, VS Flood, KM Bryant, PR Huang, ME AF Roberts, TL Pasquina, PF Nelson, VS Flood, KM Bryant, PR Huang, ME TI Limb deficiency and prosthetic management. 4. Comorbidities associated with limb loss SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE amputation; comorbidity; outcome assessment (health care); pain; rehabilitation ID PERIPHERAL-ARTERIAL-DISEASE; LOWER-EXTREMITY AMPUTATIONS; REHABILITATION; DEPRESSION; ADULTS; DISABILITY; AMPUTEES; PATIENT; POPULATION; PREVALENCE AB This self-directed learning module highlights common comorbidities found in people with amputations and their impact on functional outcome. It is part of the study guide on limb deficiency and vascular rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article focuses on prosthetic considerations, functional outcome, and potential complications for a woman with the comorbidities of stroke and diabetes who experiences a dysvascular amputation. Formulation of the differential diagnosis, management of limb pain, and evaluation of the potential psychosocial issues arising after amputation are also discussed. Overall Article Objective: To analyze common comorbidities of people with amputations and to delineate their impact on functional outcome. C1 George E Wahlen Dept Vet Affairs, Med Ctr, Phys Med & Rehabil Serv, Salt Lake City, UT 84148 USA. Walter Reed Army Med Ctr, Phys Med & Rehabil Serv, Washington, DC 20307 USA. Univ Michigan, Sch Med, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA. Vet Affairs Pittsburgh Healthcare Syst, Phys Med & Rehabil Program, Pittsburgh, PA USA. Good Shepherd Rehabil Hosp, Allentown, PA USA. Northwestern Univ, Rehabil Inst Chicago, Feinberg Sch Med, Dept Phys Med & Rehabil, Chicago, IL 60611 USA. RP Roberts, TL (reprint author), George E Wahlen Dept Vet Affairs, Med Ctr, Phys Med & Rehabil Serv, 500 Foothill Blvd,117, Salt Lake City, UT 84148 USA. EM Toni.Roberts@med.va.gov NR 51 TC 11 Z9 11 U1 2 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2006 VL 87 IS 3 SU 1 BP S21 EP S27 DI 10.1016/j.apmr.2005.11.025 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 024PK UT WOS:000236208200005 PM 16500190 ER EF