FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Yu, CS Negishi, K Shek, S Chan, N Chan, HHL AF Yu, Carol S. Negishi, Kei Shek, Samantha Chan, Nicola Chan, Henry H. L. TI A PROSPECTIVE MULTI-CENTER CLINICAL STUDY OF PHOTOREJUVENTATION IN ASIAN SKIN USING 2,790 nm INFRARED LASER SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 29th Annual Conference of the American-Society-for-Laser-Medicine and Surgery CY APR 01-05, 2009 CL National Harbor, MD SP Amer Soc Laser Med & Surg C1 Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Tokyo Womens Med Univ, Tokyo, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2009 SU 21 BP 42 EP 42 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 464RV UT WOS:000267524700120 ER PT J AU Tsao, S Yao, M Henry, F Tsao, H Redmond, R Kochevar, I AF Tsao, Sandy Yao, Min Henry, Frank Tsao, Hensin Redmond, Robert Kochevar, Irene TI LASER-ACTIVATED EXCISIONAL WOUND REPAIR WITH PHOTOCHEMICAL TISSUE BONDING SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 29th Annual Conference of the American-Society-for-Laser-Medicine and Surgery CY APR 01-05, 2009 CL National Harbor, MD SP Amer Soc Laser Med & Surg C1 [Tsao, Sandy; Yao, Min; Henry, Frank; Tsao, Hensin; Redmond, Robert; Kochevar, Irene] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2009 BP 108 EP 108 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 464RV UT WOS:000267524700316 ER PT S AU Goldman, S Turner, CD AF Goldman, Stewart Turner, Christopher D. BE Goldman, S Turner, CD TI Introduction to Brain Tumor Survivorship and Historical Perspective SO LATE EFFECTS OF TREATMENT FOR BRAIN TUMORS SE Cancer Treatment and Research LA English DT Editorial Material; Book Chapter ID SURVIVING ADULT CANCERS; CENTRAL-NERVOUS-SYSTEM; NEUROCOGNITIVE SEQUELAE; CHILDHOOD; CHILDREN C1 [Goldman, Stewart] Northwestern Univ, Childrens Mem Hosp, Fienberg Sch Med, Chicago, IL 60614 USA. [Turner, Christopher D.] Dana Farber Canc Inst, Leonard P Zakim Ctr Integrat Therapies, Boston, MA 02115 USA. [Turner, Christopher D.] Harvard Univ, Sch Med, Boston, MA USA. RP Goldman, S (reprint author), Northwestern Univ, Childrens Mem Hosp, Fienberg Sch Med, 2300 Childrens Plaza,Box 30, Chicago, IL 60614 USA. EM sgoldman@childrensmemorial.org; christopher_turner@dfci.harvard.edu NR 22 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0927-3042 BN 978-0-387-77102-1 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2009 VL 150 BP 3 EP 6 DI 10.1007/b109924_1 D2 10.1007/b109924 PG 4 WC Oncology; Neurosciences SC Oncology; Neurosciences & Neurology GA BKX35 UT WOS:000269522400001 PM 19834658 ER PT S AU Shih, HA Loeffler, JS Tarbell, NJ AF Shih, Helen A. Loeffler, Jay S. Tarbell, Nancy J. BE Goldman, S Turner, CD TI Late Effects of CNS Radiation Therapy SO LATE EFFECTS OF TREATMENT FOR BRAIN TUMORS SE Cancer Treatment and Research LA English DT Article; Book Chapter ID LONG-TERM SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHILDHOOD-CANCER SURVIVOR; LOW-GRADE GLIOMAS; EXTERNAL-BEAM IRRADIATION; GAMMA-KNIFE RADIOSURGERY; CENTRAL-NERVOUS-SYSTEM; PRIMARY BRAIN-TUMORS; TIME-DOSE FACTORS; PITUITARY-ADENOMAS C1 [Shih, Helen A.; Loeffler, Jay S.; Tarbell, Nancy J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Tarbell, Nancy J.] Massachusetts Gen Hosp, Div Pediat Radiat Oncol, Boston, MA 02114 USA. [Shih, Helen A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Shih, HA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM hshih@partners.org; jloeffler@partners.org; tarbell.nancy@mgh.harvard.edu NR 71 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0927-3042 BN 978-0-387-77102-1 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2009 VL 150 BP 23 EP 41 DI 10.1007/b109924_3 D2 10.1007/b109924 PG 19 WC Oncology; Neurosciences SC Oncology; Neurosciences & Neurology GA BKX35 UT WOS:000269522400003 PM 19834660 ER PT S AU Dietrich, J Kesari, S AF Dietrich, Joerg Kesari, Santosh BE Goldman, S Turner, CD TI Effect of Cancer Treatment on Neural Stem and Progenitor Cells SO LATE EFFECTS OF TREATMENT FOR BRAIN TUMORS SE Cancer Treatment and Research LA English DT Article; Book Chapter ID CENTRAL-NERVOUS-SYSTEM; PRIMARY CNS LYMPHOMA; ADULT HUMAN BRAIN; ACUTE LYMPHOBLASTIC-LEUKEMIA; GLIAL PRECURSOR CELL; HIPPOCAMPAL NEUROGENESIS; DENTATE GYRUS; ADJUVANT CHEMOTHERAPY; SUBVENTRICULAR ZONE; COGNITIVE FUNCTION C1 [Dietrich, Joerg; Kesari, Santosh] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Dietrich, Joerg] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Kesari, Santosh] Harvard Univ, Sch Med, Boston, MA USA. [Kesari, Santosh] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Dietrich, J (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM jdietrich1@partners.org; skesari@partners.org RI Kesari, Santosh/E-8461-2013 NR 101 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0927-3042 BN 978-0-387-77102-1 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2009 VL 150 BP 81 EP 95 DI 10.1007/b109924_6 D2 10.1007/b109924 PG 15 WC Oncology; Neurosciences SC Oncology; Neurosciences & Neurology GA BKX35 UT WOS:000269522400006 PM 19834663 ER PT S AU Monje, M Wen, PY AF Monje, Michelle Wen, Patrick Y. BE Goldman, S Turner, CD TI Neurological Complications in Adults SO LATE EFFECTS OF TREATMENT FOR BRAIN TUMORS SE Cancer Treatment and Research LA English DT Article; Book Chapter ID CENTRAL-NERVOUS-SYSTEM; OF-THE-LITERATURE; RADIATION-INDUCED TELANGIECTASIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE LYMPHOCYTIC-LEUKEMIA; DOSE CYTOSINE-ARABINOSIDE; MOTOR-NEURON SYNDROME; BRAIN-TUMOR PATIENTS; CRANIAL IRRADIATION; COGNITIVE FUNCTION C1 [Wen, Patrick Y.] Packard Hosp, Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Div Neurooncol, Boston, MA 02115 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. [Monje, Michelle] Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Wen, PY (reprint author), Packard Hosp, Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Div Neurooncol, SW430,44 Binney St, Boston, MA 02115 USA. EM pwen@partners.org NR 90 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0927-3042 BN 978-0-387-77102-1 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2009 VL 150 BP 113 EP 132 DI 10.1007/b109924_8 D2 10.1007/b109924 PG 20 WC Oncology; Neurosciences SC Oncology; Neurosciences & Neurology GA BKX35 UT WOS:000269522400008 PM 19834665 ER PT S AU Rosenthal, DS Turner, CD Doherty-Gilman, AM Dean-Clower, E AF Rosenthal, David S. Turner, Christopher D. Doherty-Gilman, Anne M. Dean-Clower, Elizabeth BE Goldman, S Turner, CD TI Integrative Oncology as Part of the Treatment for Brain Tumors SO LATE EFFECTS OF TREATMENT FOR BRAIN TUMORS SE Cancer Treatment and Research LA English DT Article; Book Chapter ID ALTERNATIVE MEDICINE USE; STAGE BREAST-CANCER; COMPLEMENTARY THERAPIES; CONTROLLED-TRIAL; CLINICAL-TRIAL; UNITED-STATES; ACUPUNCTURE; WOMEN; CHEMOTHERAPY; SAFETY C1 [Rosenthal, David S.; Turner, Christopher D.; Doherty-Gilman, Anne M.; Dean-Clower, Elizabeth] Dana Farber Canc Inst, Leonard P Zakim Ctr Integrat Therapies, Boston, MA 02115 USA. [Rosenthal, David S.; Turner, Christopher D.; Dean-Clower, Elizabeth] Harvard Univ, Sch Med, Boston, MA USA. RP Rosenthal, DS (reprint author), Dana Farber Canc Inst, Leonard P Zakim Ctr Integrat Therapies, 44 Binney St, Boston, MA 02115 USA. EM drose@uhs.harvard.edu; christopher_turner@dfci.harvard.edu NR 42 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0927-3042 BN 978-0-387-77102-1 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2009 VL 150 BP 353 EP 362 DI 10.1007/b109924_23 D2 10.1007/b109924 PG 10 WC Oncology; Neurosciences SC Oncology; Neurosciences & Neurology GA BKX35 UT WOS:000269522400023 PM 19834680 ER PT J AU Bredy, TW Barad, M AF Bredy, Timothy W. Barad, Mark TI Social modulation of associative fear learning by pheromone communication SO LEARNING & MEMORY LA English DT Article ID AMINE-ASSOCIATED RECEPTOR-1; TRACE AMINES; ANIMAL-MODEL; STRESS; MICE; PHENYLETHYLAMINE; RATS; AMYGDALA; HUMANS; ODORS AB Mice communicate through visual, vocal, and olfactory cues that influence innate, nonassociative behavior. We here report that exposure to a recently fear-conditioned familiar mouse impairs acquisition of conditioned fear and facilitates fear extinction, effects mimicked by both an olfactory chemosignal emitted by a recently fear-conditioned familiar mouse and by the putative stress-related anxiogenic pheromone beta-phenylethylamine (beta-PEA). Together, these findings suggest social modulation of higher-order cognitive processing through pheromone communication and support the concurrent excitor hypothesis of extinction learning. C1 [Bredy, Timothy W.; Barad, Mark] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Bredy, Timothy W.; Barad, Mark] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Barad, Mark] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Bredy, TW (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. EM tbredy@mednet.ucla.edu FU NIMH; Tennenbaum Family Foundation FX This work was supported in part by grants from the NIMH and the Tennenbaum Family Foundation (to M. B.) and by postdoctoral fellowships from NSERC and CIHR (to T. W. B.). We thank James McGaugh, Richard Brown, and Terra Branton for their helpful comments on and discussion of this work. NR 35 TC 23 Z9 24 U1 0 U2 12 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD JAN PY 2009 VL 16 IS 1 BP 12 EP 18 DI 10.1101/lm.1226009 PG 7 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 389MO UT WOS:000262097500003 PM 19117912 ER PT J AU Podar, K Chauhan, D Anderson, KC AF Podar, K. Chauhan, D. Anderson, K. C. TI Bone marrow microenvironment and the identification of new targets for myeloma therapy SO LEUKEMIA LA English DT Review DE multiple myeloma; bone marrow; novel therapies ID HUMAN MULTIPLE-MYELOMA; NF-KAPPA-B; ENDOTHELIAL GROWTH-FACTOR; MEDIATED DRUG-RESISTANCE; NON-HODGKINS-LYMPHOMA; LENALIDOMIDE PLUS DEXAMETHASONE; SUBEROYLANILIDE HYDROXAMIC ACID; PROTEASOME INHIBITOR BORTEZOMIB; PLASMA-CELL DIFFERENTIATION; TRANSCRIPTION FACTOR XBP-1 AB The development of multiple myeloma (MM) is a complex multistep process involving both early and late genetic changes in the tumor cell as well as selective supportive conditions by the bone marrow (BM) microenvironment. Indeed, it is now well established that MM cell-induced disruption of the BM homeostasis between the highly organized cellular and extracellular compartments supports MM cell proliferation, survival, migration and drug resistance through activation of various signaling (for example, PI3K/Akt, JAK/Stat-, Raf/MEK/MAPK-, NF kappa B- and Wnt-) pathways. Based on our enhanced understanding of the functional importance of the MM BM microenvironment and its inter-relation with the MM cell resulting in homing, seeding, proliferation and survival, new molecular targets have been identified and derived treatment regimens in MM have already changed fundamentally during recent years. These agents include thalidomide, its immunomodulatory derivative lenalidomide and the proteasome inhibitor bortezomib, which mediate tumor cytotoxicity in the BM milieu. Ongoing studies are further delineating MM pathogenesis in the BM to enhance cytotoxicity, avoid drug resistance and improve patient outcome. C1 [Podar, K.; Chauhan, D.; Anderson, K. C.] Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Dana Farber Canc Inst,LeBow Inst Myeloma Therapeu, Boston, MA 02115 USA. RP Podar, K (reprint author), Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Dana Farber Canc Inst,LeBow Inst Myeloma Therapeu, 44 Binney St, Boston, MA 02115 USA. EM klaus_podar@dfci.harvard.edu FU Multiple Myeloma Research Foundation (MMRF); Dunkin' Donuts Rising Star Award (KP); National Institutes of Health [IP50 CA100707, PO-1 78378, RO-1 CA 50947]; The Myeloma Research Fund; LeBow Family Fund to Cure Myeloma (KCA) FX This work was supported by Multiple Myeloma Research Foundation (MMRF) Senior Research Grant Award and Dunkin' Donuts Rising Star Award (KP), as well as National Institutes of Health Grants IP50 CA100707, PO-1 78378 and RO-1 CA 50947; The Myeloma Research Fund; and the LeBow Family Fund to Cure Myeloma (KCA) NR 175 TC 165 Z9 176 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JAN PY 2009 VL 23 IS 1 BP 10 EP 24 DI 10.1038/leu.2008.259 PG 15 WC Oncology; Hematology SC Oncology; Hematology GA 394TL UT WOS:000262470700003 PM 18843284 ER PT J AU Friese, CR Abel, GA Magazu, LS Neville, BA Richardson, LC Earle, CC AF Friese, Christopher R. Abel, Gregory A. Magazu, Lysa S. Neville, Bridget A. Richardson, Lisa C. Earle, Craig C. TI Diagnostic delay and complications for older adults with multiple myeloma SO LEUKEMIA & LYMPHOMA LA English DT Article CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol DE Multiple myeloma; diagnostic delay; health services research; quality of care ID ACUTE MYOCARDIAL-INFARCTION; FAMILY PHYSICIANS KNOWLEDGE; CANCER REFERRAL GUIDELINES; GENDER-DIFFERENCES; NATIONAL-SURVEY; BREAST-CANCER; NHS-PATIENTS; PRIMARY-CARE; SYMPTOMS; STAGE AB Increased attention to timely diagnosis motivated us to study 5483 patients diagnosed with multiple myeloma using Medicare claims linked to tumor registries in the Surveillance, Epidemiology and End Results programme. We calculated the time between initial visits for anemia or back pain and for myeloma diagnosis, and used logistic regression to predict the likelihood of diagnostic delay, and also the likelihood of renal or skeletal complications. The median time between sign or symptom and myeloma diagnosis was 99 days. Patients with anemia, back pain and comorbidities were more likely to experience diagnostic delay (OR 1.6, 95% CI 1.3-2.0). Diagnosis while hospitalised (OR 2.5, 95% CI 2.2-2.9) and chemotherapy treatment within 6 months of diagnosis (OR 1.4, 95% CI 1.2-1.6) significantly predicted complications; diagnostic delay did not (OR 0.9, 95% CI 0.8-1.1). Our data suggest that complications are more strongly associated with health status and myeloma severity than with diagnostic delays. C1 [Earle, Craig C.] Sunnybrook Hlth Sci Ctr, Inst Clin Evaluat Sci, Toronto, ON M4N 3M5, Canada. [Friese, Christopher R.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. [Abel, Gregory A.; Magazu, Lysa S.; Neville, Bridget A.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Abel, Gregory A.] Harvard Univ, Sch Med, Dept Med, Div Med Oncol, Boston, MA USA. [Richardson, Lisa C.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. RP Earle, CC (reprint author), Sunnybrook Hlth Sci Ctr, Inst Clin Evaluat Sci, 2075 Bayview Ave,Room G-106, Toronto, ON M4N 3M5, Canada. EM craig.earle@ices.on.ca RI Friese, Christopher/D-2097-2013 OI Friese, Christopher/0000-0002-2281-2056 FU NCI NIH HHS [R25 CA 057711-12, R25 CA057711, T32 CA009172]; NINR NIH HHS [K99 NR010750, K99 NR010750-02, R00 NR010750]; PHS HHS [200-2002-00575] NR 48 TC 17 Z9 17 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2009 VL 50 IS 3 BP 392 EP 400 AR PII 909597695 DI 10.1080/10428190902741471 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 435RN UT WOS:000265361100018 PM 19294556 ER PT J AU Laubach, JP Mitsiades, CS Roccaro, AM Ghobrial, IM Anderson, KC Richardson, PG AF Laubach, Jacob P. Mitsiades, Constantine S. Roccaro, Aldo M. Ghobrial, Irene M. Anderson, Kenneth C. Richardson, Paul G. TI Clinical challenges associated with bortezomib therapy in multiple myeloma and Waldenstroms Macroglobulinemia SO LEUKEMIA & LYMPHOMA LA English DT Review DE Drug resistance; myeloma; pharmacotherapeutics; clinical result ID INDUCED PERIPHERAL NEUROPATHY; STEM-CELL TRANSPLANTATION; PEGYLATED LIPOSOMAL DOXORUBICIN; PROTEASOME INHIBITOR BORTEZOMIB; HIGH-DOSE THERAPY; AUTOLOGOUS TRANSPLANTATION; CHEMOTHERAPEUTIC-AGENTS; REFRACTORY MYELOMA; RANDOMIZED-TRIAL; CANCER-TREATMENT AB Rapid development of the small molecule proteasome inhibitor bortezomib has yielded important clinical benefit for patients with multiple myeloma. Early phase clinical trials suggest the agent has similar efficacy in Waldenstroms Macroglobulinemia. Optimization of bortezomib-based therapy, though, requires an understanding of the various challenges associated with use of the drug. This review highlights the rationale for bortezomib therapy in patients with multiple myeloma and Waldenstroms Macroglobulinemia, mechanisms of bortezomib resistance, important therapy-related side effects, and new directions for the use of proteasome inhibitors in these disorders. C1 [Laubach, Jacob P.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Laubach, JP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM jacobp_laubach@dfci.harvard.edu OI Roccaro, Aldo/0000-0002-1872-5128 FU NCI NIH HHS [R21 CA126119, R21 CA126119-02] NR 68 TC 18 Z9 18 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2009 VL 50 IS 5 BP 694 EP 702 AR PII 911397794 DI 10.1080/10428190902866732 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 447OW UT WOS:000266201800007 PM 19452315 ER PT J AU Slack, GW Ferry, JA Hasserjian, RP Sohani, AR Longtine, JA Harris, NL Zukerberg, LR AF Slack, Graham W. Ferry, Judith A. Hasserjian, Robert P. Sohani, Aliyah R. Longtine, Janina A. Harris, Nancy L. Zukerberg, Lawrence R. TI Lymphocyte depleted Hodgkin lymphoma: an evaluation with immunophenotyping and genetic analysis SO LEUKEMIA & LYMPHOMA LA English DT Article DE Classical Hodgkin lymphoma; lymphocyte depleted Hodgkin lymphoma; morphologic features; immunophenotype; immunoglobulin gene rearrangement ID REED-STERNBERG CELLS; TISSUE MICROARRAY ANALYSIS; B-CELL; TRANSCRIPTION FACTORS; IMMUNOGLOBULIN TRANSCRIPTION; DIFFERENTIAL-DIAGNOSIS; DISEASE; EXPRESSION; MARKERS; BOB.1 AB Lymphocyte depleted classical Hodgkin lymphoma (LDHL) is a vanishing category of classical Hodgkin lymphoma (CHL); many cases previously placed in this category are now recognised as diffuse large B-cell lymphoma (DLBCL), anaplastic large-cell lymphoma (ALCL), or nodular sclerosis CHL with lymphocyte depletion. In addition, the recent recognition of high grade B-cell lymphomas intermediate between DLBCL and CHL (grey-zone lymphomas) raises the question of whether LDHL exists at all as a category of CHL. We studied eight cases that fulfilled diagnostic criteria of LDHL according to the 2008 WHO Classification. The cases involved lymph nodes (7 cases) and pleura (1 case) from four males and four females (age 30-71 years; median 62 years). All tumors contained numerous Hodgkin-Reed-Sternberg (HRS) cells, fibroblasts and histiocytes and scattered lymphocytes. In three cases the tumors had a more diffuse fibrotic appearance, while in five cases they appeared reticular and anaplastic. Neoplastic cells in all cases expressed CD30, CD15, fascin, weak PAX5 and MUM-1 and lacked CD45, Alk-1, EMA, CD3, CD68, Mart-1 and cytokeratin. Oct.2 and/or Bob-1 were expressed in all cases. Two cases variably expressed CD20 but were CD79a negative. Four cases were positive for EBV. All the four cases with adequate DNA had clonally rearranged IGH genes. The combined morphologic, immunophenotypic and molecular genetic features of this group of cases distinguish LDHL from other disease entities, including grey-zone lymphomas. C1 [Ferry, Judith A.] Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Longtine, Janina A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Longtine, Janina A.] 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, Warren 2,55 Fruit St, Boston, MA 02114 USA. EM jferry@partners.org NR 33 TC 10 Z9 10 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2009 VL 50 IS 6 BP 937 EP 943 AR PII 911420949 DI 10.1080/10428190902930488 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 456AS UT WOS:000266810900015 PM 19455461 ER PT J AU Zivkovic, SA Lacomis, D Lentzsch, S AF Zivkovic, Sasa A. Lacomis, David Lentzsch, Suzanne TI Paraproteinemic neuropathy SO LEUKEMIA & LYMPHOMA LA English DT Review DE M-protein; neuropathy; MGUS; multiple myeloma; POEMS ID MYELIN-ASSOCIATED GLYCOPROTEIN; STEM-CELL TRANSPLANTATION; TERM-FOLLOW-UP; CHRONIC LYMPHOCYTIC-LEUKEMIA; PRIMARY SYSTEMIC AMYLOIDOSIS; MULTIFOCAL MOTOR NEUROPATHY; IGM MONOCLONAL GAMMOPATHY; ANTI-MAG ANTIBODIES; UNDETERMINED SIGNIFICANCE; PERIPHERAL NEUROPATHY AB Monoclonal proteins (paraproteins) may be detected in the sera in similar to 1% of the general population and are frequently associated with peripheral neuropathy. Paraproteinemic neuropathy (PPN) is most commonly associated with monoclonal gammopathy of undetermined significance, and may also occur in the context of multiple myeloma, amyloidosis, cryoglobulinemia, and other hematologic malignant and nonmalignant conditions. Possible malignant conversion of underlying benign monoclonal gammopathy should be closely monitored, and risk factors include progression of neuropathy and rising titers of monoclonal protein. PPN is frequently associated with autoantibodies targeting peripheral nerve antigens, including anti-MAG and anti-GM1 antibodies. Therapy is mostly based on the treatment of the underlying hematologic disorder. Risks and benefits should be carefully evaluated as treatment may be associated with considerable morbidity. Rituximab may be helpful in treatment of IgM-PPN, and paraproteinemic multifocal motor neuropathy usually responds to IVIG. Plasmapheresis is more effective with IgG/IgA paraproteinemic neuropathies. At this time it is not clear whether mere presence of neuropathy warrants more aggressive treatment of otherwise quiescent hematologic malignances (e.g. smoldering myeloma). C1 [Zivkovic, Sasa A.] Univ Pittsburgh, Dept Neurol, Med Ctr, Sch Med, Pittsburgh, PA 15213 USA. [Zivkovic, Sasa A.; Lacomis, David] MSSL Neurol, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Lacomis, David] Univ Pittsburgh, Sch Med, Dept Pathol Neuropathol, Pittsburgh, PA 15213 USA. [Lentzsch, Suzanne] Univ Pittsburgh, Sch Med, Dept Internal Med Hematol, Pittsburgh, PA 15213 USA. RP Zivkovic, SA (reprint author), Univ Pittsburgh, Dept Neurol, Med Ctr, Sch Med, 3471 5th Ave 811, Pittsburgh, PA 15213 USA. EM zivkovics@upmc.edu NR 126 TC 14 Z9 15 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2009 VL 50 IS 9 BP 1422 EP 1433 DI 10.1080/10428190903111922 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA 503QC UT WOS:000270552100008 PM 19637090 ER PT J AU Burzynski, JA Toro, JJ Patel, RC Lee, S Greene, RE Ochoa-Bayona, JL Frei, CR Freytes, CO AF Burzynski, Julianna Aleathea Toro, Juan J. Patel, Rakhi Chhaganbhai Lee, Shuko Greene, Rebecca Elizabeth Ochoa-Bayona, Jose Leonel Frei, Christopher Raymond Freytes, Cesar O. TI Toxicity of a second autologous peripheral blood stem cell transplant in patients with relapsed or recurrent multiple myeloma SO LEUKEMIA & LYMPHOMA LA English DT Article DE Multiple myeloma; autologous; hematopoietic stem cell transplantation salvage therapy; toxicity ID HIGH-DOSE CHEMOTHERAPY; LENALIDOMIDE PLUS DEXAMETHASONE; RANDOMIZED CLINICAL-TRIAL; SALVAGE THERAPY; ALLOGENEIC TRANSPLANTATION; MARROW TRANSPLANTATION; THALIDOMIDE; AUTOGRAFT; SURVIVAL; PHASE-2 AB Toxicity associated with a second autologous peripheral blood stem cell transplant (APBSCT) in patients who relapse following initial APBSCT for multiple myeloma (MM) has not been well described. We conducted a retrospective, case-series of 25 consecutive patients who received a second APBSCT for relapsed or progressive disease following prior APBSCT to describe associated toxicity. Grade 3 or 4 toxicities were observed in 92% of patients after each APBSCT. More patients developed an elevated serum creatinine (4% vs. 36%; p = 0.011) following the second APBSCT. Median time to neutrophil engraftment was 10 days following both transplants (p = 0.428). Platelet engraftment was delayed by 2 days after the second APBSCT (median 12 vs. 14 days; p < 0.025). There were two deaths before day 100. In conclusion, patients who undergo a second APBSCT for relapsed MM experience more nephrotoxicity. Delayed platelet engraftment and an 8% treatment-related mortality were observed following the second APBSCT. C1 [Burzynski, Julianna Aleathea; Patel, Rakhi Chhaganbhai; Greene, Rebecca Elizabeth] S Texas Vet Healthcare Syst, Dept Pharm, San Antonio, TX USA. [Burzynski, Julianna Aleathea; Patel, Rakhi Chhaganbhai; Greene, Rebecca Elizabeth; Frei, Christopher Raymond] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Toro, Juan J.; Ochoa-Bayona, Jose Leonel; Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, Div Hematol Med Oncol, San Antonio, TX 78229 USA. [Lee, Shuko; Ochoa-Bayona, Jose Leonel; Freytes, Cesar O.] S Texas Vet Hlth Care Syst, Div Hematol Med Oncol, San Antonio, TX USA. RP Burzynski, JA (reprint author), Mayo Clin, 201 W Ctr St,Ei 1-420B, Rochester, MN 55904 USA. EM burzynski.julianna@mayo.edu NR 27 TC 27 Z9 27 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2009 VL 50 IS 9 BP 1442 EP 1447 DI 10.1080/10428190903085936 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 503QC UT WOS:000270552100010 PM 19637091 ER PT J AU Smith, SM Johnson, J Cheson, BD Canellos, G Petroni, G Oken, M Duggan, D Hurd, D Gockerman, JP Parker, B Prchal, J Peterson, BA AF Smith, S. M. Johnson, J. Cheson, B. D. Canellos, G. Petroni, G. Oken, M. Duggan, D. Hurd, D. Gockerman, J. P. Parker, B. Prchal, J. Peterson, B. A. CA Canc Leukemia Grp B Eastern Cooperative Oncology Grp TI Recombinant interferon-alpha 2b added to oral cyclophosphamide either as induction or maintenance in treatment-naive follicular lymphoma: final analysis of CALGB 8691 SO LEUKEMIA & LYMPHOMA LA English DT Article DE Follicular lymphoma; interferon; maintenance; cyclophosphamide ID NON-HODGKINS-LYMPHOMA; LOW-GRADE; COMBINATION IMMUNOTHERAPY; CLINICAL-TRIALS; SINGLE-AGENT; RITUXIMAB; CHEMOTHERAPY; SURVIVAL; ALPHA-2A AB Recombinant interferon alpha-2b (IFN-alpha 2) has direct and indirect antiproliferative effects in lymphoma, and may augment cytotoxicity when combined with chemotherapy. CALGB 8691 is a randomized study of daily oral cyclophosphamide (CPA) at 100 mg/m(2) with or without IFN-alpha 2 at 2 x 10(6) IU/m(2) three times per week, followed by a second randomization between IFN-alpha 2 maintenance (2 x 10(6) IU/m(2) three times weekly) versus observation in treatment-naive patients with follicular lymphoma (FL). Five hundred eighty-one patients were randomized to either CPA (n = 293) or CPA plus IFN-alpha 2 (n 288). One hundred five responding patients were randomized to observation and 99 to maintenance IFN-alpha 2. With a median follow-up of 11.5 years, the median event-free and overall survival (OS) for CPA induction alone were 2.5 years (95% CI 2.2, 3.0) and 9 years (95% CI 7.7, 10.2), compared to 2.4 years (95% CI 2.1, 3.1) and 8.4 years (95% CI 7.5, 11.1) for the combination arm (p = NS). Patients with a partial response (PR) and randomized to observation had the worst outcome (event-free survival (EFS) 1.8 years versus 3.9 years; p = 0.002). Patients with a PR randomized to IFN-alpha 2 had a similar EFS to compared to patients with complete response (CR), but this did not translate into a survival advantage. Myelosuppression was increased in IFN-alpha 2-containing arms. Despite the small benefit in EFS in patients with PR randomized to IFN-alpha 2 maintenance, we conclude that the addition of low dose IFN-alpha 2 did not significantly improve the response rate, duration of response, event-free, or OS obtained with single-agent daily oral CPA in patients with previously untreated FL. C1 [Smith, S. M.] Univ Chicago, Hematol Oncol Sect, Dept Med, Chicago, IL 60637 USA. [Johnson, J.; Petroni, G.] Georgetown Univ, Med Ctr, Durham, NC USA. [Cheson, B. D.] Duke Univ, Med Ctr, CALGB Stat Ctr, Washington, DC USA. [Canellos, G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Oken, M.] Eastern Cooperat Oncol Grp, Philadelphia, PA USA. [Duggan, D.] SUNY Upstate Med Univ, Syracuse, NY USA. [Hurd, D.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Parker, B.] Moores Univ Calif San Diego, Ctr Canc, San Diego, CA USA. [Prchal, J.] McGill Univ, Dept Oncol, Montreal, PQ, Canada. [Peterson, B. A.] Univ Minnesota, Div Oncol, Minneapolis, MN USA. RP Smith, SM (reprint author), Univ Chicago, Hematol Oncol Sect, Dept Med, 5841 S Maryland Ave MC2115, Chicago, IL 60637 USA. EM smsmith@medicine.bsd.uchicago.edu FU National Cancer Institute [CA31946, CA33601, CA04326, CA47577, CA12449, CA04457, CA02599, CA21060, CA11789, CA47642, CA37135, CA12046, CA47559, CA47555, CA26806, CA07968, CA21115]; CALGB Statistical Center; Columbia University, New York, NY; Dana-Farber Cancer Institute, Boston; Dartmouth Medical School Norris Cotton Cancer Center, Lebanon, NH; Duke University Medical Center, Durham; Finsen Institute, Copenhagen, DK; Long Island Jewish Medical Center, Lake Success, NY; Massachusetts General Hospital, Boston; Mount Sinai School of Medicine, New York; Roswell Park Cancer Institute, Buffalo; State University of New York Upstate Medical University, Syracuse; SunyMaimonides Medical Center, Brooklyn, NY; University of Alabama Birmingham, Birmingham, AL-; University of California at San Diego, San Diego; University of Chicago, Chicago, IL; University of Iowa, Iowa City; University of Maryland Greenebaum Cancer Center, Baltimore, MD; University of Massachusetts Medical School, Worcester; University of Minnesota, Minneapolis, MN; University of Missouri/ Ellis Fischel Cancer Center, Columbia; University of North Carolina at Chapel Hill; University of Tennessee Memphis, Memphis; Wake Forest University School of Medicine, Winston-Salem; Walter Reed Army Medical Center, Washington; Washington University School of Medicine, St. Louis, MO; Weill Medical College of Cornell University, New York; Eastern Cooperative Oncology Group; [CA32291]; [CA11028]; [CA47545]; [CA41287]; [CA31983]; [CA16450]; [CA03927]; [CA77440] FX The research for CALGB 8691 was supported, in part, by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, MD, Chairman) and to the CALGB Statistical Center (Stephen George, PhD, CA33601). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. S. M. smith is supported by grant CA41287; J. Johnson and G. Petroni by CA33601; B. D. Cheson by CA77597; G. Canellos by CA32291; M. Oken by CA21115; D. Duggan by CA21060; D. Hurd by CA03927; P. Gockerman by CA 47577; B. Parker by CA11789, and B. A. Peterson by CA16450. The following institutions participated in this study: Columbia University, New York, NY; Dana-Farber Cancer Institute, Boston, MA-Eric P. Winer, M. D., supported by CA32291; Dartmouth Medical School Norris Cotton Cancer Center, Lebanon, NH Marc S. Ernstoff, M. D., supported by CA04326; Duke University Medical Center, Durham, NC Jeffrey Crawford, M. D., supported by CA47577; Finsen Institute, Copenhagen, DK; Long Island Jewish Medical Center, Lake Success, NY-Kanti R. Rai, M. D., supported by CA11028; Massachusetts General Hospital, Boston, MA-Jeffrey W. Clark, M. D., supported by CA12449; McGill University, Montreal, QC-Gerald Batist, M. D.; Mount Sinai School of Medicine, New York, NY-Lewis R. Silverman, M. D., supported by CA04457; Rhode Island Hospital, Providence, RI-William Sikov, M. D., supported by CA08025; Roswell Park Cancer Institute, Buffalo, NY-Ellis Levine, M. D., supported by CA02599; State University of New York Upstate Medical University, Syracuse, NY-Stephen L. Graziano, M. D., supported by CA21060; SunyMaimonides Medical Center, Brooklyn, NY; University of Alabama Birmingham, Birmingham, AL-Robert Diasio, M. D., supported by CA47545; University of California at San Diego, San Diego, CA Barbara A. Parker, M. D., supported by CA11789; University of Chicago, Chicago, IL-Gini Fleming, M. D., supported by CA41287; University of Iowa, Iowa City, IA-Daniel A. Vaena, M. D., supported by CA47642; University of Maryland Greenebaum Cancer Center, Baltimore, MD-Martin Edelman, M. D., supported by CA31983; University of Massachusetts Medical School, Worcester, MA-William V. Walsh, M. D., supported by CA37135; University of Minnesota, Minneapolis, MN-Bruce A Peterson, M. D., supported by CA16450; University of Missouri/ Ellis Fischel Cancer Center, Columbia, MO-Michael C Perry, M. D., supported by CA12046; University of North Carolina at Chapel Hill, Chapel Hill, NC Thomas C. Shea, M. D., supported by CA47559; University of Tennessee Memphis, Memphis, TN Harvey B. Niell, M. D., supported by CA47555; Wake Forest University School ofMedicine, Winston-Salem, NC-David D Hurd, M. D., supported by CA03927; Walter Reed Army Medical Center, Washington, DC Thomas Reid, M. D., supported by CA26806; Washington University School of Medicine, St. Louis, MO-Nancy Bartlett, M. D., supported by CA77440; Weill Medical College of Cornell University, New York, NY-John Leonard, M. D., supported by CA07968; Eastern Cooperative Oncology Group, Philadelphia, PA-Robert L. Comis, M. D., Chairman; supported by CA21115. NR 21 TC 4 Z9 4 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2009 VL 50 IS 10 BP 1606 EP 1617 DI 10.3109/10428190903093807 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA 516PJ UT WOS:000271554400011 PM 19626540 ER PT J AU Wiernik, PH Hong, FX Glick, JH Bennett, JM AF Wiernik, Peter H. Hong, Fangxin Glick, John H. Bennett, John M. TI Radiation therapy compared with chemotherapy for consolidation of chemotherapy-induced remission of advanced Hodgkin lymphoma: a study by the Eastern Co-operative Oncology Group (E1476) with > 20 years follow-up SO LEUKEMIA & LYMPHOMA LA English DT Article DE Hodgkin lymphoma; chemotherapy; radiation therapy; long-term follow-up ID INVOLVED-FIELD RADIOTHERAPY; PROSPECTIVE CLINICAL-TRIAL; DES LYMPHOMES; H89 TRIAL; 6 CYCLES; DISEASE; MOPP; CHILDREN; ABVD; BLEOMYCIN AB MOPP-Bleo (nitrogen mustard, vincristine, procarbazine, prednisone and bleomycin) induction therapy was given to 253 evaluable patients with Hodgkin lymphoma, stages IIIB, IIIs, or IV. Complete response (CR) occurred in 145 patients (57%) and partial response (PR) in 93 (37%). Of those 238 responders, 178 were randomized to consolidation therapy, and 164 were eligible and analyzable, including 114 CRs [55 patients randomized to ABVD and 59 to radiation therapy (RT)] and 50 partial responders (PRs) (25 each randomized to ABVD and RT). Among the 50 patients with PR, 34 (68%) converted to CR (16 with ABVD and 18 with RT). Therefore, of 253 patients, 182(72%) achieved CR and 56 (22%), PR. Median follow-up for all patients is 22.3 years and the estimated overall survival (OS) rate at 20 years is 48%. Of the 148 eligible, analyzable patients with CR, the estimated proportion remaining in CR at 20 years is 62%. OS at 20 years was significantly greater for patients receiving ABVD consolidation (66%) when compared with those who received RT consolidation (43%) (p = 0.002). Treatment toxicity was acceptable. After MOPP-Bleo induction for advanced Hodgkin lymphoma, ABVD provides better consolidation than local RT. C1 [Wiernik, Peter H.] New York Med Coll, Ctr Canc, Montefiore Med Ctr N Div, Bronx, NY USA. [Hong, Fangxin] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Glick, John H.] Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. [Bennett, John M.] Univ Rochester, Ctr Canc, Rochester, NY USA. RP Wiernik, PH (reprint author), Ctr Canc, Montefiore N Div, 600 E 233rd St, Bronx, NY 10466 USA. EM pwiernik@aol.com FU Eastern Cooperative Oncology Group; Public Health Service [CA21115, CA23318, CA66636, CA14958, CA15488, CA11083]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services; National Cancer Institute FX This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M. D., Chair) and supported in part by Public Health Service Grants CA21115, CA23318, CA66636, CA14958, CA15488, CA11083, and from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. The contents of the study are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 27 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2009 VL 50 IS 10 BP 1632 EP 1641 DI 10.3109/10428190903161075 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 516PJ UT WOS:000271554400014 PM 19863338 ER PT J AU Martin, NE Ng, AK AF Martin, Neil E. Ng, Andrea K. TI Good things come in small packages: low-dose radiation as palliation for indolent non-Hodgkin lymphomas SO LEUKEMIA & LYMPHOMA LA English DT Review DE Non-Hodgkin lymphoma; palliation; low-dose radiation; chronic lymphocytic leukemia ID TOTAL-BODY IRRADIATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; INVOLVED-FIELD RADIOTHERAPY; FOLLICULAR LYMPHOMA; COMBINATION CHEMOTHERAPY; LOCAL RADIOTHERAPY; INDUCED APOPTOSIS; RANDOMIZED-TRIAL; SINGLE-AGENT; FOLLOW-UP AB Numerous management options are available to patients with advanced-stage or relapsed/refractory indolent non-Hodgkin lymphomas (NHLs). These include observation in patients with low-volume disease, systemic therapy including radioimmunotherapy, and high-dose therapy with stem cell transplant. In selected patients with localized symptomatic disease, local radiation therapy to sites of involvement can offer effective palliation. However, systemic therapy and standard-dose radiation therapy can be associated with significant toxicities. Over the past 15 years, several groups have investigated the role of low-dose radiation therapy - typically 4 Gy in two fractions - to an involved-field as an option for palliation in patients with NHL. Overall response rates of more than 80% have been consistently reported with local control maintained for 2 years. In this review, we outline the clinical experience with this approach in NHL of various histologies. C1 [Ng, Andrea K.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Martin, Neil E.] Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ng, AK (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St,L-2 Level, Boston, MA 02115 USA. EM ang@lroc.harvard.edu RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 NR 41 TC 2 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2009 VL 50 IS 11 BP 1765 EP 1772 DI 10.3109/10428190903186510 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 524LO UT WOS:000272145000013 PM 19883306 ER PT S AU Park, EJ Shimaoka, M AF Park, Eun Jeong Shimaoka, Motomu BE Ley, K TI Activation of Leukocyte Integrins SO LEUKOCYTE ADHESION SE Current Topics in Membranes LA English DT Review; Book Chapter ID I-LIKE DOMAIN; FUNCTION-ASSOCIATED ANTIGEN-1; T-CELL; STRUCTURAL BASIS; CONFORMATIONAL REGULATION; CRYSTAL-STRUCTURE; LYMPH-NODES; EXTRACELLULAR SEGMENT; ADHESION DEFICIENCY; DENDRITIC CELLS C1 [Park, Eun Jeong; Shimaoka, Motomu] Childrens Hosp Boston, Program Cellular & Mol Med, Immune Dis Inst, Boston, MA 02115 USA. [Park, Eun Jeong; Shimaoka, Motomu] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Park, EJ (reprint author), Childrens Hosp Boston, Program Cellular & Mol Med, Immune Dis Inst, Boston, MA 02115 USA. NR 87 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1063-5823 BN 978-0-12-374909-3 J9 CURR TOP MEMBR JI Curr. Top. Membr. PY 2009 VL 64 BP 115 EP 132 DI 10.1016/S1063-5823(09)64004-7 PG 18 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BMF85 UT WOS:000272212100004 ER PT J AU Curran, SP AF Curran, Sean P. BE Sell, C Lorenzini, A BrownBorg, HM TI Conserved Mechanisms of Life-Span Regulation and Extension in Caenorhabditis elegans SO LIFE-SPAN EXTENSION: SINGLE-CELL ORGANISMS TO MAN SE Aging Medicine LA English DT Article; Book Chapter DE Caenorhabditis elegans; aging; insulin; dietary restriction; mitochondria; RNA interference; postdevelopmental life span; chemical screens ID FORKHEAD TRANSCRIPTION FACTOR; PROTEIN-KINASE B; RESTRICTION-INDUCED LONGEVITY; CONTROLLING DAUER FORMATION; HETEROCHRONIC GENE LIN-14; SYSTEMATIC RNAI SCREEN; C-ELEGANS; INSULIN-RECEPTOR; SIGNALING PATHWAY; OXIDATIVE STRESS AB Human aging correlates with stereotypical changes in physical attributes as well as with an increased incidence of many diseases: atherosclerotic heart disease, cancer, neurological disorders, osteoporosis, obesity, and diabetes. Before we can successfully combat such a wide range of debilitating conditions, a more thorough understanding of the molecular determinants of aging is required. The use of Caenorhabditis elegans to identify the basis of human aging has facilitated the rapid identification of genes through a combination of genetic and RNA interference screens. These life-span-controlling genes identified in the worm regulate life span in many organisms and have been shown to play roles in endocrine signaling, reproduction, stress adaptation, metabolism, and genomic maintenance. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Curran, SP (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 185 Cambridge St,CPZN 7250, Boston, MA 02114 USA. EM curran@molbio.mgh.harvard.edu NR 155 TC 0 Z9 0 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-507-1 J9 AGING MED PY 2009 BP 33 EP 56 DI 10.1007/978-1-60327-507-1_3 D2 10.1007/978-1-60327-507-1 PG 24 WC Biochemistry & Molecular Biology; Cell Biology; Geriatrics & Gerontology SC Biochemistry & Molecular Biology; Cell Biology; Geriatrics & Gerontology GA BLP79 UT WOS:000270739400005 ER PT B AU Yang, MF Tuchin, VV Yaroslavsky, AN AF Yang, Marjorie F. Tuchin, Valery V. Yaroslavsky, Anna N. BE Baron, ED TI Principles of Light-Skin Interactions SO LIGHT-BASED THERAPIES FOR SKIN OF COLOR LA English DT Article; Book Chapter ID TOPICAL PHOTODYNAMIC THERAPY; OPTICAL COHERENCE TOMOGRAPHY; DELTA-AMINOLEVULINIC-ACID; PORT-WINE STAINS; LASER-SCANNING MICROSCOPY; MODE CONFOCAL MICROSCOPY; SQUAMOUS-CELL CARCINOMA; IN-VIVO DIAGNOSIS; PULSED-DYE-LASER; SELECTIVE PHOTOTHERMOLYSIS C1 [Yaroslavsky, Anna N.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. [Yaroslavsky, Anna N.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA USA. [Yaroslavsky, Anna N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yang, Marjorie F.] Indiana Univ Sch Med, Dept Dermatol, Indianapolis, IN USA. [Tuchin, Valery V.] Saratov NG Chernyshevskii State Univ, Inst Opt & Biophoton, Dept Opt & Biomed Phys, Saratov, Russia. RP Yaroslavsky, AN (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. EM mfyang@hotmail.com; yaroslav@helix.mgh.harvard.edu NR 130 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND BN 978-1-84882-327-3 PY 2009 BP 1 EP 44 DI 10.1007/978-1-84882-328-0_1 D2 10.1007/978-1-84882-328-0 PG 44 WC Dermatology SC Dermatology GA BKK12 UT WOS:000268357300001 ER PT B AU Faes, C Geys, H Catalano, P AF Faes, Christel Geys, Helena Catalano, Paul BE Fitzmaurice, G Davidian, M Verbeke, G Molenberghs, G TI Joint models for continuous and discrete longitudinal data SO LONGITUDINAL DATA ANALYSIS SE Chapman & Hall-CRC Handbooks of Modern Statistical Methods LA English DT Article; Book Chapter ID DEVELOPMENTAL TOXICOLOGY; CONTINUOUS OUTCOMES; REGRESSION-MODELS; CATEGORICAL-DATA; RISK-ESTIMATION; MIXED DISCRETE; BINARY C1 [Faes, Christel] Hasselt Univ, Ctr Stat, Diepenbeek, Belgium. [Geys, Helena] Johnson & Johnson, Biometr & Reporting, Beerse, Belgium. [Catalano, Paul] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Faes, C (reprint author), Hasselt Univ, Ctr Stat, Diepenbeek, Belgium. RI Faes, Christel/E-1384-2017 OI Faes, Christel/0000-0002-1878-9869 NR 25 TC 4 Z9 4 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-58488-658-7 J9 CH CRC HANDB MOD STA PY 2009 BP 327 EP 348 PG 22 WC Statistics & Probability SC Mathematics GA BKC26 UT WOS:000267748700014 ER PT B AU Oh, KS Sundaram, B Krishnamurthy, V Pickens, A Venkatram, M Kazerooni, EA Pan, C Hayman, J AF Oh, Kevin S. Sundaram, Baskaran Krishnamurthy, Venkataramu Pickens, Allan Venkatram, Malini Kazerooni, Ella A. Pan, Charlie Hayman, James BE Keshamouni, V Arenberg, D Kalemkerian, G TI Site-Directed Therapy for Lung Cancer Metastases SO LUNG CANCER METASTASIS: NOVEL BIOLOGICAL MECHANISMS AND IMPACT ON CLINICAL PRACTICE LA English DT Article; Book Chapter ID PERCUTANEOUS RADIOFREQUENCY ABLATION; BODY RADIATION-THERAPY; COLORECTAL LIVER METASTASES; PROPHYLACTIC CRANIAL IRRADIATION; SOLITARY BRAIN METASTASIS; PAINFUL BONE METASTASES; LONG-TERM SURVIVAL; INTENSITY-MODULATED RADIOSURGERY; SINGLE FRACTION RADIOTHERAPY; PULMONARY MALIGNANT-TUMORS AB At the time of diagnosis, 40% of patients with non-small cell lung cancer (NSCLC) and nearly 70% of patients with small cell lung cancer (SCLC) have advanced metastatic disease. The prognosis of patients with advanced lung cancer is dismal, with a 5-year overall survival rate of 1-2%. The primary treatment of advanced disease is supportive care and palliative chemotherapy. However, there is a growing body of evidence suggesting that highly selected patients with oligometastatic disease can achieve long-term survival with ablative forms of site-directed therapy, including surgical resection, external beam radiation therapy (EBRT), stereotactic radiosurgery (SRS), stereotactic body radiation therapy (SBRT), and radiofrequency ablation (RFA). This chapter summarizes the experience with site-directed therapy in the management of metastatic lung cancer in the most commonly involved sites: brain, adrenal gland, liver, lung, and bone. C1 [Oh, Kevin S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Sundaram, Baskaran; Krishnamurthy, Venkataramu; Kazerooni, Ella A.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Pickens, Allan] Univ Michigan, Thorac Surg Sect, Dept Surg, Ann Arbor, MI 48109 USA. [Venkatram, Malini] Sinai Grace Wayne State Univ, Dept Internal Med, Detroit, MI USA. [Pan, Charlie; Hayman, James] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. RP Oh, KS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM kohz@partners.org; sundbask@umich.edu; venkkris@umcih.edu; allanp@umich.edu; malinive@umich.edu; ellakaz@umich.edu; cpan@umich.edu; hayman@umich.edu NR 209 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0771-4 PY 2009 BP 351 EP 381 DI 10.1007/978-1-4419-0772-1_16 PG 31 WC Oncology SC Oncology GA BMT77 UT WOS:000273557900016 ER PT B AU Reddy, K Moore, D Gilman, R AF Reddy, Krishna Moore, David Gilman, Robert BE Ehiri, J TI Tuberculosis in Childhood and Pregnancy SO MATERNAL AND CHILD HEALTH: GLOBAL CHALLENGES, PROGRAMS AND POLICIES LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; MULTIDRUG-RESISTANT TUBERCULOSIS; DRUG-SUSCEPTIBILITY ASSAY; PULMONARY TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; BCG VACCINE; INTRATHORACIC TUBERCULOSIS; CONGENITAL TUBERCULOSIS; GLOBAL EPIDEMIOLOGY; ACTIVE TUBERCULOSIS C1 [Reddy, Krishna] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moore, David] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England. [Gilman, Robert] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Gilman, Robert] Univ Peruana Cayetano Heredia, Lima, Peru. RP Reddy, K (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 91 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-89244-3 PY 2009 BP 245 EP 269 DI 10.1007/b106524_14 D2 10.1007/b106524 PG 25 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BMH55 UT WOS:000272391600014 ER PT J AU Zhang, L Strouthos, CG Wang, Z Deisboeck, TS AF Zhang, Le Strouthos, Costas G. Wang, Zhihui Deisboeck, Thomas S. TI Simulating brain tumor heterogeneity with a multiscale agent-based model: Linking molecular signatures, phenotypes and expansion rate SO MATHEMATICAL AND COMPUTER MODELLING LA English DT Article DE Glioma; Epidermal growth factor receptor; Cancer heterogeneity; Agent-based model ID EPIDERMAL-GROWTH-FACTOR; MULTICELLULAR PATTERNS; SECONDARY GLIOBLASTOMA; MATHEMATICAL-MODEL; CELL LOCOMOTION; CANCER; DYNAMICS; MIGRATION; GLIOMA; EGF AB We have extended our previously developed 3D multi-scale agent-based brain tumor model to simulate cancer heterogeneity and to analyze its impact across the scales of interest. While our algorithm continues to employ an epidermal growth factor receptor (EGFR) gene-protein interaction network to determine the cells' phenotype, it now adds an implicit treatment of tumor cell adhesion related to the model's biochemical microenvironment. We simulate a simplified tumor progression pathway that leads to the emergence of five distinct glioma cell clones with different EGFR density and cell 'search precisions'. The in silico results show that microscopic tumor heterogeneity can impact the tumor system's multicellular growth patterns. Our findings further confirm that EGFR density results in the more aggressive clonal populations switching earlier from proliferation-dominated to a more migratory phenotype. Moreover, analyzing the dynamic molecular profile that triggers the phenotypic switch between proliferation and migration, our in silico oncogenomics data display spatial and temporal diversity in documenting the regional impact of tumorigenesis, and thus support the added value of multi-site and repeated assessments in vitro and in vivo. Potential implications from this in silico work for experimental and computational studies are discussed. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Zhang, Le] Michigan Technol Univ, Dept Math Sci, Houghton, MI 49931 USA. [Strouthos, Costas G.; Wang, Zhihui; Deisboeck, Thomas S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Harvard MIT HST, Complex Biosyst Modeling Lab, Charlestown, MA 02129 USA. RP Deisboeck, TS (reprint author), Massachusetts Gen Hosp E, Athinoula A Martinos Ctr Biomed Imaging, Harvard MIT HST, Complex Biosyst Modeling Lab, 2301 Bldg 149,13th St, Charlestown, MA 02129 USA. EM strouthos@ucy.ac.cy; deisboec@helix.mgh.harvard.edu RI Strouthos, Costas/C-7086-2011 OI Strouthos, Costas/0000-0001-9972-6925 FU NIH [CA 085139, CA 113004]; Harvard-MIT (HST) Athinoula A. Martinos Center; Department of Radiology FX This work has been supported in part by NIH grants CA 085139 and CA 113004 (The Center for the Development of a Virtual Tumor, CViT at http://www.cvit.org) and by the Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital. NR 41 TC 34 Z9 34 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-7177 J9 MATH COMPUT MODEL JI Math. Comput. Model. PD JAN PY 2009 VL 49 IS 1-2 BP 307 EP 319 DI 10.1016/j.mcm.2008.05.011 PG 13 WC Computer Science, Interdisciplinary Applications; Computer Science, Software Engineering; Mathematics, Applied SC Computer Science; Mathematics GA 372LW UT WOS:000260904100029 PM 20047002 ER PT J AU Bainey, KR Bhatt, DL AF Bainey, Kevin R. Bhatt, Deepak L. TI Acute Pericarditis: Appendicitis of the Heart? SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID ST-SEGMENT ELEVATION; CARDIAC TROPONIN-I; MYOCARDIAL-INFARCTION; PR-SEGMENT; MYOPERICARDITIS; THERAPY C1 [Bainey, Kevin R.; Bhatt, Deepak L.] Brigham & Womens Hosp, Div Cardiovasc, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Bhatt, DL (reprint author), Brigham & Womens Hosp, Div Cardiol, 75 Francis St, Boston, MA 02115 USA. EM dlbhattmd@alum.mit.edu NR 16 TC 4 Z9 4 U1 0 U2 0 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JAN PY 2009 VL 84 IS 1 BP 5 EP 6 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 388PT UT WOS:000262032400002 PM 19121246 ER PT S AU Chen, ACH Huang, YY Arany, PR Hamblin, MR AF Chen, Aaron Chih-Hao Huang, Ying-Ying Arany, Praveen R. Hamblin, Michael R. BE Hamblin, MR Waynant, RW Anders, J TI Role of Reactive Oxygen Species in Low Level Light Therapy SO MECHANISMS FOR LOW-LIGHT THERAPY IV SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Mechanisms for Low-Light Therapy IV CY JAN 24, 2009 CL San Jose, CA SP SPIE DE biostimulation; low level laser therapy; mitochondria; reactive oxygen species; redox-sensitive signal transduction; transcription factor ID NF-KAPPA-B; CYTOCHROME-C-OXIDASE; HELIUM-NEON LASER; RAT-LIVER MITOCHONDRIA; TRANSCRIPTION FACTOR; KINASE COMPLEX; IKK-ALPHA; ACTIVATION; IRRADIATION; CELLS AB This review will focus on the role of reactive oxygen species in the cellular and tissue effects of low level light therapy (LLLT). Coincidentally with the increase in electron transport and in ATP, there has also been observed by intracellular fluorescent probes and electron spin resonance an increase in intracellular reactive oxygen species (ROS) such as superoxide, hydrogen peroxide, singlet oxygen and hydroxyl radical. ROS scavengers, antioxidants and ROS quenchers block many LLLT processes. It has been proposed that light between 400-500-nm may produce ROS by a photosensitization process involving flavins, while longer wavelengths may directly produce ROS from the mitochondria. Several redox-sensitive transcription factors are known such as NF-kB and AP1, that are able to initiate transcription of genes involved in protective responses to oxidative stress. It may be the case that LLLT can be pro-oxidant in the short-term, but anti-oxidant in the long-term. C1 [Chen, Aaron Chih-Hao; Huang, Ying-Ying; Arany, Praveen R.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu; hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 NR 57 TC 3 Z9 3 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7411-7 J9 P SOC PHOTO-OPT INS PY 2009 VL 7165 AR 716502 DI 10.1117/12.814890 PG 11 WC Engineering, Biomedical; Optics; Physics, Applied SC Engineering; Optics; Physics GA BSS59 UT WOS:000285712700001 ER PT S AU Chen, ACH Arany, PR Huang, YY Tomkinson, EM Saleem, T Yull, FE Blackwell, TS Hamblin, MR AF Chen, Aaron Chih-Hao Arany, Praveen R. Huang, Ying-Ying Tomkinson, Elizabeth M. Saleem, Taimur Yull, Fiona E. Blackwell, Timothy S. Hamblin, Michael R. BE Hamblin, MR Waynant, RW Anders, J TI Low Level Laser Therapy activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts SO MECHANISMS FOR LOW-LIGHT THERAPY IV SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Mechanisms for Low-Light Therapy IV CY JAN 24, 2009 CL San Jose, CA SP SPIE DE photobiomudulation; low level laser therapy; reactive oxygen species; NF-kB transcription factor; luciferase reporter mice ID CYTOCHROME-C-OXIDASE; KAPPA-B ACTIVATION; PROTEIN-KINASE-D; TRANSCRIPTION FACTOR; SIGNALING PATHWAY; GENE-EXPRESSION; RED-LIGHT; STRESS; CELLS; IRRADIATION AB Despite over forty years of investigation on low-level light therapy (LLLT), the fundamental mechanisms underlying photobiomodulation remain unclear. In this study, we isolated murine embryonic fibroblasts (MEF) from transgenic NF-kB luciferase reporter mice and studied their response to 810-nm laser radiation. Significant activation of NF-kB was observed for fluences higher than 0.003 J/cm(2). NF-kB activation by laser was detectable at 1-hour time point. Moreover, we demonstrated that laser phosphorylated both IKK alpha/beta NF-kB 15 minutes after irradiation, which implied that laser activates NF-kB via phosphorylation of IKK alpha/beta. Suspecting mitochondria as the source of NF-kB activation signaling pathway, we demonstrated that laser increased both intracellular reactive oxygen species (ROS) by fluorescence microscopy with dichlorodihydrofluorescein and ATP synthesis by luciferase assay. Mitochondrial inhibitors, such as antimycin Lambda, rotenone and paraquat increased ROS and NF-kB activation but had no effect on ATP. The ROS quenchers N-acetyl-L-cysteine and ascorbic acid abrogated laser-induced NF-kB and ROS but not ATP. These results suggested that ROS might play an important role in the signaling pathway of laser induced NF-kB activation. However, the western blot showed that antimycin A, a mitochondrial inhibitor, did not activate NF-kB via serine phosphorylation of IKK alpha/beta as the laser did. On the other hand, LLLT, unlike mitochondrial inhibitors, induced increased cellular ATP levels, which indicates that light also upregulates mitochondrial respiration. ATP upregulation reached a maximum at 0.3 J/cm(2) or higher. We conclude that LLLT not only enhances mitochondrial respiration, but also activates the redox-sensitive transcription factor NF-kB by generating ROS as signaling molecules. C1 [Chen, Aaron Chih-Hao; Arany, Praveen R.; Huang, Ying-Ying; Tomkinson, Elizabeth M.; Saleem, Taimur; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Hamblin, MR (reprint author), BAR414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu; hamblin@helix.mgh.harvard.edu NR 34 TC 5 Z9 5 U1 3 U2 4 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7411-7 J9 P SOC PHOTO-OPT INS PY 2009 VL 7165 AR 71650B DI 10.1117/12.809605 PG 10 WC Engineering, Biomedical; Optics; Physics, Applied SC Engineering; Optics; Physics GA BSS59 UT WOS:000285712700008 ER PT J AU Warren, LA Rossi, DJ AF Warren, Luigi A. Rossi, Derrick J. TI Stem cells and aging in the hematopoietic system SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Review DE Hematopoietic stem cells; Aging; Ageing; HSC; Immunodecline ID REPLICATIVE LIFE-SPAN; AGE-RELATED-CHANGES; SERIAL TRANSPLANTATION; SELF-RENEWAL; IN-VIVO; REPOPULATING ABILITY; OXIDATIVE STRESS; BONE-MARROW; ASYMMETRIC DIVISION; PROGENITOR CELLS AB The effector cells of the blood have limited lifetimes and must be replenished continuously throughout life from a small reserve of hematopoietic stem cells (HSCs) in the bone marrow. Although serial bone marrow transplantation experiments in mice suggest that the replicative potential of HSCs is finite, there is little evidence that replicative senescence causes depletion of the stem cell pool during the normal lifespan of either mouse or man. Studies conducted in murine genetic models defective in DNA repair, intracellular ROS management, and telomere maintenance indicate that all these pathways are critical to the longevity and stress response of the stem cell pool. With age, HSCs show an increased propensity to differentiate towards myeloid rather than lymphoid lineages, which may contribute to the decline in lymphopoiesis that attends aging. Challenges for the future include assessing the significance of lineage skewing' to immune dysfunction, and investigating the role of epigenetic dysregulation in HSC aging. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Warren, Luigi A.; Rossi, Derrick J.] Harvard Univ, Harvard Med Sch, Dept Pathol, Harvard Stem Cell Inst,Immune Dis Inst, Boston, MA 02115 USA. RP Rossi, DJ (reprint author), Harvard Univ, Harvard Med Sch, Dept Pathol, Harvard Stem Cell Inst,Immune Dis Inst, 200 Longwood Ave, Boston, MA 02115 USA. EM rossi@idi.harvard.edu FU NIA NIH HHS [R00 AG029760, R00 AG029760-02] NR 98 TC 50 Z9 52 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JAN-FEB PY 2009 VL 130 IS 1-2 BP 46 EP 53 DI 10.1016/j.mad.2008.03.010 PG 8 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 407XT UT WOS:000263398300008 PM 18479735 ER PT J AU Singer, SJ Gaba, DM Falwell, A Lin, S Hayes, J Baker, L AF Singer, Sara J. Gaba, David M. Falwell, Alyson Lin, Shoutzu Hayes, Jennifer Baker, Laurence TI Patient Safety Climate in 92 US Hospitals Differences by Work Area and Discipline SO MEDICAL CARE LA English DT Article DE safety climate; professional differences; work areas; survey research ID HIGH-RELIABILITY; HEALTH-CARE; CULTURE; PERCEPTIONS; TEAMWORK; ORGANIZATIONS; ATTITUDES; UNITS; QUESTIONNAIRE; VALIDATION AB Background: Concern about patient safety has promoted efforts to improve safety climate. A better understanding of how patient safety climate differs among distinct work areas and disciplines in hospitals would facilitate the design and implementation of interventions. Objectives: To understand workers' perceptions of safety climate and ways in which climate varies among hospitals and by work area and discipline. Research Design: We administered the Patient Safety Climate in Healthcare Organizations survey in 2004-2005 to personnel in a stratified random sample of 92 US hospitals. Subjects: We sampled 100% of senior managers and physicians and 10% of all other workers. We received 18,361 completed surveys (52% response). Measures: The survey measured safety climate perceptions and worker and job characteristics of hospital personnel. We calculated and compared the percent of responses inconsistent with a climate of safety among hospitals, work areas, and disciplines. Results: Overall, 17% of responses were inconsistent with a safety climate. Patient safety climate differed by hospital and among and within work areas and disciplines. Emergency department personnel perceived worse safety climate and personnel in nonclinical areas perceived better safety climate than workers in other areas. Nurses were more negative than physicians regarding their work unit's support and recognition of safety efforts, and physicians showed marginally more fear of shame than nurses. For other dimensions of safety climate, physician-nurse differences depended on their work area. Conclusions: Differences among and within hospitals suggest that strategies for improving safety climate and patient safety should be tailored for work areas and disciplines. C1 [Singer, Sara J.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Singer, Sara J.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Singer, Sara J.; Gaba, David M.; Falwell, Alyson; Lin, Shoutzu; Hayes, Jennifer; Baker, Laurence] Stanford Univ, Ctr Primary Care & Outcomes Res, Ctr Hlth Policy, Stanford, CA 94305 USA. [Gaba, David M.] Palo Alto Healthcare Syst, Palo Alto, CA USA. [Baker, Laurence] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. RP Singer, SJ (reprint author), 677 Huntington Ave,Kresge 3,Room 336, Boston, MA 02115 USA. EM ssinger@hsph.harvard.edu OI Baker, Laurence/0000-0001-5032-794X FU Agency for Healthcare Research and Quality [RO1 HSO13920]; Harvard Business School; Kennedy School of Government FX Supported by the Agency for Healthcare Research and Quality RO1 HSO13920 and, fellowships provided by the Harvard Business School and the Center for Public Leadership at the Kennedy School of Government (to SIS.). NR 48 TC 81 Z9 82 U1 0 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2009 VL 47 IS 1 BP 23 EP 31 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 390TL UT WOS:000262186500004 PM 19106727 ER PT J AU Nietert, PJ Tilley, BC Zhao, WL Edwards, PF Wessell, AM Mauldin, PD Polk, PP AF Nietert, Paul J. Tilley, Barbara. C. Zhao, Wenle Edwards, Peter F. Wessell, Andrea M. Mauldin, Patrick D. Polk, Pam P. TI Two Pharmacy Interventions to Improve Refill Persistence for Chronic Disease Medications A Randomized, Controlled Trial SO MEDICAL CARE LA English DT Article DE community pharmacy services; randomized controlled trial; chronic disease; patient compliance ID ACTIVE ANTIRETROVIRAL THERAPY; PATIENT COMPLIANCE; DRUG-THERAPY; ADHERENCE; METAANALYSIS; POPULATION; HEALTH; HYPERTENSION; SENSITIVITY; PREDICTORS AB Background: Despite the proven effectiveness of many medications for chronic diseases, many patients do not refill their prescriptions in the required timeframe. Objective: Compare the effectiveness of 3 pharmacist strategies to decrease time to refill of prescriptions for common chronic diseases. Research Design/Subjects: A randomized, controlled clinical trial with patients as the unit of randomization. Nine pharmacies within a medium-sized grocery store chain in South Carolina were included, representing urban, suburban, and rural areas and patients from a variety of socioeconomic backgrounds. Patients (n = 3048) overdue for refills for selected medications were randomized into 1 of 3 treatment arms: (1) pharmacist contact with the patient via telephone, (2) pharmacist contact with the patient's prescribing physician via facsimile, and (31) usual care. Measures: The primary outcome was the number of days from their recommended refill date until the patient filled a prescription for an), medication relevant to his/her chronic disease. Prescription refill data were obtained routinely from the pharmacy district office's centralized database. Patient disposition codes were obtained by pharmacy employees. An intent-to-treat approach was used for all analyses. Results: There were no significant differences by treatment arm in the study outcomes. Conclusions: Neither of the interventions is more effective than usual care at improving persistence of prescription refills for chronic diseases in overdue patients. C1 [Nietert, Paul J.; Tilley, Barbara. C.; Zhao, Wenle] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. [Edwards, Peter F.; Wessell, Andrea M.; Mauldin, Patrick D.] S Carolina Coll Pharm, Dept Pharm & Clin Sci, Charleston, SC USA. [Mauldin, Patrick D.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Polk, Pam P.] Piggly Wiggly Carolina Co Inc, Charleston, SC USA. RP Nietert, PJ (reprint author), Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, 135 Cannon St,Suite 303,POB 250835, Charleston, SC 29425 USA. EM nieterpj@musc.edu OI Nietert, Paul/0000-0002-3933-4986 FU Agency for Healthcare Research and Quality [P01 HS 10871] FX Supported by grant P01 HS 10871 from the Agency for Healthcare Research and Quality. NR 36 TC 21 Z9 22 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2009 VL 47 IS 1 BP 32 EP 40 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 390TL UT WOS:000262186500005 PM 19106728 ER PT J AU Leveille, SG Huang, A Tsai, SB Allen, M Weingart, SN Iezzoni, LT AF Leveille, Suzanne G. Huang, Annong Tsai, Stephanie B. Allen, Marybeth Weingart, Saul N. Iezzoni, Lisa T. TI Health Coaching via an Internet Portal for Primary Care Patients With Chronic Conditions A Randomized Controlled Trial SO MEDICAL CARE LA English DT Article DE internet; physician-patient relations; randomized controlled trial; primary health care; chronic illness ID QUALITY-OF-LIFE; GENERAL-PRACTICE; AGENDA FORMS; DEPRESSION; VALIDITY; PROGRAM; SYSTEM; IMPACT; PROFESSIONALS; CONSULTATIONS AB Background: Efforts to enhance patient-physician communication may improve management of underdiagnosed chronic conditions. Patient internet portals offer an efficient venue for coaching patients to discuss chronic conditions with their primary care physicians (PCP). Objectives: We sought to test the effectiveness of an internet portal-based coaching intervention to promote patient-PCP discussion about chronic conditions. Research Design: We conducted a randomized trial of a nurse coach intervention conducted entirely through a patient internet-portal. Subjects: Two hundred forty-one patients who were registered portal users with scheduled PCP appointments were screened through the portal for 3 target conditions, depression, chronic pain, mobility difficulty, and randomized to intervention and control groups. Measures: One-week and 3-month patient surveys assessed visit experiences, target conditions, and quality of life; chart abstractions assessed diagnosis and management during PCP visit. Results: Similar high percentages of intervention (85%) and control (80%) participants reported discussing their screened condition during their PCP visit. More intervention than control patients reported their PCP gave them specific advice about their health (94% vs. 84%; P = 0.03) and referred them to a specialist (51% vs. 28%; P = 0.002). Intervention participants reported somewhat higher satisfaction than controls (P = 0.07). Results showed no differences in detection or management of screened conditions, symptom ratings, and quality of life between groups. Conclusions: Internet portal-based coaching produced some possible benefits in care for chronic conditions but without significantly changing patient outcomes. Limited sample sizes may have contributed to insignificant findings. Further research should explore ways internet portals may improve patient outcomes in primary care. Clinical Trials.gov registration NCT00130416. C1 [Leveille, Suzanne G.; Huang, Annong; Tsai, Stephanie B.; Allen, Marybeth; Iezzoni, Lisa T.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Brookline, MA 02446 USA. [Leveille, Suzanne G.; Weingart, Saul N.; Iezzoni, Lisa T.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Weingart, Saul N.] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA USA. [Iezzoni, Lisa T.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. RP Leveille, SG (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 1309 Beacon St CO-219, Brookline, MA 02446 USA. EM sleveill@bidmc.harvard.edu NR 36 TC 36 Z9 37 U1 1 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2009 VL 47 IS 1 BP 41 EP 47 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 390TL UT WOS:000262186500006 PM 19106729 ER PT J AU McGinnis, KA Skanderson, M Levin, FL Brandt, C Erdos, J Justice, AC AF McGinnis, Kathleen A. Skanderson, Melissa Levin, Forrest L. Brandt, Cynthia Erdos, Joseph Justice, Amy C. TI Comparison of Two VA Laboratory Data Repositories Indicates That Missing Data Vary Despite Originating From the Same Source SO MEDICAL CARE LA English DT Article DE laboratory; DSS; ICR; VA ID HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; VETERANS; HIV; INFECTION; ASSOCIATION; COINFECTION; COHORT AB Background: Assessing accuracy and completeness of data is an important component of conducting research. VA Healthcare System benefits from a highly developed electronic medical information system. The Immunology Case Registry was designed to monitor costs and quality of HIV care. The Decision Support System was developed to monitor utilization and costs of veterans in care. Because these systems extract data from the same source using independent methods, they provide an opportunity to compare the accuracy and completeness of each. Objective: To compare overlapping laboratory data from the Veterans Affairs Health Information System between 2 data repositories. Research Design: For hemoglobin, CD4(+) lymphocyte counts (CD4), HIV RNA viral load, aspartate aminotransferase, alanine aminotransferase, glycosylated hemoglobin, creatinine, and white blood count, we calculated the percent of individuals with a value from each Source. For results in both repositories, we calculated Pearson's correlation coefficients. Subjects: A total of 22,647 HIV+ veterans in the Virtual Cohort with a visit in fiscal year 2002. Results: For 6 out of 9 tests, 68% to 72% of the observations overlapped. For CD4, viral load, and glycosylated hemoglobin less than 31% of observations overlapped. Overlapping results were nearly perfectly correlated except for CD4. Conclusions: Six of the laboratory tests demonstrated remarkably similar amounts of overlap, though Immunology Case Registry and Decision Support System both have missing data. Findings indicate that validation of laboratory data should be conducted before its use in quality and efficiency projects. When 2 databases arc not available for comparison, other methods of validation should be implemented. C1 [Levin, Forrest L.; Brandt, Cynthia; Erdos, Joseph; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [McGinnis, Kathleen A.; Skanderson, Melissa] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Brandt, Cynthia; Erdos, Joseph; Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA. RP Justice, AC (reprint author), VA Connecticut Healthcare Syst, 950 Campbell Ave,11 ACSLG, West Haven, CT USA. EM amy.justice2@va.go FU NIAAA [U01-13566]; Veterans Affairs Public Health Strategic Healthcare Group FX Supported by NIAAA U01-13566 and the Veterans Affairs Public Health Strategic Healthcare Group. NR 20 TC 9 Z9 9 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2009 VL 47 IS 1 BP 121 EP 124 PG 4 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 390TL UT WOS:000262186500017 PM 19106740 ER PT J AU Bianchi, MT Alexander, BM Cash, SS AF Bianchi, Matt T. Alexander, Brian M. Cash, Sydney S. TI Incorporating Uncertainty Into Medical Decision Making: An Approach to Unexpected Test Results SO MEDICAL DECISION MAKING LA English DT Article DE pretest probability; uncertainty; Bayes; unexpected; decision theory ID NONINVASIVE CARDIOVASCULAR TESTS; LIKELIHOOD RATIO COMPUTATION; PREDICTIVE POWER; CLINICAL UTILITY; DIAGNOSTIC-TEST; PROBABILITY; PERSPECTIVE; DISEASE AB The utility of diagnostic tests derives from the ability to translate the population concepts of sensitivity and specificity into information that will be useful for the individual patient: the predictive value of the result. As the array of available diagnostic testing broadens, there is a temptation to de-emphasize history and physical findings and defer to the objective rigor of technology. However, diagnostic test interpretation is not always straightforward. One significant barrier to routine use of probability-based test interpretation is the uncertainty inherent in pretest probability estimation, the critical first step of Bayesian reasoning. The context in which this uncertainty presents the greatest challenge is when test results oppose clinical judgment. It is this situation when decision support would be most helpful. The authors propose a simple graphical approach that incorporates uncertainty in pretest probability and has specific application to the interpretation of unexpected results. This method quantitatively demonstrates how uncertainty in disease probability may be amplified when test results are unexpected ( opposing clinical judgment), even for tests with high sensitivity and specificity. The authors provide a simple nomogram for determining whether an unexpected test result suggests that one should "switch diagnostic sides.'' This graphical framework overcomes the limitation of pretest probability uncertainty in Bayesian analysis and guides decision making when it is most challenging: interpretation of unexpected test results. C1 [Bianchi, Matt T.] Massachusetts Gen Hosp, Neurol Clin, Wang Ambulatory Ctr, Boston, MA 02114 USA. [Bianchi, Matt T.; Cash, Sydney S.] Brigham & Womens Hosp, Wang Ambulatory Ctr, Boston, MA 02115 USA. [Alexander, Brian M.] Brigham & Womens Hosp, Massachusetts Gen Hosp, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Alexander, Brian M.] Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Neurol Clin, Wang Ambulatory Ctr, 8th Floor, Boston, MA 02114 USA. EM thebianchi@gmail.com NR 24 TC 13 Z9 13 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD JAN-FEB PY 2009 VL 29 IS 1 BP 116 EP 124 DI 10.1177/0272989X08323620 PG 9 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 421KD UT WOS:000264356900011 PM 18812583 ER PT J AU Chen, ALC Chen, TJH Waite, RL Reinking, J Tung, HL Rhoades, P Downs, BW Braverman, E Braverman, D Kerner, M Blum, SH DiNubile, N Smith, D Oscar-Berman, M Prihoda, TJ Floyd, JB O'Brien, D Liu, HH Blum, K AF Chen, Amanda L-C. Chen, Thomas J. H. Waite, Roger L. Reinking, Jeffrey Tung, Howard L. Rhoades, Patrick Downs, B. William Braverman, Eric Braverman, Dasha Kerner, Mallory Blum, Seth H. DiNubile, Nicholas Smith, David Oscar-Berman, Marlene Prihoda, Thomas J. Floyd, John B. O'Brien, David Liu, H. H. Blum, Kenneth TI Hypothesizing that brain reward circuitry genes are genetic antecedents of pain sensitivity and critical diagnostic and pharmacogenomic treatment targets for chronic pain conditions SO MEDICAL HYPOTHESES LA English DT Article ID VENTRAL TEGMENTAL AREA; POSTTRAUMATIC-STRESS-DISORDER; CHRONIC WIDESPREAD PAIN; D2 RECEPTOR-BINDING; NUCLEUS-ACCUMBENS; DRD2 GENE; TENDER POINTS; FORMALIN TEST; DOPAMINE; ANALGESIA AB While it is well established that the principal ascending pathways for pain originate in the dorsal horn of the spinal cord and in the medulla, the control and sensitivity to pain may reside in additional neurological loci, especially in the mesolimbic system of the brain (i.e., a reward center), and a number of genes and associated polymorphisms may indeed impact pain tolerance and or sensitivity. It is hypothesized that these polymorphisms associate with a predisposition to intolerance or tolerance to pain. It is further hypothesized that identification of certain gene polymorphisms provides a unique therapeutic target to assist in the treatment of pain. It is hereby proposed that pharmacogenetic testing of certain candidate genes (i.e., mu receptors, PENK etc.) will result in pharmacogenomic solutions personalized to the individual patient, with potential improvement in clinical outcomes. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Liu, H. H.; Blum, Kenneth] Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA. [Chen, Amanda L-C.; Chen, Thomas J. H.] Chang Jung Christian Univ, Tainan, Taiwan. [Chen, Thomas J. H.] Changhua Christian Hosp, Changhua, Taiwan. [Waite, Roger L.; Downs, B. William; Blum, Kenneth] LifeGen Inc, La Jolla, CA USA. [Reinking, Jeffrey] Univ Calif Davis, Sch Med, Dept Rehabil Med, Davis, CA 95616 USA. [Tung, Howard L.] Univ Calif La Jolla, Div Neurol Surg, La Jolla, CA USA. [Rhoades, Patrick] Comprehens Pain Clin, Modesto, CA USA. [Braverman, Eric] Weill Cornell Sch Med, Dept Neurol Surg, New York, NY USA. [Braverman, Eric; Braverman, Dasha; Kerner, Mallory] PATH Res Fdn, Dept Res, New York, NY USA. [Blum, Seth H.; Blum, Kenneth] Synaptamine Inc, San Antonio, TX USA. [DiNubile, Nicholas; Blum, Kenneth] Hosp Univ Penn, Dept Orthopaed Surg, Philadelphia, PA 19104 USA. [Smith, David] Comprehens Pain Management Clin, San Diego, CA USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Oscar-Berman, Marlene] Boston VA Healthcare Syst, Boston, MA USA. [Prihoda, Thomas J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Floyd, John B.; O'Brien, David] Floyd Skeren & Kelly PC, Los Angeles, CA USA. [Liu, H. H.] Chung Shan Med Univ, Taichung, Taiwan. RP Liu, HH (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM drd2gene@aol.com FU Path Research Foundation, New York; Synaptamine Inc., San Antonio, TX; LifeGen Inc., La Jolla, CA; Electronic Waveform Lab, Huntington, Beach, California FX The authors want to thank the staff and financial support of Path Research Foundation, New York, Synaptamine Inc., San Antonio, TX, LifeGen Inc., La Jolla, CA, and Electronic Waveform Lab, Huntington, Beach, California. NR 43 TC 12 Z9 12 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 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD JAN PY 2009 VL 72 IS 1 BP 14 EP 22 DI 10.1016/j.mehy.2008.07.059 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 385YZ UT WOS:000261850800004 PM 18951726 ER PT J AU Henderson, DC Miley, K AF Henderson, David C. Miley, Kathleen BE Meyer, JM Nasrallah, HA TI Glucose Intolerance and Diabetes in Patients With Schizophrenia SO MEDICAL ILLNESS AND SCHIZOPHRENIA, 2ND EDITION LA English DT Article; Book Chapter ID INDUCED WEIGHT-GAIN; ATYPICAL ANTIPSYCHOTIC AGENTS; CORONARY-HEART-DISEASE; DRUG-NAIVE PATIENTS; DOUBLE-BLIND; 1ST-EPISODE SCHIZOPHRENIA; INSULIN-RESISTANCE; METABOLIC SYNDROME; CONTROLLED-TRIAL; LIFE-STYLE C1 [Henderson, David C.] Massachusetts Gen Hosp, Schizophrenia Diabet & Weight Reduct Res Program, Boston, MA 02114 USA. [Henderson, David C.] Harvard Univ, Sch Med, Boston, MA USA. RP Henderson, DC (reprint author), Massachusetts Gen Hosp, Schizophrenia Diabet & Weight Reduct Res Program, Boston, MA 02114 USA. NR 94 TC 0 Z9 0 U1 2 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-346-4 PY 2009 BP 91 EP 115 PG 25 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA BWM13 UT WOS:000294221400006 ER PT J AU Viguera, AC Varkula, M Donovan, K Baldessarini, RJ AF Viguera, Adele C. Varkula, Mackenzie Donovan, Katherine Baldessarini, Ross J. BE Meyer, JM Nasrallah, HA TI Managing Health Outcomes of Women With Schizophrenia During Pregnancy and Breastfeeding SO MEDICAL ILLNESS AND SCHIZOPHRENIA, 2ND EDITION LA English DT Article; Book Chapter ID HIGH-RISK GROUP; POSTPARTUM PSYCHOSES; ELECTROCONVULSIVE-THERAPY; PSYCHOTROPIC MEDICATIONS; ANTIDEPRESSANT TREATMENT; ATYPICAL ANTIPSYCHOTICS; MAJOR DEPRESSION; DECISION-MAKING; DISORDERS; MOTHERS C1 [Viguera, Adele C.; Varkula, Mackenzie] Cleveland Clin Fdn, Dept Psychiat & Psychol, Cleveland, OH 44195 USA. [Donovan, Katherine] Massachusetts Gen Hosp, Ctr Womens Hlth, Boston, MA 02114 USA. [Baldessarini, Ross J.] Harvard Univ, Sch Med, Boston, MA USA. [Baldessarini, Ross J.] McLean Hosp, Int Consortium Psychot Disorders Res, Belmont, MA 02178 USA. RP Viguera, AC (reprint author), Cleveland Clin Fdn, Dept Psychiat & Psychol, 9500 Euclid Ave, Cleveland, OH 44195 USA. NR 75 TC 0 Z9 0 U1 0 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-346-4 PY 2009 BP 415 EP 433 PG 19 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA BWM13 UT WOS:000294221400016 ER PT S AU Jayender, J Patel, RV Michaud, GF Hata, N AF Jayender, Jagadeesan Patel, Rajni V. Michaud, Gregory F. Hata, Nobuhiko BE Yang, GZ Hawkes, D Rueckert, D Nobel, A Taylor, C TI Optimal Transseptal Puncture Location for Robot-Assisted Left Atrial Catheter Ablation SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2009, PT I, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 12th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI2009) CY SEP 20-24, 2009 CL Imperial Coll, London, ENGLAND HO Imperial Coll ID PORT PLACEMENT; SURGERY AB The preferred method of treatment for Atrial Fibrillation (AF) is by catheter ablation wherein a catheter is guided into the left atrium through a transseptal puncture. However, the transseptal puncture constrains, the catheter, thereby limiting it's maneuverability and increasing the difficulty in reaching various locations in the left, atrium. In this paper, we address the problem of choosing the optimal transseptal puncture location for performing cardiac ablation to obtain maximum maneuverability of the catheter. We have employed all optimization algorithm to maximize the Global Isotropy Index (GII) to evaluate the opt inial transseptal puncture location. As part of this algorithm, a, novel kinematic model for the Catheter has been developed based oil a continuum robot model. Preoperative MR/CT images of the heart are segmented using the open source, image-guided therapy soft,ware, Slicer 3, to Obtain models Of the left, atrium and septal wall. These models are input, to the, optimization algorithm to evaluate the optimal transseptal puncture location. Simulation results for the optimization algorithm are presented in this paper. C1 [Jayender, Jagadeesan; Hata, Nobuhiko] Brigham & Womens Hosp, Harvard Med Sch, Dept Radiol, Surg Planning Lab, 75 Francis St, Boston, MA 02115 USA. [Patel, Rajni V.] Canadian Surg Technol & Adv Robot CSTAR, Univ Western Ontario, Dept Elect Engn & Comp Engn, Dept Surg, London, ON, Canada. [Michaud, Gregory F.] Brigham & Womens Hosp, Harvard Med Sch, Dept Cardiol, Boston, MA USA. [Hata, Nobuhiko] Massachusetts Gen Hosp, Ctr Integrat Med & Innovat Technol, Clinic Image Guidance Lab, Boston, MA USA. RP Jayender, J (reprint author), Brigham & Womens Hosp, Harvard Med Sch, Dept Radiol, Surg Planning Lab, 75 Francis St, Boston, MA 02115 USA. EM jayender@bwh.harvard.edu; rajni.patel@lhsc.on.ca; gfmichaud@partners.org; hata@bwh.harvard.edu RI Hata, Nobuhiko/L-5221-2014 OI Hata, Nobuhiko/0000-0002-6818-7700 FU METI Grant, Japan FX This research was supported by the Intelligent SurgicalInstruments Project, METI Grant, Japan. NR 9 TC 3 Z9 3 U1 1 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-04267-6 J9 LECT NOTES COMPUT SC PY 2009 VL 5761 BP 1 EP + PG 2 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BMU82 UT WOS:000273617300001 ER PT J AU Marty, FM Koo, S AF Marty, Francisco M. Koo, Sophia TI Role of (1 -> 3)-beta-D-glucan in the diagnosis of invasive aspergillosis SO MEDICAL MYCOLOGY LA English DT Article DE glucan; galactomannan; invasive aspergillosis; diagnosis; transplantation ID LIMULUS AMEBOCYTE LYSATE; PLASMA (1->3)-BETA-D-GLUCAN MEASUREMENT; LINKED-IMMUNOSORBENT-ASSAY; COMPUTED TOMOGRAPHIC SCAN; BETA-D-GLUCAN; FUNGAL-INFECTIONS; PULMONARY ASPERGILLOSIS; NEUTROPENIC PATIENTS; CIRCULATING GALACTOMANNAN; CELL TRANSPLANTATION AB Measurement of serum (1 -> 3)-beta-D-Glucan (BG) is an aid in the diagnosis of fungemia and deep-seated mycoses, including invasive aspergillosis (IA). BG is present in the cell wall of most pathogenic fungi (including Pneumocystis jiroveci) in significant amounts with some notable exceptions such as Cryptococcus neoformans and Zygomycetes. Commercially available assays can detect serum BG concentrations as low as 1pg/mL. Published validation studies have included patients with IA and other invasive fungal diseases (IFD). BG detection appears to be more sensitive than galactomannan detection in patients with IA, but BG's intrinsic lack of mycological specificity requires the integration of clinical, radiological, and microbiological data for proper interpretation. BG assay test characteristics can be used, for example, to exclude IA in some clinical scenarios, to increase the certainty of IA in the presence of an isolated positive galactomannan result or when testing follows initiation of antifungal treatment. BG may be falsely elevated in the serum in the absence of IFD in patients undergoing hemodialysis with cellulose membranes, in patients treated with immunoglobulin, albumin, or other blood products filtered through cellulose filters containing BG, and in patients with serosal exposure to glucan-containing gauze or to certain intravenous antimicrobials. These potential sources of false positivity should be considered when interpreting BG results. BG may be useful as a sensitive screening tool for surveillance of IA and other IFD in populations at risk. Stratified IFD screening and diagnostic strategies using both galactomannan and BG should be explored. Factors affecting the production and clearance of BG during IA and other IFD need additional study to further refine its diagnostic utility. C1 [Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Marty, FM (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB A4, Boston, MA 02115 USA. EM fmarty@partners.org OI Koo, Sophia/0000-0002-4973-7439 NR 72 TC 53 Z9 53 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PY 2009 VL 47 BP S233 EP S240 AR PII 901566810 DI 10.1080/13693780802308454 PG 8 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 435RZ UT WOS:000265362300031 PM 18720216 ER PT J AU Patterson, TF AF Patterson, Thomas F. TI Risk stratification for invasive aspergillosis: early assessment of host susceptibility SO MEDICAL MYCOLOGY LA English DT Article DE invasive aspergillosis; epidemiology; non-culture-based diagnostics; diagnosis; therapy ID BRONCHOALVEOLAR LAVAGE FLUID; ORGAN-TRANSPLANT RECIPIENTS; POLYMERASE-CHAIN-REACTION; HEMATOPOIETIC STEM-CELL; FUNGAL-INFECTIONS; PULMONARY ASPERGILLOSIS; AMPHOTERICIN-B; HEMATOLOGIC MALIGNANCIES; NEUTROPENIC PATIENTS; ACUTE-LEUKEMIA AB Outcomes of invasive aspergillosis are substantially improved with early initiation of therapy. Unfortunately, the diagnosis remains difficult to establish so that early suspicion of infection is imperative. Identification of high risk patients and use of non-culture-based diagnostics and radiographic studies can facilitate earlier recognition of infection. It is important to realize that the timing and spectrum of risk for invasive aspergillosis have expanded. While patients with hematological malignancies and hematopoietic stem cell transplants make up the highest risk groups, patients such as those receiving steroids and other immunosuppressive therapies are also at risk. Non-culture-based methods (including galactomannan, 1,3-beta-D-glucan, and PCR-based methods) are actively being pursued to improve early diagnosis. Thus, identifying patients at high risk for infection and utilizing non-culture-based methods and radiologic studies to assist in establishing a likely diagnosis of invasive aspergillosis will further enhance the role of new agents in the early, effective treatment and prophylaxis of invasive aspergillosis. C1 [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. [Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Patterson, TF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr,MSC 7881, San Antonio, TX 78229 USA. EM Patterson@uthscsa.edu FU National Institutes of Health; National Institute of Allergy and Infectious Diseases [N01-AI-30041]; Basilea; Merck Co.; Pfizer Inc.; Schering-Plough Corporation FX Potential conflicts of interest and financial support: T. F. P. has had grant support from Basilea, Merck & Co., Pfizer Inc., and Schering-Plough Corporation and has been a consultant for Basilea, Merck & Co., Pfizer Inc., and has been on the speaker's bureau for Merck & Co. and Pfizer Inc. T. F. P. is supported by the National Institutes of Health, National Institute of Allergy and Infectious Diseases, under Contract No. N01-AI-30041. NR 49 TC 9 Z9 10 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PY 2009 VL 47 BP S255 EP S260 AR PII 909142557 DI 10.1080/13693780902718339 PG 6 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 435RZ UT WOS:000265362300034 PM 19253143 ER PT J AU McDermott, DF AF McDermott, David F. TI The application of high-dose interleukin-2 for metastatic renal cell carcinoma SO MEDICAL ONCOLOGY LA English DT Article DE Immunotherapy; Renal cancer; Interleukin-2; Carbonic anhydrase IX ID CARBONIC-ANHYDRASE-IX; PHASE-III TRIAL; SUBCUTANEOUS INTERLEUKIN-2; RECOMBINANT INTERLEUKIN-2; INTERFERON-ALPHA; ADVANCED CANCER; SPONTANEOUS REGRESSION; IMMUNOTHERAPY; SURVIVAL; THERAPY AB Renal cell carcinoma (RCC) evokes an immune response, which has occasionally resulted in spontaneous and dramatic remissions [1-3]. In an attempt to reproduce or accentuate this response, various immunotherapeutic strategies have been studied. The most consistent anti-tumor activity has been reported with interferon alfa (IFN-alpha) and interleukin 2 (IL-2). In recent years, randomized trials have suggested that high-dose intravenous bolus IL-2 is superior in terms of response rate and possibly response quality to regimens that involve either low-dose IL-2 and IFN-alpha, intermediate- or low-dose IL-2 alone, or low-dose IFN-alpha alone. As this list of effective therapies for RCC grows, improvements in patient selection will be necessary to ensure that the only therapy capable of producing durable remissions will remain available to the patients who should receive it [4-7]. C1 [McDermott, David F.] Beth Israel Deaconess Med Ctr, Biol Therapy Program, Boston, MA 02215 USA. [McDermott, David F.] Harvard Univ, Sch Med, Boston, MA USA. [McDermott, David F.] Dana Farber Harvard Canc Ctr Renal Canc Program, Clin Res Sub Comm, Boston, MA USA. RP McDermott, DF (reprint author), Beth Israel Deaconess Med Ctr, Biol Therapy Program, 375 Longwood Ave,MS-428, Boston, MA 02215 USA. EM dmcdermo@bidmc.harvard.edu FU DF/HCC Renal Cancer SPORE [P50 CA101942-01] FX This work was supported in part by the DF/HCC Renal Cancer SPORE: P50 CA101942-01. NR 30 TC 16 Z9 16 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1357-0560 J9 MED ONCOL JI Med. Oncol. PD JAN PY 2009 VL 26 BP 13 EP 17 DI 10.1007/s12032-008-9152-1 PG 5 WC Oncology SC Oncology GA 403KN UT WOS:000263081600003 PM 19148594 ER PT J AU Atkins, MB AF Atkins, Michael B. TI Treatment selection for patients with metastatic renal cell carcinoma: identification of features favoring upfront IL-2-based immunotherapy SO MEDICAL ONCOLOGY LA English DT Article DE Renal cell carcinoma; Immunotherapy; Interleukin-2; Treatment selection ID CARBONIC-ANHYDRASE-IX; PHASE-III TRIAL; INTERFERON-ALPHA; INTERLEUKIN-2 THERAPY; DOSE INTERLEUKIN-2; PROGNOSIS; SURVIVAL; CANCER AB The availability of approved agents with distinct mechanisms of action (immunotherapy, vascular endothelial growth factor pathway, and mTOR inhibitors) has complicated treatment decisions for patients with advanced kidney cancer. High-dose IL-2 therapy is the only treatment that can produce durable complete responses; however, it has significant side effects and the vast majority of patients do not benefit. Thus, identifying the optimal patients to receive first-line IL-2 therapy is a priority. Past studies have identified some clinical features that might be associated with benefit from IL-2-based immunotherapy. Subsequent investigations of tumors from patients treated with IL-2 suggested that response was unlikely in patients with tumors with papillary features or low carbonic anhydrase IX (CAIX) expression. A model combining histologic features and CAIX expression separated patients into two groups of roughly equal size, with 96% of long-term responding patients being in the favorable prognostic group. This model is currently undergoing prospective validation. More recent studies involving gene expression profiling and array CGH have begun to identify additional features that might predict response to IL-2 therapy. Taken together, these data offer the possibility to limit the use of this toxic therapy to those most likely to benefit. C1 [Atkins, Michael B.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Atkins, Michael B.] Dana Farber Harvard Canc Ctr, Kidney Canc Program, Boston, MA 02215 USA. [Atkins, Michael B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Atkins, MB (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, MASCO Bldg,Rm 412,375 Longwood Ave, Boston, MA 02215 USA. EM matkins@bidmc.harvard.edu FU DF/HCC Renal Cancer SPORE-NIH/NCI [P50CA101942] FX This work was supported in part by DF/HCC Renal Cancer SPORE-NIH/NCI P50CA101942. Michael B. Atkins has served as a consultant for Antigenics, Aveo, Bayer, Bristol Myers Squibb, Genetech, Novartis, Onyx, and Wyeth and has received research funding from Bayer and Novartis. NR 17 TC 12 Z9 12 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1357-0560 J9 MED ONCOL JI Med. Oncol. PD JAN PY 2009 VL 26 BP 18 EP 22 DI 10.1007/s12032-008-9148-x PG 5 WC Oncology SC Oncology GA 403KN UT WOS:000263081600004 PM 19165638 ER PT J AU Unkelbach, J Bortfeld, T Martin, BC Soukup, M AF Unkelbach, Jan Bortfeld, Thomas Martin, Benjamin C. Soukup, Martin TI Reducing the sensitivity of IMPT treatment plans to setup errors and range uncertainties via probabilistic treatment planning SO MEDICAL PHYSICS LA English DT Article DE IMPT optimization; range uncertainty; setup error ID MODULATED PROTON THERAPY; RADIATION-THERAPY; DOSE UNCERTAINTIES; IMRT OPTIMIZATION; LUNG-TUMORS; RADIOTHERAPY; HETEROGENEITIES; MOTION AB Treatment plans optimized for intensity modulated proton therapy (IMPT) may be very sensitive to setup errors and range uncertainties. If these errors are not accounted for during treatment planning, the dose distribution realized in the patient may by strongly degraded compared to the planned dose distribution. The authors implemented the probabilistic approach to incorporate uncertainties directly into the optimization of an intensity modulated treatment plan. Following this approach, the dose distribution depends on a set of random variables which parameterize the uncertainty, as does the objective function used to optimize the treatment plan. The authors optimize the expected value of the objective function. They investigate IMPT treatment planning regarding range uncertainties and setup errors. They demonstrate that incorporating these uncertainties into the optimization yields qualitatively different treatment plans compared to conventional plans which do not account for uncertainty. The sensitivity of an IMPT plan depends on the dose contributions of individual beam directions. Roughly speaking, steep dose gradients in beam direction make treatment plans sensitive to range errors. Steep lateral dose gradients make plans sensitive to setup errors. More robust treatment plans are obtained by redistributing dose among different beam directions. This can be achieved by the probabilistic approach. In contrast, the safety margin approach as widely applied in photon therapy fails in IMPT and is neither suitable for handling range variations nor setup errors. (C) 2009 American Association of Physicists in Medicine. [DOI: 10.1118/1.3021139] C1 [Unkelbach, Jan; Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Unkelbach, Jan; Bortfeld, Thomas] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Martin, Benjamin C.] Boston Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. [Soukup, Martin] Univ Hosp Radiat Oncol, Sect Biomed Phys, Tubingen, Germany. RP Unkelbach, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM jan.unkelbach@googlemail.com; tbortfeld@partners.org FU NCI NIH HHS [R01 CA103904, P01 CA021239, P01-CA21239, R01 CA118200, R01-CA103904, R01-CA118200] NR 27 TC 91 Z9 91 U1 0 U2 10 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 JAN PY 2009 VL 36 IS 1 BP 149 EP 163 DI 10.1118/1.3021139 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 389OU UT WOS:000262105200019 PM 19235384 ER PT J AU Winey, B Zygmanski, P Lyatskaya, Y AF Winey, Brian Zygmanski, Piotr Lyatskaya, Yulia TI Evaluation of radiation dose delivered by cone beam CT and tomosynthesis employed for setup of external breast irradiation SO MEDICAL PHYSICS LA English DT Article DE CB-CT; CB-TS; dose measurements; breast setup ID COMPUTED-TOMOGRAPHY; DIGITAL TOMOSYNTHESIS; LUMPECTOMY CAVITY; SURGICAL CLIPS; THERAPY; RADIOTHERAPY; LOCALIZATION; SURGERY; TARGET; CANCER AB A systematic set of measurements is reported for evaluation of doses to critical organs resulting from cone-beam CT (CB-CT) and cone-beam tomosynthesis (CB-TS) as applied to breast setup for external beam irradiation. The specific focus of this study was on evaluation of doses from these modalities in a setting of volumetric breast imaging for target localization in radiotherapy treatments with the goal of minimizing radiation to healthy organs. Ion chamber measurements were performed in an anthropomorphic female thorax phantom at the center of each breast and lung and on the phantom surface at one anterior and two lateral locations (seven points total). The measurements were performed for three different isocenters located at the center of the phantom and at offset locations of the right and left breast. The dependence of the dose on angle selection for the CB-TS arc was also studied. For the most typical situation of centrally located CB-CT isocenter the measured doses ranged between 3 and 7 cGy, in good agreement with previous reports. Dose measurements were performed for a range of start/stop angles commonly used for CB-TS and the impact of direct and scatter dose on organs at risk was analyzed. All measured CB-TS doses were considerably lower than CB-CT doses, with greater decrease in dose for the organs outside of the beam (up to 98% decrease in dose). Remarkably, offsetting the isocenter towards the ipsilateral breast resulted on average to additional 46% dose reduction to organs at risk. The lowest doses to the contralateral breast and lung were less than 0.1 cGy when they were measured for the offset isocenter. The biggest reduction in dose was obtained by using CB-TS beams that completely avoid the critical organ. For points inside the CB-TS beam, the dose was reduced in a linear relation with distance from the center of the imaging arc. The data indicate that it is possible to reduce substantially radiation doses to the contralateral organs by proper selection of CB-TS angles and imaging field sizes. Our results provide the first systematic study on CB-TS doses from setup imaging for external breast irradiation and can be a useful resource for estimating anticipated radiation doses as a function of the conditions chosen for imaging breast setup. (C) 2009 American Association of Physicists in Medicine. [DOI: 10.1118/1.3036113] C1 [Winey, Brian; Zygmanski, Piotr; Lyatskaya, Yulia] Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. RP Lyatskaya, Y (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. EM ylyatskaya@lroc.harvard.edu NR 32 TC 21 Z9 22 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2009 VL 36 IS 1 BP 164 EP 173 DI 10.1118/1.3036113 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 389OU UT WOS:000262105200020 PM 19235385 ER PT J AU Rosenbaum, BP Gorrindo, TL Patel, SG McTigue, MP Rodgers, SM Miller, BM AF Rosenbaum, Benjamin P. Gorrindo, Tristan L. Patel, Sanjay G. McTigue, Michael P. Rodgers, Scott M. Miller, Bonnie M. TI Medical student involvement in website development SO MEDICAL TEACHER LA English DT Article ID WEB; EDUCATION AB Background: The digital management of educational resources and information is becoming an important part of medical education. Aims: At Vanderbilt University School of Medicine, two medical students sought to create a website for all medical students to act as each student's individual homepage. Method: Using widely available software and database technology, a highly customized Web portal, known as the VMS Portal, was created for medical students. Access to course material, evaluations, academic information, and community assets were customized for individual users. Modular features were added over the course of a year in response to student requests, monitoring of usage habits, and solicitation of direct student feedback. Results: During the first 742 days of the VMS Portal's release, there were 209,460 student login sessions ( 282 average daily). Of 348 medical students surveyed (71% response rate), 84% agreed or strongly agreed that 'consolidated student resources made their lives easier' and 82% agreed or strongly agreed that their needs were represented by having medical students design and create the VMS Portal. Conclusion: In the VMS Portal project, medical students were uniquely positioned to help consolidate, integrate, and develop Web resources for peers. As other medical schools create and expand digital resources, the valuable input and perspective of medical students should be solicited. C1 [Rosenbaum, Benjamin P.; Gorrindo, Tristan L.; Patel, Sanjay G.; McTigue, Michael P.; Rodgers, Scott M.; Miller, Bonnie M.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Gorrindo, Tristan L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Miller, BM (reprint author), VUMC, 203 Light Hall, Nashville, TN 37232 USA. EM bonnie.m.miller@vanderbilt.edu NR 12 TC 2 Z9 2 U1 2 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0142-159X J9 MED TEACH JI Med. Teach. PY 2009 VL 31 IS 7 BP 627 EP 633 DI 10.1080/01421590802206713 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 481DS UT WOS:000268788000008 PM 19811147 ER PT J AU Dhaliwal, G Sharpe, BA AF Dhaliwal, Gurpreet Sharpe, Bradley A. TI Twelve tips for presenting a clinical problem solving exercise SO MEDICAL TEACHER LA English DT Editorial Material ID MEDICAL GRAND ROUNDS; ATTENDING PHYSICIANS; MODELS AB Background: Lectures are moderately effective for teaching medical knowledge but generally fail at promoting clinical reasoning. In a clinical problem solving (CPS) conference, a clinician is presented an unknown medical case in a stepwise fashion. These popular conferences highlight clinical reasoning and foster active learning to a greater degree than lecture-based education. Aim: In the absence of literature which addresses the organization of these conferences, we present a guide for the teacher (case presenter) to maximize the session's educational value. Methods: Practical issues for case selection, preparation, and presentation are addressed. The predominant theme is to retain an emphasis on real-time reasoning and to minimize the artificial nature of solving an unknown case from presented material rather than a live patient. Conclusions: The successful execution of the CPS engages both the audience and the discussant in real-time problem solving and relies upon the tenants of experiential learning and clinical reasoning rather than the traditional structure of the medical case presentation. C1 [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Sharpe, Bradley A.] Univ Calif San Francisco, Hosp Med, San Francisco, CA 94143 USA. RP Dhaliwal, G (reprint author), San Francisco VA Med Ctr, 4150 Clement St 111, San Francisco, CA 94121 USA. EM gurpreet.dhaliwal@va.gov NR 26 TC 3 Z9 3 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0142-159X J9 MED TEACH JI Med. Teach. PY 2009 VL 31 IS 12 BP 1056 EP 1059 DI 10.3109/01421590902912103 PG 4 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 538CL UT WOS:000273161700004 PM 19995167 ER PT B AU Najavits, LM Schmitz, M Johnson, KM Smith, C North, T Hamilton, N Walser, R Reeder, K Norman, S Wilkins, K AF Najavits, Lisa M. Schmitz, Martha Johnson, Kay M. Smith, Cary North, Terry Hamilton, Nancy Walser, Robyn Reeder, Kevin Norman, Sonya Wilkins, Kendall BE Katlin, LJ TI SEEKING SAFETY THERAPY FOR MEN: CLINICAL AND RESEARCH EXPERIENCES SO MEN AND ADDICTIONS: NEW RESEARCH SE Substance Abuse Assessment Interventions and Treatment LA English DT Article; Book Chapter ID VETERANS; DISORDER AB This chapter highlights clinical and research experience on the use of Seeking Safety therapy with men clients. Seeking Safety is a present-focused, coping skills model that addresses trauma and/or substance abuse, from the start of treatment. Its major goal is to help clients increase safety in their lives. The model was designed for both genders, and all types of traumas and substances. We describe how it has been implemented in various settings with men including mental health and substance abuse programs, veterans' hospitals, correctional settings, and residential treatment. The authors represent a range of clinicians and researchers who have conducted the model with men for many years. We describe key themes, treatment strategies, and research studies on Seeking Safety with men. C1 [Najavits, Lisa M.] Harvard Univ, Sch Med, McLean Hosp, Boston, MA 02115 USA. [Schmitz, Martha] San Francisco VA Med Ctr, San Francisco, CA USA. [Johnson, Kay M.] St Lukes Roosevelt Hosp, Crime Victims Treatment Ctr, New York, NY 10025 USA. [Smith, Cary] Vet Ctr, Readjustment Counseling Serv, Dept Vet Affairs, Washington, DC USA. [North, Terry] VA Omaha, Omaha, NE USA. [Hamilton, Nancy] Operat PAR, St Petersburg, FL USA. [Walser, Robyn] VA Palo Alto, Palo Alto, CA USA. [Norman, Sonya] VA San Diego Healthcare Syst, San Diego, CA USA. [Norman, Sonya; Wilkins, Kendall] Univ Calif San Diego, San Diego, CA 92103 USA. [Wilkins, Kendall] San Diego State Univ, San Diego, CA 92182 USA. RP Najavits, LM (reprint author), Harvard Univ, Sch Med, McLean Hosp, Boston, MA 02115 USA. NR 11 TC 6 Z9 6 U1 1 U2 2 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60692-098-5 J9 SUBST ABUS ASSESS IN PY 2009 BP 37 EP 58 PG 22 WC Substance Abuse SC Substance Abuse GA BKU81 UT WOS:000269297300002 ER PT J AU Bailey, A AF Bailey, Allison TI Risk factors for low back pain in women: still more questions to be answered SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID DWELLING SENIOR-CITIZENS; PHYSICAL-DISABILITY; MENSTRUAL-CYCLE; PREGNANCY; PREVALENCE; ASSOCIATION; SYMPTOMS; ADULTS C1 Massachusetts Gen Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. RP Bailey, A (reprint author), Massachusetts Gen Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. NR 19 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN-FEB PY 2009 VL 16 IS 1 BP 3 EP 4 DI 10.1097/gme.0b013e31818e10a7 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 392WO UT WOS:000262333100002 PM 19002014 ER PT B AU Tracy, EE AF Tracy, Erin E. BE Keel, MI TI MENTORING IN MEDICINE SO MENTORING: PROGRAM DEVELOPMENT, RELATIONSHIPS AND OUTCOMES SE Education in a Competitive and Globalizing World LA English DT Article; Book Chapter ID ACADEMIC MEDICINE; FACULTY; PROGRAMS; JUNIOR C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tracy, EE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,406 Founders House, Boston, MA 02114 USA. EM EETracy@partners.org NR 34 TC 0 Z9 0 U1 0 U2 0 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60692-287-3 J9 EDUC COMPET GLOB WOR PY 2009 BP 153 EP 160 PG 8 WC Education & Educational Research SC Education & Educational Research GA BLV69 UT WOS:000271186800011 ER PT B AU Kotz, KT Irimia, D Tompkins, RG Toner, M AF Kotz, Kenneth T. Irimia, Daniel Tompkins, Ronald G. Toner, Mehmet BE Nahmias, Y Bhatia, SN TI Immunoaffinity Capture of Cells from Whole Blood SO METHODS IN BIOENGINEERING: MICRODEVICES IN BIOLOGY AND MEDICINE SE Artech House Methods in Bioengineering Series LA English DT Article; Book Chapter DE microfluidics; PDMS; immunoaffinity capture; whole blood; fractionation ID MICROFLUIDIC CHAMBERS; FLOW AB Cellular-based diagnostics are of increasing importance in health and disease monitoring as well as basic science research. Isolating purified, homogeneous cells from complex biological samples, however, is a lengthy process suited for specialized, well-equipped research laboratories and difficult to implement in clinical medicine. Here we outline a rapid and easy process for utilizing state-of-the-art microfluidic technology to isolate leukocyte subpopulations directly from whole blood using neutrophils as an example. C1 [Kotz, Kenneth T.; Irimia, Daniel; Tompkins, Ronald G.; Toner, Mehmet] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Surg Serv, Boston, MA 02114 USA. [Kotz, Kenneth T.; Irimia, Daniel; Tompkins, Ronald G.; Toner, Mehmet] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Kotz, Kenneth T.; Irimia, Daniel; Tompkins, Ronald G.; Toner, Mehmet] Shriners Hosp Children, Dept Surg, Boston, MA 02114 USA. [Kotz, Kenneth T.; Irimia, Daniel; Tompkins, Ronald G.; Toner, Mehmet] Harvard Univ, Sch Med, Boston, MA USA. [Kotz, Kenneth T.; Irimia, Daniel; Toner, Mehmet] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Charlestown, MA 02114 USA. [Tompkins, Ronald G.] Shriners Hosp Children, Ctr Engn Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kotz, KT (reprint author), Massachusetts Gen Hosp, BioMEMS Resource Ctr, Surg Serv, Boston, MA 02114 USA. EM kkotz@partners.org; dirimia@partners.org; rtompkins@partners.org; mtoner@hms.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 1 PU ARTECH HOUSE PI NORWOOD PA 685 CANTON ST, NORWOOD, MA 02062 USA BN 978-1-59693-404-7 J9 ARTECH HSE METH BIOE JI Art. Hse. Meth. Bioengr. Ser. PY 2009 BP 1 EP 24 PG 24 WC Engineering, Biomedical SC Engineering GA BKT27 UT WOS:000269157400001 ER PT B AU King, KR Jindal, R Nahmias, Y Yarmush, ML AF King, Kevin R. Jindal, Rohit Nahmias, Yaakov Yarmush, Martin L. BE Nahmias, Y Bhatia, SN TI Dynamic Gene-Expression Analysis in a Microfluidic Living Cell Array (mLCA) SO METHODS IN BIOENGINEERING: MICRODEVICES IN BIOLOGY AND MEDICINE SE Artech House Methods in Bioengineering Series LA English DT Article; Book Chapter DE gene expression dynamics; fluorescent reporter cells; systems biology ID NF-KAPPA-B; P53-MDM2 FEEDBACK LOOP; SINGLE; STOCHASTICITY; HETEROGENEITY; OSCILLATIONS; NOISE AB Gene expression is a fundamental cellular process that allows for the dynamic regulation of protein production, adapting the cellular response to environmental changes. The ability to measure changes in gene expression is currently limited by the use of destructive techniques that measure only bulk properties of cell populations and by the inability to dynamically control the microenvironment of cells in culture. This chapter describes an integrated and highly scalable functional genomics platform called the microfluidic living cell array (mLCA) that combines a library of green fluorescent protein (GFP) transcriptional reporters with a high-throughput fluid-addressable cell array, enabling dynamic gene expression profiling in living cells. By creating a window to the temporal patterns of transcriptional regulation, the mLCA is poised to make important contributions to our understanding of transcription factor networks and dynamic processes such as development, wound healing, or disease. C1 [King, Kevin R.; Yarmush, Martin L.] Harvard MIT Div Hlth Sci & Technol, Boston, MA USA. [Jindal, Rohit; Nahmias, Yaakov; Yarmush, Martin L.] Shriners Hosp Children, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Jindal, Rohit; Nahmias, Yaakov; Yarmush, Martin L.] Harvard Univ, Sch Med, Boston, MA USA. [King, Kevin R.] MIT, Dept Hlth Sci & Technol, Ctr Engn Med, Boston, MA 02114 USA. [Nahmias, Yaakov] Massachusetts Gen Hosp, BioMEMs Resource Ctr, Charlestown, MA 02129 USA. RP King, KR (reprint author), Harvard MIT Div Hlth Sci & Technol, Boston, MA USA. EM krking@mit.edu; rjindal@partners.org; ynahmias@partners.org; ireis@sbi.org; ynahmias@partners.org RI Nahmias, Yaakov/H-4725-2013 NR 27 TC 1 Z9 1 U1 0 U2 0 PU ARTECH HOUSE PI NORWOOD PA 685 CANTON ST, NORWOOD, MA 02062 USA BN 978-1-59693-404-7 J9 ARTECH HSE METH BIOE JI Art. Hse. Meth. Bioengr. Ser. PY 2009 BP 25 EP 41 PG 17 WC Engineering, Biomedical SC Engineering GA BKT27 UT WOS:000269157400002 ER PT B AU McCarthy, JR Jaffer, FA Weissleder, R AF McCarthy, Jason R. Jaffer, Farouc A. Weissleder, Ralph BE Rege, K Medintz, IL TI Imaging and Therapy of Atherosclerotic Lesions with Theranostic Nanoparticles SO METHODS IN BIOENGINEERING: NANOSCALE BIOENGINEERING AND NANOMEDICINE SE Artech House Methods in Bioengineering Series LA English DT Article; Book Chapter DE theranostic nanoagent; intravital fluorescence microscopy; iron oxide; nanoparticles; molecular imaging; light-activated therapy ID ULTRASMALL SUPERPARAMAGNETIC PARTICLES; IRON-OXIDE; CAROTID PLAQUES; MACROPHAGE; INFLAMMATION; FERUMOXTRAN-10; ATHEROMA; EFFICACY; CANCER; AGENT AB Theranostic nanomaterials, or those bearing both therapeutic and diagnostic entities, are capable of simultaneously imaging and treating disease. In this method, we synthesize a novel atherosclerosis-targeted theranostic nanoagent based upon crosslinked iron oxide nanoparticles (CLIO) bearing fluorophores for near infrared fluorescence imaging, and near infrared light activated therapeutic (NILAT) agents for therapy. These macrophage-targeted nanoparticles are applied to the detection and localized therapy of atherosclerotic lesions in apolipoprotein E deficient mice. Intravital fluorescence microscopy enables the longitudinal examination of nanoparticle uptake before and after therapy, thus allowing for an in vivo determination of therapeutic efficacy. While theranostic nanoagents have unique strengths, including the concomitant assessment of the diagnosis and therapy of disease, the field is still in its infancy. This method provides for further study of these capabilities. C1 [McCarthy, Jason R.; Weissleder, Ralph] Harvard Univ, Sch Med, Ctr Syst Biol, Charlestown, MA 02129 USA. [McCarthy, Jason R.; Jaffer, Farouc A.; Weissleder, Ralph] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Jaffer, Farouc A.] Harvard Univ, Sch Med, Div Cardiol, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP McCarthy, JR (reprint author), Harvard Univ, Sch Med, Ctr Syst Biol, 149 13th St,Rm 5406, Charlestown, MA 02129 USA. EM jason_mccarthy@hms.harvard.edu NR 24 TC 3 Z9 3 U1 0 U2 4 PU ARTECH HOUSE PI NORWOOD PA 685 CANTON ST, NORWOOD, MA 02062 USA BN 978-1-59693-410-8 J9 ARTECH HSE METH BIOE JI Art. Hse. Meth. Bioengr. Ser. PY 2009 BP 137 EP 151 PG 15 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA BKZ87 UT WOS:000269709900009 ER PT B AU Purton, LE Scadden, DT AF Purton, Louise E. Scadden, David T. BE Parekkadan, B Yarmush, ML TI Analysis of Mouse Hematopoietic Stem and Progenitor Cells SO METHODS IN BIOENGINEERING: STEM CELL BIOENGINEERING SE Artech House Methods in Bioengineering Series LA English DT Article; Book Chapter DE Limiting dilution assay; competitive repopulating assay; colony-forming unit-spleen; colony-forming cells; HSC immunophenotype; HSC transplants ID BONE MARROW CELLS; IN-VIVO; C-KIT; COMPETITIVE REPOPULATION; SELF-RENEWAL; ABILITY; DIFFERENTIATION; PURIFICATION; POPULATION; CAPACITY AB Hematopoiesis (the process by which blood cell formation occurs) is a finely regulated process involving both self-renewal and differentiation decisions of hematopoietic stem cells. In this chapter we provide detailed instructions on how to perform some of the in vitro and in vivo methods routinely used to assess hematopoietic stem and progenitor cell content in the mouse model, which is the most commonly used small-animal model for hematopoiesis studies in research laboratories around the world. C1 [Purton, Louise E.] Univ Melbourne, St Vincents Hosp, Dept Med, St Vincents Inst, Fitzroy, Vic 3065, Australia. [Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Purton, LE (reprint author), Univ Melbourne, St Vincents Hosp, Dept Med, St Vincents Inst, 9 Princes St, Fitzroy, Vic 3065, Australia. NR 27 TC 0 Z9 0 U1 0 U2 1 PU ARTECH HOUSE PI NORWOOD PA 685 CANTON ST, NORWOOD, MA 02062 USA BN 978-1-59693-402-3 J9 ARTECH HSE METH BIOE JI Art. Hse. Meth. Bioengr. Ser. PY 2009 BP 89 EP 106 PG 18 WC Engineering, Biomedical SC Engineering GA BKT28 UT WOS:000269158200007 ER PT B AU Elmoazzen, HY Toner, M AF Elmoazzen, Heidi Y. Toner, Mehmet BE Parekkadan, B Yarmush, ML TI A Novel Method for the Preservation of Embryonic Stem Cells Using a Quartz Capillary Freezing System SO METHODS IN BIOENGINEERING: STEM CELL BIOENGINEERING SE Artech House Methods in Bioengineering Series LA English DT Article; Book Chapter DE Cryopreservation; slow freezing; vitrification; mouse embryonic stem cells; human embryonic stem cells; quartz capillaries ID AQUEOUS-SOLUTIONS; VITRIFICATION; CRYOPRESERVATION; OOCYTES; WATER AB To have widespread application of embryonic stem cells, effective long-term storage of these cells is essential. There are currently two approaches to achieving cryopreservation of cells: the conventional slow-freezing approach, which uses low cooling rates; and the vitrification approach, which uses rapid cooling rates. With slow freezing, the cryoprotectant concentrations used are low and nontoxic to the cells. However, the challenge is that slow freezing is associated with injury resulting from ice formation. Vitrification involves the solidification of a supercooled liquid while maintaining the absence of ice, such that a glass is formed. However, to achieve vitrification, rapid cooling rates and very high toxic concentrations of cocktails of cryoprotectants are required. The ideal cryopreservation protocol, then, would be one that combines the benefits of conventional slow freezing (reduced toxicity secondary to low cryoprotectant levels) with the benefits of vitrification (absence of intracellular ice crystal formation). A method of cellular cryopreservation using quartz capillary freezing has shown that the process of vitrification can be optimized by maximizing the rate at which the sample is cooled, which allows for the use of lower cryoprotectant concentrations. The quartz capillary freezing technique can be used to preserve embryonic stem cells. C1 [Elmoazzen, Heidi Y.; Toner, Mehmet] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Ctr Engn Med,Shiners Hosp Childrens, Boston, MA 02114 USA. RP Elmoazzen, HY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Ctr Engn Med,Shiners Hosp Childrens, 51 Blossom St, Boston, MA 02114 USA. NR 28 TC 0 Z9 0 U1 0 U2 1 PU ARTECH HOUSE PI NORWOOD PA 685 CANTON ST, NORWOOD, MA 02062 USA BN 978-1-59693-402-3 J9 ARTECH HSE METH BIOE JI Art. Hse. Meth. Bioengr. Ser. PY 2009 BP 167 EP 178 PG 12 WC Engineering, Biomedical SC Engineering GA BKT28 UT WOS:000269158200012 ER PT S AU Campanella, GSV Luster, AD AF Campanella, Gabriele S. V. Luster, Andrew D. BE Handel, TM Hamel, DJ TI A CHEMOKINE-MEDIATED IN VIVO T-CELL RECRUITMENT ASSAY SO METHODS IN ENZYMOLOGY, VOL 461: CHEMOKINES, PART B SE Methods in Enzymology LA English DT Review; Book Chapter ID EPITHELIAL-CELLS; CXCL10; IP-10; CXCR3; INFECTION; SELECTION AB The ability of chemokines to induce the migration of cells expressing their cognate G-protein-coupled receptor is a characteristic property of chemokine function. To study this important function, in vitro chemotaxis assays are most often used, which, although useful, lack many components of the complex in vivo trafficking process. Reliable in vivo recruitment assays have been very difficult to establish. We describe a robust in vivo T-cell recruitment assay for adoptively transferred T lymphocytes in mice. Instillation of the CXCR3 chemokine ligands IP-10/CXCL10 or I-TAC/CXCL11 into the airways results in robust recruitment of transferred T lymphocytes. The assay thereby models the natural environment of chemokine function, as chemokines are expressed in the airways during inflammation, inducing selective leukocyte homing. This assay is particularly useful for the analysis of chemokine and chemokine receptor mutants in structure function studies and for testing the in vivo efficacy of inhibitory chemokine and chemokine receptor antibodies and small molecule antagonists. C1 [Campanella, Gabriele S. V.; Luster, Andrew D.] Harvard Univ, Sch Med,Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. RP Campanella, GSV (reprint author), Harvard Univ, Sch Med,Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01 CA069212, CA069212] NR 13 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374907-9 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2009 VL 461 BP 397 EP 412 DI 10.1016/S0076-6879(09)05418-4 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJW03 UT WOS:000267287900018 PM 19480929 ER PT S AU Eeckhoute, J Lupien, M Brown, M AF Eeckhoute, Jerome Lupien, Mathieu Brown, Myles BE Pollack, JR TI Combining Chromatin Immunoprecipitation and Oligonucleotide Tiling Arrays (ChIP-Chip) for Functional Genomic Studies SO MICROARRAY ANALYSIS OF THE PHYSICAL GENOME: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Chromatin immunoprecipitation; tiling arrays; ChIP-chip; epigenetic; epigenomic; genomic; cistrome ID CROSS-LINKING; IDENTIFICATION; TRANSCRIPTION; NETWORK; FOXA1 AB Central to systems biology are genome-wide technologies and high-throughput experimental approaches. Completion of the sequencing of the human genome as well as those of a number of other higher eukaryotes now allows for the first time the mapping of all of the cis-regulatory regions of genes as well as the details of nucleosome position and modification. One approach to achieving this goal involves chromatin immunoprecipitation combined with DNA oligonucleotide tiling arrays (ChIP-chip). This allows for the identification of genomic regions bound by a given factor, its cistrome, or harboring a given epigenomic modification through hybridization on tiling arrays covering the entire genome or specific regions of interest. This technology offers all unbiased assessment of the potential biological function of any DNA associated factor or epigenomic mark. Through integration of ChIP-chip data with complementary genome-wide approaches including expression profiling, CGH and SNP arrays, novel paradigms of transcriptional regulation and chromatin structure are emerging. C1 [Eeckhoute, Jerome; Lupien, Mathieu; Brown, Myles] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Mol & Cellular Oncol, Boston, MA 02115 USA. RP Eeckhoute, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Mol & Cellular Oncol, 44 Binney St, Boston, MA 02115 USA. OI Brown, Myles/0000-0002-8213-1658; Eeckhoute, Jerome/0000-0002-7222-9264 NR 14 TC 3 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-191-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 556 BP 155 EP 164 DI 10.1007/978-1-60327-192-9_11 D2 10.1007/978-1-60327-192-9 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BKY57 UT WOS:000269618600011 PM 19488877 ER PT S AU Liu, XS Meyer, CA AF Liu, X. Shirley Meyer, Clifford A. BE Pollack, JR TI ChIP-Chip: Algorithms for Calling Binding Sites SO MICROARRAY ANALYSIS OF THE PHYSICAL GENOME: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE ChIP-chip; probe modeling; normalization; peak detection ID GENOME-WIDE ANALYSIS AB Genome-wide ChIP-chip assays of protein-DNA interactions yield large volumes of data requiring effective statistical analysis to obtain reliable results. Successful analysis methods need to be tailored to platform specific characteristics such as probe density, genome coverage,and the nature of the controls. We describe the use of the respective software packages MAT and MA2C for the analysis of ChIP-chip data from one-color Affymetrix and two-color NimbleGen or Agilent tiling microarrays. C1 [Liu, X. Shirley; Meyer, Clifford A.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Liu, XS (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. FU NHGRI NIH HHS [R01 HG004069-03, R01 HG004069] NR 13 TC 2 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-191-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 556 BP 165 EP 175 DI 10.1007/978-1-60327-192-9_12 D2 10.1007/978-1-60327-192-9 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BKY57 UT WOS:000269618600012 PM 19488878 ER PT B AU King, KR Yarmush, ML Jayaraman, A AF King, Kevin R. Yarmush, Martin L. Jayaraman, Arul BE Dill, K Liu, RH Grodzinski, P TI Expression Profiling Using Microfluidic Living Cell Arrays SO MICROARRAYS: PREPARATION, MICROFLUIDICS, DETECTION METHODS, AND BIOLOGICAL APPLICATIONS SE Integrated Analytical Systems LA English DT Article; Book Chapter ID GREEN FLUORESCENT PROTEIN; GENE-EXPRESSION; BIOLOGY; NETWORKS; DYNAMICS; REPORTER; CULTURE; DEVICE; NOISE; FLOW C1 [King, Kevin R.; Yarmush, Martin L.] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [King, Kevin R.; Yarmush, Martin L.] Harvard Univ, Sch Med, Boston, MA USA. [Jayaraman, Arul] Texas A&M Univ, Artie McFerrin Dept Chem Engn, College Stn, TX USA. RP King, KR (reprint author), Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. NR 33 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-72716-5 J9 INTEGR ANAL SYST PY 2009 BP 211 EP 226 DI 10.1007/978-0-387-72719-6_10 D2 10.1007/978-0-387-72719-6 PG 16 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA BJY42 UT WOS:000267419200010 ER PT J AU Kling, DE Cavicchio, AJ Sollinger, CA Madoff, LC Schnitzer, JJ Kinane, TB AF Kling, David E. Cavicchio, Amanda J. Sollinger, Christina A. Madoff, Lawrence C. Schnitzer, Jay J. Kinane, Thomas B. TI Lactic acid is a potential virulence factor for group B Streptococcus SO MICROBIAL PATHOGENESIS LA English DT Article DE Lung; Neonate; Streptococcus agalactiae infection; Acidosis; Acidemia; pH; Virulence; Fetal; Rat; Respiratory; Invasive; Pathogen ID ALPHA-C-PROTEIN; HUMAN-EPITHELIAL-CELLS; LACTATE-DEHYDROGENASE; PROTECTIVE EPITOPES; SURFACE-PROTEINS; DENTAL-CARIES; VAGINAL PH; AGALACTIAE; BINDING; RAT AB Group B Streptococcus (GBS) is a Gram-positive bacterium that Causes sepsis and meningitis in neonates and infants. Although several GBS-associated virulence factors have been described, the mechanisms of GBS invasive disease are not well understood. To characterize additional virulence factors, a novel in vitro infection assay was developed using rat fetal lung explants. However, application of GBS to the system induced rapid lung tissue destruction associated with increased media acidity. Since lactic acid produced by other streptococci is an important virulence factor, we hypothesized that lactic acid contributed to the virulence of GBS. Spent growth media and neutralized-spent media were applied to explants and results indicated that neutralization of the media completely protected the tissue from degradation. These results were verified using multiple viability assays and with transformed cell lines. Furthermore, comparable spent media from Escherichia coli did not induce tissue cytotoxicity, suggesting that GBS produces organic acids in excess of other potential bacterial pathogens. Analysis of the spent media indicated that L-lactate levels reached similar to 70 mM, indicating that lactic acid is a major constituent of the metabolic acid produced by GBS. Treatment of explants with lactic acid alone produced dose-dependent tissue degradation, indicating that lactic acid is independently sufficient to induce target-tissue cytotoxicity. Finally, both spent media and 23.6 mM lactic acid produced dramatic tissue autofluorescence; the basis for this is currently unknown. These studies demonstrate that GBS-produced lactic acid is a potential virulence factor and may contribute to GBS invasive disease. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Kling, David E.; Kinane, Thomas B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Lab Dev Immunol, Boston, MA 02114 USA. [Cavicchio, Amanda J.; Sollinger, Christina A.; Schnitzer, Jay J.] Massachusetts Gen Hosp, Dept Pediat Surg CPZ6 100, Boston, MA 02114 USA. [Madoff, Lawrence C.] Univ Massachusetts, Med Ctr, Div Infect Dis & Immunol, Jamaica Plain, MA 02130 USA. [Madoff, Lawrence C.] William Hinton State Lab Inst, Massachusetts Dept Publ Hlth, Jamaica Plain, MA 02130 USA. RP Kling, DE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Lab Dev Immunol, 55 Fruit St,GRJ 1402, Boston, MA 02114 USA. EM dkling@partners.org NR 50 TC 5 Z9 5 U1 0 U2 5 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD JAN PY 2009 VL 46 IS 1 BP 43 EP 52 DI 10.1016/j.micpath.2008.10.009 PG 10 WC Immunology; Microbiology SC Immunology; Microbiology GA 400RB UT WOS:000262885100007 PM 19010409 ER PT J AU Schulz, C Von Andrian, UH Massberg, S AF Schulz, Christian Von Andrian, Ulrich H. Massberg, Steffen TI Trafficking of Murine Hematopoietic Stem and Progenitor Cells in Health and Vascular Disease SO MICROCIRCULATION LA English DT Article DE stem cells; progenitor cells; trafficking; vascular disease; mouse model ID COLONY-STIMULATING FACTOR; BONE-MARROW MICROVESSELS; IN-VIVO; ENDOTHELIAL-CELLS; PERIPHERAL-BLOOD; E-SELECTIN; SPHINGOSINE 1-PHOSPHATE; ADHESION MOLECULE-1; DEFICIENT MICE; P-SELECTIN AB Hematopoietic stem cells (HSCs) possess the unique capacity for self-renewal and differentiation into various hematopoietic cell lineages. Here we summarize the processes that underlie their mobilization and directed migration from bone marrow into peripheral tissues and back to the bone marrow compartment. We specifically focus on the potential role of hematopoietic stem and progenitor cell (HSPC) migration in vascular diseases and review data from recent studies on mice. A better understanding of the mechanisms that guide HSPCs to vascular tissues will be critical for the development of novel therapeutic strategies to prevent or reverse cardiovascular diseases. C1 [Schulz, Christian; Massberg, Steffen] Tech Univ Munich, Deutsch Herzzentrum, D-80636 Munich, Germany. [Von Andrian, Ulrich H.; Massberg, Steffen] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Von Andrian, Ulrich H.; Massberg, Steffen] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Massberg, S (reprint author), Tech Univ Munich, Deutsch Herzzentrum, Lazarettstr 36, D-80636 Munich, Germany. EM massberg@idi.harvard.edu RI Schulz, Christian/J-8545-2012; von Andrian, Ulrich/A-5775-2008 OI Schulz, Christian/0000-0003-3878-7833; NR 92 TC 6 Z9 6 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1073-9688 J9 MICROCIRCULATION JI Microcirculation PY 2009 VL 16 IS 6 BP 497 EP 507 AR PII 911730231 DI 10.1080/10739680902948351 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 470MY UT WOS:000267980000002 PM 19479622 ER PT J AU Rowe, EL Gradus, JL Pineles, SL Batten, SV Davison, EH AF Rowe, Erin L. Gradus, Jaimie L. Pineles, Suzanne L. Batten, Sonja V. Davison, Eve H. TI Military Sexual Trauma in Treatment-Seeking Women Veterans SO MILITARY PSYCHOLOGY LA English DT Article ID HEALTH-CARE; FEMALE VETERANS; ASSAULT; PTSD; STRESS; RISK AB As the number of women serving in the military continues to grow, it is increasingly important to explore the sequelae of military sexual trauma (MST) among female veterans. The current study included 232 female veterans who sought outpatient mental health treatment at an urban Veterans Affairs hospital. The study's aims were to (a) describe and compare the demographic characteristics, health behaviors, and psychological symptoms of female veterans who have experienced MST to those veterans who do not report this experience; and (b) examine the associations between psychological symptoms and health behaviors in this sample, stratified by MST status. Results indicate that treatment-seeking women veterans who reported experiencing MST endorsed more psychological distress compared to those who did not report experiencing MST. In addition, psychological symptoms were associated with engaging in problematic health behaviors, such as binge eating and infrequent physical exercise among both those women who experienced MST and those who did not. C1 [Rowe, Erin L.] Northeastern Univ, Inst Urban Hlth Res, Boston, MA 02115 USA. [Gradus, Jaimie L.; Pineles, Suzanne L.; Davison, Eve H.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Gradus, Jaimie L.; Pineles, Suzanne L.; Davison, Eve H.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Batten, Sonja V.] Univ Maryland, Sch Med, VA Maryland Healthcare Syst, Baltimore, MD 21201 USA. RP Davison, EH (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div 116B 3, 150 S Huntington Ave, Boston, MA 02130 USA. EM Eve.Davison@va.gov NR 18 TC 14 Z9 14 U1 2 U2 7 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0899-5605 J9 MIL PSYCHOL JI Milit. Psychol. PY 2009 VL 21 IS 3 BP 387 EP 395 DI 10.1080/08995600802565768 PG 9 WC Psychology, Multidisciplinary SC Psychology GA 557AN UT WOS:000274640000006 ER PT B AU Jho, DH Jho, HD AF Jho, David H. Jho, Hae-Dong BE Ozgur, B Benzel, E Garfin, S TI Anterior Cervical Foraminotomy SO MINIMALLY INVASIVE SPINE SURGERY: A PRACTICAL GUIDE TO ANATOMY AND TECHNIQUES LA English DT Article; Book Chapter ID LATERAL APPROACH; RADICULOPATHY C1 [Jho, David H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Jho, Hae-Dong] Drexel Univ, Coll Med, Dept Neuroendoscopy, Allegheny Gen Hosp, Pittsburgh, PA USA. RP Jho, DH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. EM davidjho@gmail.com NR 20 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-89830-8 PY 2009 BP 23 EP 32 DI 10.1007/978-0-387-89831-5_3 D2 10.1007/978-0-387-89831-5 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA BLF55 UT WOS:000270065900003 ER PT B AU Slover, J Wetter, E Malchau, H AF Slover, James Wetter, Erik Malchau, Henrik BE McMinn, DJW TI Computer Templating of Hip Resurfacing Arthroplasty SO MODERN HIP RESURFACING LA English DT Article; Book Chapter C1 [Slover, James] NYU Hosp Joint Dis, Dept Orthopaed Surg, New York, NY USA. [Wetter, Erik] RSA Biomed AB, Amea, Sweden. [Malchau, Henrik] Massachusetts Gen Hosp, Dept Orthopaed, Adult Reconstruct Unit, Boston, MA 02114 USA. [Malchau, Henrik] Harvard Univ, Sch Med, Boston, MA USA. [Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Slover, J (reprint author), NYU Hosp Joint Dis, Dept Orthopaed Surg, New York, NY USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-84800-087-2 PY 2009 BP 185 EP 188 DI 10.1007/978-1-84800-088-9_18 D2 10.1007/978-1-84800-088-9 PG 4 WC Orthopedics SC Orthopedics GA BKI61 UT WOS:000268220700018 ER PT J AU Koplin, SA Nielsen, GP Rosenberg, AE AF Koplin, S. A. Nielsen, G. P. Rosenberg, A. E. TI Heterotopic Bone in Epithelioid Sarcomas: A Histopathological Review of 4 Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Koplin, S. A.; Nielsen, G. P.; Rosenberg, A. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 59 BP 16A EP 16A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500060 ER PT J AU Morgan, EA Kozono, DE Butrynski, JE Baldini, EH Raut, CP Nascimento, AF AF Morgan, E. A. Kozono, D. E. Butrynski, J. E. Baldini, E. H. Raut, C. P. Nascimento, A. F. TI Radiation-Associated Sarcoma of Soft Tissue and Bone: A Clinicopathologic Study of 70 Cases in a Single Institution SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 BWH, Boston, MA USA. DFCI, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 76 BP 19A EP 20A PG 2 WC Pathology SC Pathology GA 393KF UT WOS:000262371500077 ER PT J AU Nielsen, GP Deshpande, U Rosenberg, AE Batten, JM Hornicek, F Lafrate, J AF Nielsen, G. P. Deshpande, U. Rosenberg, A. E. Batten, J. M. Hornicek, F. Lafrate, J. TI Recurrent Chromosomal Copy Number Alterations in Chordoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Nielsen, G. P.; Deshpande, U.; Rosenberg, A. E.; Batten, J. M.; Hornicek, F.; Lafrate, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 78 BP 20A EP 20A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500079 ER PT J AU Romeo, S Duim, RAJ Mertens, F De Jong, D Dal Cin, P Debiec-Rychter, M Sciot, R Rosenberg, A Szuhai, K Hogendoorn, PCW AF Romeo, S. Duim, R. A. J. Mertens, F. De Jong, D. Dal Cin, P. Debiec-Rychter, M. Sciot, R. Rosenberg, A. Szuhai, K. Hogendoorn, P. C. W. TI Balanced and Unbalanced Rearrangement of Chromosome Arm 6q in Chondromyxoid Fibroma (CMF): Delineation of Breakpoints and Analysis of Candidate Target Genes SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Leiden Univ, Med Ctr, Leiden, Netherlands. Univ Lund Hosp, S-22185 Lund, Sweden. Brigham & Womens Hosp, Boston, MA 02115 USA. Catholic Univ Louvain, B-3000 Louvain, Belgium. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Szuhai, Karoly/A-1100-2008 OI Szuhai, Karoly/0000-0002-1228-4245 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 84 BP 21A EP 21A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500085 ER PT J AU Belsley, NA Collins, LC Rice, MS Walker, S Tworoger, S Frank, DA AF Belsley, N. A. Collins, L. C. Rice, M. S. Walker, S. Tworoger, S. Frank, D. A. TI Expression of Phospho(p)STAT3 and Phospho(p)STAT5 in Breast Cancer and Correlation with Plasma Prolactin Levels SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Channing Inst, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 121 BP 30A EP 30A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500122 ER PT J AU Corben, AD Abi-Raad, R Boutrus, R Sgrai, DC Taghian, A Brachtel, EF AF Corben, A. D. Abi-Raad, R. Boutrus, R. Sgrai, D. C. Taghian, A. Brachtel, E. F. TI Pathologic Response and Microvascular Surface Area in Breast Cancer Treated with Neoadjuvant Chemotherapy SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Corben, A. D.; Abi-Raad, R.; Boutrus, R.; Sgrai, D. C.; Taghian, A.; Brachtel, E. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 148 BP 35A EP 36A PG 2 WC Pathology SC Pathology GA 393KF UT WOS:000262371500149 ER PT J AU Culhane, AC Nastr, A Chen, DT Venkataramu, C White, J Anderson, T Gruidl, M Bloom, G Rubio, R Centeno, BA Quackenbush, J Yeatman, TJ AF Culhane, A. C. Nastr, A. Chen, D. T. Venkataramu, C. White, J. Anderson, T. Gruidl, M. Bloom, G. Rubio, R. Centeno, B. A. Quackenbush, J. Yeatman, T. J. TI A 19-Gene Classifier Distinguishes Invasive Ductal and Classic Lobular Breast Carcinomas: Amplification of Chromosome 8q Characterizes Ductal While Estrogen-Related EGR-1 Characterizes Lobular Cancers SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 149 BP 36A EP 36A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500150 ER PT J AU Gill, RM Brachtel, EF Horvai, AE Chen, YY Rabban, JT AF Gill, R. M. Brachtel, E. F. Horvai, A. E. Chen, Y. Y. Rabban, J. T. TI Immunoexpression of Fli-1 by Metaplastic Breast Cancer: A Potential Pitfall in Cases Morphologically Resembling Epithelioid Angiosarcoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 UCSF, San Francisco, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 177 BP 42A EP 42A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500178 ER PT J AU Herberger, SD Kaul, D Adkins, CB Smith, BL Cheng, LL Lentz, MR Brachtel, EF AF Herberger, S. D. Kaul, D. Adkins, C. B. Smith, B. L. Cheng, L. L. Lentz, M. R. Brachtel, E. F. TI A Glimpse into Tumor Metabolism by Magnetic Resonance Spectroscopy: Choline Compounds and Choline Kinase Gene Expression in Human Breast Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Herberger, S. D.; Kaul, D.; Adkins, C. B.; Smith, B. L.; Cheng, L. L.; Lentz, M. R.; Brachtel, E. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 196 BP 46A EP 46A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500197 ER PT J AU Morgan, EA Mery, CM Kozono, DE Butrynski, JE Baldini, EH Raut, CP Nascimento, AF AF Morgan, E. A. Mery, C. M. Kozono, D. E. Butrynski, J. E. Baldini, E. H. Raut, C. P. Nascimento, A. F. TI Angiosarcoma of the Breast: A Rare Complication of Radiation Therapy. Clinicopathologic Study of 33 Cases in a Single Institution SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 247 BP 57A EP 57A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500248 ER PT J AU Nasir, A Chen, DT Culhane, AC Gruidl, M McCarthy, SM Venkataramu, C Quackenbush, J Yeatman, TJ AF Nasir, A. Chen, D. T. Culhane, A. C. Gruidl, M. McCarthy, S. M. Venkataramu, C. Quackenbush, J. Yeatman, T. J. TI Immunohistochemical Validation of Topoisomerase 2 alpha and BubR1 as Novel Breast Cancer Risk Genes in Benign Breast Tissue SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 250 BP 58A EP 58A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500251 ER PT J AU Faquin, WC Baloch, ZW AF Faquin, W. C. Baloch, Z. W. TI Fine-Needle Aspiration of Follicular Patterned Lesions of the Thyroid: Diagnosis, Management and Follow-Up According to National Cancer Institute Recommendations SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. UPENN 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 367 BP 84A EP 84A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500368 ER PT J AU Pitman, MB Desphpande, V AF Pitman, M. B. Desphpande, V. TI Tissue Microarray Immunohistochemical Analysis To Distinguish Contaminating Gastrointestinal Epithelium from Non-Malignant Branch Duct IPMN SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Pitman, M. B.; Desphpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 408 BP 93A EP 93A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500409 ER PT J AU Shen, J Pinkus, GS Deshpande, V Cibas, ES AF Shen, J. Pinkus, G. S. Deshpande, V. Cibas, E. S. TI Utility of EMA, XIAP, and GLUT-1 for the Diagnosis of Malignant Mesothelioma in Body Cavity Fluids SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 419 BP 95A EP 96A PG 2 WC Pathology SC Pathology GA 393KF UT WOS:000262371500420 ER PT J AU Wilbur, DC Black-Schaffer, WS Luff, RD Mohn, TM PAbraham, K Kemper, C Tench, WD AF Wilbur, D. C. Black-Schaffer, W. S. Luff, R. D. Mohn, T. M. PAbraham, K. Kemper, C. Tench, W. D. TI Clinical Trials of the FocalPoint GS System Show Significant Improvements in Sensitivity for the Detection of Squamous Intraepithelial Lesions When Compared to Manual Screening SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Quest Diagnost, Teterboro, NJ USA. Cyto Labs, San Antonio, TX USA. Quest Diagnost, Schaumburg, IL USA. Boyce & Bynum Pathol, Columbia, MO USA. Palomar Med Ctr, Escondido, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 426 BP 97A EP 97A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500427 ER PT J AU Mandal, RV Murali, R Lundquist, KF Ragsdale, BD Heenan, PJ McCarthy, SW Mihm, MJ Scolyer, RA Zembowicz, A AF Mandal, R. V. Murali, R. Lundquist, K. F. Ragsdale, B. D. Heenan, P. J. McCarthy, S. W. Mihm, M. J. Scolyer, R. A. Zembowicz, A. TI Long Term Follow-Up in Patients with Pigmented Epithelioid Melanocytoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia. Cent Coast Pathol, San Luis Obispo, CA USA. Cutaneous Pathol, Nedlands, WA, Australia. Lahey Clin Fdn, Burlington, MA USA. Dermatopathol Consultat Com, Belmont, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 470 BP 106A EP 107A PG 2 WC Pathology SC Pathology GA 393KF UT WOS:000262371500471 ER PT J AU Nazarian, RM Kapur, P Piris, A Mihm, MC Hoang, MP AF Nazarian, R. M. Kapur, P. Piris, A. Mihm, M. C. Hoang, M. P. TI Expression of Ki-67 in Benign, Atypical, and Malignant Hidradenomas SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 476 BP 108A EP 108A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500477 ER PT J AU Valentino, CM Krouse, R Bradely-Dunlop, D Nagle, R Akporiaye, E Prasad, A AF Valentino, C. M. Krouse, R. Bradely-Dunlop, D. Nagle, R. Akporiaye, E. Prasad, A. TI Immunopathological Features of Cutaneous Squamous Cell Carcinomas in Immunocompromised Patients SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Univ Arizona, Tucson, AZ USA. US Dept Vet Affairs, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 495 BP 111A EP 112A PG 2 WC Pathology SC Pathology GA 393KF UT WOS:000262371500496 ER PT J AU Sohani, AR Chande, H Vyas, V AF Sohani, A. R. Chande, H. Vyas, V. TI Diagnostic and Educational Support to Pathologists in the Developing World through Telepathology SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Aga Khan Hosp, Dar Es Salaam, Tanzania. NR 0 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 510 BP 115A EP 115A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500511 ER PT J AU Lovitch, SB Faquin, W Nose, V AF Lovitch, S. B. Faquin, W. Nose, V. TI Cribriform-Morular Variant of Thyroid Carcinoma: Distinct Immunohistochemical Profile from Other Papillary Thyroid Carcinoma Variants SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 523 BP 117A EP 118A PG 2 WC Pathology SC Pathology GA 393KF UT WOS:000262371500524 ER PT J AU Nucera, C Porrello, A Antonello, Z Finn, S Priolo, C Giordano, T Jarzab, B Trimarchi, F Pontecorvi, A Nose, U Lawler, J Parangi, S AF Nucera, C. Porrello, A. Antonello, Z. Finn, S. Priolo, C. Giordano, T. Jarzab, B. Trimarchi, F. Pontecorvi, A. Nose, U. Lawler, J. Parangi, S. TI Thrombospondin-1 Is Modulated by the B-Raf(V600E) Pathway in Papillary Thyroid Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Harvard Univ, Sch Med, MGH, Boston, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Duke Univ, Durham, NC 27706 USA. Harvard Univ, Sch Med, DFCI, Boston, MA USA. Univ Michigan, Ann Arbor, MI 48109 USA. Gliwice Univ, Gliwice, Poland. Univ Messina, Messina, Italy. Univ Cattolica Sacro Cuore, Rome, Italy. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 528 BP 118A EP 119A PG 2 WC Pathology SC Pathology GA 393KF UT WOS:000262371500529 ER PT J AU Brown, IS Whiteman, DC Lauwers, GY AF Brown, I. S. Whiteman, D. C. Lauwers, G. Y. TI Gastric Foveolar Type Dysplasia Is Common Adjacent to Esophageal Invasive Adenocarcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Sullivan Nicolaides Pathol, Brisbane, Qld, Australia. Queensland Inst Med Res, Brisbane, Qld 4006, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 555 BP 124A EP 125A PG 2 WC Pathology SC Pathology GA 393KF UT WOS:000262371500556 ER PT J AU Brown, IS Carr, NJ Srivastava, A Lauwers, G AF Brown, I. S. Carr, N. J. Srivastava, A. Lauwers, G. Y. TI Collagenous Gastritis - A Clinicopathological Study of Nineteen (19) Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Sullivan Nicolaides Pathol, Brisbane, Qld, Australia. So IML Pathol, Wollongong, NSW, Australia. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 556 BP 125A EP 125A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500557 ER PT J AU Fan, XS Yu, HP Wu, HY Zhou, Q Huang, Q AF Fan, X. S. Yu, H. P. Wu, H. Y. Zhou, Q. Huang, Q. TI Expression of Lgr5 in Colorectal Carcinoma Correlates with That of beta-catenin: A Tissue Microarray Study SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Nanjing Drum Tower Hosp, Nanjing, Peoples R China. Boston VA Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 574 BP 129A EP 129A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500575 ER PT J AU Firestein, R Shima, K Nosho, K Kure, S Irahara, N Bojarski, E Kirkner, GJ Hahn, WC Giovannucci, EL Fuchs, CS Ogino, S AF Firestein, R. Shima, K. Nosho, K. Kure, S. Irahara, N. Bojarski, E. Kirkner, G. J. Hahn, W. C. Giovannucci, E. L. Fuchs, C. S. Ogino, S. TI CDK8 Expression Is Associated with beta-Catenin Activation and Poor Outcome in Colon Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 578 BP 129A EP 129A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500579 ER PT J AU Huang, Q Fan, XS Agoston, AT Feng, AN Lauwers, G Odze, RD Zhang, LH AF Huang, Q. Fan, X. S. Agoston, A. T. Feng, A. N. Lauwers, G. Odze, R. D. Zhang, L. H. TI Gastroesophageal Junctional Carcinomas in Chinese Patients Show Distinct Clinicopathologic Features SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Boston VA Healthcare Syst, Boston, MA USA. Nanjing Drum Tower Hosp, Nanjing, Peoples R China. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 598 BP 133A EP 134A PG 2 WC Pathology SC Pathology GA 393KF UT WOS:000262371500599 ER PT J AU Kang, HJ Kim, HY Kim, GH Shin, DH Song, GA Kim, DH Jeon, TY Kim, DH Cho, BM Lauwers, GY Park, DY AF Kang, H. J. Kim, H. Y. Kim, G. H. Shin, D. H. Song, G. A. Kim, D. H. Jeon, T. Y. Kim, D. H. Cho, B. M. Lauwers, G. Y. Park, D. Y. TI Mucin Phenotype and beta-Catenin Are Useful Markers To Predict Submucosal Invasion and Lymph Node Metastasis in Intestinal Type Early Gastric Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Pusan Natl Univ Hosp, Pusan, South Korea. Pusan Natl Univ, Sch Med, Pusan, South Korea. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 604 BP 135A EP 135A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500605 ER PT J AU Kang, HJ Lee, JH Kim, GH Lauwers, GY Shia, DH Chai, KU Lee, CH Hu, GY Sol, MY Park, DY AF Kang, H. J. Lee, J. H. Kim, G. H. Lauwers, G. Y. Shia, D. H. Chai, K. U. Lee, C. H. Hu, G. Y. Sol, M. Y. Park, D. Y. TI Variants of Gastric Epithelial Dysplasia Display Different Biologic Characteristics: An Immunohistochemical Study of p53, Ki-67, beta Catenin and Smad4 Expression SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Pusan Natl Univ Hosp, Pusan, South Korea. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 603 BP 135A EP 135A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500604 ER PT J AU Nosho, K Shima, K Kure, S Irahara, N Baba, Y Chen, L Kirkner, GJ Fuchs, CS Ogino, S AF Nosho, K. Shima, K. Kure, S. Irahara, N. Baba, Y. Chen, L. Kirkner, G. J. Fuchs, C. S. Ogino, S. TI JC Virus T-Antigen Is Associated with p53 Expression, Chromosomal Instability and LINE-1 Hypomethylation in Colorectal Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 638 BP 142A EP 142A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500639 ER PT J AU Ogawa, F Genevay, M Lisovsky, M Mino-Kenudson, M Deshpande, V Odze, RD Lauwers, GY AF Ogawa, F. Genevay, M. Lisovsky, M. Mino-Kenudson, M. Deshpande, V. Odze, R. D. Lauwers, G. Y. TI Natural History of Sporadic Gastric Dysplasia in the USA: Follow up Study of 54 Patients SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol 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 NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 640 BP 142A EP 142A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500641 ER PT J AU Ogawa, F Srivastava, A Lauwers, GY Mino-Kenudson, M AF Ogawa, F. Srivastava, A. Lauwers, G. Y. Mino-Kenudson, M. TI Development of Multilayerd Epithelium (ME)after Photodynamic Therapy (PDT): Does MLE Represent an Inevitable Progression to Barrett's Esophagus (BE)? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 639 BP 142A EP 142A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500640 ER PT J AU Ogino, S Nosho, K Kirkner, GJ Kawasaki, T Chan, AT Schernhammer, ES Giovannucci, EL Fuchs, CS AF Ogino, S. Nosho, K. Kirkner, G. J. Kawasaki, T. Chan, A. T. Schernhammer, E. S. Giovannucci, E. L. Fuchs, C. S. TI LINE-1 Hypomethylation Is an Independent Predictor of Poor Prognosis in Colon Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Bigham & Womens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 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 NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 641 BP 142A EP 143A PG 2 WC Pathology SC Pathology GA 393KF UT WOS:000262371500642 ER PT J AU Ogino, S Nosho, K Kirkner, GJ Shima, K Irahara, N Kure, S Chan, AT Engelman, JA Kraft, P Cantley, LC Giovannucci, EL Fuchs, CS AF Ogino, S. Nosho, K. Kirkner, G. J. Shima, K. Irahara, N. Kure, S. Chan, A. T. Engelman, J. A. Kraft, P. Cantley, L. C. Giovannucci, E. L. Fuchs, C. S. TI PIK3CA Mutation Predicts Poor Prognosis in Stage I-III Colorectal Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 642 BP 143A EP 143A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500643 ER PT J AU Ogino, S Nosho, K Kure, S Irahara, N Shima, K Baba, Y Giovannucci, EL Fuchs, CS AF Ogino, S. Nosho, K. Kure, S. Irahara, N. Shima, K. Baba, Y. Giovannucci, E. L. Fuchs, C. S. TI Cyclin D1 Expression Marks a Subset of Colon Cancer with Good Prognosis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 643 BP 143A EP 143A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500644 ER PT J AU Pettus, JR Butterly, L Lauwers, GY Srivastava, A AF Pettus, J. R. Butterly, L. Lauwers, G. Y. Srivastava, A. TI Sessile Serrated Adenoma: Do Clinicians Understand the Concept and Manage Patients Appropriately? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 653 BP 145A EP 145A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500654 ER PT J AU Soucy, G Schmidt, JF Greenberg, JA Cerda, S Dendrinos, K Farraye, F Farris, AB Lauwers, GY Wang, HH Odze, RD AF Soucy, G. Schmidt, J. F. Greenberg, J. A. Cerda, S. Dendrinos, K. Farraye, F. Farris, A. B. Lauwers, G. Y. Wang, H. H. Odze, R. D. TI Colonic Crohn's Disease: A Clinical/Pathologic and Outcome Study of 120 Patients SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Univ, Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 669 BP 149A EP 149A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500670 ER PT J AU Fiorentino, M Mucci, L Fall, K Bailey, D Fiore, C Judson, G Andren, O Andersson, SO Loda, M AF Fiorentino, M. Mucci, L. Fall, K. Bailey, D. Fiore, C. Judson, G. Andren, O. Andersson, S. O. Loda, M. TI Immunohistochemical Expression of BRCA1 in Prostate Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Orebro, Orebro, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 760 BP 169A EP 169A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500761 ER PT J AU Genega, EM Ghebremichael, M Najarian, R Wang, Y Grisanzio, C Signoretti, S AF Genega, E. M. Ghebremichael, M. Najarian, R. Wang, Y. Grisanzio, C. Signoretti, S. TI CAIX Expression in Renal Neoplasms: Correlation with Tumor Type and Grade SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 768 BP 170A EP 170A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500769 ER PT J AU Svensson, MA Perner, S Demichelis, F Helenius, G Kantoff, PW Andersson, SO Andren, O Rubin, MA AF Svensson, M. A. Perner, S. Demichelis, F. Helenius, G. Kantoff, P. W. Andersson, S. O. Andren, O. Rubin, M. A. TI Frequency of ERG Rearrangement in a Swedish Hospital Based Biopsy Cohort SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Weill Cornell Med Coll, New York, NY USA. Orebro Univ Hosp, Orebro, Sweden. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 885 BP 195A EP 195A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500886 ER PT J AU Umar, SA Fiorentino, M Magi-Galluzzi, C Bailey, D Fiore, C Montironi, R Loda, M AF Umar, S. A. Fiorentino, M. Magi-Galluzzi, C. Bailey, D. Fiore, C. Montironi, R. Loda, M. TI Different Immunohistochemical Expression of CD44v6 and ALDH1 in Prostate Cancer before and after Androgen Deprivation Therapy SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Ancona, Ancona, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 902 BP 199A EP 199A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500903 ER PT J AU DeLair, D Soslow, R Gilks, B Macias, A Oliva, E AF DeLair, D. Soslow, R. Gilks, B. Macias, A. Oliva, E. TI The Morphologic Spectrum of Immunohistochemically Characterized Clear Cell Carcinoma of the Ovary: A Study of 83 Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vancouver Gen Hosp, Vancouver, BC, Canada. NR 0 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 961 BP 211A EP 211A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500962 ER PT J AU Gupta, M Gonzalez, JL Lefferts, JA Quer, A Tsongalis, GJ Oliva, E AF Gupta, M. Gonzalez, J. L. Lefferts, J. A. Quer, A. Tsongalis, G. J. Oliva, E. TI Primary Ovarian Mucinous Tumors (OMT) Lack Loss of MLH-1 and MGMT and Are Characterized by KRAS Mutations and Aberrant p53 Expression When They Progress to Carcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 984 BP 216A EP 216A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500985 ER PT J AU Kojiro, S Growdon, WB Orezzoli, JP Borger, DR Rueda, BR Boisvert, SL Iafrate, AJ Oliva, E AF Kojiro, S. Growdon, W. B. Orezzoli, J. P. Borger, D. R. Rueda, B. R. Boisvert, S. L. Iafrate, A. J. Oliva, E. TI Expression of p16, p53 and EGFR in Squamous Cell Carcinoma (SCC) of the Vulva: A Study of 96 Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Kojiro, S.; Growdon, W. B.; Orezzoli, J. P.; Borger, D. R.; Rueda, B. R.; Boisvert, S. L.; Iafrate, A. J.; Oliva, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1009 BP 221A EP 221A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501010 ER PT J AU Kajiro, S Quer, A Snuderl, M Daya, D Hayashi, T Bosincu, L Ogawa, F Vu, Q Rosenberg, AE Iafrate, AJ Oliva, E AF Kajiro, S. Quer, A. Snuderl, M. Daya, D. Hayashi, T. Bosincu, L. Ogawa, F. Vu, Q. Rosenberg, A. E. Iafrate, A. J. Oliva, E. TI Primitive Neuroectodermal Tumors (PNETs) of the Female Genital Tract (FGT): A Morphologic, Immunohistochemical, and Molecular Study of 18 Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. McMaster Hosp, Hamilton, ON, Canada. Saitama Int Med Ctr, Hidaka, Saitama, Japan. Univ Sassari, I-07100 Sassari, Italy. Prefectural Miyazaki Hosp, Miyazaki, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1010 BP 222A EP 222A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501011 ER PT J AU Lamb, CA Young, RH AF Lamb, C. A. Young, R. H. TI Apoplectic Change in Uterine Leiomyomas: An Analysis of 70 Cases Highlighting Previously Underemphasized Aspects SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Lamb, C. A.; Young, R. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 1018 BP 223A EP 223A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501019 ER PT J AU Lamb, CA Young, RH AF Lamb, C. A. Young, R. H. TI Myxoid Leiomyomas of the Uterus: A Report of 14 Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Lamb, C. A.; Young, R. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 1017 BP 223A EP 223A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501018 ER PT J AU Levanon, K Folkins, AK Drapkin, RI AF Levanon, K. Folkins, A. K. Drapkin, R. I. TI Novel Model Systems To Study the Fallopian Tube Secretory Epithelium - The Cell-of-Origin of Serous Pelvic Carcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Dana Farber Canc Inst, Boston, MA 02115 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 1022 BP 224A EP 224A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501023 ER PT J AU Levanon, K Ng, V Chang, MC Vermeer, PD Zabner, JL Crum, CP Drapkin, RI AF Levanon, K. Ng, V. Chang, M. C. Vermeer, P. D. Zabner, J. L. Crum, C. P. Drapkin, R. I. TI The DNA Damage Response of Fallopian Tube Secretory Epithelial Cells Renders Them Susceptible to Carcinogenesis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Iowa, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 1021 BP 224A EP 224A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501022 ER PT J AU Lin, MC Burkholder, KA Viswanathan, AN Neuberg, D Mutter, GL AF Lin, M. C. Burkholder, K. A. Viswanathan, A. N. Neuberg, D. Mutter, G. L. TI Involution of Latent Endometrial Precancers by Hormonal and Non Hormonal Mechanisms SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1023 BP 224A EP 224A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501024 ER PT J AU McAlhany, SJ Lerwill, MF Zaloudek, CJ Rabban, JT AF McAlhany, S. J. Lerwill, M. F. Zaloudek, C. J. Rabban, J. T. TI Diagnostic Value of PAX2, a Urogenital Tract Transcription Factor, in Distinguishing Mesonephric Duct Proliferations of the Cervix from Endocervical Adenocarcinoma and Its Mimics SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 UCSF, San Francisco, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 1036 BP 227A EP 228A PG 2 WC Pathology SC Pathology GA 393KF UT WOS:000262371501037 ER PT J AU McDonald, AG Cin, PD Ganguly, A Campbell, S Imai, Y Rosenberg, AE Oliva, E AF McDonald, A. G. Cin, P. D. Ganguly, A. Campbell, S. Imai, Y. Rosenberg, A. E. Oliva, E. TI Liposarcoma Arising in Uterine Lipoleiomyoma: A Report of Three Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Kobe City Gen Hosp, Kobe, Hyogo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 1039 BP 228A EP 228A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501040 ER PT J AU McDonald, AG Della Pelle, P De Nictolis, M Garcia-Fernandez, E Hardisson, D Prat, J Oliva, E AF McDonald, A. G. Della Pelle, P. De Nictolis, M. Garcia-Fernandez, E. Hardisson, D. Prat, J. Oliva, E. TI Expression of Platelet-Derived Growth Factor Receptor alpha (PDGF-R alpha) and Vascular Endothelial Growth Factor (VEGF) in Intravenous Leiomyomatosis (IVL): An Immunohistochemical Study of 29 Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Ist Anat & Istol Patol, Ancona, Italy. Hosp Univ La Paz, Madrid, Spain. Hosp Santa Creu & Sant Pau, Barcelona, Spain. RI Hardisson, David/E-2832-2010 OI Hardisson, David/0000-0002-2183-3699 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 1038 BP 228A EP 228A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501039 ER PT J AU Pinto, AP Miron, A Yassin, Y Monte, N Woo, TYC Medeiros, F Crum, CP AF Pinto, A. P. Miron, A. Yassin, Y. Monte, N. Woo, T. Y. C. Medeiros, F. Crum, C. P. TI Differentiated Vulvar Intraepithelial Neoplasia Contains p53 Mutations and Is Genetically Linked to Vulvar Squamous Cell Carcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Univ Fed Parana, BR-80060000 Curitiba, Parana, Brazil. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1056 BP 232A EP 232A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501057 ER PT J AU Roh, MH Yassin, Y Miron, A Crum, CP Hirsch, MS AF Roh, M. H. Yassin, Y. Miron, A. Crum, C. P. Hirsch, M. S. TI High Grade Serous and Endometrioid Carcinomas: A Convergence of Two Pathways in Pelvic Cancer Differentiation? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1067 BP 234A EP 234A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501068 ER PT J AU Santacana, M Pallares, J Lopez, S Yeramian, A Dolcet, X Oliva, E Matias-Guiu, X AF Santacana, M. Pallares, J. Lopez, S. Yeramian, A. Dolcet, X. Oliva, E. Matias-Guiu, X. TI Immunohistochemical Features of Post-Radiation Recurrences of Endometrioid Carcinomas of the Endometrium SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Hosp U Arnau de Vilanova, Lleida, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Pallares, Judit/A-6635-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1075 BP 236A EP 236A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501076 ER PT J AU Sioletic, S Orezzoli, JP Olawaiye, A Russell, AH Del Carmen, M Oliva, E AF Sioletic, S. Orezzoli, J. P. Olawaiye, A. Russell, A. H. Del Carmen, M. Oliva, E. TI Cervical Stromal Invasion in Endometrioid Endometrial Carcinoma (EEC) Does Not Correlate with Overall Survival SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Sioletic, S.; Orezzoli, J. P.; Olawaiye, A.; Russell, A. H.; Del Carmen, M.; Oliva, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1084 BP 237A EP 238A PG 2 WC Pathology SC Pathology GA 393KF UT WOS:000262371501085 ER PT J AU Turbiner, J Ferry, JA Harris, NL Young, RH Zukerberg, LR AF Turbiner, J. Ferry, J. A. Harris, N. L. Young, R. H. Zukerberg, L. R. TI Lymphoma-Like Lesions of the Lower Female Genital Tract: Morphology, Immunophenotype and Molecular Features SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Turbiner, J.; Ferry, J. A.; Harris, N. L.; Young, R. H.; Zukerberg, L. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1090 BP 239A EP 239A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501091 ER PT J AU Turbiner, J Pilch, BZ Harris, NL Stone, JH Ganguly, A Ferry, JA Deshpande, V AF Turbiner, J. Pilch, B. Z. Harris, N. L. Stone, J. H. Ganguly, A. Ferry, J. A. Deshpande, V. TI Kuttner's Tumor Is a IgG4 Associated Disease SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Turbiner, J.; Pilch, B. Z.; Harris, N. L.; Stone, J. H.; Ganguly, A.; Ferry, J. A.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1148 BP 252A EP 252A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501149 ER PT J AU Kluk, M Toomey, C Hochberg, E Hasserjian, R AF Kluk, M. Toomey, C. Hochberg, E. Hasserjian, R. TI Myelodysplastic Syndromes Following Therapy with Purine Analogues - Therapy Related Myeloid Neoplasms? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Kluk, M.; Toomey, C.; Hochberg, E.; Hasserjian, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 1234 BP 272A EP 272A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501234 ER PT J AU Kluk, MJ Hoyt, KM Bifulco, C AF Kluk, M. J. Hoyt, K. M. Bifulco, C. TI Role of Macrophage Migration Inhibitory Factor (MIF) in Hodgkin Lymphoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Yale New Haven Med Ctr, New Haven, CT 06504 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 1235 BP 272A EP 272A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501235 ER PT J AU Rodig, SJ Juszczynski, P Takeyama, K Ouyang, J Faber, J Armstrong, S Shipp, MA Kutok, JL AF Rodig, S. J. Juszczynski, P. Takeyama, K. Ouyang, J. Faber, J. Armstrong, S. Shipp, M. A. Kutok, J. L. TI Selective Expression of the Immunoregulatory Lectin, Galectin-1, Identifies Precursor B Cell Acute Lymphoblastic Leukemias (ALL) with MLL Rearrangements SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Brrigham & Womens Hosp, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens 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 ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1280 BP 282A EP 282A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501280 ER PT J AU Sohani, AR Brodsky, V Ackerman, AM Hochberg, EP Gilbertson, JR AF Sohani, A. R. Brodsky, V. Ackerman, A. M. Hochberg, E. P. Gilbertson, J. R. TI Three-Dimensional (3D) Image Analysis of Benign vs Malignant Follicular Lymphoid Proliferations (FLPs) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mass Gen Hosp Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1299 BP 287A EP 287A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501299 ER PT J AU Brodsky, V Louissaint, A Gilbertson, J Yogi, Y AF Brodsky, V. Louissaint, A. Gilbertson, J. Yogi, Y. TI Case of the Month and the Virtual Slidebox Implementation SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Brodsky, V.; Louissaint, A.; Gilbertson, J.; Yogi, Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1351 BP 298A EP 299A PG 3 WC Pathology SC Pathology GA 393KF UT WOS:000262371501351 ER PT J AU Collins, AB Farris, AB Wong, W Saidman, S Tolkoff-Rubin, N Goes, NB Ko, DS Cosimi, AB Colvin, RB AF Collins, A. B. Farris, A. B. Wong, W. Saidman, S. Tolkoff-Rubin, N. Goes, N. B. Ko, D. S. Cosimi, A. B. Colvin, R. B. TI De Novo Membranous Glomerulonephritis Is Associated with C4d Depostion in Peritubular Capillaries and Basement Membrane Multilamination: Putative Variant of Chronic Humoral Rejection SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Collins, A. B.; Farris, A. B.; Wong, W.; Saidman, S.; Tolkoff-Rubin, N.; Goes, N. B.; Ko, D. S.; Cosimi, A. B.; Colvin, R. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 1363 BP 301A EP 301A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501363 ER PT J AU Collins, AB Farris, AB Smith, RN Adams, CD Della Pelle, PA Saidman, S Wong, W Colvin, RB AF Collins, A. B. Farris, A. B. Smith, R. N. Adams, C. D. Della Pelle, P. A. Saidman, S. Wong, W. Colvin, R. B. TI Challenges in the Diagnosis of Chronic Antibody Mediated Rejection Due to Loss of Peritubular Capillaries and Low Extent and Transient Nature of Cod Deposition SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Collins, A. B.; Farris, A. B.; Smith, R. N.; Adams, C. D.; Della Pelle, P. A.; Saidman, S.; Wong, W.; Colvin, R. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 1364 BP 301A EP 302A PG 3 WC Pathology SC Pathology GA 393KF UT WOS:000262371501364 ER PT J AU Farris, AB Adams, CD Brousaides, N Della Pelle, PA Collins, AB Colvin, RB AF Farris, A. B. Adams, C. D. Brousaides, N. Della Pelle, P. A. Collins, A. B. Colvin, R. B. TI Novel Subtraction Morphometry Technique for Assessing Fibrosis in Renal Biopsies SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 1368 BP 302A EP 302A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501368 ER PT J AU Farris, AB Gaut, J Wong, W Della Pelle, P Brousaides, N Collins, AB Saidman, S Schneeberger, EE Smith, RN Colvin, RB AF Farris, A. B. Gaut, J. Wong, W. Della Pelle, P. Brousaides, N. Collins, A. B. Saidman, S. Schneeberger, E. E. Smith, R. N. Colvin, R. B. TI Pathology, Serology and Clinical Characteristics of 68 Patients with Chronic Humoral Renal Allograft Rejection (CHR) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Farris, A. B.; Gaut, J.; Wong, W.; Della Pelle, P.; Brousaides, N.; Collins, A. B.; Saidman, S.; Schneeberger, E. E.; Smith, R. N.; Colvin, R. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 1369 BP 302A EP 303A PG 2 WC Pathology SC Pathology GA 393KF UT WOS:000262371501369 ER PT J AU Kanstantinidis, I Ferrone, CR Genevay, M Lauwerse, GY AF Kanstantinidis, I. Ferrone, C. R. Genevay, M. Lauwerse, G. Y. TI Intrapancreatic Cholanglocarcinomas. A Clinicopathological Study SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Kanstantinidis, I.; Ferrone, C. R.; Genevay, M.; Lauwerse, G. Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1416 BP 313A EP 313A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501415 ER PT J AU Levy, M Dhall, D Zhang, J Miles, L Misdraji, J Yerian, LM Xu, H Aguilar, CE Wang, HL AF Levy, M. Dhall, D. Zhang, J. Miles, L. Misdraji, J. Yerian, L. M. Xu, H. Aguilar, C. E. Wang, H. L. TI Expression of Glypican-3 in Embryonal Sarcoma (ES) and Mesenchymal Hamartoma (MH) of the Liver: A Potential Diagnostic Pitfall SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Mayo Clin, Rochester, MN USA. Cincinnati Childrens Hosp, Cincinnati, OH USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Cleveland Clin, Cleveland, OH USA. Univ Rochester, Med Ctr, Rochester, NY 14627 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 1423 BP 314A EP 314A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501422 ER PT J AU Mandal, RV Notohara, K Deshpande, V Farris, AB Lisovsky, M Smyrk, TC Lauwers, GY Mino-Kenudson, M AF Mandal, R. V. Notohara, K. Deshpande, V. Farris, A. B. Lisovsky, M. Smyrk, T. C. Lauwers, G. Y. Mino-Kenudson, M. TI Foxp3 and IgG4 Expression in Subtypes of Autoimmune Pancreatitis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Kurashiki Cent Hosp, Kurashiki, Okayama, Japan. Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1429 BP 315A EP 316A PG 2 WC Pathology SC Pathology GA 393KF UT WOS:000262371501428 ER PT J AU Mino-Kenudson, M Smyrk, TC Notohara, K AF Mino-Kenudson, M. Smyrk, T. C. Notohara, K. TI Pathology of Pancreas in Inflammatory Bowel Disease: An Etiology of Idiopathic Ductocentric Chronic Pancreatitis? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. Kurashiki Cent Hosp, Kurashiki, Okayama, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1435 BP 317A EP 317A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501434 ER PT J AU Notohara, K Smyrk, TC Mizuno, N Mino-Kenudson, M AF Notohara, K. Smyrk, T. C. Mizuno, N. Mino-Kenudson, M. TI The Role of Biopsies in the Diagnosis of Autoimmune Pancreatitis (Lymphoplasmacytic Sclerosing Pancreatitis) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Kurashiki Cent Hosp, Kurashiki, Okayama, Japan. Mayo Clin, Rochester, MN USA. Aichi Canc Ctr Hosp, Nagoya, Aichi 464, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1441 BP 318A EP 318A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501440 ER PT J AU Rubbia-Brandt, L Lauwers, GY Wang, H Majno, PE Tanabe, K Zhu, A Brezault, C Soubrane, O Abdalla, EK Vauthey, JN Mentha, G Terris, B AF Rubbia-Brandt, L. Lauwers, G. Y. Wang, H. Majno, P. E. Tanabe, K. Zhu, A. Brezault, C. Soubrane, O. Abdalla, E. K. Vauthey, J-N Mentha, G. Terris, B. TI Sinusoidal Obstruction Syndrome and Nodular Regenerative Hyperplasia Are Major Hepatic Lesions Associated with Oxaliplatin Based Chemotherapy for Colorectal Liver Metastases and Partially Prevented by Bevacizumab SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Univ Hosp, Geneva, Switzerland. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. Hop Cochin, F-75674 Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1452 BP 320A EP 320A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501451 ER PT J AU Snyder, EL Sandstrom, DJ Law, K Sicinska, E Loda, M Rodig, SJ Dal Cin, P Fletcher, CDM AF Snyder, E. L. Sandstrom, D. J. Law, K. Sicinska, E. Loda, M. Rodig, S. J. Dal Cin, P. Fletcher, C. D. M. TI c-Jun Amplification and Overexpression Are Oncogenic in Liposarcoma but Not Sufficient To Inhibit Adipocytic Differentiation SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1553 BP 343A EP 343A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501552 ER PT J AU Zhang, X Parangi, S Lawler, J AF Zhang, X. Parangi, S. Lawler, J. TI Regulation of VEGF-Induced Vascular Permeability and VEGFR2 Signaling by Thrombospondin-1 SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1559 BP 344A EP 344A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501558 ER PT J AU Beheshti, J Xiao, Y Yonesaka, K Jackman, D Joshi, V Lee, C Janne, P Lindeman, N AF Beheshti, J. Xiao, Y. Yonesaka, K. Jackman, D. Joshi, V. Lee, C. Janne, P. Lindeman, N. TI Amphiregulin-2 Immunoreactivity Is Superior to EGFR FISH for Predicting Favorable Response to Tyrosine Kinase Inhibitors in EGFR-Wild Type Lung Adenocarcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Partners Ctr Genet & Genom, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1585 BP 350A EP 350A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501584 ER PT J AU Matsubara, O Ohba, T Ninomiya, H Ishikawa, Y Mark, EJ AF Matsubara, O. Ohba, T. Ninomiya, H. Ishikawa, Y. Mark, E. J. TI Histological Characteristics in the Prediction of Acute Exacerbation of Idiopathic Pulmonary Fibrosis (IPF) Following Surgery for Primary Lung Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Natl Def Med Coll, Tokorozawa, Saitama 359, Japan. Japanese Fdn Canc Res, Inst Canc, Tokyo 170, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1623 BP 358A EP 358A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501621 ER PT J AU Rodig, SJ Dacic, S Yeap, BY Barletta, JA Law, K Lindeman, N Iafrate, AJ Chirieac, LR AF Rodig, S. J. Dacic, S. Yeap, B. Y. Barletta, J. A. Law, K. Lindeman, N. Iafrate, A. J. Chirieac, L. R. TI Phenotype of Lung Adenocarcinoma with EML-ALK Fusion in the Western Population SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1635 BP 360A EP 360A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501633 ER PT J AU Ruzinova, MB Joshi, V Jackman, D Janne, P Lindeman, NI AF Ruzinova, M. B. Joshi, V. Jackman, D. Janne, P. Lindeman, N. I. TI ERK Immunostaining Predicts EGFR and/or KRAS Mutation in Lung Adenocarcinomas, and Can Be Used To Prescreen Tumors for Subsequent Molecular Testing SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Beigham & Womens Hosp, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1637 BP 361A EP 361A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501635 ER PT J AU Sholl, LM Joshi, V Jackman, D Xiao, Y Lee, C Janne, P Lindeman, N AF Sholl, L. M. Joshi, V. Jackman, D. Xiao, Y. Lee, C. Janne, P. Lindeman, N. TI EGFR Mutation Is a Better Predictor of Response to TKIs in NSCLC Than FISH, CISH, or IHC SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1639 BP 361A EP 361A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501637 ER PT J AU Wagner, PL Perner, S Solterman, A LaFargue, CL Tischler, V Weir, BA Weder, W Meyerson, M Giordano, TJ Moch, H Rubin, MA AF Wagner, P. L. Perner, S. Solterman, A. LaFargue, C. L. Tischler, V. Weir, B. A. Weder, W. Meyerson, M. Giordano, T. J. Moch, H. Rubin, M. A. TI TTF1 Expression in Non-Small Cell Lung Carcinoma: Association with TTF1 Gene Amplification and Improved Survival SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Univ Zurich Hosp, CH-8091 Zurich, Switzerland. Univ Zurich, Zurich, Switzerland. Univ Michigan, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1648 BP 363A EP 363A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501646 ER PT J AU Yu, J Benedettini, E Li, DQ Gu, T Herebert, H Smith, B Polakiewicz, R Zhou, XM Loda, M Comb, M AF Yu, J. Benedettini, E. Li, D. Q. Gu, T. Herebert, H. Smith, B. Polakiewicz, R. Zhou, X. M. Loda, M. Comb, M. TI Mutation-Specific Antibodies for the Detection of EGFR Mutations in Non-Small-Cell Lung Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Cell Signaling Technol Inc, Danvers, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Second Xiangya Hosp, Changsha, Hunan, Peoples R China. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1651 BP 364A EP 364A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501649 ER PT J AU Benedettini, E Saad, AG Loda, M Chirieac, LR AF Benedettini, E. Saad, A. G. Loda, M. Chirieac, L. R. TI Molecular Characteristics of Matched Primary Non-Small-Cell Lung Carcinomas (NSCLC) and Metastases to the Brain SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1670 BP 368A EP 368A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501668 ER PT J AU Demichelis, F Setlur, SR Beroukhim, R Perner, S Korbel, JO Lafargue, C Pflueger, D Pina, C Hofer, MD Shoner, A Svensson, MA Rickman, DS Meyerson, M Lee, C Gerstein, MB Kuefer, R Rubin, MA AF Demichelis, F. Setlur, S. R. Beroukhim, R. Perner, S. Korbel, J. O. Lafargue, C. Pflueger, D. Pina, C. Hofer, M. D. Shoner, A. Svensson, M. A. Rickman, D. S. Meyerson, M. Lee, C. Gerstein, M. B. Kuefer, R. Rubin, M. A. TI Distinct Genomic Aberrations Associated with TMPRSS2-ERG Fusion Prostate Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Weill Cornell Med Coll, New York, NY USA. Brigham & Womens Hosp, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Cambridge, MA USA. Yale Univ, New Haven, CT USA. Univ Hosp Ulm, Ulm, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1677 BP 370A EP 370A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501675 ER PT J AU Firestein, R Barlena, JA Ligon, A Loda, M Hahn, WC Chirieac, LR AF Firestein, R. Barlena, J. A. Ligon, A. Loda, M. Hahn, W. C. Chirieac, L. R. TI IKBKe Copy Number Gain in Lung Adenocarcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1683 BP 371A EP 371A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501681 ER PT J AU Priolo, C Lamb, J Zadra, G Oldridge, D Palescandolo, E Sicinska, E Loda, M AF Priolo, C. Lamb, J. Zadra, G. Oldridge, D. Palescandolo, E. Sicinska, E. Loda, M. TI A Bioinformatic Approach to Identify New Metabolic Targets in Prostate Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard & MIT, Broad Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1699 BP 375A EP 375A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501697 ER PT J AU Roehrl, MH Rho, JH Wang, JY AF Roehrl, M. H. Rho, J. H. Wang, J. Y. TI Lung Adenocarcinoma and Its Stroma: Tissue Proteomics Reveals Differential and Compartment-Specific Roles for the Homologs Transgelin and Transgelin-2 SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1700 BP 375A EP 375A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501698 ER PT J AU Kindelberger, DW Flores, LM Cibas, ES Ligon, AH Loda, MF Krop, IE Janne, PA AF Kindelberger, D. W. Flores, L. M. Cibas, E. S. Ligon, A. H. Loda, M. F. Krop, I. E. Janne, P. A. TI Determining the Recovery Efficiency and Relative Enrichment of Circulating Tumor Cells Using the CellSearch System in Patients with Metastatic Lung Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1738 BP 384A EP 384A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501736 ER PT J AU Burger, R Le Gouill, S Tai, YT Shringarpure, R Tassone, P Neri, P Podar, K Catley, L Hideshinl, T Chauhan, D Caulder, E Neilan, CL Vaddi, K Li, J Gramatzki, M Fridman, JS Anderson, KC AF Burger, Renate Le Gouill, Steven Tai, Yu-Tzu Shringarpure, Reshma Tassone, Pierfrancesco Neri, Paola Podar, Klaus Catley, Laurence Hideshinl, Teru Chauhan, Dharminder Caulder, Eian Neilan, Claire L. Vaddi, Kris Li, Jun Gramatzki, Martin Fridman, Jordan S. Anderson, Kenneth C. TI Janus kinase inhibitor INCB20 has antiproliferative and apoptotic effects on human myeloma cells in vitro and in vivo SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID HUMAN INTERLEUKIN-6 RECEPTOR; ADVANCED MULTIPLE-MYELOMA; JAK-TYK KINASES; CONSTITUTIVE ACTIVATION; SIGNAL TRANSDUCER; GROWTH; PATHWAY; STAT3; SURVIVAL; CYTOKINE AB Protein tyrosine kinases of the Janus kinase (JAK) family are associated with many cytokine receptors, which, on ligand binding, regulate important cellular functions such as proliferation, survival, and differentiation. In multiple myeloma, JAKs may be persistently activated due to a constant stimulation by interleukin (IL)-6, which is produced in the bone marrow environment. INCB20 is a synthetic molecule that potently inhibits all members of the JAK family with a 100- to 1,000-fold selectivity for JAKs over >70 other kinases. Treatment of multiple myeloma cell lines and patient tumor cells with INCB20 resulted in a significant and dose-dependent inhibition of spontaneous as well as IL-6-induced cell growth. Importantly, multiple myeloma cell growth was inhibited in the presence of bone marrow stromal cells. The IL-6 dependent cell line INA-6 was particularly sensitive to the drug (IC(50) < 1 mu mol/L). Growth suppression of INA-6 correlated with an increase in the percentage of apoptotic cells and inhibition of signal transducer and activator of transcription 3 phosphorylation. INCB20 also abrogated the protective effect of IL-6 against dexamethasone by blocking phosphorylation of SHP-2 and AKT. In contrast, AKT phosphorylation induced by insulin-like growth factor-I remained unchanged, showing selectivity of the compound. In a s.c. severe combined immunodeficient mouse model with INA-6, INCB20 significantly delayed INA-6 tumor growth. Our studies show that disruption of JAKs and downstream signaling pathways may both inhibit multiple myeloma cell growth and survival and overcome cytokine-mediated drug resistance, thereby providing the preclinical rationale for the use of JAK inhibitors as a novel therapeutic approach in multiple myeloma. [Mol Cancer Ther 2009;8(1):26 - 35] C1 [Burger, Renate; Le Gouill, Steven; Tai, Yu-Tzu; Shringarpure, Reshma; Tassone, Pierfrancesco; Neri, Paola; Podar, Klaus; Catley, Laurence; Hideshinl, Teru; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Burger, Renate; Gramatzki, Martin] Univ Kiel, Dept Med 2, Div Stem Cell Transplantat & Immunotherapy, Kiel, Germany. [Caulder, Eian; Neilan, Claire L.; Vaddi, Kris; Li, Jun; Fridman, Jordan S.] Incyte Corp, Wilmington, DE USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Kenneth_Anderson@dfci.harvard.edu RI Gramatzki, Martin/A-9533-2010; Catley, Laurence/E-5313-2013 FU NIH [RO-1 50947, PO-1 78378, P50 CA100707]; Multiple Myeloma Research Foundation; Fund to Cure Myeloma; Doris Duke Distinguished Clinical Research Scientist Award FX Grant support: NIH grants RO-1 50947, PO-1 78378, and P50 CA100707; The Multiple Myeloma Research Foundation, The Fund to Cure Myeloma, and Doris Duke Distinguished Clinical Research Scientist Award. NR 49 TC 29 Z9 31 U1 1 U2 3 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 JAN PY 2009 VL 8 IS 1 BP 26 EP 35 DI 10.1158/1535-7163.MCT-08-0149 PG 10 WC Oncology SC Oncology GA 395BM UT WOS:000262497100004 PM 19139110 ER PT J AU Frost, P Shi, YJ Hoang, B Gera, J Lichtenstein, A AF Frost, Patrick Shi, Yijiang Hoang, Bao Gera, Joseph Lichtenstein, Alan TI Regulation of D-cyclin translation inhibition in myeloma cells treated with mammalian target of rapamycin inhibitors: rationale for combined treatment with extracellular signal-regulated kinase inhibitors and rapamycin SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID RIBOSOME ENTRY SEGMENT; MYC PROTEIN-SYNTHESIS; MULTIPLE-MYELOMA; AKT ACTIVITY; ENHANCED SENSITIVITY; MTOR INHIBITORS; MESSENGER-RNA; TUMOR-CELLS; IN-VIVO; APOPTOSIS AB We have shown that heightened AKT activity sensitized multiple myeloma cells to the antitumor effects of the mammalian target of rapamycin inhibitor CCI-779. To test the mechanism of the AKT regulatory role, we stably transfected U266 multiple myeloma cell lines with an activated AKT allele or empty vector. The AKT-transfected cells were more sensitive to cytostasis induced in vitro by rapamycin or in vivo by its analogue, CCI-779, whereas cells with quiescent AKT were resistant. The ability of mammalian target of rapamycin inhibitors to down-regulate D-cyclin expression was significantly greater in AKT-transfected multiple myeloma cells due, in part, to the ability of AKT to curtail cap-independent translation and internal ribosome entry site (IRES) activity of D-cyclin transcripts. Similar AKT-dependent regulation of rapamycin responsiveness was shown in a second myeloma model: the PTEN-null OPM-2 cell line transfected with wild-type PTEN. Because extracellular signal - regulated kinase (ERK)/p38 activity facilitates [RES-mediated translation of some transcripts, we investigated ERK/p38 as regulators of AKT-dependent effects on rapamycin sensitivity. AKT-transfected U266 cells showed significantly decreased ERK and p38 activity. However, only an ERK inhibitor prevented D-cyclin IRES activity in resistant "low-AKT" myeloma cells. Furthermore, the ERK inhibitor successfully sensitized myeloma cells to rapamycin in terms of down-regulated D-cyclin protein expression and G, arrest. However, ectopic overexpression of an activated MEK gene did not increase cap-independent translation of D-cyclin in "high-AKT" myeloma cells, indicating that mitogen-activated protein kinase/ERK kinase/ERK activity was required, but not sufficient, for activation of the IRES. These data support a scenario where heightened AKT activity down-regulates D-cyclin [RES function in multiple myeloma cells and ERK facilitates activity. [Mol Cancer Ther 2009;8(1):83 - 93] C1 Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Med, Los Angeles, CA 90024 USA. W Los Angeles VA Med Ctr, Dept Hematol Oncol, Los Angeles, CA USA. RP Frost, P (reprint author), VA W Los Angeles Hosp, Dept Hematol Oncol, W111H,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM pfrost@ucla.edu OI Frost, Patrick/0000-0003-3348-5983 FU Multiple Myeloma Research Foundation; NIH [K01CA111623, R01CA96920, R01CA111448]; Veteran Administration FX Grant support: Multiple Myeloma Research Foundation; NIH grants K01CA111623, R01CA96920, and R01CA111448; and research funds of the Veteran Administration. NR 36 TC 22 Z9 22 U1 0 U2 0 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 JAN PY 2009 VL 8 IS 1 BP 83 EP 93 DI 10.1158/1535-7163.MCT-08-0254 PG 11 WC Oncology SC Oncology GA 395BM UT WOS:000262497100010 PM 19139116 ER PT J AU Prajapati, SI Martinez, CO Bahadur, AN Wu, IQ Zheng, W Lechleiter, JD McManus, LM Chisholm, GB Michalek, JE Shireman, PK Keller, C AF Prajapati, Suresh I. Martinez, Carlo O. Bahadur, Ali N. Wu, Isabel Q. Zheng, Wei Lechleiter, James D. McManus, Linda M. Chisholm, Gary B. Michalek, Joel E. Shireman, Paula K. Keller, Charles TI Near-Infrared Imaging of Injured Tissue in Living Subjects Using IR-820 SO MOLECULAR IMAGING LA English DT Article ID SKELETAL-MUSCLE; CONTRAST AGENTS; CCR2-/-MICE; REGENERATION; INFLAMMATION; CELLS AB The unprecedented increase in preclinical studies necessitates high-throughput, inexpensive, and straightforward methods for evaluating diseased tissues. Near-infrared imaging of live subjects is a versatile, cost-effective technology that can be effectively used in a variety of pathologic conditions. We have characterized an inexpensive optoelectronic chemical, IR-820, as an infrared blood pool contrast agent to detect and quantify diseased tissue in live animals. IR-820 has maximal excitation and emission wavelengths of 710 and 820 nm, respectively. IR-820 emission is significantly improved in vivo on serum binding to albumin, and elimination occurs predominantly via the gastrointestinal tract. We demonstrate the utility of this contrast agent for serially imaging of traumatized tissue (muscle), tissue following reperfusion leg, stroke), and tumors. IR-820 can also be employed to map regional lymph nodes. This novel contrast agent is anticipated to be a useful and an inexpensive tool for screening a wide variety of preclinical models of human diseases. C1 Univ Texas Hlth Sci Ctr San Antonio, Grechey Childrens Canc Res Inst, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Keller, C (reprint author), 8403 Floyd Curl Dr,MC-7784, San Antonio, TX 78229 USA. EM kellerc2@uthscsa.edu RI ZHENG, WEI/B-9482-2012; OI Keller, Charles/0000-0003-2505-7487 FU Cancer Therapy and Research Center [P30 CA 54174]; Veterans Administration; [HL090196]; [HL074236] FX Financial disclosure of authors: Charles Keller is a member of the UTII SCSA. Cancer Therapy and Research Center (P30 CA 54174). Supported in part by HL090196 (C.O.M.), HL074236, and the Veterans Administration (P.K.S.). NR 19 TC 19 Z9 19 U1 4 U2 16 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 JAN-FEB PY 2009 VL 8 IS 1 BP 45 EP 54 DI 10.2310/7290.2009.00005 PG 10 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA 414RT UT WOS:000263883600005 PM 19344575 ER PT J AU Roedl, JB Halpern, EF Colen, RR Sahani, DV Fischman, AJ Blake, MA AF Roedl, Johannes B. Halpern, Elkan F. Colen, Rivka R. Sahani, Dushyant V. Fischman, Alan J. Blake, Michael A. TI Metabolic Tumor Width Parameters as Determined on PET/CT Predict Disease-free Survival and Treatment Response in Squamous Cell Carcinoma of the Esophagus SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Esophageal cancer; Positron emission tomography; Computed tomography; Response; Chemoradiotherapy; Radiation esophagitis; FDG ID POSITRON-EMISSION-TOMOGRAPHY; STANDARDIZED UPTAKE VALUES; ESOPHAGOGASTRIC JUNCTION; ADDITIONAL VALUE; CANCER; CHEMOTHERAPY; CHEMORADIOTHERAPY; RADIOCHEMOTHERAPY; ADENOCARCINOMAS; RESECTION AB Materials and Methods: We investigated the utility of metabolic tumor width parameters in predicting response to chemoradiotherapy and in predicting disease-free survival in patients with esophageal cancer. Furthermore, we evaluated the possible confounding effect of therapy-induced esophagitis on the evaluation of treatment response. Forty-nine patients with squamous cell carcinoma, who had undergone positron emission tomography/computed tomography (PET/CT) exams before and after neoadjuvant chemoradiotherapy, were included in the study. In the slice with the maximum 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake of the tumor, the following metabolic tumor width parameters were measured: Area of the tumor, maximum diameter of the tumor, maximum and mean standardized uptake value (SUV). Furthermore, the "diameter-SUV index" was calculated by multiplying the tumor diameter by the mean SUV. Results: The decrease of the metabolic tumor diameter between pre- and post-treatment PET/CT scans was the single best predictor of treatment response and tumor-free survival. However, the accuracy of predicting response and survival was even higher when using the decrease of the "diameter-SUV index" as the metabolic criterion for treatment response. A decrease by more than 55% of the diameter-SUV index identified pathologic responders (n=22) with a sensitivity of 91% and a specificity of 93%. Radiation esophagitis was found to have a significant impact on the assessment of treatment response when evaluating therapy response based on the maximum SUV, whereas no confounding effect of radiation esophagitis was seen when evaluating therapy response based on the tumor diameter or the diameter-SUV index. Conclusion: The present study shows that tumor width parameters, especially the tumor diameter or the combination of diameter and SUV in the "diameter-SUV index",are valuable for predicting tumor-free survival and treatment response independent from the presence of radiation esophagitis. C1 [Roedl, Johannes B.; Colen, Rivka R.; Sahani, Dushyant V.; Blake, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. [Roedl, Johannes B.; Colen, Rivka R.; Fischman, Alan J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Nucl Med, Boston, MA 02114 USA. [Halpern, Elkan F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA 02114 USA. RP Roedl, JB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. EM johannes.roedl@gmail.com NR 19 TC 35 Z9 41 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD JAN PY 2009 VL 11 IS 1 BP 54 EP 60 DI 10.1007/s11307-008-0169-9 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 403XV UT WOS:000263116200008 PM 18769974 ER PT J AU Zurawski, DV Mumy, KL Faherty, CS McCormick, BA Maurelli, AT AF Zurawski, Daniel V. Mumy, Karen L. Faherty, Christina S. McCormick, Beth A. Maurelli, Anthony T. TI Shigella flexneri type III secretion system effectors OspB and OspF target the nucleus to downregulate the host inflammatory response via interactions with retinoblastoma protein SO MOLECULAR MICROBIOLOGY LA English DT Article ID ENTEROPATHOGENIC ESCHERICHIA-COLI; PHOSPHOTHREONINE LYASE ACTIVITY; VIRULENCE-PLASMID; INTESTINAL EPITHELIUM; IMMUNE-RESPONSES; GENE-EXPRESSION; TRANSEPITHELIAL MIGRATION; VIBRIO-PARAHAEMOLYTICUS; CELLS; DISTINCT AB OspF, OspG and IpaH(9.8) are type III secretion system (T3SS) effectors of Shigella flexneri that downregulate the host innate immune response. OspF modifies mitogen-activated protein kinase pathways and polymorphonuclear leucocyte transepithelial migration associated with Shigella invasion. OspF also localizes in the nucleus to mediate chromatin remodelling, resulting in reduced transcription of inflammatory cytokines. We now report that OspB can be added to the set of S. flexneri T3SS effectors required to modulate the innate immune response. T84 cells infected with a Delta ospB mutant resulted in reduced polymorphonuclear leucocyte transepithelial migration and mitogen-activated protein kinase signalling. Tagged versions of OspB localized with endosomes and the nucleus. Further, T84 cells infected with the Delta ospB mutant showed increased levels of secreted IL-8 compared with wild-type infected cells. Both GST-OspB and GST-OspF coprecipitated retinoblastoma protein from host cell lysates. Because Delta ospB and Delta ospF mutants share similar phenotypes, and OspB and OspF share a host binding partner, we propose that OspB and OspF facilitate the remodelling of chromatin via interactions with retinoblastoma protein, resulting in diminished inflammatory cytokine production. The requirement of multiple T3SS effectors to modulate the innate immune response correlates to the complexity of the human immune system. C1 [Zurawski, Daniel V.; Faherty, Christina S.; Maurelli, Anthony T.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Mumy, Karen L.; McCormick, Beth A.] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA USA. [Mumy, Karen L.; McCormick, Beth A.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Maurelli, AT (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. EM daniel.zurawski@amedd.army.mil; amaurelli@usuhs.mil RI Zurawski, Daniel/B-6578-2009 OI Zurawski, Daniel/0000-0002-7920-5601 FU National Institutes of Allergy and Infectious Diseases [AI24656]; National Institutes of Health [DK56754, DK33506]; Harvard Medical School; Department of Surgery at Massachusetts General Hospital; Henry M. Jackson Foundation; Uniformed Services University of the Health Sciences FX We would like to acknowledge Nancy Adams and Reinaldo Fernandez for technical assistance, Dr. Chou-Zen Giam for use of the inverted fluorescence microscope, and Dr. Anne-Laure Prunier for critical reading of this manuscript. We would also like to thank our colleagues at the Walter Reed Institute of Army Research for reagents and the time to allow D.V.Z. to finish this manuscript, especially the members of the Oaks laboratory and Dr Ryan Ranallo for supplying the Gateway vectors. This work was supported by National Institutes of Allergy and Infectious Diseases Grant AI24656 (to A.T.M.). B.A.M. is supported by National Institutes of Health Grants DK56754 and DK33506. K.L.M. is supported by a T32 Training Grant sponsored by Harvard Medical School and the Department of Surgery at Massachusetts General Hospital. C.S.F. is supported by the Val G. Hemming Fellowship sponsored by the Henry M. Jackson Foundation and Uniformed Services University of the Health Sciences. NR 67 TC 52 Z9 54 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2009 VL 71 IS 2 BP 350 EP 368 DI 10.1111/j.1365-2958.2008.06524.x PG 19 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 392LO UT WOS:000262304400006 PM 19017275 ER PT J AU Xu, PS Gullotti, E Tong, L Highley, CB Errabelli, DR Hasan, T Cheng, JX Kohane, DS Yeo, Y AF Xu, Peisheng Gullotti, Emily Tong, Ling Highley, Christopher B. Errabelli, Divya R. Hasan, Tayyaba Cheng, Ji-Xin Kohane, Daniel S. Yeo, Yoon TI Intracellular Drug Delivery by Poly(lactic-co-glycolic acid) Nanoparticles, Revisited SO MOLECULAR PHARMACEUTICS LA English DT Article DE PLGA nanoparticles; intracellular drug delivery; cellular uptake; contact-based transfer ID PLGA NANOPARTICLES; CELLULAR UPTAKE; POLY(D,L-LACTIDE-CO-GLYCOLIDE) NANOPARTICLES; MACROMOLECULAR THERAPEUTICS; CANCER-CHEMOTHERAPY; GENE DELIVERY; ORAL DELIVERY; NILE RED; PACLITAXEL; CELLS AB We reexamined the cellular drug delivery mechanism by poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) to determine their utility and limitations as an intracellular drug delivery system. First, we prepared PLGA NPs which physically encapsulated Nile red (a hydrophobic fluorescent dye), in accordance with the usual procedure for labeling PLGA NPs, incubated them with mesothelial cells, and observed an increase in the intracellular fluorescence. We then prepared NPs from PLGA chemically conjugated to a fluorescent dye and observed their uptake by the mesothelial cells using confocal microscopy. We also used coherent anti-Stokes Raman scattering (CARS) microscopy to image cellular uptake of unlabeled PLGA NPs. Results of this study coherently suggest that PLGA NPs (i) are not readily taken up by cells, but (ii) deliver the payload to cells by extracellular drug release and/or direct drug transfer to contacting cells, which are contrasted with the prevalent view. From this alternative standpoint, we analyzed cytotoxicities of doxorubicin and paclitaxel delivered by PLGA NPs and compared with those of free drugs. Finally, we revisit previous findings in the literature and discuss potential strategies to achieve efficient drug delivery to the target tissues using PLGA NPs. C1 [Xu, Peisheng; Yeo, Yoon] Purdue Univ, Dept Ind & Phys Pharm, W Lafayette, IN 47907 USA. [Gullotti, Emily; Tong, Ling; Cheng, Ji-Xin; Yeo, Yoon] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA. [Highley, Christopher B.; Kohane, Daniel S.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Errabelli, Divya R.; Hasan, Tayyaba] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kohane, Daniel S.] Harvard Univ, Sch Med, Childrens Hosp, Dept Anesthesiol,Lab Biomat & Drug Delivery, Boston, MA 02115 USA. RP Yeo, Y (reprint author), Purdue Univ, Dept Ind & Phys Pharm, 575 Stadium Mall Dr G22, W Lafayette, IN 47907 USA. EM yyeo@purdue.edu FU 3M Nontenured Faculty; Showalter Trust Award; NIH [R01 CA119388, R01 GM073626] FX The authors thank 3M Nontenured Faculty Grant and Showalter Trust Award (Y.Y.), NIH R01 CA119388 (T.H.), and NIH R01 GM073626 (D.S.K.) for financial support. The authors also thank Dr. Michael D. Tsifansky for critical reading of the manuscript. NR 37 TC 105 Z9 108 U1 3 U2 36 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD JAN-FEB PY 2009 VL 6 IS 1 BP 190 EP 201 DI 10.1021/mp800137z PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 402TC UT WOS:000263035000020 PM 19035785 ER PT J AU Simons, EJ Bellas, E Lawlor, MW Kohane, DS AF Simons, Emmanuel J. Bellas, Evangelia Lawlor, Michael W. Kohane, Daniel S. TI Effect of Chemical Permeation Enhancers on Nerve Blockade SO MOLECULAR PHARMACEUTICS LA English DT Article DE Sciatic nerve blockade; local anesthetic; tetrodotoxin; bupivacaine; chemical permeation enhancer ID TRANSDERMAL DRUG-DELIVERY; PENETRATION ENHANCERS; SYSTEMIC TOXICITY; MYELINATED NERVE; LOCAL-ANESTHESIA; STRATUM-CORNEUM; SODIUM-CHANNELS; CONSCIOUS DOG; TETRODOTOXIN; BUPIVACAINE AB Chemical permeation enhancers (CFEs) have the potential to improve access of local anesthetics to the nerve, thereby improving nerve block performance. We assessed the effects of six CPEs on nerve blockade from tetrodotoxin (TTX) and from bupivacaine. Each of the six surfactants, representing three CPE subgroups (anionic, cationic, and nonionic surfactants) was coinjected with TTX or bupivacaine at the sciatic; nerve of Sprague-Dawley rats. Myotoxicity of CPEs, alone and with TTX, was assessed in vitro in C2C12 myotubes and in vivo via histological analysis. All enhancers produced marked concentration-dependent improvements in the frequency and duration of block with TTX but not bupivacaine. An in vitro toxicity assay showed a wide range of CPE myotoxicity, but in vivo histological assessment showed no signs of muscle car nerve damage at concentrations of CPEs that produced a half-maximal increase in the duration of block of TTX (except in the case of the cationic surfactant DDAB). This study demonstrates that CPEs can provide marked prolongation of nerve blockade from TTX but not bupivacaine, without apparent local tissue toxicity. These results may enhance the clinical applicability of TTX for prolonged-duration local anesthesia. C1 [Kohane, Daniel S.] Harvard Univ, Sch Med, Childrens Hosp,Lab Biomat & Drug Delivery, Div Crit Care Med,Dept Anesthesiol, Boston, MA 02115 USA. [Simons, Emmanuel J.] Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA. [Bellas, Evangelia] MIT, Dept Chem Engn, Boston, MA USA. [Lawlor, Michael W.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kohane, DS (reprint author), Harvard Univ, Sch Med, Childrens Hosp,Lab Biomat & Drug Delivery, Div Crit Care Med,Dept Anesthesiol, Bader 628,300 Longwood Ave, Boston, MA 02115 USA. EM daniel.kohane@childrens.harvard.edu FU NIGMS (National Institute of General Medical Sciences) [GM073626]; NIH/NIDCD (National Institute of Deafness and Other Communication Disorders) [T32/DC000038] FX The following financial support is gratefully acknowledged: GM073626 (to D.S.K.) from NIGMS (National Institute of General Medical Sciences); T32/DC000038 (to E.J.S.) from NIH/NIDCD (National Institute of Deafness and Other Communication Disorders). NR 29 TC 13 Z9 13 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD JAN-FEB PY 2009 VL 6 IS 1 BP 265 EP 273 DI 10.1021/mp800167a PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 402TC UT WOS:000263035000027 PM 19105721 ER PT J AU Lan, HX Teeter, MM Gurevich, VV Neve, KA AF Lan, Hongxiang Teeter, Martha M. Gurevich, Vsevolod V. Neve, Kim A. TI An Intracellular Loop 2 Amino Acid Residue Determines Differential Binding of Arrestin to the Dopamine D-2 and D-3 Receptors SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; BETA-ARRESTIN; CRYSTAL-STRUCTURE; ALPHA(2)-ADRENERGIC RECEPTORS; NEOSTRIATAL NEURONS; RHODOPSIN; PHOSPHORYLATION; DESENSITIZATION; MECHANISM; DOMAINS AB Dopamine D-2 and D-3 receptors are similar subtypes with distinct interactions with arrestins; the D-3 receptor mediates less agonist-induced translocation of arrestins than the D-2 receptor. The goals of this study were to compare nonphosphorylated arrestin-binding determinants in the second intracellular domain (IC2) of the D-2 and D-3 receptors to identify residues that contribute to the differential binding of arrestin to the subtypes. Arrestin3 bound to glutathione transferase (GST) fusion proteins of the D-2 receptor IC2 more avidly than to the D-3 receptor IC2. Mutagenesis of the fusion proteins identified a residue at the C terminus of IC2, Lys149, that was important for the preferential binding of arrestin3 to D-2-IC2; arrestin binding to D-2-IC2-K149C was greatly decreased compared with wild-type D-2-IC2, whereas binding to the reciprocal mutant D-3-IC2-C147K was enhanced compared with wild-type D-3-IC2. Mutating this lysine in the full-length D-2 receptor to cysteine decreased the ability of the D-2 receptor to mediate agonist-induced arrestin3 translocation to the membrane and decreased agonist-induced receptor internalization in human embryonic kidney 293 cells. The reciprocal mutation in the D-3 receptor increased receptor-mediated translocation of arrestin3 without affecting agonist-induced receptor internalization. G protein-coupled receptor crystal structures suggest that Lys149, at the junction of IC2 and the fourth membrane-spanning helix, has intramolecular interactions that contribute to maintaining an inactive receptor state. It is suggested that the preferential agonist-induced binding of arrestin3 to the D-2 receptor over the D-3 receptor is due in part to Lys149, which could be exposed as a result of receptor activation. C1 [Neve, Kim A.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Lan, Hongxiang] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. [Neve, Kim A.] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Portland, OR 97201 USA. [Teeter, Martha M.] UC Davis Med Ctr, Dept Psychiat, Scaramento, CA USA. [Teeter, Martha M.] Univ Calif Davis, Dept Chem, Davis, CA 95616 USA. [Gurevich, Vsevolod V.] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA. RP Neve, KA (reprint author), Portland VA Med Ctr, R&D 30, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM nevek@ohsu.edu RI Gurevich, Vsevolod/A-3236-2008 OI Gurevich, Vsevolod/0000-0002-3950-5351 FU United States Public Health Service [MH045372, GM077561, EY011500]; VA Merit Review and Career Scientist programs FX This work was supported by United States Public Health Service grants MH045372 (to K.A.N.), GM077561 (to V.V.G.), and EY011500 (to V.V. G.), and the VA Merit Review and Career Scientist programs (to K.A.N.). NR 29 TC 22 Z9 23 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 2009 VL 75 IS 1 BP 19 EP 26 DI 10.1124/mol.108.050542 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 386AK UT WOS:000261854500003 PM 18820126 ER PT J AU Lan, HX Liu, Y Bell, MI Gurevich, VV Neve, KA AF Lan, Hongxiang Liu, Yong Bell, Michal I. Gurevich, Vsevolod V. Neve, Kim A. TI A Dopamine D-2 Receptor Mutant Capable of G Protein-Mediated Signaling but Deficient in Arrestin Binding SO MOLECULAR PHARMACOLOGY LA English DT Article ID 3RD INTRACELLULAR LOOP; BETA-ARRESTIN; COUPLED RECEPTORS; ALPHA(2)-ADRENERGIC RECEPTORS; BETA(2)-ADRENERGIC RECEPTOR; NEOSTRIATAL NEURONS; ADENYLATE-CYCLASE; HORMONE RECEPTOR; CYTOPLASMIC LOOP; PHOSPHORYLATION AB Arrestins mediate G protein-coupled receptor desensitization, internalization, and signaling. Dopamine D-2 and D-3 receptors have similar structures but distinct characteristics of interaction with arrestins. The goals of this study were to compare arrestin-binding determinants in D-2 and D-3 receptors other than phosphorylation sites and to create a D-2 receptor that is deficient in arrestin binding. We first assessed the ability of purified arrestins to bind to glutathione transferase (GST) fusion proteins containing the receptor third intracellular loops (IC3). Arrestin3 bound to IC3 of both D-2 and D-3 receptors, with the affinity and localization of the binding site indistinguishable between the receptor subtypes. Mutagenesis of the GST-IC3 fusion proteins identified an important determinant of the binding of arrestin3 in the N-terminal region of IC3. Alanine mutations of this determinant (IYIV212-215) in the full-length D-2 receptor generated a signaling-biased receptor with intact ligand binding and G-protein coupling and activation, but deficient in receptor-mediated arrestin3 translocation to the membrane, agonist-induced receptor internalization, and agonist-induced desensitization in human embryonic kidney 293 cells. This mutation also decreased arrestin-dependent activation of extracellular signal-regulated kinases. The finding that nonphosphorylated D-2-IC3 and D-3-IC3 have similar affinity for arrestin is consistent with previous suggestions that the differential effects of D-2 and D-3 receptor activation on membrane translocation of arrestin and receptor internalization are due, at least in part, to differential phosphorylation of the receptors. In addition, these results imply that the sequence IYIV212-215 at the N terminus of IC3 of the D-2 receptor is a key element of the arrestin binding site. C1 Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Portland, OR 97201 USA. [Liu, Yong; Bell, Michal I.; Neve, Kim A.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Lan, Hongxiang] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. [Gurevich, Vsevolod V.] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA. RP Neve, KA (reprint author), Portland VA Med Ctr, R&D 30, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM nevek@ohsu.edu RI Gurevich, Vsevolod/A-3236-2008 OI Gurevich, Vsevolod/0000-0002-3950-5351 FU United States Public Health Service [MH045372, GM077561, EY011500]; VA Merit Review and Career Scientist programs FX This work was supported by United States Public Health Service grants MH045372 (to K.A.N.), GM077561 (to V.V.G.), and EY011500 (to V.V.G.), and the VA Merit Review and Career Scientist programs (to K.A.N.). NR 48 TC 28 Z9 29 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 2009 VL 75 IS 1 BP 113 EP 123 DI 10.1124/mol.108.050534 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 386AK UT WOS:000261854500012 PM 18809670 ER PT J AU Cichon, S Craddock, N Daly, M Faraone, SV Gejman, PV Kelsoe, J Lehner, T Levinson, DF Moran, A Sklar, P Sullivan, PF AF Cichon, Sven Craddock, Nick Daly, Mark Faraone, Stephen V. Gejman, Pablo V. Kelsoe, John Lehner, Thomas Levinson, Douglas F. Moran, Audra Sklar, Pamela Sullivan, Patrick F. CA Psychiatric GWAS Consortium Steeri TI A framework for interpreting genome-wide association studies of psychiatric disorders The Psychiatric GWAS Consortium Steering Committee SO MOLECULAR PSYCHIATRY LA English DT Article DE genome-wide association; attention-deficit hyperactivity disorder; autism; bipolar disorder; major depressive disorder; schizophrenia ID COMMON DISEASE; HAPLOTYPE MAP; SCHIZOPHRENIA; PSYCHOSIS; VARIANTS; OBESITY; RISK; GENE AB Genome-wide association studies (GWAS) have yielded a plethora of new findings in the past 3 years. By early 2009, GWAS on 47 samples of subjects with attention-deficit hyperactivity disorder, autism, bipolar disorder, major depressive disorder and schizophrenia will be completed. Taken together, these GWAS constitute the largest biological experiment ever conducted in psychiatry ( 59 000 independent cases and controls, 7700 family trios and > 40 billion genotypes). We know that GWAS can work, and the question now is whether it will work for psychiatric disorders. In this review, we describe these studies, the Psychiatric GWAS Consortium for meta-analyses of these data, and provide a logical framework for interpretation of some of the conceivable outcomes. C1 [Sklar, Pamela] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Cichon, Sven] Univ Bonn, D-5300 Bonn, Germany. [Craddock, Nick] Cardiff Univ, Cardiff, S Glam, Wales. [Daly, Mark] Harvard Univ, Sch Med, Broad Inst, Cambridge, MA 02138 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, New York, NY USA. [Gejman, Pablo V.] Northwestern Univ, Evanston NW Healthcare & Feinberg Sch Med, Evanston, IL 60208 USA. [Kelsoe, John] Univ Calif San Diego, San Diego, CA 92103 USA. [Lehner, Thomas] NIMH, Bethesda, MD 20892 USA. [Levinson, Douglas F.] Stanford Univ, Stanford, CA 94305 USA. [Sklar, Pamela] Massachusetts Gen Hosp, Broad Inst, Boston, MA 02114 USA. RP Sullivan, PF (reprint author), Univ N Carolina, Dept Genet, CB 7264,4109D Neurosci Res Bldg, Chapel Hill, NC 27599 USA. EM pfsulliv@med.unc.edu RI turton, miranda/F-4682-2011; Franke, Barbara/D-4836-2009; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014 OI Franke, Barbara/0000-0003-4375-6572; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X FU NIMH [MH085520]; Netherlands Scientific Organization [NWO 480-05-003]; Dutch Brain Foundation; NARSAD FX This article was written early in the history of the PGC by its coordinating committee who takes responsibility for its content. We wish to acknowledge our enduring debt to our PGC colleagues for their many contributions to this work. The members of the PGC Coordinating Committee are: Sven Cichon (University of Bonn), Nick Craddock (Cardiff University), Mark Daly (Harvard Medical School, Broad Institute), Stephen V Faraone (SUNY Upstate Medical University), Pablo V Gejman (Evanston Northwestern Healthcare and Feinberg School of Medicine, Northwestern University), John Kelsoe (University of California, San Diego), Thomas Lehner (NIMH), Douglas F Levinson (Stanford University), Audra Moran (NARSAD, ex officio), Pamela Sklar (Massachusetts General Hospital, Broad Institute) and Patrick F Sullivan (University of North Carolina at Chapel Hill). The PGC is supported by NIMH MH085520 (http://www.nimh.gov). Statistical analyses are conducted on the Genetic Cluster Computer, which is supported by the Netherlands Scientific Organization (NWO 480-05-003, PI Danielle Posthuma) along with a supplement from the Dutch Brain Foundation (http://www.hersenstichting.nl, PI Roel Ophoff). We are indebted to NARSAD for infrastructure support. NR 28 TC 103 Z9 104 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JAN PY 2009 VL 14 IS 1 BP 10 EP 17 DI 10.1038/mp.2008.126 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 386EY UT WOS:000261866300004 ER PT J AU Aghi, MK Liu, TC Rabkin, S Martuza, RL AF Aghi, Manish K. Liu, Ta-Chiang Rabkin, Samuel Martuza, Robert L. TI Hypoxia Enhances the Replication of Oncolytic Herpes Simplex Virus SO MOLECULAR THERAPY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; MALIGNANT GLIOMA; TENSION MEASUREMENTS; VIRAL REPLICATION; RESPONSE ELEMENTS; TUMOR HYPOXIA; DNA-REPAIR; IN-VITRO; PROTEIN; CANCER AB Hypoxia contributes to the resistance of tumors to conventional therapies. We hypothesized that their replication in hypoxic environments like brain or oral mucosa would make oncolytic herpes simplex viruses (HSVs) such as G207 (which has undergone clinical trials) replicate to a greater extent in hypoxic tumors like glioblastoma. Hypoxic cultured U87 cells yielded 4% more wild-type HSV (P = 0.04) and 3.6-fold more G207 (P = 0.001) after 48 hours of infection when compared with normoxic cells. Real-time RT-PCR confirmed a fivefold hypoxia-induced U87 upregulation of GADD34 mRNA, a factor complementing the gamma 34.5 gene deletion in G207. The viral yield under conditions of hypoxia, as against normoxia, in GADD34 siRNA-treated U87 cells was 65% of that in control siRNA-treated cells. Treating subcutaneous U87 tumors in athymic mice with erythropoietin lowered the tumoral hypoxic fraction from 57.5 to 24.5%. Tumoral hypoxia dropped to 2.5% during 4 hours/day of hyperbaric chamber treatment. Each tumor-oxygenating maneuver reduced the G207 yield fourfold (P = 0.0001). Oncolytic HSV G207 exhibited enhanced replication in hypoxic environments, partly on account of increased GADD34 expression in hypoxic cells. The unique tropism of oncolytic HSVs for hypoxic environments contrasts with the hypoxia-mediated impairment of standard (radiation, chemotherapy) and other experimental therapies, and enhances HSV's appeal and efficacy in treating tumors like glioblastoma. C1 [Aghi, Manish K.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. [Liu, Ta-Chiang] Washington Univ, Dept Pathol & Immunol, St Louis, MO USA. [Rabkin, Samuel; Martuza, Robert L.] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Rabkin, Samuel; Martuza, Robert L.] Harvard Univ, Sch Med, Boston, MA USA. RP Aghi, MK (reprint author), Univ Calif San Francisco, Dept Neurosurg, 505 Parnassus Ave M779, San Francisco, CA 94143 USA. EM AghiM@neurosurg.ucsf.edu RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU National Institutes of Health [NS32677, P30 NS045776] FX This work was supported in part by National Institutes of Health Grants NS32677 (to R. L. M.) and P30 NS045776 (to S. R.) for the real-time PCR core. Robert Martuza and Samuel Rabkin are consultants to MediGene AG, which has a license from Georgetown University for G207. NR 36 TC 29 Z9 30 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JAN PY 2009 VL 17 IS 1 BP 51 EP 56 DI 10.1038/mt.2008.232 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 390AQ UT WOS:000262137100009 PM 18957963 ER PT B AU Dupin, MM AF Dupin, Michael M. BE Martin, S Williams, JR TI MODELING EXPLICITLY THE FLOW OF THREE DIMENSIONAL DEFORMABLE PARTICLES AND DROPLETS, AT HIGH CONCENTRATION SO MULTIPHASE FLOW RESEARCH LA English DT Article; Book Chapter ID RED-BLOOD-CELLS AB This chapter considers what happens when a multi-component system is subjected to a flow. More precisely, how to model it to better understand it. Two state of the art techniques for modeling multi-component flow are presented, based on the type of multi-component is considered. The first technique is to model a large amount of non-coalescing fluid droplets in flow, all of which have possibly different parameters (surface tensions, viscosities, radius, etc.). The second technique is to model a large amount of deformable cells or vesicles in flow, all of which have individual sets of parameters such as shape, rest curvature, elasticity, elasticity response, volume,etc. The underlying fluid dynamics of these two techniques is based on the lattice Boltzmann method, which was chosen for its efficiency and great versatility compared to other techniques. The chapter begins by deriving it, showing how it relates to more commonly known methods. The bulk of the chapter consists of proof of concepts and engineering applications for each technique, in order to demonstrate their efficiency, accuracy, versatility and potential. C1 [Dupin, Michael M.] Massachusetts Gen Hosp, Steele Lab, Boston, MA 02114 USA. [Dupin, Michael M.] Harvard Univ, Sch Med, Boston, MA USA. RP Dupin, MM (reprint author), Massachusetts Gen Hosp, Steele Lab, Boston, MA 02114 USA. NR 20 TC 0 Z9 0 U1 0 U2 1 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60692-448-8 PY 2009 BP 359 EP 395 PG 37 WC Engineering, Mechanical; Mechanics SC Engineering; Mechanics GA BKQ94 UT WOS:000268975800006 ER PT J AU King, DW King, LA McArdle, JJ Shalev, AY Doron-LaMarca, S AF King, Daniel W. King, Lynda A. McArdle, John J. Shalev, Arieh Y. Doron-LaMarca, Susan TI Sequential Temporal Dependencies in Associations Between Symptoms of Depression and Posttraumatic Stress Disorder: An Application of Bivariate Latent Difference Score Structural Equation Modeling SO MULTIVARIATE BEHAVIORAL RESEARCH LA English DT Article ID CONFIRMATORY FACTOR-ANALYSIS; ADMINISTERED PTSD SCALE; LONGITUDINAL TRAUMA RESEARCH; PSYCHOMETRIC PROPERTIES; MENTAL-DISORDERS; EVENT SCALE; CANCER-SURVIVORS; MAJOR DEPRESSION; WAR VETERANS; INVENTORY AB Depression and posttraumatic stress disorder (PTSD) are highly comorbid conditions that may arise following exposure to psychological trauma. This study examined their temporal sequencing and mutual influence using bivariate latent difference score structural equation modeling. Longitudinal data from 182 emergency room patients revealed level of depression symptom severity to be positively associated with changes in PTSD intrusion, avoidance, and hyperarousal over 3 time intervals, beginning shortly after the traumatic event. Higher score on depression anticipated increases (or worsening) in PTSD symptom severity. The pattern of influence from PTSD symptom severity to change in depression symptom severity simply followed the general trend toward health and well-being. Results are discussed in terms of the dynamic interplay and associated mechanisms of posttrauma depression and PTSD symptom severity. C1 [Doron-LaMarca, Susan] Boston Univ, Sch Med, Boston, MA 02215 USA. [King, Lynda A.; Doron-LaMarca, Susan] VA Boston Healthcare Syst, Boston, MA USA. [McArdle, John J.] Univ So Calif, Los Angeles, CA 90089 USA. [Shalev, Arieh Y.] Hadassah Univ Hosp, Jerusalem, Israel. RP King, DW (reprint author), Natl Ctr Posttraumat Stress Disorder 116B5, 150 S Huntington Ave, Boston, MA 02130 USA. EM danking@bu.edu OI Shalev, Arieh/0000-0001-9425-050X FU National Institute of Mental Health [R01MH68626, R01MH50379] FX This study was supported by National Institute of Mental Health Grants R01MH68626 (Daniel W. King, principal investigator) and R01MH50379 (Arieh Y. Shalev, principal investigator). We thank our colleagues, Brett Litz, Mark Miller, and Jeffrey Knight, for their contributions to the interpretation of findings. NR 64 TC 25 Z9 25 U1 4 U2 11 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0027-3171 J9 MULTIVAR BEHAV RES JI Multivariate Behav. Res. PY 2009 VL 44 IS 4 BP 437 EP 464 DI 10.1080/00273170903103308 PG 28 WC Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods; Psychology, Experimental; Statistics & Probability SC Mathematics; Mathematical Methods In Social Sciences; Psychology GA 503TM UT WOS:000270563100002 PM 26735592 ER PT J AU Veal, E Olahova, M Taylor, SR Khazaipoul, S Wang, J Crook, H Day, A Morgan, B Matsumoto, K Blackwell, K AF Veal, Elizabeth Olahova, Monika Taylor, Sarah R. Khazaipoul, Siavash Wang, Jinling Crook, Helen Day, Alison Morgan, Brian Matsumoto, Kunihiro Blackwell, Keith TI Redox-sensitive peroxiredoxins play multiple roles in the oxidative stress resistance of Caenorhabditis elegans SO MUTAGENESIS LA English DT Meeting Abstract ID LUNG-CANCER C1 [Veal, Elizabeth; Olahova, Monika; Taylor, Sarah R.; Khazaipoul, Siavash; Crook, Helen; Day, Alison; Morgan, Brian] Newcastle Univ, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Wang, Jinling; Blackwell, Keith] Joslin Diabet Ctr, Boston, MA 02215 USA. [Matsumoto, Kunihiro] Nagoya Univ, Chikusa Ku, Nagoya, Aichi 4648602, Japan. NR 5 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD JAN PY 2009 VL 24 IS 1 MA 13 BP 101 EP 101 PG 1 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 388CK UT WOS:000261997700025 ER PT B AU Barteneva, N Vorobjev, I AF Barteneva, Natasha Vorobjev, Ivan BE Laudon, M Romanowicz, B TI The development of multicolor panels with Quantum Dots-conjugated antibodies for diagnostics of Chronic Lymphoid Leukemia (CLL) by conventional flow cytometer SO NANOTECH CONFERENCE & EXPO 2009, VOL 2, TECHNICAL PROCEEDINGS LA English DT Proceedings Paper CT Nanotech 2009 Conference CY MAY 03-07, 2009 CL Houston, TX SP Acctron AG, Adv Energy Consortium, Alliance NanoHealth, Appl Mat, Bayer MaterialScience, Buchanan Ingersoll & Rooney PC, Buhler PARTEC GmbH, Ctr Appl Nanotechnol GmbH, Ctr Biol & Environm Nanotechnol, Clean Technol & Sustainable Ind Org, CMP, CTC Nanotechnol GmbH, DREEBIT GmbH, ETH Zurich, ETH Transfer, ETH Zurich, MNSP, Folcy & Lardner LLP, FDA, Goodwin Procter LLC, HiNanoAnalytics, Houston Technol Ctr, Inno X GmbH, Innovat Alliance Carbon Nanotubes, Italian Tradde Commiss, Jackson Walket LLP, JENOPTIK, Lockheed Martin, Nano Sci & Technol Inst, nano tech 2009 Japan, NanoEurope Fair & Conf, Nanograde Llc, NanoInk, NANOSENSORS, NanoSPRINT, NanoWorld AG, NCI, NIH, Opportun Houston, OSEC, Pearland Econ Dev Corp, Res Germany Land Ideas, Richard Smalley Inst Nanoscale Sci & Technol, Taylor & Francis Grp LLC, CRC Press, TechConnect, Texas Nanotechnol Initiat, IEEE Stand Assoc, Russian Corp Nanotechnologies, TurboBeads Llc, Weidmann Plast Technol AG DE quantum dots; antibodies; chronic lymphoid leukemia; flow cytometry ID ACUTE MYELOID-LEUKEMIA; SENSITIVITY AB The standard flow cytometry diagnostics approach (3 colors) requires 10-15 tubes per patient and does not allow identification of small populations of tumor cells. Quantum dots (QDots) offer new possibilities in polychromatic clinical cytometry resolving organic and tandem dyes issues with stability and donor bleed-through. We used combinations of beads stained with different antibody conjugates with QDots and standard fluorochromes to calculate signal to noise ratio and stain index for QD605, QD655 and QD705-conjugated antibodies alone and included in our CLL panels. We developed 8-color panel (CD3/CD5/CD19/CD23/CD38/CD10/CD45/ Sytox Blue viability dye) panel incorporating QD605, QD655 and QD705 direct antibody conjugates (Invitrogen) for differential diagnostics of CLL. Using this panel we were able to define the population of CLL cells that was as small as 1% of the overall PBMC population - it was determined in dilution experiments (adding mixture of similar to 0.2% CLL to the normal blood). C1 [Barteneva, Natasha] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Barteneva, N (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 200 Longwood,Room D-239, Boston, MA 02115 USA. EM barteneva@idi.harvard.edu; ivorobjev@mail.ru NR 4 TC 0 Z9 1 U1 1 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-1783-4 PY 2009 BP 26 EP 28 PG 3 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BMQ02 UT WOS:000273330500008 ER PT J AU Lo Celso, C Fleming, HE Wu, JWW Zhao, CX Miake-Lye, S Fujisaki, J Cote, D Rowe, DW Lin, CP Scadden, DT AF Lo Celso, Cristina Fleming, Heather E. Wu, Juwell W. Zhao, Cher X. Miake-Lye, Sam Fujisaki, Joji Cote, Daniel Rowe, David W. Lin, Charles P. Scadden, David T. TI Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche SO NATURE LA English DT Article ID BONE-MARROW NICHE; STEM-CELL; IN-VIVO; PROGENITOR CELLS; IDENTIFICATION; OSTEOPONTIN; ENGRAFTMENT; EXPRESSION; COMPONENT; RECEPTOR AB Stem cells reside in a specialized, regulatory environment termed the niche that dictates how they generate, maintain and repair tissues(1,2). We have previously documented that transplanted haematopoietic stem and progenitor cell populations localize to subdomains of bone- marrow microvessels where the chemokine CXCL12 is particularly abundant(3). Using a combination of high-resolution confocal microscopy and two- photon video imaging of individual haematopoietic cells in the calvarium bone marrow of living mice over time, we examine the relationship of haematopoietic stem and progenitor cells to blood vessels, osteoblasts and endosteal surface as they home and engraft in irradiated and c-Kit-receptor-deficient recipient mice. Osteoblasts were enmeshed in microvessels and relative positioning of stem/ progenitor cells within this complex tissue was nonrandom and dynamic. Both cell autonomous and non- autonomous factors influenced primitive cell localization. Different haematopoietic cell subsets localized to distinct locations according to the stage of differentiation. When physiological challenges drove either engraftment or expansion, bone- marrow stem/ progenitor cells assumed positions in close proximity to bone and osteoblasts. Our analysis permits observing in real time, at a single cell level, processes that previously have been studied only by their long- term outcome at the organismal level. C1 [Lo Celso, Cristina; Fleming, Heather E.; Zhao, Cher X.; Miake-Lye, Sam; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Scadden, David T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Wu, Juwell W.; Fujisaki, Joji; Cote, Daniel; Lin, Charles P.] Massachusetts Gen Hosp, Adv Microscopy Program, Ctr Syst Biol, Boston, MA 02114 USA. [Wu, Juwell W.; Fujisaki, Joji; Cote, Daniel; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Lo Celso, Cristina; Fleming, Heather E.; Wu, Juwell W.; Zhao, Cher X.; Fujisaki, Joji; Lin, Charles P.; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Rowe, David W.] Univ Connecticut, Ctr Hlth, Farmington, CT 06030 USA. [Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA. EM lin@helix.mgh.harvard.edu; dscadden@mgh.harvard.edu RI Cote, Daniel/D-5185-2011; Fang, Zhijun/L-9620-2013; OI Lo Celso, Cristina/0000-0002-1163-4207 FU EMBO; HFSP; National Institutes of Health; Harvard Stem Cell Institute FX We thank E. Schipani for providing the PPR mice. We are grateful for help and advice from A. Catic, L. Purton, V. Janzen, G. Adams, J. Spencer, J. Runnels and P. O'Donovan. We thank Y. Tang for the mice husbandry care; D. Dombkowski, L. Prickett and K. Folz-Donahue for cell sorting expertise; R. Klein and K. Chomsky-Higgins for technical assistance; and C. Pasker, V. Shannon, M. Indico Miklosik and D. Machon for administrative assistance. C. L. C. was funded by EMBO and HFSP. The project was funded by the National Institutes of Health (to D.T.S. and C.P.L.), the Harvard Stem Cell Institute (to C.P.L.) and philanthropic sources (to D.T.S. and C.L.C.). NR 33 TC 399 Z9 401 U1 6 U2 42 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 1 PY 2009 VL 457 IS 7225 BP 92 EP U96 DI 10.1038/nature07434 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 389OR UT WOS:000262104900037 PM 19052546 ER PT J AU Du, JY Bernasconi, P Clauser, KR Mani, DR Finn, SP Beroukhim, R Burns, M Julian, B Peng, XP Hieronymus, H Maglathlin, RL Lewis, TA Liau, LM Nghiemphu, P Mellinghoff, IK Louis, DN Loda, M Carr, SA Kung, AL Golub, TR AF Du, Jinyan Bernasconi, Paula Clauser, Karl R. Mani, D. R. Finn, Stephen P. Beroukhim, Rameen Burns, Melissa Julian, Bina Peng, Xiao P. Hieronymus, Haley Maglathlin, Rebecca L. Lewis, Timothy A. Liau, Linda M. Nghiemphu, Phioanh Mellinghoff, Ingo K. Louis, David N. Loda, Massimo Carr, Steven A. Kung, Andrew L. Golub, Todd R. TI Bead-based profiling of tyrosine kinase phosphorylation identifies SRC as a potential target for glioblastoma therapy SO NATURE BIOTECHNOLOGY LA English DT Article ID BRAIN-TUMORS; STEM-CELLS; AMPLIFICATION; GROWTH; CANCER; GENE; RESISTANCE; INHIBITOR; GLIOMA; MET AB The aberrant activation of tyrosine kinases represents an important oncogenic mechanism, and yet the majority of such events remain undiscovered. Here we describe a bead-based method for detecting phosphorylation of both wild-type and mutant tyrosine kinases in a multiplexed, high-throughput and low-cost manner. With the aim of establishing a tyrosine kinase-activation catalog, we used this method to profile 130 human cancer lines. Follow-up experiments on the finding that SRC is frequently phosphorylated in glioblastoma cell lines showed that SRC is also activated in primary glioblastoma patient samples and that the SRC inhibitor dasatinib (Sprycel) inhibits viability and cell migration in vitro and tumor growth in vivo. Testing of dasatinib-resistant tyrosine kinase alleles confirmed that SRC is indeed the relevant target of dasatinib, which inhibits many tyrosine kinases. These studies establish the feasibility of tyrosine kinome-wide phosphorylation profiling and point to SRC as a possible therapeutic target in glioblastoma. (C) 2009 Nature America, Inc. All rights reserved. C1 [Du, Jinyan; Bernasconi, Paula; Clauser, Karl R.; Mani, D. R.; Beroukhim, Rameen; Burns, Melissa; Julian, Bina; Peng, Xiao P.; Hieronymus, Haley; Maglathlin, Rebecca L.; Lewis, Timothy A.; Carr, Steven A.; Golub, Todd R.] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. [Du, Jinyan; Bernasconi, Paula; Clauser, Karl R.; Mani, D. R.; Beroukhim, Rameen; Burns, Melissa; Julian, Bina; Peng, Xiao P.; Hieronymus, Haley; Maglathlin, Rebecca L.; Lewis, Timothy A.; Carr, Steven A.; Golub, Todd R.] MIT, Cambridge, MA 02142 USA. [Du, Jinyan; Bernasconi, Paula; Burns, Melissa; Hieronymus, Haley; Kung, Andrew L.; Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Finn, Stephen P.; Beroukhim, Rameen; Loda, Massimo] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Finn, Stephen P.; Beroukhim, Rameen; Loda, Massimo] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Julian, Bina; Peng, Xiao P.; Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Liau, Linda M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurosurg, Los Angeles, CA 90095 USA. [Nghiemphu, Phioanh] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Mellinghoff, Ingo K.] Mem Sloan Kettering Canc Ctr, Dept Neurol, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Louis, David N.] Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA. [Louis, David N.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Louis, David N.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Golub, TR (reprint author), Harvard Univ, Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM golub@broad.mit.edu OI Kung, Andrew/0000-0002-9091-488X; Finn, Stephen/0000-0002-8628-5814 FU Leukemia and Lymphoma Society; Irving Family; Brain Tumor Funders' Collaborative; National Cancer Institute's (NCI) Initiative for Chemical Genetics, National Institutes of Health [N01-CO-12400] FX We would like to thank Levi Garraway and Johnathan Fletcher for cell lines. We thank Julie Dang for her technical support on the pY419SRC IHC experiment. J.D. is supported by a fellowship from the Leukemia and Lymphoma Society and The Irving Family. I. K. M. is funded by the Brain Tumor Funders' Collaborative. The project has been funded in part with funds from the National Cancer Institute's (NCI) Initiative for Chemical Genetics, National Institutes of Health, under contract no. N01-CO-12400, and through the NCI's Integrative Cancer Biology Program. NR 28 TC 131 Z9 134 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2009 VL 27 IS 1 BP 77 EP 83 DI 10.1038/nbt.1513 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 394TP UT WOS:000262471200026 PM 19098899 ER PT J AU Foudi, A Hochedlinger, K Van Buren, D Schindler, JW Jaenisch, R Carey, V Hock, H AF Foudi, Adlen Hochedlinger, Konrad Van Buren, Denille Schindler, Jeffrey W. Jaenisch, Rudolf Carey, Vincent Hock, Hanno TI Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cells SO NATURE BIOTECHNOLOGY LA English DT Article ID MULTIPOTENT PROGENITORS; SELF-RENEWAL; BONE-MARROW; QUIESCENCE; NICHE; PROLIFERATION; MICE; DIFFERENTIATION; P21(CIP1/WAF1); 5-FLUOROURACIL AB Hematopoietic stem cells (HSCs) are thought to divide infrequently based on their resistance to cytotoxic injury targeted at rapidly cycling cells(1,2) and have been presumed to retain labels such as the thymidine analog 5-bromodeoxyuridine (BrdU). However, BrdU retention is neither a sensitive nor specific marker for HSCs(3). Here we show that transient, transgenic expression of a histone 2B (H2B)-green fluorescent protein (GFP) fusion protein in mice has several advantages for label-retention studies over BrdU, including rapid induction of H2B-GFP in virtually all HSCs, higher labeling intensity and the ability to prospectively study label-retaining cells, which together permit a more precise analysis of division history. Mathematical modeling of H2B-GFP dilution in HSCs, identified with a stringent marker combination (L-K(+)S(+)CD48(-)CD150(+))(4), revealed unexpected heterogeneity in their proliferation rates and showed that similar to 20% of HSCs divide at an extremely low rate (<= 0.8-1.8% per day). (C) 2009 Nature America, Inc. All rights reserved. C1 [Foudi, Adlen; Hochedlinger, Konrad; Van Buren, Denille; Schindler, Jeffrey W.; Hock, Hanno] Ctr Canc, Boston, MA 02114 USA. [Foudi, Adlen; Hochedlinger, Konrad; Van Buren, Denille; Schindler, Jeffrey W.; Hock, Hanno] Ctr Regenerat Med, Boston, MA 02114 USA. [Foudi, Adlen; Hochedlinger, Konrad; Van Buren, Denille; Schindler, Jeffrey W.; Hock, Hanno] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Foudi, Adlen; Hochedlinger, Konrad; Carey, Vincent; Hock, Hanno] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hochedlinger, Konrad; Hock, Hanno] Harvard Stem Cell Inst, Boston, MA 02114 USA. [Jaenisch, Rudolf] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Jaenisch, Rudolf] MIT, Cambridge, MA 02142 USA. [Carey, Vincent] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Hock, H (reprint author), Ctr Canc, 185 Cambridge St, Boston, MA 02114 USA. EM Hock.Hanno@mgh.harvard.edu FU Ellison Foundation; Harvard Stem Cell Institute; NIH; Kimmel Foundation; V Foundation; [RO1CA122726] FX We thank Laura Prickett and Kat Folz-Donahue from the HSCI Flow-core at Massachusetts General Hospital (MGH) for their expert assistance, Geoffrey Wahl for providing the H2B-GFP cDNA, and Matthias Stadtfeld, Wenjun Guo and Ben Wittner for valuable input. We thank Linheng Li for the kind gift of biotinylated MNCD-2. We thank Mark Kiel and Sean Morrison for sharing unpublished results and for the gift of excised bone marrow of conditional N-cadherin mutant mice. We thank Glenn Radice for permission to use bone marrow from conditional N-cadherin mutant mice. This work was supported by a contribution from the Ellison Foundation to MGH startup funds for H. H., a seed grant by Harvard Stem Cell Institute to H. H. and by RO1CA122726. H. H. is the recipient of an ASH Scholar Award. K. H. was supported by the NIH Director's Innovator Award, the Harvard Stem Cell Institute, the Kimmel Foundation and the V Foundation. A. F. was the recipient of an MGH ECOR Fund for Medical Discovery Award. NR 38 TC 231 Z9 233 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2009 VL 27 IS 1 BP 84 EP 90 DI 10.1038/nbt.1517 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 394TP UT WOS:000262471200027 PM 19060879 ER PT J AU Refaat, M Isselbacher, EM AF Refaat, Marwan Isselbacher, Eric M. TI A case of giant thoracic aortic aneurysm that initially presented as an altered mental state SO NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE LA English DT Editorial Material C1 [Refaat, Marwan] Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA 15213 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Heart, Boston, MA USA. RP Refaat, M (reprint author), Univ Pittsburgh, Med Ctr, Cardiovasc Inst, 200 Lothrop St,B 571-3 Scaife Hall, Pittsburgh, PA 15213 USA. EM refaatm@upmc.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1743-4297 J9 NAT CLIN PRACT CARD JI Nat. Clin. Pract. Cardiovasc. Med. PD JAN PY 2009 VL 6 IS 1 BP 82 EP 82 DI 10.1038/ncpcardio1412 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 384IZ UT WOS:000261739800014 PM 19047994 ER PT J AU Deisboeck, TS Zhang, L Yoon, J Costa, J AF Deisboeck, Thomas S. Zhang, Le Yoon, Jeongah Costa, Jose TI In silico cancer modeling: is it ready for prime time? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Review DE brain tumor; computational biology; in silico cancer modeling; systems biology ID TUMOR-INDUCED ANGIOGENESIS; MATHEMATICAL-MODEL; BRAIN-TUMORS; CELLULAR-AUTOMATON; GROWTH DYNAMICS; GLIOMA GROWTH; MULTICELLULAR PATTERNS; COMPUTER-SIMULATION; SELF-ORGANIZATION; SYSTEMS BIOLOGY AB At the dawn of the era of personalized, systems-driven medicine, computational or in silico modeling and the simulation of disease processes is becoming increasingly important for hypothesis generation and data integration in both experiments and clinics alike. Arguably, the use of these techniques is nowhere more visible than in oncology. To illustrate the field's vast potential, as well as its current limitations, we briefly review selected studies on modeling malignant brain tumors. Implications for clinical practice, and for clinical trial design and outcome prediction, are also discussed. C1 [Deisboeck, Thomas S.] Massachusetts Gen Hosp, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Complex Biosyst Modeling Lab, Charlestown, MA USA. [Zhang, Le] Michigan Technol Univ, Dept Math Sci, Houghton, MI 49931 USA. [Costa, Jose] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. RP Deisboeck, TS (reprint author), Massachusetts Gen Hosp E, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Complex Biosyst Modeling Lab, Bldg 149,13th St, Charlestown, MA 02129 USA. EM deisboec@helix.mgh.harvard.edu FU NIH [CA 085139, CA 113004]; Harvard-MIT (HST) Athinoula A Martinos Center for Biomedical Imaging; Department of Radiology at Massachusetts General Hospital FX This work has been supported, in part, by NIH grants CA 085139 and CA 113004 (CViT; https://www.cvit.org) and by the Harvard-MIT (HST) Athinoula A Martinos Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital. NR 72 TC 70 Z9 70 U1 1 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD JAN PY 2009 VL 6 IS 1 BP 34 EP 42 DI 10.1038/ncponc1237 PG 9 WC Oncology SC Oncology GA 385WW UT WOS:000261845300009 PM 18852721 ER PT J AU Gaffo, AL Saag, KG AF Gaffo, Angelo L. Saag, Kenneth G. TI Are glucocorticoids equivalent to NSAIDs for the treatment of gout flares? SO NATURE CLINICAL PRACTICE RHEUMATOLOGY LA English DT Editorial Material DE glucocorticoids; gout; NSAIDs; therapy ID DOUBLE-BLIND; ARTHRITIS; PREVALENCE; TRIAL AB NSAIDs are the current mainstay of treatment for gout flares, despite being associated with an increased risk of gastrointestinal bleeding and cardiovascular events. Janssens et al. conducted a randomized, double-blind, equivalence clinical trial to determine whether the glucocorticoid prednisolone can be used as an alternative to NSAIDs in this setting. Patients referred from primary care community clinics with monosodium urate crystal-proven acute gout flares (n=120) underwent treatment with once-daily oral prednisolone 35 mg or twice-daily oral naproxen 500 mg for 5 days. The results revealed a nonsignificant difference between the two groups, both in the primary outcome measure of pain reduction and in the secondary outcomes of disability related to the affected joint and walking, suggesting equivalence between the two agents. This study helps to position oral glucocorticoids as effective and safe alternatives in the management of acute gout flares. Future studies should address the treatment of acute gout in elderly populations and in those with multiple comorbidities. C1 [Saag, Kenneth G.] Univ Alabama, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Gaffo, Angelo L.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Saag, KG (reprint author), Univ Alabama, Div Clin Immunol & Rheumatol, 820 Fac Off Tower 1530 3rd Ave, Birmingham, AL 35294 USA. EM ksaag@uab.edu NR 6 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1745-8382 J9 NAT CLIN PRACT RHEUM JI Nat. Clin. Pract. Rheumatol. PD JAN PY 2009 VL 5 IS 1 BP 12 EP 13 DI 10.1038/ncprheum0962 PG 2 WC Rheumatology; Social Issues SC Rheumatology; Social Issues GA 387GN UT WOS:000261939800005 PM 19048008 ER PT J AU Willer, CJ Speliotes, EK Loos, RJF Li, SX Lindgren, CM Heid, IM Berndt, SI Elliott, AL Jackson, AU Lamina, C Lettre, G Lim, N Lyon, HN McCarroll, SA Papadakis, K Qi, L Randall, JC Roccasecca, RM Sanna, S Scheet, P Weedon, MN Wheeler, E Zhao, JH Jacobs, LC Prokopenko, I Soranzo, N Tanaka, T Timpson, NJ Almgren, P Bennett, A Bergman, RN Bingham, SA Bonnycastle, LL Brown, M Burtt, NLP Chines, P Coin, L Collins, FS Connell, JM Cooper, C Smith, GD Dennison, EM Deodhar, P Elliott, P Erdos, MR Estrada, K Evans, DM Gianniny, L Gieger, C Gillson, CJ Guiducci, C Hackett, R Hadley, D Hall, AS Havulinna, AS Hebebrand, J Hofman, A Isomaa, B Jacobs, KB Johnson, T Jousilahti, P Jovanovic, Z Khaw, KT Kraft, P Kuokkanen, M Kuusisto, J Laitinen, J Lakatta, EG Luan, J Luben, RN Mangino, M McArdle, WL Meitinger, T Mulas, A Munroe, PB Narisu, N Ness, AR Northstone, K O'Rahilly, S Purmann, C Rees, MG Ridderstraale, M Ring, SM Rivadeneira, F Ruokonen, A Sandhu, MS Saramies, J Scott, LJ Scuteri, A Silander, K Sims, MA Song, K Stephens, J Stevens, S Stringham, HM Tung, YCL Valle, TT Van Duijn, CM Vimaleswaran, KS Vollenweider, P Waeber, G Wallace, C Watanabe, RM Waterworth, DM Watkins, N Witteman, JCM Zeggini, E Zhai, GJ Zillikens, MC Altshuler, D Caulfield, MJ Chanock, SJ Farooqi, IS Ferrucci, L Guralnik, JM Hattersley, AT Hu, FB Jarvelin, MR Laakso, M Mooser, V Ong, KK Ouwehand, WH Salomaa, V Samani, NJ Spector, TD Tuomi, T Tuomilehto, J Uda, M Uitterlinden, AG Wareham, NJ Deloukas, P Frayling, TM Groop, LC Hayes, RB Hunter, DJ Mohlke, KL Peltonen, L Schlessinger, D Strachan, DP Wichmann, HE McCarthy, MI Boehnke, M Barroso, I Abecasis, GR Hirschhorn, JN AF Willer, Cristen J. Speliotes, Elizabeth K. Loos, Ruth J. F. Li, Shengxu Lindgren, Cecilia M. Heid, Iris M. Berndt, Sonja I. Elliott, Amanda L. Jackson, Anne U. Lamina, Claudia Lettre, Guillaume Lim, Noha Lyon, Helen N. McCarroll, Steven A. Papadakis, Konstantinos Qi, Lu Randall, Joshua C. Roccasecca, Rosa Maria Sanna, Serena Scheet, Paul Weedon, Michael N. Wheeler, Eleanor Zhao, Jing Hua Jacobs, Leonie C. Prokopenko, Inga Soranzo, Nicole Tanaka, Toshiko Timpson, Nicholas J. Almgren, Peter Bennett, Amanda Bergman, Richard N. Bingham, Sheila A. Bonnycastle, Lori L. Brown, Morris Burtt, Noel L. P. Chines, Peter Coin, Lachlan Collins, Francis S. Connell, John M. Cooper, Cyrus Smith, George Davey Dennison, Elaine M. Deodhar, Parimal Elliott, Paul Erdos, Michael R. Estrada, Karol Evans, David M. Gianniny, Lauren Gieger, Christian Gillson, Christopher J. Guiducci, Candace Hackett, Rachel Hadley, David Hall, Alistair S. Havulinna, Aki S. Hebebrand, Johannes Hofman, Albert Isomaa, Bo Jacobs, Kevin B. Johnson, Toby Jousilahti, Pekka Jovanovic, Zorica Khaw, Kay-Tee Kraft, Peter Kuokkanen, Mikko Kuusisto, Johanna Laitinen, Jaana Lakatta, Edward G. Luan, Jian'an Luben, Robert N. Mangino, Massimo McArdle, Wendy L. Meitinger, Thomas Mulas, Antonella Munroe, Patricia B. Narisu, Narisu Ness, Andrew R. Northstone, Kate O'Rahilly, Stephen Purmann, Carolin Rees, Matthew G. Ridderstrale, Martin Ring, Susan M. Rivadeneira, Fernando Ruokonen, Aimo Sandhu, Manjinder S. Saramies, Jouko Scott, Laura J. Scuteri, Angelo Silander, Kaisa Sims, Matthew A. Song, Kijoung Stephens, Jonathan Stevens, Suzanne Stringham, Heather M. Tung, Y. C. Loraine Valle, Timo T. Van Duijn, Cornelia M. Vimaleswaran, Karani S. Vollenweider, Peter Waeber, Gerard Wallace, Chris Watanabe, Richard M. Waterworth, Dawn M. Watkins, Nicholas Witteman, Jacqueline C. M. Zeggini, Eleftheria Zhai, Guangju Zillikens, M. Carola Altshuler, David Caulfield, Mark J. Chanock, Stephen J. Farooqi, I. Sadaf Ferrucci, Luigi Guralnik, Jack M. Hattersley, Andrew T. Hu, Frank B. Jarvelin, Marjo-Riitta Laakso, Markku Mooser, Vincent Ong, Ken K. Ouwehand, Willem H. Salomaa, Veikko Samani, Nilesh J. Spector, Timothy D. Tuomi, Tiinamaija Tuomilehto, Jaakko Uda, Manuela Uitterlinden, Andre G. Wareham, Nicholas J. Deloukas, Panagiotis Frayling, Timothy M. Groop, Leif C. Hayes, Richard B. Hunter, David J. Mohlke, Karen L. Peltonen, Leena Schlessinger, David Strachan, David P. Wichmann, H-Erich McCarthy, Mark I. Boehnke, Michael Barroso, Ines Abecasis, Goncalo R. Hirschhorn, Joel N. CA Wellcome Trust Case Control Giant Consortium TI Six new loci associated with body mass index highlight a neuronal influence on body weight regulation SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; FTO GENE; ALCOHOL DEPENDENCE; COMMON VARIANTS; NEURITE OUTGROWTH; CHILDHOOD OBESITY; ADULT OBESITY; EXPRESSION; MICE AB Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity. C1 [Speliotes, Elizabeth K.; Lyon, Helen N.; Hirschhorn, Joel N.] Harvard & Massachusetts Inst Technol, Broad Inst, Metabol Initiat, Cambridge, MA 02142 USA. [Speliotes, Elizabeth K.; Lyon, Helen N.; Hirschhorn, Joel N.] Harvard & Massachusetts Inst Technol, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Speliotes, Elizabeth K.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Willer, Cristen J.; Jackson, Anne U.; Scott, Laura J.; Stringham, Heather M.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Loos, Ruth J. F.; Li, Shengxu; Zhao, Jing Hua; Gillson, Christopher J.; Luan, Jian'an; Sandhu, Manjinder S.; Sims, Matthew A.; Vimaleswaran, Karani S.; Wareham, Nicholas J.] Addenbrookes Hosp, MRC, Epidemiol Unit, Cambridge CB2 0QQ, England. [Loos, Ruth J. F.; Li, Shengxu; Zhao, Jing Hua; Gillson, Christopher J.; Jovanovic, Zorica; Luan, Jian'an; Purmann, Carolin; Sims, Matthew A.; Farooqi, I. Sadaf; Ong, Ken K.; Wareham, Nicholas J.] Addenbrookes Hosp, Inst Metab Sci, Cambridge CB2 0QQ, England. [Lindgren, Cecilia M.; Randall, Joshua C.; Prokopenko, Inga; Zeggini, Eleftheria; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Heid, Iris M.; Gieger, Christian; Wichmann, H-Erich] Helmholtz Zentrum Munchen, Inst Epidemiol, D-85764 Neuherberg, Germany. [Berndt, Sonja I.; Chanock, Stephen J.; Hayes, Richard B.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Lettre, Guillaume; McCarroll, Steven A.; Bennett, Amanda; Burtt, Noel L. P.; Kuokkanen, Mikko; Hunter, David J.; Peltonen, Leena] MIT & Harvard, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Elliott, Amanda L.; McCarroll, Steven A.; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Lettre, Guillaume; Lyon, Helen N.; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Lettre, Guillaume; Lyon, Helen N.; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Lettre, Guillaume; Lyon, Helen N.; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Papadakis, Konstantinos; Hadley, David; Strachan, David P.] Univ London, Div Commun Hlth Sci, London SW17 0RE, England. [Qi, Lu; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Qi, Lu; Hu, Frank B.; Hunter, David J.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Roccasecca, Rosa Maria; Wheeler, Eleanor; Ouwehand, Willem H.; Deloukas, Panagiotis; Peltonen, Leena; Barroso, Ines] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Sanna, Serena; Uda, Manuela] CNR, Inst Neurogenet & Neurofarmacol, I-09042 Cagaliai, Italy. [Scheet, Paul; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Weedon, Michael N.; Frayling, Timothy M.] Peninsula Med Sch, Exeter EX1 2LU, Devon, England. [Jacobs, Leonie C.; Zillikens, M. Carola; Uitterlinden, Andre G.] Eramus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Prokopenko, Inga; McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England. [Soranzo, Nicole; Zhai, Guangju; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21225 USA. [Timpson, Nicholas J.; Smith, George Davey; Evans, David M.] Univ Bristol, Dept Social Med, Ctr Causal Analyses Translat Epidemiol, MRC, Bristol BS8 2PR, Avon, England. [Almgren, Peter; Groop, Leif C.] Lund Univ, Dept Clin Sci, Ctr Diabet, Malmo 20502, Sweden. [Bennett, Amanda] Churchill Hosp, OCDEM, DRL, Oxford OX3 7LJ, England. [Bergman, Richard N.] Univ So Calif, Sch Med, Los Angeles, CA 90033 USA. [Bingham, Sheila A.] MRC, Dunn Human Nutr Unit, Cambridge CB2 0XY, England. [Bingham, Sheila A.] MRC, Ctr Nutr Epidemiol Canc Prevent & Survival, Cambridge CB1 8RN, England. [Bonnycastle, Lori L.; Chines, Peter; Collins, Francis S.; Deodhar, Parimal; Erdos, Michael R.; Rees, Matthew G.] NHGRI, Bethesda, MD 20892 USA. [Brown, Morris] Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge CB2 0QQ, England. [Coin, Lachlan; Elliott, Paul; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England. [Connell, John M.] Univ Glasgow, Fac Med, Glasgow Cardiovasc Res Ctr, British Heart Fdn, Glasgow G12 8TA, Lanark, Scotland. [Cooper, Cyrus; Dennison, Elaine M.] Univ Southampton, Southampton Gen Hosp, Epidemiol Resource Ctr, MRC, Southampton SO16 6YD, Hants, England. [Hall, Alistair S.] Leeds Gen Infirm, Yorkshire Heart Ctr, Leeds LS1 3EX, W Yorkshire, England. [Havulinna, Aki S.; Jousilahti, Pekka; Salomaa, Veikko] Natl Publ Hlth Inst, KTL, FI-00300 Helsinki, Finland. [Hebebrand, Johannes] Univ Duisburg Essen, Dept Child & Adolescent Psychiat, D-45147 Essen, Germany. [Hofman, Albert; Van Duijn, Cornelia M.; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Isomaa, Bo] Malmska Municipal Hlth Ctr & Hosp, Folkhalsan Res Ctr, FIN-00014 Helsinki, Finland. [Jacobs, Kevin B.] Bioinformed Consulting Serv, Gaithersburg, MD 20877 USA. [Johnson, Toby] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland. [Johnson, Toby] CHU Vaudois, Univ Inst Social & Preventat Med, CH-1005 Lausanne, Switzerland. [Johnson, Toby] Swiss Inst Bioinformat, CH-1005 Lausanne, Switzerland. [Jovanovic, Zorica; O'Rahilly, Stephen; Purmann, Carolin; Tung, Y. C. Loraine] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Cambridge CB2 0QQ, England. [Khaw, Kay-Tee; Luben, Robert N.; Sandhu, Manjinder S.; Farooqi, I. Sadaf] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge CB2 0SR, England. [Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Silander, Kaisa] Natl Publ Hlth Inst, Dept Mol Med, FIN-00300 Helsinki, Finland. [Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Laitinen, Jaana] Finnish Inst Occupat Hlth, FIN-90220 Oulu, Finland. [Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Mangino, Massimo; Stevens, Suzanne; Samani, Nilesh J.] Univ Leicester, Glenfield Gen Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England. [McArdle, Wendy L.; Northstone, Kate; Ring, Susan M.] Univ Bristol, Dept Social Med, ALSPAC, Bristol BS8 1TQ, Avon, England. [Meitinger, Thomas] Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany. [Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, D-81765 Munich, Germany. [Munroe, Patricia B.; Wallace, Chris; Caulfield, Mark J.; McCarthy, Mark I.] Barts & London Queen Marys Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England. [Ness, Andrew R.] Univ Bristol, Dept Oral & Dent Sci, Bristol BS1 2LY, Avon, England. [Ruokonen, Aimo] Univ Oulu, Dept Clin Chem, FIN-90220 Oulu, Finland. [Saramies, Jouko] Savitaipale Hlth Ctr, FIN-54800 Savitaipale, Finland. [Scuteri, Angelo] Ist Nazl Ricovero & Cura Anziani, Unita Operat Geriatria, I-00189 Rome, Italy. [Stephens, Jonathan; Watkins, Nicholas] Univ Cambridge, Dept Haematol, NHS Blood & Transplant, Cambridge CB2 2PR, England. [Valle, Timo T.] Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, FIN-00300 Helsinki, Finland. [Vollenweider, Peter] BH 10 Ctr Hosp Univ Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Div Biostat, Dept Prevent Med, Los Angeles, CA 90089 USA. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Gerontol Res Ctr, Bethesda, MD 20892 USA. [Hattersley, Andrew T.] Peninsula Med Sch, Exeter EX5 2DW, Devon, England. [Groop, Leif C.] Univ Helsinki, Cent Hosp, Dept Med, FIN-00290 Helsinki, Finland. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Peltonen, Leena] Univ Helsinki, Inst Mol Med, FIN-00014 Helsinki, Finland. [Schlessinger, David] NIA, US Natl Inst Hlth Biomed Res Ctr, Genet Lab, Baltimore, MD 21224 USA. [Wichmann, H-Erich] Univ Munich, Inst Med Informat Proc Biometry & Epidemiol, D-81377 Munich, Germany. [McCarthy, Mark I.] Univ Oxford, Oxford Biomed Res Ctr, Natl Inst Hlth Res, Oxford OX3 7LJ, England. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Hirschhorn, JN (reprint author), Harvard & Massachusetts Inst Technol, Broad Inst, Metabol Initiat, Cambridge, MA 02142 USA. EM mark.mccarthy@drl.ox.ac.uk; boehnke@umich.edu; ib1@sanger.ac.uk; goncalo@umich.edu; joelh@broad.mit.edu RI Evans, David/H-6325-2013; Colaus, PsyColaus/K-6607-2013; Ness, Andy/M-7612-2013; Meitinger, Thomas/O-1318-2015; Rivadeneira, Fernando/O-5385-2015; Prokopenko, Inga/H-3241-2014; mangino, massimo/F-5134-2011; Kuokkanen, Mikko/M-8247-2016; Coin, Lachlan/A-9001-2014; Davey Smith, George/A-7407-2013; Northstone, Kate/A-8165-2011; Li, Shengxu/D-8915-2012; Spector, Tim/F-6533-2012; McCarroll, Steven/A-8433-2009; Abecasis, Goncalo/B-7840-2010; Altshuler, David/A-4476-2009; Ridderstrale, Martin/F-7678-2012; Elliott, Amanda/G-5120-2012; Lamina, Claudia/F-7608-2010; Hadley, David/I-6902-2012; Deloukas, Panos/B-2922-2013; OI Ness, Andy/0000-0003-3548-9523; Rivadeneira, Fernando/0000-0001-9435-9441; Prokopenko, Inga/0000-0003-1624-7457; mangino, massimo/0000-0002-2167-7470; Kuokkanen, Mikko/0000-0003-4375-9327; Coin, Lachlan/0000-0002-4300-455X; Davey Smith, George/0000-0002-1407-8314; Mulas, Antonella/0000-0002-6856-1483; Karani, Vimal/0000-0002-8485-8930; Northstone, Kate/0000-0002-0602-1983; Altshuler, David/0000-0002-7250-4107; Deloukas, Panos/0000-0001-9251-070X; Zeggini, Eleftheria/0000-0003-4238-659X; Soranzo, Nicole/0000-0003-1095-3852; Willer, Cristen/0000-0001-5645-4966; sanna, serena/0000-0002-3768-1749; Johnson, Toby/0000-0002-5998-3270; Monsalve, Beatriz Elena/0000-0002-5994-866X; Brown, Matthew A/0000-0003-0538-8211; Abecasis, Goncalo/0000-0003-1509-1825; Luben, Robert/0000-0002-5088-6343; Gieger, Christian/0000-0001-6986-9554; Hayes, Richard/0000-0002-0918-661X; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Farooqi, Sadaf/0000-0001-7609-3504; Tuomi, Tiinamaija/0000-0002-8306-6202; Wallace, Chris/0000-0001-9755-1703; Evans, David/0000-0003-0663-4621; Timpson, Nicholas/0000-0002-7141-9189 FU British Heart Foundation [FS/05/061/19501]; Intramural NIH HHS; Medical Research Council [G0000649, G0000934, G0400874, G0401527, G0600705, G0601261, G0701863, G0800582, G9521010, G9815508, G9824984, MC_U105630924, MC_U106179471, MC_U106179472, MC_U106188470, MC_U147585819, MC_UP_A620_1014, U.1475.00.003.00010.02 (85819)]; NCI NIH HHS [5UO1CA098233, CA49449, CA50385, CA65725, CA67262, CA87969, P01 CA087969, R01 CA049449, R01 CA050385, R01 CA065725, R01 CA067262, U01 CA049449, U01 CA067262, U01 CA098233]; NHGRI NIH HHS [01-HG-65403, 1Z01 HG000024, HG02651, N01HG65403, R01 HG002651, Z01 HG000024]; NHLBI NIH HHS [HL084729, HL087679, R01 HL087679, U01 HL084729]; NIA NIH HHS [N01-AG-1-2109]; NIDDK NIH HHS [K23 DK080145-01, DK062370, DK072193, DK075787, F32 DK079466, F32 DK079466-01, K23 DK067288, K23 DK080145, R01 DK029867, R01 DK062370, R01 DK072193, R01 DK075787, R56 DK062370, T32 DK007191, T32DK07191, U01 DK062370]; NIMH NIH HHS [1RL1MH083268, RL1 MH083268]; Wellcome Trust [068545/Z/02, 076113, 076467/Z/05/Z, 077011, 077016, 079557, 082390, 089061, 090532] NR 49 TC 936 Z9 964 U1 15 U2 137 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2009 VL 41 IS 1 BP 25 EP 34 DI 10.1038/ng.287 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 389IE UT WOS:000262085300013 PM 19079261 ER PT J AU Sabatti, C Service, SK Hartikainen, AL Pouta, A Ripatti, S Brodsky, J Jones, CG Zaitlen, NA Varilo, T Kaakinen, M Sovio, U Ruokonen, A Laitinen, J Jakkula, E Coin, L Hoggart, C Collins, A Turunen, H Gabriel, S Elliot, P McCarthy, MI Daly, MJ Jarvelin, MR Freimer, NB Peltonen, L AF Sabatti, Chiara Service, Susan K. Hartikainen, Anna-Liisa Pouta, Anneli Ripatti, Samuli Brodsky, Jae Jones, Chris G. Zaitlen, Noah A. Varilo, Teppo Kaakinen, Marika Sovio, Ulla Ruokonen, Aimo Laitinen, Jaana Jakkula, Eveliina Coin, Lachlan Hoggart, Clive Collins, Andrew Turunen, Hannu Gabriel, Stacey Elliot, Paul McCarthy, Mark I. Daly, Mark J. Jarvelin, Marjo-Riitta Freimer, Nelson B. Peltonen, Leena TI Genome-wide association analysis of metabolic traits in a birth cohort from a founder population SO NATURE GENETICS LA English DT Article ID CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN; BODY-MASS INDEX; NORTHERN FINLAND; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; LINKAGE DISEQUILIBRIUM; LIPID CONCENTRATIONS; QUANTITATIVE TRAITS; COMMON DISEASES AB Genome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protein, body mass index, and systolic and diastolic blood pressure) in the Northern Finland Birth Cohort 1966 (NFBC1966), drawn from the most genetically isolated Finnish regions. We replicate most previously reported associations for these traits and identify nine new associations, several of which highlight genes with metabolic functions: high-density lipoprotein with NR1H3 (LXRA), low-density lipoprotein with AR and FADS1-FADS2, glucose with MTNR1B, and insulin with PANK1. Two of these new associations emerged after adjustment of results for body mass index. Gene-environment interaction analyses suggested additional associations, which will require validation in larger samples. The currently identified loci, together with quantified environmental exposures, explain little of the trait variation in NFBC1966. The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci. C1 [Service, Susan K.; Jones, Chris G.; Freimer, Nelson B.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA. [Sabatti, Chiara] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA. [Sabatti, Chiara; Brodsky, Jae] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA 90095 USA. [Hartikainen, Anna-Liisa] Univ Oulu, Dept Obstet & Gynaecol, FIN-90220 Oulu, Finland. [Pouta, Anneli; Jarvelin, Marjo-Riitta] Natl Publ Hlth Inst, Dept Child & Adolescent Hlth, FIN-90101 Oulu, Finland. [Ripatti, Samuli; Jakkula, Eveliina; Turunen, Hannu; Peltonen, Leena] Univ Helsinki, Inst Mol Med FIMM, FIN-00014 Helsinki, Finland. [Jones, Chris G.; Zaitlen, Noah A.] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90095 USA. [Varilo, Teppo] Univ Helsinki, Dept Med Genet, Helsinki, Finland. [Varilo, Teppo] Natl Publ Hlth Inst, Biomedicum Helsinki, Dept Mol Med, Helsinki 00290, Finland. [Kaakinen, Marika] Inst Hlth Sci, FIN-90220 Oulu, Finland. [Coin, Lachlan; Hoggart, Clive; Elliot, Paul; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England. [Ruokonen, Aimo] Univ Oulu, Dept Clin Chem, FIN-90220 Oulu, Finland. [Laitinen, Jaana] Finnish Inst Occupat Hlth, FIN-90220 Oulu, Finland. [Collins, Andrew] Univ Southampton, Southampton Gen Hosp, Human Genet Res Div, Southampton SO16 6YA, Hants, England. [Gabriel, Stacey; Daly, Mark J.; Peltonen, Leena] Harvard & MIT, Broad Inst, Cambridge, MA 02142 USA. [McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England. [McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [McCarthy, Mark I.; Daly, Mark J.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Daly, Mark J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Daly, Mark J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Daly, Mark J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, FIN-90014 Oulu, Finland. [Freimer, Nelson B.] Univ Calif Los Angeles, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Freimer, Nelson B.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA. [Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England. RP Freimer, NB (reprint author), Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA. EM nfreimer@mednet.ucla.edu; leena@sanger.ac.uk RI Coin, Lachlan/A-9001-2014; Collins, Andrew/A-6595-2010; Ripatti, Samuli/H-9446-2014 OI Coin, Lachlan/0000-0002-4300-455X; Kaakinen, Marika/0000-0002-9228-0462; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Varilo, Teppo/0000-0002-5839-8854; Collins, Andrew/0000-0001-7108-0771; Ripatti, Samuli/0000-0002-0504-1202 FU NCRR NIH HHS [U54 RR020278]; NHGRI NIH HHS [T32 HG002536]; NHLBI NIH HHS [R01 HL087679]; NIGMS NIH HHS [GM053275-14, R01 GM053275]; NIMH NIH HHS [MH083268, RL1 MH083268]; Wellcome Trust [089061] NR 50 TC 400 Z9 408 U1 4 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2009 VL 41 IS 1 BP 35 EP 46 DI 10.1038/ng.271 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 389IE UT WOS:000262085300014 PM 19060910 ER PT J AU Kathiresan, S Willer, CJ Peloso, GM Demissie, S Musunuru, K Schadt, EE Kaplan, L Bennett, D Li, Y Tanaka, T Voight, BF Bonnycastle, LL Jackson, AU Crawford, G Surti, A Guiducci, C Burtt, NP Parish, S Clarke, R Zelenika, D Kubalanza, KA Morken, MA Scott, LJ Stringham, HM Galan, P Swift, AJ Kuusisto, J Bergman, RN Sundvall, J Laakso, M Ferrucci, L Scheet, P Sanna, S Uda, M Yang, Q Lunetta, KL Dupuis, J de Bakker, PIW O'Donnell, CJ Chambers, JC Kooner, JS Hercberg, S Meneton, P Lakatta, EG Scuteri, A Schlessinger, D Tuomilehto, J Collins, FS Groop, L Altshuler, D Collins, R Lathrop, GM Melander, O Salomaa, V Peltonen, L Orho-Melander, M Ordovas, JM Boehnke, M Abecasis, GR Mohlke, KL Cupples, LA AF Kathiresan, Sekar Willer, Cristen J. Peloso, Gina M. Demissie, Serkalem Musunuru, Kiran Schadt, Eric E. Kaplan, Lee Bennett, Derrick Li, Yun Tanaka, Toshiko Voight, Benjamin F. Bonnycastle, Lori L. Jackson, Anne U. Crawford, Gabriel Surti, Aarti Guiducci, Candace Burtt, Noel P. Parish, Sarah Clarke, Robert Zelenika, Diana Kubalanza, Kari A. Morken, Mario A. Scott, Laura J. Stringham, Heather M. Galan, Pilar Swift, Amy J. Kuusisto, Johanna Bergman, Richard N. Sundvall, Jouko Laakso, Markku Ferrucci, Luigi Scheet, Paul Sanna, Serena Uda, Manuela Yang, Qiong Lunetta, Kathryn L. Dupuis, Josee de Bakker, Paul I. W. O'Donnell, Christopher J. Chambers, John C. Kooner, Jaspal S. Hercberg, Serge Meneton, Pierre Lakatta, Edward G. Scuteri, Angelo Schlessinger, David Tuomilehto, Jaakko Collins, Francis S. Groop, Leif Altshuler, David Collins, Rory Lathrop, G. Mark Melander, Olle Salomaa, Veikko Peltonen, Leena Orho-Melander, Marju Ordovas, Jose M. Boehnke, Michael Abecasis, Goncalo R. Mohlke, Karen L. Cupples, L. Adrienne TI Common variants at 30 loci contribute to polygenic dyslipidemia SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; HIGH-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; HEPATOCYTE NUCLEAR FACTOR-1-ALPHA; PHOSPHOLIPID TRANSFER PROTEIN; HEART-DISEASE; LDL-CHOLESTEROL; GENE-EXPRESSION; PLASMA-LIPIDS; RECEPTOR AB Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P < 5 x 10(-8)), including 11 loci that reached genome-wide significance for the first time. The 11 newly defined loci include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1L2, FADS1-FADS2-FADS3 and PLTP. The proportion of individuals exceeding clinical cut points for high LDL cholesterol, low HDL cholesterol and high triglycerides varied according to an allelic dosage score (P < 10(-15) for each trend). These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia. C1 [Kathiresan, Sekar; Musunuru, Kiran] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar; Musunuru, Kiran] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kathiresan, Sekar; Musunuru, Kiran; Voight, Benjamin F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar; Voight, Benjamin F.; Crawford, Gabriel; Surti, Aarti; Guiducci, Candace; Burtt, Noel P.; Altshuler, David; Peltonen, Leena] Harvard & Massachusetts Inst, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Kathiresan, Sekar; Peloso, Gina M.; Demissie, Serkalem; Yang, Qiong; Lunetta, Kathryn L.; Dupuis, Josee; O'Donnell, Christopher J.; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Kathiresan, Sekar; Peloso, Gina M.; Demissie, Serkalem; Yang, Qiong; Lunetta, Kathryn L.; Dupuis, Josee; O'Donnell, Christopher J.; Cupples, L. Adrienne] Boston Univ, Framingham, MA 01702 USA. [Kathiresan, Sekar; Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Willer, Cristen J.; Li, Yun; Jackson, Anne U.; Scott, Laura J.; Stringham, Heather M.; Scheet, Paul; Peltonen, Leena; Boehnke, Michael; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Bonnycastle, Lori L.; Kubalanza, Kari A.; Morken, Mario A.; Swift, Amy J.; Collins, Francis S.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Schadt, Eric E.] Merck & Co Inc, Rosetta Inpharmat LLC, Seattle, WA 98109 USA. [Kaplan, Lee] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. [Bennett, Derrick; Parish, Sarah; Clarke, Robert; Collins, Rory] Univ Oxford, Clin Trial Serv Unit, Oxford OX3 7LF, England. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Baltimore, MD 21225 USA. [Voight, Benjamin F.; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Kubalanza, Kari A.; Morken, Mario A.; Swift, Amy J.; Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA. [Zelenika, Diana; Lathrop, G. Mark] Inst Genom Commissariat Energie Atom, Ctr Natl Genotypage, F-91057 Evry, France. [Galan, Pilar; Hercberg, Serge] Paris 13 SMBH, CNAM, INRA, INSERM,U557,U1125, Bobigny, France. [Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Bergman, Richard N.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [Sundvall, Jouko; Tuomilehto, Jaakko] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Diabet Unit, SF-00300 Helsinki, Finland. [Sanna, Serena; Uda, Manuela] CNR, Ist Neurogenet & Neurofarmacol, I-08045 Cagliari, Italy. [de Bakker, Paul I. W.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [O'Donnell, Christopher J.] Natl Lung & Blood Inst, NIH, Framingham, MA 01702 USA. [Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England. [Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Hammersmith Hosp, London W12 0NN, England. [Meneton, Pierre] Ctr Rech Cordeliers, INSERM, U872, F-75270 Paris 06, France. [Lakatta, Edward G.] NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. [Scuteri, Angelo] Ist Nazl Ricovero & Cura Anziani, Unita Operat Geriatria, I-00189 Rome, Italy. [Schlessinger, David] NIA, Genet Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Groop, Leif; Orho-Melander, Marju] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, S-20502 Malmo, Sweden. [Groop, Leif] Helsinki Univ Hosp, Dept Med, Helsinki 00029, Finland. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Melander, Olle] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Hypertens & Cardiovasc Dis, S-20502 Malmo, Sweden. [Peltonen, Leena] Univ Helsinki, Inst Mol Med, Helsinki 00029, Finland. [Salomaa, Veikko] Natl Publ Hlth Inst, Chron Dis Epidemiol Unit, Dept Hlth Promot & Chron Dis Prevent, SF-00300 Helsinki, Finland. [Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Ordovas, Jose M.] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Nutr & Genom Lab, Boston, MA 02111 USA. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM skathiresan@partners.org; goncalo@umich.edu; mohlke@med.unc.edu; adrienne@bu.edu RI Abecasis, Goncalo/B-7840-2010; Altshuler, David/A-4476-2009; Voight, Benjamin/F-1775-2011; de Bakker, Paul/B-8730-2009; Yang, Qiong/G-5438-2014 OI Lunetta, Kathryn/0000-0002-9268-810X; Willer, Cristen/0000-0001-5645-4966; sanna, serena/0000-0002-3768-1749; Cupples, L. Adrienne/0000-0003-0273-7965; Abecasis, Goncalo/0000-0003-1509-1825; Dupuis, Josee/0000-0003-2871-3603; Ordovas, Jose/0000-0002-7581-5680; Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858; FU British Heart Foundation; Cancer Research UK; Department of Health; Intramural NIH HHS; Medical Research Council [, MC_U137686857]; NHGRI NIH HHS [HG02651, N01HG65403, R01 HG002651, Z01 HG000024]; NHLBI NIH HHS [HL-54776, HL084729, K23 HL083102, K23 HL083102-03, N01-HC-25195, N01HC25195, R01 HL054776, U01 HL084729]; NIDDK NIH HHS [DK062370, DK072193, P30 DK040561, P30 DK040561-13, R01 DK029867, R01 DK062370, R01 DK072193, R01 DK075030, R56 DK062370, U01 DK062370]; PHS HHS [53-K06-5-10]; Wellcome Trust [089061] NR 50 TC 748 Z9 762 U1 3 U2 53 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2009 VL 41 IS 1 BP 56 EP 65 DI 10.1038/ng.291 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 389IE UT WOS:000262085300016 PM 19060906 ER PT J AU Prokopenko, I Langenberg, C Florez, JC Saxena, R Soranzo, N Thorleifsson, G Loos, RJF Manning, AK Jackson, AU Aulchenko, Y Potter, SC Erdos, MR Sanna, S Hottenga, JJ Wheeler, E Kaakinen, M Lyssenko, V Chen, WM Ahmadi, K Beckmann, JS Bergman, RN Bochud, M Bonnycastle, LL Buchanan, TA Cao, A Cervino, A Coin, L Collins, FS Crisponi, L De Geus, EJC Dehghan, A Deloukas, P Doney, ASF Elliott, P Freimer, N Gateva, V Herder, C Hofman, A Hughes, TE Hunt, S Illig, T Inouye, M Isomaa, B Johnson, T Kong, A Krestyaninova, M Kuusisto, J Laakso, M Lim, N Lindblad, U Lindgren, CM McCann, OT Mohlke, KL Morris, AD Naitza, S Orru, M Palmer, CNA Pouta, A Randall, J Rathmann, W Saramies, J Scheet, P Scott, LJ Scuteri, A Sharp, S Sijbrands, E Smit, JH Song, K Steinthorsdottir, V Stringham, HM Tuomi, T Tuomilehto, J Uitterlinden, AG Voight, BF Waterworth, D Wichmann, HE Willemsen, G Witteman, JCM Yuan, X Zhao, JH Zeggini, E Schlessinger, D Sandhu, M Boomsma, DI Uda, M Spector, TD Penninx, BWJH Altshuler, D Vollenweider, P Jarvelin, MR Lakatta, E Waeber, G Fox, CS Peltonen, L Groop, LC Mooser, V Cupples, LA Thorsteinsdottir, U Boehnke, M Barroso, IS Van Duijn, C Dupuis, J Watanabe, RM Stefansson, K McCarthy, MI Wareham, NJ Meigs, JB Abecasis, GR AF Prokopenko, Inga Langenberg, Claudia Florez, Jose C. Saxena, Richa Soranzo, Nicole Thorleifsson, Gudmar Loos, Ruth J. F. Manning, Alisa K. Jackson, Anne U. Aulchenko, Yurii Potter, Simon C. Erdos, Michael R. Sanna, Serena Hottenga, Jouke-Jan Wheeler, Eleanor Kaakinen, Marika Lyssenko, Valeriya Chen, Wei-Min Ahmadi, Kourosh Beckmann, Jacques S. Bergman, Richard N. Bochud, Murielle Bonnycastle, Lori L. Buchanan, Thomas A. Cao, Antonio Cervino, Alessandra Coin, Lachlan Collins, Francis S. Crisponi, Laura De Geus, Eco J. C. Dehghan, Abbas Deloukas, Panos Doney, Alex S. F. Elliott, Paul Freimer, Nelson Gateva, Vesela Herder, Christian Hofman, Albert Hughes, Thomas E. Hunt, Sarah Illig, Thomas Inouye, Michael Isomaa, Bo Johnson, Toby Kong, Augustine Krestyaninova, Maria Kuusisto, Johanna Laakso, Markku Lim, Noha Lindblad, Ulf Lindgren, Cecilia M. McCann, Owen T. Mohlke, Karen L. Morris, Andrew D. Naitza, Silvia Orru, Marco Palmer, Colin N. A. Pouta, Anneli Randall, Joshua Rathmann, Wolfgang Saramies, Jouko Scheet, Paul Scott, Laura J. Scuteri, Angelo Sharp, Stephen Sijbrands, Eric Smit, Jan H. Song, Kijoung Steinthorsdottir, Valgerdur Stringham, Heather M. Tuomi, Tiinamaija Tuomilehto, Jaakko Uitterlinden, Andre G. Voight, Benjamin F. Waterworth, Dawn Wichmann, H-Erich Willemsen, Gonneke Witteman, Jacqueline C. M. Yuan, Xin Zhao, Jing Hua Zeggini, Eleftheria Schlessinger, David Sandhu, Manjinder Boomsma, Dorret I. Uda, Manuela Spector, Tim D. Penninx, Brenda W. J. H. Altshuler, David Vollenweider, Peter Jarvelin, Marjo Riitta Lakatta, Edward Waeber, Gerard Fox, Caroline S. Peltonen, Leena Groop, Leif C. Mooser, Vincent Cupples, L. Adrienne Thorsteinsdottir, Unnur Boehnke, Michael Barroso, Ines Van Duijn, Cornelia Dupuis, Josee Watanabe, Richard M. Stefansson, Kari McCarthy, Mark I. Wareham, Nicholas J. Meigs, James B. Abecasis, Goncalo R. TI Variants in MTNR1B influence fasting glucose levels SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; BETA-CELL FUNCTION; GENE-EXPRESSION; PLASMA-GLUCOSE; RISK LOCI; MELATONIN; TRIGLYCERIDE; REPLICATION; HAPLOTYPE; IMPACT AB To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci. C1 [Jackson, Anne U.; Gateva, Vesela; Scheet, Paul; Scott, Laura J.; Stringham, Heather M.; Boehnke, Michael; Abecasis, Goncalo R.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Prokopenko, Inga; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England. [Prokopenko, Inga; Lindgren, Cecilia M.; Randall, Joshua; Zeggini, Eleftheria; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Langenberg, Claudia; Loos, Ruth J. F.; Sharp, Stephen; Waterworth, Dawn; Zhao, Jing Hua; Sandhu, Manjinder; Wareham, Nicholas J.] Addenbrookes Hosp, Epidemiol Unit, MRC, Cambridge CB2 0QQ, England. [Florez, Jose C.; Saxena, Richa; Voight, Benjamin F.; Altshuler, David] Harvard & MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Florez, Jose C.; Altshuler, David; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, Jose C.; Waterworth, Dawn; Altshuler, David] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.; Waterworth, Dawn; Altshuler, David] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. [Saxena, Richa; Voight, Benjamin F.; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Ctr Human Genet Res, Boston, MA 02114 USA. [Soranzo, Nicole; Potter, Simon C.; Wheeler, Eleanor; Deloukas, Panos; Hunt, Sarah; Inouye, Michael; McCann, Owen T.; Peltonen, Leena; Barroso, Ines] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Soranzo, Nicole; Ahmadi, Kourosh; Cervino, Alessandra; Spector, Tim D.] Kings Coll London, Twin Res & Genet Epidemiol Dept, London SE1 7EH, England. [Thorleifsson, Gudmar; Kong, Augustine; Steinthorsdottir, Valgerdur; Stefansson, Kari] deCODE Genet, IS-101 Reykjavik, Iceland. [Manning, Alisa K.; Cupples, L. Adrienne; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Aulchenko, Yurii; Dehghan, Abbas; Hofman, Albert; Witteman, Jacqueline C. M.; Van Duijn, Cornelia] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Erdos, Michael R.; Bonnycastle, Lori L.; Collins, Francis S.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Sanna, Serena; Cao, Antonio; Crisponi, Laura; Naitza, Silvia; Orru, Marco; Uda, Manuela] Cittadella Univ Monserrato, CNR, INN, I-09042 Cagliari, Italy. [Hottenga, Jouke-Jan; De Geus, Eco J. C.; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands. [Kaakinen, Marika; Jarvelin, Marjo Riitta] Univ Oulu, Inst Hlth Sci & Biocenter Oulu, Oulu 90014, Finland. [Lyssenko, Valeriya; Groop, Leif C.] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden. [Chen, Wei-Min] Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA 22908 USA. [Chen, Wei-Min] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA. [Beckmann, Jacques S.; Johnson, Toby] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland. [Beckmann, Jacques S.] CHU Vaudois, Serv Med Genet, CH-1011 Lausanne, Switzerland. [Bergman, Richard N.; Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [Bochud, Murielle] CHU Vaudois, Univ Inst Social & Prevent Med, CH-1011 Lausanne, Switzerland. [Buchanan, Thomas A.] Univ So Calif, Keck Sch Med, Div Endocrinol, Dept Med, Los Angeles, CA 90033 USA. [Coin, Lachlan; Elliott, Paul; Jarvelin, Marjo Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England. [Doney, Alex S. F.; Morris, Andrew D.] Univ Dundee, Ninewells Hosp & Med Sch, Div Med & Therapeut, Diabet Res Grp, Dundee DD1 9SY, Scotland. [Freimer, Nelson] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA. [Herder, Christian; Johnson, Toby] Univ Dusseldorf, Leibniz Inst, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany. [Hughes, Thomas E.] Novartis Inst BioMed Res, Diabet & Metab Dis Area, Cambridge, MA 02139 USA. [Illig, Thomas; Wichmann, H-Erich] Helmholtz Zentrum Muenchen, Natl Res Ctr Environm Hlth, Inst Epidemiol, Neuherberg, Germany. [Isomaa, Bo] Malmska Municipal Hlth Ctr & Hosp, Pietarsaari, Finland. [Krestyaninova, Maria; Yuan, Xin] European Bioinformat Inst, EMBL, Hinxton, England. [Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Lim, Noha; Song, Kijoung; Mooser, Vincent] Glaxo SmithKline, Med Genet Clin Pharmacol & Discovery Med, King Of Prussia, PA 19406 USA. [Lindblad, Ulf] Skaraborg Inst, Skovde, Sweden. [Lindblad, Ulf] Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Malmo, Sweden. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Ctr, Populat Pharmacogenet Grp, Dundee DD1 9SY, Scotland. [Pouta, Anneli] Oulu Univ Hosp, Dept Obstet & Gynaecol, Oulu, Finland. [Jarvelin, Marjo Riitta] Natl Publ Hlth Inst KLT, Dept Child & Adolescent Hlth, Oulu 90101, Finland. [Rathmann, Wolfgang] Univ Dusseldorf, Leibniz Inst, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany. [Saramies, Jouko] Savitaipale Hlth Ctr, Savitaipale 54800, Finland. [Scuteri, Angelo] Ist Patol Endocrina & Metabol, Unita Operat Geriatria, Rome, Italy. [Sijbrands, Eric; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Smit, Jan H.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 GZ Groningen, Netherlands. [Tuomi, Tiinamaija] Univ Helsinki, Helsinki Univ Hosp, Dept Med, FIN-00014 Helsinki, Finland. [Tuomilehto, Jaakko] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Diabet Unit, SF-00300 Helsinki, Finland. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Senajoki 60220, Finland. [Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Schlessinger, David; Lakatta, Edward] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Sandhu, Manjinder; Penninx, Brenda W. J. H.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England. [Penninx, Brenda W. J. H.] Leiden Univ, Med Ctr, Dept Psychiat, NL-2300 RC Leiden, Netherlands. [Penninx, Brenda W. J. H.] Vrije Univ Amsterdam Med Ctr, Inst Neurosci, EMGO Inst, Dept Psychiat, NL-1081 AL Amsterdam, Netherlands. [Vollenweider, Peter; Waeber, Gerard] CHU Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Peltonen, Leena] Inst Mol Med, Biomedicum, Helsinki 00290, Finland. [Peltonen, Leena] MIT, Broad Inst, Cambridge, MA 02141 USA. [Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Abecasis, GR (reprint author), Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. EM mark.mccarthy@drl.ox.ac.uk; nick.wareham@mrc-epid.cam.ac.uk; jmeigs@partners.org; goncalo@umich.edu RI Deloukas, Panos/B-2922-2013; Palmer, Colin/C-7053-2008; Chen, Wei-Min/A-8469-2009; Morris, Andrew/C-2837-2009; Abecasis, Goncalo/B-7840-2010; Bochud, Murielle/A-3981-2010; Altshuler, David/A-4476-2009; Voight, Benjamin/F-1775-2011; Beckmann, Jacques S /A-9772-2008; Spector, Tim/F-6533-2012; Colaus, PsyColaus/K-6607-2013; Aulchenko, Yurii/M-8270-2013; de Geus, Eco/M-9318-2015; Prokopenko, Inga/H-3241-2014; Study, GoDARTS/K-9448-2016; Coin, Lachlan/A-9001-2014; Naitza, Silvia/D-5620-2017; OI Tuomi, Tiinamaija/0000-0002-8306-6202; Dehghan, Abbas/0000-0001-6403-016X; Deloukas, Panos/0000-0001-9251-070X; Palmer, Colin/0000-0002-6415-6560; Bochud, Murielle/0000-0002-5727-0218; Altshuler, David/0000-0002-7250-4107; Beckmann, Jacques S /0000-0002-9741-1900; Aulchenko, Yurii/0000-0002-7899-1575; Hunt, Sarah/0000-0002-8350-1235; Cupples, L. Adrienne/0000-0003-0273-7965; Abecasis, Goncalo/0000-0003-1509-1825; Zeggini, Eleftheria/0000-0003-4238-659X; Dupuis, Josee/0000-0003-2871-3603; Soranzo, Nicole/0000-0003-1095-3852; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; de Geus, Eco/0000-0001-6022-2666; Prokopenko, Inga/0000-0003-1624-7457; Coin, Lachlan/0000-0002-4300-455X; Krestyaninova, Maria/0000-0002-8705-8111; Kaakinen, Marika/0000-0002-9228-0462; Sijbrands, Eric/0000-0001-8857-7389; sanna, serena/0000-0002-3768-1749; Johnson, Toby/0000-0002-5998-3270 FU Intramural NIH HHS; Medical Research Council [G0000649, G016121, G0500539, G0601261, G0701863, MC_U106179471, MC_U106188470]; NCRR NIH HHS [RR-163736]; NHGRI NIH HHS [HG-02651, R01 HG002651, R01 HG002651-05, Z01 HG000024]; NHLBI NIH HHS [HC-25195, HL-084729, HL-087679, N01 HC025195, N01HC25195, N02-HL-6-4278, R01 HL087679, R01 HL087679-02, U01 HL084729, U01 HL084729-03]; NIDA NIH HHS [DA-021519, U54 DA021519, U54 DA021519-04]; NIDDK NIH HHS [DK-062370, DK-065978, DK-072193, DK-078616, DK-080140, DK069922, K23 DK065978, K23 DK065978-05, K24 DK080140, K24 DK080140-01, K24 DK080140-02, R01 DK029867, R01 DK062370, R01 DK062370-05, R01 DK069922, R01 DK069922-02, R01 DK072193, R01 DK072193-04, R01 DK078616, R01 DK078616-01A1, R56 DK062370, U01 DK062370, U01 DK078616]; NIMH NIH HHS [MH059160, R01 MH059160, R01 MH059160-04]; Wellcome Trust [089061, 076113, 077011, 077016, 079557, 083948, 090532, GR069224, GR072960] NR 30 TC 377 Z9 386 U1 2 U2 30 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2009 VL 41 IS 1 BP 77 EP 81 DI 10.1038/ng.290 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 389IE UT WOS:000262085300019 PM 19060907 ER PT J AU Lyssenko, V Nagorny, CLF Erdos, MR Wierup, N Jonsson, A Spegel, P Bugliani, M Saxena, R Fex, M Pulizzi, N Isomaa, B Tuomi, T Nilsson, P Kuusisto, J Tuomilehto, J Boehnke, M Altshuler, D Sundler, F Eriksson, JG Jackson, AU Laakso, M Marchetti, P Watanabe, RM Mulder, H Groop, L AF Lyssenko, Valeriya Nagorny, Cecilia L. F. Erdos, Michael R. Wierup, Nils Jonsson, Anna Spegel, Peter Bugliani, Marco Saxena, Richa Fex, Malin Pulizzi, Nicolo Isomaa, Bo Tuomi, Tiinamaija Nilsson, Peter Kuusisto, Johanna Tuomilehto, Jaakko Boehnke, Michael Altshuler, David Sundler, Frank Eriksson, Johan G. Jackson, Anne U. Laakso, Markku Marchetti, Piero Watanabe, Richard M. Mulder, Hindrik Groop, Leif TI Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; BETA-CELL; MELATONIN RECEPTORS; PANCREATIC-ISLETS; MINIMAL MODEL; SENSITIVITY; LOCI; EXPRESSION; REPLICATION; PATHWAYS AB Genome-wide association studies have shown that variation in MTNR1B (melatonin receptor 1B) is associated with insulin and glucose concentrations. Here we show that the risk genotype of this SNP predicts future type 2 diabetes (T2D) in two large prospective studies. Specifically, the risk genotype was associated with impairment of early insulin response to both oral and intravenous glucose and with faster deterioration of insulin secretion over time. We also show that the MTNR1B mRNA is expressed in human islets, and immunocytochemistry confirms that it is primarily localized in beta cells in islets. Nondiabetic individuals carrying the risk allele and individuals with T2D showed increased expression of the receptor in islets. Insulin release from clonal beta cells in response to glucose was inhibited in the presence of melatonin. These data suggest that the circulating hormone melatonin, which is predominantly released from the pineal gland in the brain, is involved in the pathogenesis of T2D. Given the increased expression of MTNR1B in individuals at risk of T2D, the pathogenic effects are likely exerted via a direct inhibitory effect on beta cells. In view of these results, blocking the melatonin ligand-receptor system could be a therapeutic avenue in T2D. C1 [Lyssenko, Valeriya; Jonsson, Anna; Groop, Leif] Lund Univ, Univ Hosp, Dept Clin Sci Malmoe, Unit Diabet & Endocrinol,Diabet Ctr, S-20520 Malmo, Sweden. [Nagorny, Cecilia L. F.; Spegel, Peter; Mulder, Hindrik] Lund Univ, Ctr Diabet, Dept Clin Sci Malmoe, Unit Mol Metab, S-20502 Malmo, Sweden. [Erdos, Michael R.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Wierup, Nils; Sundler, Frank] Lund Univ, Dept Expt Med Sci, Unit Neuroendocrine Cell Biol, S-22184 Lund, Sweden. [Bugliani, Marco; Pulizzi, Nicolo; Marchetti, Piero] Univ Pisa, Dept Endocrinol & Metab, I-56124 Pisa, Italy. [Saxena, Richa; Altshuler, David] Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02142 USA. [Saxena, Richa; Altshuler, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fex, Malin] Lund Univ, Ctr Diabet, Dept Clin Sci Malmoe, Unit Diabet & Celiac Dis, S-20502 Malmo, Sweden. [Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki 00251, Finland. [Tuomi, Tiinamaija; Groop, Leif] Univ Helsinki, Cent Hosp, Dept Med, Helsinki 00140, Finland. [Tuomi, Tiinamaija; Groop, Leif] Univ Helsinki, Res Program Mol Med, Helsinki 00140, Finland. [Nilsson, Peter] Lund Univ, Dept Clin Sci, S-20502 Malmo, Sweden. [Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Tuomilehto, Jaakko] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Diabet Unit, SF-00300 Helsinki, Finland. [Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki 00014, Finland. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Senajoki 60220, Finland. [Boehnke, Michael; Jackson, Anne U.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, FIN-00014 Helsinki, Finland. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. RP Groop, L (reprint author), Lund Univ, Univ Hosp, Dept Clin Sci Malmoe, Unit Diabet & Endocrinol,Diabet Ctr, S-20520 Malmo, Sweden. EM Leif.Groop@med.lu.se RI Altshuler, David/A-4476-2009; Mulder, Hindrik/E-1045-2012; Marchetti, Piero/J-7439-2013; OI Altshuler, David/0000-0002-7250-4107; Tuomi, Tiinamaija/0000-0002-8306-6202; Eriksson, Johan/0000-0002-2516-2060; Marchetti, Piero/0000-0003-4907-0635; Fex, Malin/0000-0003-0675-7576 FU Novartis; Swedish Research Council [31475113580]; Lund University; Pahlsson Foundation; Heart and Lung Foundation; Wallenberg Foundation; Swedish Diabetes Research Society; Crafoord Foundation; Swedish Medical Society; Swedish Royal Physiographic Society; Nordic Centre of Excellence Grant in Disease Genetics; Finnish Diabetes Research Society; Sigrid Juselius Foundation; Folkhalsan Research Foundation; Novo Nordisk Foundation; European Network of Genomic and Genetic Epidemiology (ENGAGE); Italian Ministry of University and Research [PRIN 2007-2008]; European Community [LSHM-CT-2006-518153]; NIH [DK062370]; American Diabetes Association [1-05-RA-140, DK072193]; Academy of Finland [124243] FX The DGI study was supported by a grant from Novartis. Studies in Malmoe were supported by grants from the Swedish Research Council, including a Linne grant (No. 31475113580), the Diabetes Programme at Lund University, the Pahlsson Foundation, the Heart and Lung Foundation, the Wallenberg Foundation, the Swedish Diabetes Research Society, the Crafoord Foundation, Swedish Medical Society, Swedish Royal Physiographic Society, a Nordic Centre of Excellence Grant in Disease Genetics, the Finnish Diabetes Research Society, the Sigrid Juselius Foundation, Folkhalsan Research Foundation, Novo Nordisk Foundation, the European Network of Genomic and Genetic Epidemiology (ENGAGE), the Wallenberg Foundation, the European Foundation for the Study of Diabetes (EFSD) and the Human Tissue facility at the Lund University Diabetes Center. Studies in human islets were supported in part by the Italian Ministry of University and Research (PRIN 2007-2008) and the European Community (LSHM-CT-2006-518153). Pancreatic islets at US National Institutes of Health were obtained through the ICR Basic Science Islet Distribution Program (City of Hope Hospital, Joslin Diabetes Center, Northwestern University, Southern California Islet Consortium, University of Alabama Birmingham, University of Illinois, University of Miami, University of Minnesota, University of Pennsylvania, University of Wisconsin and Washington University), the Juvenile Diabetes Research Foundation Islet Resources (Washington University) and the National Disease Resource Interchange (NDRI). The FUSION study would like to thank the many research volunteers who generously participated in the various studies represented in FUSION. We also thank A. J. Swift, M. Morken, P. S. Chines and N. Narisu for genotying and informatics support. Support for FUSION was provided by the following: NIH grant DK062370 (M. Boehnke), American Diabetes Association research grant 1-05-RA-140 ( R. M. W.), DK072193 ( K. L. Mohlke) and National Human Genome Research Institute intramural project number 1 Z01 HG000024 ( F. S. Collins). The METSIM study was supported by Academy of Finland grant 124243 ( M. L.). NR 30 TC 324 Z9 333 U1 1 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2009 VL 41 IS 1 BP 82 EP 88 DI 10.1038/ng.288 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 389IE UT WOS:000262085300020 PM 19060908 ER PT J AU Rao, A AF Rao, Anjana TI Signaling to gene expression: calcium, calcineurin and NFAT SO NATURE IMMUNOLOGY LA English DT Article ID ACTIVATED T-CELLS; KAPPA-B SITE; TRANSCRIPTION FACTOR; NUCLEAR FACTOR; IMMUNOSUPPRESSIVE DRUGS; CYCLOSPORINE-A; CRAC CHANNEL; FOS; PROMOTER; TARGET C1 Dept Pathol, Boston, MA 02115 USA. [Rao, Anjana] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Rao, A (reprint author), Dept Pathol, Boston, MA 02115 USA. EM arao@idi.harvard.edu NR 26 TC 35 Z9 37 U1 7 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2009 VL 10 IS 1 BP 3 EP 5 DI 10.1038/ni0109-3 PG 3 WC Immunology SC Immunology GA 385BV UT WOS:000261788800002 PM 19088731 ER PT J AU Georgopoulos, K AF Georgopoulos, Katia TI From immunity to tolerance through HDAC SO NATURE IMMUNOLOGY LA English DT Editorial Material ID TRANSCRIPTION; INFLAMMATION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biol Res Ctr, Charlestown, MA 02129 USA. RP Georgopoulos, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biol Res Ctr, Charlestown, MA 02129 USA. EM katia.georgopoulos@cbrc2.mgh.harvard.edu NR 8 TC 9 Z9 11 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2009 VL 10 IS 1 BP 13 EP 14 DI 10.1038/ni0109-13 PG 2 WC Immunology SC Immunology GA 385BV UT WOS:000261788800005 PM 19088734 ER PT J AU Blackburn, SD Shin, H Haining, WN Zou, T Workman, CJ Polley, A Betts, MR Freeman, GJ Vignali, DAA Wherry, EJ AF Blackburn, Shawn D. Shin, Haina Haining, W. Nicholas Zou, Tao Workman, Creg J. Polley, Antonio Betts, Michael R. Freeman, Gordon J. Vignali, Dario A. A. Wherry, E. John TI Coregulation of CD8(+) T cell exhaustion by multiple inhibitory receptors during chronic viral infection SO NATURE IMMUNOLOGY LA English DT Article ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; ACTIVATION GENE-3 CD223; THERAPEUTIC VACCINATION; EFFECTOR FUNCTION; DISEASE PROGRESSION; PD-1 EXPRESSION; SELF-TOLERANCE; UP-REGULATION; CUTTING EDGE; 2B4 CD244 AB T cell exhaustion often occurs during chronic infection and prevents optimal viral control. The molecular pathways involved in T cell exhaustion remain poorly understood. Here we show that exhausted CD8(+) T cells are subject to complex layers of negative regulation resulting from the coexpression of multiple inhibitory receptors. Exhausted CD8(+) T cells expressed up to seven inhibitory receptors. Coexpression of multiple distinct inhibitory receptors was associated with greater T cell exhaustion and more severe infection. Regulation of T cell exhaustion by various inhibitory pathways was nonredundant, as blockade of the T cell inhibitory receptors PD-1 and LAG-3 simultaneously and synergistically improved T cell responses and diminished viral load in vivo. Thus, CD8(+) T cell responses during chronic viral infections are regulated by complex patterns of coexpressed inhibitory receptors. C1 [Blackburn, Shawn D.; Shin, Haina; Zou, Tao; Polley, Antonio; Wherry, E. John] Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA. [Blackburn, Shawn D.; Shin, Haina; Zou, Tao; Polley, Antonio; Wherry, E. John] Wistar Inst Anat & Biol, Wistar Vaccine Ctr, Philadelphia, PA 19104 USA. [Haining, W. Nicholas] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Freeman, Gordon J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Betts, Michael R.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. [Workman, Creg J.; Vignali, Dario A. A.] St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38105 USA. RP Wherry, EJ (reprint author), Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA. EM jwherry@wistar.org FU National Institute of Allergy and Infectious Diseases [AI071309, HHSN26620050030C]; Bill and Melinda Gates Foundation Grand Challenge in Global Health FX We thank E. Long, V. Kumar and S. Reiner for comments and suggestions, and B. Laidlaw for critically reading the manuscript. Supported by the National Institute of Allergy and Infectious Diseases (AI071309 to E. J. W and HHSN26620050030C to E. J. W. and G. J. F.) and the Bill and Melinda Gates Foundation Grand Challenge in Global Health ( G. J. F. and E. J. W.). NR 56 TC 644 Z9 657 U1 5 U2 34 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2009 VL 10 IS 1 BP 29 EP 37 DI 10.1038/ni.1679 PG 9 WC Immunology SC Immunology GA 385BV UT WOS:000261788800009 PM 19043418 ER PT J AU Hartner, JC Walkley, CR Lu, J Orkin, SH AF Hartner, Jochen C. Walkley, Carl R. Lu, Jun Orkin, Stuart H. TI ADAR1 is essential for the maintenance of hematopoiesis and suppression of interferon signaling SO NATURE IMMUNOLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; ADENOSINE-DEAMINASE ADAR1; SLAM FAMILY RECEPTORS; EDITING ENZYME ADAR1; STEM-CELLS; GENE-EXPRESSION; HUMAN TRANSCRIPTOME; ACTIVATION; INFECTION; MUTATION AB The deaminase ADAR1 edits adenosines in nuclear transcripts of nervous tissue and is required in the fetal liver of the developing mouse embryo. Here we show by inducible gene disruption in mice that ADAR1 is essential for maintenance of both fetal and adult hematopoietic stem cells. Loss of ADAR1 in hematopoietic stem cells led to global upregulation of type I and II interferon-inducible transcripts and rapid apoptosis. Our findings identify ADAR1 as an essential regulator of hematopoietic stem cell maintenance and suppressor of interferon signaling that may protect organisms from the deleterious effects of interferon activation associated with many pathological processes, including chronic inflammation, autoimmune disorders and cancer. C1 [Hartner, Jochen C.; Walkley, Carl R.; Lu, Jun; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Hartner, Jochen C.; Walkley, Carl R.; Orkin, Stuart H.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Lu, Jun] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Orkin, Stuart H.] Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu OI Walkley, Carl/0000-0002-4784-9031 FU Leukemia and Lymphoma Society; Howard Hughes Medical Institute FX Supported by the Leukemia and Lymphoma Society ( C. R. W.) and the Howard Hughes Medical Institute ( S. H. O.). NR 43 TC 152 Z9 160 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2009 VL 10 IS 1 BP 109 EP 115 DI 10.1038/ni.1680 PG 7 WC Immunology SC Immunology GA 385BV UT WOS:000261788800018 PM 19060901 ER PT J AU Cusick, ME Yu, HY Smolyar, A Venkatesan, K Carvunis, AR Simonis, N Rual, JF Borick, H Braun, P Dreze, M Vandenhaute, J Galli, M Yazaki, J Hill, DE Ecker, JR Roth, FP Vidal, M AF Cusick, Michael E. Yu, Haiyuan Smolyar, Alex Venkatesan, Kavitha Carvunis, Anne-Ruxandra Simonis, Nicolas Rual, Jean-Francois Borick, Heather Braun, Pascal Dreze, Matija Vandenhaute, Jean Galli, Mary Yazaki, Junshi Hill, David E. Ecker, Joseph R. Roth, Frederick P. Vidal, Marc TI Literature-curated protein interaction datasets SO NATURE METHODS LA English DT Article ID MOLECULAR INTERACTION DATABASE; INTERACTION NETWORK DATABASE; SYSTEMS BIOLOGY; SACCHAROMYCES-CEREVISIAE; STRUCTURAL DISORDER; MASS-SPECTROMETRY; SCALE; COMPLEXES; UPDATE; MAP AB High-quality datasets are needed to understand how global and local properties of protein-protein interaction, or 'interactome', networks relate to biological mechanisms, and to guide research on individual proteins. In an evaluation of existing curation of protein interaction experiments reported in the literature, we found that curation can be error-prone and possibly of lower quality than commonly assumed. C1 [Cusick, Michael E.; Yu, Haiyuan; Smolyar, Alex; Venkatesan, Kavitha; Carvunis, Anne-Ruxandra; Simonis, Nicolas; Rual, Jean-Francois; Borick, Heather; Braun, Pascal; Dreze, Matija; Hill, David E.; Roth, Frederick P.; Vidal, Marc] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Cusick, Michael E.; Yu, Haiyuan; Smolyar, Alex; Venkatesan, Kavitha; Carvunis, Anne-Ruxandra; Simonis, Nicolas; Rual, Jean-Francois; Borick, Heather; Braun, Pascal; Dreze, Matija; Hill, David E.; Roth, Frederick P.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Cusick, Michael E.; Yu, Haiyuan; Smolyar, Alex; Venkatesan, Kavitha; Carvunis, Anne-Ruxandra; Simonis, Nicolas; Rual, Jean-Francois; Borick, Heather; Braun, Pascal; Dreze, Matija; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Carvunis, Anne-Ruxandra] Univ Grenoble 1, Fac Med, CNRS, TIMC IMAG,Unite Mixte Rech 5525, F-38706 La Tronche, France. [Vandenhaute, Jean] Fac Univ Notre Dame Paix, Unite Rech Biol Mol, B-5000 Namur, Wallonia, Belgium. [Yazaki, Junshi; Ecker, Joseph R.] Salk Inst Biol Studies, Plant Biol Lab, La Jolla, CA 92037 USA. [Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Vidal, M (reprint author), Dana Farber Canc Inst, CCSB, 44 Binney St, Boston, MA 02115 USA. EM marc_vidal@dfci.harvard.edu RI Simonis, Nicolas/E-5124-2010; Yazaki, Junshi/B-1557-2012; Hill, David/B-6617-2011; Ecker, Joseph/B-9144-2008; Roth, Frederick/H-6308-2011; Braun, Pascal/B-9669-2013; OI Ecker, Joseph/0000-0001-5799-5895; Braun, Pascal/0000-0003-2012-6746; , /0000-0001-7002-8488; Rual, Jean-Francois/0000-0003-4465-8819; Roth, Frederick/0000-0002-6628-649X; Carvunis, Anne-Ruxandra/0000-0002-6474-6413 FU NHGRI NIH HHS [P50 HG004233, P50 HG004233-01, P50 HG004233-02, R01 HG 001715, R01 HG 003224, R01 HG001715, R01 HG001715-09, R01 HG001715-10, P50 HG 004233, R01 HG003224, R01 HG003224-02, R01 HG003224-03] NR 70 TC 157 Z9 160 U1 2 U2 22 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 JAN PY 2009 VL 6 IS 1 BP 39 EP 46 DI 10.1038/NMETH.1284 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 393JS UT WOS:000262370200022 PM 19116613 ER PT J AU Simonis, N Rual, JF Carvunis, AR Tasan, M Lemmens, I Hirozane-Kishikawa, T Hao, T Sahalie, JM Venkatesan, K Gebreab, F Cevik, S Klitgord, N Fan, CY Braun, P Li, N Ayivi-Guedehoussou, N Dann, E Bertin, N Szeto, D Dricot, A Yildirim, MA Lin, CW de Smet, AS Kao, HL Simon, C Smolyar, A Ahn, JS Tewari, M Boxem, M Milstein, S Yu, HY Dreze, M Vandenhaute, J Gunsalus, KC Cusick, ME Hill, DE Tavernier, J Roth, FP Vidal, M AF Simonis, Nicolas Rual, Jean-Francois Carvunis, Anne-Ruxandra Tasan, Murat Lemmens, Irma Hirozane-Kishikawa, Tomoko Hao, Tong Sahalie, Julie M. Venkatesan, Kavitha Gebreab, Fana Cevik, Sebiha Klitgord, Niels Fan, Changyu Braun, Pascal Li, Ning Ayivi-Guedehoussou, Nono Dann, Elizabeth Bertin, Nicolas Szeto, David Dricot, Ameli Yildirim, Muhammed A. Lin, Chenwei de Smet, Anne-Sophie Kao, Huey-Ling Simon, Christophe Smolyar, Alex Ahn, Jin Sook Tewari, Muneesh Boxem, Mike Milstein, Stuart Yu, Haiyuan Dreze, Matija Vandenhaute, Jean Gunsalus, Kristin C. Cusick, Michael E. Hill, David E. Tavernier, Jan Roth, Frederick P. Vidal, Marc TI Empirically controlled mapping of the Caenorhabditis elegans protein-protein interactome network SO NATURE METHODS LA English DT Article ID C-ELEGANS; EARLY EMBRYOGENESIS; INTERACTION MAP; PERTURBATION; ANNOTATION; RESOURCE; SEQUENCE AB To provide accurate biological hypotheses and elucidate global properties of cellular networks, systematic identification of protein-protein interactions must meet high quality standards. We present an expanded C. elegans protein-protein interaction network, or 'interactome' map, derived from testing a matrix of similar to 10,000 x similar to 10,000 proteins using a highly specific, high-throughput yeast two-hybrid system. Through a new empirical quality control framework, we show that the resulting data set ( Worm Interactome 2007, or WI-2007) was similar in quality to low-throughput data curated from the literature. We filtered previous interaction data sets and integrated them with WI-2007 to generate a high-confidence consolidated map ( Worm Interactome version 8, or WI8). This work allowed us to estimate the size of the worm interactome at similar to 116,000 interactions. Comparison with other types of functional genomic data shows the complementarity of distinct experimental approaches in predicting different functional relationships between genes or proteins. C1 [Simonis, Nicolas; Rual, Jean-Francois; Carvunis, Anne-Ruxandra; Hirozane-Kishikawa, Tomoko; Hao, Tong; Sahalie, Julie M.; Venkatesan, Kavitha; Gebreab, Fana; Cevik, Sebiha; Klitgord, Niels; Fan, Changyu; Braun, Pascal; Li, Ning; Ayivi-Guedehoussou, Nono; Dann, Elizabeth; Bertin, Nicolas; Szeto, David; Dricot, Ameli; Yildirim, Muhammed A.; Lin, Chenwei; Simon, Christophe; Smolyar, Alex; Ahn, Jin Sook; Tewari, Muneesh; Boxem, Mike; Milstein, Stuart; Yu, Haiyuan; Dreze, Matija; Cusick, Michael E.; Hill, David E.; Roth, Frederick P.; Vidal, Marc] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Simonis, Nicolas; Rual, Jean-Francois; Carvunis, Anne-Ruxandra; Hirozane-Kishikawa, Tomoko; Hao, Tong; Sahalie, Julie M.; Venkatesan, Kavitha; Gebreab, Fana; Cevik, Sebiha; Klitgord, Niels; Fan, Changyu; Braun, Pascal; Li, Ning; Ayivi-Guedehoussou, Nono; Dann, Elizabeth; Bertin, Nicolas; Szeto, David; Dricot, Ameli; Yildirim, Muhammed A.; Lin, Chenwei; Simon, Christophe; Smolyar, Alex; Ahn, Jin Sook; Tewari, Muneesh; Boxem, Mike; Milstein, Stuart; Yu, Haiyuan; Dreze, Matija; Cusick, Michael E.; Hill, David E.; Roth, Frederick P.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Simonis, Nicolas; Rual, Jean-Francois; Carvunis, Anne-Ruxandra; Hirozane-Kishikawa, Tomoko; Hao, Tong; Sahalie, Julie M.; Venkatesan, Kavitha; Gebreab, Fana; Cevik, Sebiha; Klitgord, Niels; Fan, Changyu; Braun, Pascal; Li, Ning; Ayivi-Guedehoussou, Nono; Dann, Elizabeth; Bertin, Nicolas; Szeto, David; Dricot, Ameli; Yildirim, Muhammed A.; Lin, Chenwei; Simon, Christophe; Smolyar, Alex; Ahn, Jin Sook; Tewari, Muneesh; Boxem, Mike; Milstein, Stuart; Yu, Haiyuan; Dreze, Matija; Cusick, Michael E.; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Carvunis, Anne-Ruxandra] Univ Grenoble 1, Fac Med, CNRS, TIMC IMAG,Unite Mixte Rech 5525, F-38706 La Tronche, France. [Tasan, Murat; Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Lemmens, Irma; Tavernier, Jan] Univ Ghent, Fac Med & Hlth Sci, Vlaams Inst Biotechnol, Dept Med Prot Res, B-9000 Ghent, Belgium. [Lemmens, Irma; Tavernier, Jan] Univ Ghent, Fac Med & Hlth Sci, Dept Biochem, B-9000 Ghent, Belgium. [Yildirim, Muhammed A.] Harvard Univ, Div Engn & Appl Sci, Cambridge, MA 02138 USA. [Kao, Huey-Ling; Gunsalus, Kristin C.] NYU, Dept Biol, Ctr Genom & Syst Biol, New York, NY 10003 USA. [Boxem, Mike] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02129 USA. [Dreze, Matija; Vandenhaute, Jean] Fac Univ Notre Dame Paix, Unite Rech Biol Mol, B-5000 Namur, Belgium. RP Vidal, M (reprint author), Dana Farber Canc Inst, CCSB, 44 Binney St, Boston, MA 02115 USA. EM david_hill@dfci.harvard.edu; jan.tavernier@ugent.be; fritz_roth@hms.harvard.edu; marc_vidal@dfci.harvard.edu RI Bertin, Nicolas/C-3025-2008; Klitgord, Niels/B-5121-2009; Boxem, Mike/B-8857-2011; Simonis, Nicolas/E-5124-2010; Hill, David/B-6617-2011; Roth, Frederick/H-6308-2011; Yildirim, Muhammed/J-3695-2014; Braun, Pascal/B-9669-2013; OI Roth, Frederick/0000-0002-6628-649X; Carvunis, Anne-Ruxandra/0000-0002-6474-6413; Bertin, Nicolas/0000-0002-9835-9606; Boxem, Mike/0000-0003-3966-4173; Yildirim, Muhammed/0000-0003-2826-1766; Braun, Pascal/0000-0003-2012-6746; , /0000-0001-7002-8488; Cevik, Sebiha/0000-0002-0935-1929; Rual, Jean-Francois/0000-0003-4465-8819 FU US National Institutes of Health [R01 HG001715, R01 HG003224, F32 HG004098, T32 CA09361]; University of Ghent [GOA12051401]; Fonds Wetenschappelijk Onderzoek - Vlaanderen (FWO-V) [G.0031.06]; US Department of the Army [W81XWH-04-1-0307]; State of New York's Science and Tech Resources [C040066]; Fonds de la Recherche Scientifique (FRS-FNRS, French Community of Belgium). FX We thank F. Piano and members of the Cancer Center for System Biology and the Vidal laboratory for discussions, A. Petcherski from WormBase for assistance with worm genetic interactions, and Z. Hu for VisANT assistance. The worm interactome project was supported by grants from the US National Institutes of Health-R01 HG001715 (M. V. and F. P. R.), R01 HG003224 (F. P. R.), F32 HG004098 (M. Tasan), T32 CA09361 (K. V.) - a University of Ghent grant GOA12051401 (J. T.), and the Fonds Wetenschappelijk Onderzoek - Vlaanderen (FWO-V) G.0031.06 (J. T.). I. L. was supported by a postdoctoral fellowship from the FWO- V. K. C. G. and H.-L. K. were supported by US Department of the Army Award W81XWH-04-1-0307 and the State of New York's Science and Tech Resources contract C040066. M. V. is a Chercheur Qualifie Honoraire from the Fonds de la Recherche Scientifique (FRS-FNRS, French Community of Belgium). NR 32 TC 144 Z9 146 U1 0 U2 12 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 JAN PY 2009 VL 6 IS 1 BP 47 EP 54 DI 10.1038/NMETH.1279 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 393JS UT WOS:000262370200023 PM 19123269 ER PT J AU Venkatesan, K Rual, JF Vazquez, A Stelzl, U Lemmens, I Hirozane-Kishikawa, T Hao, T Zenkner, M Xin, XF Goh, KI Yildirim, MA Simonis, N Heinzmann, K Gebreab, F Sahalie, JM Cevik, S Simon, C de Smet, AS Dann, E Smolyar, A Vinayagam, A Yu, HY Szeto, D Borick, H Dricot, A Klitgord, N Murray, RR Lin, C Lalowski, M Timm, J Rau, K Boone, C Braun, P Cusick, ME Roth, FP Hill, DE Tavernier, J Wanker, EE Barabasi, AL Vidal, M AF Venkatesan, Kavitha Rual, Jean-Francois Vazquez, Alexei Stelzl, Ulrich Lemmens, Irma Hirozane-Kishikawa, Tomoko Hao, Tong Zenkner, Martina Xin, Xiaofeng Goh, Kwang-Il Yildirim, Muhammed A. Simonis, Nicolas Heinzmann, Kathrin Gebreab, Fana Sahalie, Julie M. Cevik, Sebiha Simon, Christophe de Smet, Anne-Sophie Dann, Elizabeth Smolyar, Alex Vinayagam, Arunachalam Yu, Haiyuan Szeto, David Borick, Heather Dricot, Amelie Klitgord, Niels Murray, Ryan R. Lin, Chenwei Lalowski, Maciej Timm, Jan Rau, Kirstin Boone, Charles Braun, Pascal Cusick, Michael E. Roth, Frederick P. Hill, David E. Tavernier, Jan Wanker, Erich E. Barabasi, Albert-Laszlo Vidal, Marc TI An empirical framework for binary interactome mapping SO NATURE METHODS LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; MOLECULAR INTERACTION DATABASE; INTERACTION NETWORK; YEAST; PROTEOMICS; RESOURCE; MAP AB Several attempts have been made to systematically map protein-protein interaction, or 'interactome', networks. However, it remains difficult to assess the quality and coverage of existing data sets. Here we describe a framework that uses an empirically-based approach to rigorously dissect quality parameters of currently available human interactome maps. Our results indicate that high-throughput yeast two-hybrid (HT-Y2H) interactions for human proteins are more precise than literature-curated interactions supported by a single publication, suggesting that HT-Y2H is suitable to map a significant portion of the human interactome. We estimate that the human interactome contains similar to 130,000 binary interactions, most of which remain to be mapped. Similar to estimates of DNA sequence data quality and genome size early in the Human Genome Project, estimates of protein interaction data quality and interactome size are crucial to establish the magnitude of the task of comprehensive human interactome mapping and to elucidate a path toward this goal. C1 [Venkatesan, Kavitha; Rual, Jean-Francois; Vazquez, Alexei; Hirozane-Kishikawa, Tomoko; Hao, Tong; Goh, Kwang-Il; Yildirim, Muhammed A.; Simonis, Nicolas; Heinzmann, Kathrin; Gebreab, Fana; Sahalie, Julie M.; Cevik, Sebiha; Simon, Christophe; Dann, Elizabeth; Smolyar, Alex; Yu, Haiyuan; Szeto, David; Borick, Heather; Dricot, Amelie; Klitgord, Niels; Murray, Ryan R.; Lin, Chenwei; Braun, Pascal; Cusick, Michael E.; Roth, Frederick P.; Hill, David E.; Barabasi, Albert-Laszlo; Vidal, Marc] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Venkatesan, Kavitha; Rual, Jean-Francois; Vazquez, Alexei; Hirozane-Kishikawa, Tomoko; Hao, Tong; Goh, Kwang-Il; Yildirim, Muhammed A.; Simonis, Nicolas; Heinzmann, Kathrin; Gebreab, Fana; Sahalie, Julie M.; Cevik, Sebiha; Simon, Christophe; Dann, Elizabeth; Smolyar, Alex; Yu, Haiyuan; Szeto, David; Borick, Heather; Dricot, Amelie; Klitgord, Niels; Murray, Ryan R.; Lin, Chenwei; Braun, Pascal; Cusick, Michael E.; Roth, Frederick P.; Hill, David E.; Barabasi, Albert-Laszlo; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Venkatesan, Kavitha; Rual, Jean-Francois; Hirozane-Kishikawa, Tomoko; Hao, Tong; Yildirim, Muhammed A.; Simonis, Nicolas; Heinzmann, Kathrin; Gebreab, Fana; Sahalie, Julie M.; Cevik, Sebiha; Simon, Christophe; Dann, Elizabeth; Smolyar, Alex; Yu, Haiyuan; Szeto, David; Borick, Heather; Dricot, Amelie; Klitgord, Niels; Murray, Ryan R.; Lin, Chenwei; Braun, Pascal; Cusick, Michael E.; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Vazquez, Alexei; Goh, Kwang-Il; Barabasi, Albert-Laszlo] Univ Notre Dame, Ctr Complex Network Res, Notre Dame, IN 46556 USA. [Vazquez, Alexei; Goh, Kwang-Il; Barabasi, Albert-Laszlo] Univ Notre Dame, Dept Phys, Notre Dame, IN 46556 USA. [Vazquez, Alexei] Inst Adv Study, Simons Ctr Syst Biol, Princeton, NJ 08540 USA. [Stelzl, Ulrich; Zenkner, Martina; Vinayagam, Arunachalam; Lalowski, Maciej; Timm, Jan; Rau, Kirstin; Wanker, Erich E.] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. [Stelzl, Ulrich] Max Planck Inst Mol Genet, Otto Warburg Lab, D-14195 Berlin, Germany. [Lemmens, Irma; de Smet, Anne-Sophie; Tavernier, Jan] Univ Ghent, Vlaams Inst Biotechnol, Dept Med Prot Res, B-9000 Ghent, Belgium. [Lemmens, Irma; de Smet, Anne-Sophie; Tavernier, Jan] Univ Ghent, Fac Med & Hlth Sci, Dept Biochem, B-9000 Ghent, Belgium. [Xin, Xiaofeng; Boone, Charles] Univ Toronto, Terrence Donnelly Ctr Cellular & Biomol Res, Banting & Best Dept Med Res, Toronto, ON M5S 3E1, Canada. [Xin, Xiaofeng; Boone, Charles] Univ Toronto, Terrence Donnelly Ctr Cellular & Biomol Res, Dept Mol Genet, Toronto, ON M5S 3E1, Canada. [Goh, Kwang-Il] Korea Univ, Dept Phys, Seoul 136713, South Korea. [Yildirim, Muhammed A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biochem & Mol Pharmacol, Boston, MA 02115 USA. RP Vidal, M (reprint author), Dana Farber Canc Inst, Ctr Canc Syst Biol, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM jan.tavernier@ugent.be; ewanker@mdc-berlin.de; a.barabasi@neu.edu; marc_vidal@dfci.harvard.edu RI Klitgord, Niels/B-5121-2009; Simonis, Nicolas/E-5124-2010; Arunachalam, Vinayagam/J-7925-2012; Hill, David/B-6617-2011; Roth, Frederick/H-6308-2011; Yildirim, Muhammed/J-3695-2014; Stelzl, Ulrich/J-9506-2015; Braun, Pascal/B-9669-2013; Xin, Xiaofeng/G-7736-2016; OI Rual, Jean-Francois/0000-0003-4465-8819; Roth, Frederick/0000-0002-6628-649X; Wanker, Erich/0000-0001-8072-1630; Arunachalam, Vinayagam/0000-0003-0091-4497; Yildirim, Muhammed/0000-0003-2826-1766; Stelzl, Ulrich/0000-0003-2500-3585; Braun, Pascal/0000-0003-2012-6746; Xin, Xiaofeng/0000-0002-2439-7183; Cevik, Sebiha/0000-0002-0935-1929 FU US National Human Genome Research Institute [2R01HG001715, 5P50HG004233]; US National Cancer Institute [5U54CA112952, 5U01CA105423]; US National Institutes of Health [IH U01 A1070499-01, U56 CA113004, T32CA09361]; Ellison Foundation; W. M. Keck Foundation; Dana-Farber Cancer Institute Institute Sponsored Research funds; US National Science Foundation [ITR DMR-0926737, IIS-0513650]; Deutsche Forschungsgemeinschaft [SFB 577, SFB618]; University of Ghent [G. 0031.06, G0A12051401]; National Cancer Institute of Canada; Fonds de la Recherche Scientifique FX We thank members of CCSB and the Vidal, Barabasi, Wanker and Tavernier laboratories and S. Sahasrabuddhe, R. Bell, R. Chettier and C. Wiggins for helpful discussions; E. Smith for help generating Figure 1; and Agencourt Biosciences for sequencing assistance. This work was supported by the US National Human Genome Research Institute (2R01HG001715 and 5P50HG004233 to M. V. and F. P. R.), the US National Cancer Institute (5U54CA112952 to J. Nevins, subcontract to M. V.; and 5U01CA105423 to S. H. Orkin, project to M. V.), the US National Institutes of Health (IH U01 A1070499-01 and U56 CA113004 to A.-L. B. and postdoctoral training grant fellowship T32CA09361 to K. V.), the Ellison Foundation (to M. V.), the W. M. Keck Foundation (to M. V.), Dana-Farber Cancer Institute Institute Sponsored Research funds (to M. V.), the US National Science Foundation (ITR DMR-0926737 and IIS-0513650 to A.- L. B.), Deutsches Bundesministerium fur Bildung und Forschung (NGFN2, KB-P04T01, KB-P04T03 and 01GR0471 to E. E. W. and U. S.), Deutsche Forschungsgemeinschaft (SFB 577 and SFB618 to E. E. W.), the University of Ghent and the "Fonds Wetenschappelijk Onderzoek-Vlaanderen'' (FWO-V) G. 0031.06 (G0A12051401 to J. Tavernier) and the National Cancer Institute of Canada (to C. B.). I. L. is a postdoctoral fellow with the FWO- V. M. V. is a "Chercheur Qualifie Honoraire'' from the Fonds de la Recherche Scientifique (French Community of Belgium). NR 32 TC 388 Z9 390 U1 7 U2 55 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD JAN PY 2009 VL 6 IS 1 BP 83 EP 90 DI 10.1038/NMETH.1280 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 393JS UT WOS:000262370200030 PM 19060904 ER PT J AU Braun, P Tasan, M Dreze, M Barrios-Rodiles, M Lemmens, I Yu, HY Sahalie, JM Murray, RR Roncari, L de Smet, AS Venkatesan, K Rual, JF Vandenhaute, J Cusick, ME Pawson, T Hill, DE Tavernier, J Wrana, JL Roth, FP Vidal, M AF Braun, Pascal Tasan, Murat Dreze, Matija Barrios-Rodiles, Miriam Lemmens, Irma Yu, Haiyuan Sahalie, Julie M. Murray, Ryan R. Roncari, Luba de Smet, Anne-Sophie Venkatesan, Kavitha Rual, Jean-Francois Vandenhaute, Jean Cusick, Michael E. Pawson, Tony Hill, David E. Tavernier, Jan Wrana, Jeffrey L. Roth, Frederick P. Vidal, Marc TI An experimentally derived confidence score for binary protein-protein interactions SO NATURE METHODS LA English DT Article ID INTERACTION NETWORK; SACCHAROMYCES-CEREVISIAE; INTERACTION DATABASE; MAMMALIAN-CELLS; 2-HYBRID; MAP; PREDICTION; UPDATE AB Information on protein-protein interactions is of central importance for many areas of biomedical research. At present no method exists to systematically and experimentally assess the quality of individual interactions reported in interaction mapping experiments. To provide a standardized confidence-scoring method that can be applied to tens of thousands of protein interactions, we have developed an interaction tool kit consisting of four complementary, high-throughput protein interaction assays. We benchmarked these assays against positive and random reference sets consisting of well documented pairs of interacting human proteins and randomly chosen protein pairs, respectively. A logistic regression model was trained using the data from these reference sets to combine the assay outputs and calculate the probability that any newly identified interaction pair is a true biophysical interaction once it has been tested in the tool kit. This general approach will allow a systematic and empirical assignment of confidence scores to all individual protein-protein interactions in interactome networks. C1 [Braun, Pascal; Dreze, Matija; Yu, Haiyuan; Sahalie, Julie M.; Murray, Ryan R.; Venkatesan, Kavitha; Rual, Jean-Francois; Cusick, Michael E.; Hill, David E.; Roth, Frederick P.; Vidal, Marc] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Braun, Pascal; Dreze, Matija; Yu, Haiyuan; Sahalie, Julie M.; Murray, Ryan R.; Venkatesan, Kavitha; Rual, Jean-Francois; Cusick, Michael E.; Hill, David E.; Roth, Frederick P.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Braun, Pascal; Dreze, Matija; Yu, Haiyuan; Sahalie, Julie M.; Murray, Ryan R.; Venkatesan, Kavitha; Rual, Jean-Francois; Cusick, Michael E.; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Tasan, Murat; Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Dreze, Matija; Vandenhaute, Jean] Fac Univ Notre Dame Paix, B-5000 Namur, Belgium. [Barrios-Rodiles, Miriam; Roncari, Luba; Pawson, Tony; Wrana, Jeffrey L.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ctr Syst Biol, Toronto, ON M5G 1X5, Canada. [Lemmens, Irma; de Smet, Anne-Sophie; Tavernier, Jan] Univ Ghent, Flanders Inst Biotechnol, Dept Med Prot Res, B-9000 Ghent, Belgium. [Lemmens, Irma; de Smet, Anne-Sophie; Tavernier, Jan] Univ Ghent, Fac Med & Hlth Sci, Dept Biochem, B-9000 Ghent, Belgium. RP Vidal, M (reprint author), Dana Farber Canc Inst, CCSB, 44 Binney St, Boston, MA 02115 USA. EM pascal_braun@dfci.harvard.edu; jan.tavernier@ugent.be; wrana@lunenfeld.ca; fritz_roth@hms.harvard.edu; marc_vidal@dfci.harvard.edu RI Braun, Pascal/B-9669-2013; Hill, David/B-6617-2011; Pawson, Tony/E-4578-2013; Wrana, Jeffrey/F-8857-2013; Roth, Frederick/H-6308-2011; OI Braun, Pascal/0000-0003-2012-6746; , /0000-0001-7002-8488; Rual, Jean-Francois/0000-0003-4465-8819; Roth, Frederick/0000-0002-6628-649X FU W. M. Keck Foundation; Ellison Foundation; Dana-Farber Cancer Institute Strategic Initiative awarded; US National Institutes of Health [5P50HG004233, 2R01HG001715]; University of Ghent [GOA12051401]; Fonds Wetenschappelijk Onderzoek-Vlanderen [G. 0031.06]; FWO-V awarded; Genome Canada; Ontario Genomics Institute awarded; Fonds de la Recherche Scientifique; [R01 ES015728]; [5U54CA112952]; [5U01CA105423]; [R01 HG003224]; [F32 HG004098] FX We thank S. Michnick and N. Ramachandran for reagents and technical help for the PCA and wNAPPA assays, respectively. We thank A. Datti, T. Sun and F. Vizeacoumar from the SMART Robotics Facility at the Samuel Lunenfeld Research Institute for help with the automated version of LUMIER assay. We thank all members of the Vidal, Tavernier, Roth, and Wrana laboratories for helpful discussions, Agencourt Biosciences for sequencing assistance, and A. Bird and D. Maher for administrative assistance. This work was supported by contributions from the W. M. Keck Foundation awarded to M. V., F. P. R. and D. E. H.; by the Ellison Foundation awarded to M. V.; by Institute Sponsored Research funds from the Dana-Farber Cancer Institute Strategic Initiative awarded to M. V. and CCSB; by US National Institutes of Health grants 5P50HG004233 and 2R01HG001715 awarded to M. V., F. P. R. and D. E. H., R01 ES015728 awarded to M. V., 5U54CA112952 awarded to J. Nevins (M. V. subcontract), 5U01CA105423 awarded to S. H. Orkin (M. V. project), R01 HG003224 awarded to F. P. R. and F32 HG004098 awarded to M. T.; by a University of Ghent grant GOA12051401 and the Fonds Wetenschappelijk Onderzoek-Vlanderen (FWO-V) G. 0031.06 awarded to J. T., by a postdoctoral fellowship from the FWO-V awarded to I. L.; and by a grant from Genome Canada and funds from the Ontario Genomics Institute awarded to J. L. W. M. V. is a Chercheur Qualifie Honoraire from the Fonds de la Recherche Scientifique (FRS-FNRS, French Community of Belgium). NR 32 TC 221 Z9 223 U1 0 U2 33 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 JAN PY 2009 VL 6 IS 1 BP 91 EP 98 DI 10.1038/NMETH.1281 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 393JS UT WOS:000262370200031 PM 19060903 ER PT J AU Chiang, DY Getz, G Jaffe, DB O'Kelly, MJT Zhao, XJ Carter, SL Russ, C Nusbaum, C Meyerson, M Lander, ES AF Chiang, Derek Y. Getz, Gad Jaffe, David B. O'Kelly, Michael J. T. Zhao, Xiaojun Carter, Scott L. Russ, Carsten Nusbaum, Chad Meyerson, Matthew Lander, Eric S. TI High-resolution mapping of copy-number alterations with massively parallel sequencing SO NATURE METHODS LA English DT Article ID ARRAY CGH DATA; STRUCTURAL VARIATION; HUMAN GENOME; CANCER; AMPLIFICATIONS; REARRANGEMENTS; DELETIONS; CELLS AB Cancer results from somatic alterations in key genes, including point mutations, copy-number alterations and structural rearrangements. A powerful way to discover cancer-causing genes is to identify genomic regions that show recurrent copy-number alterations (gains and losses) in tumor genomes. Recent advances in sequencing technologies suggest that massively parallel sequencing may provide a feasible alternative to DNA microarrays for detecting copy-number alterations. Here we present: (i) a statistical analysis of the power to detect copy-number alterations of a given size; (ii) SegSeq, an algorithm to segment equal copy numbers from massively parallel sequence data; and (iii) analysis of experimental data from three matched pairs of tumor and normal cell lines. We show that a collection of similar to 14 million aligned sequence reads from human cell lines has comparable power to detect events as the current generation of DNA microarrays and has over twofold better precision for localizing breakpoints (typically, to within similar to 1 kilobase). C1 [Chiang, Derek Y.; Getz, Gad; Jaffe, David B.; O'Kelly, Michael J. T.; Carter, Scott L.; Russ, Carsten; Nusbaum, Chad; Meyerson, Matthew] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Chiang, Derek Y.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chiang, Derek Y.; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Zhao, Xiaojun] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. [Carter, Scott L.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Lander, ES (reprint author), Broad Inst MIT & Harvard, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM lander@broad.mit.edu RI Sincan, Murat /A-3794-2010; Meyerson, Matthew/E-7123-2012; OI Chiang, Derek/0000-0002-1131-6065 FU US National Institutes of Health [5U24CA126546, 5U54HG003] FX We thank C. Mermel, M. Berger and E. Hom for commenting on the manuscript. This work was supported by the US National Institutes of Health (grants 5U24CA126546 to M. M. and 5U54HG003-67 to E. S. L.). NR 28 TC 264 Z9 271 U1 2 U2 17 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 JAN PY 2009 VL 6 IS 1 BP 99 EP 103 DI 10.1038/NMETH.1276 PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 393JS UT WOS:000262370200032 PM 19043412 ER PT J AU Staley, KJ Anderson, AE AF Staley, Kevin J. Anderson, Anne E. TI Hyperactive interneurons impair learning in a neurofibromatosis model SO NATURE NEUROSCIENCE LA English DT Editorial Material ID SYNAPTIC PLASTICITY; PATHWAYS; MEMORY; TYPE-1; MOUSE AB Neurofibromatosis type I is often associated with learning disabilities. Recent work shows that lack of neurofibromin impairs memory because overactive ERK signaling in hippocampal interneurons causes excessive GABA release. C1 [Staley, Kevin J.] Massachusetts Gen Hosp, Div Pediat Neurol, Boston, MA 02114 USA. [Staley, Kevin J.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Anderson, Anne E.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Anderson, Anne E.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Anderson, Anne E.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. RP Staley, KJ (reprint author), Massachusetts Gen Hosp, Div Pediat Neurol, 55 Fruit St, Boston, MA 02114 USA. EM kstaley@partners.org NR 12 TC 2 Z9 2 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 2009 VL 12 IS 1 BP 8 EP + PG 3 WC Neurosciences SC Neurosciences & Neurology GA 388HL UT WOS:000262010800004 PM 19107143 ER PT J AU Starkey, M Rahme, LG AF Starkey, Melissa Rahme, Laurence G. TI Modeling Pseudomonas aeruginosa pathogenesis in plant hosts SO NATURE PROTOCOLS LA English DT Article ID III SECRETION SYSTEM; VIRULENCE FACTORS; STAPHYLOCOCCUS-AUREUS; MOLECULAR-MECHANISMS; ARABIDOPSIS-THALIANA; PATHOGENICITY; INFECTION; DROSOPHILA; RESPONSES; ANIMALS AB A pathogenic model in which both the pathogen and its host are amenable to genetic manipulation can greatly facilitate the understanding of bacterial pathogenesis. Plants are genetically tractable and can be used as experimental models for human microbial pathogenesis. We present protocols for both lettuce and Arabidopsis leaf infection models using the opportunistic human bacterial pathogen, Pseudomonas aeruginosa. The lettuce model allows for high-throughput qualitative analysis of virulence and is suitable for screening large numbers of bacterial strains, whereas the Arabidopsis model provides a quantitative approach and permits the tracking of bacterial cell proliferation in planta. The lettuce model takes similar to 24 h including bacterial growth using store-bought lettuce, and the Arabidopsis model takes 4-6 weeks to grow the plants and a similar time as with lettuce to infect the plants. Both models are monitored for up to 5 d post-infection. These methodologies can and have been used to identify novel and critical P. aeruginosa pathogenicity agents, as virulence factors are often conserved across phylogeny. C1 [Starkey, Melissa; Rahme, Laurence G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Starkey, Melissa; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Starkey, Melissa; Rahme, Laurence G.] Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. RP Rahme, LG (reprint author), Massachusetts Gen Hosp, Dept Surg, 50 Blossom St, Boston, MA 02114 USA. EM rahme@molbio.mgh.harvard.edu FU Shriners Research Fellowship [8506]; [R01AI063433] FX This work was partially supported by the research grant R01AI063433. M. S. was supported by the Shriners Research Fellowship no. 8506. Thank you to Jenifer Bush for growing and maintaining our Arabidopsis plants. NR 37 TC 32 Z9 32 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 2 BP 117 EP 124 DI 10.1038/nprot.2008.224 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 441PT UT WOS:000265781900001 PM 19180083 ER PT J AU Streeck, H Frahm, N Walker, BD AF Streeck, Hendrik Frahm, Nicole Walker, Bruce D. TI The role of IFN-gamma Elispot assay in HIV vaccine research SO NATURE PROTOCOLS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD8(+) T-CELLS; CYTOTOXIC LYMPHOCYTES-T; IMMUNE-RESPONSES; SECRETING CELLS; ESCAPE VARIANTS; INFECTION; VIREMIA; TYPE-1; INDIVIDUALS AB The interferon (IFN)-gamma Elispot assay has been widely used as a general screening method for the quantification and characterization of the human immunodeficiency virus (HIV)-specific CD8+ T cell responses. However, the predictive power of this assay has been challenged due to the lack of efficacy of a recently conducted HIV vaccine phase IIb trial, despite induction of robust Elispot responses. This finding plus improvements in multiparameter flow cytometry, which has the potential advantage of simultaneously quantifying numerous parameters, raises questions regarding the future role of IFN-gamma Elispot as a gateway to moving forward with clinical trials of candidate vaccines. However, the IFN-gamma Elispot assay has been, unlike other techniques, evaluated and validated in several proficiency panels and is advantageous in cost-effectively detecting and mapping T-cell responses. Here we present a detailed protocol for a state-of-the-art 3-d IFN-gamma Elispot assay and review further advantages and disadvantages of this method for the characterization of HIV-specific CD8+ T cell responses. C1 [Streeck, Hendrik; Frahm, Nicole; Walker, Bruce D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst HGH MITand Harvard, Boston, MA 02115 USA. [Streeck, Hendrik; Frahm, Nicole; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Streeck, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst HGH MITand Harvard, Boston, MA 02115 USA. EM hstreeck@partners.org NR 35 TC 67 Z9 71 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 4 BP 461 EP 469 DI 10.1038/nprot.2009.7 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 441PV UT WOS:000265782100003 PM 19282851 ER PT J AU Kim, J Cantor, AB Orkin, SH Wang, JL AF Kim, Jonghwan Cantor, Alan B. Orkin, Stuart H. Wang, Jianlong TI Use of in vivo biotinylation to study protein-protein and protein-DNA interactions in mouse embryonic stem cells SO NATURE PROTOCOLS LA English DT Article ID CHROMATIN IMMUNOPRECIPITATION; PLURIPOTENCY; PURIFICATION; COMPLEXES; NETWORK; CHIP AB In gene regulation, proteins function as members of protein complexes to recognize chromosomal target DNA loci. In dissecting the pluripotent state in mouse embryonic stem (mES) cells, we have used in vivo biotinylation of critical transcription factors for affinity purification of protein complexes and chromatin immunoprecipitation (ChIP)-on-chip for target identification, respectively. Here, we describe detailed procedures for such studies to dissect protein-protein and protein-DNA interactions in mES cells. Specifically, the following three procedures will be described: (i) in vivo biotinylation system setup in mES cells; (ii) affinity purification of multiprotein complexes by one-step streptavidin capture and tandem anti-FLAG/streptavidin affinity purification; (iii) biotin-mediated ChIP (bioChIP). The system setup takes similar to 50 d to complete, and it takes another similar to 15 d and similar to 3 d to perform affinity purification of protein complexes and bioChIP, respectively. C1 [Kim, Jonghwan; Cantor, Alan B.; Orkin, Stuart H.; Wang, Jianlong] Harvard Univ, Sch Med, Harvard Stem Cell Inst,Div Hematol Oncol, Dept Pediat Oncol,Childrens Hosp, Boston, MA 02115 USA. [Kim, Jonghwan; Cantor, Alan B.; Orkin, Stuart H.; Wang, Jianlong] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kim, Jonghwan; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Wang, JL (reprint author), Harvard Univ, Sch Med, Harvard Stem Cell Inst,Div Hematol Oncol, Dept Pediat Oncol,Childrens Hosp, Boston, MA 02115 USA. EM wang@bloodgroup.tch.harvard.edu FU Harvard Stem Cell Institute Cell Reprogramming Program; Howard Hughes Medical Institute; NIH [R01 HL075705]; Investigator of Howard Hughes Medical Institute FX We acknowledge Tyler Moran for his technical assistance in developing these protocols. This work is supported by Seed Grant from the Harvard Stem Cell Institute Cell Reprogramming Program to J.W.J.K. is a Howard Hughes Medical Institute research associate. A. B. C. is supported by NIH Grant R01 HL075705. S.H.O. is an Investigator of Howard Hughes Medical Institute. NR 18 TC 54 Z9 55 U1 4 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 4 BP 506 EP 517 DI 10.1038/nprot.2009.23 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 441PV UT WOS:000265782100007 PM 19325547 ER PT J AU Tannous, BA AF Tannous, Bakhos A. TI Gaussia luciferase reporter assay for monitoring biological processes in culture and in vivo SO NATURE PROTOCOLS LA English DT Article ID DYT1 DYSTONIA CELLS; ALKALINE-PHOSPHATASE; SECRETORY PATHWAY; GENE-EXPRESSION; LIVING MICE; PROMOTER ACTIVITY; EX-VIVO; BIOLUMINESCENCE; CANCER; ANTIGEN AB Secreted reporters are a useful tool in the monitoring of different biological processes in the conditioned medium of cultured cells as well in the blood and urine of experimental animals. Described here is a protocol for detecting the recently established naturally secreted Gaussia luciferase (Gluc) in cultured cells as well as in blood and urine in vivo. Furthermore, the assay for detecting the secreted alkaline phosphatase (SEAP), the most commonly used secreted reporter in serum, is also presented. The Gluc reporter system has several advantages over the SEAP assay, including a much reduced assay time (1-10 min versus 1.5-2 h), 20,000-fold (in vitro) or 1,000-fold (in vivo) increased sensitivity and a linear range covering over five orders of magnitude of cell number. Additionally, the Gluc signal can be detected in urine and the signal can be localized in animals using in vivo bioluminescence imaging. C1 [Tannous, Bakhos A.] Harvard Univ, Sch Med, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. [Tannous, Bakhos A.] Harvard Univ, Sch Med, Ctr Mol Imaging Res, Dept Radiol, Boston, MA 02114 USA. [Tannous, Bakhos A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. RP Tannous, BA (reprint author), Harvard Univ, Sch Med, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. EM btannous@hms.harvard.edu FU Brain Tumor Society; [NIH-NCI P50 CA86355-04]; [1K99CA126839-01] FX I acknowledge all the members of the Tannous laboratory, who contributed to the development of the Gluc blood/urine monitoring of in vivo processes, especially Dr Thomas Wurdinger and Christian Badr. This work was supported partly by grants from NIH-NCI P50 CA86355-04, 1K99CA126839-01 and the Brain Tumor Society. NR 38 TC 100 Z9 103 U1 0 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 4 BP 582 EP 591 DI 10.1038/nprot.2009.28 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 441PV UT WOS:000265782100013 PM 19373229 ER PT J AU Apidianakis, Y Rahme, LG AF Apidianakis, Yiorgos Rahme, Laurence G. TI Drosophila melanogaster as a model host for studying Pseudomonas aeruginosa infection SO NATURE PROTOCOLS LA English DT Article ID PEPTIDOGLYCAN RECOGNITION PROTEIN; ANTIMICROBIAL PEPTIDE GENES; INNATE IMMUNE-RESPONSE; VIRULENCE FACTORS; BACTERIAL-INFECTION; TOLL PATHWAY; PATHOGENESIS; ACTIVATION; DEFENSE; EXPRESSION AB Conservation of host signaling pathways and tissue physiology between Drosophila melanogaster and mammals allows for the modeling of human host-pathogen interactions in Drosophila. Here we present the use of genetically tractable Drosophila models of bacterial pathogenesis to study infection with the human opportunistic pathogen Pseudomonas aeruginosa. We describe and compare two protocols commonly used to infect Drosophila with P. aeruginosa: needle-pricking and injector-pumping. Each model has relevance for examining host components and bacterial factors in host defense and virulence. Fly survival and bacterial proliferation within host flies can be assessed as a measure of host susceptibility and pathogen virulence potential. The profiles of host responses toward P. aeruginosa virulent and non-virulent strains can be determined, enabling the identification of interaction-specific genes that could potentially favor or limit the initiation and progression of infection. Both of the protocols presented herein may be adapted for the inoculation and study of other microbial pathogens. P. aeruginosa cell preparation requires 24 h, fly inoculation 1 h, and fly survival and bacterial proliferation 1-4 d. C1 [Apidianakis, Yiorgos; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Apidianakis, Yiorgos; Rahme, Laurence G.] Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. [Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Rahme, LG (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM rahme@molbio.mgh.harvard.edu OI Apidianakis, Yiorgos/0000-0002-7465-3560 FU Shriners [8892, R01AI063433, 8508] FX This work was partially supported by the research grants, Shriners #8892 and R01AI063433. Y.A. was supported by Shriners research fellowship #8508. NR 71 TC 61 Z9 64 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 9 BP 1285 EP 1294 DI 10.1038/nprot.2009.124 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 504FQ UT WOS:000270601700006 PM 19680242 ER PT J AU Kaufman, CK White, RM Zon, L AF Kaufman, Charles K. White, Richard M. Zon, Leonard TI Chemical genetic screening in the zebrafish embryo SO NATURE PROTOCOLS LA English DT Article ID SMALL-MOLECULE; REGENERATION; PROTEINS; MODELS; CELLS AB Chemical genetic screening can be described as a discovery approach in which chemicals are assayed for their effects on a defined biological system. The zebrafish, Danio rerio, is a well-characterized and genetically tractable vertebrate model organism that produces large numbers of rapidly developing embryos that develop externally. These characteristics allow for flexible, rapid and scalable chemical screen design using the zebrafish. We describe a protocol for screening compounds from a chemical library for effects on early zebrafish development using an automated in situ based read-out. As screenings are carried out in the context of a complete, developing organism, this approach allows for a more comprehensive analysis of the range of a chemical's effects than that provided by, for example, a cell culture-based or in vitro biochemical assay. Using a 24-h chemical treatment, one can complete a round of screening in 6 d. C1 [Kaufman, Charles K.; White, Richard M.; Zon, Leonard] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zon, Leonard] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Zon, Leonard] Harvard Univ, Sch Med, Dept Pediat Med, Boston, MA USA. [Zon, Leonard] Harvard Univ, Sch Med, Dept Stem Cell & Regenerat Biol, Boston, MA USA. RP Zon, L (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU NIH [5T32CA09172-34, 1K08AR055368] FX The authors would like to thank T. North and W. Goessling for use of runx1/cmyb in situ figures. We thank S. Datta and P. Manos for informative discussions. Thanks to C. Mosimann and J. Dejong for critical reading of the manuscript. C. K. K. is supported by NIH grant 5T32CA09172-34. R. M. W. is supported by NIH grant 1K08AR055368. NR 29 TC 77 Z9 77 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 10 BP 1422 EP 1432 DI 10.1038/nprot.2009.144 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 566JV UT WOS:000275367400003 PM 19745824 ER PT J AU Maeder, ML Thibodeau-Beganny, S Sander, JD Voytas, DF Joung, JK AF Maeder, Morgan L. Thibodeau-Beganny, Stacey Sander, Jeffry D. Voytas, Daniel F. Joung, J. Keith TI Oligomerized pool engineering (OPEN): an 'open-source' protocol for making customized zinc-finger arrays SO NATURE PROTOCOLS LA English DT Article ID ARTIFICIAL TRANSCRIPTION FACTORS; DNA-BINDING PROTEINS; CONTROLLING GENE-EXPRESSION; 2-HYBRID SELECTION SYSTEM; GROWTH-FACTOR-A; HUMAN-CELLS; MAMMALIAN-CELLS; HOMOLOGOUS RECOMBINATION; RESTRICTION ENZYMES; CHIMERIC NUCLEASES AB Engineered zinc-finger nucleases (ZFNs) form the basis of a broadly applicable method for targeted, efficient modification of eukaryotic genomes. In recent work, we described OPEN (oligomerized pool engineering), an 'open-source,' combinatorial selection-based method for engineering zinc-finger arrays that function well as ZFNs. We have also shown in direct comparisons that the OPEN method has a higher success rate than previously described 'modular-assembly' methods for engineering ZFNs. OPEN selections are carried out in Escherichia coli using a bacterial two-hybrid system and do not require specialized equipment. Here we provide a detailed protocol for carrying out OPEN to engineer zinc-finger arrays that have a high probability of functioning as ZFNs. Using OPEN, researchers can generate multiple, customized ZFNs in similar to 8 weeks. C1 [Maeder, Morgan L.; Thibodeau-Beganny, Stacey; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA USA. [Maeder, Morgan L.; Thibodeau-Beganny, Stacey; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Maeder, Morgan L.; Joung, J. Keith] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA USA. [Sander, Jeffry D.; Voytas, Daniel F.] Iowa State Univ, Dept Genet Dev & Cell Biol, Roy J Carver Co Lab, Ames, IA USA. [Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Voytas, Daniel F.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA. [Voytas, Daniel F.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN USA. RP Joung, JK (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA USA. EM JJOUNG@PARTNERS.ORG FU National Institutes of Health [R01 GM069906, R24 GM078369, R21 RR024189, R33 GM066387]; MGH Pathology Service; National Science Foundation [DBI 0501678]; Pioneer-Hi-Bred International 2008 Graduate Fellowship; Iowa State University CIAG FX We thank M. Eichtinger, T. Jiang and S. Pruett-Miller for technical assistance and M. Porteus for helpful discussions during early stages of protocol development. M. L. M., S. T.-B. and J. K. J. are supported by grants from the National Institutes of Health (R01 GM069906, R24 GM078369, R21 RR024189) and the MGH Pathology Service. D. F. V. is supported by the National Science Foundation (DBI 0501678). J. D. S. is supported by a Pioneer-Hi-Bred International 2008 Graduate Fellowship, the National Institutes of Health (R33 GM066387) and the Iowa State University CIAG. Note added in proof Shukla et al.78 recently demonstrated ZFN-enhanced gene targeting of an endogenous plant gene. NR 79 TC 104 Z9 111 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 10 BP 1471 EP 1501 DI 10.1038/nprot.2009.98 PG 31 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 566JV UT WOS:000275367400008 PM 19798082 ER PT J AU Foley, JE Maeder, ML Pearlberg, J Joung, JK Peterson, RT Yeh, JRJ AF Foley, Jonathan E. Maeder, Morgan L. Pearlberg, Joseph Joung, J. Keith Peterson, Randall T. Yeh, Jing-Ruey J. TI Targeted mutagenesis in zebrafish using customized zinc-finger nucleases SO NATURE PROTOCOLS LA English DT Article ID TRANSCRIPTION FACTORS; RESTRICTION ENZYMES; MAMMALIAN-CELLS; CLEAVAGE DOMAIN; DROSOPHILA; BINDING; PLANT; CONSTRUCTION; SELECTION; TOXICITY AB Zebrafish mutants have traditionally been obtained by using random mutagenesis or retroviral insertions, methods that cannot be targeted to a specific gene and require laborious gene mapping and sequencing. Recently, we and others have shown that customized zinc-finger nucleases (ZFNs) can introduce targeted frame-shift mutations with high efficiency, thereby enabling directed creation of zebrafish gene mutations. Here we describe a detailed protocol for constructing ZFN expression vectors, for generating and introducing ZFN-encoding RNAs into zebrafish embryos and for identifying ZFN-generated mutations in targeted genomic sites. All of our vectors and methods are compatible with previously described Zinc-Finger Consortium reagents for constructing engineered zinc-finger arrays. Using these methods, zebrafish founders carrying targeted mutations can be identified within 4 months. C1 [Foley, Jonathan E.; Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Foley, Jonathan E.; Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Foley, Jonathan E.; Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA USA. [Maeder, Morgan L.; Joung, J. Keith] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA USA. [Pearlberg, Joseph] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Peterson, Randall T.; Yeh, Jing-Ruey J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Peterson, Randall T.; Yeh, Jing-Ruey J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Peterson, Randall T.] MIT, Broad Inst, Cambridge, MA USA. [Peterson, Randall T.] Harvard Univ, Cambridge, MA 02138 USA. RP Yeh, JRJ (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. EM jyeh1@partners.org FU NIH [R01GM069906, R21RR024189, R21HL091808, CA118498, GM88040, AG031300]; MGH Pathology Service; Ned Sahin Fund; Claflin Distinguished Scholar Award FX We thank Dr. A. J. Giraldez for valuable suggestions and D. Cotelle for technical help on the fluorescent PCR analysis, Drs. P. Schlueter and C. Sachidanandan for helpful suggestions on the manuscript. J. E. F., M. L. M. and J. K. J. are supported by the NIH (R01GM069906, R21RR024189, and R21HL091808) and the MGH Pathology Service. R. T. P. and J.-R. J. Y. are supported by the NIH (CA118498 and GM88040) and the Ned Sahin Fund. J.-R. J. Y. is also supported by the NIH (AG031300) and the Claflin Distinguished Scholar Award. NR 45 TC 66 Z9 67 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 12 BP 1855 EP 1868 DI 10.1038/nprot.2009.209 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 551RG UT WOS:000274226100014 PM 20010934 ER PT J AU Zhang, JM Yang, PL Gray, NS AF Zhang, Jianming Yang, Priscilla L. Gray, Nathanael S. TI Targeting cancer with small molecule kinase inhibitors SO NATURE REVIEWS CANCER LA English DT Review ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; RECEPTOR TYROSINE KINASE; ACTIVATED PROTEIN-KINASE; GROWTH-FACTOR RECEPTOR; RIBOSOMAL S6 KINASE; ABL KINASE; BCR-ABL; ANTITUMOR-ACTIVITY; CRYSTAL-STRUCTURE AB Deregulation of kinase activity has emerged as a major mechanism by which cancer cells evade normal physiological constraints on growth and survival. To date, 11 kinase inhibitors have received US Food and Drug Administration approval as cancer treatments, and there are considerable efforts to develop selective small molecule inhibitors for a host of other kinases that are implicated in cancer and other diseases. Herein we discuss the current challenges in the field, such as designing selective inhibitors and developing strategies to overcome resistance mutations. This Review provides a broad overview of some of the approaches currently used to discover and characterize new kinase inhibitors. C1 [Zhang, Jianming; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Dana Farber Canc Inst,Dept Canc Biol, Boston, MA 02115 USA. [Yang, Priscilla L.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Gray, NS (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Dana Farber Canc Inst,Dept Canc Biol, 250 Longwood Ave, Boston, MA 02115 USA. EM NathanaelGray@dfci.harvard.edu FU NIAID NIH HHS [R01 AI076442] NR 105 TC 1155 Z9 1179 U1 36 U2 355 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X EI 1474-1768 J9 NAT REV CANCER JI Nat. Rev. Cancer PD JAN PY 2009 VL 9 IS 1 BP 28 EP 39 DI 10.1038/nrc2559 PG 12 WC Oncology SC Oncology GA 387CQ UT WOS:000261929700017 PM 19104514 ER PT J AU Patapoutian, A Tate, S Woolf, CJ AF Patapoutian, Ardem Tate, Simon Woolf, Clifford J. TI Transient receptor potential channels: targeting pain at the source SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID GLUTAMATERGIC SYNAPTIC-TRANSMISSION; SUBSTANTIA-GELATINOSA NEURONS; HEAT-EVOKED ACTIVATION; P38 MAPK ACTIVATION; MICE LACKING TRPV4; RAT SPINAL-CORD; VANILLOID RECEPTOR; ION-CHANNEL; SENSORY NEURONS; CAPSAICIN-RECEPTOR AB Pain results from the complex processing of neural signals at different levels of the central nervous system, with each signal potentially offering multiple opportunities for pharmacological intervention. A logical strategy for developing novel analgesics is to target the beginning of the pain pathway, and aim potential treatments directly at the nociceptors -the high-threshold primary sensory neurons that detect noxious stimuli. The largest group of receptors that function as noxious stimuli detectors in nociceptors is the transient receptor potential (TRP) channel family. This Review highlights evidence supporting particular TRP channels as targets for analgesics, indicates the likely efficacy profiles of TRP-channel-acting drugs, and discusses the development pathways needed to test candidates as analgesics in humans. C1 [Woolf, Clifford J.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Woolf, Clifford J.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Patapoutian, Ardem] Scripps Res Inst, La Jolla, CA 92037 USA. [Patapoutian, Ardem] Genom Inst Novartis Res Fdn, San Diego, CA 92121 USA. [Tate, Simon] GlaxoSmithKline Res & Dev Ltd, Harlow CM19 5AW, Essex, England. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, 149 13th, Charlestown, MA 02129 USA. EM cwoolf@partners.org FU NINDS NIH HHS [R01 NS039518-08, R01 NS038253, R01 NS038253-10, R01 NS039518] NR 163 TC 265 Z9 273 U1 0 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD JAN PY 2009 VL 8 IS 1 BP 55 EP 68 DI 10.1038/nrd2757 PG 14 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 390IJ UT WOS:000262157200018 PM 19116627 ER PT J AU Kolesnikova, T Kazarov, A Lemieux, ME Lafleur, M Kesari, S Kung, AL Hemler, ME AF Kolesnikova, Tatiana Kazarov, Alexander Lemieux, Madeleine E. Lafleur, Marc Kesari, Santosh Kung, Andrew L. Hemler, Martin E. TI Glioblastoma Inhibition by Cell Surface Immunoglobulin Protein EWI-2, In Vitro and In Vivo SO NEOPLASIA LA English DT Article ID GLIOMA INVASION; CANCER-CELLS; MATRIX METALLOPROTEINASES; GRADE ASTROCYTOMAS; TETRASPANIN WEB; FACTOR-ALPHA; MOUSE-BRAIN; MAJOR CD9; EXPRESSION; MEMBRANE AB EWI-2, a cell surface IgSF protein, is highly expressed in normal human brain but is considerably diminished in glioblastoma tumors and cell lines. Moreover, loss of EWI-2 expression correlated with a shorter survival time in human glioma patients, suggesting that EWI-2 might be a natural inhibitor of glioblastoma. In support of this idea, EWI-2 expression significantly impaired both ectopic and orthotopic tumor growth in nude mice in vivo. In vitro assays provided clues regarding EWI-2 functions. Expression of EWI-2 in T98G and/or U87-MG malignant glioblastoma cell lines failed to alter two-dimensional cell proliferation but inhibited glioblastoma colony formation in soft agar and caused diminished cell motility and invasion. At the biochemical level, EWI-2 markedly affects the organization of four molecules (tetraspanin proteins CD9 and CD81 and matrix metalloproteinases MMP-2 and MT1-MMP), which play key roles in the biology of astrocytes and gliomas. EWI-2 causes CD9 and CD81 to become more associated with each other, whereas CD81 and other tetraspanins become less associated with MMP-2 and MT1-MMP. We propose that EWI-2 inhibition of glioblastoma growth in vivo is at least partly explained by the capability of EWI-2 to inhibit growth and/or invasion in vitro. Underlying these functional effects, EWI-2 causes a substantial molecular reorganization of multiple molecules (CD81, CD9, MMP-2, and MT1-MMP) known to affect proliferation and/or invasion of astrocytes and/or glioblastomas. C1 [Hemler, Martin E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Rm D1430,44 Binney St, Boston, MA 02115 USA. EM martin_hemler@dfci.harvard.edu RI Kesari, Santosh/E-8461-2013; OI Lemieux, Madeleine/0000-0001-6355-8691; Kung, Andrew/0000-0002-9091-488X FU National Institutes of Health [GM38903, CA42368]; Ruth L. Kirschstein National Research Service Award [T32]; Sidney Kimmel Foundation; Canadian Institutes of Health Research Fellowship; National Institutes of Health K08 [K08CA124804]; Sontag Foundation Distinguished Scientist Award FX This work was supported by grants from the National Institutes of Health (GM38903, CA42368) to M. E. H., Ruth L. Kirschstein National Research Service Award (T32) to T. V. K., Sidney Kimmel Foundation grant to A. L. K., Canadian Institutes of Health Research Fellowship to M. A. L, and National Institutes of Health K08 (K08CA124804) and Sontag Foundation Distinguished Scientist Award to S.K. NR 59 TC 27 Z9 27 U1 0 U2 1 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 JAN PY 2009 VL 11 IS 1 BP 77 EP U99 DI 10.1593/neo.81180 PG 14 WC Oncology SC Oncology GA 385XO UT WOS:000261847100009 PM 19107234 ER PT J AU Nosho, K Shima, K Kure, S Irahara, N Baba, Y Chen, L Kirkner, GJ Fuchs, CS Ogino, S AF Nosho, Katsuhiko Shima, Kaori Kure, Shoko Irahara, Natsumi Baba, Yoshifumi Chen, Li Kirkner, Gregory J. Fuchs, Charles S. Ogino, Shuji TI JC Virus T-Antigen in Colorectal Cancer Is Associated with p53 Expression and Chromosomal Instability, Independent of CpG Island Methylator Phenotype SO NEOPLASIA LA English DT Article ID ABERRANT PROMOTER METHYLATION; POPULATION-BASED SAMPLE; GROWTH-FACTOR RECEPTOR; EPSTEIN-BARR-VIRUS; MICROSATELLITE INSTABILITY; DNA METHYLATION; COLON-CANCER; BETA-CATENIN; HEPATOCELLULAR-CARCINOMA; TUMOR-SUPPRESSOR AB JC virus has a transforming gene encoding JC virus T-antigen (JCVT). JCVT may inactivate wild-type p53, cause chromosomal instability (CIN), and stabilize beta-catenin. A link between JCVT and CpG island methylator phenotype (CIMP) has been suggested. However, no large-scale study has examined the relations of JCVT with molecular alterations, clinical outcome, or prognosis in colon cancer. We detected JCVT expression (by immunohistochemistry) in 271 (35%) of 766 colorectal cancers. We quantified DNA methylation in eight CIMP-specific promoters (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1) and eight other loci (CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14, WRN) by MethyLight. We examined loss of heterozygosity in 2p, 5q, 17q, and 18q. JCVT was significantly associated with p53 expression (P < .0001), p21 loss (P < .0001), CIN (>= 2 chromosomal segments with LOH; P < .0001), nuclear beta-catenin (P = .006), LINE-1 hypomethylation (P = .002), and inversely with CIMP-high (P = .0005) and microsatellite instability (MSI) (P < .0001), but not with PIK3CA mutation. In multivariate logistic regression analysis, the associations of JCVT with p53 [adjusted odds ratio (OR), 8.45; P < .0001], CIN (adjusted OR, 2.53; P = .003), cyclin D1 (adjusted OR, 1.57; P = .02), LINE-1 hypomethylation (adjusted OR, 1.97 for a 30% decline as a unit; P = .03), BRAF mutation (adjusted OR, 2.20; P = .04), and family history of colorectal cancer (adjusted OR, 0.64; P = .04) remained statistically significant. However, JCVT was no longer significantly associated with CIMP, MSI, beta-catenin, or cyclooxygenase-2 expression in multivariate analysis. JCVT was unrelated with patient survival. In conclusion, JCVT expression in colorectal cancer is independently associated with p53 expression and CIN, which may lead to uncontrolled cell proliferation. C1 [Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Ctr Mol Oncol Pathol, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Ctr Mol Oncol Pathol, 44 Binney St,Room JF-215C, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU US National Institutes of Health (NIH) [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA122826]; Bennett Family Fund; Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance; Japan Society for Promotion of Science FX This work was supported by US National Institutes of Health (NIH) grants P01 CA87969, P01 CA55075, P50 CA127003, and K07 CA122826 (to S.O.) and in part by grants from the Bennett Family Fund and from the Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance. K.N. was supported by a fellowship grant from the Japan Society for Promotion of Science. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 34 Z9 34 U1 0 U2 4 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 JAN PY 2009 VL 11 IS 1 BP 87 EP 95 DI 10.1593/neo.81188 PG 9 WC Oncology SC Oncology GA 385XO UT WOS:000261847100010 PM 19107235 ER PT J AU Drzezga, A AF Drzezga, A. TI Clinical value of nuclear medicine approaches in the diagnosis of dementia SO NERVENHEILKUNDE LA German DT Review DE PET; FDG; PIB; dementia; Alzheimer's disease ID MILD COGNITIVE IMPAIRMENT; FRONTOTEMPORAL LOBAR DEGENERATION; CEREBRAL GLUCOSE-METABOLISM; POSITRON-EMISSION-TOMOGRAPHY; PITTSBURGH COMPOUND-B; PRECLINICAL ALZHEIMERS-DISEASE; PRIMARY PROGRESSIVE APHASIA; LONGITUDINAL PET EVALUATION; FDG-PET; LEWY BODIES AB So far, a definite diagnosis of different forms of neurodegenerative dementias can only be carried out by post-mortem histopathological evaluation of brain tissue. It is accepted that the pathological changes in the brain start years to decades ahead of the onset of clinical symptoms. The utility of clinical/neuropsychological test measures for early diagnosis of these disorders in mild or asymptomatic stages is therefore limited. Additionally, the symptomatic overlap between different forms of dementia hampers clinical differential diagnosis. Particularly new treatment approaches constitute the need for reliable early and differential diagnosis, which underlines the need for suitable biomarkers. Here, we will discuss the value of two functional/ molecular imaging procedures, which are most promising and well-evaluated for this purpose FDG PET (positron emission tomography) as a measure of neuronal dysfunction and amyloid-plaque imaging using modern PET tracer such as PIB. The value of these imaging tools for early and differential diagnosis as well as for patient selection for therapy studies and for objective therapy control will be discussed. C1 [Drzezga, A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Drzezga, A.] Tech Univ Munich, Nukl Med Klin, Klinikum Rechts Isar, D-8000 Munich, Germany. RP Drzezga, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Room 2301, Charlestown, MA 02129 USA. EM adrzezga@nmr.mgh.harvard.edu NR 101 TC 2 Z9 2 U1 5 U2 8 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0722-1541 J9 NERVENHEILKUNDE JI Nervenheilkunde PY 2009 VL 28 IS 10 BP 709 EP 717 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 509SY UT WOS:000271039900005 ER PT J AU Goyal, S Pless, M Krishnamoorthy, K Butler, WE Noviski, N Gupta, P AF Goyal, Sunali Pless, Misha L. Krishnamoorthy, Kalapathy Butler, William E. Noviski, Natan Gupta, Punkaj TI What's New in Childhood Idiopathic Intracranial Hypertension? SO NEURO-OPHTHALMOLOGY LA English DT Review DE Childhood idiopathic intracranial hypertension; pseudotumour cerebri; papilloedema; cerebrospinal fluid pressure; optic nerve sheath fenestration; obesity; lumbo peritoneal shunt ID NERVE SHEATH DECOMPRESSION; PEDIATRIC PSEUDOTUMOR CEREBRI; GROWTH-HORMONE THERAPY; PERCUTANEOUS LUMBOPERITONEAL SHUNT; L-THYROXINE THERAPY; INDUCED WEIGHT-LOSS; CEREBROSPINAL-FLUID; VISUAL-LOSS; FOLLOW-UP; VENTRICULOPERITONEAL SHUNT AB Idiopathic Intracranial Hypertension (IIH) occurs quite rarely in the paediatric population and its clinical features differ from adults in many ways. Childhood IIH has no sex predilection, and obesity does not appear to be an important factor, especially in prepubertal patients. Newer associations of this disease have been reported that were never reported in the past, mainly due to better understanding of the disease process, changing clinical practice, and technological advancement. Understanding of childhood IIH is very limited as most of the studies regarding the pathogenesis of IIH relate to adults. Prompt diagnosis and treatment is important as children can sustain loss of visual field and acuity despite apparently adequate treatment. Children with IIH should be managed by a multi-disciplinary team consisting of a general paediatrician, a neuro-ophthalmologist, a neurologist, a neurosurgeon, and when appropriate a paediatric neuro-intensivist. The goal of treatment is to relieve symptoms and to preserve vision by normalizing intracranial pressure. Children with IIH should be kept under close surveillance and evaluated for visual acuity, visual fields, colour vision, pupillary function and optic disc oedema. C1 [Goyal, Sunali] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Pless, Misha L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuroophthalmol,Dept Gen Neurol, Boston, MA USA. [Krishnamoorthy, Kalapathy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Gen Neurol, Boston, MA USA. [Butler, William E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Noviski, Natan; Gupta, Punkaj] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Paediat Intens Care, Boston, MA USA. RP Goyal, S (reprint author), 160 Pleasant St,Apt 510, Malden, MA 02148 USA. EM sunali_goyal@hotmail.com NR 160 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0165-8107 J9 NEURO-OPHTHALMOLOGY JI Neuro-Ophthalmol. PY 2009 VL 33 IS 1-2 BP 23 EP 35 AR PII 910575935 DI 10.1080/01658100902717074 PG 13 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 435YG UT WOS:000265378800004 ER PT J AU Goyal, S Pless, ML AF Goyal, Sunali Pless, Misha L. TI Isolated Inferior Rectus Palsy: A Case Report and Review of Literature SO NEURO-OPHTHALMOLOGY LA English DT Article DE Diplopia; oculomotor nerve; extraocular movements; inferior rectus paralysis ID CONGENITAL ABSENCE; OCULOMOTOR PARESIS; CRANIAL NERVES; MUSCLE PALSY; INFARCTION; METASTASIS; PARALYSIS; NUCLEUS AB A case of sudden-onset isolated inferior rectus paresis is described. This is a rare presentation of isolated oculomotor nerve paresis and its features are described. Lesions of the oculomotor nerve can affect any of the functions of the extraocular muscles depending on the location and the aetiology of the lesion. An interesting subgroup of patients having isolated paresis of inferior rectus muscle without involvement of the other muscles has always drawn special interest. The purpose of this article is to report a case of binocular vertical diplopia resulting from an isolated, unilateral inferior rectus paresis followed by a review of the existing literature along with a discussion of neuroanatomy, aetiology, clinical features and management. Clinicians may increase their awareness of the spectrum of various possible causes that can present with isolated IRM palsy. C1 [Goyal, Sunali] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Pless, Misha L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuroophthalmol,Dept Gen Neurol, Boston, MA USA. RP Goyal, S (reprint author), 160 Pleasant St,Apt 510, Malden, MA 02148 USA. EM sunali_goyal@hotmail.com NR 31 TC 1 Z9 1 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0165-8107 J9 NEURO-OPHTHALMOLOGY JI Neuro-Ophthalmol. PY 2009 VL 33 IS 1-2 BP 52 EP 58 AR PII 910575809 DI 10.1080/01658100802590803 PG 7 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 435YG UT WOS:000265378800008 ER PT J AU Mejia, NI Pless, M AF Mejia, Nicte I. Pless, Misha TI Downbeat Nystagmus in Wernicke Encephalopathy SO NEURO-OPHTHALMOLOGY LA English DT Article C1 [Mejia, Nicte I.; Pless, Misha] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Mejia, NI (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM nmejia@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0165-8107 J9 NEURO-OPHTHALMOLOGY JI Neuro-Ophthalmol. PY 2009 VL 33 IS 4 BP 178 EP 179 AR PII 913871834 DI 10.1080/01658100902842666 PG 2 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 497EL UT WOS:000270038400004 ER PT J AU Dumitrascu, OM Costa, RMS Kirsch, C Arnold, AC Gordon, LK AF Dumitrascu, Oana M. Costa, Roberta M. S. Kirsch, Claudia Arnold, Anthony C. Gordon, Lynn K. TI Cavernous Sinus Syndrome Resulting from Contiguous Spread of Adenoid Cystic Carcinoma: A Systematic Analysis of Reported Cases SO NEURO-OPHTHALMOLOGY LA English DT Review DE cavernous sinus; adenoid cystic; carcinoma ID MINOR SALIVARY-GLANDS; PERINEURAL SPREAD; SKULL BASE; LACRIMAL GLAND; NECK; HEAD; TUMOR; METASTASIS; EXTENSION; INVOLVEMENT AB Purpose: The aim of this review is to analyze all reported cases of histologically confirmed adenoid cystic carcinoma (ACC) with cavernous sinus involvement identified in the literature in order to elucidate the clinical symptoms, neuro-ophthalmic and neuro-imaging findings. Methods: A systematic electronic database search (Medline, Biosis and Cochrane) and a literature review were used to identify reported cases which were assessed for demographic information; primary tumour site; pattern of spread; extent and timing of cranial nerve involvement; and neuro-imaging findings. Conclusions: Neuro-ophthalmologic evaluation is extremely important in the diagnosis of this disease which has a propensity for perineural and direct orbital invasion. C1 [Dumitrascu, Oana M.; Costa, Roberta M. S.; Arnold, Anthony C.; Gordon, Lynn K.] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Kirsch, Claudia] Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA 90095 USA. [Gordon, Lynn K.] W Los Angeles Vet Affairs Healthcare Ctr, Los Angeles, CA USA. RP Gordon, LK (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM lgordon@ucla.edu NR 41 TC 0 Z9 0 U1 2 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0165-8107 J9 NEURO-OPHTHALMOLOGY JI Neuro-Ophthalmol. PY 2009 VL 33 IS 6 BP 300 EP 307 DI 10.3109/01658100903226208 PG 8 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 586PH UT WOS:000276922500003 ER PT S AU Bertram, L AF Bertram, Lars BE Minagar, A TI ALZHEIMER'S DISEASE GENETICS: CURRENT STATUS AND FUTURE PERSPECTIVES SO NEUROBIOLOGY OF DEMENTIA SE International Review of Neurobiology LA English DT Review ID GENOME-WIDE ASSOCIATION; NICOTINIC ACETYLCHOLINE-RECEPTORS; AMYLOID PRECURSOR PROTEIN; SYSTEMATIC METAANALYSES; MISSENSE MUTATIONS; APOLIPOPROTEIN-E; ONSET; SUSCEPTIBILITY; AGE; LINKAGE AB Alzheimer's disease (AD) is a genetically complex disease whose pathogenesis is largely influenced by genetic factors. Three decades of intensive research have yielded four established AD genes (APP, PSEN1, PSEN2, APOE), and hundreds of potential susceptibility loci, none of which has been unequivocally shown to modify disease risk using conventional methodologies. The results of genome-wide association studies (GWAS) are now adding to an already vast and complicated body of data. To facilitate the evaluation and interpretation of these findings, we have recently created a database for genetic association studies in AD ("AlzGene"; available at http://www.alzgene.org). In addition to systematically screening and summarizing the scientific literature for eligible studies, AlzGene provides the results of allele-based meta-analyses for all polymorphisms with sufficient genotype data. Currently, these meta-analyses highlight over 20 different potential AD genes, several of which were originally implicated by a GWAS. First follow-up analyses in a large collection of over 1300 AD families reveal that-in addition to APOE-genetic variants in CHRNB2, GAB2, and TF show the most consistent risk effects across a wide range of independent samples and study designs. The chapter highlights these and other promising findings from the recent AD genetics literature and provides an overview of the powerful new tools aiding researchers today to unravel the genetic underpinnings of this devastating disease. C1 [Bertram, Lars] Max Planck Inst Mol Genet, Neuropsychiat Genet Grp, Dept Vertebrate Genom, D-14195 Berlin, Germany. [Bertram, Lars] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Bertram, L (reprint author), Max Planck Inst Mol Genet, Neuropsychiat Genet Grp, Dept Vertebrate Genom, Ihnestr 73, D-14195 Berlin, Germany. RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X NR 57 TC 34 Z9 37 U1 1 U2 12 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 978-0-12-374833-1 J9 INT REV NEUROBIOL PY 2009 VL 84 BP 167 EP 184 DI 10.1016/S0074-7742(09)00409-7 PG 18 WC Neurosciences SC Neurosciences & Neurology GA BKB54 UT WOS:000267693100009 PM 19501718 ER PT J AU Dragileva, E Hendricks, A Teed, A Gillis, T Lopez, ET Friedberg, EC Kucherlapati, R Edelmann, W Lunetta, KL MacDonald, ME Wheeler, VC AF Dragileva, Ella Hendricks, Audrey Teed, Allison Gillis, Tammy Lopez, Edith T. Friedberg, Errol C. Kucherlapati, Raju Edelmann, Winfried Lunetta, Kathryn L. MacDonald, Marry E. Wheeler, Vanessa C. TI Intergenerational and striatal CAG repeat instability in Huntington's disease knock-in mice involve different DNA repair genes SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Huntington's disease; Trinucleotide; Instability; Repeat; Striatum; Repair; Mouse; Knock-in; Pathogenesis ID NUCLEOTIDE EXCISION-REPAIR; SACCHAROMYCES-CEREVISIAE MSH2; TRINUCLEOTIDE REPEAT; SOMATIC INSTABILITY; TRANSGENIC MICE; LENGTH; MUTATION; EXPANSION; NUCLEAR; BINDS AB Modifying the length of the Huntington's disease (HD) CAG repeat, the major determinant of age of disease onset, is an attractive therapeutic approach. To explore this we are investigating mechanisms of intergenerational and somatic HD CAG repeat instability. Here, we have crossed HD CAG knock-in mice onto backgrounds deficient in mismatch repair genes, Msh3 and Msh6, to discern the effects on CAG repeat size and disease pathogenesis. We find that different mechanisms predominate in inherited and somatic instability, with Msh6 protecting against intergenerational contractions and Msh3 required both for increasing CAG length and for enhancing an early disease phenotype in striatum. Therefore, attempts to decrease inherited repeat size may entail a full understanding of Msh6 complexes, while attempts to block the age-dependent increases in CAG size in striatal neurons and to slow the disease process will require a full elucidation of Msh3 complexes and their function in CAG repeat instability. (c) 2008 Elsevier Inc. All rights reserved. C1 [Dragileva, Ella; Teed, Allison; Gillis, Tammy; Lopez, Edith T.; MacDonald, Marry E.; Wheeler, Vanessa C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. [Hendricks, Audrey; Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Friedberg, Errol C.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Kucherlapati, Raju] Harvard Partners Ctr Genet & Genom, Cambridge, MA 02139 USA. [Kucherlapati, Raju] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Edelmann, Winfried] Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. RP Wheeler, VC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. EM wheeler@helix.mgh.harvard.edu RI Hendricks, Audrey/I-4127-2016; OI Hendricks, Audrey/0000-0002-7152-0287; Lunetta, Kathryn/0000-0002-9268-810X FU National Institutes of Health [NS049206, NS532167, NS16367] FX We would like to thank Dr. Xiao jiang Li for generously providing the EM48 polyclonal antibody, Dr. Hein to Riele for the Msh2 knockout mice and Dr. Susan Cotman for discussion and critical reading of the manuscript. This work was funded by the National Institutes of Health NS049206 (V.C.W), NS532167 (M.E.M), NS16367 (M.E.M, K.L.L.); The Huntington's Disease Society of America (V.C.W); The Jerry MacDonald HD Research Fund (K.L.L). NR 47 TC 74 Z9 74 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JAN PY 2009 VL 33 IS 1 BP 37 EP 47 DI 10.1016/j.nbd.2008.09.014 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 394PB UT WOS:000262457900005 PM 18930147 ER PT J AU Yao, JK Wengenack, TM Curran, GL Poduslo, JF AF Yao, Jeffrey K. Wengenack, Thomas M. Curran, Geoffry L. Poduslo, Joseph F. TI Reduced Membrane Lipids in the Cortex of Alzheimer's Disease Transgenic Mice SO NEUROCHEMICAL RESEARCH LA English DT Article DE Alzheimer's disease; Double transgenic mice; Cortex; Lipids; Polyunsaturated fatty acids ID AMYLOID BETA-PROTEIN; N-3 FATTY-ACIDS; DOCOSAHEXAENOIC ACID; MOUSE MODEL; BRAIN; CHOLESTEROL; RISK; PHOSPHOLIPIDS; PATHOGENESIS; METABOLISM AB Accumulating evidence suggests that the conversion of A beta peptides to soluble, neurotoxic polymers is the key event in the development of Alzheimer's disease (AD). Moreover, interactions between A beta peptides and neuronal membrane lipids likely play a vital role in developing the neurotoxicity associated with AD. The aim of this study is to assess whether lipid matrix of neuronal membranes is affected by the accumulation of A beta peptides in double transgenic mouse model of AD expressing both mutant human beta-amyloid precursor protein (APP) and presenilin 1 (PS1). We apply high pressure liquid chromatography with an evaporative light scattering detector to compare levels of cholesterol, galactocerebrosides, and phospholipid subclasses simultaneously in cortex samples between AD double transgenic mice at 4 months of age when A beta production and amyloid plaque deposition is just beginning and at 9 months, when there is advanced A beta levels and plaque deposition compared to age-matched wild-type (B6/SJL) mice. Both cholesterol (CL) and phospholipids (PL) are significantly lower in 9-month-old AD mice than the same age of B6/SJL mice. Among PL subclasses, phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylcholine (PC) are selectively reduced in 9-month-old AD mice. The molar ratios of CL to PL in 9-month-old AD mice (1.19 +/- A 0.27) were significantly higher than those of 9-month-old B6/SJL mice (0.81 +/- A 0.08). In keeping with decreased levels of PL, there are also significant reductions of very long-chain n-3 fatty acids (docosahexaenoic acid) and n-6 fatty acid (arachidonic acid) in 9-month-old AD mice. On the other hand, ratios of total n-6 to total n-3 fatty acids were significantly higher in 9-month-old AD mice than in the same age of B6/SJL mice. Taken together, our present data support a role for the interactions of amyloid-beta peptide and neuronal membranes in the subsequent development of AD. C1 [Yao, Jeffrey K.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA 15206 USA. [Yao, Jeffrey K.] Univ Pittsburgh, Dept Psychiat, Med Ctr, Pittsburgh, PA 15213 USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15238 USA. [Wengenack, Thomas M.; Curran, Geoffry L.; Poduslo, Joseph F.] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN 55905 USA. [Wengenack, Thomas M.; Curran, Geoffry L.; Poduslo, Joseph F.] Mayo Clin, Coll Med, Dept Neurosci, Rochester, MN 55905 USA. [Wengenack, Thomas M.; Curran, Geoffry L.; Poduslo, Joseph F.] Mayo Clin, Coll Med, Dept Biochem Mol Biol, Rochester, MN 55905 USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, Med Res Serv, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM jkyao@pitt.edu FU Office of Research and Development; Department of Veterans Affairs; National Institute of Health [AG22034]; Highland Drive VA Pittsburgh Healthcare System FX This work was supported in part by the grants from Office of Research and Development, Department of Veterans Affairs [Senior Research Career Scientist Award (JKY)], and National Institute of Health [AG22034 (JFP)], and the Highland Drive VA Pittsburgh Healthcare System. The authors are grateful to Dr. Karen Duff for the PS1 transgenic mouse line and to J. J. Carroll and C. Runyan for their technical assistance. NR 40 TC 28 Z9 28 U1 0 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD JAN PY 2009 VL 34 IS 1 BP 102 EP 108 DI 10.1007/s11064-008-9673-1 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 393VS UT WOS:000262403000013 PM 18373196 ER PT J AU Irizarry, MC Raman, R Schwarzschild, MA Becerra, LM Thomas, RG Peterson, RC Ascherio, A Aisen, PS AF Irizarry, Michael C. Raman, Rema Schwarzschild, Michael A. Becerra, Lida M. Thomas, Ronald G. Peterson, Ronald C. Ascherio, Alberto Aisen, Paul S. TI Plasma Urate and Progression of Mild Cognitive Impairment SO NEURODEGENERATIVE DISEASES LA English DT Article DE Alzheimer's disease; Mild cognitive impairment; Urate; Oxidative stress; Biomarkers ID SERUM URIC-ACID; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; OXIDATIVE STRESS; RISK; ANTIOXIDANTS; PREDICTOR; DEMENTIA; ADULTS AB Background: Impaired antioxidant defenses are implicated in neurodegenerative disease. The plasma levels of urate, a water-soluble antioxidant, are reduced in Alzheimer's disease (AD). Objective: We aimed to test the hypotheses that high plasma urate at baseline is associated with: (1) a reduced rate of conversion from mild cognitive impairment (MCI) to AD and (2) a lower rate of cognitive decline in MCI. Methods: Plasma urate was obtained at baseline from 747 participants in a 3-year, randomized, double-blind, placebo-controlled study of donepezil, vitamin E or placebo for delaying the progression of MCI to AD. The association between baseline urate and conversion from MCI to AD was examined by Cox proportional hazards regression. The relationship between baseline urate and cognitive change on the cognitive subscale of the Alzheimer's Disease Assessment Scale was evaluated by longitudinal analysis. Results: Baseline plasma urate was not associated with the rate of conversion of MCI to AD. In the placebo arm, high plasma urate was related to a slower rate of cognitive decline over 3 years, although this was not reproduced in the other treatment arms. Conclusion: While plasma urate levels did not predict the progression of MCI to AD, high urate may be associated with a reduced rate of cognitive decline in MCI patients not treated with donepezil or vitamin E. The results support the investigation of biomarkers of antioxidant status as risk factors for cognitive decline in MCI. Copyright (C) 2008 S. Karger AG, Basel C1 [Irizarry, Michael C.; Schwarzschild, Michael A.] Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Raman, Rema; Becerra, Lida M.; Thomas, Ronald G.] Univ Calif San Diego, Dept Family & Prevent Med, Div Biostat & Bioinformat, San Diego, CA 92103 USA. [Raman, Rema; Thomas, Ronald G.; Aisen, Paul S.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Peterson, Ronald C.] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN USA. RP Irizarry, MC (reprint author), GlaxoSmithKline Inc, WW Epidemiol, 5 Moore Dr,17-2123, Res Triangle Pk, NC 27709 USA. EM michael.c.irizarry@gsk.com FU Alzheimer's Disease Cooperative Study Group; NIH [U01AG10483, R01ES010804] FX Supported by the Alzheimer's Disease Cooperative Study Group, NIH U01AG10483 and R01ES010804. NR 17 TC 45 Z9 48 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2009 VL 6 IS 1-2 BP 23 EP 28 DI 10.1159/000170883 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 381FY UT WOS:000261522300004 PM 19066433 ER PT J AU Pitteloud, N Thambundit, A Dwyer, AA Falardeau, JL Plummer, L Caronia, LM Hayes, FJ Lee, H Boepple, PA Crowley, WF AF Pitteloud, Nelly Thambundit, Apisadaporn Dwyer, Andrew A. Falardeau, John L. Plummer, Lacey Caronia, Lisa M. Hayes, Frances J. Lee, Hang Boepple, Paul A. Crowley, William F., Jr. TI Role of Seminiferous Tubular Development in Determining the FSH versus LH Responsiveness to GnRH in Early Sexual Maturation SO NEUROENDOCRINOLOGY LA English DT Article DE GnRH; LH; FSH; Puberty; Gonadal development ID GONADOTROPIN-RELEASING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; FOLLICLE-STIMULATING-HORMONE; SERUM INHIBIN B; ADRENAL HYPOPLASIA CONGENITA; LUTEINIZING-HORMONE; KALLMANN-SYNDROME; ESTRADIOL LEVELS; NORMAL BOYS; NORMAL MEN AB Background: The onset of sexual maturation at puberty is a unique developmental period from a neuroendocrine perspective in that it is characterized by enhanced FSH secretion and FSH responsiveness to exogenous GnRH (vs. LH) from the gonadotrope, yet the mechanism of these dynamics remains unclear. This study aimed to elucidate this phenomenon using a human disease model of GnRH deficiency (idiopathic hypogonadotropic hypogonadism, IHH) in which GnRH input can be experimentally controlled. Methods: 25 GnRH-deficient men were selected for study based upon their baseline testicular volumes (TV) and serum inhibin B (I-B) levels to represent a spectrum of pubertal/testicular development. Subjects underwent: (i) a 12-hour overnight neuroendocrine evaluation for hormonal profiling and determination of endogenous LH secretion pattern, and (ii) a 7-day exposure to a physiologic regimen of exogenous pulsatile GnRH (25 ng/kg every 2 h). Daily measurements of serum testosterone (T) and I-B levels were made and a 2-hour window of frequent blood sampling was monitored to measure LH and FSH following a single i.v. GnRH bolus (25 ng/kg). All subjects were screened for known loci underlying GnRH deficiency and the response to GnRH was tracked according to genotype. Results: Among the entire cohort, no changes were noted in serum T or I-B during the 7 days, thus keeping gonadal feedback relatively constant. However, serum LH and FSH levels increased significantly (p < 0.0001) in the entire cohort. When analyzed by degree of pubertal/testicular development, men with no evidence of prior spontaneous pubertal development (TV <= 3 ml, Group I) showed sharp increases in serum FSH compared to men with some prior evidence of partial puberty (TV > 3 ml, Group II, p < 0.0001). Group I exhibited a decreased LH response to GnRH on day 2 compared to day 1 (p < 0.01), which did not recover until day 5 (1-4 vs. 5-7 days, p < 0.0001). Group II displayed robust and equivalent LH responses to GnRH throughout the 7-day study. Genetic studies identified 8 mutations in 4 different loci (DAX1, KAL1, GNRHR, and FGFR1) in this cohort. Conclusions: GnRH-deficient men undergoing GnRH-induced sexual maturation display an inverse relationship between FSH responsiveness to GnRH and baseline testicular size and I-B levels. This observation implies that increasing seminiferous tubule maturity represents the major constraint on FSH responsiveness to GnRH in early puberty. In contrast, LH responsiveness to GnRH correlates directly with duration of GnRH exposure. Attenuated pituitary gonadotropin responses were noted in subjects harboring DAX1 mutations, consistent with known pituitary defects. Copyright (C) 2009 S. Karger AG, Basel C1 [Pitteloud, Nelly; Thambundit, Apisadaporn; Dwyer, Andrew A.; Falardeau, John L.; Plummer, Lacey; Caronia, Lisa M.; Hayes, Frances J.; Boepple, Paul A.; Crowley, William F., Jr.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Pitteloud, Nelly; Thambundit, Apisadaporn; Dwyer, Andrew A.; Falardeau, John L.; Plummer, Lacey; Caronia, Lisa M.; Hayes, Frances J.; Boepple, Paul A.; Crowley, William F., Jr.] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Clin Res Ctr, Boston, MA 02114 USA. RP Pitteloud, N (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, 55 Fruit St, Boston, MA 02114 USA. EM pitteloud.nelly@mgh.harvard.edu RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014 OI Dwyer, Andrew/0000-0002-7023-6794; FU NIH [R01 HD15788-15, M01-RR-01066]; National Institutes of Health; National Center for Research Resources; General Clinical Research Centers Program; Eunice Kennedy Shriver NICHD/NIH [U54-HD28138] FX This work was supported by NIH R01 HD15788-15 and M01-RR-01066, National Institutes of Health, National Center for Research Resources, General Clinical Research Centers Program and the Eunice Kennedy Shriver NICHD/NIH through cooperative agreement U54-HD28138 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research. NR 47 TC 2 Z9 3 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2009 VL 90 IS 3 BP 260 EP 268 DI 10.1159/000245383 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 506MV UT WOS:000270780100005 PM 19829004 ER PT J AU Kiank, C Mundt, A Schuett, C AF Kiank, Cornelia Mundt, Alice Schuett, Christine TI Mild postnatal separation stress reduces repeated stress-induced immunosuppression in adult BALB/c mice SO NEUROENDOCRINOLOGY LETTERS LA English DT Article DE maternal separation; glucocorticoids; body weight; interleukin-10; repeated psychological stress; stress coping; BALB/c mice ID NEONATAL MATERNAL SEPARATION; CHRONIC PSYCHOLOGICAL STRESS; ENVIRONMENTAL ENRICHMENT; INDIVIDUAL-DIFFERENCES; CHILDHOOD TRAUMA; ADOLESCENT RATS; HPA AXIS; RESPONSES; BEHAVIOR; IMMUNE AB OBJECTIVES: Different inbred mouse strains but also each animal of the same strain show an individually different stress response which is influenced by genetic and environmental factors such as early life experiences. In this study, we investigated consequences of mild postnatal stress exposure on the stress coping style of adult BALB/c mice. METHODS: We used a model of mild early life stress where neonatal mice were repeatedly separated from the dam staying with their siblings for I-h each day during the first two postnatal weeks. The environment during maternal separation was adapted to the nest (bedding, 37 degrees C warm). RESULTS: Adult female BALB/s mice that underwent the maternal separation protocol or were not isolated from the dam in early life were exposed to combined acoustic and restraint stress in adulthood. Repeated maternal separation which was performed under ambient conditions increased the stress coping ability of mice at the age of 12 weeks when exposed to this psychological stressors. By acoustic and restraint stress-induced alterations such as high corticosterone levels, an anti-inflammatory immune conditioning with an ex vivo hyperinducibility of interleukin-10 of splenocytes and a massive loss of body weight were significantly reduced in the maternally separated group compared with conventionally bred control mice. CONCLUSIONS: Mild maternal separation in early life modifies the stress coping style of adult female BALB/c mice to a more stress-resistant phenotype which shows reduced repeated stress-induced immune suppression and weight loss and is linked to reduced release of glucocorticoids after stress exposure. C1 [Kiank, Cornelia] Univ Calif Los Angeles, CURE, Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Kiank, Cornelia; Mundt, Alice; Schuett, Christine] Ernst Moritz Arndt Univ Greifswald, Dept Immunol, DFG Grad Kolleg 840, Greifswald, Germany. [Kiank, Cornelia] Univ Calif Los Angeles, Ctr Neurobiol Stress, Div Digest Dis, Dept Med,David Geffen Sch Med,VA Greater Los Ange, Los Angeles, CA 90073 USA. [Mundt, Alice] Univ Georgia, Poultry Diagnost & Res Ctr, Athens, GA 30602 USA. RP Kiank, C (reprint author), Univ Calif Los Angeles, CURE, Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM ckiank@mednet.ucla.edu FU Deutsche Forschungsgemeinschaft (DFG) [GRK-840]; Fonds der Chemischen Industrie; Alfried Krupp von Bohlen and Halbach Stiftung, Essen, Germany FX Deutsche Forschungsgemeinschaft (DFG, GRK-840, projects BI, Cl); Fonds der Chemischen Industrie (C.S.); Alfried Krupp von Bohlen and Halbach Stiftung, Essen, Germany (C.S.). NR 38 TC 6 Z9 6 U1 0 U2 1 PU MAGHIRA & MAAS PUBLICATIONS PI STOCKHOLM PA PO BOX 26132, S-100 41 STOCKHOLM, SWEDEN SN 0172-780X J9 NEUROENDOCRINOL LETT JI Neuroendocrinol. Lett. PY 2009 VL 30 IS 6 BP 761 EP 768 PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 565CK UT WOS:000275266400015 PM 20038927 ER PT J AU Haneuse, S Schildcrout, J Crane, P Sonnen, J Breitner, J Larson, E AF Haneuse, S. Schildcrout, J. Crane, P. Sonnen, J. Breitner, J. Larson, E. TI Adjustment for Selection Bias in Observational Studies with Application to the Analysis of Autopsy Data SO NEUROEPIDEMIOLOGY LA English DT Article DE Alzheimer's disease; Autopsy; Bootstrap; Dementia; Regression analysis; Selection bias; Weighted estimating equations ID ALZHEIMER-DISEASE; COGNITIVE IMPAIRMENT; DEMENTIA; POPULATION; PREVALENCE; DISORDERS; COHORT AB Background: The interpretation of neuropathological studies of dementia and Alzheimer's disease is complicated by potential selection mechanisms that can drive whether or not a study participant is observed to undergo autopsy. Notwithstanding this, there appears to have been little emphasis placed on potential selection bias in published reports from population-based neuropathological studies of dementia. Methods: We provide an overview of methodological issues relating to the identification of and adjustment for selection bias. When information is available on factors that govern selection, inverse-probability weighting provides an analytic approach to adjust for selection bias. The weights help alleviate bias by serving to bridge differences between the population from which the observed data may be viewed as a representative sample and the target population, identified as being of scientific interest. Results: We illustrate the methods with data obtained from the Adult Changes in Thought study. Adjustment for potential selection bias yields pathological measurements and risk of dementia. Conclusions: Armed with analytic techniques to adjust for selection bias and to ensure generalizability of results from population-based neuropathological studies, researchers should consider incorporating information related to selection into their data collection schemes. Copyright (C) 2009 S. Karger AG, Basel C1 [Haneuse, S.; Larson, E.] Univ Washington, Grp Hlth Ctr Hlth Studies, Seattle, WA 98101 USA. [Haneuse, S.; Crane, P.] Univ Washington, Dept Biostat, Seattle, WA 98101 USA. [Crane, P.] Univ Washington, Div Gen Internal Med, Seattle, WA 98101 USA. [Sonnen, J.] Univ Washington, Dept Pathol, Seattle, WA 98101 USA. [Breitner, J.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98101 USA. [Breitner, J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98101 USA. [Schildcrout, J.] Vanderbilt Univ, Dept Biostat, Nashville, TN USA. RP Haneuse, S (reprint author), Univ Washington, Grp Hlth Ctr Hlth Studies, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM haneuse.s@ghc.org RI Crane, Paul/C-8623-2014; Sonnen, 37382016/H-3738-2016; OI Sonnen, 37382016/0000-0001-9267-8705; Crane, Paul/0000-0003-4278-7465 FU NIH [U01 AG 06781] FX Data collection and analyses were supported by NIH grant U01 AG 06781 (E. Larson). The funding agency had no impact on the decision to perform these analyses or to publish the results. NR 26 TC 26 Z9 26 U1 1 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2009 VL 32 IS 3 BP 229 EP 239 DI 10.1159/000197389 PG 11 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 409VO UT WOS:000263534100011 PM 19176974 ER PT J AU Schwartzman, A Dougherty, RF Lee, J Ghahremani, D Taylor, JE AF Schwartzman, Armin Dougherty, Robert F. Lee, Jongho Ghahremani, Dara Taylor, Jonathan E. TI Empirical null and false discovery rate analysis in neuroimaging SO NEUROIMAGE LA English DT Article ID DIFFUSION DIRECTION MAPS; FMRI DATA; ACTIVATION; HYPOTHESIS; IMAGES AB Current strategies for thresholding statistical parametric maps in neuroimaging include control of the family-wise error rate, control of the false discovery rate (FDR) and thresholding of the posterior probability of a voxel being active given the data, the latter derived from a mixture model of active and inactive voxels. Correct inference using any of these criteria depends crucially on the specification of the null distribution of the test statistics. In this article we show examples from fMRI and DTI data where the theoretical null distribution does not match well the observed distribution of the test statistics. As a solution, we introduce the use of an empirical null, a null distribution empirically estimated from the data itself, allowing for global corrections of theoretical null assumptions. The theoretical null distributions considered are normal, t, chi(2) and F, all commonly encountered in neuroimaging. The empirical null estimate is accompanied by an estimate of the proportion of non-active voxels in the data. Based on the two-class mixture model, we present the equivalence between the strategies of controlling FDR and thresholding posterior probabilities in the context of neuroimaging and show that the FDR estimates derived from the empirical null can be seen as empirical Bayes estimates. (C) 2008 Elsevier Inc. All rights reserved. C1 [Schwartzman, Armin] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Dougherty, Robert F.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. [Lee, Jongho] NINDS, Adv MRI Sect, LFMI, NIH, Bethesda, MD 20824 USA. [Ghahremani, Dara] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Taylor, Jonathan E.] Stanford Univ, Dept Stat, Stanford, CA 94305 USA. RP Schwartzman, A (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, CLS-11007,44 Binney St, Boston, MA 02115 USA. EM armins@hsph.harvard.edu OI Schwartzman, Armin/0000-0001-5335-1611 FU NEI NIH HHS [EY-015000, R01 EY015000]; NIMH NIH HHS [MH15157-20] NR 31 TC 28 Z9 28 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2009 VL 44 IS 1 BP 71 EP 82 DI 10.1016/j.neuroimage.2008.04.182 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 392KF UT WOS:000262300900009 PM 18547821 ER PT J AU Gallagher, RM AF Gallagher, Rollin M. BE Krames, ES Peckham, PH Rezai, AR TI Management Strategies for Chronic Pain SO NEUROMODULATION, VOLS 1 AND 2 LA English DT Article; Book Chapter ID LOW-BACK-PAIN; FIBROMYALGIA FIBROSITIS SYNDROME; MYOFASCIAL FACE PAIN; RETURN-TO-WORK; NEUROPATHIC PAIN; OPIOID THERAPY; DEPRESSION; MEDICINE; POLYMORPHISM; DISORDERS C1 [Gallagher, Rollin M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Gallagher, Rollin M.] Philadelphia Vet Med Ctr, Philadelphia, PA USA. [Gallagher, Rollin M.] Philadelphia VA Med Ctr, Pain Med Serv, Philadelphia, PA USA. RP Gallagher, RM (reprint author), Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 93 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-092139-6 PY 2009 BP 313 EP 331 DI 10.1016/B978-0-12-374248-3.00024-0 PG 19 WC Anesthesiology; Clinical Neurology; Rehabilitation SC Anesthesiology; Neurosciences & Neurology; Rehabilitation GA BGD74 UT WOS:000322479800028 ER PT J AU Memon, M Rizzo, JF AF Memon, Muhammad Rizzo, Joseph F., III BE Krames, ES Peckham, PH Rezai, AR TI The Development of Visual Prosthetic Devices to Restore Vision to the Blind SO NEUROMODULATION, VOLS 1 AND 2 LA English DT Article; Book Chapter ID RETINITIS-PIGMENTOSA PATIENTS; ELECTRICAL-STIMULATION; RETINAL PROSTHESIS; UNITED-STATES; PERCEPTUAL THRESHOLDS; MACULAR DEGENERATION; SENSORY SUBSTITUTION; EPITHELIAL-CELL; FIRST DECADE; TRANSPLANTATION C1 [Memon, Muhammad] Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Neuroophthalmol, Boston, MA 02114 USA. [Memon, Muhammad] Univ London Imperial Coll Sci Technol & Med, Dept Neurosurg, London, England. [Rizzo, Joseph F., III] Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Memon, M (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Neurosurg, London, England. NR 70 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-092139-6 PY 2009 BP 723 EP 742 DI 10.1016/B978-0-12-374248-3.00060-4 PG 20 WC Anesthesiology; Clinical Neurology; Rehabilitation SC Anesthesiology; Neurosciences & Neurology; Rehabilitation GA BGD74 UT WOS:000322479800068 ER PT J AU Hammerness, P McCarthy, K Mancuso, E Gendron, C Geller, D AF Hammerness, Paul McCarthy, Katherine Mancuso, Elizabeth Gendron, Cassandra Geller, Daniel TI Atomoxetine for the treatment of attention-deficit/hyperactivity disorder in children and adolescents: a review SO NEUROPSYCHIATRIC DISEASE AND TREATMENT LA English DT Review DE ADHD; atomoxetine; pediatric AB Objective: This review examines and summarizes the pharmacodynamic and pharmacokinetic properties, short- and longer-term efficacy, the moderating effect of comorbid disorders, as well as short- and long-term safety and tolerability of atomoxetine for the treatment of pediatric attention-deficit/hyperactivity disorder (ADHD). Methods: A systematic literature search was performed to review the extant literature on articles pertaining to the pharmacological treatment with atomoxetine in pediatric and/or adolescent ADHD. Results: There is an extensive literature on atomoxetine; over 4000 children have participated in clinical trials of atomoxetine, demonstrating its short- and longer-term efficacy. In addition, studies have examined the moderating effect of comorbid disorders on atomoxetine response, as well as atomoxetine's therapeutic potential for other psychiatric conditions. Short- and longer-term safety and tolerability continue to be reported. Conclusions: Atomoxetine is indicated for both acute and maintenance/extended treatment of pediatric ADHD. Clinicians and families must be familiar with atomoxetine's evidence base, including its profile of clinical response and its possible effectiveness in the presence of comorbidity. C1 [Hammerness, Paul] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Hammerness, P (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM phammerness@partners.org FU Eli Lilly and Co.; Forest Laboratories; Glaxo-SmithKline; Boehringer Ingelheim Pharmaceuticals, Inc; Eli Lilly FX Dr. Daniel Geller MD receives(ed) lifetime; Research support: Eli Lilly and Co., Forest Laboratories, Glaxo-SmithKline, Boehringer Ingelheim Pharmaceuticals, Inc.; Speaker Honoraria: Alza, Bristol-Myers-Squibb, Eli Lilly, Forest Laboratories, Glaxo-SmithKline, Novartis, Pfizer, Shire, Wyeth.; Medical Advisory Boards/Consulting: Eli Lilly, Solvay, Pfizer, Lundbeck and Glaxo-SmithKline.; Private Foundations: Obsessive Compulsive Foundation, Tourette Syndrome Association, Wallace Foundation, McIngvale Family Foundation.; NIH: National Institute of Mental Health, National Institute of Neurological Disorders and Stroke; Dr. Daniel Geller MD receives/d inlast 12 months (to November 2008).; Research support: Eli Lilly.; Speaker Honoraria: Eli Lilly.; Medical Advisory Boards/Consulting: Eli Lilly.; Private Foundations: McIngvale Family Foundation.; NIH: National Institute of Neurological Disorders and Stroke, National Institute of Mental Health. NR 68 TC 27 Z9 28 U1 8 U2 9 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-6328 J9 NEUROPSYCH DIS TREAT JI Neuropsychiatr. Dis. Treat. PY 2009 VL 5 BP 215 EP 226 PG 12 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA V19JX UT WOS:000208069800024 PM 19557116 ER PT J AU Amsterdam, JD Williams, D Michelson, D Adler, LA Dunner, DL Nierenberg, AA Reimherr, FW Schatzberg, AF AF Amsterdam, Jay D. Williams, David Michelson, David Adler, Lenard A. Dunner, David L. Nierenberg, Andrew A. Reimherr, Frederick W. Schatzberg, Alan F. TI Tachyphylaxis after Repeated Antidepressant Drug Exposure in Patients with Recurrent Major Depressive Disorder SO NEUROPSYCHOBIOLOGY LA English DT Article DE Tachyphylaxis; Treatment resistant depression; Antidepressant drug therapy; Serotonin reuptake inhibitor; Major depressive disorder ID SEROTONIN TRANSPORTER GENE; TREATMENT-RESISTANT DEPRESSION; STAR-ASTERISK-D; LONG-TERM TREATMENT; REUPTAKE INHIBITORS; ALLELIC VARIATION; VENLAFAXINE; EFFICACY; POLYMORPHISM; MIRTAZAPINE AB Objective: The aim of this post hoc analysis was to examine whether tachyphylaxis occurs after repeated courses of antidepressant drug therapy. Method: 276 patients with major depressive disorder (MDD) were treated with sertraline (150-200 mg daily) for 8 weeks. Patients with persistent MDD after sertraline therapy were randomized to continuation therapy with either sertraline plus atomoxetine (n = 72) or sertraline plus placebo (n = 74) for 8 additional weeks. Logistic regression was used to test the hypothesis that an increase in prior antidepressant drug exposure is associated with a reduced responsiveness to sertraline therapy. Results: The number of prior antidepressant drug exposures was negatively associated with response to initial sertraline therapy (odds ratio = 0.81, p = 0.0035). The odds ratio indicates a 19.9% reduced likelihood of response with each prior antidepressant treatment trial. In contrast, the number of prior antidepressant treatment trials was not associated with response to continuation sertraline plus atomoxetine or sertraline plus placebo therapy. Conclusion: This observation supports the hypothesis that tachyphylaxis may develop after repeated antidepressant drug trials. Copyright (C) 2009 S. Karger AG, Basel C1 [Amsterdam, Jay D.] Univ Penn, Sch Med, Dept Psychiat, Depress Res Unit,Univ Sci Ctr, Philadelphia, PA 19104 USA. [Williams, David] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Michelson, David] Merck & Co Inc, Merck Res Labs, Rahway, NJ 07065 USA. [Adler, Lenard A.] NYU, Dept Psychiat, New York, NY 10016 USA. [Dunner, David L.] Ctr Anxiety & Depress, Mercer Isl, WA USA. [Nierenberg, Andrew A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program,Dept Psychiat, Boston, MA USA. [Reimherr, Frederick W.] Univ Utah, Hlth Sci Ctr, Dept Psychiat, Mood Disorders Clin, Salt Lake City, UT USA. [Schatzberg, Alan F.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Amsterdam, JD (reprint author), Univ Penn, Sch Med, Dept Psychiat, Depress Res Unit,Univ Sci Ctr, 3rd Floor 3535 Market St, Philadelphia, PA 19104 USA. EM jamsterd@mail.med.upenn.edu OI Adler, Len/0000-0002-9812-8234 NR 44 TC 13 Z9 13 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-282X J9 NEUROPSYCHOBIOLOGY JI Neuropsychobiology PY 2009 VL 59 IS 4 BP 227 EP 233 DI 10.1159/000226611 PG 7 WC Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 479RW UT WOS:000268679600006 PM 19571597 ER PT J AU Rauschecker, AM Deutsch, GK Ben-Shachar, M Schwartzman, A Perry, LM Dougherty, RF AF Rauschecker, Andreas M. Deutsch, Gayle K. Ben-Shachar, Michal Schwartzman, Armin Perry, Lee M. Dougherty, Robert F. TI Reading impairment in a patient with missing arcuate fasciculus SO NEUROPSYCHOLOGIA LA English DT Article DE Reading; Arcuate; Superior longitudinal fasciculus; Diffusion tensor imaging; DTI; fMRI; Dyslexia; Radiation necrosis; Radiation treatment; Late-delayed radiation damage; White matter ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CENTRAL-NERVOUS-SYSTEM; DIFFUSION DIRECTION MAPS; WHITE-MATTER ANISOTROPY; TEMPORAL-LOBE EPILEPSY; MAGNETIC-RESONANCE; HUMAN BRAIN; DISCONNECTION SYNDROME; CRANIAL RADIATION; VERB GENERATION AB We describe the case of a child ("S") who was treated with radiation therapy at age 5 for a recurrent malignant brain tumor. Radiation successfully abolished the tumor but caused radiation-induced tissue necrosis, primarily affecting cerebral white matter. S was introduced to us at age 15 because of her profound dyslexia. We assessed cognitive abilities and performed diffusion tensor imaging (DTI) to measure cerebral white matter pathways. Diffuse white matter differences were evident in T1-weighted, T2-weighted, diffusion anisotropy, and mean diffusivity measures in S compared to a group of 28 normal female controls. In addition, we found specific white matter pathway deficits by comparing tensor-orientation directions in S's brain with those of the control brains. While her principal diffusion direction maps appeared consistent with those of controls over most of the brain, there were tensor-orientation abnormalities in the fiber tracts that form the superior longitudinal fasciculus (SLF) in both hemispheres. Tractography analysis indicated that the left and right arcuate fasciculus (AF), as well as other tracts within the SLF, were missing in S. Other major white matter tracts, such as the corticospinal and inferior occipitofrontal pathways, were intact. Functional MRI measurements indicated left-hemisphere dominanance for language with a normal activation pattern. Despite the left AF abnormality, S had preserved oral language with average sentence repetition skills. In addition to profound dyslexia, S exhibited visuospatial, calculation, and rapid naming deficits and was impaired in both auditory and spatial working memory. We propose that the reading and visuospatial deficits were due to the abnormal left and right SLF pathways, respectively. These results advance our understanding of the functional significance of the SLF and are the first to link radiation necrosis with selective damage to a specific set of fiber tracts. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Rauschecker, Andreas M.; Deutsch, Gayle K.; Ben-Shachar, Michal; Perry, Lee M.; Dougherty, Robert F.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. [Rauschecker, Andreas M.] Stanford Univ, Sch Med, MSTP, Stanford, CA 94305 USA. [Rauschecker, Andreas M.] Stanford Univ, Sch Med, Neurosci Program, Stanford, CA 94305 USA. [Schwartzman, Armin] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Schwartzman, Armin] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Rauschecker, AM (reprint author), Stanford Univ, Dept Psychol, Jordan Hall,450 Serra Mall, Stanford, CA 94305 USA. EM andreasr@stanford.edu OI Schwartzman, Armin/0000-0001-5335-1611 FU NIH [EY015000, GM07365]; Stanford School of Medicine FX First and foremost we thank S for her willingness to share her story with us and her patient cooperation during our testing. S's courage and determination to overcome the challenges that she faced were deeply inspiring. We also thank S's mother for her extensive help in arranging the measurements, compiling medical records, and for her general persistence in seeing the project through. Brian Wandell provided guidance, Adele Behn performed neuropsychological testing, and Arvel Hernandez assisted with data collection and analysis. S's physicians and the imaging center where her clinical scans were performed provided films and digital files. We also thank Dr. Michael Greicius for comments on the manuscript.; Supported by NIH grant EY015000. AMR was supported by NIH MSTP Grant GM07365 and the Stanford School of Medicine. NR 88 TC 38 Z9 40 U1 2 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JAN PY 2009 VL 47 IS 1 BP 180 EP 194 DI 10.1016/j.neuropsychologia.2008.08.011 PG 15 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 396TM UT WOS:000262614100020 PM 18775735 ER PT J AU Sweet, RA Henteleff, RA Zhang, W Sampson, AR Lewis, DA AF Sweet, Robert A. Henteleff, Ruth A. Zhang, Wei Sampson, Allan R. Lewis, David A. TI Reduced Dendritic Spine Density in Auditory Cortex of Subjects with Schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE auditory cortex; schizophrenia; synapse; dendrite; pathology ID SUPERIOR TEMPORAL GYRUS; BINDING PROTEIN IMMUNOREACTIVITY; MISMATCH NEGATIVITY GENERATION; CORTICAL PYRAMIDAL NEURONS; PRIMATE CEREBRAL-CORTEX; FEMALE RHESUS-MONKEYS; PREFRONTAL CORTEX; PLANUM TEMPORALE; BRAIN VOLUME; 1ST-EPISODE SCHIZOPHRENIA AB We have previously identified reductions in mean pyramidal cell somal volume in deep layer 3 of BA 41 and 42 and reduced axon terminal density in deep layer 3 of BA 41. In other brain regions demonstrating similar deficits, reduced dendritic spine density has also been identified, leading us to hypothesize that dendritic spine density would also be reduced in BA 41 and 42. Because dendritic spines and their excitatory inputs are regulated in tandem, we further hypothesized that spine density would be correlated with axon terminal density. We used stereologic methods to quantify a marker of dendritic spines, spinophilin-immunoreactive (SP-IR) puncta, in deep layer 3 of BA 41 and 42 of 15 subjects with schizophrenia, each matched to a normal comparison subject. The effect of long-term haloperidol exposure on SP-IR puncta density was evaluated in nonhuman primates. SP-IR puncta density was significantly lower by 27.2% in deep layer 3 of BA 41 in the schizophrenia subjects, and by 22.2% in deep layer 3 of BA 42. In both BA 41 and 42, SP-IR puncta density was correlated with a marker of axon terminal density, but not with pyramidal cell somal volume. SP-IR puncta density did not differ between haloperidol-exposed and control monkeys. Lower SP-IR puncta density in deep layer 3 of BA 41 and 42 of subjects with schizophrenia may reflect concurrent reductions in excitatory afferent input. This may contribute to impairments in auditory sensory processing that are present in subjects with schizophrenia. C1 [Sweet, Robert A.; Henteleff, Ruth A.; Lewis, David A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. [Zhang, Wei; Sampson, Allan R.] Univ Pittsburgh, Dept Stat, Pittsburgh, PA 15213 USA. [Lewis, David A.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15213 USA. RP Sweet, RA (reprint author), Univ Pittsburgh, Dept Psychiat, Biomed Sci Tower,Rm W-1645,3811 OHara St, Pittsburgh, PA 15213 USA. EM sweetra@upmc.edu RI Lewis, David/G-4053-2014 OI Lewis, David/0000-0002-3225-6778 FU USPHS [MH 045156, MH 071533]; VISN 4 Mental Illness Research, Education; Clinical Center, VA Pittsburgh Healthcare System FX This work was supported by USPHS grants MH 045156 and MH 071533 and by the VISN 4 Mental Illness Research, Education and Clinical Center, VA Pittsburgh Healthcare System. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. We thank Dr Ken Fish for the conduct of the primary neuronal culture assessment of antibody specificity, and Mrs Mary Brady for assistance with the figures. We acknowledge the efforts of the research staff of the Translational Neuroscience Program and the Conte Center for Neuroscience of Mental Disorders at the University of Pittsburgh. NR 117 TC 113 Z9 114 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2009 VL 34 IS 2 BP 374 EP 389 DI 10.1038/npp.2008.67 PG 16 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 386DN UT WOS:000261862600013 PM 18463626 ER PT J AU Evans, KC Simon, NM Dougherty, DD Hoge, EA Worthington, JJ Chow, C Kaufman, RE Gold, AL Fischman, AJ Pollack, MH Rauch, SL AF Evans, Karleyton C. Simon, Naomi M. Dougherty, Darin D. Hoge, Elizabeth A. Worthington, John J. Chow, Candice Kaufman, Rebecca E. Gold, Andrea L. Fischman, Alan J. Pollack, Mark H. Rauch, Scott L. TI A PET Study of Tiagabine Treatment Implicates Ventral Medial Prefrontal Cortex in Generalized Social Anxiety Disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE positron emission tomography; social anxiety disorder; tiagabine; prefrontal cortex; neuroimaging ID CEREBRAL-BLOOD-FLOW; PHOBIA; AMYGDALA; EXTINCTION; ACTIVATION; PLACEBO; HUMANS; BRAIN; FACES; GABA AB Corticolimbic circuitry has been implicated in generalized social anxiety disorder (gSAD) by several neuroimaging symptom provocation studies. However, there are limited data regarding resting state or treatment effects on regional cerebral metabolic rate of glucose uptake (rCMRglu). Given evidence for anxiolytic effects conferred by tiagabine, a gamma-aminobutyric acid (GABA) reuptake inhibitor, the present [(18)F] fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) study sought to ( 1) compare resting rCMRglu between healthy control (HC) and pretreatment gSAD cohorts, (2) examine pre- to post-tiagabine treatment rCMRglu changes in gSAD, and (3) determine rCMRglu predictors of tiagabine treatment response. Fifteen unmedicated individuals with gSAD and ten HCs underwent a baseline (pretreatment) resting-state (18)FDG-PET scan. Twelve of the gSAD individuals completed an open, 6-week, flexible dose trial of tiagabine, and underwent a second (posttreatment) resting-state (18)FDG-PET scan. Compared to the HC subjects, individuals with gSAD demonstrated less pretreatment rCMRglu within the anterior cingulate cortex and ventral medial prefrontal cortex (vmPFC) at baseline. Following tiagabine treatment, vmPFC rCMRglu increased significantly in the gSAD group. Further, the magnitude of treatment response was inversely correlated with pretreatment rCMRglu within vmPFC. Taken together the present findings converge with neuroimaging findings from studies of social cognition in healthy individuals and symptom provocation in gSAD to support a role for the vmPFC in the pathophysiology of gSAD. Given the pharmacological profile of tiagabine, these findings suggest that its therapeutic effects in gSAD may be mediated by GABAergic modulation within the vmPFC. C1 [Evans, Karleyton C.; Simon, Naomi M.; Dougherty, Darin D.; Hoge, Elizabeth A.; Worthington, John J.; Chow, Candice; Kaufman, Rebecca E.; Gold, Andrea L.; Pollack, Mark H.; Rauch, Scott L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Psychiat Neurosci Div, Boston, MA USA. [Evans, Karleyton C.; Dougherty, Darin D.; Fischman, Alan J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Rauch, Scott L.] Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. RP Evans, KC (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, Psychiat Neurosci Div, 13th St,Bldg 149,Suite 2625, Charlestown, MA 02129 USA. EM kcevans@partners.org RI Hoge, Elizabeth/H-5879-2012; OI Hoge, Elizabeth/0000-0002-5513-2292; Gold, Andrea/0000-0003-4447-776X; Sripada, Rebecca/0000-0002-2844-3458 FU NIBIB NIH HHS [EB T32 1632-03]; NIMH NIH HHS [R01 MH070730, MH T32 19126, R01 MH074848, R01 MH60219] NR 51 TC 30 Z9 30 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2009 VL 34 IS 2 BP 390 EP 398 DI 10.1038/npp.2008.69 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 386DN UT WOS:000261862600014 PM 18536708 ER PT J AU Kondo, M Schmucker, D Iwata, K AF Kondo, Masahiro Schmucker, Dietmar Iwata, Koichi TI Dscam is required for axonal targeting specificity of mechanosensory neurons in Drosophila SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Kondo, Masahiro; Iwata, Koichi] Nihon Univ, Sch Dent, Dept Physiol, Tokyo 101, Japan. [Schmucker, Dietmar] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2009 VL 65 SU 1 BP S197 EP S197 DI 10.1016/j.neures.2009.09.1073 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 528DK UT WOS:000272421101437 ER PT J AU McCarley, RW AF McCarley, Robert W. TI Schizophrenia as a progressive brain disorder: A challenge for neuroscience discovery SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [McCarley, Robert W.] VA Boston Healthcare Syst, Neurosci Lab, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2009 VL 65 SU 1 BP S1 EP S1 DI 10.1016/j.neures.2009.09.007 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 528DK UT WOS:000272421100003 ER PT J AU Aghi, MK Carter, BS Cosgrove, GR Ojemann, RG Amin-Hanjani, S Martuza, RL Curry, WT Barker, FG AF Aghi, Manish K. Carter, Bob S. Cosgrove, Garth R. Ojemann, Robert G. Amin-Hanjani, Sepideh Martuza, Robert L. Curry, William T., Jr. Barker, Fred G., II TI LONG-TERM RECURRENCE RATES OF ATYPICAL MENINGIOMAS AFTER GROSS TOTAL RESECTION WITH OR WITHOUT POSTOPERATIVE ADJUVANT RADIATION SO NEUROSURGERY LA English DT Article DE Atypical meningioma; Gross total resection; Radiation; Recurrence ID MALIGNANT MENINGIOMAS; CLASSIFICATION; PROGNOSIS AB OBJECTIVE: Atypical meningioma (AM) patients often undergo gross total resection (GTR) at the time of presentation, but subsequent prognosis and optimal management remain unclear. We sought to define the long-term recurrence rate of AMs after GTR, along with factors predicting recurrence, including postoperative radiation. METHODS: We performed a retrospective review of 108 AMs after GTR at our institution from 1993 to 2004. Recurrence risk factors were analyzed using multivariate Cox regression. RESULTS: There were 600 patient-years of imaging follow-up on 48 men and 60 women. Of 108 tumours, 30 (28%) recurred 3 to 144 months after GTR (mean, 36 months). Actuarial tumor recurrence rates were 7% (1 year), 41% (5 years), and 48% (10 years). Of 108 patients, 8 received postoperative radiation without recurrence (P = 0.1). Multivariate analysis including age, sex, postoperative radiation, tumor location, MIB-1 labeling index, and 6 atypical-defining histological features identified recurrence-predicting factors: older age (hazard ratio, 1.6/decade; P = 0.01), sheeting (hazard ratio, 2.2; P = 0.025), and prominent nucleoli (hazard ratio, 2.1; P = 0.034). Recursive partitioning identified a subset, men with mitoses and prominent nucleoli, with 70% recurrence (n = 14). All patients with recurrences received radiation, and 22 of 30 patients underwent craniotomies (average, 2.7 craniotomies per patient with recurrence; range, 1-7 craniotomies). Only 1 of 22 re-resected meningiomas underwent malignant transformation. of 30 patients with recurrence, 10 experienced tumor-induced mortality an average of 7 years after recurrence (range, 1-14 years). CONCLUSION: After GTR without postoperative radiation, AMs have a high recurrence rate. Most recurrences occurred within 5 years after resection. Recurrences caused numerous reoperations per patient and shortened survival. Our finding suggesting lower recurrence rates in patients undergoing immediate postoperative radiation should be investigated in larger, prospective series. C1 [Aghi, Manish K.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. [Carter, Bob S.; Ojemann, Robert G.; Martuza, Robert L.; Curry, William T., Jr.; Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Cosgrove, Garth R.] Lahey Clin Fdn, Dept Neurosurg, Burlington, MA USA. [Amin-Hanjani, Sepideh] Univ Illinois, Dept Neurosurg, Chicago, IL USA. RP Aghi, MK (reprint author), Univ Calif San Francisco, Dept Neurosurg, 505 Parnassus Ave,Room M779, San Francisco, CA 94143 USA. EM AghiM@neurosurg.ucsf.edu NR 13 TC 131 Z9 133 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JAN PY 2009 VL 64 IS 1 BP 56 EP 60 DI 10.1227/01.NEU.0000330399.55586.63 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 393MO UT WOS:000262377600010 PM 19145156 ER PT J AU Nogueira, RG Dabus, G Rabinov, JD Ogilvy, CS Hirsch, JA Pryor, JC AF Nogueira, Raul G. Dabus, Guilherme Rabinov, James D. Ogilvy, Christopher S. Hirsch, Joshua A. Pryor, Johnny C. TI ONYX EMBOLIZATION FOR THE TREATMENT OF SPINAL DURAL ARTERIOVENOUS FISTULAE: INITIAL EXPERIENCE WITH LONG-TERM FOLLOW-UP: TECHNICAL CASE REPORT SO NEUROSURGERY LA English DT Article DE Dural arteriovenous fistula; Onyx; Spinal AB OBJECTIVE: Spinal dural arteriovenous fistulae (SDAVF) are the most common variety of spinal vascular malformations. The Onyx liquid embolic system (ev3 Neurovascular, Irvine, CA) was recently approved for the treatment of intracranial arteriovenous malformations, but its use to treat SDAVFs is not yet well established. We report our initial experience with Onyx LEC embolization in the treatment of SDAVFs. METHODS: Retrospective analysis of 3 consecutive patients with SDAVFs who were treated with the Onyx as the single treatment modality was performed. Demographic, clinical, and radiographic presentations as well as long-term outcomes were reviewed. RESULTS: Four procedures were performed in 3 patients. In all cases, transarterial microcatheterization was performed with a Marathon microcatheter (ev3 Neurovascular) and Onyx-18 (ev3 Neurovascular) was used. All 3 patients were men (age, 75-78 years) and presented with progressive myelopathy. Two patients underwent only 1 procedure, with a single pedicle embolized to achieve angiographic cure. In the remaining patient, 2 procedures with embolization through 3 different pedicles from 2 adjacent levels were necessary to achieve angiographic cure. No procedure-related complications were noted. No evidence of residual or recurrent SDAVF was seen on magnetic resonance imaging (mean, 10.6 months; range, 7.1-14.6 months), angiographic (mean, 12.2 months; range, 10.2-14.9 months), or clinical (mean, 13 months; range, 10.2-14.9 months) follow-up examination. CONCLUSION: Our initial experience suggests that the endovascular treatment of SDAVFs with the Onyx is feasible, safe, and highly effective, as it allows for a controlled penetration of the embolic agent into the draining vein. In this small series, we found no evidence of clinical, magnetic resonance imaging, or angiographic recurrence during the long-term follow-up period. C1 [Nogueira, Raul G.; Dabus, Guilherme; Rabinov, James D.; Hirsch, Joshua A.; Pryor, Johnny C.] Massachusetts Gen Hosp, Div Intervent Neuroradiol & Endovasc Neurosurg, Boston, MA 02114 USA. [Nogueira, Raul G.] Massachusetts Gen Hosp, Div Vasc & Crit Care Neurol, Boston, MA 02114 USA. [Ogilvy, Christopher S.] Massachusetts Gen Hosp, Div Vasc Neurosurg, Boston, MA 02114 USA. RP Nogueira, RG (reprint author), Massachusetts Gen Hosp, Div Intervent Neuroradiol & Endovasc Neurosurg, Boston, MA 02114 USA. NR 0 TC 22 Z9 30 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 JAN PY 2009 VL 64 IS 1 BP 197 EP 198 DI 10.1227/01.NEU.0000335157.90249.97 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 393MO UT WOS:000262377600048 PM 19145148 ER PT J AU Petzer, JP Castagnoli, N Schwarzschild, MA Chen, JF Van der Schyf, CJ AF Petzer, Jacobus P. Castagnoli, Neal, Jr. Schwarzschild, Michael A. Chen, Jiang-Fan Van der Schyf, Cornelis J. TI Dual-Target-Directed Drugs that Block Monoamine Oxidase B and Adenosine A(2A) Receptors for Parkinson's Disease SO NEUROTHERAPEUTICS LA English DT Review DE Parkinson's disease; monoamine oxidase B; adenosine A(2A) receptor; dual-target-directed drug; caffeine ID INDUCED MOTOR COMPLICATIONS; MPTP-TREATED MONKEYS; L-DOPA; HUMAN-BRAIN; 6-HYDROXYDOPAMINE-LESIONED RATS; MAO-B; DOPAMINERGIC NEUROTOXICITY; ANTAGONIST ISTRADEFYLLINE; SELECTIVE-INHIBITION; SUBSTANTIA-NIGRA AB Inadequacies of the current pharmacotherapies to treat Parkinson's disease (PD) have prompted efforts to identify novel drug targets. The adenosine A(2A) receptor is one such target. Antagonists of this receptor (A(2A) antagonists) are considered promising agents for the symptomatic treatment of PD. Evidence suggests that A(2A) antagonists may also have neuroprotective properties that may prevent the development of the dyskinesia that often complicates levodopa treatment. Because the therapeutic benefits of A(2A) antagonists are additive to that of dopamine replacement therapy, it may be possible to reduce the dose of the dopaminergic drugs and therefore the occurrence of side effects. Inhibitors of monoamine oxidase (MAO)-B also are considered useful tools for the treatment of PD. When used in combination with levodopa, inhibitors of MAO-B may enhance the elevation of dopamine levels after levodopa treatment, particularly when used in early stages of the disease when dopamine production may not be so severely compromised. Furthermore, MAO-B inhibitors may also possess neuroprotective properties in part by reducing the damaging effect of dopamine turnover in the brain. These effects of MAO-B inhibitors are especially relevant when considering that the brain shows an age-related increase in MAO-B activity. Based on these observations, dual-target-directed drugs, compounds that inhibit MAO-B and antagonize A(2A) receptors, may have value in the management of PD. This review summarizes recent efforts to develop such dual-acting drugs using caffeine as the lead compound. C1 [Petzer, Jacobus P.] North West Univ, Sch Pharm, ZA-2520 Potchefstroom, South Africa. [Castagnoli, Neal, Jr.] Virginia Tech, Dept Chem, Blacksburg, VA 24061 USA. [Castagnoli, Neal, Jr.] Edward Via Coll Osteopath Med, Blacksburg, VA 24061 USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. [Chen, Jiang-Fan] Boston Univ, Sch Med, Dept Neurol, Mol Neuropharmacol Lab, Boston, MA 02118 USA. [Van der Schyf, Cornelis J.] Northeastern Ohio Univ Coll Med & Pharm, Dept Pharmaceut Sci, Rootstown, OH 44272 USA. RP Petzer, JP (reprint author), North West Univ, Sch Pharm, Private Bag X6001, ZA-2520 Potchefstroom, South Africa. EM jacques.petzer@nwu.ac.za RI Petzer, Jacobus/E-8747-2011; OI Petzer, Jacobus/0000-0002-7114-8120 FU National Research Foundation and Medical Research Council, South Africa FX Financial support from the National Research Foundation and Medical Research Council, South Africa is acknowledged. NR 115 TC 39 Z9 39 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2009 VL 6 IS 1 BP 141 EP 151 PG 11 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 387WU UT WOS:000261983100012 PM 19110205 ER PT J AU Cristofaro, V Yalla, SV Sullivan, MP AF Cristofaro, Vivian Yalla, Subbarao V. Sullivan, Maryrose P. TI ALTERED CAVEOLAE-MEDIATED ADRENERGIC SIGNALING IN SPONTANEOUSLY HYPERTENSIVE RATS WITH DETRUSOR OVERACTIVITY SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT 6th Annual Winter Meeting of the Society-for-Urodynamics-and-Female-Urology CY FEB 25-28, 2009 CL Las Vegas, NV SP Soc Urodynam & Female Urol C1 [Cristofaro, Vivian; Yalla, Subbarao V.; Sullivan, Maryrose P.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2009 VL 28 IS 2 BP 109 EP 109 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 412XL UT WOS:000263757400009 ER PT J AU Marley, C Lerner, L Panagopoulos, G Kavaler, E AF Marley, Ciara Lerner, Lori Panagopoulos, Georgia Kavaler, Elizabeth TI HAVING IT ALL! SATISFACTION AMONG US WOMEN UROLOGISTS; PERSONALLY, PROFESSIONALLY, AND FINANCIALLY SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT 6th Annual Winter Meeting of the Society-for-Urodynamics-and-Female-Urology CY FEB 25-28, 2009 CL Las Vegas, NV SP Soc Urodynam & Female Urol C1 [Marley, Ciara; Panagopoulos, Georgia; Kavaler, Elizabeth] Lenox Hill Hosp, New York, NY 10021 USA. [Lerner, Lori] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2009 VL 28 IS 2 BP 138 EP 138 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 412XL UT WOS:000263757400079 ER PT J AU Tan-Kim, J Weinstein, M Nager, C AF Tan-Kim, J. Weinstein, M. Nager, C. TI URETHRAL SLEEVE SENSOR: A BETTER METHOD TO MEASURE URETHRAL PRESSURE DURING DYNAMIC CONDITIONS SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT 39th Annual Meeting of the International-Continence-Society CY SEP 29-OCT 03, 2009 CL San Francisco, CA SP Int Continence Soc C1 [Tan-Kim, J.; Nager, C.] Univ Calif San Diego, San Diego, CA 92103 USA. [Weinstein, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2009 VL 28 IS 7 MA 223 BP 852 EP 854 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 493DI UT WOS:000269713200206 ER PT J AU Awada, H Fletter, P Cooper, M Zaszczurynski, P Damaser, M AF Awada, H. Fletter, P. Cooper, M. Zaszczurynski, P. Damaser, M. TI PERFORMANCE OF DISPOSABLE PRESSURE-SENSING CATHETERS DURING SIMULATED URODYNAMIC EVENTS SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT 39th Annual Meeting of the International-Continence-Society CY SEP 29-OCT 03, 2009 CL San Francisco, CA SP Int Continence Soc C1 [Awada, H.; Cooper, M.; Damaser, M.] Cleveland Clin, Cleveland, OH USA. [Fletter, P.; Zaszczurynski, P.] US Dept Vet Affairs, Washington, DC USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2009 VL 28 IS 7 MA 224 BP 855 EP 856 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 493DI UT WOS:000269713200207 ER PT J AU Markland, A Goode, P Burgio, K Redden, D Richter, HE Allman, R Sawyer, P AF Markland, A. Goode, P. Burgio, K. Redden, D. Richter, H. E. Allman, R. Sawyer, P. TI INCIDENCE AND RISK FACTORS FOR FECAL INCONTINENCE IN OLDER MEN AND WOMEN SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT 39th Annual Meeting of the International-Continence-Society CY SEP 29-OCT 03, 2009 CL San Francisco, CA SP Int Continence Soc C1 [Markland, A.; Goode, P.; Burgio, K.; Redden, D.] Birmingham VA Med Ctr, Birmingham, AL USA. [Richter, H. E.; Allman, R.; Sawyer, P.] Univ Alabama, Birmingham, AL USA. RI Allman, Richard/D-5964-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2009 VL 28 IS 7 MA 247 BP 886 EP 887 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 493DI UT WOS:000269713200230 ER PT J AU Saunders, GH Griest, SE AF Saunders, Gabrielle H. Griest, Susan E. TI Hearing loss in veterans and the need for hearing loss prevention programs SO NOISE & HEALTH LA English DT Article DE Veterans; hearing loss prevention; health promotion; multimedia program AB Currently, there are more than 445,000 veterans receiving compensation for hearing loss associated with military service, and 395,000 receiving compensation for service-related tinnitus. In addition to compensation payments, service-related hearing disorders cost the US Department of Veterans Affairs in terms of provision of hearing aids, hearing aid-related services, and clinical services at its 220 facilities nationwide. It is imperative that hearing conservation among military personnel and veterans be addressed. In this paper, we describe the rationale for and the development of a multimedia Hearing Loss Prevention Program aimed at preventing the progression of hearing loss among veterans associated with social, recreational, and nonmilitary occupational noise exposure. The program was developed based on the principles outlined in the Health Belief Model of Rosenstock (1966) and the Health Promotion Model of Pender et al. (2002). C1 [Saunders, Gabrielle H.] Oregon Hlth & Sci Univ, Natl Ctr Rehabilitat Auditory Res, Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97239 USA. RP Saunders, GH (reprint author), Oregon Hlth & Sci Univ, Natl Ctr Rehabilitat Auditory Res, Portland VA Med Ctr, 3710 SW US Vet Hosp Rd NCRAR, Portland, OR 97239 USA. EM gabrielle.saunders@va.gov FU RRD VA [I01 RX000192] NR 74 TC 29 Z9 30 U1 3 U2 10 PU MEDKNOW PUBLICATIONS PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1463-1741 J9 NOISE HEALTH JI Noise Health PD JAN-MAR PY 2009 VL 11 IS 42 BP 14 EP 21 DI 10.4103/1463-1741.45308 PG 8 WC Audiology & Speech-Language Pathology; Public, Environmental & Occupational Health SC Audiology & Speech-Language Pathology; Public, Environmental & Occupational Health GA V15SC UT WOS:000207820700004 PM 19265249 ER PT J AU Dording, CM Sinicropi-Yao, L Papakostas, G Matthews, JD Nierenberg, AA Fava, M Mischoulon, D AF Dording, Christina M. Sinicropi-Yao, Lara Papakostas, George Matthews, John D. Nierenberg, Andrew A. Fava, Maurizio Mischoulon, David TI The response of psychotic-like symptoms to fluoxetine monotherapy in non-psychotic major depressive disorder SO NORDIC JOURNAL OF PSYCHIATRY LA English DT Article DE Fluoxetine; Major depressive disorder; Paranoia; Psychotic depression; SCID; SCID-II ID DEXAMETHASONE SUPPRESSION TEST; DOUBLE-BLIND; DELUSIONAL DEPRESSION; PLACEBO-RESPONSE; FLUVOXAMINE; IMIPRAMINE; SERTRALINE AB Objective: To determine the prevalence of psychotic-like symptoms in non-psychotic major depressive disorder and to monitor the response of these symptoms to monotherapy with fluoxetine. Methods: We reviewed the charts of 384 subjects (54.7% women; mean age 39.9 +/- 10), all outpatients diagnosed with non-psychotic major depressive disorder by the Structured Clinical Interview for DSM-IV (SCID), aged 18-65 years, with an initial 17-item Hamilton Depression (HAM-D-17) score of 16 or greater. Subjects were treated openly with fluoxetine 20 mg/day for 8 weeks. Subjects were administered the SCID-II (Structured Clinical Diagnostic Interview for Personality Disorder) prior to entering acute treatment and at the completion of the acute phase of treatment. We monitored the course of psychotic-like symptoms following this course of therapy. Results: 187 subjects endorsed at least one psychotic-like symptom, including not trusting close acquaintances (item 51), picking up hidden meanings (item 52), believing that others were talking about them (item 57), magical thinking (item 60) or unusual perceptual experiences (item 62). None of these patients met criteria for delusional depression as defined by the SCID. Overall response rates were 36.4% for patients who endorsed psychotic-like symptoms, and 53.3% for those who did not endorse psychotic-like symptoms (chi-squared = 11.1, P=0.001). The decrease in psychotic-like symptoms during the course of fluoxetine monotherapy was significant (P0.05) in both responders and non-responders to treatment. Conclusion: A significant percentage of patients with non-psychotic major depression endorse subtle psychotic-like symptoms, many of which abate during monotherapy with fluoxetine regardless of response of the depressive symptoms. C1 [Dording, Christina M.; Sinicropi-Yao, Lara; Papakostas, George; Matthews, John D.; Nierenberg, Andrew A.; Fava, Maurizio; Mischoulon, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Depress Clin & Res Program, Boston, MA 02114 USA. RP Dording, CM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Depress Clin & Res Program, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM CDording@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 NR 33 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0803-9488 J9 NORD J PSYCHIAT JI Nord. J. Psychiatr. PY 2009 VL 63 IS 5 BP 420 EP 425 AR PII 912370383 DI 10.1080/08039480903015396 PG 6 WC Psychiatry SC Psychiatry GA 498VL UT WOS:000270173200010 PM 19521922 ER PT J AU Mazan-Mamczarz, K Kuwano, Y Zhan, M White, EJ Martindale, JL Lal, A Gorospe, M AF Mazan-Mamczarz, Krystyna Kuwano, Yuki Zhan, Ming White, Elizabeth J. Martindale, Jennifer L. Lal, Ashish Gorospe, Myriam TI Identification of a signature motif in target mRNAs of RNA-binding protein AUF1 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RICH ELEMENT; 3'-UNTRANSLATED REGION; HNRNP-D; GENE-EXPRESSION; NUCLEAR IMPORT; TRANSLATION; HUR; STABILITY; TURNOVER; DECAY AB The ubiquitous RNA-binding protein AUF1 promotes the degradation of some target mRNAs, but increases the stability and translation of other targets. Here, we isolated AUF1-associated mRNAs by immunoprecipitation of (AUF1RNA) ribonucleoprotein (RNP) complexes from HeLa cells, identified them using microarrays, and used them to elucidate a signature motif shared among AUF1 target transcripts. The predicted AUF1 motif (2939 nucleotides) contained 79 As and Us, consistent with the AU-rich sequences of reported AUF1 targets. Importantly, 10 out of 15 previously reported AUF1 target mRNAs contained the AUF1 motif. The predicted interactions between AUF1 and target mRNAs were recapitulated in vitro using biotinylated RNAs. Interestingly, further validation of predicted AUF1 target transcripts revealed that AUF1 associates with both the pre-mRNA and the mature mRNA forms. The consequences of AUF1 binding to 10 predicted target mRNAs were tested by silencing AUF1, which elevated the steady-state levels of only four mRNAs, and by overexpressing AUF1, which also lowered the levels of only four mRNAs. In total, we have identified a signature motif in AUF1 target mRNAs, have found that AUF1 also associates with the corresponding pre-mRNAs, and have discovered that altering AUF1 levels alone only modifies the levels of subsets of target mRNAs. C1 [Mazan-Mamczarz, Krystyna; Kuwano, Yuki; White, Elizabeth J.; Martindale, Jennifer L.; Lal, Ashish; Gorospe, Myriam] NIA, Lab Cellular & Mol Biol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Mazan-Mamczarz, Krystyna] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Zhan, Ming] NIA, Res Resources Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Lal, Ashish] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Lal, Ashish] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Gorospe, M (reprint author), NIA, Lab Cellular & Mol Biol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov FU National Institutes of Health [Z01-AG000392] FX This research was supported entirely by the Intramural Research Program of the NIA-IRP, National Institutes of Health. Funding for open access charge: Project number Z01-AG000392. NR 58 TC 50 Z9 53 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2009 VL 37 IS 1 BP 204 EP 214 DI 10.1093/nar/gkn929 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 392XO UT WOS:000262335700018 PM 19033365 ER PT J AU Chatr-aryamontri, A Ceol, A Peluso, D Nardozza, A Panni, S Sacco, F Tinti, M Smolyar, A Castagnoli, L Vidal, M Cusick, ME Cesareni, G AF Chatr-aryamontri, Andrew Ceol, Arnaud Peluso, Daniele Nardozza, Aurelio Panni, Simona Sacco, Francesca Tinti, Michele Smolyar, Alex Castagnoli, Luisa Vidal, Marc Cusick, Michael E. Cesareni, Gianni TI VirusMINT: a viral protein interaction database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID INFORMATION; RESOURCE; TEXT AB Understanding the consequences on host physiology induced by viral infection requires complete understanding of the perturbations caused by virus proteins on the cellular protein interaction network. The VirusMINT database (http://mint.bio.uniroma2.it/virusmint/) aims at collecting all protein interactions between viral and human proteins reported in the literature. VirusMINT currently stores over 5000 interactions involving more than 490 unique viral proteins from more than 110 different viral strains. The whole data set can be easily queried through the search pages and the results can be displayed with a graphical viewer. The curation effort has focused on manuscripts reporting interactions between human proteins and proteins encoded by some of the most medically relevant viruses: papilloma viruses, human immunodeficiency virus 1, Epstein-Barr virus, hepatitis B virus, hepatitis C virus, herpes viruses and Simian virus 40. C1 [Chatr-aryamontri, Andrew; Ceol, Arnaud; Peluso, Daniele; Nardozza, Aurelio; Sacco, Francesca; Tinti, Michele; Castagnoli, Luisa; Cesareni, Gianni] Univ Roma Tor Vergata, Dept Biol, I-00133 Rome, Italy. [Peluso, Daniele; Cesareni, Gianni] IRCCS Fdn Santa Lucia, I-00143 Rome, Italy. [Panni, Simona] Univ Calabria, Dept Cell Biol, Arcavacata Di Rende, Cs, Italy. [Smolyar, Alex; Vidal, Marc; Cusick, Michael E.] Harvard Univ, Sch Med, CCSB, Boston, MA 02115 USA. [Smolyar, Alex; Vidal, Marc; Cusick, Michael E.] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Smolyar, Alex; Vidal, Marc; Cusick, Michael E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Cesareni, G (reprint author), Univ Roma Tor Vergata, Dept Biol, Via Ric Sci, I-00133 Rome, Italy. EM cesareni@uniroma2.it RI Ceol, Arnaud/H-3386-2012; OI Ceol, Arnaud/0000-0001-9533-4246; panni, simona/0000-0002-7500-4028 FU Associazione Italiana per la Ricerca sul Cancro; ENFIN Network of Excellence [LSHG-CT-2005-518254]; Dana-Farber Cancer Institute Strategic Initiative; National Human Genome Research Institute [P50-HG004233]; National Institute of Environmental Health Science [R01-ES015728] FX Associazione Italiana per la Ricerca sul Cancro; ENFIN Network of Excellence (LSHG-CT-2005-518254); Dana-Farber Cancer Institute Strategic Initiative; National Human Genome Research Institute (P50-HG004233); and National Institute of Environmental Health Science (R01-ES015728). NR 11 TC 104 Z9 106 U1 3 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2009 VL 37 BP D669 EP D673 DI 10.1093/nar/gkn739 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386TT UT WOS:000261906200119 PM 18974184 ER PT J AU Fu, F Sander, JD Maeder, M Thibodeau-Beganny, S Joung, JK Dobbs, D Miller, L Voytas, DF AF Fu, Fengli Sander, Jeffry D. Maeder, Morgan Thibodeau-Beganny, Stacey Joung, J. Keith Dobbs, Drena Miller, Leslie Voytas, Daniel F. TI Zinc Finger Database (ZiFDB): a repository for information on C2H2 zinc fingers and engineered zinc-finger arrays SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ARTIFICIAL TRANSCRIPTION FACTORS; DNA-SEQUENCES; RECOGNITION; PROTEINS; DOMAINS; NUCLEASES; CONSTRUCTION; SELECTION; DESIGN; FAMILY AB Zinc fingers are the most abundant DNA-binding motifs encoded by eukaryotic genomes and one of the best understood DNA-recognition domains. Each zinc finger typically binds a 3-nt target sequence, and it is possible to engineer zinc-finger arrays (ZFAs) that recognize extended DNA sequences by linking together individual zinc fingers. Engineered zinc-finger proteins have proven to be valuable tools for gene regulation and genome modification because they target specific sites in a genome. Here we describe ZiFDB (Zinc Finger Database; http://bindr.gdcb.iastate.edu/ZiFDB), a web-accessible resource that compiles information on individual zinc fingers and engineered ZFAs. To enhance its utility, ZiFDB is linked to the output from ZiFiT-a software package that assists biologists in finding sites within target genes for engineering zinc-finger proteins. For many molecular biologists, ZiFDB will be particularly valuable for determining if a given ZFA (or portion thereof) has previously been constructed and whether or not it has the requisite DNA-binding activity for their experiments. ZiFDB will also be a valuable resource for those scientists interested in better understanding how zinc-finger proteins recognize target DNA. C1 [Voytas, Daniel F.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. [Voytas, Daniel F.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA. [Fu, Fengli; Sander, Jeffry D.; Dobbs, Drena] Iowa State Univ, Dept Genet Dev & Cell Biol, Roy J Carver CoLab 1043, Ames, IA 50011 USA. [Fu, Fengli; Sander, Jeffry D.; Miller, Leslie] Iowa State Univ, Interdept Grad Program Bioinformat & Computat Bio, Ames, IA 50011 USA. [Maeder, Morgan; Thibodeau-Beganny, Stacey; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA 02129 USA. [Maeder, Morgan; Thibodeau-Beganny, Stacey; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA. [Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Miller, Leslie] Iowa State Univ, Dept Comp Sci, Ames, IA 50011 USA. RP Voytas, DF (reprint author), Univ Minnesota, Dept Genet Cell Biol & Dev, 321 Church St SE, Minneapolis, MN 55455 USA. EM voytas@iastate.edu FU National Science Foundation [0501678, 0209818]; National Institutes of Health [GM069906, GM078369] FX The National Science Foundation ( 0501678 and 0209818 to D. F. V.); National Institutes of Health (GM069906 and GM078369 to J.K.J.). Funding for open access charge: National Science Foundation 0501678. NR 21 TC 46 Z9 47 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2009 VL 37 BP D279 EP D283 DI 10.1093/nar/gkn606 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386TT UT WOS:000261906200050 PM 18812396 ER PT J AU Reynolds, MA Dawson, DR Novak, KF Ebersole, JL Gunsolley, JC Branch-Mays, GL Holt, SC Mattison, JA Ingram, DK Novak, MJ AF Reynolds, Mark A. Dawson, Dolphus R. Novak, Karen F. Ebersole, Jeffrey L. Gunsolley, John C. Branch-Mays, Grishondra L. Holt, Stanley C. Mattison, Julie A. Ingram, Donald K. Novak, M. John TI Effects of caloric restriction on inflammatory periodontal disease SO NUTRITION LA English DT Article DE Monkey; Caloric restriction; Inflammation; Periodontal disease; Sex ID REAL-TIME PCR; POLYMERASE-CHAIN-REACTION; RHESUS-MONKEYS; CARDIOVASCULAR-DISEASE; DIETARY RESTRICTION; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; NONHUMAN-PRIMATES; BACTERIA; ADULTS; RISK AB Objective: Dietary caloric restriction (CR) has been found to reduce systemic markers of inflammation and may attenuate the effects of chronic inflammatory conditions. The purpose of this study was to examine the effects of long-term CR on naturally occurring chronic inflammatory periodontal disease in a nonhuman primate model. Methods: The effects of long-term CR on extent and severity of naturally occurring chronic periodontal disease, local inflammatory and immune responses, and periodontal microbiology, were evaluated in a cohort of 81 (35 female and 46 male; 13-40 y of age) rhesus monkeys (Macaca mulatta) with no previous exposure to routine oral hygiene. CR monkeys had been subjected to 30% CR for 13-17 y relative to control-fed (CON) animals starting at 3-5 y of age. Results: Same sex CR and CON monkeys exhibited similar levels of plaque, calculus, and bleeding on probing. Among CON animals, males showed significantly greater periodontal breakdown, as reflected by higher mean clinical attachment level and periodontal probing depth scores, than females. CR males exhibited significantly less periodontal pocketing, lower IgG antibody response, and lower IL-8 and beta-glucuronidase levels compared to CON males, whereas CR females showed a lower IgG antibody response but comparable clinical parameters and inflammatory marker levels relative to CON females. Long-term CR had no demonstrable effect on the periodontal microbiota. Conclusion: Males demonstrated greater risk for naturally occurring periodontal disease than females. Long-term CR may differentially reduce the production of local inflammatory mediators and risk for inflammatory periodontal disease among males but not females. (C) 2009 Elsevier Inc. All rights reserved. C1 [Reynolds, Mark A.; Branch-Mays, Grishondra L.] Univ Maryland, Sch Dent, Dept Periodont, Baltimore, MD 21201 USA. [Dawson, Dolphus R.; Novak, Karen F.; Ebersole, Jeffrey L.; Novak, M. John] Univ Kentucky, Coll Dent, Ctr Oral Hlth Res, Lexington, KY USA. [Gunsolley, John C.] Virginia Commonwealth Univ, Sch Dent, Richmond, VA USA. [Holt, Stanley C.] Forsyth Inst, Boston, MA USA. [Mattison, Julie A.] NIA, Lab Expt Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Ingram, Donald K.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA USA. RP Reynolds, MA (reprint author), Univ Maryland, Sch Dent, Dept Periodont, Baltimore, MD 21201 USA. EM mreynolds@umaryland.edu FU USPHS; National Institute of Aging [U01 AG-021406] FX This work was supported by USPHS grant U01 AG-021406 from the National Institute of Aging and by funds from the Intramural Research Program of the National Institute on Aging and the Veterinary Research Program of the Division of Research Resources of the National Institutes of Health. NR 64 TC 19 Z9 19 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 JAN PY 2009 VL 25 IS 1 BP 88 EP 97 DI 10.1016/j.nut.2008.07.003 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 383AH UT WOS:000261646000016 PM 18929461 ER PT J AU Shannon, J Phoutrides, E Palma, A Farris, P Peters, L Forester, A Tillotson, CJ Garzotto, M AF Shannon, Jackilen Phoutrides, Elena Palma, Amy Farris, Paige Peters, Laura Forester, Anna Tillotson, Carrie J. Garzotto, Mark TI Folate Intake and Prostate Cancer Risk: A Case-Control Study SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID ONE-CARBON METABOLISM; ALCOHOL-CONSUMPTION; PROSPECTIVE COHORT; DNA METHYLATION; DIETARY-FOLATE; BREAST-CANCER; FOLIC-ACID; MEN; MANAGEMENT AB Folate deficiency has been implicated in the carcinogenesis of several tumor types. The role of folate in prostate cancer remains indeterminate. We investigated folate as a risk factor for prostate cancer among 140 biopsy-confirmed prostate cancer patients, 230 age-matched clinic controls, and 250 negative prostate biopsy controls. Dietary folate intake was inversely associated with overall risk of prostate cancer as compared to clinic controls (P for a linear trend = 0.003). When stratified by disease severity, dietary folate and folate from natural sources were associated with reduced risk of high-grade cancer as compared to both clinic controls (P for a linear trend = 0.0009 and 0.02, respectively) and biopsy negative controls (P for a linear trend = 0.03 and 0.05, respectively). There was no interaction between alcohol consumption and folate intake. These analyses support an inverse association between dietary folate intake and prostate cancer risk and primarily risk of high-grade prostate cancer. C1 [Shannon, Jackilen; Phoutrides, Elena; Palma, Amy; Farris, Paige; Forester, Anna; Tillotson, Carrie J.; Garzotto, Mark] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Shannon, Jackilen; Palma, Amy; Farris, Paige; Peters, Laura; Garzotto, Mark] Portland VA Med Ctr, Portland, OR USA. RP Shannon, J (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd L606, Portland, OR 97239 USA. EM shannoja@ohsu.edu FU United States Public Health Service [5 M01 RR000334, 1 UL1 RR024120-01, K22CA94973]; VA Advanced Career Development Award; OHSU Cancer Institute Biostatistics Shared Resource [P30 CA069533-09]; Oregon Clinical and Translational Research Institute [UL1 RR024140] FX This study was supported by United States Public Health Service grants 5 M01 RR000334, 1 UL1 RR024120-01, and K22CA94973 and the resources and facilities of the Portland Veterans Affairs Medical Center. VA Advanced Career Development Award (M. Garzotto) Biostatistics support was provided through the OHSU Cancer Institute Biostatistics Shared Resource (P30 CA069533-09) and the Oregon Clinical and Translational Research Institute (UL1 RR024140). NR 31 TC 21 Z9 22 U1 2 U2 5 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2009 VL 61 IS 5 BP 617 EP 628 DI 10.1080/01635580902846593 PG 12 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 502AU UT WOS:000270427100006 PM 19838935 ER PT J AU Katiyar, S Elmets, CA Katiyar, SK AF Katiyar, Suchitra Elmets, Craig A. Katiyar, Santosh K. BE Tabor, A Blair, RM TI Green Tea and Skin Cancer: Immunological Modulation and DNA Repair SO NUTRITIONAL COSMETICS: BEAUTY FROM WITHIN LA English DT Article; Book Chapter ID RADIATION-INDUCED IMMUNOSUPPRESSION; ULTRAVIOLET-B RADIATION; POLYPHENOL (-)-EPIGALLOCATECHIN-3-GALLATE TREATMENT; INDUCED IMMUNE SUPPRESSION; ANTIGEN-PRESENTING CELL; T4 ENDONUCLEASE-V; CONTACT HYPERSENSITIVITY; HAIRLESS MICE; MOUSE SKIN; IN-VIVO C1 [Katiyar, Suchitra; Elmets, Craig A.; Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Katiyar, S (reprint author), Univ Alabama Birmingham, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557,Box 202, Birmingham, AL 35294 USA. EM skatiyar@uab.edu NR 116 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-8155-2030-6 PY 2009 BP 471 EP 499 DI 10.1016/B978-0-8155-2029-0.50031-4 PG 29 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA BFB47 UT WOS:000319112900027 ER PT J AU Hatoum, IJ Stein, HK Merrifield, BF Kaplan, LM AF Hatoum, Ida J. Stein, Heather K. Merrifield, Benjamin F. Kaplan, Lee M. TI Capacity for Physical Activity Predicts Weight Loss After Roux-en-Y Gastric Bypass SO OBESITY LA English DT Article ID BODY-MASS INDEX; BARIATRIC SURGERY; MORBID-OBESITY; VISCERAL OBESITY; UNITED-STATES; PATIENT CHARACTERISTICS; MARITAL-STATUS; MORTALITY; WOMEN; US AB Despite its overall excellent outcomes, weight loss after Roux-en-Y gastric bypass (RYGB) is highly variable. We conducted this study to identify clinical predictors of weight loss after RYGB. We reviewed charts from 300 consecutive patients who underwent RYGB from August 1999 to November 2002. Data collected included patient demographics, medical comorbidities, and diet history. Of the 20 variables selected for univariate analysis, 9 with univariate P values <= 0.15 were entered into a multivariable regression analysis. Using backward selection, covariates with P < 0.05 were retained. Potential confounders were added back into the model and assessed for effect on all model variables. Complete records were available for 246 of the 300 patients (82%). The patient characteristics were 75% female, 93% white, mean age of 45 years, and mean initial BMI of 52.3 kg/m(2). One year after surgery, patients lost an average of 64.8% of their excess weight (s.d. = 20.5%). The multivariable regression analysis revealed that limited physical activity, higher initial BMI, lower educational level, diabetes, and decreased attendance at postoperative appointments had an adverse effect on weight loss after RYGB. A model including these five factors accounts for 41% of the observed variability in weight loss (adjusted r(2) = 0.41). In this cohort, higher initial BMI and limited physical activity were the strongest predictors of decreased excess weight loss following RYGB. Limited physical activity may be particularly important because it represents an opportunity for potentially meaningful pre- and postsurgical intervention to maximize weight loss following RYGB. C1 [Hatoum, Ida J.; Stein, Heather K.; Merrifield, Benjamin F.; Kaplan, Lee M.] Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. [Hatoum, Ida J.; Stein, Heather K.; Merrifield, Benjamin F.; Kaplan, Lee M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hatoum, Ida J.; Stein, Heather K.; Merrifield, Benjamin F.; Kaplan, Lee M.] Harvard Univ, Sch Med, Boston, MA USA. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. EM lmkaplan@partners.org FU NIH [DK046200, DK043351, DK057478, DK007533] FX We thank Scott Newberg, David Lee, and John Orav for their statistical contributions and valuable discussions. In addition, we thank Denise Viscardi for her helpful administrative assistance. This work was supported by NIH grants DK046200, DK043351, and DK057478 (L.M.K.) and training award DK007533 (B.F.M.). NR 71 TC 35 Z9 35 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD JAN PY 2009 VL 17 IS 1 BP 92 EP 99 DI 10.1038/oby.2008.507 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 389QQ UT WOS:000262110000014 PM 18997674 ER PT J AU Chen, L Pai, V Levinson, R Sharpe, AH Freeman, GJ Braun, J Gordon, LK AF Chen, Ling Pai, Vicky Levinson, Ralph Sharpe, Arlene H. Freeman, Gordon J. Braun, Jonathan Gordon, Lynn K. TI Constitutive Neuronal Expression of the Immune Regulator, Programmed Death 1 (PD-1), Identified During Experimental Autoimmune Uveitis SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE Brain; experimental autoimmune uveitis (EAU); immune-privilege; programmed death 1 (PD-1); retina ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENE POLYMORPHISM; MICE; ASSOCIATION; PATHWAY; ENCEPHALOMYELITIS; PLASTICITY; PRIVILEGE; DISEASES; RECEPTOR AB Purpose: Programmed death-1 (PD-1) ligation downregulates active lymphocyte responses. The authors tested whether PD-1 or its ligands are expressed in the posterior segment during active intraocular inflammation. Methods: Experimental autoimmune uveitis (EAU) was induced using interphotoreceptor retinoid-binding protein (IRBP 161-180). Ocular inflammation was evaluated by histology and expression of PD-1 ligand tested by immunohistochemistry. PD-1 expression was evaluated by immunohistochemistry, RT-PCR, and Western immunoblotting. Results: Using immunohistochemistry, PD-1, but not its ligands, was constitutively expressed in retinal neurons of naive mouse retina. Both PD-1 and its ligands were observed, as expected, in sites of active inflammation. Conclusions: PD-1 and its ligands were expressed in sites of active inflammation, in accordance with many other models of inflammatory disease. Surprisingly, PD-1, not previously described outside the immune system, was constitutively expressed in retinal neurons, raising the possibility that PD-1 signaling may be important for neuronal function in the absence of an inflammatory insult. C1 [Chen, Ling; Pai, Vicky; Levinson, Ralph; Gordon, Lynn K.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Inst, Dept Ophthalmol, Los Angeles, CA 90095 USA. [Chen, Ling; Braun, Jonathan] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Inst, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Sharpe, Arlene H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Braun, Jonathan] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Inst, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Gordon, Lynn K.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Gordon, LK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Inst, Dept Ophthalmol, Los Angeles, CA 90095 USA. EM lgordon@ucla.edu FU Research to Prevent Blindness; Ruzic Medical Research Foundation FX This work was supported by Research to Prevent Blindness (Dr. Gordon) and the Ruzic Medical Research Foundation (Dr. Braun). NR 29 TC 11 Z9 15 U1 0 U2 3 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. PY 2009 VL 17 IS 1 BP 47 EP 55 AR PII 909596485 DI 10.1080/09273940802491884 PG 9 WC Ophthalmology SC Ophthalmology GA 420EN UT WOS:000264271800012 PM 19294574 ER PT J AU Zhu, AX Clark, JW AF Zhu, Andrew X. Clark, Jeffrey W. TI Commentary: Sorafenib Use in Patients with Advanced Hepatocellular Carcinoma and Underlying Child-Pugh B Cirrhosis-Evidence and Controversy SO ONCOLOGIST LA English DT Article ID ANTITUMOR-ACTIVITY; INHIBITION C1 [Zhu, Andrew X.; Clark, Jeffrey W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Canc Ctr, Tucker Gosnell Ctr Gastrointestinal Canc, Boston, MA 02114 USA. RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Canc Ctr, Tucker Gosnell Ctr Gastrointestinal Canc, Lawrence House POB 232,55 Fruit St, Boston, MA 02114 USA. EM ahezel@partners.org; jclark@partners.org NR 14 TC 24 Z9 24 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 JAN PY 2009 VL 14 IS 1 BP 67 EP 69 DI 10.1634/theoncologist.2008-0281 PG 3 WC Oncology SC Oncology GA 407MJ UT WOS:000263368100008 PM 19147690 ER PT J AU Fritz, S Warshaw, AL Thayer, SP AF Fritz, Stefan Warshaw, Andrew L. Thayer, Sarah P. TI Management of Mucin-Producing Cystic Neoplasms of the Pancreas SO ONCOLOGIST LA English DT Review DE Pancreas; Intraductal papillary mucinous neoplasm; Mucinous cystic neoplasm; Pancreatectomy; IPMN; MCN ID INTRADUCTAL PAPILLARY NEOPLASMS; K-RAS MUTATIONS; TERM-FOLLOW-UP; CLINICOPATHOLOGICAL FEATURES; PERORAL PANCREATOSCOPY; SURGICAL RESECTION; DIFFERENTIAL-DIAGNOSIS; DUCTAL ADENOCARCINOMA; ENDOSCOPIC RETROGRADE; SYMPTOMATIC PATIENTS AB During the last decade small lesions of the pancreas have been increasingly recognized in clinical practice. Among these lesions, mucin-producing cystic neoplasms represent a recently described and unique entity among pancreatic tumors. In 1996, the World Health Organization distinguished two different types of mucinous cystic tumors: intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, which are characterized by mucin production, cystic dilation of the pancreatic ducts, and intrapapillary growth, and mucinous cystic neoplasms (MCNs), which are defined by ovarian-like stroma and in most cases do not communicate with pancreatic ducts. Further, IPMNs can be subdivided into main-duct type, mixed-type, and branch-duct type tumors. Older data did not distinguish among different subsets of cystic neoplasms of the pancreas, and consequently many databases were inconsistent. Histopathologically, both IPMNs and MCNs demonstrate a wide spectrum of cellular atypia ranging from mild mucinous hyperplasia to invasive adenocarcinoma. Because mucinous cystic neoplasms of the pancreas show significant differences in clinical behavior from patient to patient, knowledge of the clinicopathologic characteristics and natural history of specific sub-types of IPMNs and MCNs has become crucial for physicians working in the field of gastroenterology. The present work offers an overview of current and generally accepted clinical guidelines for the diagnosis and treatment of IPMNs and MCNs. The Oncologist 2009; 14: 125-136 C1 [Fritz, Stefan; Warshaw, Andrew L.; Thayer, Sarah P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Thayer, SP (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Pkman St,WAC460, Boston, MA 02114 USA. EM sthayer@partners.org FU Karin Grunebaum Cancer Research Foundation; German Research Foundation FX This work was supported by funding from the Karin Grunebaum Cancer Research Foundation and the German Research Foundation (S. F.). NR 133 TC 23 Z9 31 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 2 BP 125 EP 136 DI 10.1634/theoncologist.2008-0200 PG 12 WC Oncology SC Oncology GA 417ZD UT WOS:000264116100005 PM 19211618 ER PT J AU Pennell, NA Lynch, TJ AF Pennell, Nathan A. Lynch, Thomas J., Jr. TI Combined Inhibition of the VEGFR and EGFR Signaling Pathways in the Treatment of NSCLC SO ONCOLOGIST LA English DT Article DE NSCLC; VEGFR; EGFR; Vandetanib; Bevacizumab; Erlotinib ID CELL LUNG-CANCER; GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; HUMAN PANCREATIC-CANCER; CLINICAL-TRIALS GROUP; RANDOMIZED PHASE-II; GENE COPY NUMBER; SOLID TUMORS; ACQUIRED-RESISTANCE; PROTEIN EXPRESSION AB Multitargeted agents represent the next generation of targeted therapies in solid tumors. The benefits of individually targeting the vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) signaling pathways have been clinically validated in recent years in a number of solid tumor types including non-small cell lung cancer (NSCLC). Given the heterogeneity of this tumor type and potential crosstalk between these key signaling pathways (which are known to play a critical role in tumor growth, metastasis, and angiogenesis), dual inhibition of the VEGFR and EGFR signaling pathways has the potential to offer additional clinical benefits in NSCLC. A number of approaches to inhibiting both VEGFR and EGFR signaling are currently under investigation, including monotherapy with a multitargeted tyrosine kinase inhibitor (e.g., vandetanib, AEE788, XL647, BMS-690514) or a combination of single-targeted therapies (e. g., bevacizumab, cetuximab, erlotinib, gefitinib). Preclinical and early clinical data (phase I and II trials) support combined inhibition of the VEGFR and EGFR pathways in NSCLC. Overall, combined inhibition strategies are well tolerated and have shown promise in early clinical studies. Ongoing phase II and phase III trials will determine the clinical potential of a number of dual inhibition strategies in the treatment of advanced NSCLC. The Oncologist 2009; 14: 399-411 C1 [Pennell, Nathan A.] Cleveland Clin, Dept Solid Tumor Oncol, Taussig Canc Inst, Cleveland, OH 44195 USA. [Pennell, Nathan A.; Lynch, Thomas J., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pennell, NA (reprint author), Cleveland Clin, Dept Solid Tumor Oncol, Taussig Canc Inst, R-35,9500 Euclid Ave, Cleveland, OH 44195 USA. EM penneln@ccf.org NR 98 TC 60 Z9 64 U1 0 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 4 BP 399 EP 411 DI 10.1634/theoncologist.2008-0276 PG 13 WC Oncology SC Oncology GA 439QD UT WOS:000265641200009 PM 19357226 ER PT J AU Bates, SE Benz, EJ AF Bates, Susan E. Benz, Edward J., Jr. TI Troublesome Words, Linguistic Precision, and Medical Oncology SO ONCOLOGIST LA English DT Editorial Material C1 [Bates, Susan E.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Benz, Edward J., Jr.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bates, SE (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bldg 10,Room 12N226,MSC 1903,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sebates@helix.nih.gov FU Intramural NIH HHS; PHS HHS [0] NR 14 TC 1 Z9 1 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 4 BP 445 EP 447 DI 10.1634/theoncologist.2008-0253 PG 3 WC Oncology SC Oncology GA 439QD UT WOS:000265641200013 PM 19357227 ER PT J AU Chi, AS Sorensen, AG Jain, RK Batchelor, TT AF Chi, Andrew S. Sorensen, A. Gregory Jain, Rakesh K. Batchelor, Tracy T. TI Angiogenesis as a Therapeutic Target in Malignant Gliomas SO ONCOLOGIST LA English DT Review DE Malignant glioma; Glioblastoma; Angiogenesis; Vascular endothelial growth factor; Cerebral edema ID ENDOTHELIAL-GROWTH-FACTOR; PHASE-II TRIAL; HIGH-GRADE GLIOMAS; NEWLY-DIAGNOSED GLIOBLASTOMA; BEVACIZUMAB PLUS IRINOTECAN; LOW-DOSE CHEMOTHERAPY; INHIBITS TUMOR-GROWTH; RENAL-CELL CARCINOMA; BRAIN-TUMORS; IN-VIVO AB Currently, adult glioblastoma (GBM) patients have poor outcomes with conventional cytotoxic treatments. Because GBMs are highly angiogenic tumors, inhibitors that target tumor vasculature are considered promising therapeutic agents in these patients. Encouraging efficacy and tolerability in preliminary clinical trials suggest that targeting angiogenesis may be an effective therapeutic strategy in GBM patients. However, the survival benefits observed to date in uncontrolled trials of antiangiogenic agents have been modest, and several obstacles have limited their effectiveness. This article reviews the rationale for antiangiogenic agents in GBM, their potential mechanisms of action, and their clinical development in GBM patients. Although challenges remain with this approach, ongoing studies may improve upon the promising initial benefits already observed in GBM patients. The Oncologist 2009; 14: 621-636 C1 [Chi, Andrew S.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Ctr Canc, Div Hematol & Oncol,Dept Neurol, Boston, MA 02114 USA. [Sorensen, A. Gregory] AA Martinos Ctr Biomed Imaging, Boston, MA USA. [Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Chi, Andrew S.; Sorensen, A. Gregory; Jain, Rakesh K.; Batchelor, Tracy T.] Harvard Univ, Sch Med, Boston, MA USA. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Ctr Canc, Div Hematol & Oncol,Dept Neurol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM tbatchelor@partners.org FU NCI NIH HHS [P01 CA080124] NR 175 TC 56 Z9 60 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 6 BP 621 EP 636 DI 10.1634/theoncologist.2008-0272 PG 16 WC Oncology SC Oncology GA 463IC UT WOS:000267424500009 PM 19487335 ER PT J AU Vora, SR Zheng, H Stadler, ZK Fuchs, CS Zhu, AX AF Vora, Sadhna R. Zheng, Hui Stadler, Zsofia K. Fuchs, Charles S. Zhu, Andrew X. TI Serum alpha-Fetoprotein Response as a Surrogate for Clinical Outcome in Patients Receiving Systemic Therapy for Advanced Hepatocellular Carcinoma SO ONCOLOGIST LA English DT Article DE Carcinoma; Hepatocellular; alpha-fetoprotein; Drug response biomarkers; Clinical trial ID PHASE-II; UNITED-STATES; GROWTH-FACTOR; CHEMOTHERAPY; GEMCITABINE; SURVIVAL; CANCER; THALIDOMIDE; OXALIPLATIN; COMBINATION AB Background. The role of serum alpha-fetoprotein (AFP) as a marker for treatment response in patients with hepatocellular carcinoma (HCC) receiving systemic therapy is poorly defined. Methods. A retrospective study was performed on patients with advanced HCC enrolled in five phase II clinical trials. Serum AFP was prospectively collected at baseline and at different time points through treatment in parallel with radiologic response and clinical outcome. Patients were separated into three groups based on a 50% change in serum AFP from baseline. Overall survival (OS), progression-free survival (PFS), and radiologic responses were compared between groups using log-rank and Wilcoxon tests. Results. Of 144 patients, 107 met the eligibility criteria. Eighteen patients experienced a >50% AFP decline, 57 patients had a >50% AFP increase, and 32 patients had a <50% change in serum AFP in either direction. Compared with patients with a <50% change in serum AFP (median PFS, 5.6 months), patients with a >50% AFP decrease had a longer PFS time (median, 16.9 months; p = .029), whereas those with a >50% increase had a shorter PFS time (median, 2.3 months; p = .038). Patients with a >50% rise in AFP had a shorter OS time than those with a <50% change (median, 6.3 months versus 11.1 months, respectively; p = .004), whereas a >50% AFP decrease was not associated with a significant difference in OS (median, 13.0 months; p = .87). AFP changes were significantly associated with radiologic response. Conclusions. Our study suggests that serum AFP change during treatment may serve as a useful surrogate marker for clinical outcome in patients with advanced HCC receiving systemic therapy. The Oncologist 2009;14:717-725 C1 [Zhu, Andrew X.] Massachusetts Gen Hosp, Ctr Canc, Tucker Gosnell Ctr Gastrointestinal Canc, Dept Med, Boston, MA 02114 USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Canc, Ctr Biostat, Boston, MA 02114 USA. [Zheng, Hui; Stadler, Zsofia K.; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA USA. [Stadler, Zsofia K.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Zhu, AX (reprint author), Massachusetts Gen Hosp, Ctr Canc, Tucker Gosnell Ctr Gastrointestinal Canc, Dept Med, Lawrence House POB 232,55 Fruit St, Boston, MA 02114 USA. EM azhu@partners.org NR 38 TC 52 Z9 58 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 7 BP 717 EP 725 DI 10.1634/theoncologist.2009-0038 PG 9 WC Oncology SC Oncology GA 477EO UT WOS:000268501600008 PM 19581525 ER PT J AU Lee, AI LaCasce, AS AF Lee, Alfred Ian LaCasce, Ann S. TI Nodular Lymphocyte Predominant Hodgkin Lymphoma SO ONCOLOGIST LA English DT Article DE Hodgkin lymphoma; Nodular lymphocyte Hodgkin lymphoma; LP cell ID REED-STERNBERG CELLS; DISTINCT CLINICOPATHOLOGICAL ENTITY; TRANSFORMED GERMINAL-CENTERS; EUROPEAN TASK-FORCE; STUDY-GROUP GHSG; PROGRESSIVE TRANSFORMATION; CLINICAL PRESENTATION; MONOCLONAL-ANTIBODIES; PHASE-2 TRIAL; GENE REARRANGEMENTS AB Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of HL with unique clinicopathologic features. The hallmark histologic feature is the presence of malignant LP cells, unusual CD20(+)CD15(-)CD30(-) variants of Reed-Sternberg cells, embedded within a nodular pattern of infiltrating lymphocytes. Compared with classical HL, NLPHL shows a slightly older median age at presentation (30-40 years), greater male predominance (3:1), less mediastinal involvement (<15%), and lower occurrence of classical HL risk factors. The differential diagnosis includes progressive transformation of germinal centers, lymphocyte-rich classical HL, and T-cell/histiocyte-rich large B-cell lymphoma, the latter of which may share a common biologic relationship. The vast majority of patients present with limited stage disease (70%-80%), the standard treatment for which is involved field radiotherapy at 30-36 Gy. Response rates to primary therapy exceed 90%, although relapses are common and may occur years after the initial diagnosis. Secondary malignancies, particularly non-Hodgkin lymphoma, may also occur at a frequency similar to that of relapsed NLPHL. Patients with advanced stage disease may have lower response rates and overall survival times than those with limited stage disease. For relapsed disease, treatment options include the salvage therapies used in classical HL, and rituximab. The Oncologist 2009;14:739-751 C1 [LaCasce, Ann S.] Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. [Lee, Alfred Ian] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP LaCasce, AS (reprint author), Dana Farber Canc Inst, Ctr Hematol Oncol, D1B05,44 Binney St, Boston, MA 02115 USA. EM Ann_Lacasce@dfci.harvard.edu NR 100 TC 19 Z9 22 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 7 BP 739 EP 751 DI 10.1634/theoncologist.2009-0099 PG 13 WC Oncology SC Oncology GA 477EO UT WOS:000268501600010 PM 19605845 ER PT J AU Yoon, SS Yang, HK AF Yoon, Sam S. Yang, Han-Kwang TI Lymphadenectomy for Gastric Adenocarcinoma: Should West Meet East? SO ONCOLOGIST LA English DT Article DE Gastric cancer; Surgery; Lymphadenectomy; Outcomes; Review ID LYMPH-NODE DISSECTION; RANDOMIZED CONTROLLED-TRIAL; PRESERVING TOTAL GASTRECTOMY; MARUYAMA COMPUTER-PROGRAM; DUTCH D1-D2 TRIAL; CANCER DATA-BASE; UNITED-STATES; COMBINED PANCREATICOSPLENECTOMY; D2 GASTRECTOMY; SURGICAL TRIAL AB The extent of lymphadenectomy that should be performed for gastric adenocarcinoma has been a topic of persistent debate. In countries such as Japan and Korea, where the incidence of gastric adenocarcinoma is high, more extensive (e.g., D2) lymphadenectomies are routinely performed, usually by experienced surgeons with low morbidity and mortality. In western countries such as the U. S., where the incidence of gastric adenocarcinoma is tenfold lower, the performance of more extensive lymphadenectomies is generally limited to specialized centers, and quite possibly the majority of patients are treated at non-referral centers with less than a D1 lymphadenectomy. There is little disagreement among gastric cancer experts that the minimum lymphadenectomy that should be performed for gastric adenocarcinoma should be at least a D1 lymphadenectomy. Two large, prospective randomized trials performed in the United Kingdom and the Netherlands failed to demonstrate a survival benefit of D2 over D1 lymphadenectomy, but these trials have been criticized for high surgical morbidity and mortality rates in the D2 group. More recent studies have demonstrated that western surgeons can be trained to perform D2 lymphadenectomies on western patients with low morbidity and mortality. Retrospective analyses and one prospective, randomized trial suggest that there may be some benefits to more extensive lymphadenectomies when performed safely, but this assertion requires further validation. This article provides an update on the current literature regarding the extent of lymphadenectomy for gastric adenocarcinoma. The Oncologist 2009; 14: 871- 882 C1 [Yoon, Sam S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Surg Oncol,Dept Surg, Boston, MA 02114 USA. [Yang, Han-Kwang] Univ Seoul, Coll Med, Seoul Natl Univ Hosp, Dept Surg, Seoul, South Korea. RP Yoon, SS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Surg Oncol,Dept Surg, Yawkey 7B-7926,55 Fruit St, Boston, MA 02114 USA. EM syoon@partners.org RI Yang, Han-Kwang/J-2767-2012 NR 69 TC 30 Z9 30 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 PY 2009 VL 14 IS 9 BP 871 EP 882 DI 10.1634/theoncologist.2009-0070 PG 12 WC Oncology SC Oncology GA 497FJ UT WOS:000270042200002 PM 19738001 ER PT J AU Cleary, JM Tanabe, KT Lauwers, GY Zhu, AX AF Cleary, James M. Tanabe, Kenneth T. Lauwers, Gregory Y. Zhu, Andrew X. TI Hepatic Toxicities Associated with the Use of Preoperative Systemic Therapy in Patients with Metastatic Colorectal Adenocarcinoma to the Liver SO ONCOLOGIST LA English DT Article DE Colorectal cancer; Liver metastases; Chemotherapy; Targeted agents; Hepatic toxicity ID OXALIPLATIN-BASED CHEMOTHERAPY; MULTICENTER RANDOMIZED-TRIAL; PORTAL-VEIN EMBOLIZATION; LONG-TERM SURVIVAL; 1ST-LINE TREATMENT; MAJOR HEPATECTOMY; PHASE-III; NONALCOHOLIC STEATOHEPATITIS; OBSTRUCTION SYNDROME; PLUS IRINOTECAN AB Colorectal cancer patients with isolated liver metastasis are potentially cured with surgical resection. Recent advances in systemic chemotherapy have increased the ability to convert unresectable metastatic liver lesions to resectable lesions. The cost in toxicity of these therapeutic advances is increasingly being recognized. Numerous reports have demonstrated an association between irinotecan and steatohepatitis as well as between oxaliplatin and sinusoidal dilation. In this review, we summarize the current clinical experience with these hepatic toxicities and discuss the role they play in determining postoperative morbidity. We also review emerging safety data regarding the use of bevacizumab and cetuximab. Finally, we give specific clinical examples of how multidisciplinary teams can best manage patients receiving preoperative chemotherapy for potentially resectable liver metastases. The Oncologist 2009;14:1095-1105 C1 [Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Tucker Gosnell Ctr Gastrointestinal Canc,Med Sch, Boston, MA 02114 USA. RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Tucker Gosnell Ctr Gastrointestinal Canc,Med Sch, Lawrence House,POB 232,55 Fruit St, Boston, MA 02114 USA. EM azhu@partners.org NR 76 TC 35 Z9 40 U1 1 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 PY 2009 VL 14 IS 11 BP 1095 EP 1105 DI 10.1634/theoncologist.2009-0152 PG 11 WC Oncology SC Oncology GA 524TS UT WOS:000272166800006 PM 19880627 ER PT J AU Canellos, GP AF Canellos, George P. TI Is Chemotherapy Alone for Early Hodgkin Lymphoma an Emerging Therapeutic Option? SO ONCOLOGIST LA English DT Editorial Material 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, Boston, MA 02115 USA. EM george_canellos@dfci.harvard.edu NR 4 TC 2 Z9 2 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 12 BP 1167 EP 1168 DI 10.1634/theoncologist.2009-0288 PG 2 WC Oncology SC Oncology GA 536BG UT WOS:000273016500001 PM 20008306 ER PT J AU de Miguel-Yanes, JM Meigs, JB AF de Miguel-Yanes, Jose M. Meigs, James B. TI When "Flawed" Translates into "Flood": The Unproven Association Between Cancer Incidence and Glargine Insulin Therapy SO ONCOLOGIST LA English DT Editorial Material ID MALIGNANCIES; ANALOGS; RISK C1 [de Miguel-Yanes, Jose M.; Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02114 USA. [de Miguel-Yanes, Jose M.] Hosp Gregorio Maranon, Dept Internal Med, Madrid, Spain. RP Meigs, JB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org NR 14 TC 2 Z9 2 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 12 BP 1175 EP 1177 DI 10.1634/theoncologist.2009-0278 PG 3 WC Oncology SC Oncology GA 536BG UT WOS:000273016500003 PM 20007646 ER PT J AU Chong, CR Chabner, BA AF Chong, Curtis R. Chabner, Bruce A. TI Mysterious Metformin SO ONCOLOGIST LA English DT Editorial Material ID BREAST-CANCER CELLS; DIABETES-MELLITUS; PANCREATIC-CANCER; INSULIN GLARGINE; IN-VITRO; RISK; METAANALYSIS; GROWTH; KINASE; EPIDEMIOLOGY C1 [Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Chong, Curtis R.; Chabner, Bruce A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Chabner, BA (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,LH 214, Boston, MA 02114 USA. EM bchabner@partners.org NR 46 TC 31 Z9 34 U1 0 U2 5 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 12 BP 1178 EP 1181 DI 10.1634/theoncologist.2009-0286 PG 4 WC Oncology SC Oncology GA 536BG UT WOS:000273016500004 PM 20007645 ER PT J AU Lipworth, AD Robert, C Zhu, AX AF Lipworth, Adam D. Robert, Caroline Zhu, Andrew X. TI Hand-Foot Syndrome (Hand-Foot Skin Reaction, Palmar-Plantar Erythrodysesthesia): Focus on Sorafenib and Sunitinib SO ONCOLOGY LA English DT Review DE Acral erythema; Burgdorf reaction; Hand-foot skin reaction; Hand-foot syndrome; Multireceptor tyrosine kinase inhibitors; Palmar-plantar erythrodysesthesia; Sorafenib; Sunitinib; Toxic erythema ID RENAL-CELL CARCINOMA; INDUCED ACRAL ERYTHEMA; PEGYLATED LIPOSOMAL DOXORUBICIN; METASTATIC BREAST-CANCER; ADVANCED HEPATOCELLULAR-CARCINOMA; DOSE CYTOSINE-ARABINOSIDE; MULTICENTER PHASE-II; VERSUS-HOST DISEASE; COLORECTAL-CANCER; COMBINATION CHEMOTHERAPY AB Hand-foot syndrome (HFS), also called hand-foot skin reaction, palmar-plantar erythrodysesthesia, acral erythema, and Burgdorf reaction, is a dose-limiting cutaneous toxicity of many chemotherapeutic agents. Recently, the multiple tyrosine kinase inhibitor class of novel targeted therapies, including sorafenib and sunitinib, has emerged as an important cause of HFS, with 10-28% of patients treated with sunitinib and 10-62% of patients treated with sorafenib reporting HFS. This review examines the epidemiology, clinical features, histopathology, pathogenesis models, prognostic implications, and management of HFS, with particular attention to HFS induced by sorafenib and sunitinib. The high prevalence of HFS reported by patients treated with these medications underscores the need for greater understanding of the pathogenesis and management of this syndrome. Copyright (C) 2009 S. Karger AG, Basel C1 [Zhu, Andrew X.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Med,Div Hematol Oncol, Tucker Gosnell Ctr Gastrointestinal Canc,Canc Ctr, Boston, MA 02114 USA. [Lipworth, Adam D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Robert, Caroline] Inst Gustave Roussy, Dept Dermatol, Villejuif, France. RP Zhu, AX (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Med,Div Hematol Oncol, Tucker Gosnell Ctr Gastrointestinal Canc,Canc Ctr, Lawrence House,POB 232 55 Fruit St, Boston, MA 02114 USA. EM azhu@partners.org NR 123 TC 84 Z9 85 U1 1 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2009 VL 77 IS 5 BP 257 EP 271 DI 10.1159/000258880 PG 15 WC Oncology SC Oncology GA 524JX UT WOS:000272140700001 PM 19923864 ER PT J AU Ruddy, KJ Partridge, AH AF Ruddy, Kathryn J. Partridge, Ann H. TI Ovarian Suppression/Ablation in Premenopausal ER-Positive Breast Cancer Patients Issues and Recommendations The Pritchard Article Reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 [Partridge, Ann H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 7 TC 0 Z9 1 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 JAN PY 2009 VL 23 IS 1 BP 34 EP + PG 2 WC Oncology SC Oncology GA 399UC UT WOS:000262823800002 PM 19283919 ER PT J AU Raut, CP Bertagnolli, MM AF Raut, Chandrajit P. Bertagnolli, Monica M. TI Perioperative Treatment of Gastrointestinal Stromal Tumors The dos Santos Fernandes/Blanke/Freitas et al Article Reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID IMATINIB MESYLATE IM; SURGICAL RESECTION; PROGNOSTIC-FACTORS; THERAPY; GIST; SURGERY; MUTATIONS C1 [Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Raut, CP (reprint author), Brigham & Womens Hosp, Dept Surg, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 19 TC 2 Z9 2 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 JAN PY 2009 VL 23 IS 1 BP 69 EP + PG 4 WC Oncology SC Oncology GA 399UC UT WOS:000262823800007 PM 19283924 ER PT J AU Toschi, L Cappuzzo, F AF Toschi, Luca Cappuzzo, Federico TI Gemcitabine for the treatment of advanced nonsmall cell lung cancer SO ONCOTARGETS AND THERAPY LA English DT Review DE gemcitabine; chemotherapy; pharmacoeconomics; nonsmall cell lung cancer AB Gemcitabine is a pyrimidine nucleoside antimetabolite agent which is active in several human malignancies, including nonsmall cell lung cancer (NSCLC). Because of its acceptable toxicity profile, with myelosuppression being the most common adverse event, gemcitabine can be safely combined with a number of cytotoxic agents, including platinum derivatives and new-generation anticancer compounds. In fact, the combination of gemcitabine and cisplatin is a first-line treatment for patients with advanced NSCLC, pharmacoeconomic data indicating that it represents the most cost-effective regimen among platinum-based combinations with third-generation cytotoxic drugs. The drug has been investigated in the context of nonplatinum-based regimens in a number of prospective clinical trials, and might provide a suitable alternative for patients with contraindications to platinum. Recently, gemcitabine- based doublets have been successfully tested in association with novel targeted agents with encouraging results, providing further evidence for the role of the drug in the treatment of NSCLC. In the last few years several attempts have been pursued in order to identify molecular predictors of gemcitabine activity, and recent data support the feasibility of genomic-based approaches to customize treatment with the ultimate goal of improving patient outcome. C1 [Cappuzzo, Federico] Ist Clin Humanitas IRCCS, Dept Oncohematol, I-20086 Rozzano, Italy. [Toschi, Luca] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cappuzzo, F (reprint author), Ist Clin Humanitas IRCCS, Dept Oncohematol, Via Manzoni 56, I-20086 Rozzano, Italy. EM federico.cappuzzo@humanitas.it RI Mendez, Pedro /J-8955-2016; OI Mendez, Pedro /0000-0001-6713-7907; Cappuzzo, Federico/0000-0002-6295-6767 NR 84 TC 9 Z9 9 U1 1 U2 3 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-6930 J9 ONCOTARGETS THER PY 2009 VL 2 BP 209 EP 217 PG 9 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA V15TL UT WOS:000207824200001 PM 20616908 ER PT J AU Hatton, MP Durand, ML Burns, SM Hanna, E Jakobiec, FA AF Hatton, Mark P. Durand, Marlene L. Burns, Sean M. Hanna, Eissa Jakobiec, Frederick A. TI Exaggerated Postsurgical Inflammation in a Patient With Insufficiently Treated Addison Disease SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB A patient with Addison disease developed fever, pain, and marked orbital inflammation 3 days after evisceration in the setting of perforated corneal ulcer. He was treated for presumed orbital cellulitis without improvement. Increasing the corticosteroid dose for his Addison disease resulted in complete resolution of the inflammation. C1 [Hatton, Mark P.] Ophthalm Consultants Boston, Boston, MA 02114 USA. [Durand, Marlene L.; Burns, Sean M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Durand, Marlene L.; Hanna, Eissa; Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Hatton, MP (reprint author), Ophthalm Consultants Boston, 50 Staniford St, Boston, MA 02114 USA. EM mphatton@eyeboston.com 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 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JAN-FEB PY 2009 VL 25 IS 1 BP 67 EP 69 DI 10.1097/IOP.0b013e3181935b09 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 398LR UT WOS:000262734100024 PM 19273936 ER PT J AU Chen, JH Shah, HA Herbert, C Loewenstein, JI Rizzo, JF AF Chen, Jinghua Shah, Hassan A. Herbert, Charles Loewenstein, John I. Rizzo, Joseph F., III TI Extraction of a Chronically Implanted, Microfabricated, Subretinal Electrode Array SO OPHTHALMIC RESEARCH LA English DT Article DE Retinal prosthesis; Subretinal electrode array; Vitreoretinal surgery ID ELECTRICAL-STIMULATION; RETINAL PROSTHESIS; RETINITIS-PIGMENTOSA; MICROELECTRODE ARRAYS; VISUAL-PERCEPTION; BUCKLE REMOVAL; BLIND; EFFICACY; SURGERY; RABBITS AB Purpose: To assess the feasibility of extraction of a chronically implanted subretinal electrode array. Methods: Inactive, polyimide strips (10 mm x 1.5 mm x 15 mu m) were surgically implanted into the subretinal space of 8 rabbits using a mostly ab externo approach. Pre- and postoperative clinical examinations, electroretinography and in some cases optical coherence tomography were performed to follow the course of the eyes. Two months after implantation, the polyimide strips were extracted from 5 eyes; 2 animals kept the implants and served as controls. All animals were then sacrificed and eyes enucleated for histological examination. Results: All 8 surgeries yielded successful placement of the arrays into the subretinal space. All 5 extraction surgeries were performed without obvious complications. Clinical examinations and electroretinography did not reveal any significant abnormalities. The histological examinations showed alterations from normal anatomy in all animals; the anatomical changes in the explanted animals were relatively mild and confined to the area of the surgery. Conclusions: Successful extraction of electrode arrays from the subretinal space of rabbits can be reliably performed 2 months after implantation, which is beyond the time period when postoperative scarring would be most intense. Copyright (C) 2009 S. Karger AG, Basel C1 [Rizzo, Joseph F., III] Massachusetts Eye & Ear Infirm, Neuroophthalmol Serv, Boston, MA 02114 USA. [Chen, Jinghua; Shah, Hassan A.; Loewenstein, John I.; Rizzo, Joseph F., III] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Herbert, Charles; Rizzo, Joseph F., III] VA Boston Healthcare Syst, Ctr Innovat Visual Rehabil, Boston, MA USA. RP Rizzo, JF (reprint author), Massachusetts Eye & Ear Infirm, Neuroophthalmol Serv, 243 Charles St, Boston, MA 02114 USA. EM Joseph_Rizzo@meei.harvard.edu FU Department of Veterans Affairs (Rehabilitation Research and Development Service; Massachusetts Lions Club FX The authors would like to thank James Fujimoto, PhD and Tony H. Ko, PhD of the Massachusetts Institute of Technology for providing the OCT machine; Douglas Shire, PhD and Marcus Gingerich, PhD of our group for developing the polyimide implants, and Robert Marini, DVM, Kathryn Madden and Diane Ghera of the animal care facilities at the Massachusetts Institute of Technology and the Boston VA Medical Center, Jamaica Plain. This work was supported by the Department of Veterans Affairs (Rehabilitation Research and Development Service), and the Massachusetts Lions Club. NR 38 TC 8 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3747 EI 1423-0259 J9 OPHTHALMIC RES JI Ophthalmic Res. PY 2009 VL 42 IS 3 BP 128 EP 137 DI 10.1159/000227278 PG 10 WC Ophthalmology SC Ophthalmology GA 516IL UT WOS:000271535500003 PM 19590253 ER PT B AU Namati, E Suter, MJ McLennan, G AF Namati, E. Suter, M. J. McLennan, G. BE Rosenthal, E Zinn, KR TI Endoscopic Techniques for Optical Imaging SO OPTICAL IMAGING OF CANCER: CLINICAL APPLICATIONS LA English DT Article; Book Chapter ID IN-VIVO DIAGNOSIS; CONFOCAL REFLECTANCE MICROSCOPE; MAGNETIC NAVIGATION SYSTEM; WHITE-LIGHT BRONCHOSCOPY; PERIPHERAL LUNG LESIONS; COHERENCE TOMOGRAPHY; VIRTUAL BRONCHOSCOPY; ELECTROMAGNETIC NAVIGATION; LASER ENDOMICROSCOPY; FLUORESCENCE BRONCHOSCOPY C1 [Namati, E.; McLennan, G.] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. [Suter, M. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [McLennan, G.] Univ Iowa, Dept Biomed Engn, Carver Coll Med, Iowa City, IA 52242 USA. [McLennan, G.] Univ Iowa, Dept Radiol, Carver Coll Med, Iowa City, IA 52242 USA. RP McLennan, G (reprint author), Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. EM geoffrey-mclennan@uiowa.edu NR 158 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-93873-8 PY 2009 BP 25 EP 48 DI 10.1007/978-0-387-93874-5_2 PG 24 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BLU36 UT WOS:000271043900002 ER PT B AU Yip, S Shah, K AF Yip, Stephen Shah, Khalid BE Rosenthal, E Zinn, KR TI Optical Imaging of Cancer: Neuro-oncologic Applications SO OPTICAL IMAGING OF CANCER: CLINICAL APPLICATIONS LA English DT Article; Book Chapter ID INDUCED PROTOPORPHYRIN-IX; INTERSTITIAL PHOTODYNAMIC THERAPY; GROWTH-FACTOR RECEPTOR; IN-VIVO; QUANTUM DOTS; BRAIN-TUMORS; STEM-CELLS; GLIOBLASTOMA-MULTIFORME; MALIGNANT GLIOMAS; TECHNICAL NOTE C1 [Yip, Stephen; Shah, Khalid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurotherapy & Imaging Lab, Boston, MA 02129 USA. RP Shah, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurotherapy & Imaging Lab, Bldg 149,13th St, Boston, MA 02129 USA. EM kshah@helix.mgh.harvard.edu NR 62 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-93873-8 PY 2009 BP 251 EP 264 DI 10.1007/978-0-387-93874-5_12 PG 14 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BLU36 UT WOS:000271043900012 ER PT S AU Gagnon, L Desjardins, M Bherer, L Lesage, F AF Gagnon, Louis Desjardins, Michele Bherer, Louis Lesage, Frederic BE Tromberg, BJ Yodh, AG Tamura, M SevickMuraca, EM TI Double layer estimation of flow changes using diffuse correlation spectroscopy SO OPTICAL TOMOGRAPHY AND SPECTROSCOPY OF TISSUE VIII SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Optical Tomography and Spectroscopy of Tissue VIII CY JAN 25-27, 2009 CL San Jose, CA SP SPIE DE Blood flow measurement; Near-infrared spectroscopy; Speckle ID TIME-RESOLVED REFLECTANCE; PHOTON DENSITY WAVES; MONTE-CARLO SIMULATIONS; 2-LAYERED TURBID MEDIA; OPTICAL-PROPERTIES; NONINVASIVE MEASUREMENT; RADIATIVE-TRANSFER; LIGHT TRANSPORT; HUMAN BRAIN; SCATTERING AB In this work, we explore diffuse correlation spectroscopy (DCS) in a two-layered geometry. We compare the effiency of an homogeneous and a two-layered model to recover flow changes. By simulating a realistic human head with MRI anatomical data, we show that the two-layered model allows distinction between superficial layers and brain hemodynamic changes. The results show that the two-layered model provides a better estimate for the flow change than the homogeneous one. Experimental measurements with a two-layered dynamical phantom confirm the ability of the two-layered analytical model to distinguish flow increase in each layer. C1 [Gagnon, Louis] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Gagnon, L (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM lgagnon@nmr.mgh.harvard.edu NR 44 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7420-9 J9 P SOC PHOTO-OPT INS PY 2009 VL 7174 AR 717407 DI 10.1117/12.808272 PG 12 WC Optics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Optics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA BSS71 UT WOS:000285714800006 ER PT J AU Martinez, BS Williams, M Fuhr, P AF Martinez, Bethany S. Williams, Michael Fuhr, Patti TI Visually impaired caregivers: Perspectives from patient focus groups SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION LA English DT Article DE Visual impairment; Caregiver; Low vision rehabilitation; Focus groups AB BACKGROUND: With the aging of the population, more persons who are severely visually impaired are now caring for a spouse or significant other. The purpose of this qualitative study is to learn more about this previously unreported, yet vulnerable, population of visually impaired caregivers. METHODS: Focus groups and 1-on-1 interviews were conducted with legally blind U.S. English-speaking adults who served as informal caregivers of adults. Visually impaired caregivers discussed the challenges of caregiving and how their visual impairment affected their caregiving responsibilities. Interview transcripts were analyzed using grounded theory. Standardized questionnaires captured demographic and social characteristics. RESULTS: Fourteen adults participated. Seven major themes emerged from the interviews: (1) impact of lack of transportation, (2) concern over care recipient's quality of life, (3) utilization of support, (4) all encompassing demand, (5) cyclical adaptations, (6) anxieties of the caregivers, and (7) positive aspects of caregiving. CONCLUSIONS: Although visually impaired caregivers experience challenges similar to other caregivers, they differ in their report of added burden because of visual impairment, with extraordinary difficulty in transportation issues and the necessity of cyclical adaptations as their vision worsens. This is, to our knowledge, the first qualitative study of visually impaired caregivers and brings to light the unique problems faced by this special cohort of caregivers. Optometry 2009;80:11-22 C1 [Martinez, Bethany S.; Fuhr, Patti] Univ Alabama, Vet Affairs Med Ctr, Birmingham Dept, Birmingham Sch Optometry, Birmingham, AL 35233 USA. [Williams, Michael] Georgia Inst Technol, Rehabil R&D Ctr Excellence Aging Vet Vis Loss, Vet Affairs Med Ctr, Ctr Assist Technol & Environm Access,Atlanta Dept, Atlanta, GA 30332 USA. [Williams, Michael] Blind Rehabil Serv, US Dept Vet Affairs, Natl Program Off, Washington, DC USA. RP Martinez, BS (reprint author), Univ Alabama, Vet Affairs Med Ctr, Birmingham Dept, Birmingham Sch Optometry, Optometry 112 C,700 S 19th St, Birmingham, AL 35233 USA. EM Bethany.Martinez@va.gov NR 57 TC 0 Z9 0 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-1839 J9 OPTOMETRY JI Optometry PD JAN PY 2009 VL 80 IS 1 BP 11 EP 22 DI 10.1016/j.optm.2008.04.100 PG 12 WC Ophthalmology SC Ophthalmology GA V18QB UT WOS:000208018200004 PM 19111253 ER PT J AU Duszak, RS AF Duszak, Robert S. TI Congenital rubella syndrome major-review SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION LA English DT Review DE Rubella; Congenital rubella syndrome ID 50-YEAR FOLLOW-UP; PRENATAL-DIAGNOSIS; TERATOGEN UPDATE; INFECTION; MANIFESTATIONS; REINFECTION; PREGNANCY; VIRUS; NEOVASCULARIZATION; EPIDEMIOLOGY AB Congenital rubella syndrome is a rare disorder with devastating ocular and systemic consequences. Although efforts to eradicate the disease have been in place for some time, some areas of the world continue to be affected by this disease. The burden of the disease weighs heavily on patients and society; therefore, vaccination and other preventative strategies should continue to be strongly encouraged. Optometry 2009;80:36-43 C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19103 USA. RP Duszak, RS (reprint author), Philadelphia Vet Affairs Med Ctr, 2112 Pine St,Apt 2, Philadelphia, PA 19103 USA. EM bduszak@mac.com NR 77 TC 26 Z9 29 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-1839 J9 OPTOMETRY JI Optometry PD JAN PY 2009 VL 80 IS 1 BP 36 EP 43 DI 10.1016/j.optm.2008.03.006 PG 8 WC Ophthalmology SC Ophthalmology GA V18QB UT WOS:000208018200007 PM 19111256 ER PT J AU Treister, N Sheehy, N Bae, EH Friedland, B Lerman, M Woo, S AF Treister, N. Sheehy, N. Bae, E. H. Friedland, B. Lerman, M. Woo, S. TI Dental panoramic radiographic evaluation in bisphosphonate-associated osteonecrosis of the jaws SO ORAL DISEASES LA English DT Article DE osteonecrosis of the jaws; bisphosphonates; panoramic radiography ID RISK-FACTORS; TOMOGRAPHIC FINDINGS; COMPUTED-TOMOGRAPHY; CANCER AB To determine the extent to which clinical and radiographic features of bisphosphonate-associated osteonecrosis of the jaw (BONJ) are correlated. Retrospective case review. The records of 39 patients diagnosed with BONJ and examined by panoramic radiography were retrospectively evaluated. The arches were divided into sextants (n = 234) and evaluated for the following signs: sclerosis, surface irregularity, sockets, fragmentation and lysis. The McNemar, Kruskall-Wallis and equivalency tests were performed to analyze the association between clinical and radiographic signs and BONJ severity. Sixty-two out of 234 sextants were abnormal by clinical criteria and 61 out of 234 sextants demonstrated at least one radiographic abnormality. There was agreement between clinical and radiographic detection in 41 sextants. The data showed equivalency between BONJ diagnosis and both sclerosis and surface irregularity. The correlation between number of clinical sites and any radiographic finding was significant in the maxilla (P < 0.001) but not in the mandible (P = 0.178). The total number of radiographic signs per patient increased with BONJ stage. Focal panoramic radiographic findings of sclerosis and surface irregularity correlate with clinical sites of BONJ. This may be a useful and reliable tool to detect early changes of BONJ or to confirm a clinical diagnosis. C1 [Treister, N.; Lerman, M.; Woo, S.] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. [Treister, N.; Friedland, B.; Lerman, M.; Woo, S.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Sheehy, N.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Bae, E. H.] Beth Israel Deaconess Med Ctr, Dept Biostat, Boston, MA 02215 USA. RP Treister, N (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 75 Francis St, Boston, MA 02115 USA. EM ntreister@partners.org NR 25 TC 31 Z9 32 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1354-523X J9 ORAL DIS JI Oral Dis. PD JAN PY 2009 VL 15 IS 1 BP 88 EP 92 DI 10.1111/j.1601-0825.2008.01494.x PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 382OY UT WOS:000261616500013 PM 18992020 ER PT J AU Mawardi, H Cutler, C Treister, N AF Mawardi, Hani Cutler, Corey Treister, Nathaniel TI Medical management update: Non-Hodgkin lymphoma SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY LA English DT Review ID B-CELL LYMPHOMA; BONE-MARROW-TRANSPLANTATION; HEALTH-ORGANIZATION CLASSIFICATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDER; ANTI-CD20 MONOCLONAL-ANTIBODY; SEVERE ODONTOGENIC INFECTIONS; PREVIOUSLY UNTREATED PATIENTS; POSITRON-EMISSION-TOMOGRAPHY; FINE-NEEDLE-ASPIRATION AB Lymphoma is a heterogeneous malignancy of the lymphatic system characterized by proliferation of lymphoid cells or their precursors. Non-Hodgkin lymphoma (NHL) is associated with significant morbidity and is the seventh leading cause of death in the United States. Manifestations of NHL as well as complications of the disease and its management are frequently encountered in the head and neck region and often require specific treatment and modifications in the provision of oral health care. The purpose of this article is to review current concepts of the pathophysiology, as well as medical and oral health care management of NHL. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 107;e19-e33) C1 [Cutler, Corey] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Cutler, Corey] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA USA. [Treister, Nathaniel] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. [Treister, Nathaniel] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Cambridge, MA 02138 USA. RP Mawardi, H (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 75 Francis St, Boston, MA 02115 USA. EM hmawardi@partners.org NR 157 TC 12 Z9 12 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JAN PY 2009 VL 107 IS 1 BP E19 EP E33 DI 10.1016/j.tripleo.2008.08.054 PG 15 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 387JU UT WOS:000261949300028 PM 19101479 ER PT J AU McCarthy, JR Bhaumik, J Merbouh, N Weissleder, R AF McCarthy, Jason R. Bhaumik, Jayeeta Merbouh, Nabyl Weissleder, Ralph TI High-yielding syntheses of hydrophilic conjugatable chlorins and bacteriochlorins SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID PHOTODYNAMIC THERAPY; GLUCURONIC-ACID; NANOPARTICLES; CANCER; PHOTOIMMUNOTHERAPY; PHOTOSENSITIZER; EFFICACY; PDT AB Next-generation photodynamic therapy agents based upon the conjugation of multiple photosensitizers to a targeting backbone will allow for more efficacious light-based therapies. To this end, we have developed glucose-modified chlorins and bacteriochlorins featuring a reactive carboxylic acid linker for conjugation to targeting moieties. The photosensitizers were synthesized in relatively high yields from meso-tetra(p-aminophenyl) porphyrin, and resulted in neutral, hydrophilic chromophores with superb absorption profiles in the far-red and near-infrared portions of the electromagnetic spectrum. In addition, conjugation of these photosensitizers to a model nanoscaffold (crosslinked dextran-coated nanoparticles) demonstrated that the inclusion of hydrophilic sugar moieties increased the number of dyes that can be loaded while maintaining suspension stability. The described compounds are expected to be particularly useful in the synthesis of a number of targeted nanotherapeutic systems. C1 [McCarthy, Jason R.; Bhaumik, Jayeeta; Weissleder, Ralph] Harvard Univ, Ctr Mol Imaging Res, Sch Med, Charlestown, MA 02129 USA. [McCarthy, Jason R.; Bhaumik, Jayeeta; Weissleder, Ralph] Harvard Univ, Ctr Syst Biol, Sch Med, Charlestown, MA 02129 USA. [McCarthy, Jason R.; Bhaumik, Jayeeta; Weissleder, Ralph] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Merbouh, Nabyl] Simon Fraser Univ, Dept Chem, Burnaby, BC V5A 1S6, Canada. RP McCarthy, JR (reprint author), Harvard Univ, Ctr Mol Imaging Res, Sch Med, 149 13th St,Rm 5406, Charlestown, MA 02129 USA. EM jason_mccarthy@hms.harvard.edu FU NIH [U24-CA092782, U01-HL080731, U54-CA119349, U54-CA126515] FX This work was supported by an NIH grant U24-CA092782 (RW), U01-HL080731 (JM, RW), NIH grants U54-CA119349 (RW), U54-CA126515 (RW). Special thanks to Dr Martha Morton for expertise and assistance with acquisition of NMR spectra. NR 29 TC 27 Z9 27 U1 0 U2 5 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2009 VL 7 IS 17 BP 3430 EP 3436 DI 10.1039/b908713c PG 7 WC Chemistry, Organic SC Chemistry GA 483OA UT WOS:000268975300012 PM 19675897 ER PT B AU Bono, CM Bhattacharyya, T AF Bono, Christopher M. Bhattacharyya, Timothy BE Duque, G Kiel, DP TI Fracture Care in the Elderly SO OSTEOPOROSIS IN OLDER PERSONS: PATHOPHYSIOLOGY AND THERAPEUTIC APPROACH LA English DT Article; Book Chapter ID BONE MORPHOGENETIC PROTEIN-2; TOTAL HIP-ARTHROPLASTY; VERTEBRAL COMPRESSION FRACTURES; LUMBAR INTERBODY FUSION; ILIAC CREST AUTOGRAFT; OP-1 PUTTY RHBMP-7; PERCUTANEOUS VERTEBROPLASTY; ODONTOID FRACTURES; INTERNAL-FIXATION; OLDER PATIENTS C1 [Bono, Christopher M.; Bhattacharyya, Timothy] Harvard Univ, Sch Med, Orthopaed Trauma Serv, Dept Orthopaed Surg,Brigham & Womens Hosp, Boston, MA 02115 USA. [Bono, Christopher M.] Brigham & Womens Hosp, Dept Orthopaed Surg, Spine Serv, Boston, MA 02115 USA. [Bhattacharyya, Timothy] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bono, CM (reprint author), Harvard Univ, Sch Med, Orthopaed Trauma Serv, Dept Orthopaed Surg,Brigham & Womens Hosp, Boston, MA 02115 USA. NR 66 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-84882-924-4 PY 2009 BP 163 EP 180 DI 10.1007/978-1-84628-697-1_13 PG 18 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA BQT60 UT WOS:000281801800013 ER PT J AU Richer, SL Wenig, BL AF Richer, Sara L. Wenig, Barry L. TI The efficacy of preoperative screening and the treatment of methicillin-resistant Staphylococcus aureus in an otolaryngology surgical practice SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID INTRANASAL MUPIROCIN; NASAL COLONIZATION; UNITED-STATES; INFECTIONS; RHINOSINUSITIS; SURVEILLANCE; PROPHYLAXIS; SURGERY; COST; RISK AB OBJECTIVE: To examine file efficacy of preoperative Staphylococcus aureus screening oil postoperative methicillin-resistant S aureus (MRSA) infection rates in otolaryngology. STUDY DESIGN: Chart review. SUBJECTS AND METHODS: Postoperative MRSA infection rates in Unscreened patients during a I-year period were compared with infection rates in patients after preoperative S aureus screening was initiated. Colonized patients were treated with mupirocin and chlorhexidine preoperatively. RESULTS: Records of 420 patients were reviewed. In the 241 patients Without screening, nine patients had S aureus infections, and there were two (0.8%) postoperative MRSA surgical-site infections. Of 179 patients after screening was initiated, 24 patients (13.4%) were colonized with S aureus and underwent preoperative treatment. There were no MRSA infections in the postoperative period. CONCLUSION: Early results show the potential benefit of preoperative S aureus screening in MRSA infection rate reduction. Although larger studies are needed, screening and treatment of MRSA colonized patients preoperatively may reduce infectious complications in otolaryngology. (C) 2009 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved. C1 [Richer, Sara L.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Wenig, Barry L.] Evanston NW Healthcare, Evanston, IL USA. RP Richer, SL (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM sara.richer@gmail.com NR 21 TC 9 Z9 9 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JAN PY 2009 VL 140 IS 1 BP 29 EP 32 DI 10.1016/j.otohns.2008.10.021 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 394PD UT WOS:000262458100007 PM 19130957 ER PT S AU Farley, J Birrer, MJ AF Farley, John Birrer, Michael J. BE Stack, MS Fishman, DA TI Novel Therapeutic Targets SO OVARIAN CANCER, SECOND EDITION SE Cancer Treatment and Research LA English DT Article; Book Chapter ID EPITHELIAL OVARIAN-CANCER; PHASE-II TRIAL; GYNECOLOGIC-ONCOLOGY-GROUP; GROWTH-FACTOR RECEPTORS; MATRIX-METALLOPROTEINASE INHIBITORS; PACLITAXEL-MEDIATED CYTOTOXICITY; METASTATIC COLORECTAL-CANCER; PRIMARY PERITONEAL CARCINOMA; DEPENDENT KINASE INHIBITOR; MONOCLONAL-ANTIBODY C225 C1 [Birrer, Michael J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Birrer, Michael J.] Harvard Canc Ctr, Gynecol Canc Res Program, Boston, MA 02114 USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Farley, John] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. [Farley, John] NCI, Christina Annunziata Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. RP Birrer, MJ (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM mbirrer@partners.org NR 119 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0927-3042 BN 978-0-387-98093-5 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2009 VL 149 BP 63 EP 84 DI 10.1007/978-0-387-98094-2_3 PG 22 WC Oncology SC Oncology GA BMT32 UT WOS:000273526200003 PM 19763431 ER PT J AU Wang, SX Lim, GW Mao, J Sung, B Mao, JR AF Wang, Shuxing Lim, Grewo Mao, Ji Sung, Backil Mao, Jianren TI Regulation of the trigeminal NR1 subunit expression induced by inflammation of the temporomandibular joint region in rats SO PAIN LA English DT Article DE NF-kappaB Inhibitor; NF-kappa B; Neuropathic pain; IL-6; NMDA receptor; NR1; Trigeminal; Temporomandibular joint inflammation; TMJ ID MEDULLARY DORSAL-HORN; PERIPHERAL-NERVE INJURY; CENTRAL GLUCOCORTICOID-RECEPTORS; BRAIN-STEM MECHANISMS; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; NEUROPATHIC PAIN; INTRACEREBROVENTRICULAR INJECTION; SUBNUCLEUS CAUDALIS; CENTRAL SENSITIZATION AB Expression of the N-methyl-D-aspartate (NMDA) receptor in trigeminal nuclei has been shown to play a role in the mechanisms of trigeminal pain. Here, we examined the hypothesis that the upregulation of the NR1 subunit of the NMDA receptor (NR1) in the trigeminal subnucleus caudalis (Sp5c) following inflammation of the temporomandibular joint (TMJ) region would be regulated by interleukin-6 (IL-6) and the nuclear factor-kappa B (NF-kappa B). inflammation of a unilateral TMJ region was produced in rats by injecting 50 pi of complete Freund's adjuvant (CFA) into a TMJ and adjacent tissues, which resulted in persistent pain behavior as assessed using algometer before (baseline) and on days 1, 3, and 7 after the CFA injection. The CFA injection also induced a significant upregulation of NR1 and NF-kappa B on days 3 and 7, and of IL-6 on clays 1, 3, and 7, within the ipsilateral Sp5c, as compared with the sham TMJ injection group, Once daily intracisternal injection of an IL-6 antiserum or NF-kappa B inhibitor (PDTC) for 6 days. beginning on day I immediately after the CFA injection, prevented both the upregulation of NR1 in the ipsilateral Sp5C and pain behavior. Moreover, once daily intracisternal IL-6 administration for 6 days in naive rats induced the NR1 upregulation and pain behavior similar to that after TMJ inflammation. These results indicate that the upregulation of IL-6 and NF-kappa B after inflammation of the unilateral TMJ region is a critical regulatory mechanism for the expression of NR1 in the ipsilateral Sp5c, which contributed to the development of TMJ pain behavior in rats. 0 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Wang, Shuxing; Lim, Grewo; Mao, Ji; Sung, Backil; Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,MGH Ctr Translat Pain, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,MGH Ctr Translat Pain, WACC 324, Boston, MA 02114 USA. EM jmao@partners.org FU NIH [DE1 8214, DE1 8538, NS45681] FX This study is supported by NIH RO1 Grants DE1 8214, DE1 8538, and NS45681. The authors claim no conflict of interest. NR 54 TC 14 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JAN PY 2009 VL 141 IS 1-2 BP 97 EP 103 DI 10.1016/j.pain.2008.10.021 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 402LE UT WOS:000263014400017 PM 19058915 ER PT J AU Manchikanti, L Singh, V Pampati, V Smith, HS Hirsch, J AF Manchikanti, Laxmaiah Singh, Vijay Pampati, Vidyasagar Smith, Howard S. Hirsch, Joshua TI Analysis of Growth of Interventional Techniques in Managing Chronic Pain in the Medicare Population: A 10-Year Evaluation from 1997 to 2006 SO PAIN PHYSICIAN LA English DT Review DE Interventional techniques; interventional pain management; facet joint injections; epidural steroid injections; sacroiliac joint injections; chronic pain; chronic spinal pain; ambulatory surgery center (ASC); hospital outpatient department (HOPD) ID LOW-BACK-PAIN; FACET JOINT PAIN; CAUDAL EPIDURAL INJECTIONS; MEDICINE PRACTICE GUIDELINES; POSITIVE PREDICTIVE-VALUE; CHRONIC WIDESPREAD PAIN; LUMBAR-DISK HERNIATION; BLIND CONTROLLED-TRIAL; MENTAL-HEALTH SURVEYS; MEDIAL BRANCH BLOCKS AB Background: Recent reports of the United States Government Accountability Office (GAO), the Medicare Payment Advisory Commission (MedPAC), and the Office of Inspector General (OIG) expressed significant concern with overall fiscal sustainability of Medicare and exponential increase in costs for interventional pain management techniques. Interventional pain management (IPM) is an evolving specialty amenable to multiple influences. Evaluation and isolation of appropriate factors for increasing growth patterns have not been performed. Study Design: Analysis of the growth of interventional techniques in managing chronic pain in Medicare beneficiaries from 1997 to 2006. Objective: To evaluate the use of all interventional techniques. Methods: The standard 5% national sample of the CMS carrier claim record data for 1997, 2002, and 2006 was utilized. This data set provides information on Medicare enrollees in the fee-for-service Medicare program. Current procedural technology (CPT) codes for 1997, 2002, and 2006 were used to identify the number of procedures performed each year, and trends in expenditures. Results: Interventional techniques increased significantly in Medicare beneficiaries from 1997 to 2006. Overall, there was an increase of 137% in patients utilizing IPM services with an increase of 197% in IPM services, per 100,000 Medicare beneficiaries. The majority of the increases were attributed to exponential growth in the performance of facet joint interventions. There was a 13.9-fold difference in the increase between the state with the lowest rate and the state with the highest rate in utilization patterns of interventional techniques (California 37% vs. Connecticut 514%), with an 11.6-fold difference between Florida and California (431% vs. 37% increase). In 2006, Florida showed a 12.7-fold difference compared to Hawaii with the lowest utilization rate. Hospital outpatient department (HOPD) expenses constituted the highest increase with fewer patients treated either in an ambulatory surgery center (ASC) or in-off ice setting. Overall HOPD payments constituted 5% of total 2006 Medicare payments, in contrast to 57% of total IPM payments, an 11.4-fold difference. Limitations: The limitations of this study include a lack of inclusion of Medicare participants in Medicare Advantage plans and potential documentation, coding, and billing errors. Conclusion: This study shows an overall increase of IPM services of 197% compared to an increase of 137% in patients utilizing IPM services from 1997 to 2006. C1 [Manchikanti, Laxmaiah; Pampati, Vidyasagar] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA. [Smith, Howard S.] Albany Med Coll, Dept Anesthesiol, Albany, NY 12208 USA. [Hirsch, Joshua] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Joshua] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Hirsch, Joshua] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 164 TC 124 Z9 128 U1 0 U2 4 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD JAN-FEB PY 2009 VL 12 IS 1 BP 9 EP 33 PG 25 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 406SC UT WOS:000263314200001 PM 19165296 ER PT J AU Manchikanti, L Benyamin, R Helm, S Hirsch, JA AF Manchikanti, Laxmaiah Benyamin, Ramsin Helm, Standiford, II Hirsch, Joshua A. TI Evidence-Based Medicine, Systematic Reviews, and Guidelines in Interventional Pain Management: Part 3: Systematic Reviews and Meta-Analyses of Randomized Trials SO PAIN PHYSICIAN LA English DT Review DE Randomized trials; pragmatic trials; evidence-based medicine; systematic reviews; meta-analyses; guidelines; bias; interventional pain management; Quality of Reporting of Meta-analysis (QUOROM); Cochrane reviews ID LOW-BACK-PAIN; CAUDAL EPIDURAL INJECTIONS; CLINICAL-PRACTICE GUIDELINES; HEALTH-CARE INTERVENTIONS; BLIND CONTROLLED-TRIAL; MEDIAL BRANCH BLOCKS; PAPER-BASED JOURNALS; 2000-2010 TASK-FORCE; FACET JOINT PAIN; COCHRANE-COLLABORATION AB In recent years, progress and innovations in healthcare are measured by evidence-based medicine (EBM), systematic reviews, and meta-analyses. A systematic review is defined as, "the application of scientific strategies that limit bias by the systematic assembly, critical appraisal, and synthesis of all relevant studies on a specific topic." In contrast, meta-analysis is the statistical pooling of data across studies to generate pooled estimates of effects. Meta-analysis usually is the final step in a systematic review. Systematic reviews and meta-analyses are labor intensive, requiring expertise in both the subject matter and review methodology, and also must follow the rules of EBM which suggest that a formal set of rules must complement medical training and common sense for clinicians to interpret the results of clinical research effectively. While expertise in the subject matter is crucial, expertise in review methods is also particularly important. Despite an explosion of systematic reviews and meta-analyses, the empiric research on the quality of systematic reviews has shown that not all systematic reviews are truly systematic, having highly variable quality, deficiencies in methodologic assessment of the quality of the included manuscripts, and bias. Even then, systematic review of the literature is currently the best, least biased, and most rational way to organize, cull, evaluate, and integrate the research evidence from among the expanding medical and healthcare literature. However, a dangerous discrepancy between the experts and the evidence continues to persist in part because multiple instruments are available to assess the quality of systematic reviews or meta-analyses. Steps in conducting systematic reviews include planning, conducting, reporting, and disseminating the results. The Quality of Reporting of Meta-analysis (QUOROM) statement provides a checklist and a flow diagram. The checklist describes the preferred way to present the abstract, introduction, methods, results, and discussion sections of the report of an analysis. This review describes various aspects of systematic reviews and meta-analyses of randomized trials with a special focus on interventional pain management. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Benyamin, Ramsin] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin] Univ Illinois, Coll Med, Dept Surg, Urbana, IL 61801 USA. [Helm, Standiford, II] Pacific Coast Pain Management Ctr, Laguna Hills, CA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 301 TC 175 Z9 181 U1 1 U2 18 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD JAN-FEB PY 2009 VL 12 IS 1 BP 35 EP 72 PG 38 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 406SC UT WOS:000263314200002 PM 19165297 ER PT J AU Manchikanti, L Singh, V Smith, HS Hirsch, JA AF Manchikanti, Laxmaiah Singh, Vijay Smith, Howard S. Hirsch, Joshua A. TI Evidence-Based Medicine, Systematic Reviews, and Guidelines in Interventional Pain Management: Part 4: Observational Studies SO PAIN PHYSICIAN LA English DT Review DE Observational studies; cohort studies; case control studies; cross-sectional studies; allocation bias; sample size; Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE) ID RANDOMIZED CONTROLLED-TRIALS; LOW-BACK-PAIN; CAUDAL EPIDURAL INJECTIONS; CLINICAL-PRACTICE GUIDELINES; PERCUTANEOUS RADIOFREQUENCY NEUROTOMY; INTRACRANIAL ARTERIAL BYPASS; SAMPLE-SIZE ESTIMATION; BLIND CONTROLLED-TRIAL; LUMBAR RADICULAR PAIN; MEDIAL BRANCH BLOCKS AB Evidence-based medicine (EBM) stresses the examination of evidence from clinical research and describes it as a shift in medical paradigms, in contrast to intuition, unsystematic clinical experience, and pathophysiologic rationale. While the importance of randomized trials has been created by the concept of the hierarchy of evidence in guiding therapy, much of the medical research is observational. There is competition, contrast, and a feeling of inferiority and uselessness for observational studies, created by a lack of understanding of medical research. However, observational studies and randomized clinical trials (RCTs) can be viewed as the steps of observation and experimentation that form the basis of the scientific methodology. Further, rational healthcare practices require knowledge about the etiology and pathogenesis, diagnosis, prognosis, and treatment of disorders. The reporting of observational research is often not detailed and clear enough with insufficient quality and poor reporting, which hampers the assessment of strengths and weaknesses of the study and the generalizability of the mixed results. Thus, design, implementation, and reporting of observational studies is crucial. The biased interpretation of results from observational studies, either in favor of or opposed to a treatment, and lack of proper understanding of observational studies, leads to a poor appraisal of the quality. Similar to the Consolidated Standards of Reporting Trials (CONSORT) statement for the reporting of randomized trials, the Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE) statement was developed with recommendations to improve the quality of reporting observational studies. The STROBE statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Multiple types of observational studies are conducted; however, 3 types have been highlighted in the STROBE document and also in the present review, which include cohort studies, case-controlled studies, and cross-sectional studies. This comprehensive review provides an introduction and rationale, types, design, and reporting of observational studies; outcomes assessment and data presentation and analysis; statistical analysis, results, and a discussion of observational studies. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA. [Smith, Howard S.] Albany Med Coll, Dept Anesthesiol, Albany, NY 12208 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 359 TC 86 Z9 87 U1 1 U2 5 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD JAN-FEB PY 2009 VL 12 IS 1 BP 73 EP 108 PG 36 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 406SC UT WOS:000263314200003 PM 19165298 ER PT J AU Davila, JA Chiao, EY Hasche, JC Petersen, NJ McGlynn, KA Shaib, YH AF Davila, Jessica A. Chiao, Elizabeth Y. Hasche, Jennifer C. Petersen, Nancy J. McGlynn, Katherine A. Shaib, Yasser H. TI Utilization and Determinants of Adjuvant Therapy Among Older Patients Who Receive Curative Surgery for Pancreatic Cancer SO PANCREAS LA English DT Article DE pancreatic cancer; adjuvant therapy; SEER-Medicare ID LONG-TERM SURVIVAL; DUCTAL ADENOCARCINOMA; ELDERLY-PATIENTS; RESECTION; PANCREATICODUODENECTOMY; CHEMORADIOTHERAPY; CHEMOTHERAPY; CARCINOMA; REGION; TRIAL AB Objective: We conducted a population-based study to describe the utilization, determinants, and survival effects of adjuvant therapies after surgery among older patients with pancreatic cancer. Methods: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified patients older than 65 years who received surgical resection for pancreatic cancer during 1992-2002. We constructed multiple logistic regression models to examine patient, clinical, and hospital factors associated with receiving adjuvant therapy. Cox proportional hazards models were used to examine the effect of therapy on survival. Results: Approximately 49% of patients received adjuvant therapy after surgery. Patient factors associated with increased receipt of adjuvant therapy included more recent diagnosis, younger age, stage II disease, higher income, and geographic location. Hospital factors associated with increased receipt of adjuvant therapy included cooperative group membership and larger size. Adjuvant treatments associated with a significant reduction in 2-year mortality (relative to surgery alone) were chemoradiation or radiation alone but not chemotherapy alone. Conclusions: Our findings suggest that adjuvant chemoradiation and, to a lesser degree, radiation only are associated with a reduction in the risk of mortality among older patients who undergo surgery for pancreatic cancer. However, receipt of adjuvant therapy varied by period and geography as well as by certain patient and hospital factors. C1 [Davila, Jessica A.; Chiao, Elizabeth Y.; Hasche, Jennifer C.; Petersen, Nancy J.; Shaib, Yasser H.] Baylor Coll Med, Sect Hlth Serv Res, Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. [Chiao, Elizabeth Y.] Baylor Coll Med, Infect Dis Sect, Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. [McGlynn, Katherine A.] NCI DHHS, Div Canc Epidemiol & Genet, Bethesda, MD USA. [Shaib, Yasser H.] Baylor Coll Med, Gastroenterol Sect, Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Davila, JA (reprint author), Baylor Coll Med, Sect Hlth Serv Res, Houston Vet Affairs Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM jdavila@bcm.tmc.edu FU Dan L. Duncan Cancer Center, Baylor College of Medicine FX This study was supported by pilot funding from the Dan L. Duncan Cancer Center, Baylor College of Medicine. NR 18 TC 19 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD JAN PY 2009 VL 38 IS 1 BP E18 EP E25 DI 10.1097/MPA.0b013e318187eb3f PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 392QP UT WOS:000262317600025 PM 18797424 ER PT J AU Sahani, D Catalano, OA AF Sahani, Dushyant Catalano, Onofrio A. BE Heiken, J TI Imaging evaluation of cystic pancreatic neoplasms SO PANCREATIC CANCER SE Contemporary Issues in Cancer Imaging LA English DT Article; Book Chapter ID PAPILLARY-MUCINOUS TUMORS; CLINICOPATHOLOGICAL FEATURES; SYMPTOMATIC PATIENTS; MANAGEMENT; DIAGNOSIS; SPECTRUM C1 [Sahani, Dushyant; Catalano, Onofrio A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Sahani, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 33 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-88692-5 J9 CONT ISS CANC IMAG PY 2009 BP 83 EP 103 PG 21 WC Oncology; Endocrinology & Metabolism; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Endocrinology & Metabolism; Radiology, Nuclear Medicine & Medical Imaging GA BDK54 UT WOS:000313590200008 ER PT J AU LaFemina, J Roberts, PA Hung, YP Gusella, JF Sahani, D Fernandez-del Castillo, C Warshaw, AL Thayer, SP AF LaFemina, Jennifer Roberts, Penelope A. Hung, Yin P. Gusella, James F. Sahani, Dushyant Fernandez-del Castillo, Carlos Warshaw, Andrew L. Thayer, Sarah P. TI Identification of a Novel Kindred with Familial Pancreatitis and Pancreatic Cancer SO PANCREATOLOGY LA English DT Article DE Pancreatitis, hereditary; Pancreatic cancer, hereditary; Familial pancreatitis/pancreatic cancer ID CATIONIC TRYPSINOGEN GENE; SERINE-PROTEASE INHIBITOR; HEREDITARY PANCREATITIS; CYSTIC-FIBROSIS; KAZAL TYPE-1; RISK-FACTORS; MUTATIONS; CARCINOMA; SMOKING AB Background/Aims: Hereditary pancreatic cancer comprises about 10% of pancreatic cancer cases. Multiple causative mutations have been identified. Here we describe a pancreatitis/pancreatic cancer (P/PC) family, which demonstrates pancreatitis and pancreatic cancer resulting from an uncharacterized mutation. Methods: Family members completed evaluations to determine signs of mutation status. Select patients were screened for mutations associated with hereditary pancreatic diseases. Results: In generation II, 12 siblings exhibit 6 cases of pancreatitis, 3 pancreatic cancer, and 2 obligate carrier status. The average age at pancreatitis diagnosis of enrolled members is 32.5 years; average age at pancreatic cancer diagnosis is 59 years. There is no association with known cancer syndromes. Those affected generally present with mild epigastric pain, and CT scans demonstrate characteristic fatty infiltration of the pancreatic body and tail with sparing of the head and neck. Full sequence analysis of genes associated with hereditary pancreatic disease failed to demonstrate known mutations or polymorphisms. Conclusion: Based upon pedigree evaluation and preliminary DNA analysis, we believe that the family members with P/PC carry a novel genetic mutation resulting in hereditary pancreatitis. This mutation is autosomal dominant, expressed with high penetrance, and is part of a unique hereditary syndrome that significantly increases pancreatic cancer risk. Copyright (C) 2009 S. Karger AG, Basel and IAP C1 [LaFemina, Jennifer; Hung, Yin P.; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Thayer, Sarah P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Roberts, Penelope A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Gusella, James F.] Harvard Univ, Sch Med, Harvard Partners Ctr Genet & Genom, Boston, MA USA. [Sahani, Dushyant] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thayer, SP (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,WAC 4-460, Boston, MA 02114 USA. EM sthayer@partners.org FU NCI NIH HHS [P01 CA117969, P50 CA127003, P50 CA127003-01, P01 CA117969-03, P50 CA127003-02, P01 CA117969-02]; NIDDK NIH HHS [K08 DK071329] NR 31 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 J9 PANCREATOLOGY JI Pancreatology PY 2009 VL 9 IS 3 BP 273 EP 279 DI 10.1159/000201553 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 487WU UT WOS:000269309500014 PM 19407482 ER PT J AU Olson, JM Hogan, MT Pogach, LM Rajan, M Raugi, GJ Reiber, GE AF Olson, Jonathan M. Hogan, Molly T. Pogach, Leonard M. Rajan, Mangala Raugi, Gregory J. Reiber, Gayle E. TI Foot care education and self management behaviors in diverse veterans with diabetes SO PATIENT PREFERENCE AND ADHERENCE LA English DT Article DE diabetes mellitus; diabetic foot; patient self-management; ethnic groups; education AB The objective of this study was to examine differences in self-reported diabetes foot care education, self management behaviors, and barriers to good foot care among veterans with diabetes by race and ethnicity. Data was collected using the Veterans Health Administration Footcare Survey, a validated tool that assessed demographic, general health, diabetes and foot self-care information, barriers to foot self-care, receipt of professional foot care, and satisfaction with current care. We mailed surveys to a random sample of patients with diabetes from eight VA medical centers. Study participants were 81% White; 13% African American; 4% Asian, and 2% American Indian and Pacific Islanders. The majority of respondents felt that they did not know enough about foot self-care. There were large gaps between self-reported knowledge and actual foot care practices, even among those who reported "knowing enough" on a given topic. There were significant differences in self-reported foot care behaviors and education by race and ethnicity. These findings document the need for culturally-specific self-management education to address unique cultural preferences and barriers to care. C1 [Reiber, Gayle E.] VA Puget Sound Healthcare Syst, Res & Dev, Dept Vet Affairs, Seattle, WA USA. [Hogan, Molly T.] Univ Washington, Sch Med, Dept Internal Med, Seattle, WA USA. [Pogach, Leonard M.; Rajan, Mangala] New Jersey Healthcare Syst, Ctr Healthcare Knowledge Management, Dept Vet Affairs, E Orange, NJ USA. [Raugi, Gregory J.] VA Puget Sound Healthcare Syst, Dept Vet Affairs, Div Dermatol, Seattle, WA USA. RP Reiber, GE (reprint author), VA HSR&D, 1100 Olive Way,Ste 1400, Seattle, WA 98101 USA. EM greiber@u.washington.edu FU VA Health Services Research and Development; Rehabilitation Research and Development FX The authors wish to thank VA Health Services Research and Development and Rehabilitation Research and Development for their support. The authors report no conflicts of interest in this work. NR 23 TC 6 Z9 6 U1 1 U2 3 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-889X J9 PATIENT PREFER ADHER JI Patient Prefer. Adherence PY 2009 VL 3 BP 45 EP 50 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA V21NU UT WOS:000208215100006 PM 19936144 ER PT S AU Hait, EJ Arnold, JH Sands, BE Fishman, L AF Hait, Elizabeth J. Arnold, Janis H. Sands, Bruce E. Fishman, Laurie BE WalkerSmith, JA Lebenthal, E Branski, D TI Transition to Adult Care SO PEDIATRIC AND INFLAMMATORY BOWEL DISEASE: PERSPECTIVE AND CONSEQUENCES SE Pediatric and Adolescent Medicine LA English DT Article; Book Chapter ID HEALTH-CARE; YOUNG-ADULTS; RECOMMENDATIONS; ADOLESCENTS AB Young adults with inflammatory bowel disease need to be transitioned to the adult medical system with as much continuity of care as possible. Transition from pediatric to adult medical care continues to present significant barriers. Transitioning inflammatory bowel disease patients involves a careful process involving concrete steps that help patients prepare for new responsibilities. The aim of this review is to propose a clinical and developmental timeline for both patients and their medical team, in order to promote a successful transition. Copyright (C) 2009 S. Karger AG, Basel C1 [Fishman, Laurie] Childrens Hosp, Div Gastroenterol & Nutr, Ctr Inflammatory Bowel Dis, Boston, MA 02115 USA. [Sands, Bruce E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Crohns & Colitis Ctr,Gastrointestinal Unit, Boston, MA USA. RP Fishman, L (reprint author), Childrens Hosp, Div Gastroenterol & Nutr, Ctr Inflammatory Bowel Dis, 300 Longwood Ave, Boston, MA 02115 USA. EM Laurie.Fishman@childrens.harvard.edu NR 13 TC 2 Z9 2 U1 2 U2 3 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1017-5989 BN 978-3-8055-9134-8 J9 PEDIATR ADOLESC MED JI Pediatr. Adolesc. Med. PY 2009 VL 14 BP 191 EP 198 DI 10.1159/000226315 PG 8 WC Gastroenterology & Hepatology; Pediatrics SC Gastroenterology & Hepatology; Pediatrics GA BKY16 UT WOS:000269605300013 ER PT J AU Cote, CJ AF Cote, Charles J. TI The WFSA pediatric anesthesia fellowships: origins and perspectives SO PEDIATRIC ANESTHESIA LA English DT Editorial Material C1 [Cote, Charles J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Cote, Charles J.] Mass Gen Hosp Children, Div Pediat Anesthesia, Boston, MA USA. [Cote, Charles J.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Cote, CJ (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1155-5645 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD JAN PY 2009 VL 19 IS 1 BP 31 EP 32 DI 10.1111/j.1460-9592.2008.02867.x PG 2 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 377RC UT WOS:000261267300007 PM 19076499 ER PT J AU Sobota, A Neufeld, EJ Lapsia, S Bennett, CM AF Sobota, Amy Neufeld, Ellis J. Lapsia, Sameer Bennett, Carolyn M. TI Response to Mercaptopurine for Refractory AutoImmune Cytopenias in Children SO PEDIATRIC BLOOD & CANCER LA English DT Article DE 6MP; AIHA; Evans; ITP; mercaptopurine; pediatric ID IDIOPATHIC-THROMBOCYTOPENIC-PURPURA; MYCOPHENOLATE-MOFETIL; ADULT PATIENTS; AZATHIOPRINE; THERAPY; EFFICACY; SPLENECTOMY; MANAGEMENT; CHILDHOOD; RITUXIMAB AB Background. Several treatment strategies are available for children with severe immune thrombocytopenic purpura (ITP) and other immune cytopenias refractory to initial therapies. 6-Mercapto-purine (6MP) is one option, however it has not been well studied in children, especially as a single agent, and no pediatric case series have been reported since 1970. Patients and Methods. We reviewed the experience at our institution over 8 years, using 6MP as a steroid sparing treatment for children with ITP, auto-immune hemolytic anemia (AIHA) or Evans syndrome. A total of 29 pediatric patients were treated with 6MP from 2000 to 2007. Results. Response was defined as a rise in hemoglobin by at least 1.5g/dl and to a level of 10 g/dl or greater in patients treated for anemia, or a platelet count >= 50 x 10(9)/L in patients treated for thrombocytopenia. We found an overall response rate of 83% among all patients. Fourteen percent of patients stopped drug because of side effects. Conclusions. These results suggest that 6MP call be in effective single-agent treatment for refractory immune cytopenias in children. Prospective studies are warranted to determine long-term efficacy and toxicity and to more clearly define patient populations most likely to respond. Pediatr Blood Cancer 2009;52:80-84. (c) 2008 Wiley-Liss, Inc. C1 [Sobota, Amy; Neufeld, Ellis J.; Lapsia, Sameer; Bennett, Carolyn M.] Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. [Sobota, Amy; Neufeld, Ellis J.; Bennett, Carolyn M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sobota, Amy; Neufeld, Ellis J.; Bennett, Carolyn M.] Harvard Univ, Sch Med, Boston, MA USA. RP Neufeld, EJ (reprint author), Childrens Hosp Boston, Div Hematol Oncol, Room RB 08210,300 Longwood Ave, Boston, MA 02115 USA. EM ellis.neufeld@childrens.harvard.edu RI Neufeld, Ellis/F-9331-2011; OI Sobota, Amy/0000-0003-3979-7435 FU NIH [K24HL04184]; St. Giles Foundation FX Grant sponsor: NIH: Grant number: K24HL04184: Grant sponsor: St. Giles Foundation. NR 20 TC 10 Z9 12 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JAN PY 2009 VL 52 IS 1 BP 80 EP 84 DI 10.1002/pbc.21729 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 378CZ UT WOS:000261300000019 PM 18726904 ER PT J AU Cioffredi, LA Janne, PA Jackman, DM AF Cioffredi, Leigh-Anne Jaenne, Pasi A. Jackman, David M. TI Treatment of Peritoneal Mesothelioma in Pediatric Patients SO PEDIATRIC BLOOD & CANCER LA English DT Article DE chemotherapy; pediatric oncology; solid tumors ID MALIGNANT PLEURAL MESOTHELIOMA; UNITED-STATES; CHEMOTHERAPY; EPIDEMIOLOGY; CISPLATIN; ASBESTOS AB Peritoneal mesothelioma is a rare and often aggressive malignancy, mostly affecting asbestos exposed adults. We present four pediatric peritoneal cases treated with a cisplatin-based doublet regimen, the standard of care in the systemic therapy Of adult mesothelioma. Treatment was well tolerated, and three of these patients have achieved long-term survival. The fathers of three of the patients worked in the Construction industry and may have been the Source of indirect asbestos exposure. Pediatr Blood Cancer 2009;52:127-129. (C) 2008 Wiley-Liss, Inc. C1 [Cioffredi, Leigh-Anne; Jaenne, Pasi A.; Jackman, David M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jaenne, Pasi A.; Jackman, David M.] Harvard Univ, Sch Med, Boston, MA USA. RP Jackman, DM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM david_jackman@dfci.harvard.com NR 11 TC 7 Z9 7 U1 2 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JAN PY 2009 VL 52 IS 1 BP 127 EP 129 DI 10.1002/pbc.21718 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 378CZ UT WOS:000261300000029 PM 18819151 ER PT J AU Ramirez-Schrempp, D Dorfman, DH Baker, WE Liteplo, AS AF Ramirez-Schrempp, Daniela Dorfman, David H. Baker, William E. Liteplo, Andrew S. TI Ultrasound Soft Tissue Applications in the Pediatric Emergency Department To drain or not to drain? SO PEDIATRIC EMERGENCY CARE LA English DT Article DE bedside ultrasound; soft tissue infection ID RESISTANT STAPHYLOCOCCUS-AUREUS; FOREIGN-BODIES; MUSCULOSKELETAL INFECTIONS; PERITONSILLAR ABSCESS; NECROTIZING FASCIITIS; BLADDER ULTRASOUND; CHILDREN; DIAGNOSIS; COMMUNITY; SKIN AB Soft tissue infections frequently prompt visits to the pediatric emergency department. The incidence of these infections has increased markedly in recent years. The emergence of community-acquired methicillin-resistant Staphylococcus aureus is associated with an increasing morbidity, mortality, and frequency of abscess formation. Bedside ultrasound may have a significant impact in the management of patients that present to the pediatric emergency department with soft tissue infections, including cellulitis, cutaneous abscess, peritonsillar abscess, and necrotizing fasciitis. Ultrasound is in efficient, noninvasive diagnostic tool which can augment the physicians clinical examination. Ultrasound has been shown to be superior to clinical judgment alone in determining the presence or the absence of occult abscess formation, ensuring appropriate management and limiting unnecessary invasive procedures. C1 [Ramirez-Schrempp, Daniela; Dorfman, David H.] Boston Univ, Sch Med, Boston Med Ctr, Div Pediat Emergency Med,Dept Pediat, Boston, MA 02118 USA. [Baker, William E.] Boston Univ, Sch Med, Boston Med Ctr, Dept Emergency Med, Boston, MA 02118 USA. [Liteplo, Andrew S.] Massachusetts Gen Hosp, Div Emergency Ultrasound, Boston, MA 02114 USA. RP Ramirez-Schrempp, D (reprint author), Boston Univ, Sch Med, Boston Med Ctr, Div Pediat Emergency Med,Dept Pediat, 91 E Concord St,6th Floor, Boston, MA 02118 USA. EM daniela.ramirez-schrempp@bmc.org OI Baker, William/0000-0002-4915-2553 NR 49 TC 19 Z9 19 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-5161 J9 PEDIATR EMERG CARE JI Pediatr. Emerg. Care PD JAN PY 2009 VL 25 IS 1 BP 44 EP 48 PG 5 WC Emergency Medicine; Pediatrics SC Emergency Medicine; Pediatrics GA 395YJ UT WOS:000262559100013 PM 19148015 ER PT J AU Quintero-Rivera, F Abreu-e-Lima, P Zhang, IH Parast, MM AF Quintero-Rivera, Fabiola Abreu-e-Lima, Paula Zhang, Inga Hofmann Parast, Mana M. TI HOMOZYGOUS -THALASSEMIA WITH TRISOMY 7 MOSAICISM IN A LIVE-BORN INFANT SO PEDIATRIC HEMATOLOGY AND ONCOLOGY LA English DT Article DE cytogenetics; mosaicism; -thalassemia; trisomy 7 ID ALPHA-THALASSEMIA; DEFECTS AB The authors report a male infant born at 35 weeks gestational age with an atypical presentation of homozygous -thalassemia. The live-born infant displayed abnormalities of the upper limbs and genitalia, which are vascular-type disruptive defects associated with this disease. Cardiomegaly and placentomegaly were the only evidence of fetal hydrops. Postnatal karyotype revealed mosaicism for trisomy 7, yet another rare finding in a live-born. The authors discuss their institutional experience with each of these rare conditions and the potential contribution of each to the overall unusual clinical presentation in this patient. This is the first report of these simultaneous diagnoses. C1 [Quintero-Rivera, Fabiola] Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Quintero-Rivera, Fabiola] Brigham & Womens Hosp, Dept Pathol, Cytogenet Div, Boston, MA 02115 USA. [Abreu-e-Lima, Paula; Parast, Mana M.] Div Womens & Perinatal Pathol, Dept Pathol, Boston, MA USA. [Zhang, Inga Hofmann] Dana Farber Canc Inst, Dept Pediat, Div Pediat Hematol Oncol, Boston, MA 02115 USA. RP Quintero-Rivera, F (reprint author), Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geffen Sch Med, 1000 Veteran Ave,Room 22-26, Los Angeles, CA 90024 USA. EM fquintero@mednet.ucla.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0888-0018 J9 PEDIATR HEMAT ONCOL JI Pediatr. Hematol. Oncol. PY 2009 VL 26 IS 6 BP 426 EP 431 AR PII 913560538 DI 10.1080/08880010903044847 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 480CD UT WOS:000268708600005 PM 19657992 ER PT J AU Shaikh, N Hoberman, A Paradise, JL Wald, ER Switze, GE Kurs-Lasky, M Colborn, DK Kearney, DH Zoffel, LM AF Shaikh, Nader Hoberman, Alejandro Paradise, Jack L. Wald, Ellen R. Switze, Galen E. Kurs-Lasky, Marcia Colborn, D. Kathleen Kearney, Diana H. Zoffel, Lisa M. TI Development and Preliminary Evaluation of a Parent-Reported Outcome Instrument for Clinical Trials in Acute Otitis Media SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE actue otitis media; validation study; patient-reported outcome measure; pediatrics ID QUALITY-OF-LIFE; AMOXICILLIN; CHILDREN AB Background: Acute otitis media (AOM) is the most common childhood diagnosis, leading to prescription of all antibiotic in the United States. Although antibiotics are used in children with AOM, in part, to Shorten the duration of symptoms, no instruments have been developed to track early changes in Symptoms from the parent's point The goal of the present study was to develop and evaluate a parent-reported symptom scale for children with AOM (AOM-SOS) for use as an outcome measure in AOM treatment trials. Methods: From a pool of 28 potential symptoms, we selected 7 on the basis of parent questionnaire, expert interviews, and review of the literature (or inclusion in the AOM-SOS. We administered the AOM-SOS to a primary-care sample of children aged 6-25 months enrolled in a study of nasopharyngeal bacterial colonization. Children were seen for well visits, illness visits, and AOM follow-up visits. At each visit, parents completed the AOM-SOS and their children were examined by trained otoseopists, As part of the evaluation of the AOM-SOS, we examined the association between each item on the questionnaire and the clinical diagnosis of AOM while adjusting for the presence of upper respiratory tract infection. To assess responsiveness, we examined the change in AOM-SOS scores in patients with AOM who were seen for follow-up within 3 weeks of diagnosis. Results: We evaluated 264 children (mean age, 12.5 months at entry) at a total of 642 visits. We diagnosed AOM at 24% of the visits. Each item on the questionnaire was significantly associated with the clinical diagnosis of AOM (P < 0.001 for each), before and after adjusting for the presence or absence of upper respiratory infection. The mean AOM-SOS score at visits when AOM was diagnosed was 3.71, compared with 0.96 at visits when AOM was not diagnosed (P < 0.001). Internal reliability of the scale its measured by Cronbach's alpha was 0.84. AOM-SOS scores in children with AOM who were otoscopically improved decreased by all average of 2.81 points (standardized response mean = 0.73). Conclusions: We have developed a short symptom scale for children with AOM. This study provides preliminary data on the performance of the AOM-SOS in a primary care sample of children. C1 [Shaikh, Nader; Hoberman, Alejandro; Paradise, Jack L.; Colborn, D. Kathleen; Kearney, Diana H.; Zoffel, Lisa M.] Univ Pittsburgh, Sch Med, Childrens Hosp Pittsburgh, Div Gen Acad Pediat, Pittsburgh, PA 15213 USA. [Wald, Ellen R.] Univ Wisconsin, Sch Med, Dept Pediat, Pittsburgh, PA USA. [Kurs-Lasky, Marcia] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15213 USA. [Switze, Galen E.] Univ Pittsburgh, Dept Internal Med, Pittsburgh, PA 15213 USA. [Switze, Galen E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Switze, Galen E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Shaikh, N (reprint author), Univ Pittsburgh, Sch Med, Childrens Hosp Pittsburgh, Div Gen Acad Pediat, 3705 5th Ave, Pittsburgh, PA 15213 USA. EM nader.shaikh@chp.edu NR 14 TC 23 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JAN PY 2009 VL 28 IS 1 BP 5 EP 8 DI 10.1097/INF.0b013e318185a387 PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 391QG UT WOS:000262247200002 PM 19077917 ER PT S AU Feldman, MJ AF Feldman, Mitchell J. BE Lehmann, CU Kim, GR Johnson, KB TI Diagnostic Decision Support SO PEDIATRIC INFORMATICS: COMPUTER APPLICATIONS IN CHILD HEALTH SE Health Informatics Series LA English DT Article; Book Chapter ID COMPUTER-PROGRAM GIDEON; MEDICAL INFORMATICS; INFECTIOUS-DISEASES; INTERNAL-MEDICINE; SYSTEMS; CARE; CONSULTATION; PERFORMANCE; PEDIATRICS; QUALITY C1 [Feldman, Mitchell J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Feldman, Mitchell J.] Massachusetts Gen Hosp, Dept Med & Pediat, Boston, MA 02114 USA. RP Feldman, MJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 46 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1431-1917 BN 978-0-387-76445-0 J9 HEALTH INFORM SER PY 2009 BP 161 EP 183 DI 10.1007/978-0-387-76446-7_12 D2 10.1007/978-0-387-76446-7 PG 23 WC Computer Science, Interdisciplinary Applications; Medical Informatics; Pediatrics SC Computer Science; Medical Informatics; Pediatrics GA BLA93 UT WOS:000269797000012 ER PT B AU Ashland, JE AF Ashland, Jean E. BE Mitchell, RB Pereira, KD TI Speech, Voice, and Swallowing Assessment SO PEDIATRIC OTOLARYNGOLOGY FOR THE CLINICIAN LA English DT Article; Book Chapter DE Speech; Articulation; Resonance; Velopharyngeal dysfunction; Hypernasality; Dysphagia; Aspiration; Modified barium swallow; FEES; Feeding team ID FIBEROPTIC ENDOSCOPIC EVALUATION; PEDIATRIC FEEDING DISORDERS; VELI PALATINI MUSCLE; VELOPHARYNGEAL DYSFUNCTION; MULTIVIEW VIDEOFLUOROSCOPY; VELOCARDIOFACIAL SYNDROME; SPHINCTER PHARYNGOPLASTY; DIFFERENTIAL-DIAGNOSIS; SURGICAL-MANAGEMENT; CHILDHOOD APRAXIA AB This chapter provides a summary of pediatric speech, resonance, and feeding/swallowing disorders. Information regarding normal development, assessment procedures, and referral guidelines are outlined in each of these topic areas. There is discussion of how the speech language pathologist and otolaryngologist may collaborate in such clinical cases. Differential diagnosis of speech disorders includes developmental, structural, and neurological causes. Both instrumental and noninstrumental assessment of resonance issues involving velopharyngeal dysfunction is discussed including nasopharyngoscopy, multiview videofluoroscopy, and nasometry. Feeding and swallowing disorders are differentiated to assist with the diagnosis and referral process. Sample parent interview questions are provided to assist the practitioner in discerning underlying problems in these three areas of speech, voice, and swallowing. C1 Harvard Univ, Massachusetts Gen Hosp, Div Patient Care Serv, Dept Speech Language & Swallowing Disorders, Boston, MA 02115 USA. RP Ashland, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Patient Care Serv, Dept Speech Language & Swallowing Disorders, Boston, MA 02115 USA. EM jashland@partners.org NR 54 TC 1 Z9 1 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-542-2 PY 2009 BP 21 EP 28 DI 10.1007/978-1-60327-127-1_3 D2 10.1007/978-1-60327-127-1 PG 8 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA BMQ05 UT WOS:000273331600003 ER PT J AU Liu, L Bouma, BE Rowe, SM Tearney, GJ AF Liu, L. Bouma, B. E. Rowe, S. M. Tearney, G. J. TI VTDEO-RATE ULTRAHIGH-RESOLUTION 3D OPTICAL IMAGING OF THE PULMONARY AIRWAYS SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Liu, L.; Bouma, B. E.; Tearney, G. J.] Harvard Univ, Sch Med, Boston, MA USA. [Liu, L.; Bouma, B. E.; Tearney, G. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rowe, S. M.] Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2009 MA 120 BP 252 EP 252 PG 1 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 505OL UT WOS:000270703400199 ER PT J AU Tamang, DL Pirzai, W Hurley, BP AF Tamang, D. L. Pirzai, W. Hurley, B. P. TI EXPRESSION OF ALOX12 AND ALOX15 IN LUNG EPITHELIAL CELLS IS ENHANCED UPON INFECTION WITH PSEUDOMONAS AERUGINOSA SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Tamang, D. L.; Pirzai, W.; Hurley, B. P.] Massachusetts Gen Hosp, Charlestown, MA USA. [Tamang, D. L.; Hurley, B. P.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2009 MA 152 BP 263 EP 264 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 505OL UT WOS:000270703400231 ER PT J AU Schwarzer, C Wong, S Shi, J Matthes, E Fu, Z Illek, B Hofer, A Machen, T AF Schwarzer, C. Wong, S. Shi, J. Matthes, E. Fu, Z. Illek, B. Hofer, A. Machen, T. TI P. AERUGINOSA HOMOSERINE LACTONE AND FLAGELLIN STIMULATE CL- SECRETION BY HUMAN AIRWAY EPITHELIAL CELLS: ROLES FOR CALCIUM AND CYCLIC AMP? SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Illek, B.] Childrens Hosp, Oakland Res Inst, Ctr Nutr & Metab, Oakland, CA 94609 USA. [Schwarzer, C.; Wong, S.; Shi, J.; Matthes, E.; Fu, Z.; Machen, T.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Hofer, A.] VA Boston Healthcare Syst, W Roxbury, MA USA. [Hofer, A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, W Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2009 SU 32 MA 314 BP 322 EP 322 PG 1 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 505OL UT WOS:000270703400393 ER PT J AU Georgiopoulos, AM Hua, L AF Georgiopoulos, A. M. Hua, L. TI A RETROSPECTIVE STUDY OF THE DIAGNOSIS AND TREATMENT OF ATTENTION DEFICIT-HYPERACTIVITY DISORDER IN CHILDREN AND ADOLESCENTS WITH CF SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Georgiopoulos, A. M.; Hua, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2009 MA 595 BP 425 EP 425 PG 1 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 505OL UT WOS:000270703400673 ER PT J AU Lipstein, EA Perrin, JM Kuhlthau, KA AF Lipstein, Ellen A. Perrin, James M. Kuhlthau, Karen A. TI School Absenteeism, Health Status, and Health Care Utilization Among Children With Asthma: Associations With Parental Chronic Disease SO PEDIATRICS LA English DT Article DE asthma; parental perceptions; chronic disease; health services utilization; absenteeism ID MEDICAL-CARE; VULNERABILITY; ILLNESS; POPULATION; MANAGEMENT; PERCEPTION; MOTHERS AB OBJECTIVE. Parents with chronic disease may be more likely than healthy parents to perceive their children with chronic conditions as medically vulnerable. Our objective for this study was to determine if children with asthma whose parents have chronic disease differ in health care utilization, school absenteeism, and reported child health status compared with those whose parents do not have chronic disease. PATIENTS AND METHODS. We selected children with asthma, 5 to 17 years of age, and their parents from the 2003 National Health Interview Survey. We determined whether parents had chronic disease and examined associations of parental chronic disease with child health status, school absenteeism, and health care utilization. We controlled for factors known to influence our dependent variables, including an indicator of child disease severity, in multivariable regression. RESULTS. Among 561 parent-child dyads, children with asthma whose parents had chronic disease were more likely to have less than very good health and missed an average of 1.3 more school days annually than other children with asthma. Among children with less severe asthma, those whose parents had chronic disease had lower reported health status but did not miss more school (mean difference: 0.39) than children whose parents did not have chronic disease. Having a parent with chronic disease was not associated with increased health care utilization. CONCLUSIONS. Compared with other children with asthma, children whose parents have chronic disease have worse health status and miss more school, particularly among children with more severe asthma. Understanding how parents' health influences children's health care and health status may help providers work with parents to more effectively and efficiently manage their children's asthma care so they can more fully participate in school and other activities. Pediatrics 2009;123:e60-e66 C1 [Lipstein, Ellen A.; Perrin, James M.; Kuhlthau, Karen A.] MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Perrin, James M.; Kuhlthau, Karen A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lipstein, EA (reprint author), MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM elipstein@partners.org FU Health Resources and Services Administration [T32 HP10018] FX Dr Lipstein's effort was supported by Health Resources and Services Administration grant T32 HP10018 to the Harvard Pediatric Health Services Research Fellowship Program. Dr Lipstein had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 24 TC 10 Z9 11 U1 0 U2 0 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 JAN PY 2009 VL 123 IS 1 BP E60 EP E66 DI 10.1542/peds.2008-1890 PG 7 WC Pediatrics SC Pediatrics GA 388UZ UT WOS:000262046400067 PM 19117848 ER PT J AU Winickoff, JP Friebely, J Tanski, SE Sherrod, C Matt, GE Hovell, MF McMillen, RC AF Winickoff, Jonathan P. Friebely, Joan Tanski, Susanne E. Sherrod, Cheryl Matt, Georg E. Hovell, Melbourne F. McMillen, Robert C. TI Beliefs About the Health Effects of "Thirdhand" Smoke and Home Smoking Bans SO PEDIATRICS LA English DT Article DE smoking; tobacco; pediatrics; family practice; parent; smoking cessation; secondhand smoke; environmental tobacco smoke; tobacco control ID ENVIRONMENTAL TOBACCO-SMOKE; CROSS-SECTIONAL SURVEY; GAS-PHASE ORGANICS; HOUSEHOLD SMOKING; EMISSION FACTORS; ANTISMOKING SOCIALIZATION; ADOLESCENT SMOKING; WORKPLACE SMOKING; PARENTAL SMOKING; EXPOSURE AB OBJECTIVE. There is no safe level of exposure to tobacco smoke. Thirdhand smoke is residual tobacco smoke contamination that remains after the cigarette is extinguished. Children are uniquely susceptible to thirdhand smoke exposure. The objective of this study was to assess health beliefs of adults regarding thirdhand smoke exposure of children and whether smokers and nonsmokers differ in those beliefs. We hypothesized that beliefs about thirdhand smoke would be associated with household smoking bans. METHODS. Data were collected by a national random-digit-dial telephone survey from September to November 2005. The sample was weighted by race and gender within Census region on the basis of US Census data. The study questions assessed the level of agreement with statements that breathing air in a room today where people smoked yesterday can harm the health of children. RESULTS. Of 2000 eligible respondents contacted, 1510 (87%) completed surveys, 1478 (97.9%) answered all questions pertinent to this analysis, and 273 (18.9%) were smokers. Overall, 95.4% of nonsmokers versus 84.1% of smokers agreed that secondhand smoke harms the health of children, and 65.2% of nonsmokers versus 43.3% of smokers agreed that thirdhand smoke harms children. Strict rules prohibiting smoking in the home were more prevalent among nonsmokers: 88.4% vs 26.7%. In multivariate logistic regression, after controlling for certain variables, belief that thirdhand smoke harms the health of children remained independently associated with rules prohibiting smoking in the home. Belief that secondhand smoke harms the health of children was not independently associated with rules prohibiting smoking in the home and car. CONCLUSIONS. This study demonstrates that beliefs about the health effects of thirdhand smoke are independently associated with home smoking bans. Emphasizing that thirdhand smoke harms the health of children may be an important element in encouraging home smoking bans. Pediatrics 2009;123:e74-e79 C1 [Winickoff, Jonathan P.; Friebely, Joan; Sherrod, Cheryl] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Tanski, Susanne E.] Dartmouth Med Sch, Dept Pediat, Lebanon, NH USA. [Matt, Georg E.] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA. [Hovell, Melbourne F.] San Diego State Univ, Grad Sch Publ Hlth, Ctr Behav Epidemiol & Community Hlth, San Diego, CA 92182 USA. [McMillen, Robert C.] Mississippi State Univ, Social Sci Res Ctr, Starkville, MS USA. [McMillen, Robert C.] Mississippi State Univ, Dept Psychol, Starkville, MS USA. RP Winickoff, JP (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM jwinickoff@partners.org FU Flight Attendant Medical Research Institute [FAMRI 024032]; National Cancer Institute [K07 CA100213 A 01]; Office of Rural Health Policy of the Department of Health and Human Services through the Rural Health Safety and Security Institute [4 D1A RH 00005-01-01]; Social Science Research Center; Mississippi State University; American Academy of Pediatrics Julius B. Richmond Center of Excellence; FAMRI FX Dr Winickoff was supported by a grant from the Flight Attendant Medical Research Institute (FAMRI 024032) and the National Cancer Institute (K07 CA100213 A 01). This publication was also made possible by grant 4 D1A RH 00005-01-01 from the Office of Rural Health Policy of the Department of Health and Human Services through the Rural Health Safety and Security Institute, Social Science Research Center, Mississippi State University, and the American Academy of Pediatrics Julius B. Richmond Center of Excellence also supported by FAMRI. NR 37 TC 123 Z9 124 U1 3 U2 27 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 JAN PY 2009 VL 123 IS 1 BP E74 EP E79 DI 10.1542/peds.2008-2184 PG 6 WC Pediatrics SC Pediatrics GA 388UZ UT WOS:000262046400069 PM 19117850 ER PT J AU Ferris, TG Johnson, SA Co, JPT Backus, M Perrin, J Bates, DW Poon, EG AF Ferris, Timothy G. Johnson, Sarah A. Co, John Patrick T. Backus, Meghan Perrin, James Bates, David W. Poon, Eric G. TI Electronic Results Management in Pediatric Ambulatory Care: Qualitative Assessment SO PEDIATRICS LA English DT Article DE clinical laboratory information systems; ambulatory care information systems; quality of health care ID MEDICAL-RECORDS; COMMUNICATION; INFORMATION; PHYSICIANS; VISITS; ERRORS; SYSTEM AB BACKGROUND. Electronic results management may improve the reliability and efficiency of test results management, but few studies have investigated this topic in pediatrics. METHODS. We conducted semi-structured, key informant interviews before and after implementation of electronic results management at 8 pediatric ambulatory care practices. We also surveyed all pediatricians at 18 practices (10 additional practices). All practices were members of Partners Healthcare and had been using an electronic health record when they were offered electronic results management. We assessed baseline processes for results management, barriers to electronic results management adoption, and the perceived impact of electronic results management on quality, efficiency, and provider satisfaction. RESULTS. From interviews, we found a range of processes in place to manage test results, but all practices reported losing some results and no practice tracked all test results from the time of ordering to parent/patient notification. Practices that fully adopted electronic results management reported gains in efficiency, reliability, timeliness, and provider satisfaction, whereas some partial adopters reported decreased efficiency and increased risk of lost test results. Barriers to electronic results management adoption included lack of inclusion of all ordered tests in the electronic results management system, user interface design issues, and lack of sufficient pediatric customization. Survey results (response rate: 62%) indicated that pediatricians thought electronic results management improved the quality and efficiency of care, with 72% of pediatricians reporting safer care and 63% reporting more-effective care. CONCLUSIONS. We found that pediatric practices have room for improvement in the management of test results, and electronic results management may be an effective method for improving the efficiency and safety of test results management. However, partial adoption of electronic results management may decrease efficiency and pose a threat to patient safety. Pediatrics 2009; 123: S85-S91 C1 [Ferris, Timothy G.; Johnson, Sarah A.; Backus, Meghan; Poon, Eric G.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Ferris, Timothy G.; Co, John Patrick T.; Perrin, James] MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. [Ferris, Timothy G.; Co, John Patrick T.; Perrin, James; Bates, David W.; Poon, Eric G.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Bates, David W.; Poon, Eric G.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Ferris, TG (reprint author), MGH MGPO, 55 Fruit St,BUL 205E, Boston, MA 02111 USA. EM tferris@partners.org FU Agency for Healthcare Research and Quality [2004-P-0020271] FX This project was funded by the Agency for Healthcare Research and Quality (grant 2004-P-0020271). NR 21 TC 11 Z9 11 U1 4 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 JAN PY 2009 VL 123 BP S85 EP S91 DI 10.1542/peds.2008-1755G PG 7 WC Pediatrics SC Pediatrics GA 413XK UT WOS:000263825800006 PM 19088235 ER PT J AU Chan, YM Broder-Fingert, S Seminara, SB AF Chan, Yee-Ming Broder-Fingert, Sarabeth Seminara, Stephanie B. TI Reproductive functions of kisspeptin and Gpr54 across the life cycle of mice and men SO PEPTIDES LA English DT Article DE GPR54; KISS1; Kisspeptin; Reproduction; Idiopathic hypogonadotropic hypogonadism ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; GONADOTROPIN-RELEASING-HORMONE; ADRENAL HYPOPLASIA CONGENITA; PITUITARY-GONADAL AXIS; KALLMANN-SYNDROME; RECEPTOR GPR54; LUTEINIZING-HORMONE; MUTATIONS; GENE; PHENOTYPES AB The reproductive phenotypes of nearly two dozen patients with mutations in GPR54 have been reported, as have the phenotypes of four mouse lines mutant for Gpr54 and two lines mutant for Kiss1. These phenotypes demonstrate that kisspeptin/Gpr54 function is required at all phases of the life cycle when the secretion of gonadotropin-releasing hormone (GnRH) is robust. Furthermore, there is phenotypic variability ranging from severe hypogonadism to partial sexual development. Collectively, these findings suggest that kisspeptin and Gpr54 serve as an essential conduit for relaying developmental information to the GnRH neuron. (C) 2008 Elsevier Inc. All rights reserved. C1 [Chan, Yee-Ming; Broder-Fingert, Sarabeth; Seminara, Stephanie B.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Chan, Yee-Ming; Broder-Fingert, Sarabeth; Seminara, Stephanie B.] Massachusetts Gen Hosp, Harvard Reprod Sci Ctr, Dept Med, Boston, MA 02114 USA. [Chan, Yee-Ming] Childrens Hosp, Div Endocrinol, Dept Med, Boston, MA 02115 USA. RP Chan, YM (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, 55 Fruit St BHX 5, Boston, MA 02114 USA. EM ymchan@partners.org; sbroder-finger@partners.org; seminara.stephanie@mgh.harvard.edu OI Broder-Fingert, Sarabeth/0000-0002-0932-4461 FU NICHD NIH HHS [R01 HD043341-06, R01 HD043341, U54 HD028138, U54 HD028138-180002] NR 44 TC 24 Z9 24 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD JAN PY 2009 VL 30 IS 1 BP 42 EP 48 DI 10.1016/j.peptides.2008.06.015 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 398ZE UT WOS:000262769400007 PM 18644412 ER PT S AU Hayashi, K Cheo, S Opare-Addo, P Khatri, A AF Hayashi, Koichiro Cheo, Sylvia Opare-Addo, Paul Khatri, Ashok BE DelValle, S Escher, E Lubell, WD TI An Efficient Approach to Synthesize Multiple Peptides with Carboxyl C-termini SO PEPTIDES FOR YOUTH SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 20th American-Peptide-Society Symposium CY JUN 26-30, 2007 CL Montreal, CANADA SP Amer Peptide Soc ID CLEAVAGE C1 [Hayashi, Koichiro; Cheo, Sylvia; Opare-Addo, Paul; Khatri, Ashok] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Hayashi, K (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 978-0-387-73656-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2009 VL 611 BP 177 EP 178 DI 10.1007/978-0-387-73657-0_81 PG 2 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BJH04 UT WOS:000265773200081 PM 19400148 ER PT S AU Cantel, S Kavishwar, A Schlimme, M Khatri, A Halperin, JA Chorev, M AF Cantel, S. Kavishwar, A. Schlimme, M. Khatri, A. Halperin, J. A. Chorev, M. BE DelValle, S Escher, E Lubell, WD TI Glycated-CD59 antigen: exploration of synthetic approaches SO PEPTIDES FOR YOUTH SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 20th American-Peptide-Society Symposium CY JUN 26-30, 2007 CL Montreal, CANADA SP Amer Peptide Soc ID COMPLICATIONS; PATHOGENESIS; CD59 C1 [Cantel, S.; Kavishwar, A.; Schlimme, M.; Halperin, J. A.; Chorev, M.] Harvard Univ, Sch Med, Lab Translat Res, Cambridge, MA 02391 USA. [Cantel, S.; Kavishwar, A.; Schlimme, M.; Halperin, J. A.; Chorev, M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Cantel, S.] Univ Montpellier 2, CNRS, Max Mousseron Inst Biomol, IBMM,UMR 5247,CC1703, F-34095 Montpellier, France. [Khatri, A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Khatri, A.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Cantel, S (reprint author), Harvard Univ, Sch Med, Lab Translat Res, 1 Kendall Sq,Bldg 600, Cambridge, MA 02391 USA. RI cantel, sonia/C-7121-2012 FU NIDDK NIH HHS [R01 DK060979, R01 DK062994] NR 3 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 978-0-387-73656-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2009 VL 611 BP 317 EP 318 DI 10.1007/978-0-387-73657-0_141 PG 2 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BJH04 UT WOS:000265773200141 PM 19400208 ER PT J AU Sasaki, Y AF Sasaki, Y. TI Perceptual learning and brain activation SO PERCEPTION LA English DT Meeting Abstract C1 [Sasaki, Y.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. EM yuka@nmr.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2009 VL 38 SU S BP 12 EP 12 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA V16YN UT WOS:000207905000034 ER PT J AU Iwaki, S Belliveau, JW AF Iwaki, S. Belliveau, J. W. TI Dynamic interactions between the dorsal and the ventral visual subsystems during the perception of 3-D structure from 2-D motion SO PERCEPTION LA English DT Meeting Abstract C1 Natl Inst Adv Ind Sci & Technol, Inst Human Sci & Biomed Engn, Tsukuba, Ibaraki, Japan. [Iwaki, S.; Belliveau, J. W.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. EM s.iwaki@aist.go.jp RI Iwaki, Sunao/B-1079-2011 OI Iwaki, Sunao/0000-0002-7123-7203 NR 0 TC 0 Z9 0 U1 1 U2 1 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2009 VL 38 SU S BP 29 EP 29 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA V16YN UT WOS:000207905000093 ER PT J AU Yue, X Holt, DJ Cassidy, BS Devaney, KJ Tootell, RBH AF Yue, X. Holt, D. J. Cassidy, B. S. Devaney, K. J. Tootell, R. B. H. TI Face selectivity is parameter-dependent in FFA SO PERCEPTION LA English DT Meeting Abstract C1 [Yue, X.; Devaney, K. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. [Holt, D. J.; Cassidy, B. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Tootell, R. B. H.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. EM xiaomin@nmr.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2009 VL 38 SU S BP 80 EP 80 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA V16YN UT WOS:000207905000258 ER PT J AU Pineles, SL Vogt, DS Orr, SP AF Pineles, Suzanne L. Vogt, Dawne S. Orr, Scott P. TI Personality and fear responses during conditioning: Beyond extraversion SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE Fear conditioning; Big Five; Personality; Extraversion; Neuroticism; Multi-level modeling; Psychophysiology ID ANXIETY DISORDERS; PSYCHOPHYSIOLOGY; ACQUISITION; MODELS AB The personality domain of introversion-extraversion has been theorized to be associated with the strength of fear conditioning, but the literature on this topic has been equivocal. Furthermore, except for extraversion and neuroticism, relationships of the other Big Five personality domains with fear response acquisition have not been explored. In the current study, multi-level modeling was used to examine the relationships of facets of the Big Five domains to fear response acquisition. Participants were 217 police and firefighter trainees who completed the Revised NEO Personality Inventory (NEO-PI-R; Costa & McCrae, 1992) and a fear conditioning task as part of a larger study. Results indicated that several facets of extraversion have opposing associations with fear response acquisition of an electrodermal response - possibly contributing to the mixed results in the literature. Additionally, facets of other Big Five domains were found to be associated with fear response acquisition. Published by Elsevier Ltd. C1 [Orr, Scott P.] Dept Vet Affairs Med Ctr, Res Serv 151, Manchester, NH 03104 USA. [Orr, Scott P.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Orr, Scott P.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Pineles, Suzanne L.; Vogt, Dawne S.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Pineles, Suzanne L.; Vogt, Dawne S.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. RP Orr, SP (reprint author), Dept Vet Affairs Med Ctr, Res Serv 151, 718 Smyth Rd, Manchester, NH 03104 USA. EM scott.orr@va.gov FU NIMH NIH HHS [R01 MH060315, R01 MH060315-05] NR 20 TC 15 Z9 16 U1 3 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD JAN PY 2009 VL 46 IS 1 BP 48 EP 53 DI 10.1016/j.paid.2008.09.003 PG 6 WC Psychology, Social SC Psychology GA 400ZE UT WOS:000262907100010 PM 20046207 ER PT J AU Shin, JM Munson, K Vagin, O Sachs, G AF Shin, Jai Moo Munson, Keith Vagin, Olga Sachs, George TI The gastric HK-ATPase: structure, function, and inhibition SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE The gastric H,K-ATPase; ATPase structure-function; Proton pump inhibitors; Acid pump antagonists; Gastric acid secretion ID PROTON PUMP INHIBITORS; PLASMA-MEMBRANE DELIVERY; K+-COMPETITIVE INHIBITOR; H,K-ATPASE BETA-SUBUNIT; ACID-SECRETION; ALPHA-SUBUNIT; H+/K+-ATPASE; CDNA CLONING; SARCOPLASMIC-RETICULUM; HEALTHY-VOLUNTEERS AB The gastric H,K-ATPase, a member of the P(2)-type ATPase family, is the integral membrane protein responsible for gastric acid secretion. It is an alpha,beta-heterodimeric enzyme that exchanges cytoplasmic hydronium with extracellular potassium. The catalytic alpha subunit has ten transmembrane segments with a cluster of intramembranal carboxylic amino acids located in the middle of the transmembrane segments TM4, TM5,TM6, and TM8. Comparison to the known structure of the SERCA pump, mutagenesis, and molecular modeling has identified these as constituents of the ion binding domain. The beta subunit has one transmembrane segment with N terminus in cytoplasmic region. The extracellular domain of the beta subunit contains six or seven N-linked glycosylation sites. N-glycosylation is important for the enzyme assembly, maturation, and sorting. The enzyme pumps acid by a series of conformational changes from an E(1) (ion site in) to an E(2) (ion site out) configuration following binding of MgATP and phosphorylation. Several experimental observations support the hypothesis that expulsion of the proton at 160 mM (pH 0.8) results from movement of lysine 791 into the ion binding site in the E(2)P configuration. Potassium access from the lumen depends on activation of a K and Cl conductance via a KCNQ1/KCNE2 complex and Clic6. K movement through the luminal channel in E(2)P is proposed to displace the lysine along with dephosphorylation to return the enzyme to the E(1) configuration. This enzyme is inhibited by the unique proton pump inhibitor class of drug, allowing therapy of acid-related diseases. C1 [Shin, Jai Moo; Munson, Keith; Vagin, Olga; Sachs, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. [Shin, Jai Moo; Munson, Keith; Vagin, Olga; Sachs, George] VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Sachs, G (reprint author), Room 324,Bldg 113,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gsachs@ucla.edu FU NIDDK NIH HHS [DK58333, DK053642, R01 DK053642, R01 DK053642-12, R01 DK053642-13, R01 DK058333, R01 DK058333-11, R01 DK077149, R01 DK077149-02, R01 DK077149-03, R56 DK058333, R56 DK058333-12] NR 73 TC 84 Z9 87 U1 2 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD JAN PY 2009 VL 457 IS 3 BP 609 EP 622 DI 10.1007/s00424-008-0495-4 PG 14 WC Physiology SC Physiology GA 393ZF UT WOS:000262414300006 PM 18536934 ER PT J AU Prela, CM Baumgardner, GA Reiber, GE McFarland, LV Maynard, C Anderson, N Maciejewski, M AF Prela, Cecilia M. Baumgardner, Greg A. Reiber, Gayle E. McFarland, Lynne V. Maynard, Charles Anderson, Nancy Maciejewski, Matthew TI Challenges in Merging Medicaid and Medicare Databases to Obtain Healthcare Costs for Dual-Eligible Beneficiaries Using Diabetes as an Example SO PHARMACOECONOMICS LA English DT Article ID QUALITY; STATE; VETERANS; OUTCOMES; RISK AB Background: Dual-eligible Medicaid-Medicare beneficiaries represent a group of people who are in the lowest income bracket in the US, have numerous co-morbidities and place a heavy financial burden on the US healthcare system. As cost-effectiveness analyses are used to inform national policy decisions and to determine the value of implemented chronic disease control programmes, it is imperative that complete and valid determination of healthcare utilization and costs can be obtained from existing state and federal databases. Differences and inconsistencies between the Medicaid and Medicare databases have presented significant challenges when extracting accurate data for dual-eligible beneficiaries. Objectives: To describe the challenges inherent in merging Medicaid and Medicare claims databases and to present a protocol that would allow successful linkage between these two disparate databases. Methods: Healthcare claims and costs were extracted from both Medicaid and Medicare databases for King County, Seattle, WA, USA. Three Medicaid files were linked to eight Medicare files for unique dual-eligible beneficiaries with type 2 diabetes mellitus. Results: Although major differences were identified in how variables and claims were defined in each database, our method enabled us to link these two different databases to compile a complete and accurate assessment of healthcare use and costs for dual-eligible beneficiaries with a costly chronic condition. For example, of the 1759 dual-eligible beneficiaries with diabetes, the average cost of healthcare was $US15 981 per capita, with an average of 76 claims per person per year. Conclusion: The resulting merged database provides a virtually complete documentation of both utilization and costs of medical care for a population who receives coverage from two different programmes. By identifying differences and implementing our linkage protocol, the merged database serves as a foundation for a broad array of analyses on healthcare use and costs for effectiveness research. C1 [Reiber, Gayle E.; McFarland, Lynne V.; Maynard, Charles] VA Puget Sound Healthcare Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Prela, Cecilia M.] Ctr Medicare & Medicaid Serv, Medicare Plan Payment Grp, Div Risk Adjustment, Baltimore, MD USA. [Baumgardner, Greg A.] Qualis Hlth, Data Anal Team, Seattle, WA USA. [Anderson, Nancy] Med Assistance Adm, Olympia, WA USA. [Maciejewski, Matthew] Univ N Carolina, Chapel Hill, NC USA. RP McFarland, LV (reprint author), VA Puget Sound Healthcare Syst, Hlth Serv Res & Dev, 1100 Olive Way 1400, Seattle, WA 98101 USA. EM lynne.mcfarland@va.gov RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 FU Centers for Medicare & Medicaid Services [500-99-WA02]; US Department of Health and Human Services; Sandy MacColl Foundation, Seattle, Washington; The Robert Wood Johnson Foundation, Princeton, New York; Adventis Pharmaceuticals Inc.; Washington State Department of Health FX The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the Department of Health and Human Services. The authors assume full responsibility for the accuracy and completeness of the ideas presented. NR 31 TC 6 Z9 6 U1 0 U2 3 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2009 VL 27 IS 2 BP 167 EP 177 PG 11 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 432IS UT WOS:000265127300007 PM 19254049 ER PT J AU Siebert, U Sroczynski, G Aidelsburger, P Rossol, S Wasem, J Manns, MP McHutchison, JG Wong, JB AF Siebert, Uwe Sroczynski, Gaby Aidelsburger, Pamela Rossol, Siegbert Wasem, Juergen Manns, Michael P. McHutchison, John G. Wong, John B. TI Clinical Effectiveness and Cost Effectiveness of Tailoring Chronic Hepatitis C Treatment with Peginterferon Alpha-2b Plus Ribavirin to HCV Genotype and Early Viral Response A Decision Analysis Based on German Guidelines SO PHARMACOECONOMICS LA English DT Article ID TERM-FOLLOW-UP; COMBINATION THERAPY; INITIAL TREATMENT; NAIVE PATIENTS; ECONOMIC-EVALUATION; CIRRHOTIC-PATIENTS; PROGNOSTIC-FACTORS; INTERFERON-ALPHA; OF-HEALTH; NON-A AB Background: Recently developed German guidelines for antiviral treatment in patients with chronic hepatitis C recommend basing drug dosage, intended treatment duration and early stopping rules on the genotype of the hepatitis C virus and early viral responses to treatment. Objectives: To evaluate effectiveness and cost effectiveness of different antiviral treatment strategies including the German guidelines, for chronic hepatitis C. Methods: A validated lifetime Markov model was used to project life expectancy, QALYs and lifetime costs for the following strategies: (i) no antiviral therapy (NoAVT); (ii) interferon-alpha-2b plus ribavirin for 48 weeks (IFN + R); (iii) peginterferon-alpha-2b plus weight-based ribavirin for 48 weeks (PEG + R); (iv) peginterferon-alpha-2b plus ribavirin according to German guidelines with genotype-dependent treatment duration, dosage and 12-week viral response evaluation (GUIDE). Clinical and resource utilization data were derived from a clinical trial, the published literature and a survey of German hepatologists. Incremental cost-effectiveness ratios (ICERs) were calculated adopting the German societal perspective. Costs (in E, year 2005 values) and health outcomes were discounted at 3% annually. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Results: Compared with NoAVT, PEG + R increased undiscounted life expectancy by 5.0 life-years (5.2 QALYs) and GUIDE increased undiscounted life expectancy by 4.9 years (5.1 QALYs). Compared with PEG + R, GUIDE saved 13% of hepatitis C virus-related lifetime costs per patient. GUIDE dominated IFN + R. Compared with NoAVT, discounted ICERs were epsilon 1500 per QALY for GUIDE and epsilon 3200 per QALY for PEG + R. Conclusion: Administering GUIDE should allow tailoring treatment efficiently to genotype, bodyweight and early viral response in patients with chronic hepatitis C, and appears cost effective compared with other well accepted medical interventions. C1 [Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Med Decis Making & Hlth Technol As, Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol, Austria. [Siebert, Uwe; Sroczynski, Gaby] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Siebert, Uwe; Sroczynski, Gaby] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Program Hlth Decis Sci, Boston, MA 02115 USA. [Aidelsburger, Pamela; Wasem, Juergen] Univ Duisburg Essen, Inst Hlth Serv Management, Essen, Germany. [Rossol, Siegbert] Univ Frankfurt, Krankenhaus Nordwest, Med Clin 1, Frankfurt, Germany. [Manns, Michael P.] Med Sch Hanover, Dept Gastroenterol & Hepatol, Hannover, Germany. [McHutchison, John G.] Scripps Clin, La Jolla, CA 92037 USA. [Wong, John B.] Tufts Univ, Sch Med, Dept Med, Div Clin Decis Making,Tufts New England Med Ctr, Boston, MA 02111 USA. RP Siebert, U (reprint author), UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Med Decis Making & Hlth Technol As, Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol, Austria. EM public-health@umit.net OI Wasem, Juergen/0000-0001-9653-168X NR 64 TC 18 Z9 19 U1 0 U2 2 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2009 VL 27 IS 4 BP 341 EP 354 PG 14 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 482DM UT WOS:000268864300006 PM 19485429 ER PT J AU Stout, NK Knudsen, AB Kong, CY McMahon, PM Gazelle, GS AF Stout, Natasha K. Knudsen, Amy B. Kong, Chung Yin McMahon, Pamela M. Gazelle, G. Scott TI Calibration Methods Used in Cancer Simulation Models and Suggested Reporting Guidelines SO PHARMACOECONOMICS LA English DT Review ID COST-EFFECTIVENESS ANALYSIS; HUMAN-PAPILLOMAVIRUS INFECTION; BREAST SCREENING-PROGRAM; NATURAL-HISTORY MODEL; CERVICAL-CANCER; COLORECTAL-CANCER; PROSTATE-CANCER; COMPUTER-SIMULATION; LUNG-CANCER; CLINICAL BENEFITS AB Increasingly, computer simulation models are used for economic and policy evaluation in cancer prevention and control. A model's predictions of key outcomes, such as screening effectiveness, depend on the values of unobservable natural history parameters. Calibration is the process of determining the values of unobservable parameters by constraining model output to replicate observed data. Because there are many approaches for model calibration and little consensus on best practices, we surveyed the literature to catalogue the use and reporting of these methods in cancer simulation models. We conducted a MEDLINE search (1980 through 2006) for articles on cancer-screening models and supplemented search results with articles from our personal reference databases. For each article, two authors independently abstracted pre-determined items using a standard form. Data items included cancer site, model type, methods used for determination of unobservable parameter values and description of any calibration protocol. All authors reached consensus on items of disagreement. Reviews and non-cancer models were excluded. Articles describing analytical models, which estimate parameters with statistical approaches (e.g. maximum likelihood) were catalogued separately. Models that included unobservable parameters were analysed and classified by whether calibration methods were reported and if so, the methods used. The review process yielded 154 articles that met our inclusion criteria and, of these, we concluded that 131 may have used calibration methods to determine model parameters. Although the term 'calibration' was not always used, descriptions of calibration or 'model fitting' were found in 50% (n = 66) of the articles, with an additional 16% (n = 21) providing a reference to methods. Calibration target data were identified in nearly all of these articles. Other methodological details, such as the goodness-of-fit metric, were discussed in 54% (n = 47 of 87) of the articles reporting calibration methods, while few details were provided on the algorithms used to search the parameter space. Our review shows that the use of cancer simulation modelling is increasing, although thorough descriptions of calibration procedures are rare in the published literature for these models. Calibration is a key component of model development and is central to the validity and credibility of subsequent analyses and inferences drawn from model predictions. To aid peer-review and facilitate discussion of modelling methods, we propose a standardized Calibration Reporting Checklist for model documentation. C1 [Stout, Natasha K.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Harvard Pilgrim Hlth Care, Boston, MA 02215 USA. [Stout, Natasha K.; Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Program Hlth Decis Sci, Boston, MA 02215 USA. [Knudsen, Amy B.; Kong, Chung Yin; McMahon, Pamela M.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Knudsen, Amy B.; Kong, Chung Yin; McMahon, Pamela M.; Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Stout, NK (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Harvard Pilgrim Hlth Care, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM natasha_stout@hms.harvard.edu FU National Cancer Institute [F32 CA 125984, R25 CA92203, K99 126147, R01 97337] FX The authors gratefully acknowledge the support of Drs Eric Feuer and Karen Kuntz and members of the NCI Cancer Intervention and Surveillance Modeling Network. This work was supported in part by grants from the National Cancer Institute: F32 CA 125984 (Natasha K. Stout), R25 CA92203 (Amy B. Knudsen), K99 126147 (Pamela M. McMahon, Chung Yin Kong) and R01 97337 (G. Scott Gazelle, Pamela M. McMahon, Chung Yin Kong). The funding agreements ensured the authors' independence in designing the study, collecting, analysing and interpreting the data and writing and publishing the report. An earlier version of this work was presented at the 2007 Society for Medical Decision Making Annual Meeting. NR 180 TC 42 Z9 42 U1 0 U2 7 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2009 VL 27 IS 7 BP 533 EP 545 PG 13 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 506YU UT WOS:000270815700002 PM 19663525 ER PT J AU Wright, DR Wittenberg, E Swan, JS Miksad, RA Prosser, LA AF Wright, Davene R. Wittenberg, Eve Swan, J. Shannon Miksad, Rebecca A. Prosser, Lisa A. TI Methods for Measuring Temporary Health States for Cost-Utility Analyses SO PHARMACOECONOMICS LA English DT Review ID QUALITY-OF-LIFE; TIME-TRADE-OFF; WELL-BEING SCALE; METHODOLOGICAL ISSUES; STANDARD GAMBLE; PREFERENCES; VALIDITY; DISEASE; QALYS; VALUATION AB A variety of methods are available to measure preferences for temporary health states for cost-utility analyses. The objectives of this review were to summarize the available temporary health-state valuation methods, identify advantages and disadvantages of each, and identify areas for future research. We describe the key aspects of each method and summarize advantages and disadvantages of each method in terms of consistency with QALY theory, relevance to temporary health-state-specific domains, ease of use, time preference, and performance in validation studies. Two broad categories of methods were identified: traditional and adapted. Traditional methods were health status instruments, time trade-off (TTO), and the standard gamble (SG). Methods adapted specifically for temporary health-state valuation were TTO with specified duration of the health state, TTO with a lifespan modification, waiting trade-off, chained approaches for TTO and SG, and sleep trade-off. Advantages and disadvantages vary by method and no 'gold standard' method emerged. Selection of a method to value temporary health states will depend on the relative importance of the following considerations: ability to accurately capture the unique characteristics of the temporary health state, level of respondent burden and cognition, theoretical consistency of elicited preference values with the overall purpose of the study, and resources available for study development and data collection. Further research should focus on evaluating validity, reliability and feasibility of temporary health-state valuation methods. C1 [Prosser, Lisa A.] Univ Michigan Hlth Syst, Child Hlth Evaluat & Res Unit, Div Gen Pediat, Ann Arbor, MI 48109 USA. [Wright, Davene R.; Wittenberg, Eve; Swan, J. Shannon; Miksad, Rebecca A.; Prosser, Lisa A.] Harvard Univ, Sch Publ Hlth, Preferences Working Grp, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Wittenberg, Eve] Brandeis Univ, Heller Sch Social Policy & Management, Schneider Inst Hlth Policy, Waltham, MA USA. [Swan, J. Shannon; Miksad, Rebecca A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Swan, J. Shannon; Miksad, Rebecca A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Miksad, Rebecca A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol & Oncol, Boston, MA 02215 USA. [Prosser, Lisa A.] Harvard Univ, Ctr Child Hlth Care Studies, Dept Ambulatory Care & Prevent, Sch Med, Boston, MA USA. [Prosser, Lisa A.] Harvard Pilgrim Hlth Care, Boston, MA USA. RP Prosser, LA (reprint author), Univ Michigan Hlth Syst, Child Hlth Evaluat & Res Unit, Div Gen Pediat, 300 N Ingalls St,Room 6E14,SPC 5456, Ann Arbor, MI 48109 USA. EM lisapros@med.umich.edu FU Center for Health Decision Science at the Harvard School of Public Health FX The authors have no conflicts of interest that are directly relevant to the content of this review. NR 53 TC 21 Z9 21 U1 2 U2 6 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2009 VL 27 IS 9 BP 713 EP 723 PG 11 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 507JE UT WOS:000270848500002 PM 19757865 ER PT J AU Haynes, K Hennessy, S Localio, AR Cohen, A Leonard, CE Kimmel, SE Feldman, HI Strom, BL Metlay, JP AF Haynes, Kevin Hennessy, Sean Localio, A. Russell Cohen, Abigail Leonard, Charles E. Kimmel, Stephen E. Feldman, Harold I. Strom, Brian L. Metlay, Joshua P. TI Increased risk of digoxin toxicity following hospitalization SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE adverse effects; drug toxicity; physician-patient relationships ID ADVERSE DRUG-REACTIONS; OLDER-ADULTS; EVENTS; CARE; DEPRESSION; IMPAIRMENT; DISCHARGE AB Purpose Adverse drug events (ADEs) are an important cause of preventable hospitalizations among elderly individuals taking high-risk medications. The objective of the study was to identify health care system factors that affect the risk of digoxin toxicity for older adults on digoxin. Methods We conducted a prospective cohort study of older adults within the Pennsylvania Pharmaceutical Assistance Contract for the Elderly (PACE) program, which provides comprehensive drug benefits for older adults with low income. Subjects were interviewed at the time of enrollment regarding the management and coordination of their health care as well as medication comprehension. Hospitalizations were identified by linking patient identifiers to a state-wide registry. Trained abstractors reviewed discharge summaries of possible digoxin related ADEs. Unadjusted and adjusted incidence rate ratios (IRR) were calculated based on person-months of exposure using Poisson regression models, with variances adjusted for within subject repeated measures. Results We enrolled a total of 2030 adults on digoxin from May 2002 to June 2003. A total of 34 hospitalizations due to digoxin toxicity occurred, equivalent to 1.12 hospitalizations per 1000 person-months of exposure. Adjusting for hospitalization in the past 2 months, age, total number physicians prescribing any medications in past 3 months, total number of pharmacies filling medications in past 3 months, and number of unique prescriptions filled in the past month had a 4.25-fold increased risk of subsequently experiencing digoxin toxicity (IRR 95%CI 1.95, 9.27). Conclusions The risk of digoxin toxicity-related hospitalization, while low, is higher in the post-hospital period. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Haynes, Kevin; Hennessy, Sean; Localio, A. Russell; Cohen, Abigail; Leonard, Charles E.; Kimmel, Stephen E.; Feldman, Harold I.; Strom, Brian L.; Metlay, Joshua P.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Haynes, Kevin; Hennessy, Sean; Localio, A. Russell; Cohen, Abigail; Leonard, Charles E.; Kimmel, Stephen E.; Feldman, Harold I.; Strom, Brian L.; Metlay, Joshua P.] Univ Penn, Dept Biostat & Epidemiol, Program Reduct Medicat Errors, Philadelphia, PA 19104 USA. [Haynes, Kevin; Hennessy, Sean; Localio, A. Russell; Leonard, Charles E.; Strom, Brian L.; Metlay, Joshua P.] Univ Penn, Dept Biostat & Epidemiol, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. [Haynes, Kevin; Hennessy, Sean; Localio, A. Russell; Cohen, Abigail; Leonard, Charles E.; Kimmel, Stephen E.; Feldman, Harold I.; Strom, Brian L.; Metlay, Joshua P.] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Metlay, Joshua P.] Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Haynes, K (reprint author), Univ Penn, Sch Med, 711 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM khaynes@mail.med.upenn.edu RI Leonard, Charles/K-3447-2012; Cohen, Abigail/K-9180-2013 OI Cohen, Abigail/0000-0002-7425-7218 FU Agency for Healthcare Research and Quality [P01-HS11530]; Health Services Research and Development Service of the Department of Veterans Affairs FX This study was suported by Grant P01-HS11530 from the Agency for Healthcare Research and Quality. Dr Metlay is supported by an Advanced Research Career Development Award from the Health Services Research and Development Service of the Department of Veterans Affairs. NR 21 TC 7 Z9 7 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JAN PY 2009 VL 18 IS 1 BP 28 EP 35 DI 10.1002/pds.1680 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 405EX UT WOS:000263206700005 PM 19040200 ER PT J AU Heist, RS Christiani, D AF Heist, Rebecca Suk Christiani, David TI EGFR-targeted therapies in lung cancer: predictors of response and toxicity SO PHARMACOGENOMICS LA English DT Review DE cancer genetics; EGFR; lung cancer; predictive markers ID GROWTH-FACTOR-RECEPTOR; METASTATIC COLORECTAL-CANCER; TYROSINE KINASE INHIBITORS; PHASE-II TRIAL; MULTIDRUG TRANSPORTER ABCG2; PREVIOUSLY TREATED PATIENTS; CETUXIMAB PLUS IRINOTECAN; KRAS MUTATIONS; GEFITINIB SENSITIVITY; MOLECULAR PREDICTORS AB The EGFR pathway has emerged as a key target in non-small-cell lung cancer. EGF receptor (EGFR) inhibition in non-small-cell lung cancer is achieved via small molecular tyrosine kinase inhibitors, such as erlotinib or gefitinib, or monoclonal antibodies such as cetuximab. A growing body of evidence is identifying potential molecular predictors of response and toxicity. This includes tumor-related molecular markers, such as EGFR mutation and copy number, as well as germline markers such as polymorphisms in EGFR or EGFR pathway-related genes. This review focuses on the current state of knowledge of predictors of response and toxicity to EGFR inhibitors in lung cancer. C1 [Heist, Rebecca Suk; Christiani, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Heist, RS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey 7B,55 Fruit St, Boston, MA 02114 USA. EM rheist@partners.org FU NIH [R01CA92824, R01CA074386, K12 CA087723] FX No writing assistance was utilized in the production of this manuscript. NR 79 TC 41 Z9 45 U1 0 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JAN PY 2009 VL 10 IS 1 BP 59 EP 68 DI 10.2217/14622416.10.1.59 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 396BR UT WOS:000262567700012 PM 19102716 ER PT J AU Jackevicius, CA Page, RL Chow, S Dunn, SP Lee, CR Ng, TMH Rodgers, JE Vardeny, O Wiggins, BS Munger, MA AF Jackevicius, Cynthia A. Page, Robert L., II Chow, Sheryl Dunn, Steven P. Lee, Craig R. Ng, Tien M. H. Rodgers, Jo E. Vardeny, Orly Wiggins, Barbara S. Munger, Mark A. TI High-Impact Articles Related to the Management of Heart Failure: 2008 Update SO PHARMACOTHERAPY LA English DT Article DE systolic heart failure; decompensated heart failure; left ventricular systolic dysfunction; diastolic heart failure AB This compilation is part of a series of articles identifying important literature in cardiovascular pharmacotherapy. This bibliography focuses on pharmacotherapeutic management of acute decompensated and chronic heart failure and provides an update of the heart failure bibliography published in Pharmacotherapy in 2004. Most of the cited works present the results of landmark clinical studies that have shaped the management of patients with heart failure. Limited primary literature is available for some topics, thus pertinent review articles are also listed. In addition, consensus documents formed by expert panels are reviewed. This compilation may serve as a teaching tool, reference resource, or update of the literature for pharmacy clinicians, physicians, and students. C1 [Jackevicius, Cynthia A.; Chow, Sheryl] Western Univ Hlth Sci, Coll Pharm, Dept Pharm Practice & Adm, Pomona, CA 91766 USA. [Jackevicius, Cynthia A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Jackevicius, Cynthia A.] Univ Toronto, Fac Med, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Hlth Network, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Page, Robert L., II] Univ Colorado Denver, Sch Pharm, Aurora, CO USA. [Page, Robert L., II] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Dunn, Steven P.] Univ Kentucky, Coll Pharm, Dept Pharm Serv, Lexington, KY USA. [Dunn, Steven P.] Univ Kentucky, Coll Pharm, Div Cardiovasc Med, Lexington, KY USA. [Lee, Craig R.; Rodgers, Jo E.] Univ N Carolina, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA. [Ng, Tien M. H.] Univ So Calif, Sch Pharm, Los Angeles, CA USA. [Vardeny, Orly] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. [Wiggins, Barbara S.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Wiggins, Barbara S.] Univ Virginia Hlth Syst, Ctr Heart, Charlottesville, VA USA. [Munger, Mark A.] Univ Utah, Sch Pharm, Dept Pharmacotherapy, Salt Lake City, UT USA. RP Jackevicius, CA (reprint author), Western Univ Hlth Sci, Coll Pharm, Dept Pharm Practice & Adm, 309 E 2nd St, Pomona, CA 91766 USA. EM cjackevicius@westernu.edu RI Dunn, Steven/I-9480-2012; OI Lee, Craig/0000-0003-3595-5301 NR 1 TC 1 Z9 1 U1 1 U2 1 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JAN PY 2009 VL 29 IS 1 BP 82 EP 120 PG 39 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 392HS UT WOS:000262294400009 PM 19113799 ER PT J AU Barrett, LF Gendron, M Huang, YM AF Barrett, Lisa Feldman Gendron, Maria Huang, Yang-Ming TI Do discrete emotions exist? SO PHILOSOPHICAL PSYCHOLOGY LA English DT Article DE Affect; Categorization; Emotion ID AMYGDALA RESPONSES; ELDERLY ADULTS; NEUTRAL FACES; NATURAL KINDS; HABITUATION; FEARFUL; NOVELTY; YOUNG; RECOGNITION; FAMILIARITY AB In various guises (usually referred to as the "basic emotion" or "discrete emotion" approach), scientists and philosophers have long argued that certain categories of emotion are natural kinds. In a recent paper, Colombetti (2009) proposed yet another natural kind account, and in so doing, characterized and critiqued psychological constructionist approaches to emotion, including our own Conceptual Act Model. In this commentary, we briefly address three topics raised by Columbetti. First, we correct several common misperceptions about the discrete emotion approach to emotion. Second, we discuss misconceptions of our Conceptual Act Model. Finally, we briefly comment on Columbetti's Dynamical Discrete Emotion model. C1 [Barrett, Lisa Feldman; Gendron, Maria] Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. [Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Huang, Yang-Ming] Indiana Univ, Dept Psychol, Bloomington, IN 47405 USA. RP Barrett, LF (reprint author), Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. EM barretli@bc.edu OI Huang, Yang-Ming/0000-0001-5791-6325 NR 53 TC 12 Z9 12 U1 1 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0951-5089 J9 PHILOS PSYCHOL JI Philos. Psychol. PY 2009 VL 22 IS 4 BP 427 EP 437 DI 10.1080/09515080903153634 PG 11 WC Ethics; Psychology, Multidisciplinary SC Social Sciences - Other Topics; Psychology GA 554FE UT WOS:000274420100002 ER PT B AU Kihm, H Carp, SA Venugopalan, V AF Kihm, Hagyong Carp, Stefan A. Venugopalan, Vasan BE Wang, LV TI Interferometry-Based Optoacoustic Tomography SO PHOTOACCOUSTIC IMAGING AND SPECTROSCOPY SE Optical Science and Engineering-CRC LA English DT Article; Book Chapter ID INDUCED THERMOELASTIC DEFORMATION; FABRY-PEROT-INTERFEROMETER; FIBER-TIP SENSOR; BIOLOGICAL TISSUE; IMAGE-RECONSTRUCTION; ULTRASOUND DETECTION; HETERODYNE-DETECTION; OPTICAL-DETECTION; LASER-ABLATION; TURBID MEDIA C1 [Kihm, Hagyong] Korea Reseach Inst Stand & Sci, Space Opt Res Ctr, Taejon, South Korea. [Venugopalan, Vasan] Univ Calif Irvine, Beckman Laser Inst & Med Clin, Irvine, CA 92715 USA. [Venugopalan, Vasan] Univ Calif Irvine, Dept Chem Engn & Mat Sci, Irvine, CA 92715 USA. [Carp, Stefan A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Carp, Stefan A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Kihm, H (reprint author), Korea Reseach Inst Stand & Sci, Space Opt Res Ctr, Taejon, South Korea. NR 58 TC 0 Z9 0 U1 0 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4200-5991-5 J9 OPT SCI ENG-CRC PY 2009 VL 144 BP 239 EP 250 D2 10.1201/9781420059922 PG 12 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BJV10 UT WOS:000267232100019 ER PT J AU Rubio, N Fleury, SP Redmond, RW AF Rubio, Noemi Fleury, Sean P. Redmond, Robert W. TI Spatial and temporal dynamics of in vitro photodynamic cell killing: extracellular hydrogen peroxide mediates neighbouring cell death SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Article ID SINGLET OXYGEN; FLUENCE RATE; SUBCELLULAR-LOCALIZATION; NADPH OXIDASE; MICRONUCLEUS FORMATION; CANCER-CELLS; THERAPY; PHOTOSENSITIZERS; APOPTOSIS; PHOTOTOXICITY AB Photodynamic killing of a cell population is generally considered to result from direct effects that occur in each cell. In some scenarios this may be an over-simplification and the potential for cell-cell signaling processes to contribute to the response of a population to photodynamic stress is addressed in this paper. Photodynamic killing of EMT6 cells in culture was studied in time and space using computerized time-lapse microscopy. The rate of cell killing was dependent on the fluence with both rapid and slower processes evident, the proportion of the former increasing with fluence. The spatial distribution of cell death was non-random and for the slow cell killing process was found to occur preferentially in the vicinity of dead or dying cells, suggesting a local signaling process. An inhibitory effect of extracellular catalase indicated the involvement of hydrogen peroxide in the spread of cell death and NADPH oxidase was determined as the principal source of hydrogen peroxide. This cell signaling pathway was observed for membrane-bound and mitochondrial photosensitizers but not for a nuclear photosensitizer. These secondary cell signalling pathways extend the oxidative damage to cells in space and time. C1 [Rubio, Noemi; Fleury, Sean P.; Redmond, Robert W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Redmond, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM Redmond@helix.mgh.harvard.edu FU NIH-POI [CA095227]; BBSI HST-MGH Summer Institute for Biomedical Optics [NSF EEC-0609299] FX The authors are grateful to Chelvi Rajadurai for excellent technical help, and to Drs Hyle Park, Irene Kochevar, Howard Liber, Kevin Prise and Kathy Held for valuable discussions. This work was funded by NIH-POI CA095227. S. F. is also grateful for the award of a studentship from the BBSI HST-MGH Summer Institute for Biomedical Optics. (NSF EEC-0609299). NR 50 TC 23 Z9 23 U1 0 U2 6 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PY 2009 VL 8 IS 4 BP 457 EP 464 DI 10.1039/b815343d PG 8 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 426ZI UT WOS:000264747000004 PM 19337658 ER PT J AU George, S Hamblin, MR Kishen, A AF George, Saji Hamblin, Michael R. Kishen, Anil TI Uptake pathways of anionic and cationic photosensitizers into bacteria SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Article ID GRAM-NEGATIVE BACTERIA; METHYLENE-BLUE; PHOTODYNAMIC THERAPY; ENTEROCOCCUS-FAECALIS; OUTER-MEMBRANE; IN-VITRO; ESCHERICHIA-COLI; ANTIMICROBIAL PHOTOINACTIVATION; PHOTOCHEMICAL PROPERTIES; BIOFILM FORMATION AB The effect of divalent cations (calcium and magnesium) and a permeabilizing agent (EDTA) on the uptake of a cationic photosensitizer (PS), methylene blue (MB), and two anionic PSs, rose bengal (RB) and indocyanine green (ICG), by Gram-positive Enterococcus faecalis and Gram-negative Actinobacillus actinomycetemcomitans was examined. The possible roles of multidrug efflux pumps and protein transporters in photosensitizer uptake were assessed in E. faecalis cells by studies using an efflux pump inhibitor (verapamil) and trypsin treatment respectively. Divalent cations enhanced the uptake and photodynamic inactivation potential of both RB and ICG in E. faecalis and A. actinomycetemcomitans, while they decreased the uptake and bacterial killing by MB. Verapamil increased the uptake of RB (possibly due to efflux pump inhibition), whereas trypsin treatment resulted in significant decrease in RB and ICG uptake. The results suggested that the uptake of anionic PSs by bacterial cells may be mediated through a combination of electrostatic charge interaction and by protein transporters, while the uptake of cationic PSs, as previously reported, is mediated by electrostatic interactions and self promoted uptake pathways. C1 [George, Saji; Kishen, Anil] Natl Univ Singapore, Fac Dent, Singapore 119074, Singapore. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Cambridge, MA 02138 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP George, S (reprint author), Univ Calif Los Angeles, Div Nanomed, 10833 Le Conte Ave,13-254 Factor, Los Angeles, CA 90095 USA. EM rsdak@nus.edu.sg OI George, Saji/0000-0002-8807-0737; Hamblin, Michael/0000-0001-6431-4605 FU NUS-Academic Research [R-224-000-024-112]; NIH [AI050875] FX The project was supported by NUS-Academic Research Funding R-224-000-024-112. M. R. Hamblin was supported by NIH Grant AI050875. NR 46 TC 57 Z9 61 U1 2 U2 31 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PY 2009 VL 8 IS 6 BP 788 EP 795 DI 10.1039/b809624d PG 8 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 453GG UT WOS:000266598000007 PM 19492106 ER PT J AU Verma, S Sallum, UW Athar, H Rosenblum, L Foley, JW Hasan, T AF Verma, Sarika Sallum, Ulysses W. Athar, Humra Rosenblum, Lauren Foley, James W. Hasan, Tayyaba TI Antimicrobial Photodynamic Efficacy of Side-chain Functionalized Benzo[a]phenothiazinium Dyes SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID INTRACOLONIC VANCOMYCIN; MICROBIAL INFECTIONS; THERAPY; PHOTOSENSITIZERS; BENZOPHENOTHIAZINE; INACTIVATION; STANDARD; COLITIS; YIELD; RED AB 5-(Ethylamino)-9-diethylaminobenzo[a]phenothiazinium chloride (EtNBS) is a photosensitizer (PS) with broad antimicrobial photodynamic activity. The objective of this study was to determine the antimicrobial photodynamic effect of side chain/end group modifications of EtNBS on two representative bacterial Gram-type-specific strains. Two EtNBS derivatives were synthesized, each functionalized with a different side-chain end-group, alcohol or carboxylic acid. In solution, both exhibited photochemical properties consistent with those of the EtNBS parent molecule. In vitro photodynamic therapy experiments revealed an initial Gram-type-specificity with two representative strains; both derivatives were phototoxic to Staphylococcus aureus 29213 but the carboxylic acid derivative was nontoxic to Escherichia coli 25922. This difference in photodynamic efficacy was not due to a difference in the binding of the two molecules to the bacteria as the amount of both derivatives bound by bacteria was identical. Interestingly, the carboxylic acid derivative produced no fluorescence emission when observed in cultures of E. coli via fluorescence microscopy. These early findings suggest that the addition of small functional groups could achieve Gram-type-specific phototoxicity through altering the photodynamic activity of PSs and deserve further exploration in a larger number of representative strains of each Gram type. C1 [Verma, Sarika; Sallum, Ulysses W.; Athar, Humra; Rosenblum, Lauren; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Verma, Sarika; Sallum, Ulysses W.; Athar, Humra; Rosenblum, Lauren; Hasan, Tayyaba] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Foley, James W.] Rowland Inst Harvard, Cambridge, MA USA. RP Hasan, T (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM thasan@partners.org FU U.S. Air Force; Medical Free Electron Laser Program (MFEL) [FA9550-04-1-0079] FX We would like to acknowledge Gregory Watt, PhD, for his helpful discussions during the initial synthetic design and Xiang Zheng, PhD, for the review of this work and insightful critiques. This work was funded by the U.S. Air Force, Medical Free Electron Laser Program (MFEL) (grant FA9550-04-1-0079). NR 31 TC 20 Z9 20 U1 1 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JAN-FEB PY 2009 VL 85 IS 1 BP 111 EP 118 DI 10.1111/j.1751-1097.2008.00403.x PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 394XP UT WOS:000262486800014 PM 18657053 ER PT B AU Kahle, KT Staley, KJ AF Kahle, Kristopher T. Staley, Kevin J. BE AlvarezLeefmans, FJ Delpire, E TI Cation-chloride Cotransporters as Pharmacological Targets in the Treatment of Epilepsy SO PHYSIOLOGY AND PATHOLOGY OF CHLORIDE TRANSPORTERS AND CHANNELS IN THE NERVOUS SYSTEM: FROM MOLECULES TO DISEASES LA English DT Article; Book Chapter ID K+-CL-COTRANSPORTER; TEMPORAL-LOBE EPILEPSY; NEURONAL-SPECIFIC ISOFORM; NEONATAL SEIZURES; DEVELOPING BRAIN; INTRACELLULAR CHLORIDE; MOLECULAR PHYSIOLOGY; EXCITATORY ACTIONS; HIPPOCAMPAL SLICE; IN-VITRO C1 [Kahle, Kristopher T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Kahle, Kristopher T.; Staley, Kevin J.] Harvard Univ, Sch Med, Boston, MA USA. [Staley, Kevin J.] Massachusetts Gen Hosp, Div Pediat Neurol, Boston, MA 02114 USA. RP Kahle, KT (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. NR 100 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092203-4; 978-0-12-374373-2 PY 2009 BP 489 EP 500 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA BA4GH UT WOS:000335644100025 ER PT J AU Storey, RF Thornton, SM Lawrance, R Husted, S Wickens, M Emanuelsson, H Cannon, CP Heptinstall, S Armstrong, M AF Storey, Robert F. Thornton, S. Melissa Lawrance, Rachael Husted, Steen Wickens, Mark Emanuelsson, Hakan Cannon, Christopher P. Heptinstall, Stan Armstrong, Martin TI Ticagrelor yields consistent dose-dependent inhibition of ADP-induced platelet aggregation in patients with atherosclerotic disease regardless of genotypic variations in P2RY12, P2RY1, and ITGB3 SO PLATELETS LA English DT Article DE Coronary artery disease; platelets; platelet aggregation inhibitor; P2 receptor ID ACUTE CORONARY SYNDROME; ST-SEGMENT ELEVATION; MYOCARDIAL-INFARCTION; P2Y(12) RECEPTOR; CLOPIDOGREL THERAPY; SEQUENCE VARIATIONS; GENE POLYMORPHISM; STENT THROMBOSIS; HEALTHY-SUBJECTS; REACTIVITY AB The platelet P2Y12 receptor is the target of clopidogrel therapy, which has been shown to reduce thromboembolic complications of atherosclerotic disease but has limitations in terms of variability of response and irreversibility of effect. This receptor is also a target for ticagrelor (AZD6140), the first reversibly binding oral P2Y12 receptor antagonist that does not require metabolic activation and yields more consistent inhibition of platelet aggregation than clopidogrel therapy. Single nucleotide polymorphisms (SNPs) have been described in the gene for this receptor (P2RY12), some of which have been associated with variability in platelet reactivity. SNPs in P2RY1 and ITGB3 have also been reported by some groups to affect platelet reactivity to adenosine diphosphate (ADP). We assessed whether SNPs in these genes influenced the pharmacodynamic response to ticagrelor in patients enrolled in both the DISPERSE study (stable atherosclerotic disease) and the DISPERSE2 study (non-ST-segment elevation acute coronary syndromes). Platelet aggregation data (at baseline and 4 weeks) and DNA samples from clopidogrel-naive Caucasian patients treated with ticagrelor were available for 151 patients. Seventy four SNPs within three genes were genotyped. After adjustment for multiple comparisons, none of these SNPs were found to significantly influence inhibition of ADP-induced platelet aggregation by ticagrelor. C1 [Storey, Robert F.] Univ Sheffield, Cardiovasc Res Unit, Sch Med & Biomed Sci, Sheffield S10 2RX, S Yorkshire, England. [Thornton, S. Melissa; Lawrance, Rachael; Armstrong, Martin] AstraZeneca, Macclesfield, Cheshire, England. [Husted, Steen] Arhus Univ Hosp, Dept Med & Cardiol, Aarhus, Denmark. [Emanuelsson, Hakan] AstraZeneca R&D, Molndal, Sweden. [Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Cannon, Christopher P.] Harvard Univ, Sch Med, Boston, MA USA. [Heptinstall, Stan] Univ Nottingham, Dept Cardiovasc Med, Nottingham NG7 2RD, England. RP Storey, RF (reprint author), Univ Sheffield, Cardiovasc Res Unit, Sch Med & Biomed Sci, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England. EM r.f.storey@sheffield.ac.uk FU AstraZeneca LP FX Declaration of interest: All authors have either received research grant support and/or honoraria from, or are employees of, AstraZeneca. The authors alone are responsible for the content and writing of the paper. NR 32 TC 33 Z9 38 U1 1 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0953-7104 J9 PLATELETS JI Platelets PY 2009 VL 20 IS 5 BP 341 EP 348 AR PII 913453457 DI 10.1080/09537100903075324 PG 8 WC Cell Biology; Hematology SC Cell Biology; Hematology GA 475VU UT WOS:000268392100007 PM 19637098 ER PT J AU Taranda, J Maison, SF Ballestero, JA Katz, E Savino, J Vetter, DE Boulter, J Liberman, MC Fuchs, PA Elgoyhen, AB AF Taranda, Julian Maison, Stephane F. Ballestero, Jimena A. Katz, Eleonora Savino, Jessica Vetter, Douglas E. Boulter, Jim Liberman, M. Charles Fuchs, Paul A. Belen Elgoyhen, A. TI A Point Mutation in the Hair Cell Nicotinic Cholinergic Receptor Prolongs Cochlear Inhibition and Enhances Noise Protection SO PLOS BIOLOGY LA English DT Article ID CROSSED OLIVOCOCHLEAR BUNDLE; TEMPORARY THRESHOLD SHIFTS; ACETYLCHOLINE-RECEPTOR; ELECTRICAL-STIMULATION; SYNAPTIC-TRANSMISSION; AUDITORY-SENSITIVITY; ACOUSTIC INJURY; NERVE RESPONSE; EFFERENT; ALPHA-9 AB The transduction of sound in the auditory periphery, the cochlea, is inhibited by efferent cholinergic neurons projecting from the brainstem and synapsing directly on mechanosensory hair cells. One fundamental question in auditory neuroscience is what role(s) this feedback plays in our ability to hear. In the present study, we have engineered a genetically modified mouse model in which the magnitude and duration of efferent cholinergic effects are increased, and we assess the consequences of this manipulation on cochlear function. We generated the Chrna9L9'T line of knockin mice with a threonine for leucine change (L9'T) at position 99 of the second transmembrane domain of the alpha 9 nicotinic cholinergic subunit, rendering alpha 9-containing receptors that were hypersensitive to acetylcholine and had slower desensitization kinetics. The Chrna9L9'T allele produced a 3-fold prolongation of efferent synaptic currents in vitro. In vivo, Chrna9L9'T mice had baseline elevation of cochlear thresholds and efferent-mediated inhibition of cochlear responses was dramatically enhanced and lengthened: both effects were reversed by strychnine blockade of the alpha 9 alpha 10 hair cell nicotinic receptor. Importantly, relative to their wild-type littermates, Chrna(9L9'T/L9'T) mice showed less permanent hearing loss following exposure to intense noise. Thus, a point mutation designed to alter alpha 9 alpha 10 receptor gating has provided an animal model in which not only is efferent inhibition more powerful, but also one in which sound-induced hearing loss can be restrained, indicating the ability of efferent feedback to ameliorate sound trauma. C1 [Taranda, Julian; Ballestero, Jimena A.; Katz, Eleonora; Savino, Jessica; Belen Elgoyhen, A.] Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol, Buenos Aires, DF, Argentina. [Taranda, Julian; Vetter, Douglas E.] Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. [Maison, Stephane F.; Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Maison, Stephane F.; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Boulter, Jim] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Hatos Res Ctr Neuropharmacol, Brain Res Inst, Los Angeles, CA 90024 USA. [Boulter, Jim] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA. [Fuchs, Paul A.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. [Fuchs, Paul A.] Johns Hopkins Univ, Sch Med, Ctr Hearing & Balance, Baltimore, MD USA. [Belen Elgoyhen, A.] Univ Buenos Aires, Fac Med, Dept Farmacol, Buenos Aires, DF, Argentina. RP Elgoyhen, AB (reprint author), Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol, Buenos Aires, DF, Argentina. EM elgoyhen@dna.uba.ar FU National Institutes of Deafness and other Communication Disorders (NIDCD) [R01DC001508, R01 DC00188, P30 DC05209, R01DC006258]; University of Buenos Aires (Argentina) FX Funding. This work was supported by the National Institutes of Deafness and other Communication Disorders (NIDCD) Grant R01DC001508 to PAF and ABE, an International Research Scholar Grant from the Howard Hughes Medical Institute, the National Organization for Hearing Research, the Tinnitus Research Initiative, a research grant from ANPCyT (Argentina), and a grant from the University of Buenos Aires (Argentina) to ABE; NIDCD R01 DC00188 and NIDCD P30 DC05209 went to MCL and NIDCD R01DC006258 to DEV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 37 Z9 38 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD JAN PY 2009 VL 7 IS 1 BP 71 EP 83 AR e1000018 DI 10.1371/journal.pbio.1000018 PG 13 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 399PE UT WOS:000262811000010 PM 19166271 ER PT J AU Vasilyev, A Liu, Y Mudumana, S Mangos, S Lam, PY Majumdar, A Zhao, JH Poon, KL Kondrychyn, I Korzh, V Drummond, IA AF Vasilyev, Aleksandr Liu, Yan Mudumana, Sudha Mangos, Steve Lam, Pui-Ying Majumdar, Arindam Zhao, Jinhua Poon, Kar-Lai Kondrychyn, Igor Korzh, Vladimir Drummond, Iain A. TI Collective Cell Migration Drives Morphogenesis of the Kidney Nephron SO PLOS BIOLOGY LA English DT Article ID FLUID SHEAR-STRESS; ENDOTHELIAL-CELLS; ZEBRAFISH PRONEPHROS; ACTIVATION; EMBRYO; DIFFERENTIATION; LOCALIZATION; MECHANISMS; EXPRESSION; DROSOPHILA AB Tissue organization in epithelial organs is achieved during development by the combined processes of cell differentiation and morphogenetic cell movements. In the kidney, the nephron is the functional organ unit. Each nephron is an epithelial tubule that is subdivided into discrete segments with specific transport functions. Little is known about how nephron segments are defined or how segments acquire their distinctive morphology and cell shape. Using live, in vivo cell imaging of the forming zebrafish pronephric nephron, we found that the migration of fully differentiated epithelial cells accounts for both the final position of nephron segment boundaries and the characteristic convolution of the proximal tubule. Pronephric cells maintain adherens junctions and polarized apical brush border membranes while they migrate collectively. Individual tubule cells exhibit basal membrane protrusions in the direction of movement and appear to establish transient, phosphorylated Focal Adhesion Kinase-positive adhesions to the basement membrane. Cell migration continued in the presence of camptothecin, indicating that cell division does not drive migration. Lengthening of the nephron was, however, accompanied by an increase in tubule cell number, specifically in the most distal, ret1-positive nephron segment. The initiation of cell migration coincided with the onset of fluid flow in the pronephros. Complete blockade of pronephric fluid flow prevented cell migration and proximal nephron convolution. Selective blockade of proximal, filtration-driven fluid flow shifted the position of tubule convolution distally and revealed a role for cilia-driven fluid flow in persistent migration of distal nephron cells. We conclude that nephron morphogenesis is driven by fluid flow-dependent, collective epithelial cell migration within the confines of the tubule basement membrane. Our results establish intimate links between nephron function, fluid flow, and morphogenesis. C1 [Vasilyev, Aleksandr; Liu, Yan; Mudumana, Sudha; Mangos, Steve; Lam, Pui-Ying; Majumdar, Arindam; Zhao, Jinhua; Drummond, Iain A.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA. [Poon, Kar-Lai; Kondrychyn, Igor; Korzh, Vladimir] Inst Cell & Mol Biol, Singapore, Singapore. RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA. EM Idrummon@receptor.mgh.harvard.edu RI Kondrychyn, Igor/A-9468-2010; Korzh, Vladimir/H-1596-2011; ASTAR, IMCB/E-2320-2012; Kondrychyn, Igor/C-2621-2016 OI Korzh, Vladimir/0000-0002-6580-7986; Kondrychyn, Igor/0000-0002-2268-7291 FU National Institutes of Health [DK53093, DK071041, DK070263, T32-CA00916] FX Funding. This work was supported by National Institutes of Health grants DK53093, DK071041, and DK070263 to IAD and T32-CA00916 to AV. NR 48 TC 89 Z9 91 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD JAN PY 2009 VL 7 IS 1 BP 101 EP 114 AR e1000009 DI 10.1371/journal.pbio.1000009 PG 14 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 399PE UT WOS:000262811000012 PM 19127979 ER PT J AU Deo, RC Reich, D Tandon, A Akylbekova, E Patterson, N Waliszewska, A Kathiresan, S Sarpong, D Taylor, HA Wilson, JG AF Deo, Rahul C. Reich, David Tandon, Arti Akylbekova, Ermeg Patterson, Nick Waliszewska, Alicja Kathiresan, Sekar Sarpong, Daniel Taylor, Herman A., Jr. Wilson, James G. TI Genetic Differences between the Determinants of Lipid Profile Phenotypes in African and European Americans: The Jackson Heart Study SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; LIPOPROTEIN-LIPASE; PROSTATE-CANCER; ADMIXTURE; DISEASE; CHOLESTEROL; THERAPY; LOCUS; MUTATION; RECEPTOR AB Genome-wide association analysis in populations of European descent has recently found more than a hundred genetic variants affecting risk for common disease. An open question, however, is how relevant the variants discovered in Europeans are to other populations. To address this problem for cardiovascular phenotypes, we studied a cohort of 4,464 African Americans from the Jackson Heart Study (JHS), in whom we genotyped both a panel of 12 recently discovered genetic variants known to predict lipid profile levels in Europeans and a panel of up to 1,447 ancestry informative markers allowing us to determine the African ancestry proportion of each individual at each position in the genome. Focusing on lipid profiles-HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and triglycerides (TG)-we identified the lipoprotein lipase (LPL) locus as harboring variants that account for interethnic variation in HDL-C and TG. In particular, we identified a novel common variant within LPL that is strongly associated with TG (p = 2.7x10(-6)) and explains nearly 1% of the variability in this phenotype, the most of any variant in African Americans to date. Strikingly, the extensively studied "gain-of-function" S447X mutation at LPL, which has been hypothesized to be the major determinant of the LPL-TG genetic association and is in trials for human gene therapy, has a significantly diminished strength of biological effect when it is found on a background of African rather than European ancestry. These results suggest that there are other, yet undiscovered variants at the locus that are truly causal (and are in linkage disequilibrium with S447X) or that work synergistically with S447X to modulate TG levels. Finally, we find systematically lower effect sizes for the 12 risk variants discovered in European populations on the African local ancestry background in JHS, highlighting the need for caution in the use of genetic variants for risk assessment across different populations. C1 [Deo, Rahul C.; Reich, David; Tandon, Arti; Patterson, Nick] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Deo, Rahul C.; Kathiresan, Sekar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Deo, Rahul C.; Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Reich, David; Patterson, Nick; Waliszewska, Alicja; Kathiresan, Sekar] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Akylbekova, Ermeg; Taylor, Herman A., Jr.; Wilson, James G.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Akylbekova, Ermeg; Sarpong, Daniel; Taylor, Herman A., Jr.] Jackson State Univ, Jackson, MS USA. [Taylor, Herman A., Jr.] Tougaloo Coll, Tougaloo, MS USA. [Wilson, James G.] GV Sonny Montgomery Vet Affairs Med Ctr, Jackson, MS USA. RP Deo, RC (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM rdeo@partners.org; james.wilson3@med.va.gov FU National Heart, Lung, and Blood Institute [R01-HL-084107, N01-HC95170, N01-HC-95171, N01-HC-95172]; National Center on Minority Health and Health Disparities; National Center for Research Resources [U54 RR020278]; Burroughs Wellcome Career Development Award in the Biomedical Sciences; [U01-HG004168] FX Research support for JHS studies was provided by R01-HL-084107 (JGW) from the National Heart, Lung, and Blood Institute and contracts N01-HC95170, N01-HC-95171, and N01-HC-95172 from the National Heart, Lung, and Blood Institute and the National Center on Minority Health and Health Disparities. The Broad Institute Center for Genotyping and Analysis, which performed the genotyping for these studies, is supported by grant U54 RR020278 from the National Center for Research Resources. DR was supported by a Burroughs Wellcome Career Development Award in the Biomedical Sciences, and methodological work was supported by grant U01-HG004168 to DR and NP. The authors are solely responsible for all aspects of this research and manuscript preparation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This manuscript has been approved by the Jackson Heart Study and NHLBI. NR 40 TC 56 Z9 59 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2009 VL 5 IS 1 AR e1000342 DI 10.1371/journal.pgen.1000342 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 447VW UT WOS:000266221100024 PM 19148283 ER PT J AU Maier, LM Lowe, CE Cooper, J Downes, K Anderson, DE Severson, C Clark, PM Healy, B Walker, N Aubin, C Oksenberg, JR Hauser, SL Compston, A Sawcer, S De Jager, PL Wicker, LS Todd, JA Hafler, DA AF Maier, Lisa M. Lowe, Christopher E. Cooper, Jason Downes, Kate Anderson, David E. Severson, Christopher Clark, Pamela M. Healy, Brian Walker, Neil Aubin, Cristin Oksenberg, Jorge R. Hauser, Stephen L. Compston, Alistair Sawcer, Stephen De Jager, Philip L. Wicker, Linda S. Todd, John A. Hafler, David A. CA Int Multiple Sclerosis Genetics Co TI IL2RA Genetic Heterogeneity in Multiple Sclerosis and Type 1 Diabetes Susceptibility and Soluble Interleukin-2 Receptor Production SO PLOS GENETICS LA English DT Article ID TYROSINE-PHOSPHATASE PTPN22; GENOME-WIDE ASSOCIATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; AUTOIMMUNE-DISEASE; RHEUMATOID-ARTHRITIS; RECEPTOR LEVELS; CROHNS-DISEASE; 620W ALLELE; LARGE-SCALE; REGION AB Multiple sclerosis (MS) and type 1 diabetes (T1D) are organ-specific autoimmune disorders with significant heritability, part of which is conferred by shared alleles. For decades, the Human Leukocyte Antigen (HLA) complex was the only known susceptibility locus for both T1D and MS, but loci outside the HLA complex harboring risk alleles have been discovered and fully replicated. A genome-wide association scan for MS risk genes and candidate gene association studies have previously described the IL2RA gene region as a shared autoimmune locus. In order to investigate whether autoimmunity risk at IL2RA was due to distinct or shared alleles, we performed a genetic association study of three IL2RA variants in a DNA collection of up to 9,407 healthy controls, 2,420 MS, and 6,425 T1D subjects as well as 1,303 MS parent/child trios. Here, we report "allelic heterogeneity" at the IL2RA region between MS and T1D. We observe an allele associated with susceptibility to one disease and risk to the other, an allele that confers susceptibility to both diseases, and an allele that may only confer susceptibility to T1D. In addition, we tested the levels of soluble interleukin-2 receptor (sIL-2RA) in the serum from up to 69 healthy control subjects, 285 MS, and 1,317 T1D subjects. We demonstrate that multiple variants independently correlate with sIL-2RA levels. C1 [Maier, Lisa M.; Anderson, David E.; Severson, Christopher; De Jager, Philip L.; Hafler, David A.] Brigham & Womens Hosp, Ctr Neurol Dis, Div Mol Immunol, Boston, MA 02115 USA. [De Jager, Philip L.] Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Boston, MA USA. [Maier, Lisa M.; Aubin, Cristin; De Jager, Philip L.; Hafler, David A.] MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. [Maier, Lisa M.; Aubin, Cristin; De Jager, Philip L.; Hafler, David A.] Harvard Univ, Cambridge, MA 02138 USA. [Lowe, Christopher E.; Cooper, Jason; Downes, Kate; Clark, Pamela M.; Walker, Neil; Wicker, Linda S.; Todd, John A.] Univ Cambridge, Juvenile Diabet Res Fdn, Wellcome Trust Diabet & Inflammat Lab, Cambridge Inst Med Res, Cambridge, England. [Healy, Brian] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Healy, Brian] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Oksenberg, Jorge R.; Hauser, Stephen L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Compston, Alistair; Sawcer, Stephen] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Sch Clin Med, Cambridge CB2 2QQ, England. RP Maier, LM (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, Div Mol Immunol, Boston, MA 02115 USA. EM hafler@broad.mit.edu RI Wicker, Linda/F-7384-2010; Hauser, Stephen/J-2978-2016; OI Walker, Neil/0000-0001-9796-7688 FU Juvenile Diabetes Research Foundation (JDRF) International; Wellcome Trust; National Multiple Sclerosis Society (NMSS); National Institute for Health Research Cambridge Biomedical Research Centre; National Institutes of Health [P01 AI39571]; Wellcome Trust Strategic Award [079895]; JDRF Postdoctoral Fellowship; American Cancer Society; NIH [NS049477]; Harry Weaver Neuroscience Scholar award; Jacob Javits Merit Awar [NS2427]; National Institute of Neurological Disorders and Stroke FX This work was funded by the Juvenile Diabetes Research Foundation (JDRF) International, the Wellcome Trust, the National Multiple Sclerosis Society (NMSS), the National Institute for Health Research Cambridge Biomedical Research Centre, and the National Institutes of Health (P01 AI39571). The Cambridge Institute for Medical Research is the recipient of a Wellcome Trust Strategic Award (079895). Further supported by a JDRF Postdoctoral Fellowship (LMM), a grant by the American Cancer Society (DEA), an NIH grant (to The IMSGC, NS049477), a Harry Weaver Neuroscience Scholar award by the NMSS (PLD), and a Jacob Javits Merit Award (NS2427, to DAH) from the National Institute of Neurological Disorders and Stroke. LSW is a Wellcome Trust Principal Research Fellow. NR 34 TC 125 Z9 127 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2009 VL 5 IS 1 AR e1000322 DI 10.1371/journal.pgen.1000322 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 447VW UT WOS:000266221100005 PM 19119414 ER PT J AU Ware, NC Idoko, J Kaaya, S Biraro, IA Wyatt, MA Agbaji, O Chalamilla, G Bangsberg, DR AF Ware, Norma C. Idoko, John Kaaya, Sylvia Biraro, Irene Andia Wyatt, Monique A. Agbaji, Oche Chalamilla, Guerino Bangsberg, David R. TI Explaining Adherence Success in Sub-Saharan Africa: An Ethnographic Study SO PLOS MEDICINE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; FIXED-DOSE COMBINATION; HIV-INFECTED ADULTS; SOUTH-AFRICA; HIV-1-INFECTED ADULTS; SOCIAL RELATIONSHIPS; RANDOMIZED-TRIAL; HEALTH-WORKERS; UGANDA; AIDS AB Background Individuals living with HIV/AIDS in sub-Saharan Africa generally take more than 90% of prescribed doses of antiretroviral therapy (ART). This number exceeds the levels of adherence observed in North America and dispels early scale-up concerns that adherence would be inadequate in settings of extreme poverty. This paper offers an explanation and theoretical model of ART adherence success based on the results of an ethnographic study in three sub-Saharan African countries. Methods and Findings Determinants of ART adherence for HIV-infected persons in sub-Saharan Africa were examined with ethnographic research methods. 414 in-person interviews were carried out with 252 persons taking ART, their treatment partners, and health care professionals at HIV treatment sites in Jos, Nigeria; Dar es Salaam, Tanzania; and Mbarara, Uganda. 136 field observations of clinic activities were also conducted. Data were examined using category construction and interpretive approaches to analysis. Findings indicate that individuals taking ART routinely overcome economic obstacles to ART adherence through a number of deliberate strategies aimed at prioritizing adherence: borrowing and "begging'' transport funds, making "impossible choices'' to allocate resources in favor of treatment, and "doing without.'' Prioritization of adherence is accomplished through resources and help made available by treatment partners, other family members and friends, and health care providers. Helpers expect adherence and make their expectations known, creating a responsibility on the part of patients to adhere. Patients adhere to promote good will on the part of helpers, thereby ensuring help will be available when future needs arise. Conclusion Adherence success in sub-Saharan Africa can be explained as a means of fulfilling social responsibilities and thus preserving social capital in essential relationships. C1 [Ware, Norma C.; Wyatt, Monique A.; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Idoko, John; Agbaji, Oche] Univ Jos, Jos, Nigeria. [Kaaya, Sylvia] Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania. [Biraro, Irene Andia] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Chalamilla, Guerino] Harvard Univ, Sch Publ Hlth, HIV AIDS Care & Treatment Program, Muhimbili Univ Dar Salaam City Council, Dar Es Salaam, Tanzania. [Chalamilla, Guerino] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bangsberg, David R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bangsberg, David R.] Harvard Initiat Global Hlth, Cambridge, MA USA. RP Ware, NC (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM norma_ware@hms.harvard.edu FU U.S. National Institute of Mental Health [R21 MH077539, MH54907]; Harvard University Program on AIDS; National Institute of Alcohol and Alcoholism [K-24 AA 015287]; NIMH [MH54907] FX This study was supported by grants from the U.S. National Institute of Mental Health (NIMH, R21 MH077539, MH54907) and the Harvard University Program on AIDS. DRB was funded by a grant from the National Institute of Alcohol and Alcoholism (K-24 AA 015287) and the NIMH (MH54907). The funders played no role in the design or conduct of the research, the decision to publish, or the preparation of the manuscript. NR 57 TC 165 Z9 167 U1 1 U2 21 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 JAN PY 2009 VL 6 IS 1 BP 39 EP 47 AR e1000011 DI 10.1371/journal.pmed.1000011 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 399PF UT WOS:000262811100012 PM 19175285 ER PT J AU Hamirally, S Kamil, JP Ndassa-Colday, YM Lin, AJ Jahng, WJ Baek, MC Noton, S Silva, LA Simpson-Holley, M Knipe, DM Golan, DE Marto, JA Coen, DM AF Hamirally, Sofia Kamil, Jeremy P. Ndassa-Colday, Yasmine M. Lin, Alison J. Jahng, Wan Jin Baek, Moon-Chang Noton, Sarah Silva, Laurie A. Simpson-Holley, Martha Knipe, David M. Golan, David E. Marto, Jarrod A. Coen, Donald M. TI Viral Mimicry of Cdc2/Cyclin-Dependent Kinase 1 Mediates Disruption of Nuclear Lamina during Human Cytomegalovirus Nuclear Egress SO PLOS PATHOGENS LA English DT Article ID UL97 PROTEIN-KINASE; A-TYPE LAMINS; CELL-CYCLE; PHOSPHORYLATION SITES; RETINOBLASTOMA PROTEIN; MUTATIONAL ANALYSIS; MEMBRANE PROTEIN; CDC2 KINASE; VIRUS; INFECTION AB The nuclear lamina is a major obstacle encountered by herpesvirus nucleocapsids in their passage from the nucleus to the cytoplasm (nuclear egress). We found that the human cytomegalovirus (HCMV)-encoded protein kinase UL97, which is required for efficient nuclear egress, phosphorylates the nuclear lamina component lamin A/C in vitro on sites targeted by Cdc2/cyclin-dependent kinase 1, the enzyme that is responsible for breaking down the nuclear lamina during mitosis. Quantitative mass spectrometry analyses, comparing lamin A/C isolated from cells infected with viruses either expressing or lacking UL97 activity, revealed UL97-dependent phosphorylation of lamin A/C on the serine at residue 22 (Ser 22). Transient treatment of HCMV-infected cells with maribavir, an inhibitor of UL97 kinase activity, reduced lamin A/C phosphorylation by approximately 50%, consistent with UL97 directly phosphorylating lamin A/C during HCMV replication. Phosphorylation of lamin A/C during viral replication was accompanied by changes in the shape of the nucleus, as well as thinning, invaginations, and discrete breaks in the nuclear lamina, all of which required UL97 activity. As Ser 22 is a phosphorylation site of particularly strong relevance for lamin A/C disassembly, our data support a model wherein viral mimicry of a mitotic host cell kinase activity promotes nuclear egress while accommodating viral arrest of the cell cycle. C1 [Hamirally, Sofia; Kamil, Jeremy P.; Ndassa-Colday, Yasmine M.; Lin, Alison J.; Jahng, Wan Jin; Baek, Moon-Chang; Noton, Sarah; Silva, Laurie A.; Golan, David E.; Marto, Jarrod A.; Coen, Donald M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Ndassa-Colday, Yasmine M.; Marto, Jarrod A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lin, Alison J.; Knipe, David M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Simpson-Holley, Martha] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Golan, David E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. RP Hamirally, S (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM don_coen@hms.harvard.edu OI Kamil, Jeremy/0000-0001-8422-7656 FU NIH [RO1 AI026077, RO1 HL032852, RO1 AI063106, T32 AI07245]; Dana- Farber Cancer Institute; Korean Science and Engineering Foundation; HHMI predoctoral fellowship FX This work was supported in part by NIH grants RO1 AI026077 to D. M. C, RO1 HL032852 to D. E. G., RO1 AI063106 to D. M. K., T32 AI07245 to J. P. K., funding from the Dana- Farber Cancer Institute to J. A. M., a grant from the Korean Science and Engineering Foundation to M. C. B, and a HHMI predoctoral fellowship to Y. N. C. The funders had no role in the study and no role in the manuscript. NR 59 TC 102 Z9 104 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2009 VL 5 IS 1 AR e1000275 DI 10.1371/journal.ppat.1000275 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 415IP UT WOS:000263927800014 PM 19165338 ER PT J AU Hare, S Shun, MC Gupta, SS Valkov, E Engelman, A Cherepanov, P AF Hare, Stephen Shun, Ming-Chieh Gupta, Saumya Shree Valkov, Eugene Engelman, Alan Cherepanov, Peter TI A Novel Co-Crystal Structure Affords the Design of Gain-of-Function Lentiviral Integrase Mutants in the Presence of Modified PSIP1/LEDGF/p75 SO PLOS PATHOGENS LA English DT Article ID RETROVIRAL DNA INTEGRATION; HIV-1 INTEGRASE; IN-VITRO; BINDING DOMAIN; PREINTEGRATION COMPLEXES; CONCERTED INTEGRATION; COACTIVATOR P75; ZINC-BINDING; HUMAN-CELLS; LEDGF/P75 AB Lens epithelium derived growth factor (LEDGF), also known as PC4 and SFRS1 interacting protein 1 (PSIP1) and transcriptional co-activator p75, is the cellular binding partner of lentiviral integrase (IN) proteins. LEDGF accounts for the characteristic propensity of Lentivirus to integrate within active transcription units and is required for efficient viral replication. We now present a crystal structure containing the N-terminal and catalytic core domains (NTD and CCD) of HIV-2 IN in complex with the IN binding domain (IBD) of LEDGF. The structure extends the known IN-LEDGF interface, elucidating primarily charge-charge interactions between the NTD of IN and the IBD. A constellation of acidic residues on the NTD is characteristic of lentiviral INs, and mutations of the positively charged residues on the IBD severely affect interaction with all lentiviral INs tested. We show that the novel NTD-IBD contacts are critical for stimulation of concerted lentiviral DNA integration by LEDGF in vitro and for its function during the early steps of HIV-1 replication. Furthermore, the new structural details enabled us to engineer a mutant of HIV-1 IN that primarily functions only when presented with a complementary LEDGF mutant. These findings provide structural basis for the high affinity lentiviral IN-LEDGF interaction and pave the way for development of LEDGF-based targeting technologies for gene therapy. C1 [Hare, Stephen; Gupta, Saumya Shree; Valkov, Eugene; Cherepanov, Peter] Univ London Imperial Coll Sci Technol & Med, Div Med, London, England. [Shun, Ming-Chieh; Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Hare, S (reprint author), Univ London Imperial Coll Sci Technol & Med, Div Med, St Marys Campus, London, England. EM alan_engelman@dfci.harvard.edu; p.cherepanov@imperial.ac.uk RI Valkov, Eugene/C-1554-2010; Cherepanov, Peter/F-6859-2010; OI Cherepanov, Peter/0000-0002-0634-538X; Hare, Stephen/0000-0003-2951-1595 FU NIH [AI07245, AI39394, AI70042]; UK MRC [G0600009] FX NIH training grant AI07245 to MS. NIH grants AI39394 and AI70042 to AE. UK MRC grant G0600009 to PC. NR 62 TC 95 Z9 95 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2009 VL 5 IS 1 AR e1000259 DI 10.1371/journal.ppat.1000259 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 415IP UT WOS:000263927800026 PM 19132083 ER PT J AU Sayer, NA Cifu, DX McNamee, S Chiros, CE Sigford, BJ Scoff, S Lew, HL AF Sayer, Nina A. Cifu, David X. McNamee, Shane Chiros, Christine E. Sigford, Barbara J. Scoff, Steve Lew, Henry L. TI Rehabilitation Needs of Combat-Injured Service Members Admitted to the VA Polytrauma Rehabilitation Centers: The Role of PM&R in the Care of Wounded Warriors SO PM&R LA English DT Article AB Objective: To describe the rehabilitation course of combat-injured service members who sustained polytraumatic injuries during the current wars in and around Iraq and Afghanistan. Design: Retrospective descriptive analysis. Setting: Department of Veterans Administration Polytrauma Rehabilitation Centers (PRCs). Participants: One hundred eighty-eight consecutive, acutely combat-injured service members suffering polytraumatic injuries requiring inpatient rehabilitation and being treated at PRCs between October 2001 and January 2006. Interventions: Not applicable. Main Outcome Measures: Medications prescribed, devices used, injuries and impairment information, and consultative services. Results: Ninety-three percent of the patients had sustained a traumatic brain injury (TBI) and more than half of these were incurred secondary to blast explosions. Over half of the patients had infections or surgeries prior to PRC admission that required continued medical attention during their stay. Pain and mental health issues were present in 100% and 39%, respectively, of all patients admitted and added complexity to the brain injury rehabilitation process. Common treatment needs included cognitive-behavioral interventions, pain care, assistive devices, mental health interventions for both patients and their families, and specialty consultations, in particular to ophthalmology, otolaryngology, and neurology. Conclusions: Combat-injured polytrauma patients have complex rehabilitation needs that require a high level of specialized training and skill. Physical medicine and rehabilitation specialists treating war injured service members need a high level of expertise in assessment and treatment of co-occurring pain, TBI, and stress disorders. Physiatrists are playing an important role in providing and coordinating the rehabilitation care for individuals with significant polytraumatic war injuries from the Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) conflicts. C1 [Lew, Henry L.] VA Boston Healthcare Syst, VA Med Ctr, Phys Med & Rehabil, Boston, MA 02130 USA. [Sayer, Nina A.; Chiros, Christine E.] VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Cifu, David X.; McNamee, Shane] VA Med Ctr, Richmond, VA USA. [Scoff, Steve] VA Med Ctr, Tampa, FL USA. RP Lew, HL (reprint author), VA Boston Healthcare Syst, VA Med Ctr, Phys Med & Rehabil, 150 S Huntington Ave, Boston, MA 02130 USA. EM henry.lew@va.gov RI Sayer, Nina/E-3249-2016 FU VA Health Service Research & Development (HSRD) [RRP 06-150] FX This research was supported by VA Health Service Research & Development (HSR&D) grant RRP 06-150. NR 22 TC 39 Z9 39 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD JAN PY 2009 VL 1 IS 1 BP 23 EP 28 DI 10.1016/j.pmrj.2008.10.003 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LD UT WOS:000208411000005 PM 19627869 ER PT B AU Dang, PA Kalra, MK Schweitzer, AL Dreyer, KJ AF Dang, Pragya A. Kalra, Mannudeep K. Schweitzer, Alan L. Dreyer, Keith J. BE Branstetter, BF TI Choosing a Vendor SO PRACTICAL IMAGING INFORMATICS: FOUNDATIONS AND APPLICATIONS FOR PACS PROFESSIONALS LA English DT Article; Book Chapter C1 [Dreyer, Keith J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dreyer, Keith J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Kalra, Mannudeep K.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kalra, Mannudeep K.] Massachusetts Gen Hosp, Div Thorac Imaging, Boston, MA 02114 USA. [Schweitzer, Alan L.] RCG HealthCare Consulting, 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, UNITED STATES BN 978-1-4419-0483-6 PY 2009 BP 349 EP 363 DI 10.1007/978-1-4419-0485-0_22 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BLU65 UT WOS:000271097300022 ER PT J AU Ringburg, A de Ronde, G Thomas, S van Lieshout, E Patka, P Schipper, I AF Ringburg, Akkie N. de Ronde, Gijs Thomas, Stephen H. van Lieshout, Esther M. M. Patka, Peter Schipper, Inger B. TI Validity of Helicopter Emergency Medical Services Dispatch Criteria for Traumatic Injuries: A Systematic Review SO Prehospital Emergency Care LA English DT Article DE HEMS; helicopter emergency medical services; dispatch criteria; prehospital; systematic review ID FIELD TRIAGE GUIDELINES; SCENE FLIGHTS; LIFESAVING INTERVENTIONS; PREHOSPITAL PERSONNEL; AMERICAN-COLLEGE; BURN PATIENTS; TRANSPORT; PATIENT; MECHANISM; EXPERIENCE AB Objective. This review provides an overview of the validity of Helicopter Emergency Medical Services (HEMS) dispatch criteria for severely injured patients. Methods. A systematic literature search was performed. English written and peer-reviewed publications on HEMS dispatch criteria were included. Results. Thirty-four publications were included. Five manuscripts discussed accuracy of HEMS dispatch criteria. Criteria based upon Mechanism of Injury (MOI) have a positive predictive value (PPV) of 27%. Criteria based upon the anatomy of injury combined with MOI as a group, result in an undertriage of 13% and a considerable overtriage. The criterion 'loss of consciousness' has a sensitivity of 93-98% and a specificity of 85-96%. Criteria based on age and/or comorbidity have a poor sensitivity and specificity. Conclusion. Only 5 studies described HEMS dispatch criteria validity. HEMS dispatch based on consciousness criteria seems promising. MOI criteria lack accuracy and will lead to significant overtriage. The first categories needing revision are MOI and age/comorbidity. C1 [Ringburg, Akkie N.; de Ronde, Gijs; van Lieshout, Esther M. M.; Schipper, Inger B.] Erasmus MC, Univ Med Ctr Rotterdam, Dept Surg Traumatol, NL-3000 CA Rotterdam, Netherlands. [Thomas, Stephen H.] Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. [Thomas, Stephen H.] Harvard Univ, Sch Med, Boston, MA USA. RP Ringburg, A (reprint author), Erasmus MC, Univ Med Ctr Rotterdam, Dept Surg Traumatol, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM a.ringburg@erasmusmc.nl NR 61 TC 31 Z9 34 U1 2 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1090-3127 J9 PREHOSP EMERG CARE JI Prehosp. Emerg. Care PY 2009 VL 13 IS 1 BP 28 EP 36 AR PII 907832787 DI 10.1080/10903120802472012 PG 9 WC Emergency Medicine; Public, Environmental & Occupational Health SC Emergency Medicine; Public, Environmental & Occupational Health GA 394UQ UT WOS:000262476500005 PM 19145521 ER PT J AU Grudzen, CR Koenig, WJ Hoffman, JR Boscardin, WJ Lorenz, KA Asch, SM AF Grudzen, Corita R. Koenig, William J. Hoffman, Jerome R. Boscardin, W. John Lorenz, Karl A. Asch, Steven M. TI Potential Impact of a Verbal Prehospital DNR Policy SO PREHOSPITAL EMERGENCY CARE LA English DT Article DE ethics; resuscitation; cardiac arrest; palliative care; prehospital care ID HOSPITAL CARDIAC-ARREST; FATES; WORSE; DEATH AB Background. Forgoing resuscitation in prehospital cardiac arrest has previously required a written prehospital do-not-resuscitate (DNR) order. Some emergency medical services (EMS) agencies, including Los Angeles County (LAC), have implemented policies allowing surrogate decision makers to verbally request to forgo resuscitation. The impact of a verbal DNR policy is unclear, given the absence of information about how often cardiac arrest occurs at home, or in the presence of a family member. Objective. To determine the prevalence of written DNR forms, rate of resuscitation, location of cardiac arrest, and availability of a family member in nontraumatic cardiac arrest prior to implementation of the new policy in LAC. Methods. All prehospital run sheets for nontraumatic cardiac arrest in LAC were reviewed for the first seven days of each month (August 2006-January 2007) for DNR status, location of cardiac arrest, presence of family members, and whether resuscitation was attempted. Results. Of the 897 cardiac arrests, 492 occurred at home, 111 in a public place, and 93 in a nursing home (location was unknown for 201). Fifty-five patients (6%) had a written DNR order, although it was not always available. Of these 55 patients, ten were resuscitated, the majority of the time because the family could not produce the paperwork. A family member was listed as present 29% of the time (261 of 897 cases). A medical history was obtained in an additional 465 cases (52%), indicating that someone familiar with the patient's medical history was present more than half the time, even when a family member was not mentioned. Conclusions. A written DNR order is uncommonly used in the prehospital setting as a reason to forgo resuscitation in LAC. Even when family members state that the patient has a DNR order, patients are often resuscitated. A majority of cardiac arrests occurs at the patient's home, and in many cases in the presence of family members, some of whom may be able to express a patient's preferences regarding end-of-life care. C1 [Grudzen, Corita R.] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA USA. [Koenig, William J.] Los Angeles Cty Emergency Med Serv Agcy, Los Angeles, CA USA. [Hoffman, Jerome R.] Univ Calif Los Angeles, Dept Emergency Med, Los Angeles, CA USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Lorenz, Karl A.; Asch, Steven M.] VA Greater Los Angeles, Los Angeles, CA USA. RP Grudzen, CR (reprint author), Mt Sinai Sch Med, Dept Emergency Med, 1 Gustave L Levy Pl,Box 1620, New York, NY 10029 USA. EM corita.grudzen@mssm.edu OI Grudzen, Corita/0000-0003-3039-8497 FU California Health Care Foundation FX Supported by the California Health Care Foundation. NR 11 TC 6 Z9 6 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1090-3127 J9 PREHOSP EMERG CARE JI Prehosp. Emerg. Care PY 2009 VL 13 IS 2 BP 169 EP 172 AR PII 909573959 DI 10.1080/10903120802471923 PG 4 WC Emergency Medicine; Public, Environmental & Occupational Health SC Emergency Medicine; Public, Environmental & Occupational Health GA 419MT UT WOS:000264224400003 PM 19291552 ER PT J AU Chen, LY Reisner, AT Gribok, A Reifman, J AF Chen, Liangyou Reisner, Andrew T. Gribok, Andrei Reifman, Jaques TI Exploration of Prehospital Vital Sign Trends for the Prediction of Trauma Outcomes SO PREHOSPITAL EMERGENCY CARE LA English DT Article DE vital signs; trauma; hemorrhage; trends; variability ID INTENSIVE-CARE-UNIT; BLOOD-PRESSURE; LIFESAVING INTERVENTIONS; HYPOTENSION; MORTALITY; TRIAGE; SCORE; HYPOVOLEMIA; HELICOPTERS; TRANSPORT AB Objectives. We explored whether there are diagnostically useful temporal trends in prehospital vital signs of trauma patients. Methods. Vital signs were monitored during transport to a level I trauma center and electronically archived. Retrospectively, we identified reliable vital signs recorded from the 0- to 7-minute interval and from the 14- to 21-minute interval during transport, and, for each subject, we computed the temporal differences between the two intervals' vital signs, the intrasubject 95% data ranges, the values during the initial 2 minutes, and the 21-minute overall means. We tested for differences between subjects with major hemorrhage versus control subjects, and computed receiver-operating characteristic (ROC) curves. We conducted sensitivity analyses, exploring alternative clinical outcomes, temporal windows, and methods of identifying reliable data. Results. Comparing major hemorrhage cases versus controls, there were no discriminatory differences in temporal vital sign trends. Hemorrhage cases had significantly wider intrasubject data ranges for systolic blood pressure (SBP), respiratory rate (RR), and shock index (SI) versus controls. All results were consistent in several sensitivity analyses. Conclusions. Our findings add to a growing body of evidence that prehospital vital sign trends over 21 minutes or less are unlikely to be diagnostically useful because of substantial nondirectional fluctuations in vital signs that would obscure any subtle, progressive temporal trends. SBP, RR, and SI values were significantly different for high-acuity patients, and had more variability. Taken together, these findings suggest that higher-acuity patients experience episodes of instability rather than gradual, steady decline. Measures that account for data variability, such as taking the average of multiple measurements, may improve the diagnostic utility of prehospital vital signs. C1 [Chen, Liangyou; Reisner, Andrew T.; Gribok, Andrei; Reifman, Jaques] USA, Med Res & Mat Command, TATRC, Ft Detrick, MD USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Reifman, J (reprint author), USA, Med Res & Mat Command, TATRC, ATTN MCMR TT Bldg 363 Miller Dr, Ft Detrick, MD USA. EM reifman@us.army.mil FU Combat Casualty Care Research Area Directorate of the U. S. Army Medical Research and Materiel Command, Fort Detrick, Maryland FX Supported by the Combat Casualty Care Research Area Directorate of the U. S. Army Medical Research and Materiel Command, Fort Detrick, Maryland. The authors have no conflicts of interest to disclose. NR 32 TC 27 Z9 28 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1090-3127 J9 PREHOSP EMERG CARE JI Prehosp. Emerg. Care PY 2009 VL 13 IS 3 BP 286 EP 294 AR PII 912029366 DI 10.1080/10903120902935298 PG 9 WC Emergency Medicine; Public, Environmental & Occupational Health SC Emergency Medicine; Public, Environmental & Occupational Health GA 454AQ UT WOS:000266654400003 PM 19499463 ER PT J AU Stryker, JE Fishman, J Emmons, KM Viswanath, K AF Stryker, Jo Ellen Fishman, Jessica Emmons, Karen M. Viswanath, Kasisomayajula TI Cancer Risk Communication in Mainstream and Ethnic Newspapers SO PREVENTING CHRONIC DISEASE LA English DT Article AB Introduction We wanted to understand how cancer risks are communicated in mainstream and ethnic newspapers, to determine whether the 2 kinds of newspapers differ and to examine features of news stories and sources that might predict optimal risk communication. Methods Optimal risk communication was defined as presenting the combination of absolute risk, relative risk, and prevention response efficacy information. We collected data by conducting a content analysis of cancer news coverage from 2003 (5,327 stories in major newspapers, 565 stories in ethnic newspapers). Comparisons of mainstream and ethnic newspapers were conducted by using cross-tabulations and Pearson chi(2) tests for significance. Logistic regression equations were computed to calculate odds ratios and 95% confidence intervals for optimal risk communication. Results In both kinds of newspapers, cancer risks were rarely communicated numerically. When numeric presentations of cancer risks were used, only 26.2% of mainstream and 29.5% of ethnic newspaper stories provided estimates of both absolute and relative risk. For both kinds of papers, only 19% of news stories presented risk communication optimally. Cancer risks were more likely to be communicated optimally if they focused on prostate cancer, were reports of new research, or discussed medical or demographic risks. Conclusion Research is needed to understand how these non-numeric and decontextualized presentations of risk might contribute to inaccurate risk perceptions among news consumers. C1 [Stryker, Jo Ellen] Univ Illinois, Urbana, IL 61801 USA. [Fishman, Jessica] Univ Penn, Philadelphia, PA 19104 USA. [Emmons, Karen M.; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Boston, MA 02115 USA. [Emmons, Karen M.; Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Stryker, JE (reprint author), Emory Univ, Rollins Sch Publ Hlth, 1518 Clifton Rd NE,Rm 572, Atlanta, GA 30322 USA. EM jestryk@sph.emory.edu FU National Cancer Institute [CA98437-01A1]; American Cancer Society [MRSGT-08-013-01-CPPB] FX This research was conducted with funding from the National Cancer Institute, no. CA98437-01A1. We thank Viviana Abuchar, Ryan Hurley, Jakob Jensen, Cortney Moriarty, and Gina Tassio for their coding and data preparation. Dr Stryker acknowledges the Georgia Cancer Coalition for its support. Dr Fishman acknowledges support from the American Cancer Society, no. MRSGT-08-013-01-CPPB. NR 45 TC 4 Z9 4 U1 1 U2 2 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD JAN PY 2009 VL 6 IS 1 AR A23 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V20RU UT WOS:000208157900023 PM 19080029 ER PT B AU Lara-Castro, C Garvey, WT AF Lara-Castro, Cristina Garvey, W. Timothy BE Bendich, A Deckelbaum, RJ TI Role of Nutrition in the Pathophysiology, Prevention, and Treatment of Type 2 Diabetes and the Spectrum of Cardiometabolic Disease SO PREVENTIVE NUTRITION: THE COMPREHENSIVE GUIDE FOR HEALTH PROFESSIONALS, FOURTH EDITION SE Nutrition and Health Series LA English DT Article; Book Chapter DE Cardiometabolic disease; fiber; metabolic syndrome; monounsaturated fatty acids; prediabetes; susceptibility genes; Type 2 diabetes; weight loss ID GENOME-WIDE ASSOCIATION; INSULIN-RESISTANCE ATHEROSCLEROSIS; IMPAIRED GLUCOSE-TOLERANCE; NUCLEAR-MAGNETIC-RESONANCE; LOW-FAT DIET; METABOLIC SYNDROME; LOW-CARBOHYDRATE; WEIGHT-LOSS; CARDIOVASCULAR-DISEASE; RANDOMIZED-TRIAL AB Key Points The overlapping syndromes of prediabetes and metabolic syndrome place individuals at increased risk of Type 2 diabetes and cardiovascular disease. and in aggregate, these disorders comprise the spectrum of cardiometabolic disease. Treatment of these prediabetic states is critical for reducing patient suffering and social costs attributable to the increasing prevalence of diabetes worldwide. Insulin resistance is central to the pathophysiology of Type 2 diabetes and metabolic syndrome. While obesity can exacerbate insulin resistance, it is abnormal lipid accumulation in visceral adipose tissue, and in skeletal muscle cells and hepatocytes, that appear to be more potent and independent mediators of cardiometabolic disease. Cardiometabolic disease can be effectively treated or prevented using nutrition as a component of lifestyle therapy, which, given the underlying pathophysiology, will need to augment insulin sensitivity, enhance insulin secretion, and/or ameliorate cardiovascular risk factors. This can be accomplished via hypocaloric feeding or altered macronutrient composition of the diet. Hypocaloric diets resulting in 5-10% weight loss are effective over a wide spectrum of caloric composition ranging from low carbohydrate to low fat. Isocaloric diets can also improve insulin sensitivity and cardiovascular risk factors particularly if enriched in monounsaturated fat or fiber with reduced intake of saturated fat. Genome-wide association studies have confirmed multiple susceptibility loci (i.e., gene-based single nucleotide polymorphisms-SNPs) for Type 2 diabetes and obesity and present a powerful paradigm for the identification and study of nutrient-gene interactions, provided that investigators measure diet as an environmental variable. C1 [Lara-Castro, Cristina; Garvey, W. Timothy] Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. [Lara-Castro, Cristina] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. [Garvey, W. Timothy] UAB Diabet Res & Training Ctr, Birmingham, AL 35294 USA. RP Lara-Castro, C (reprint author), Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. EM garveyt@uab.edu NR 58 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-541-5 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2009 BP 371 EP 387 DI 10.1007/978-1-60327-542-2_15 PG 17 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA BLY65 UT WOS:000271457000015 ER PT S AU Pathak, NH Drummond, IA AF Pathak, Narendra H. Drummond, Iain A. BE Sloboda, RD TI Polyglutamylation and the fleer Gene SO PRIMARY CILIA SE Methods in Cell Biology LA English DT Review; Book Chapter ID ALPHA-TUBULIN; BETA-TUBULIN; ZEBRAFISH PRONEPHROS; TETRAHYMENA-THERMOPHILA; CILIA; TRANSPORT; MICROTUBULES; MECHANISMS; COMPONENTS; MUTATIONS C1 [Pathak, Narendra H.; Drummond, Iain A.] Harvard Univ, Sch Med, Dept Med & Genet, Charlestown, MA 02129 USA. [Pathak, Narendra H.; Drummond, Iain A.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA. RP Pathak, NH (reprint author), Harvard Univ, Sch Med, Dept Med & Genet, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK078741, DK053093, K01 DK078741] NR 37 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-375024-2 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2009 VL 94 BP 317 EP + DI 10.1016/S0091-679X(08)94016-4 PG 17 WC Cell Biology SC Cell Biology GA BMN63 UT WOS:000272975500017 PM 20362098 ER PT B AU Varadarajan, KM Gill, TJ Freiberg, AA Rubash, HE Li, GA AF Varadarajan, Kartik M. Gill, Thomas J. Freiberg, Andrew A. Rubash, Harry E. Li, Guoan GP ASME TI GENDER DIFFERENCES IN THE KINEMATICS AND MORPHOLOGY OF THE KNEE SO PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE 2008, PTS A AND B LA English DT Proceedings Paper CT ASME Summer Bioengineering Conference CY JUN 25-29, 2008 CL Marco Isl, FL SP Amer Soc Mech Engineers, Bioengn Div C1 [Varadarajan, Kartik M.; Gill, Thomas J.; Freiberg, Andrew A.; Rubash, Harry E.; Li, Guoan] Harvard Univ, Sch Med, Dept Orthoped Surg, Massachusetts Gen Hosp,Bioengn Lab, Boston, MA 02115 USA. RP Varadarajan, KM (reprint author), Harvard Univ, Sch Med, Dept Orthoped Surg, Massachusetts Gen Hosp,Bioengn Lab, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4321-5 PY 2009 BP 377 EP 378 PG 2 WC Engineering, Biomedical SC Engineering GA BIW31 UT WOS:000263364700189 ER PT B AU Varadarajan, KM Moynihan, A D'Lima, D Colwell, CW Rubash, HE Li, GA AF Varadarajan, Kartik M. Moynihan, Angela D'Lima, Darryl Colwell, Clifford W. Rubash, Harry E. Li, Guoan GP ASME TI IN VIVO TIBIOFEMORAL CONTACT KINEMATICS AND CONTACT FORCES DURING DYNAMIC WEIGHT-BEARING ACTIVITIES FOLLOWING TOTAL KNEE ARTHROPLASTY SO PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE 2008, PTS A AND B LA English DT Proceedings Paper CT ASME Summer Bioengineering Conference CY JUN 25-29, 2008 CL Marco Isl, FL SP Amer Soc Mech Engineers, Bioengn Div C1 [Varadarajan, Kartik M.; Moynihan, Angela; Rubash, Harry E.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02115 USA. RP Varadarajan, KM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4321-5 PY 2009 BP 859 EP 860 PG 2 WC Engineering, Biomedical SC Engineering GA BIW31 UT WOS:000263364700430 ER PT B AU Varadarajan, KM Moynihan, AL Seon, JK Freiberg, AA Rubash, HE Li, GA AF Varadarajan, Kartik M. Moynihan, Angela L. Seon, Jong Keun Freiberg, Andrew A. Rubash, Harry E. Li, Guoan GP ASME TI CHANGES IN TIBIOFEMORAL JOINT SPACE FOLLOWING TOTAL KNEE ARTHROPLASTY DURING WEIGHT-BEARING KNEE MOTION SO PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2009, PT A AND B LA English DT Proceedings Paper CT ASME Summer Bioengineering Conference CY JUN 17-21, 2009 CL Lake Tahoe, CA SP ASME Bioengn Div ID FLEXION C1 [Varadarajan, Kartik M.; Moynihan, Angela L.; Seon, Jong Keun; Freiberg, Andrew A.; Rubash, Harry E.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02115 USA. RP Varadarajan, KM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4891-3 PY 2009 BP 399 EP 400 PG 2 WC Cell & Tissue Engineering; Engineering, Biomedical SC Cell Biology; Engineering GA BPV38 UT WOS:000280089000200 ER PT B AU Wang, SB Passias, PG Xia, Q Wood, KB Li, GA AF Wang, Shaobai Passias, Peter G. Xia, Qun Wood, Kirkham B. Li, Guoan GP ASME TI IN-VIVO LUMBAR INTERVERTEBRAL DISC GEOMETRIC DEFORMATION DURING FUNCTIONAL POSTURES SO PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2009, PT A AND B LA English DT Proceedings Paper CT ASME Summer Bioengineering Conference CY JUN 17-21, 2009 CL Lake Tahoe, CA SP ASME Bioengn Div C1 [Wang, Shaobai; Passias, Peter G.; Xia, Qun; Wood, Kirkham B.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed,Bioengn Lab, Boston, MA 02115 USA. RP Wang, SB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed,Bioengn Lab, Boston, MA 02115 USA. NR 2 TC 0 Z9 1 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4891-3 PY 2009 BP 843 EP 844 PG 2 WC Cell & Tissue Engineering; Engineering, Biomedical SC Cell Biology; Engineering GA BPV38 UT WOS:000280089000422 ER PT B AU Hosseini, A Gill, TJ Li, GA AF Hosseini, Ali Gill, Thomas J. Li, Guoan GP ASME TI IN-VIVO FORCE ESTIMATION OF THE ANTERIOR CRUCIATE LIGAMENT SO PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2009, PT A AND B LA English DT Proceedings Paper CT ASME Summer Bioengineering Conference CY JUN 17-21, 2009 CL Lake Tahoe, CA SP ASME Bioengn Div C1 [Hosseini, Ali; Gill, Thomas J.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab, Boston, MA 02115 USA. RP Hosseini, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4891-3 PY 2009 BP 999 EP 1000 PG 2 WC Cell & Tissue Engineering; Engineering, Biomedical SC Cell Biology; Engineering GA BPV38 UT WOS:000280089000500 ER PT J AU Menesi, D Kitajka, K Molnar, E Kis, Z Belleger, J Narce, M Kang, JX Puskas, LG Das, UN AF Menesi, Dalma Kitajka, Klara Molnar, Eszter Kis, Zoltan Belleger, Jerome Narce, Michael Kang, Jing X. Puskas, Laszlo G. Das, Undurti N. TI Gene and protein expression profiling of the fat-1 mouse brain SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE Fat-1; Polyunsaturated fatty acids; Inflammation; Gene expression; Alzheimer's disease; Neuronal dysfunction ID POLYUNSATURATED FATTY-ACIDS; HEPATOCYTE NUCLEAR FACTOR-4; TYPE-2 DIABETES-MELLITUS; ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE; TRANSCRIPTION FACTOR; TRANSGENIC MICE; RAT-BRAIN; INFLAMMATORY CONDITION; METABOLIC SYNDROME AB Polyunsaturated fatty acids (PUFAs) are essential structural components of all cell membranes and, more so, of the central nervous system. Several studies revealed that n-3 PUFAs possess anti-inflammatory actions and are useful in the treatment of dyslipidemia. These actions explain the beneficial actions of n-3 PUFAs in the management of cardiovascular diseases, inflammatory conditions, neuronal dysfunction, and cancer. But, the exact molecular targets of these beneficial actions of n-3 PUFAs are not known. Mice engineered to carry a fat-1 gene from Caenorhabditis elegans add a double bond into an unsaturated fatty acid hydrocarbon chain and convert n-6 to n-3 fatty acids. This results in an abundance of n-3 eicosapentaenoic acid and docosapentaenoic acid specifically in the brain and a reduction in n-6 fatty acids of these mice that can be used to evaluate the actions of n-3 PUFAs. Gene expression profile, RT-PCR and protein microarray studies in the hippocampus and whole brain of wildtype and fat-1 transgenic mice revealed that genes and proteins concerned with inflammation, apoptosis, neurotransmission, and neuronal growth and synapse formation are specifically modulated in fat-1 mice. These results may explain as to why n-3 PUFAs are of benefit in the prevention and treatment of diseases such as Alzheimer's disease, schizophrenia and other diseases associated with neuronal dysfunction, low-grade systemic inflammatory conditions, and bronchial asthma. Based on these data, it is evident that n-3 PUFAs act to modulate specific genes and formation of their protein products and thus, bring about their various beneficial actions. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Das, Undurti N.] UND Life Sci, Shaker Hts, OH 44120 USA. [Menesi, Dalma; Kitajka, Klara; Molnar, Eszter; Kis, Zoltan; Puskas, Laszlo G.] Hungarian Acad Sci, Funct Genom Lab, Biol Res Ctr, H-6726 Szeged, Hungary. [Kang, Jing X.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Das, Undurti N.] Bharati Vidyapeeth Univ, Coll Med, Dept Med, Pune 411046, Maharashtra, India. RP Das, UN (reprint author), UND Life Sci, 13800 Fairhill Rd,32, Shaker Hts, OH 44120 USA. EM undurti@hotmail.com FU Hungarian Ministry of Education FX K.K. was supported by the janos Bolyai fellowship of the Hungarian Ministry of Education. UND was in receipt of Ramalingaswami Fellowship of the Department of Biotechnology, India during the tenure of this study. NR 75 TC 9 Z9 10 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD JAN PY 2009 VL 80 IS 1 BP 33 EP 42 DI 10.1016/j.plefa.2008.11.006 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 422NH UT WOS:000264434500005 PM 19138887 ER PT J AU Agrawal, V Gailey, R O'Toole, C Gaunaurd, I Dowell, T AF Agrawal, Vibhor Gailey, Robert O'Toole, Christopher Gaunaurd, Ignacio Dowell, Tomas TI Symmetry in External Work (SEW): A novel method of quantifying gait differences between prosthetic feet SO PROSTHETICS AND ORTHOTICS INTERNATIONAL LA English DT Article DE Gait symmetry; external mechanical work; prosthetic feet comparison; gait kinetics ID LOWER-LIMB AMPUTATION; TO-STEP TRANSITIONS; MECHANICAL WORK; HUMAN WALKING; AMPUTEES; MOTION; BODY AB Unilateral transtibial amputees (TTAs) show subtle gait variations while using different prosthetic feet. These variations have not been detected consistently with previous experimental measures. We introduce a novel measure called Symmetry in External Work (SEW) for quantifying kinetic gait differences between prosthetic feet. External work is the result of changes in kinetic and potential energy of body center of mass (CoM). SEW is computed by integrating vertical ground reaction forces obtained using F-scan in-sole sensors. Since various prosthetic feet have different designs, we hypothesized that SEW will vary with the type of foot used. This hypothesis was tested with a single unilateral TTA using four prosthetic feet (Proprio, Trias+, Seattle Lite and SACH). The Proprio (mean symmetry 94.5%1.1%) and the Trias+ (92.1%2.5%) feet exhibited higher symmetry between the intact and prosthetic limbs, as compared to the Seattle (67.8%19.3%) and SACH (35.7%11.1%) feet. There was also a good agreement in vertical CoM excursion between the intact foot and prosthetic feet with heel-toe foot plate designs. Results indicate that SEW measure may be a viable method to detect kinetic differences between prosthetic feet and could have clinical applications because of relatively low cost instrumentation and minimal subject intervention. C1 [Agrawal, Vibhor] Miami VA Healthcare Syst, US Dept Vet Affairs, Res Serv 151, Funct Outcomes Res & Evaluat Ctr, Miami, FL 33125 USA. [Agrawal, Vibhor; O'Toole, Christopher] Univ Miami, Coll Engn, Dept Biomed Engn, Coral Gables, FL 33124 USA. [Gailey, Robert; Gaunaurd, Ignacio] Univ Miami, Dept Phys Therapy, Miller Sch Med, Coral Gables, FL 33124 USA. RP Agrawal, V (reprint author), Miami VA Healthcare Syst, US Dept Vet Affairs, Res Serv 151, Funct Outcomes Res & Evaluat Ctr, 1201 NW 16th St, Miami, FL 33125 USA. EM vibhor@umail.miami.edu NR 26 TC 14 Z9 14 U1 3 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0309-3646 J9 PROSTHET ORTHOT INT JI Prosthet. Orthot. Int. PY 2009 VL 33 IS 2 BP 148 EP 156 AR PII 910430308 DI 10.1080/03093640902777254 PG 9 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 435DM UT WOS:000265323900007 PM 19367518 ER PT J AU Lichtenthall, WG Nilsson, M Zhang, BH Trice, ED Kissane, DW Breitbart, W Prigerson, HG AF Lichtenthall, Wendy G. Nilsson, Matthew Zhang, Baohui Trice, Elizabeth D. Kissane, David W. Breitbart, William Prigerson, Holly G. TI Do rates of mental disorders and existential distress among advanced stage cancer patients increase as death approaches? SO PSYCHO-ONCOLOGY LA English DT Article DE advanced cancer; oncology; mental disorders; existential distress; proximity to death; terminal illness awareness ID STRUCTURED CLINICAL INTERVIEW; KARNOFSKY PERFORMANCE STATUS; ADVANCED BREAST-CANCER; HEALTH-SERVICE USE; PALLIATIVE CARE; TERMINALLY-ILL; PSYCHIATRIC-DISORDERS; PREDICTIVE FACTORS; DEPRESSION; PREVALENCE AB Objective: To determine whether the prevalence of mental disorders and related factors increase as advanced cancer patients get closer to death. Method. Baseline, cross-sectional data from 289 patients who were assessed prior to their death as part of a multi-site, longitudinal, prospective cohort study of advanced cancer patients. Major depressive disorder, generatized anxiety disorder, panic disorder, and posttraumatic stress disorder were assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-IV Axis I Disorders. Other factors examined included existential well-being, patient grief about their illness, physical symptom burden, terminal illness acknowledgment, peacefulness, and the wish to live or die. Results: Closeness to death was not associated with higher rates of mental disorders. Patients closer to death exhibited increased existential distress and physical symptom burden, were more likely to acknowledge being terminally ill, and were more likely to report an increased wish to die. Conclusion: Results do not provide support for the common clinical assumption that the prevalence of depressive and anxiety disorders increases as death nears. However, patients' level of physical distress, acknowledgment of terminal illness, and wish to die, possibly reflecting acceptance of dying, increased as death approached. Longitudinal studies are needed to confirm individual changes in rates of mental disorder as patients approach death. Copyright (c) 2008 John Wiley & Sons, Ltd. C1 [Lichtenthall, Wendy G.; Kissane, David W.; Breitbart, William] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10022 USA. [Nilsson, Matthew; Zhang, Baohui; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Trice, Elizabeth D.] Dana Farber Canc Inst, Dept Hematol & Oncol, Boston, MA 02115 USA. RP Lichtenthall, WG (reprint author), Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, 641 Lexington Ave,7th Floor, New York, NY 10022 USA. EM lichtenw@mskcc.org OI Lichtenthal, Wendy/0000-0003-3597-7826 FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA 106370]; Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute; National Cancer Institute training [T32 CA009461-23] FX This research was supported in part by the following grants to Dr Prigerson: MH63892 from the National Institute of Mental Health and CA 106370 from the National Cancer Institute; the Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute. Support for Dr Lichtenthal was provided in part by a National Cancer Institute training grant (T32 CA009461-23). NR 56 TC 43 Z9 43 U1 0 U2 13 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JAN PY 2009 VL 18 IS 1 BP 50 EP 61 DI 10.1002/pon.1371 PG 12 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 396XP UT WOS:000262625700007 PM 18523933 ER PT J AU Allen, JD Savadatti, S Levy, AG AF Allen, Jennifer D. Savadatti, Sanghamitra Levy, Andrea Gurmankin TI The transition from breast cancer 'patient' to 'survivor' SO PSYCHO-ONCOLOGY LA English DT Article DE breast neoplasm; survivors; psychological adaptation; social adjustment ID COPING STRATEGIES; WOMEN; STRESS; LIFE; ADJUSTMENT; BEHAVIORS; DISTRESS; THERAPY; BENEFIT; SELF AB Background. While much is now known about breast cancer survivors' long-term health, quality of life, and psychological state, relatively little is known about the period immediately following completion of treatment, when women transition out of the role of breast cancer 'patient' to life as 'survivor'. Objective: To explore women's fears regarding risk of cancer recurrence, sense of loss of medical monitoring, and social support from health-care providers and other patients, and the strategies they use to cope with these issues. Method: Focus group interviews were conducted with women who had completed adjuvant chemotherapy or radiation for new stage I or II breast cancer in the prior 12 months. Interviews were audio-taped, transcribed, and analyzed using a constant comparative analysis approach. Results: Of 216 women identified as eligible, over half (155) were reached by telephone and invited to participate. Of those invited, 47 (30%) agreed. Findings suggest that while women acknowledge positive life changes as a result of the cancer experience, emotional and physical stresses are prevalent following the completion of treatment. Conclusion: The period of time when women who have been treated for breast cancer transition to life without treatment presents numerous emotional and physical challenges. By illuminating patients' experience during this transition period, this study provides insights into the development of interventions to support women after treatment. Copyright (c) 2008 John Wiley & Sons, Ltd. C1 [Allen, Jennifer D.] Boston Coll, William Connell Sch Nursing, Chestnut Hill, MA 02467 USA. [Allen, Jennifer D.; Savadatti, Sanghamitra; Levy, Andrea Gurmankin] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Allen, Jennifer D.; Levy, Andrea Gurmankin] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Allen, JD (reprint author), Boston Coll, William Connell Sch Nursing, 140 Commonwealth Ave, Chestnut Hill, MA 02467 USA. EM jennifer.allen@bc.edu RI Allen, Jennifer/M-2113-2015 FU Susan G. Komen FX This research was supported by a grant from Susan G. Komen for the Cure. The authors are grateful to Nancy Borstelmann, Carol Lowenstein, Eric Winer, and the women who participated in the study. NR 31 TC 64 Z9 64 U1 2 U2 14 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JAN PY 2009 VL 18 IS 1 BP 71 EP 78 DI 10.1002/pon.1380 PG 8 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 396XP UT WOS:000262625700009 PM 18613299 ER PT J AU de Gelder, B Bertelson, P AF de Gelder, Beatrice Bertelson, Paul TI A COMPARATIVE APPROACH TO TESTING FACE PERCEPTION: FACE AND OBJECT IDENTIFICATION BY ADULTS IN A SIMULTANEOUS MATCHING TASK SO PSYCHOLOGICA BELGICA LA English DT Article ID DEVELOPMENTAL PROSOPAGNOSIA; RECOGNITION; CONFIGURATION; SUPERIORITY; MECHANISMS; LESIONS AB Experimental studies of face perception tend to use small samples of participants taken from a narrow age range. This often makes it difficult to use the results in clinical studies. Combined with the fact that current face processing tests are of limited use for an in depth analysis of prosopagnosia it is often difficult to assess face recognition problems. Here we present the results from a study of a wide age group (21-50 yrs) tested with a comprehensive face perception battery that was developed to provide a new tool for critically measuring intact face perception. We critically review existing tests and motivate our choice for the present design which is unique in that it uses in the same task setting faces and objects and therefore allows a more specific evaluation of face specific abilities than was hitherto possible. C1 [de Gelder, Beatrice] Tilburg Univ, Dept Psychol, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. [de Gelder, Beatrice] Harvard Univ, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Sch Med, Charlestown, MA USA. [Bertelson, Paul] Univ Libre Bruxelles, Brussels, Belgium. RP de Gelder, B (reprint author), Tilburg Univ, Dept Psychol, Cognit & Affect Neurosci Lab, POB 90153, NL-5000 LE Tilburg, Netherlands. EM degelder@uvt.nl NR 29 TC 3 Z9 3 U1 1 U2 2 PU BELGIAN PSYCHOL SOC PI LOUVAIN PA TIENSESTRAAT 102, 3000 LOUVAIN, BELGIUM SN 0033-2879 J9 PSYCHOL BELG JI Psychol. Belg. PY 2009 VL 49 IS 2-3 SI SI BP 177 EP 190 PG 14 WC Psychology, Multidisciplinary SC Psychology GA 582QR UT WOS:000276613500008 ER PT J AU Brunye, TT Ditman, T Mahoney, CR Augustyn, JS Taylor, HA AF Brunye, Tad T. Ditman, Tali Mahoney, Caroline R. Augustyn, Jason S. Taylor, Holly A. TI When You and I Share Perspectives Pronouns Modulate Perspective Taking During Narrative Comprehension SO PSYCHOLOGICAL SCIENCE LA English DT Article ID LANGUAGE COMPREHENSION; SITUATION MODELS; MEMORY; ACCESSIBILITY; INFORMATION AB Readers mentally simulate the objects and events described in narratives. One common assumption is that readers mentally embody an actor's perspective; alternatively, readers might mentally simulate events from an external "onlooker" perspective. Two experiments examined the role of pronouns in modulating a reader's adopted perspective when comprehending simple event sentences. Experiment 1 demonstrated that readers embody an actor's perspective when the pronoun you or I is used, but take an external perspective when he is used. Experiment 2, however, found that a short discourse context preceding the event sentence led readers to adopt an external perspective with the pronoun I. These experiments demonstrate that pronoun variation and discourse context mediate the degree of embodiment experienced during narrative comprehension: In all cases, readers mentally simulate objects and events, but they embody an actor's perspective only when directly addressed as the subject of a sentence. C1 [Brunye, Tad T.; Mahoney, Caroline R.; Augustyn, Jason S.] USA, NSRDEC, Attn AMSRD NSC WS P, Natick, MA 01760 USA. [Brunye, Tad T.; Ditman, Tali; Mahoney, Caroline R.; Taylor, Holly A.] Tufts Univ, Medford, MA 02155 USA. [Ditman, Tali] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. RP Brunye, TT (reprint author), USA, NSRDEC, Attn AMSRD NSC WS P, 15 Kansas St, Natick, MA 01760 USA. EM tbrunye@alumni.tufts.edu RI 江, 鈺麒/G-1379-2014 NR 22 TC 66 Z9 66 U1 2 U2 16 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD JAN PY 2009 VL 20 IS 1 BP 27 EP 32 DI 10.1111/j.1467-9280.2008.02249.x PG 6 WC Psychology, Multidisciplinary SC Psychology GA 392EH UT WOS:000262285200006 PM 19076318 ER PT J AU Waltman, MA Russell, DC Coyle, CT Enright, RD Holter, AC Swoboda, C AF Waltman, Martina A. Russell, Douglas C. Coyle, Catherine T. Enright, Robert D. Holter, Anthony C. M. Swoboda, Christopher TI The effects of a forgiveness intervention on patients with coronary artery disease SO PSYCHOLOGY & HEALTH LA English DT Article DE forgiveness; anger-recall; mental stress; coronary artery disease; myocardial ischemia; myocardial perfusion imaging ID MYOCARDIAL-ISCHEMIA PIMI; STRESS-INDUCED ISCHEMIA; MENTAL STRESS; CARDIOVASCULAR REACTIVITY; PSYCHOPHYSIOLOGICAL INVESTIGATIONS; GAIN SCORES; ANGER; HOSTILITY; RESPONSES; THERAPY AB This research assesses the effects of a psychology of forgiveness pilot study on anger-recall stress induced changes in myocardial perfusion, forgiveness and related variables. Thirty-two patients were administered baseline rest and anger-recall stress imaging studies, and 17 of these participants who demonstrated anger-recall stress induced myocardial perfusion defects (forgiveness group, n = 9; control group, n = 8) were randomly assigned to a series of 10 weekly interpersonal forgiveness or control therapy sessions with a trained psychologist, and underwent additional anger-recall stress myocardial perfusion nuclear imaging studies post-test and at 10-week follow-up. Patients assigned to the forgiveness group showed significantly fewer anger-recall induced myocardial perfusion defects from pre-test to the 10-week follow-up as well as significantly greater gains in forgiveness from pre-test to post-test and from pre-test to follow-up compared to the control group. Forgiveness intervention may be an effective means of reducing anger-induced myocardial ischemia in patients with coronary artery disease. C1 [Waltman, Martina A.; Coyle, Catherine T.; Enright, Robert D.; M. Swoboda, Christopher] Univ Wisconsin, Dept Educ Psychol, Madison, WI 53706 USA. [Waltman, Martina A.; Russell, Douglas C.] William S Middleton Mem Vet Adm Med Ctr, Dept Vet Affairs, Madison, WI USA. [Russell, Douglas C.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Holter, Anthony C.] Univ Notre Dame, South Bend, IN USA. RP Enright, RD (reprint author), Univ Wisconsin, Dept Educ Psychol, Madison, WI 53706 USA. EM rd.enright@yahoo.com NR 72 TC 23 Z9 25 U1 3 U2 15 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0887-0446 EI 1476-8321 J9 PSYCHOL HEALTH JI Psychol. Health PY 2009 VL 24 IS 1 BP 11 EP 27 AR PII 794507871 DI 10.1080/08870440801975127 PG 17 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary SC Public, Environmental & Occupational Health; Psychology GA 400HZ UT WOS:000262859900003 PM 20186637 ER PT J AU Bell, ME Goodman, LA Dutton, MA AF Bell, Margret E. Goodman, Lisa A. Dutton, Mary Ann TI VARIATIONS IN HELP-SEEKING, BATTERED WOMEN'S RELATIONSHIP COURSE, EMOTIONAL WELL-BEING, AND EXPERIENCES OF ABUSE OVER TIME SO PSYCHOLOGY OF WOMEN QUARTERLY LA English DT Article ID INTIMATE PARTNER VIOLENCE; RELATIONSHIP EFFICACY; PSYCHOLOGICAL ABUSE; RISK; STAY; ACCURACY; VICTIMS; CHOICE; IMPACT; MODEL AB Despite assumptions that leaving the batterer offers the best chance for improvement in battered women's lives, few studies provide conclusive data on this issue. Although many women eventually reunite with partners, also unexamined is the influence of relationship course over time. Five waves of data from 206 low-income, largely Black, help-seeking battered women revealed minimal differences in emotional well-being either initially or over time for women following different relationship trajectories during the course of 1 year. Consistency in relationship status (completely apart, completely together) tended to be associated with sharper drops in violence during the year; abuse tended to decrease most slowly among women who were in and out of their relationship over time. Findings suggest that the act of leaving is not necessarily associated with improvements for victims-how the process of leaving occurs may be more influential. Challenging common assumptions, women remaining with partners may sometimes fare better than women who leave. C1 [Bell, Margret E.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Bell, Margret E.] VA Boston Healthcare Syst, Mil Sexual Trauma Support Team, Dept Vet Affairs, Off Mental Hlth Serv, Boston, MA 02130 USA. [Goodman, Lisa A.] Boston Coll, Dept Counseling Dev & Educ Psychol, Lynch Sch Educ, Chestnut Hill, MA 02167 USA. [Dutton, Mary Ann] Georgetown Univ, Dept Psychiat, Washington, DC 20057 USA. RP Bell, ME (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave,116B-3, Boston, MA 02130 USA. EM mebell@aya.yale.edu NR 52 TC 9 Z9 9 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-6843 J9 PSYCHOL WOMEN QUART JI Psychol. Women Q. PY 2009 VL 33 IS 2 BP 149 EP 162 DI 10.1111/j.1471-6402.2009.01485.x PG 14 WC Psychology, Multidisciplinary; Women's Studies SC Psychology; Women's Studies GA 436RG UT WOS:000265431800001 ER PT J AU Goff, DC Cather, C Freudenreich, O Henderson, DC Evins, AE Culhane, MA Walsh, JP AF Goff, Donald C. Cather, Corinne Freudenreich, Oliver Henderson, David C. Evins, A. Eden Culhane, Melissa A. Walsh, Jared P. TI A placebo-controlled study of sildenafil effects on cognition in schizophrenia SO PSYCHOPHARMACOLOGY LA English DT Article DE Schizophrenia; Cognition; Memory; NMDA ID OBJECT RECOGNITION MEMORY; NITRIC-OXIDE SYNTHASE; D-CYCLOSERINE; ERECTILE DYSFUNCTION; RAT-BRAIN; PHOSPHODIESTERASE INHIBITION; LEARNING IMPAIRMENT; CONTROLLED TRIAL; CYCLIC-GMP; CONSOLIDATION AB Phosphodiesterase 5 (PDE5) inhibitors increase cyclic guanosine monophosphate (cGMP) concentrations in the intracellular pathway activated by N-methyl-d-aspartic acid receptors which is believed to mediate long-term potentiation and memory consolidation. The PDE5 inhibitor sildenafil has been shown to enhance memory in animal models. In addition, neuronal nitric oxide synthase, another component of the NMDA/nitric oxide/cGMP intracellular pathway, has been reported to be dysregulated in schizophrenia patients. Seventeen adult schizophrenia outpatients treated with a stable dose of antipsychotic received a single oral dose of placebo, sildenafil 50 mg, and sildenafil 100 mg in random order with a 48-h interval between administrations. Psychiatric symptom ratings and a cognitive battery were performed at baseline and 1 hour following each administration of the study drug. In addition, memory consolidation was examined by testing recall 48 h later, prior to the next administration of the study drug. Fifteen subjects completed all three treatment conditions. One subject developed irritability and required hospitalization 2 days after receiving sildenafil 100 mg. Neither dose of sildenafil significantly affected cognitive performance or symptom ratings compared to the placebo. Despite evidence for cognitive-enhancing effects of sildenafil in animal models, the strategy for treating putative NMDA receptor-mediated memory deficits in schizophrenia with sildenafil 50 and 100 mg was not successful. It is possible that the doses used in this study were not optimal or that repeated dosing may be necessary to achieve therapeutic effects. Agents under development that inhibit other subtypes of PDE remain promising for schizophrenia and dementia. C1 [Goff, Donald C.; Cather, Corinne; Freudenreich, Oliver; Henderson, David C.; Evins, A. Eden; Culhane, Melissa A.; Walsh, Jared P.] Harvard Univ, Sch Med, Dept Psychiat,Massachusetts Gen Hosp, MGH Schizophrenia Program,Freedom Trail Clin, Boston, MA 02114 USA. RP Goff, DC (reprint author), Harvard Univ, Sch Med, Dept Psychiat,Massachusetts Gen Hosp, MGH Schizophrenia Program,Freedom Trail Clin, 25 Staniford St,2nd Floor, Boston, MA 02114 USA. EM goff@psych.mgh.harvard.edu FU NIMH NIH HHS [2 K24 MH002025-06, K24 MH002025] NR 43 TC 39 Z9 39 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2009 VL 202 IS 1-3 BP 411 EP 417 DI 10.1007/s00213-008-1278-5 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 402PE UT WOS:000263024800034 PM 18716761 ER PT J AU Griffin, WC Lopez, MF Yanke, AB Middaugh, LD Becker, HC AF Griffin, William C., III Lopez, Marcelo F. Yanke, Amy B. Middaugh, Lawrence D. Becker, Howard C. TI Repeated cycles of chronic intermittent ethanol exposure in mice increases voluntary ethanol drinking and ethanol concentrations in the nucleus accumbens SO PSYCHOPHARMACOLOGY LA English DT Article DE Ethanol; Dependence; Withdrawal; Self-administration; Mice; Relapse; Microdialysis; Brain ethanol levels ID SUBSEQUENT WITHDRAWAL SEIZURES; C57BL/6J MICE; MICRODIALYSIS PROBES; ALCOHOL-WITHDRAWAL; DRUG-ADDICTION; ANIMAL-MODEL; RAT-BRAIN; ALLOSTASIS; SEVERITY; DOPAMINE AB This study examined the relationship between voluntary ethanol consumption and ethanol concentrations measured in the nucleus accumbens of ethanol dependent and nondependent C57BL/6J mice. Mice were offered ethanol in a two-bottle choice; limited access paradigm and consummatory behavior was monitored with lickometers. After baseline intake stabilized, mice received chronic intermittent ethanol (EtOH group) or air (CTL group) exposure by inhalation (16 h/day for 4 days) and then resumed drinking. Brain ethanol levels during voluntary drinking were measured by microdialysis procedures and compared to brain ethanol concentrations produced during chronic intermittent ethanol vapor exposure. Voluntary ethanol consumption progressively increased over repeated cycles of chronic intermittent ethanol exposure but remained unchanged in CTL mice. Analysis of lick patterns indicated EtOH mice consumed ethanol at a faster rate compared to CTL mice. The greater and faster rate of ethanol intake in EtOH mice produced higher peak brain ethanol concentrations compared to CTL mice, and these levels were similar to levels produced during chronic intermittent ethanol exposure. These results show that in this model of dependence and relapse drinking, dependent mice exhibit enhanced voluntary ethanol consumption relative to nondependent controls, which consequently produces blood and brain ethanol concentrations similar to those experienced during chronic intermittent ethanol exposure. C1 [Griffin, William C., III] Med Univ S Carolina, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA. [Griffin, William C., III; Lopez, Marcelo F.; Yanke, Amy B.; Middaugh, Lawrence D.; Becker, Howard C.] Ctr Drug & Alcohol Programs, Charleston Alcohol Res Ctr, Dept Psychiat & Behav Sci, Charleston, SC USA. [Middaugh, Lawrence D.; Becker, Howard C.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Becker, Howard C.] Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Griffin, WC (reprint author), Med Univ S Carolina, Ctr Drug & Alcohol Programs, MSC 861, Charleston, SC 29425 USA. EM griffinw@musc.edu FU NIH [AA10716, AA14095, AA13885] FX This work was supported by NIH grants AA10716, AA14095, and AA13885. The authors thank Judi S. Randall and Kay Fernandes for excellent technical assistance in conducting this work. NR 30 TC 75 Z9 75 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2009 VL 201 IS 4 BP 569 EP 580 DI 10.1007/s00213-008-1324-3 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 377PT UT WOS:000261263800011 PM 18791704 ER PT J AU Kim, SG Kim, CM Choi, SW Jae, YM Lee, HG Son, BK Kim, JG Choi, YS Kim, HO Kim, SY Oslin, DW AF Kim, Sung-Gon Kim, Cheol-Min Choi, Sam-Wook Jae, Young-Myo Lee, Hae-Gook Son, Bong-Ki Kim, Jeong-Gee Choi, Young-Sung Kim, Han-Oh Kim, Seong-Yeon Oslin, David W. TI A mu opioid receptor gene polymorphism (A118G) and naltrexone treatment response in adherent Korean alcohol-dependent patients SO PSYCHOPHARMACOLOGY LA English DT Article DE Naltrexone; Mu opioid receptor; Polymorphism; Korean alcohol dependent ID FUNCTIONAL POLYMORPHISM; BETA-ENDORPHIN; OPRM1; ASSOCIATION; MORPHINE; THERAPY; VARIANT; SENSITIVITY; POPULATION; ACTIVATION AB Previous studies have demonstrated an association between genetic polymorphisms of the mu opioid receptor gene (OPRM1) and response to naltrexone treatment. The Asp40 variant genotype previously shown to be associated with naltrexone treatment response is known to be relatively common among Koreans. This study was conducted to prospectively investigate the relationship between genotype and response to open-label naltrexone treatment in Korean alcohol-dependent subjects. Sixty-three alcohol-dependent subjects were prescribed naltrexone for 12 weeks in combination with cognitive behavioral therapy. Thirty-two subjects were adherent, taking the medication at least 80% of the treatment days [16 Asn40 (A/A) patients and 16 Asp40 variant (A/G or G/G) patients]. Subjects adherent to naltrexone treatment with one or two copies of the Asp40 allele took a significantly longer time than the Asn40 group to relapse (p=0.014). Although not significant, the Asn40 group treated with naltrexone had a 10.6 times greater relapse rate than the Asp40 variant group. There was no significant difference between the Asn40 group and the Asp40 variant group treated with naltrexone in rates of abstinence. These results demonstrating a higher therapeutic effect of naltrexone in Korean alcohol-dependent individuals with the Asp40 variant genotype than the Asn40 genotype are consistent with previous study results in individuals of European descent. This is the first study to examine the pharmacogenetics treatment response to naltrexone in non-European subjects. C1 [Kim, Sung-Gon] Pusan Natl Univ, Sch Med, Dept Psychiat, Pusan 602739, South Korea. [Kim, Cheol-Min] Haein Hosp, Yangsan, South Korea. [Choi, Sam-Wook] Univ Ulsan, Coll Med, Dept Psychiat, Ulsan 680749, South Korea. [Jae, Young-Myo] Bongseng Mem Hosp, Dept Psychiat, Pusan, South Korea. [Lee, Hae-Gook] Catholic Univ, Coll Med, Dept Psychiat, Seoul, South Korea. [Son, Bong-Ki] Hallym Univ, Med Ctr, Chuncheon Sacred Heart Hosp, Dept Psychiat, Chunchon, South Korea. [Kim, Jeong-Gee] Maryknoll Gen Hosp, Dept Psychiat, Pusan, South Korea. [Choi, Young-Sung] St Andrews Neuropsychiat Hosp, Icheon, Inchon, South Korea. [Kim, Han-Oh] Keyo Hosp, Keyo Med Fdn, Uiwang, South Korea. [Kim, Seong-Yeon] Dong A Univ, Div Management Informat Sci, Pusan, South Korea. [Oslin, David W.] Univ Penn, Dept Psychiat, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Oslin, David W.] VISN 4 MIRECC, Philadelphia, PA USA. RP Kim, SG (reprint author), Pusan Natl Univ, Sch Med, Dept Psychiat, 1-Ga 10,Ami Dong, Pusan 602739, South Korea. EM sungkim@pusan.ac.kr RI KIM, SEONG YEON/E-4164-2012 FU Je-il Pharmaceutical Co., Seoul, South Korea FX This work was supported by Je-il Pharmaceutical Co., Seoul, South Korea. NR 47 TC 61 Z9 62 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2009 VL 201 IS 4 BP 611 EP 618 DI 10.1007/s00213-008-1330-5 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 377PT UT WOS:000261263800015 PM 18795264 ER PT J AU Demitrack, MA Thase, ME AF Demitrack, Mark A. Thase, Michael E. TI Clinical Significance of Transcranial Magnetic Stimulation (TMS) in the Treatment of Pharmacoresistant Depression: Synthesis of Recent Data SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE major depression; treatment resistance; transcranial magnetic stimulation; TMS; antidepressant; efficacy; safety; randomized clinical trial; TMS study group ID STAR-ASTERISK-D; TREATMENT-RESISTANT DEPRESSION; DRUG-ADMINISTRATION DATABASE; FAILED MEDICATION TREATMENTS; DOUBLE-BLIND; MAJOR DEPRESSION; OLANZAPINE/FLUOXETINE COMBINATION; CONTROLLED-TRIAL; ANTIDEPRESSANT THERAPY; ADJUNCTIVE THERAPY AB Transcranial magnetic stimulation (TMS) is a novel treatment for patients with major depressive disorder. Although clearly safer and better tolerated than many other pharmacotherapeutic options or electroconvulsive therapy, questions have persisted about the magnitude of the efficacy of TMS in patients with pharmacoresistant depression, and the clinical significance of these outcomes. Previous studies have explored whether specific patient characteristics are associated with a greater likelihood of clinical benefit. In the largest such analysis conducted to date, the authors confirmed previous observations that the lower the number of prior failed antidepressant treatments, the better the clinical outcome of treatment with TMS. This relationship between prior treatment resistance and subsequent treatment outcome is consistent with previous evidence from antidepressant studies. The authors examined the clinical significance of the treatment effects seen with TMS in pharmacoresistant major depression in their recently completed studies by comparing these outcomes with the results reported in several large, comprehensive published reference datasets of antidepressant medications studied in both treatment-responsive and treatment-resistant patient populations. The efficacy of TMS demonstrated in randomized controlled trials was comparable to that of pharmaceutical antidepressants studied in similarly designed registration trials and to the adjunctive use of atypical antipsychotic medications in controlled trials of antidepressant non-responders. These data may be helpful in treatment-planning decisions when using TMS in clinical practice. Psychopharmacology Bulletin. 2009;42(2):5-38. C1 [Demitrack, Mark A.] Neuronetics Inc, Malvern, PA 19355 USA. [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Demitrack, MA (reprint author), Neuronetics Inc, 31 Gen Warren Blvd, Malvern, PA 19355 USA. EM mdemitrack@neuronetics.com RI Demitrack, Mark/I-7697-2013 FU Eli Lilly and Company; Sepracor, Inc.; Neuronetics Inc. FX Clinical trial posted on www.clinicaltrials.gov. Listing No. NCT 00104611. Supported by a grant from Neuronetics Inc. Dr. Thase has served as an advisor to AstraZeneca, Bristol-Myers Squibb Company, Cephalon, Inc., Cyberonics, Inc., Eli Lilly & Co., Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, MedAvante, Inc., Neuronetics, Inc., Novartis, Organon International, Sepracor, Inc., Shire US Inc., Supernus Pharmaceuticals and Wyeth Pharmaceuticals. He has received research grant support from Eli Lilly and Company and Sepracor, Inc. He has served on the Speaker's Bureaus for AstraZeneca, Bristol-Myers Squibb Company, Cyberonics, Inc., Eli Lilly & Co., GlaxoSmithKline, Sanofi Aventis, Schering Plough (formerly Organon, Inc.) and Wyeth Pharmaceuticals. He reports having equity holdings in MedAvante, Inc. and receives royalties for work he created and was published by American Psychiatric Publishing, Inc., Guilford Publications, Herald House and W. W. Norton & Company, Inc. NR 45 TC 25 Z9 26 U1 4 U2 8 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2009 VL 42 IS 2 BP 5 EP 38 PG 34 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 641OH UT WOS:000281137100001 PM 19629020 ER PT J AU Kornstein, SG Fava, M Jiang, Q Tourian, KA AF Kornstein, Susan G. Fava, Maurizio Jiang, Qin Tourian, Karen A. TI Analysis of Depressive Symptoms in Patients With Major Depressive Disorder Treated With Desvenlafaxine or Placebo SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE desvenlafaxine; 17-item Hamiltion Rating Scale for Depression; Montgomery Asberg Depression Rating Scale; major depressive disorder; Diagnostic and Statistical Manual of Mental Disorder; Fourth Edition ID DOSE-RESPONSE; PHYSICAL SYMPTOMS; RATING-SCALE; DULOXETINE; VENLAFAXINE; ANXIETY; EFFICACY; METAANALYSIS; REPLICATION; REMISSION AB Background: The aim of this study was to evaluate the impact of desvenlafaxine on a broad range of major depressive disorder (MDD) symptoms. Methods: Data were pooled from 9 double-blind, randomized, placebo-controlled, 8-week studies of desvenlafaxine in adult outpatients with MDD. Intent-to-treat participants received fixed-(50, 100, 200, or 400 mg/d; n = 1342) or flexible-dose (100 to 400 mg/d, n = 463) desvenlafaxine or placebo (n = 1108). Final on-therapy scores for individual items of the 17-item Hamilton Rating Scale for Depression (HAMD(17)) and the Montgomery Asberg Depression Rating Scale (MADRS) were compared between groups using analysis of covariance. Efficacy at different doses was examined using the subset of fixed-dose studies. Results: Based on differences in adjusted mean changes from baseline (desvenlafaxine vs placebo), statistically significant advantages with desvenlafaxine (50 to 400 mg/d, all doses pooled) vs placebo were seen for 10 of the 17 HAM-D17 items: depressed mood (-0.4; P < 0.001), feelings of guilt (-0.2; P < 0.001), suicide (-0.1; P < 0.001), late insomnia (-0.1; P = 0.001), work and activities (-0.2; P < 0.001), psychomotor retardation (-0.1; P < 0.001), agitation (-0.1; P < 0.001), psychic anxiety (-0.3; P < 0.001), general somatic symptoms (-0.2; P < 0.001), and genital symptoms (-0.1; P = 0.003). Desvenlafaxine (50 to 400 mg/d, pooled) was significantly better than placebo on all MADRS items (range: -0.1 to -0.5; all P <= 0.019), except "reduced appetite" (-0.01, P > 0.05). Symptom relief was similar with all desvenlafaxine doses examined, including 50 mg/d. Conclusions: Shortterm desvenlafaxine therapy (50 to 400 mg/d) improved a broad range of emotional and physical symptoms in outpatients with MDD. Psychopharmacology Bulletin. 2009; 42(3): 21-35. C1 [Kornstein, Susan G.] Virginia Commonwealth Univ, Dept Psychiat, Sch Med, Mood Disorders Inst, Richmond, VA 23298 USA. [Kornstein, Susan G.] Virginia Commonwealth Univ, Inst Womens Hlth, Richmond, VA 23298 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Jiang, Qin] Wyeth Res, Collegeville, PA USA. [Tourian, Karen A.] Wyeth Res, Clin Res & Dev, Neurosci, Paris, France. RP Kornstein, SG (reprint author), Virginia Commonwealth Univ, Dept Psychiat, Sch Med, Mood Disorders Inst, POB 980710, Richmond, VA 23298 USA. EM skornste@vcu.edu FU Wyeth Research FX Research supported by Wyeth Research. The authors would like to thank Karen Dougherty, PhD of Advogent for medical writing assistance and Jennifer B. Hutcheson, BA for editing assistance on this manuscript. NR 32 TC 2 Z9 2 U1 0 U2 3 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2009 VL 42 IS 3 BP 21 EP 35 PG 15 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 696QX UT WOS:000285457600002 PM 19752839 ER PT J AU Busch, AB Frank, RG Sachs, G Normand, SLT AF Busch, Alisa B. Frank, Richard G. Sachs, Gary Normand, Sharon-Lise T. TI Bipolar-I Patient Characteristics Associated with Differences in Antimanic Medication Prescribing SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE bipolar disorder; psychopharmacology; medication therapy management; guideline adherence; quality of health care ID NUTRITION EXAMINATION SURVEY; DISEASE RISK-FACTORS; 3RD NATIONAL-HEALTH; QUALITY-OF-CARE; CARDIOVASCULAR-DISEASE; RACIAL DISPARITIES; MOOD STABILIZERS; MANAGED CARE; DOUBLE-BLIND; DISORDER AB Objective: Second-generation antipsychotics offer more choice in antimanic pharmacologic treatment. Unclear though is whether they are expanding antimantic treatment, replacing mood stabilizers, or if/which patient characteristics influence prescribing choices. We studied the association between patient characteristics and patient-reported antimanic medication use upon entry in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Experimental Design: Observational study using STEP-BD baseline data from bipolar-I patients (N = 1,943) during years 2000-2004. Two logistic regression models (binomial and multinomial) were estimated to examine associations between patient chacteristics and patient-reported drugs use: 1) any antimanic medication (antipsychotic or mood stabilizer), and 2) mood stabilizer, antipsychotic monotherapy, or neither: Principal Observations: At study entry over 80% of participants reported receiving at least one antimanic medication; 73% a mood stabilizer specifically. In general, there was no association between study year and the odds of entering on antimanic medication. Measures of psychiatric severity or complexity were more likely to be associated with differences in the drugs used; co-occuring medical conditions were not. Depressed states were associated with similar odds of antipsychotic monotherapy as elevated or mixed states. Compared to whites, blacks had greater odds of entering on antipsychotic monotherapy relative to a mood stabilizer. Conclusions: Despite increasing pharmacotherapy options, we found no evidence that over time more patients received antimanic medication. Not all prescribing differences were consistent with the medical literature. Also, blacks were more likely to receive antipsychotic monotherapy, even after adjusting for clinical characteristics. Future research examining provider characteristics that influence prescribing is needed Psychopharmacology Bulletin. 2009;42(1):35-49. C1 [Busch, Alisa B.] McLean Hosp, Alcohol & Drug Abuse Treatment Program, Belmont, MA 02478 USA. [Busch, Alisa B.; Frank, Richard G.; Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Cambridge, MA 02138 USA. [Busch, Alisa B.; Sachs, Gary] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Sachs, Gary] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Sachs, Gary] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. RP Busch, AB (reprint author), McLean Hosp, Alcohol & Drug Abuse Treatment Program, Proctor Bldg,115 Mill St, Belmont, MA 02478 USA. EM abusch@hcp.med.harvard.edu FU NIMH [K01 MH071714, R01 MH069721, R01-MH61434] FX The authors gratefully acknowledge support by the NIMH for this research: Dr. Busch (K01 MH071714), Dr. Frank (R01 MH069721), and Dr. Normand (R01-MH61434). NR 40 TC 4 Z9 4 U1 3 U2 4 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2009 VL 42 IS 1 BP 35 EP 49 PG 15 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 641OG UT WOS:000281137000003 PM 19204650 ER PT J AU Fleurence, R Williamson, R Jing, YH Kim, E Tran, QV Pikalov, A Thase, ME AF Fleurence, Rachael Williamson, Rebecca Jing, Yonghua Kim, Edward Tran, Quynh-Van Pikalov, Andrei Thase, Michael E. TI A Systematic Review of Augmentation Strategies for Patients with Major Depressive Disorder SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE major depression; treatment resistant; atypical antipsychotics; systematic review ID TREATMENT-RESISTANT DEPRESSION; PLACEBO-CONTROLLED TRIAL; STAR-ASTERISK-D; DOUBLE-BLIND; OLANZAPINE/FLUOXETINE COMBINATION; REFRACTORY DEPRESSION; LITHIUM AUGMENTATION; TRICYCLIC ANTIDEPRESSANTS; MIANSERIN AUGMENTATION; ADJUNCTIVE THERAPY AB Major depressive disorder (MDD) is a leading cause of disability worldwide. Clinicians need to determine the most appropriate and effective interventions for patients who do not benefit from first-line treatment. A systematic review of the literature on augmentation strategies for major depression was conducted. A total of 32 eligible studies were included in the final review. Identified augmentation strategies included lithium, thyroid hormone, buspirone, stimulant drugs (methylphenidate and modafinil), and atypical antipsychotics (olanzapine, quetiapine, aripiprazole, and risperidone). Additional studies used other augmentation strategies (yohimbine, atomoxetine, inositol, testosterone, and lamotrigine), or combinations with a second antidepressant (mianserin, mirtazapine, and desipramine). There was no evidence of clinical efficacy as measured by response in augmentation with buspirone, testosterone, methylphenidate, yohimbine, inositol, and atomoxetine. Although some studies of combined antidepressant therapy and lithium augmentation did show statistically significant clinical effects, results were inconsistent across studies. The only eligible study of thyroid augmentation was positive, though this study evaluated patients treated with tricyclic antidepressants. It is possible due to small sample sizes, that some of the trials failed to detect significant differences versus placebo because of inadequate statistical power. Adjunctive therapy with atypical antipsychotics showed higher response rates compared with antidepressant monotherapy and placebo but also had more withdrawals due to adverse events. Given ongoing concerns with the longer term tolerability and safety of the atypical antipsychotics, future research will need to investigate optimal duration of augmentation therapy in patients with major depressive disorder who do not respond to first line therapy. Psychopharmacology Bulletin. 2009; 42(3): 57-90. C1 [Fleurence, Rachael; Williamson, Rebecca] United BioSource Corp, Ctr Hlth Econ & Sci Policy, Bethesda, MD 20814 USA. [Jing, Yonghua] Bristol Myers Squibb, Plainsboro, NJ USA. [Kim, Edward] Eisai Inc, Woodcliff Lake, NJ USA. [Tran, Quynh-Van; Pikalov, Andrei] Otsuka Amer Pharmaceut, Rockville, MD USA. [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Fleurence, R (reprint author), United BioSource Corp, Ctr Hlth Econ & Sci Policy, 7101 Wisconsin Ave,Suite 600, Bethesda, MD 20814 USA. EM rachael.fleurence@unitedbiosource.com NR 57 TC 37 Z9 37 U1 0 U2 1 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2009 VL 42 IS 3 BP 57 EP 90 PG 34 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 696QX UT WOS:000285457600004 PM 19752841 ER PT J AU Robert, S Hamner, MB Durkalski, VL Brown, MW Ulmer, HG AF Robert, Sophie Hamner, Mark B. Durkalski, Valerie L. Brown, Mary W. Ulmer, Helen G. TI An Open-Label Assessment of Aripiprazole in the Treatment of PTSD SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE posttraumatic stress disorder; psychopharmacology; treatment; second generation antipsychotics; aripiprazole ID POSTTRAUMATIC-STRESS-DISORDER; MAJOR DEPRESSIVE DISORDER; DOUBLE-BLIND; COMBAT VETERANS; ADJUNCTIVE RISPERIDONE; PSYCHOTIC SYMPTOMS; SLEEP QUALITY; RATING-SCALE; OPEN TRIAL; PLACEBO AB Background: Recent studies suggest that atypical antipsychotics effective augmentation strategies for the treatment of posttraumatic stress (PTSD). Limited data were available on the newest agent, aripiprazole, so we aimed to evaluate its efficacy and tolerability in the treatment of PTSD. Methods: A 12-week, prospective, open-label, flexible-dose, adjunctive trial of apripiprazole was conducted in military veterans meeting DSM-IV criteria for PTSD. Concomitant psychiatric medications continued unchanged, except for other neuroleptics which were not allowed. The primary outcome variable was change from baseline in the Clincian Administered PTSD scale (CAPS). Results: All 17 subjects were male with an average age of 57 years. Total CAPS scores decreased from 78.2 (SD = 17.8) at baseline 60.0 (23.5) at study end (p = 0.002). Re-experiencing (CAPS-B) and avoidance/numbing symptoms (CAPS-C) were significantly improved, and trend level reductions were observed in hyperarousal symptoms (CAPS-D). Fifty-three percent (9/17) were considered responders, as defined by a decrease in total CAPS scores of at least 20%. Reductions in the Positive and Negative Symptom Scale (PANS) total score and positive and general psychopathology subscale scores were statistically significant. The final average dose of aripiprazole was 13.06 (SD = 6.45) mg daily. Nine patients discontinued because of side effects. The most common adverse events consisted of gastro-intestinal disturbances, sedation, and psychomotor activation Tolerability was improved with lower starting doses (e.g., 5 mg daily) and slow titration. Conclusions: Addition of aripiprazole to ongoing treatment further reduced PTSD symptoms in military veterans with severe PTSD. These preliminary findings await confirmation in randomized, controlled trials Psychopharmacology Bulletin. 2009;42(1):69-80. C1 [Robert, Sophie] Ralph H Johnson VA Med Ctr, Mental Hlth Serv 116, Charleston, SC 29401 USA. [Robert, Sophie; Hamner, Mark B.; Durkalski, Valerie L.; Brown, Mary W.; Ulmer, Helen G.] Med Univ S Carolina, Charleston, SC USA. RP Robert, S (reprint author), Ralph H Johnson VA Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM robertso@musc.edu FU Bristol-Myers Squibb; Abbott Laboratories; AstraZeneca; Forest Laboratories; Janssen Pharmaceutica; Eli Lilly; Organon; Otsuka Pharmaceutical FX This material is the result of work supported with resources and the use of facilities at the Ralph H. Johnson VA Medical Center. The study was funded by Bristol-Myers Squibb as an investigator-initiated grant to Dr. Hamner.; Dr. Robert reports no other significant commercial relationships relevant to the subject matter of this article. Dr. Hamner has been on the speaker's bureau, consultant for, and/or recipient of research grant support from Abbott Laboratories, Bristol-Myers Squibb, AstraZeneca, Forest Laboratories, Janssen Pharmaceutica, Eli Lilly, Organon, and Otsuka Pharmaceutical. He owns stock in Pfizer Inc., and Merck & Co., Other authors report no relevant financial interests or personal affiliations in connection with the content of this paper. NR 77 TC 18 Z9 18 U1 3 U2 4 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2009 VL 42 IS 1 BP 69 EP 80 PG 12 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 641OG UT WOS:000281137000005 PM 19204652 ER PT J AU Metzger, LJ Clark, CR McFarlane, AC Veltmeyer, MD Lasko, NB Paige, SR Pitman, RK Orr, SP AF Metzger, Linda J. Clark, C. Richard McFarlane, Alexander C. Veltmeyer, Melinda D. Lasko, Natasha B. Paige, Stephen R. Pitman, Roger K. Orr, Scott P. TI Event-related potentials to auditory stimuli in monozygotic twins discordant for combat: Association with PTSD SO PSYCHOPHYSIOLOGY LA English DT Article DE Twin studies; Post-traumatic stress disorder; Event-related potentials; P3b ID POSTTRAUMATIC-STRESS-DISORDER; EVOKED-POTENTIALS; P300; SCHIZOPHRENIA; SCALE; RELIABILITY; ATTENTION; DEMENTIA; VETERANS; EXPOSURE AB Studies have demonstrated ERP abnormalities related to concentration difficulties in post-traumatic stress disorder (PTSD). We used an identical-twin, case-control design to investigate whether these abnormalities reflect pre-trauma vulnerability or the acquired consequence of PTSD. Vietnam combat veterans and their non-combat-exposed, identical twins completed a three-tone oddball task. Veterans with PTSD had delayed target N2 latencies compared to veterans without PTSD. In a small nonmedicated, nonsmoking subsample, veterans with PTSD also had significantly diminished target P3b amplitudes. A mixed-model, random-effects analysis on the nonmedicated, nonsmoking subsample that included the combat-unexposed co-twins showed a significant Diagnosis x Combat Exposure interaction for target P3b amplitude. Results replicate increased N2 latency and diminished P3b amplitude in PTSD and suggest that diminished P3b amplitude is an acquired condition in PTSD. C1 [Metzger, Linda J.; Lasko, Natasha B.; Pitman, Roger K.; Orr, Scott P.] Vet Affairs Med Ctr, Manchester, NH USA. [Metzger, Linda J.; Lasko, Natasha B.; Pitman, Roger K.; Orr, Scott P.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Metzger, Linda J.; Lasko, Natasha B.; Pitman, Roger K.; Orr, Scott P.] Harvard Univ, Sch Med, Boston, MA USA. [Clark, C. Richard; Veltmeyer, Melinda D.] Flinders Univ S Australia, Cognit Neurosci Lab, Adelaide, SA, Australia. [Clark, C. Richard; Veltmeyer, Melinda D.] Flinders Univ S Australia, Sch Psychol, Adelaide, SA, Australia. [McFarlane, Alexander C.] Univ Adelaide, Queen Elizabeth Hosp, Dept Psychiat, Woodville, SA 5011, Australia. RP Orr, SP (reprint author), Dept Vet Affairs Med Ctr, Res Serv 151, 718 Smyth Rd, Manchester, NH 03104 USA. EM scott.orr@va.gov RI clark, christopher richard/B-3525-2012 FU NIMH NIH HHS [R01 MH054636, MH54636] NR 46 TC 7 Z9 7 U1 3 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JAN PY 2009 VL 46 IS 1 BP 172 EP 178 DI 10.1111/j.1469-8986.2008.00720.x PG 7 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 387WW UT WOS:000261983300019 PM 18803598 ER PT J AU Otto, MW Basden, SL McHugh, RK Kantak, KM Deckersbach, T Cather, C Goff, DC Hofmann, SG Berry, AC Smits, JAJ AF Otto, Michael W. Basden, Shawnee L. McHugh, R. Kathryn Kantak, Kathleen M. Deckersbach, Thilo Cather, Corinne Goff, Donald C. Hofmann, Stefan G. Berry, Angela C. Smits, Jasper A. J. TI Effects of D-Cycloserine Administration on Weekly Nonemotional Memory Tasks in Healthy Participants SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE D-Cycloserine; Memory tasks; Learning tasks ID OBSESSIVE-COMPULSIVE DISORDER; SOCIAL ANXIETY DISORDER; D-ASPARTATE RECEPTORS; PARTIAL AGONIST; EXPOSURE THERAPY; GLYCINE SITE; NMDA RECEPTOR; EXTINCTION; FEAR; AUGMENTATION AB Background: The application of weekly doses of D-cycloserine (DCS) to the enhancement of exposure-based treatments has been a particular achievement of translational research. It is not known, however, whether this enhancement effect can be extended to other forms of learning. In this study, we investigated the relative benefit of DCS versus placebo for enhancing nonemotional verbal and nonverbal memory across weekly trials. Methods: We randomized healthy participants to weekly doses of 50 mg DCS or placebo, with 33 participants completing a 5-week protocol. Participants completed baseline neuropsychological evaluation and then 4 subsequent weeks of repeated learning tasks. Results: No improvement was found in immediate or delayed memory following single doses of DCS for the memory tasks repeated on a weekly basis. Trends for an advantage of DCS were evident for novel word lists given each week. Conclusions: The learning tasks in our study were particularly distinct from the extinction learning paradigms that have shown strong DCS effects, and we were unable to demonstrate useful DCS effects with these nonemotional stimuli. Additional research is needed to elucidate the bounds of DCS augmentation effects on therapeutic learning. Copyright (C) 2008 S. Karger AG, Basel C1 [Otto, Michael W.; Basden, Shawnee L.; McHugh, R. Kathryn; Kantak, Kathleen M.; Hofmann, Stefan G.] Boston Univ, Boston, MA 02215 USA. [Deckersbach, Thilo; Cather, Corinne; Goff, Donald C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Berry, Angela C.; Smits, Jasper A. J.] So Methodist Univ, University Pk, TX USA. RP Otto, MW (reprint author), Boston Univ, 648 Beacon St,5th Floor, Boston, MA 02215 USA. EM mwotto@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 FU NIMH NIH HHS [K24 MH002025] NR 35 TC 20 Z9 20 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2009 VL 78 IS 1 BP 49 EP 54 DI 10.1159/000172620 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 389PY UT WOS:000262108200008 PM 19018157 ER PT J AU Fava, M Iosifescu, DV Pedrelli, P Baer, L AF Fava, Maurizio Iosifescu, Dan V. Pedrelli, Paola Baer, Lee TI Reliability and Validity of the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE Cognition; Fatigue; Depression; Cognitive and Physical Functioning Questionnaire ID MAJOR DEPRESSIVE DISORDER; BIPOLAR DISORDER; NEUROPSYCHOLOGICAL FUNCTION; ANTIDEPRESSANT TREATMENT; EUTHYMIC PATIENTS; FATIGUE; MEMORY; SCALE; PSYCHOPATHOLOGY; DYSFUNCTION AB Background: We have recently developed the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ), a brief scale to measure cognitive and executive dysfunction in mood and anxiety disorders, and we here report on its reliability and validity. Methods: The internal consistency of the CPFQ was assessed by computing Cronbach's coefficient alpha based upon the average intercorrelation of the 7 items of the CPFQ in a sample of depressed outpatients and by factor analyzing data from the same sample to confirm that the scale is unifactorial and measuring a single construct. Test-retest reliability of the CPFQ was assessed in a different sample of depressed outpatients by computing Pearson's correlation coefficient between pretreatment screening scores and pretreatment baseline scores. Sensitivity to change of the CPFQ was assessed by computing the dependent t test for the subjects in the active treatment condition in the second sample of depressed outpatients. Finally, convergent validity for the CPFQ was assessed in two different ways. Results: We found that the CPFQ is a unifactorial scale, with strong internal consistency. It has good temporal stability as indicated by high test-retest reliability. The CPFQ was also found to be sensitive to change with treatment and displayed convergent validity by significant correlations with other measures of sleepiness, fatigue, apathy and neuropsychological functioning. Although, as expected, the CPFQ was significantly correlated with a measure of depression, the moderate correlation (r similar to 0.30) indicates that the CPFQ is measuring a different construct. Conclusion: In summary, the CPFQ is a unifactorial scale, with strong internal consistency, good temporal stability and sensitivity to change with treatment. Further studies will be needed to assess the validity and reliability of this instrument in other psychiatric and neuropsychiatric conditions associated with cognitive dysfunction. Copyright (C) 2009 S. Karger AG, Basel C1 [Fava, Maurizio; Iosifescu, Dan V.; Pedrelli, Paola; Baer, Lee] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, Bulfinch 351,55 Fruit St, Boston, MA 02114 USA. EM mfava@partners.org FU Abbott Laboratories; Alkermes; Aspect Medical Systems; Astra-Zeneca; Bristol-Myers Squibb Co.; Cephalon; Eli Lilly Co.; Forest Pharmaceuticals Inc; Glaxo-Smith-Kline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Novartis; Organon Inc.; Pamlab LLC; Pfizer Inc.; Pharmavite; Roche; Sanofi/Synthelabo; Solvay Pharmaceuticals Inc.; Wyeth-Ayerst Laboratories. Advisory/Consulting: Aspect Medical Systems; Bayer AG; Auspex Pharmaceuticals; Best Practice Project Management Inc.; Biovail Pharmaceuticals Inc.; Brain Cells Inc.; Compellis; CNS Response; Cypress Pharmaceuticals; Dov Pharmaceuticals; EPIX Pharmaceuticals; Fabre-Kramer Pharmaceuticals Inc.; Forest Pharmaceuticals Inc.; Grunenthal GmbH; Janssen Pharmaceutica; Jazz Pharmaceuticals; Knoll Pharmaceutical Co.; Lundbeck; Medavante Inc.; Merck; Neuronetics; Nutrition 21 FX Abbott Laboratories; Alkermes; Aspect Medical Systems; Astra-Zeneca; Bristol-Myers Squibb Co.; Cephalon; Eli Lilly & Co.; Forest Pharmaceuticals Inc.; Glaxo-Smith-Kline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Novartis; Organon Inc.; Pamlab LLC; Pfizer Inc.; Pharmavite; Roche; Sanofi/Synthelabo; Solvay Pharmaceuticals Inc.; Wyeth-Ayerst Laboratories. Advisory/Consulting: Aspect Medical Systems; Astra-Zeneca; Bayer AG; Auspex Pharmaceuticals; Best Practice Project Management Inc.; Biovail Pharmaceuticals Inc.; Brain Cells Inc.; Bristol-Myers Squibb Co.; Cephalon; Compellis; CNS Response; Cypress Pharmaceuticals; Dov Pharmaceuticals; Eli Lilly & Co.; EPIX Pharmaceuticals; Fabre-Kramer Pharmaceuticals Inc.; Forest Pharmaceuticals Inc.; Glaxo-Smith-Kline; Grunenthal GmbH; Janssen Pharmaceutica; Jazz Pharmaceuticals; J & J Pharmaceuticals; Knoll Pharmaceutical Co.; Lundbeck; Medavante Inc.; Merck; Neuronetics; Novartis; Nutrition 21; Organon Inc.; Pamlab LLC; Pfizer Inc.; Pharmastar; Pharmavite; Precision Human Biolaboratory; Roche; Sanofi/Synthelabo; Sepracor; Solvay Pharmaceuticals Inc.; Somaxon; Somerset Pharmaceuticals; Takeda; Tetragenex Inc.; Transcept Pharmaceuticals; Wyeth-Ayerst Laboratories. Speaking: Astra-Zeneca; Boehringer-Ingelheim; Bristol-Myers Squibb Co.; Cephalon; Eli Lilly & Co.; Forest Pharmaceuticals Inc.; Glaxo-Smith-Kline; Novartis; Organon Inc.; Pfizer Inc.; Pharmastar; Wyeth-Ayerst Laboratories. Equity Holdings: Compellis; Medavante. NR 39 TC 74 Z9 74 U1 4 U2 10 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2009 VL 78 IS 2 BP 91 EP 97 DI 10.1159/000201934 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 409VT UT WOS:000263534600004 PM 19218827 ER PT J AU Warden, D Trivedi, MH Wisniewski, SR Lesser, IM Mitchell, J Balasubramani, GK Fava, M Shores-Wilson, K Stegman, D Rush, AJ AF Warden, Diane Trivedi, Madhukar H. Wisniewski, Stephen R. Lesser, Ira M. Mitchell, Jeff Balasubramani, G. K. Fava, Maurizio Shores-Wilson, Kathy Stegman, Diane Rush, A. John TI Identifying Risk for Attrition during Treatment for Depression SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE Attrition; Adherence; Depression; Antidepressant; Attitudes ID STAR-ASTERISK-D; MEASUREMENT-BASED CARE; DIAGNOSTIC SCREENING QUESTIONNAIRE; SEQUENCED TREATMENT ALTERNATIVES; REPORT QIDS-SR; ANTIDEPRESSANT TREATMENT; PHYSICIAN COMMUNICATION; PSYCHOMETRIC EVALUATION; TREATMENT GUIDELINES; CLINICAL-PRACTICE AB Background: Understanding patients' ambivalence about treatment persistence may be useful in tailoring retention interventions for individual patients with major depressive disorder. Methods: Participants (n = 265) with major depressive disorder were enrolled into an 8-week trial with a selective serotonin reuptake inhibitor. At baseline and week 2, the participants were asked about their intent to return for the next visit, complete the study and continue in the study should they experience side effects or no improvement. Dropouts were defined as participants who discontinued attending clinic visits before completing the trial. Results: Participants who at baseline reported an uncertain/negative intent to continue if they experienced side effects or no improvement dropped out at a significantly higher rate by weeks 6 and 8. Uncertain/negative intent at week 2 predicted attrition at all following visits. Dropouts without side effects were more likely to have reported an uncertain/negative intent to attend at both baseline and week 2, while dropouts who experienced side effects were more likely to have reported an uncertain/negative intent to attend only at baseline. Positive intent to continue was associated with greater symptom improvement in both dropouts and completers despite the possibility of lack of efficacy. Conclusions: Participants' pretreatment concerns about continuing antidepressant treatment in the presence of side effects signals challenges to the completion of a full 8-week acute phase treatment, even if the participant does not develop side effects. Individualized review of concerns and tailoring appropriate interventions may be necessary to reduce attrition. Copyright (C) 2009 S. Karger AG, Basel C1 [Warden, Diane; Trivedi, Madhukar H.; Shores-Wilson, Kathy; Stegman, Diane; Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Wisniewski, Stephen R.; Balasubramani, G. K.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. [Lesser, Ira M.] Harbor UCLA Med Ctr, Dept Psychiat, Torrance, CA 90509 USA. [Lesser, Ira M.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Mitchell, Jeff] Laureate Psychiat Clin & Hosp, Tulsa, OK USA. [Fava, Maurizio] Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. [Rush, A. John] Duke Natl Univ Singapore, Singapore, Singapore. RP Warden, D (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Diane.Warden@UTSouthwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Goundappa K, Balasubramani/0000-0001-7221-1825 FU National Institute of Mental Health [N01MH90003] FX This project was funded by the National Institute of Mental Health under Contract N01MH90003 to UT Southwestern Medical Center at Dallas (P. I.: M. H. Trivedi). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. This analysis was also supported in part by a National Alliance for Research on Schizophrenia and Depression Young Investigator Award (D. Warden). We would also like to acknowledge the editorial support of Jon Kilner, MS, MA. NR 47 TC 15 Z9 15 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2009 VL 78 IS 6 BP 372 EP 379 DI 10.1159/000235977 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 494CX UT WOS:000269788200010 PM 19738403 ER PT J AU Wideroff, L Phillips, KA Randhawa, G Ambs, A Armstrong, K Bennett, CL Brown, ML Donaldson, MS Follen, M Goldie, SJ Hiatt, RA Khoury, MJ Lewis, G McLeod, HL Piper, M Powell, I Schrag, D Schulman, KA Scott, J AF Wideroff, Louise Phillips, Kathryn A. Randhawa, Gurvaneet Ambs, Anita Armstrong, Katrina Bennett, Charles L. Brown, Martin L. Donaldson, Molla S. Follen, Michele Goldie, Sue J. Hiatt, Robert A. Khoury, Muin J. Lewis, Graham McLeod, Howard L. Piper, Margaret Powell, Isaac Schrag, Deborah Schulman, Kevin A. Scott, Joan TI A Health Services Research Agenda for Cellular, Molecular and Genomic Technologies in Cancer Care SO PUBLIC HEALTH GENOMICS LA English DT Review DE Genomics; Health services research; Emerging technologies; Translational research ID COST-EFFECTIVENESS ANALYSIS; METASTATIC BREAST-CANCER; REPORTS RADAR PROJECT; ADVERSE DRUG EVENTS; CLINICAL-PRACTICE; RACIAL-DIFFERENCES; CERVICAL-CANCER; PUBLIC-HEALTH; PROPHYLACTIC VACCINES; PROSTATE-CANCER AB Background: In recent decades, extensive resources have been invested to develop cellular, molecular and genomic technologies with clinical applications that span the continuum of cancer care. Methods: In December 2006, the National Cancer Institute sponsored the first workshop to uniquely examine the state of health services research on cancer-related cellular, molecular and genomic technologies and identify challenges and priorities for expanding the evidence base on their effectiveness in routine care. Results: This article summarizes the workshop outcomes, which included development of a comprehensive research agenda that incorporates health and safety endpoints, utilization patterns, patient and provider preferences, quality of care and access, disparities, economics and decision modeling, trends in cancer outcomes, and health-related quality of life among target populations. Conclusions: Ultimately, the successful adoption of useful technologies will depend on understanding and influencing the patient, provider, health care system and societal factors that contribute to their uptake and effectiveness in 'real-world' settings. Copyright (C) 2009 S. Karger AG, Basel C1 [Wideroff, Louise; Ambs, Anita; Brown, Martin L.] NCI, Bethesda, MD 20892 USA. [Phillips, Kathryn A.; Hiatt, Robert A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Randhawa, Gurvaneet] Agcy Healthcare Res & Qual, Rockville, MD USA. [Armstrong, Katrina] Univ Penn, Philadelphia, PA 19104 USA. [Bennett, Charles L.] Northwestern Univ, Evanston, IL USA. [Donaldson, Molla S.] George Washington Univ, Washington, DC USA. [Follen, Michele] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Goldie, Sue J.] Harvard Univ, Boston, MA 02115 USA. [Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Atlanta, GA USA. [McLeod, Howard L.] Univ N Carolina, Chapel Hill, NC USA. [Piper, Margaret] Blue Cross Blue Shield Assoc Technol Evaluat Ctr, Chicago, IL USA. [Powell, Isaac] Wayne State Univ, Detroit, MI USA. [Schulman, Kevin A.] Duke Univ, Durham, NC USA. [Scott, Joan] Johns Hopkins Univ, Baltimore, MD USA. [Lewis, Graham] Univ York, Heslington, England. RP Wideroff, L (reprint author), Natl Inst Drug Abuse, Epidemiol Res Branch, Div Epidemiol Serv & Prevent Res, 6001 Executive Blvd,Suite 5153 MSC 9589, Bethesda, MD 20892 USA. EM Wideroff@nih.gov RI Hernandez, Jessica/G-6527-2011; OI Piper, Margaret/0000-0002-6231-9653 FU NCI [263-MQ-610769, 263-MQ-612315, 263-MQ-612317, 263MQ-700870, 263-MQ-701381, 263-MQ612321, 263-MQ-611969, 263-MQ-612316, 263-MQ-612323, 263-MQ-611964, 263MQ-612324, 263-MQ-611967]; [HHSN261200700005C] FX The study was funded by the NCI (263-MQ-610769 to K. A. P.; 263-MQ-612315 to K. A.; 263-MQ-612317 to C. L. B.; 263MQ-700870 to M. S. D.; 263-MQ-701381 to M. F.; 263-MQ612321 to S. J. G.; 263-MQ-611969 to R. A. H.; 263-MQ-612316 to H. L. M.; 263-MQ-612323 to I. P.; 263-MQ-611964 to D. S.; 263MQ-612324 to K. A. S.; 263-MQ-611967 to the University of York; HHSN261200700005C to Scientific Consulting Group for organizational and editorial assistance). NR 83 TC 12 Z9 12 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 J9 PUBLIC HEALTH GENOMI JI Pub. Health Genomics PY 2009 VL 12 IS 4 BP 233 EP 244 DI 10.1159/000203779 PG 12 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 432LX UT WOS:000265136600004 PM 19367091 ER PT J AU Mimiaga, MJ Reisner, SL Tetu, AM Bonafide, KE Cranston, K Bertrand, T Novak, DS Mayer, KH AF Mimiaga, Matthew J. Reisner, Sari L. Tetu, Ashley M. Bonafide, Katherine E. Cranston, Kevin Bertrand, Thomas Novak, David S. Mayer, Kenneth H. TI Partner Notification After STD and HIV Exposures and Infections: Knowledge, Attitudes, and Experiences of Massachusetts Men Who Have Sex with Men SO PUBLIC HEALTH REPORTS LA English DT Article ID SEXUALLY-TRANSMITTED-DISEASES; HOMOSEXUALLY ACTIVE MEN; CAGE QUESTIONNAIRE; HIDDEN POPULATIONS; REFERRAL SERVICES; UNITED-STATES; GAY MEN; RISK; INTERNET; SURVEILLANCE AB Objectives. We assessed Boston-area men who have sex with men (MSM) in terms of their knowledge of partner notification (PN)/partner counseling and referral services (PCRS) and intentions to use such services if exposed to/infected with a sexually transmitted disease (STD) or human immunodeficiency virus (HIV) in the future. Methods. The study used a convenience sample of STD clinic patients (n=48) and a modified respondent-driven sampling method (n=70) to reach a diverse sample of MSM (total sample n=118) in Massachusetts. Participants completed a one-on-one, open-ended, semistructured qualitative interview and quantitative survey. Results. Overall, white, HIV-infected MSM had the highest level of knowledge about PN activities. MSM who were unfamiliar with PN were disproportionately nonwhite and HIV-uninfected. Participants were more likely to notify past partners of HIV exposure than STD exposure. The preferred method of PN for the majority of MSM was direct person-to-person notification. Notably, nonwhite participants were more likely to endorse Massachusetts Department of Public Health PN services than white MSM, who preferred involvement of primary care providers. Conclusions. PN is an important public health strategy for treating and preventing STDs and HIV among at-risk populations, especially MSM who engage in sexual behavior with anonymous or otherwise non-notifiable sexual partners. Although many MSM had an understanding of the ethical desirability of informing exposed partners and recognized the value of preventative behaviors, they require further education to overcome barriers to PN as well as to gain knowledge of the various methods of both traditional and nontraditional notification, such as Internet PN. C1 [Mimiaga, Matthew J.; Reisner, Sari L.; Tetu, Ashley M.; Bonafide, Katherine E.; Mayer, Kenneth H.] Fenway Community Hlth, Fenway Inst, Boston, MA 02119 USA. [Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Tetu, Ashley M.; Bertrand, Thomas] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Cranston, Kevin; Novak, David S.] Massachusetts Dept Publ Hlth, Boston, MA USA. [Mayer, Kenneth H.] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. RP Mimiaga, MJ (reprint author), Fenway Community Hlth, Fenway Inst, Prudential Tower,4th Floor,800 Boylston St, Boston, MA 02119 USA. EM mmimiaga@fenwayhealth.org NR 46 TC 22 Z9 23 U1 1 U2 2 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 2009 VL 124 IS 1 BP 111 EP 119 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 385NI UT WOS:000261820500015 PM 19413033 ER PT J AU Savoia, E Testa, MA Biddinger, PD Cadigan, RO Koh, H Campbell, P Stoto, MA AF Savoia, Elena Testa, Marcia A. Biddinger, Paul D. Cadigan, Rebecca O. Koh, Howard Campbell, Paul Stoto, Michael A. TI Assessing Public Health Capabilities During Emergency Preparedness Tabletop Exercises: Reliability and Validity of a Measurement Tool SO PUBLIC HEALTH REPORTS LA English DT Article ID SYSTEMS AB Objectives. Improving the ability of local public health agencies to respond to large-scale emergencies is an ongoing challenge. Tabletop exercises can provide an opportunity for individuals and groups to practice coordination of emergency response and evaluate performance. The purpose of this study was to develop a valid and reliable self-assessment performance measurement tool for tabletop exercise participants. Methods. The study population comprised 179 public officials who attended three tabletop exercises in Massachusetts and Maine between September 2005 and November 2006. A 42-item questionnaire was developed to assess five public health functional capabilities: (1) leadership and management, (2) mass casualty care, (3) communication, (4) disease control and prevention, and (5) surveillance and epidemiology. Analyses were undertaken to examine internal consistency, associations among scales, the empirical structure of the items, and inter-rater agreement. Results. Thirty-seven questions were retained in the final questionnaire and grouped according to the original five domains. Alpha coefficients were 0.81 or higher for all scales. The five-factor solution from the principal components analysis accounted for 60% of the total variance, and the factor structure was consistent with the five domains of the original conceptual model. Inter-rater agreement ranged from good to excellent. Conclusions. The resulting 37-item performance measurement tool was found to reliably measure public health functional capabilities in a tabletop exercise setting, with preliminary evidence of a factor structure consistent with the original conceptualization and of criterion-related validity. C1 [Savoia, Elena] Harvard Univ, Sch Publ Hlth, Div Publ Hlth Practice, Ctr Publ Hlth Preparedness, Boston, MA 02115 USA. [Testa, Marcia A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Biddinger, Paul D.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Stoto, Michael A.] Georgetown Univ, Sch Nursing & Hlth Studies, Washington, DC USA. RP Savoia, E (reprint author), Harvard Univ, Sch Publ Hlth, Div Publ Hlth Practice, Ctr Publ Hlth Preparedness, 677 Huntington Ave, Boston, MA 02115 USA. EM esavoia@hsph.harvard.edu FU Centers for Disease Control and Prevention (CDC) [U90/CCU124242-03/04] FX The work of the Harvard School of Public Health Center for Public Health Preparedness is supported under a cooperative agreement with the Centers for Disease Control and Prevention (CDC) grant number U90/CCU124242-03/04. NR 23 TC 17 Z9 17 U1 0 U2 1 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 2009 VL 124 IS 1 BP 138 EP 148 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 385NI UT WOS:000261820500018 PM 19413036 ER PT J AU Sahani, DV Yaghmai, V AF Sahani, Dushyant V. Yaghmai, Vahid TI Advances in MDCT Preface SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Abdominal Imaging, Boston, MA 02114 USA. [Yaghmai, Vahid] Northwestern Univ, Feinberg Sch Med, Dept Radiol, Chicago, IL 60611 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging, 55 Fruit St,White 2-270, Boston, MA 02114 USA. EM dsahani@partners.org; v-yaghmai@northwestern.edu NR 0 TC 0 Z9 0 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 2009 VL 47 IS 1 BP XIII EP XIV DI 10.1016/j.rcl.2009.01.003 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 414DK UT WOS:000263843900001 PM 19195529 ER PT J AU Singh, AK Hiroyuki, Y Sahani, DV AF Singh, Anand K. Hiroyuki, Yoshida Sahani, Dushyant V. TI Advanced Postprocessing and the Emerging Role of Computer-Aided Detection SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Computed tomography; Three-dimensional imaging; Postprocessing; Segmentation; Volume estimation; Virtual endoscopy; Computer-aided detection ID DONOR LIVER-TRANSPLANTATION; MULTIDETECTOR ROW CT; DIAGNOSTIC PERFORMANCE; VIRTUAL BRONCHOSCOPY; PULMONARY-EMBOLISM; VOLUME MEASUREMENT; GASTRIC-CANCER; TUBE CURRENT; MIDDLE-EAR; TOMOGRAPHY AB Advances in multidetector CT (MDCT) scanners have increased the pace of development of advanced postprocessing applications, such as virtual endoscopy (VE), segmentation and volumetry, and computer-aided postprocessing methods. Availability of thin-section MDCT data sets of isotropic voxel resolution ensures accuracy in structure segmentation, which is an important initial prerequisite on which the results of such advanced postprocessing applications are based. This article explains the technique of VE, segmentations and volumetry and various computer-aided post processing methods, with emphasis on their importance in the present clinical scenario. C1 [Sahani, Dushyant V.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Abdominal Imaging, Boston, MA 02114 USA. [Singh, Anand K.; Hiroyuki, Yoshida] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dimens Imaging 3, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Abdominal Imaging, White 2 270,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 72 TC 1 Z9 2 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 2009 VL 47 IS 1 BP 59 EP + DI 10.1016/j.rcl.2008.11.004 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 414DK UT WOS:000263843900006 PM 19195534 ER PT J AU Kambadakone, AR Sahani, DV AF Kambadakone, Avinash R. Sahani, Dushyant V. TI Body Perfusion CT: Technique, Clinical Applications, and Advances SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Functional imaging; Perfusion CT; Contrast media; Tumor angiogenesis; Surrogate bio-marker ID CEREBRAL-BLOOD-FLOW; DYNAMIC COMPUTED-TOMOGRAPHY; ADVANCED HEPATOCELLULAR-CARCINOMA; SOLITARY PULMONARY NODULES; PERIPHERAL LUNG-CARCINOMA; UPPER AERODIGESTIVE TRACT; ENDOTHELIAL GROWTH-FACTOR; SQUAMOUS-CELL CARCINOMA; MULTIDETECTOR-ROW CT; COLORECTAL-CANCER AB Perfusion CT has made tremendous progress since its inception and is gradually broadening its applications from the research realm into routine clinical care. This has been particularly noteworthy in the oncological setting, where perfusion CT is emerging as a valuable tool in tissue characterization, risk stratification and monitoring treatment effects especially assessing early response to novel targeted therapies. Recent technological advancements in CT have paved ways to overcome the initial limitations of restricted tissue coverage and radiation dose concerns. In this article, the authors review the basic principles and technique of perfusion CT and discuss its various oncologic and non-oncological clinical applications in body imaging. C1 [Kambadakone, Avinash R.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 82 TC 117 Z9 123 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 2009 VL 47 IS 1 BP 161 EP + DI 10.1016/j.rcl.2008.11.003 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 414DK UT WOS:000263843900013 PM 19195541 ER PT J AU Sahani, DV Sainani, NI Deshpande, V Shaikh, MS Frinkelberg, DL Fernandez-del Castillo, C AF Sahani, Dushyant V. Sainani, Nisha I. Deshpande, Vikram Shaikh, Mehrine S. Frinkelberg, Dmitry L. Fernandez-del Castillo, Carlos TI Autoimmune Pancreatitis: Disease Evolution, Staging, Response Assessment, and CT Features That Predict Response to Corticosteroid Therapy SO RADIOLOGY LA English DT Article ID DIAGNOSTIC-CRITERIA; SCLEROSING PANCREATITIS; SERUM IGG4; ABNORMALITY; CARCINOMA; PATHOLOGY; PROGNOSIS; CONSENSUS; PROPOSAL AB Purpose: To evaluate the evolution of morphologic features of autoimmune pancreatitis (AIP) at computed tomography (CT) and to identify imaging features that can predict AIP response to corticosteroid therapy (CST). Materials and Methods: This HIPAA-compliant retrospective study had institutional review board approval. From among a cohort of 63 patients with AIP, 15 patients (12 men, three women; mean age, 64.7 years; age range, 30-84 years) who underwent sequential CT examinations before treatment were included to assess the evolution of disease by reviewing pancreatic, peripancreatic, and ductal changes. Of these patients, 13 received CST and underwent posttreatment CT; these CT studies were evaluated to determine if there were imaging features that could predict response to CST. Results: The disease evolved from changes of diffuse (14 of 15 patients) or focal (one of 15 patients) parenchymal swelling, peripancreatic stranding (10 of 15 patients), "halo" (nine of 15 patients), pancreatic duct changes (15 of 15 patients), and distal common bile duct narrowing (12 of 15 patients) to either resolution or development of ductal strictures and/or focal masslike swelling. In 13 patients treated with CST, favorable response to treatment was seen in those with diffuse pancreatic and peripancreatic changes. Suboptimal response was seen in patients with ductal stricture formation (two of 13 patients) and in those in whom focal masslike swellings persisted after resolution of diffuse changes (seven of 13 patients). Conclusion: CT features like diffuse swelling and halo respond favorably to CST and likely reflect an early inflammatory phase, whereas features like ductal strictures and focal masslike swelling are predictive of a suboptimal response and symbolize a late stage with predominance of fibrosis. (C) RSNA, 2008 C1 [Sahani, Dushyant V.; Sainani, Nisha I.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Frinkelberg, Dmitry L.] Harvard Univ, Sch Med, Dept Gastroenterol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Deshpande, Vikram] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fernandez-del Castillo, Carlos] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shaikh, Mehrine S.] Aga Khan Univ, Karachi, Pakistan. RP Sahani, DV (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 31 TC 35 Z9 35 U1 0 U2 2 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 JAN PY 2009 VL 250 IS 1 BP 118 EP 129 DI 10.1148/radiol.2493080279 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 439QS UT WOS:000265642700016 PM 19017924 ER PT B AU El Khoury, J Hickman, SE AF El Khoury, Joseph Hickman, Suzanne E. BE Sun, MK TI Mechanisms of Amyloid -beta Clearance in Alzheimer's Disease SO RESEARCH PROGRESS IN ALZHEIMER'S DISEASE AND DEMENTIA, VOL 4 SE Research Progress in Alzheimers and Dementia LA English DT Article; Book Chapter ID ANGIOTENSIN-CONVERTING ENZYME; BLOOD-BRAIN-BARRIER; INSULIN-DEGRADING ENZYME; DENSITY-LIPOPROTEIN RECEPTOR; NEPRILYSIN GENE-TRANSFER; APP TRANSGENIC MICE; A-BETA; SCAVENGER RECEPTOR; PLASMINOGEN-ACTIVATOR; PLAQUE-FORMATION AB Amyloid-beta accumulation in the brain is regulated by equilibrium between A beta production and clearance. Three major pathways regulate A beta clearance from the brain. The first pathway involves uptake of A beta by specific receptors expressed on microglia and astrocytes followed by intracellular degradation. The second pathway for A beta clearance occurs via extracellular degradation by surface bound or released A beta-degrading enzymes. The third pathway that regulates A beta clearance is transport across the blood brain barrier (BBB) and the balance between A beta efflux and influx into the brain. In this chapter we will review these three pathways relevant to A beta clearance and discuss several recent advances in the field. We will also review the potential therapeutic applications of each of these pathways. C1 [El Khoury, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Charlestown, MA 02129 USA. [Hickman, Suzanne E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Charlestown, MA 02129 USA. RP El Khoury, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, CNY 149,Room 8301,149 13th St, Charlestown, MA 02129 USA. EM jelkhoury@partners.org; shickman@partners.org NR 157 TC 0 Z9 0 U1 0 U2 0 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60876-152-4 J9 RES PROG ALZHEIM DEM PY 2009 VL 4 BP 37 EP 66 PG 30 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA BPH23 UT WOS:000278843300002 ER PT J AU Epstein, SK Kacmarek, RM AF Epstein, Scott K. Kacmarek, Robert M. TI Noninvasive Ventilation in Acute Care: Controversies and Emerging Concepts SO RESPIRATORY CARE LA English DT Editorial Material C1 [Epstein, Scott K.] Tufts Univ, Sch Med, Off Educ Affairs, Boston, MA 02111 USA. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. RP Epstein, SK (reprint author), Tufts Univ, Sch Med, Off Educ Affairs, Boston, MA 02111 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 RESP CARE JI Respir. Care PD JAN PY 2009 VL 54 IS 1 BP 38 EP 39 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 392ND UT WOS:000262308500002 PM 19111104 ER PT J AU Holden, WE Sippel, JM Nelson, B Giraud, GD AF Holden, William E. Sippel, Jeffrey M. Nelson, Bella Giraud, George D. TI Greater nasal nitric oxide output during inhalation: Effects on air temperature and water content SO RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY LA English DT Article DE Nitric oxide; N(G)-nitro-L-arginine methyl ester (L-NAME); Humidity ID PARANASAL SINUSES; HUMAN NOSE; PHYSIOLOGY; ABILITY; HUMANS; WARM AB The nose conditions the temperature and humidity of nasal air, and the nasal mucosal vasculature Supplies heat and water for these processes. We hypothesize that nitric oxide (NO) modulates these processes through vasoactive effects on nasal mucosal vasculature. We measured the temperature, humidity and NO concentrations of nasal air during inhalation and exhalation across the nose and calculated net heat, water and NO Output before (controls, n = 7) and after inhibition of NO synthase by topical L-NAME (N = 5) in healthy humans. We found that calculated NO output across the nasal passages is approximately threefold greater during inhalation (503 +/- 105 nL/min) compared with exhalation (162 +/- 56 nL/min). Moreover, topical administration Of L-NAME decreased nasal air temperature and humidity conditioning and NO output, but these effects were limited to inhalation. We conclude that nasal NO output is greater during inhalation than exhalation in humans. Our findings also support a role of nasal NO in temperature and humidity conditioning of nasal air. Published by Elsevier B.V C1 [Holden, William E.; Sippel, Jeffrey M.; Nelson, Bella; Giraud, George D.] Portland VA Med Ctr, Dept Hosp & Specialty Med, P3 MED, Portland, OR 97201 USA. RP Holden, WE (reprint author), Portland VA Med Ctr, Dept Hosp & Specialty Med, P3 MED, 3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. EM holdenw@ohsu.edu FU Murdock Foundation Charitable Trust FX We acknowledge the assistance with experiments by Michelle Harris and the support of the Murdock Foundation Charitable Trust. NR 21 TC 3 Z9 3 U1 0 U2 3 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 JAN 1 PY 2009 VL 165 IS 1 BP 22 EP 27 DI 10.1016/j.resp.2008.09.009 PG 6 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 399HM UT WOS:000262791000004 PM 18952009 ER PT J AU Gosselin, A Monteiro, P Chomont, N Diaz-Griffero, F Wacleche, VS Said, EA Fonseca, S El-Far, M Boulassel, M Routy, J Sekaly, R Ancuta, P AF Gosselin, A. Monteiro, P. Chomont, N. Diaz-Griffero, F. Wacleche, V. S. Said, E. A. Fonseca, S. El-Far, M. Boulassel, M. Routy, J. Sekaly, R. Ancuta, P. TI Blood CCR6+Th17 and Th1Th17 but not CCR6neg Th1 cells are targets for HIV replication and their frequency is diminished in HIV-infected subjects SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Diaz-Griffero, F.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Diaz-Griffero, F.] Harvard Univ, Sch Med, Boston, MA USA. [Boulassel, M.] McGill Univ, Ctr Hlth, Div Hematol, Montreal, PQ, Canada. [Routy, J.] McGill Univ, Ctr Hlth, Montreal Chest Inst, Montreal, PQ, Canada. [Gosselin, A.; Monteiro, P.; Chomont, N.; Wacleche, V. S.; Said, E. A.; Fonseca, S.; El-Far, M.; Sekaly, R.; Ancuta, P.] Univ Montreal, CHUM Res Ctr, Montreal, PQ, Canada. [Gosselin, A.; Monteiro, P.; Chomont, N.; Wacleche, V. S.; Said, E. A.; Fonseca, S.; El-Far, M.; Sekaly, R.; Ancuta, P.] INSERM, U743, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P407 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300458 ER PT J AU Henn, MR Boutwell, C Lennon, N Power, K Malboeuf, C Charlebois, P Gladden, A Levin, J Casali, M Philips, L Berlin, A Berical, A Erlich, R Anderson, S Streeck, H Kemper, M Ryan, E Wang, Y Green, L Axten, K Brumme, Z Brumme, C Russ, C Rosenberg, E Jessen, H Altfeld, M Nusbaum, C Walker, B Birren, B Allen, TM AF Henn, M. R. Boutwell, C. Lennon, N. Power, K. Malboeuf, C. Charlebois, P. Gladden, A. Levin, J. Casali, M. Philips, L. Berlin, A. Berical, A. Erlich, R. Anderson, S. Streeck, H. Kemper, M. Ryan, E. Wang, Y. Green, L. Axten, K. Brumme, Z. Brumme, C. Russ, C. Rosenberg, E. Jessen, H. Altfeld, M. Nusbaum, C. Walker, B. Birren, B. Allen, T. M. TI Ultra-deep sequencing of full-length HIV-1 genomes identifies rapid viral evolution during acute infection SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Henn, M. R.; Lennon, N.; Malboeuf, C.; Charlebois, P.; Levin, J.; Casali, M.; Berlin, A.; Erlich, R.; Anderson, S.; Ryan, E.; Green, L.; Russ, C.; Nusbaum, C.; Birren, B.] MIT & Harvard, Broad Inst, Cambridge, MA 02139 USA. [Boutwell, C.; Power, K.; Gladden, A.; Philips, L.; Berical, A.; Streeck, H.; Kemper, M.; Wang, Y.; Axten, K.; Brumme, Z.; Brumme, C.; Rosenberg, E.; Altfeld, M.; Walker, B.; Allen, T. M.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P400 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300451 ER PT J AU Honeyborne, I Leslie, A Crawford, H Rousseau, CM Mullins, JI Walker, BD Goulder, P Prado, JG AF Honeyborne, I. Leslie, A. Crawford, H. Rousseau, C. M. Mullins, J. I. Walker, B. D. Goulder, P. Prado, J. G. TI Cw*0303/0304 HIV specific CTL response toward GagYL9 select for HIV escape variants with low fitness that is compensated by intra-codon variation SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Goulder, P.] Univ Oxford, Oxford, England. [Rousseau, C. M.; Mullins, J. I.] Univ Washington, Sch Med, Washington, WA USA. [Walker, B. D.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Honeyborne, I.; Leslie, A.; Crawford, H.; Prado, J. G.] Univ Oxford, irsiCaixa Fdn, Badalona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P131 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300183 ER PT J AU Huang, J Poole, L Burke, P Cung, T Trocha, A Pereyra, F Borges, L Lichterfeld, M Yu, X AF Huang, J. Poole, L. Burke, P. Cung, T. Trocha, A. Pereyra, F. Borges, L. Lichterfeld, M. Yu, X. TI Unique stimulatory properties of myeloid dendritic cells in individuals with "elite" HIV-1 control SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Borges, L.] Amgen Inc, Seattle, WA USA. [Huang, J.; Poole, L.; Burke, P.; Cung, T.; Trocha, A.; Pereyra, F.; Lichterfeld, M.; Yu, X.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR O24 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300025 ER PT J AU Kwon, DS Angin, M Streeck, H Brockman, MA Tighe, D Pavlik, D Hongo, T Law, K Addo, MM Walker, BD Kaufmann, DE AF Kwon, D. S. Angin, M. Streeck, H. Brockman, M. A. Tighe, D. Pavlik, D. Hongo, T. Law, K. Addo, M. M. Walker, B. D. Kaufmann, D. E. TI The role of CD4+CD25+regulatory T cells in the control of IL-10 mediated T cell impairment in chronic HIV Infection SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Kwon, D. S.; Angin, M.; Streeck, H.; Brockman, M. A.; Tighe, D.; Pavlik, D.; Hongo, T.; Law, K.; Addo, M. M.; Walker, B. D.; Kaufmann, D. E.] Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P408 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300459 ER PT J AU Lazaro, E Zhang, S Zhang, M Martinez, S Heckerman, D Walker, BD Le Gall, S AF Lazaro, E. Zhang, S. Zhang, M. Martinez, S. Heckerman, D. Walker, B. D. Le Gall, S. TI The intracellular production of HIV antigenic peptides is guided by predictable motifs and can be altered: implications for immunogen design SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Heckerman, D.] Microsoft Res, Seattle, WA USA. [Lazaro, E.; Zhang, S.; Zhang, M.; Martinez, S.; Walker, B. D.; Le Gall, S.] Harvard Univ, Sch Med, Ragon Inst MGH MIT & Harvard, Boston, MA 02115 USA. [Lazaro, E.; Zhang, S.; Zhang, M.; Martinez, S.; Walker, B. D.; Le Gall, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR O47 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300048 ER PT J AU Mikell, I Sather, D Kalams, S Altfeld, M Stamatatos, L AF Mikell, I. Sather, D. Kalams, S. Altfeld, M. Stamatatos, L. TI Prevalence of broadly neutralizing antibody responses during acute/early HIV infection SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Mikell, I.; Sather, D.; Stamatatos, L.] Seattle Biomed Res Inst, Seattle, WA 98109 USA. [Kalams, S.] Vanderbilt Univ Scho, Dept Microbiol & Immunol, Nashville, TN USA. [Altfeld, M.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P43 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300096 ER PT J AU Moodley, ES Thobakgale, C Ramkalawon, P Vanderstok, M Mncube, Z Bishop, K Reddy, S Chonco, F Walker, B Goulder, P Ndung'u, T AF Moodley, E. S. Thobakgale, C. Ramkalawon, P. Vanderstok, M. Mncube, Z. Bishop, K. Reddy, S. Chonco, F. Walker, B. Goulder, P. Ndung'u, T. TI Cytotoxic T lymphocyte-mediated immune responses in HIV-1 clade C infected mother-child pairs SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Moodley, E. S.; Thobakgale, C.; Ramkalawon, P.; Vanderstok, M.; Mncube, Z.; Bishop, K.; Ndung'u, T.] UKZN, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Walker, B.] Inst Massachusetts Gen Hosp, Massachusetts, MA USA. [Goulder, P.] Univ Oxford, Dept Pediat, Oxford, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P100 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300152 ER PT J AU Mothe, B Llano, A Ibarrondo, J Miranda, C Rolland, M Frahm, N Khatri, A Heckerman, D Mullins, J Brander, C AF Mothe, B. Llano, A. Ibarrondo, J. Miranda, C. Rolland, M. Frahm, N. Khatri, A. Heckerman, D. Mullins, J. Brander, C. TI Immune responses in controlled and uncontrolled HIV infection to a designed HIV immunogen sequence focused on conserved regions of the viral genome SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Mothe, B.; Llano, A.; Ibarrondo, J.; Brander, C.] Hosp Badalona Germans Trias & Pujol, IrsiCaixa AIDS Res Inst HIVACAT, Badalona, Spain. [Miranda, C.] Hosp Badalona Germans Trias & Pujol, Lluita Sida Fdn, Badalona, Spain. [Rolland, M.; Mullins, J.] Univ Washington, Dept Microbiol, Washington, DC USA. [Frahm, N.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Khatri, A.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Heckerman, D.] Microsoft Res, Redmond, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P175 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300226 ER PT J AU Pancera, M Majeed, S Ban, Y Chen, L Huang, C Kong, L Kwon, Y Stuckey, J Zhou, T Robinson, J Schief, W Sodroski, J Wyatt, R Kwong, P AF Pancera, M. Majeed, S. Ban, Y. Chen, L. Huang, C. Kong, L. Kwon, Y. Stuckey, J. Zhou, T. Robinson, J. Schief, W. Sodroski, J. Wyatt, R. Kwong, P. TI Structure of HIV-1 gp41 interactive region: layered architecture and basis of conformational mobility SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Pancera, M.; Majeed, S.; Chen, L.; Huang, C.; Kong, L.; Kwon, Y.; Stuckey, J.; Zhou, T.; Wyatt, R.; Kwong, P.] NIAID, NIH, VRC, Bethesda, MD 20892 USA. [Ban, Y.; Schief, W.] Univ Washington, Seattle, WA 98195 USA. [Robinson, J.] Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70118 USA. [Sodroski, J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RI Zhou, Tongqing/A-6880-2010 OI Zhou, Tongqing/0000-0002-3935-4637 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P126 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300178 ER PT J AU Porichis, F Kwon, DS Tighe, DP Pavlik, DF Kavanagh, DG Freeman, GJ Walker, BD Kaufmann, DE AF Porichis, F. Kwon, D. S. Tighe, D. P. Pavlik, D. F. Kavanagh, D. G. Freeman, G. J. Walker, B. D. Kaufmann, D. E. TI Combined blockade of the PD-1 and IL-10 pathways synergistically enhance HIV-specific CD4 T cell functions SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Porichis, F.; Kwon, D. S.; Tighe, D. P.; Pavlik, D. F.; Kavanagh, D. G.; Walker, B. D.; Kaufmann, D. E.] MIT & Harvard Med Sch, Ragon Inst MGH, Boston, MA USA. [Freeman, G. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P237 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300288 ER PT J AU Prado, JG Prendergast, A Thobakgale, C Juarez, C Tudor-Williams, A Ndung'u, T Walker, BD Goulder, P AF Prado, J. G. Prendergast, A. Thobakgale, C. Juarez, C. Tudor-Williams, A. Ndung'u, T. Walker, B. D. Goulder, P. TI Non-progressive paediatric HIV infection is associated with virus attenuation and increase in CD8+specific T cell responses over time SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Prado, J. G.; Prendergast, A.; Juarez, C.; Goulder, P.] Univ Oxford, Fdn IrsiCaixa, Badalona, Spain. [Thobakgale, C.; Ndung'u, T.] Univ KwaZulu Natal Durban, Durban, South Africa. [Tudor-Williams, A.] Univ London Imperial Coll Sci Technol & Med, Dept Paediat, London, England. [Walker, B. D.] Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P105 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300157 ER PT J AU Song, L Sun, ZJ Coleman, KE Zwick, MB Gach, JS Wang, J Reinherz, EL Wagner, G Kim, M AF Song, L. Sun, Z. J. Coleman, K. E. Zwick, M. B. Gach, J. S. Wang, J. Reinherz, E. L. Wagner, G. Kim, M. TI Broadly neutralizing anti-HIV-1 antibodies disrupt a hinge-related function of gp41 at the membrane interface SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Song, L.; Coleman, K. E.; Reinherz, E. L.; Kim, M.] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Sun, Z. J.; Wang, J.; Wagner, G.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Zwick, M. B.; Gach, J. S.] Scripps Res Inst, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR O5 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300006 ER PT J AU Subramanya, S Armant, M Kim, S Ye, C Leiberman, J Schultz, L Greiner, D Shankar, P AF Subramanya, S. Armant, M. Kim, S. Ye, C. Leiberman, J. Schultz, L. Greiner, D. Shankar, P. TI Priming with SOCS-1 silenced Dendritic cells induces robust HIV-specific CTL response in a novel HLA-A2 transgenic humanized mouse model SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Subramanya, S.; Kim, S.; Ye, C.; Shankar, P.] Texas Tech Univ, Hlth Sci Ctr, El Paso, TX USA. [Armant, M.; Leiberman, J.] Immune Dis Inst, Boston, MA USA. [Schultz, L.] Jackson Labs, Bar Harbor, ME USA. [Greiner, D.] Univ Massachusetts, Worcester, MA 01605 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P420 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300471 ER PT J AU Wheeler, L Basar, E McKernan, S Dykxhoorn, D Lieberman, J AF Wheeler, L. Basar, E. McKernan, S. Dykxhoorn, D. Lieberman, J. TI CD4-targeted delivery of HIV and CCR5 siRNAs by aptamer-siRNA chimeras suppresses HIV infection in primary cells and in human cervical explants SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Wheeler, L.] Harvard Univ, Sch Med, Div Med Sci, Boston, MA USA. [Basar, E.; McKernan, S.; Dykxhoorn, D.; Lieberman, J.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Basar, E.; McKernan, S.; Dykxhoorn, D.; Lieberman, J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RI Dykxhoorn, Derek/D-1357-2015 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P342 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300393 ER PT J AU Xu, H Scherer, E Song, L Kim, M Holmes, MA Sellhorn, G Kraft, Z Reinherz, EL Burton, DR Stamatatos, L Strong, RK AF Xu, H. Scherer, E. Song, L. Kim, M. Holmes, M. A. Sellhorn, G. Kraft, Z. Reinherz, E. L. Burton, D. R. Stamatatos, L. Strong, R. K. TI The specific phospholipid binding and neutralizing activities of the anti-HIV antibody 4E10 are separable SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Xu, H.; Holmes, M. A.; Strong, R. K.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Scherer, E.] Univ Oxford, Oxford, England. [Song, L.; Kim, M.; Reinherz, E. L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Sellhorn, G.; Kraft, Z.; Stamatatos, L.] Univ Washington, Seattle Biomed Res Inst, Seattle, WA 98109 USA. [Burton, D. R.] Scripps Res Inst, La Jolla, CA 92037 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P32 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300085 ER PT S AU Suit, H Delaney, TF Trofimov, A AF Suit, Herman Delaney, Thomas F. Trofimov, Alexei BE Chao, AW Chou, W TI Physical and Biological Basis of Proton and of Carbon Ion Radiation Therapy and Clinical Outcome Data SO REVIEWS OF ACCELERATOR SCIENCE AND TECHNOLOGY, VOL 2: MEDICAL APPLICATIONS OF ACCELERATORS SE Reviews of Accelerator Science and Technology LA English DT Article; Book Chapter DE Protons; carbon ions; beams; radiation therapy ID FAST-NEUTRON THERAPY; CELL LUNG-CANCER; BEAM RADIOTHERAPY; UVEAL MELANOMA; SKULL-BASE; DOSE DISTRIBUTIONS; SACRAL CHORDOMAS; PROSTATE-CANCER; CARCINOMA; IRRADIATION AB There is a clear basis n physics for the clinical use of proton and carbon beams in radiation therapy, namely, the finite range of the particle beam. The range is dependent on the beam initial energy, density and atomic composition of tissues along the beam path. Beams can be designed that penetrate to the required depth and deliver a uniform biologically effective dose across the depth of interest. The yield is a superior dose distribution relative to photon beams. There is a potential clinical advantage from the high linear energy transfer (LET) characteristics of carbon beams. This is based on a lower oxygen enhancement ratio (OER) and a flatter age response function. However, due to uncertainties relating OER with relative biological effectiveness (RBE), there is no clinical evidence to date that carbon ion beams have an advantage over proton beams. We strongly support performance Phase III clinical trials of protons vs carbon ion beams designed to feature a single variable, LET. Dose fractionation would be identical in both arms and dose distribution would be similar for the sites to be tested. For sites for which the carbon beam has a demonstrated important advantage in comparative treatment planning due to the narrower penumbra would not be selected for the clinical trials. C1 [Suit, Herman] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Suit, Herman; Delaney, Thomas F.; Trofimov, Alexei] Harvard Univ, Sch Med, Boston, MA USA. RP Suit, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM hsuit@partners.org; tdelaney@partners.org; atrofimov@partners.org NR 75 TC 3 Z9 3 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE SN 1793-6268 BN 978-981-429-935-0; 978-981-4299-34-3 J9 REV ACCEL SCI TECH PY 2009 VL 2 BP 1 EP 15 PG 15 WC Physics, Applied; Physics, Particles & Fields; Radiology, Nuclear Medicine & Medical Imaging SC Physics; Radiology, Nuclear Medicine & Medical Imaging GA BE2SL UT WOS:000369971700002 ER PT J AU Fraguas, R Nobre, MRC Wajngarten, M Cardeal, MV Figueiro, JAB Iosifescu, DV Teixeira, MJ AF Fraguas, Renerio Cuce Nobre, Moacyr Roberto Wajngarten, Mauricio Cardeal, Marcus Vinicius Bertuol Figueiro, Joao Augusto Iosifescu, Dan V. Teixeira, Manoel Jacobsen TI Major depression in patients with non-cardiac chest pain - Who is going to treat? SO REVISTA DE PSIQUIATRIA CLINICA LA Portuguese DT Article DE Depression; cardiology; pain; treatment; primary care ID COGNITIVE-BEHAVIORAL THERAPY; NORMAL CORONARY ANGIOGRAMS; PANIC DISORDER; RANDOMIZED-TRIAL; IMIPRAMINE; EMERGENCY; ILLNESS AB Objective: To investigate the presence of psychiatric disorders in patients with chest pain not responsive to treatment. Method: We evaluated 18 patients judged by their physicians to have a chest pain not responsive to usual treatment, which included anti-pain medicines and investigation and treatment of possible etiological causes such as coronary artery disease, and gastroesophageal reflux disease. A psychiatrist interviewed the patients using the Present State Examination and made the diagnosis based on the DSM-III-R criteria. Current major depression was diagnosed in 6 (30%) patients, somatization in 1 (6%) and panic disorder in 1 (6%) patient. Seven patients were receiving tricyclics antidepressant with doses >= 75 mg/day. Discussion: Patients were receiving doses of tricyclics antidepressants efficacious for pain but not for major depression. It is possible that the low dose of antidepressants used to treat pain may partially ameliorate depressive symptoms, making the appropriate diagnosis and treatment of major depression even more difficult, consequently contributing to the persistence of pain and other complains. Considering the wide alternatives to effectively treat depression, a focus on detection and treatment of major depression in patients with chest pain is warranted by clinicians and researchers. C1 [Fraguas, Renerio; Cardeal, Marcus Vinicius] Inst Psiquiatria Hosp Clin FMUSP, Grp Interconsultas, Dept Psiquiatria FMUSP, BR-05403903 Sao Paulo, Brazil. [Cuce Nobre, Moacyr Roberto] Inst Coracao InCor HC FMUSP, Unidade Epidemiol Clin, Sao Paulo, Brazil. [Wajngarten, Mauricio] InCor HC FMUSP, Unidade Clin Cardiogeriatria, Sao Paulo, Brazil. [Bertuol Figueiro, Joao Augusto] Ctr Dor HC FMUSP, Sao Paulo, Brazil. [Iosifescu, Dan V.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA USA. [Teixeira, Manoel Jacobsen] FMUSP, Dept Neurol, Disciplina Neurocirurgia, Sao Paulo, Brazil. RP Fraguas, R (reprint author), Inst Psiquiatria Hosp Clin FMUSP, Grp Interconsultas, Dept Psiquiatria FMUSP, Rua Dr Ovdio Pires Campus 785,3 Andar,Sala 13, BR-05403903 Sao Paulo, Brazil. EM rfraguas@hcnet.usp.br RI Teixeira, Manoel/E-3110-2012; Wajngarten, Mauricio/G-3702-2012 NR 33 TC 1 Z9 1 U1 1 U2 1 PU UNIV SAO PAULO, INST PSIQUIATRIA PI SAO PAULO PA RUA OVIDIO PIRES CAMPOS, 785, 1 ANDAR, SAO PAULO, 05403-010, BRAZIL SN 0101-6083 J9 REV PSIQUIATR CLIN JI Rev. Psiquiatr. Clin. PY 2009 VL 36 BP 83 EP 87 PG 5 WC Psychiatry SC Psychiatry GA 529YV UT WOS:000272556400003 ER PT J AU Terroni, LDN Mattos, PF Sobreiro, MDM Guajardo, VD Fraguas, R AF Niro Terroni, Luisa de Marillac Mattos, Patricia Ferreira Sobreiro, Matildes de Freitas Menezes Guajardo, Valeri Delgado Fraguas, Renerio TI Post-stroke depression: psychological, neuropsychological, HHA axis, localization of stroke aspects and treatment SO REVISTA DE PSIQUIATRIA CLINICA LA Portuguese DT Review DE post-stroke depression; stroke; depression; quality of life; cognitive dysfunction; hypercortisolism; treatment ID DEXAMETHASONE SUPPRESSION TEST; QUALITY-OF-LIFE; COGNITIVE IMPAIRMENT; MOOD DISORDERS; LESION LOCATION; POST-STROKE; ELECTROCONVULSIVE-THERAPY; COMMUNITY STROKE; FREQUENCY; SURVIVORS AB Background: The prevalence of post-stroke depression (PSD) is elevated. Some risk factors and poor outcome have been associated with PSD. The treatment of PSD reduced the negative impact in patients recovery. Appart from these data the PSD has been under diagnosed and under treated. Objective: Review some aspects such as quality of life, cognitive dysfunction, hypercortisolism, stroke localization and treatment of PSD. Methods: MedLine/PubMed database search using the terms post-stroke depression, stroke, quality of life, hypercortisolism, cognitive dysfunction and treatment, published in MedLine in the last 10 years. Results: PSD has a high rate of prevalence, from 23% to 60%. Few incidence rates are investigated. PSD is associated with poor outcome, increase of cognitive dysfunction and reduced quality of life. The hypercortisolism seems to be associated with PSD in the latter period of stroke. Stroke in the left frontal region, basal ganglia and some structures of prefrontosubcortical circuits have been related with frequency and severity of PSD. Discussion: Some programs can be used to assist the medical care researcher with these patients in diagnosis and treatment of PSD. The research needs to be continued with clear methodological protocols in order to understand the physiopathology related to the incident PSD. C1 [Niro Terroni, Luisa de Marillac; Mattos, Patricia Ferreira; Guajardo, Valeri Delgado; Fraguas, Renerio] Hosp Clin FMUSP, Dept & Inst Psiquiatria, Grp Interconsultas, BR-05403903 Sao Paulo, Brazil. [Sobreiro, Matildes de Freitas Menezes] HC FMUSP, Inst Cent, Div Psicol, Sao Paulo, Brazil. [Fraguas, Renerio] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program, Cambridge, MA 02138 USA. RP Terroni, LDN (reprint author), Hosp Clin FMUSP, Inst Psiquiatria, Rua Dr Ovidio Pires Campos 785,3 Andar,Sala 13, BR-05403903 Sao Paulo, Brazil. EM luisaterroni@usp.br NR 88 TC 2 Z9 6 U1 3 U2 10 PU UNIV SAO PAULO, INST PSIQUIATRIA PI SAO PAULO PA RUA OVIDIO PIRES CAMPOS, 785, 1 ANDAR, SAO PAULO, 05403-010, BRAZIL SN 0101-6083 J9 REV PSIQ CLIN-BRAZIL JI Rev. Psiquiatr. Clin. PY 2009 VL 36 SU 3 BP 100 EP 108 PG 9 WC Psychiatry SC Psychiatry GA 529YV UT WOS:000272556400006 ER PT J AU de Soarez, PC Castelo, A Abrao, P Holmes, WC Ciconelli, RM AF de Soarez, Patricia Coelho Castelo, Adauto Abrao, Paulo Holmes, William C. Ciconelli, Rozana Mesquita TI Brazilian-Portuguese translation and validation of the HIV/AIDS-Targeted Quality of Life Instrument SO REVISTA PANAMERICANA DE SALUD PUBLICA-PAN AMERICAN JOURNAL OF PUBLIC HEALTH LA Portuguese DT Article DE Reproducibility of results; validation studies; quality of life; Acquired Immunodeficiency Syndrome; Brazil ID CROSS-CULTURAL ADAPTATION; HAT-QOL INSTRUMENT; HEALTH SURVEY; ANTIRETROVIRAL THERAPY; HIV DISEASE; MOS-HIV; RELIABILITY; GUIDELINES; INFECTION; VALIDITY AB Objectives. To translate the HIV/AIDS-Targeted Quality of Life Instrument (HAT-QoL) into Brazilian Portuguese, culturally adapt it, and evaluate its psychometric properties (validity and reliability) as a Brazilian version. Methods. This cross-sectional study was carried out at the laboratory of infectious diseases at Escola Paulista de Medicina (Universidade Federal de Sao Paulo). Data were collected on clinical and sociodemographic characteristics of 106 HIV-infected individuals who answered the HAT-QoL and the SF-36 (R). Pearson's correlation coefficient was used to measure construct validity. Reliability was assessed using Cronbach's alpha and intraclass correlation coefficients. Results. The sample was 70.8% male. The mean age was 39.9 years, with 40.5% of the participants being homosexual or bisexual. Eleven (10.4%) patients had a CD4 cell count <= 200 cells/mm(3). A substantial ceiling effect was observed in 7 of 9 HAT-QoL domains (overall function, life satisfaction, health worries, medication worries, HIV acceptance, provider trust, and sexual function). Sexual function was the domain with the highest ceiling effect (63.2%). A substantial floor effect (30.2%) was observed for financial worries. Statistically significant associations were observed between the HAT-QoL domains and clinical and sociodemographic characteristics, as well as with SF-36 domains. Internal consistency was satisfactory (Cronbach's alpha = 0.73-0.90). Inter- and intra-observer reproducibility was very high (0.87-0.98 and 0.82-0.97, respectively). Conclusion. The Brazilian Portuguese version of the HAT-QoL is valid, reliable, and may contribute to evaluating the impact of HIV infection on the quality of life of patients in Brazil. C1 [de Soarez, Patricia Coelho; Ciconelli, Rozana Mesquita] Univ Fed Sao Paulo, Ctr Paulista Econ Saude, Sao Paulo, Brazil. [Castelo, Adauto; Abrao, Paulo; Ciconelli, Rozana Mesquita] Univ Fed Sao Paulo, Dept Med, Sao Paulo, Brazil. [Holmes, William C.] Univ Penn, Sch Med, Ctr Hlth Equ Res & Promot, Filadelfia, PA USA. [Holmes, William C.] Ctr Clin Epidemiol & Biostat, Filadelfia, PA USA. RP de Soarez, PC (reprint author), Rua Botucatu 685, BR-04023062 Sao Paulo, Brazil. EM patricia.soarez@cpes.org.br RI Ciconelli, Rozana /G-4549-2013; Abrao Ferreira, Paulo Roberto/A-5703-2016; SOAREZ, PATRICIA/D-9710-2012 OI Abrao Ferreira, Paulo Roberto/0000-0003-4858-2778; SOAREZ, PATRICIA/0000-0001-8383-0728 NR 21 TC 6 Z9 14 U1 2 U2 12 PU PAN AMER HEALTH ORGANIZATION PI WASHINGTON PA 525 23RD ST NW, WASHINGTON, DC 20037 USA SN 1020-4989 J9 REV PANAM SALUD PUBL JI Rev. Panam. Salud Publica PD JAN PY 2009 VL 25 IS 1 BP 69 EP 76 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 423YD UT WOS:000264531800011 PM 19341527 ER PT J AU Johnson, FR Ozdemir, S Mansfield, C Hass, S Siegel, CA Sands, BE AF Johnson, F. Reed Ozdemir, Semra Mansfield, Carol Hass, Steven Siegel, Corey A. Sands, Bruce E. TI Are Adult Patients More Tolerant of Treatment Risks Than Parents of Juvenile Patients ? SO RISK ANALYSIS LA English DT Article DE Benefit-risk analysis; Crohn's disease; maximum acceptable risk; stated-choice survey ID WILLINGNESS-TO-PAY; ACUTE OTITIS-MEDIA; CROHNS-DISEASE; CONJOINT-ANALYSIS; PREFERENCES; HEALTH; NATALIZUMAB; INFLIXIMAB; LOGIT; LIFE AB Understanding patient-specific differences in risk tolerance for new treatments that offer improved efficacy can assist in making difficult regulatory and clinical decisions for new treatments that offer both the potential for greater effectiveness in relieving disease symptoms, but also risks of disabling or fatal side effects. The aim of this study is to elicit benefit-risk trade-off preferences for hypothetical treatments with varying efficacy and risk levels using a stated-choice (SC) survey. We derive estimates of "maximum acceptable risk" (MAR) that can help decisionmakers identify welfare-enhancing alternatives. In the case of children, parent caregivers are responsible for treatment decisions and their risk tolerance may be quite different than adult patients' own tolerance for treatment-related risks. We estimated and compared the willingness of Crohn's disease (CD) patients and parents of juvenile CD patients to accept serious adverse event (SAE) risks in exchange for symptom relief. The analyzed data were from 345 patients over the age of 18 and 150 parents of children under the age of 18. The estimation results provide strong evidence that adult patients and parents of juvenile patients are willing to accept tradeoffs between treatment efficacy and risks of SAEs. Parents of juvenile CD patients are about as risk tolerant for their children as adult CD patients are for themselves for improved treatment efficacy. SC surveys provide a systematic method for eliciting preferences for benefit-risk tradeoffs. Understanding patients' own risk perceptions and their willingness to accept risks in return for treatment benefits can help inform risk management decision making. C1 [Johnson, F. Reed; Ozdemir, Semra; Mansfield, Carol] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. [Ozdemir, Semra] Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Hass, Steven] Elan Pharmaceut, San Francisco, CA USA. [Siegel, Corey A.] Dartmouth Hitchcock Med Ctr, Sect Gastroenterol & Hepatol, BD Ctr, Lebanon, NH 03766 USA. [Sands, Bruce E.] Massachusetts Gen Hosp, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. [Sands, Bruce E.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Sands, Bruce E.] Harvard Univ, Sch Med, Boston, MA USA. RP Johnson, FR (reprint author), RTI Hlth Solut, 200 Pk Dr,POB 12194, Res Triangle Pk, NC 27709 USA. EM frjohnson@rti.org OI Hass, Steven/0000-0002-1686-030X FU Elan Pharmaceuticals, San Diego, California FX This study was funded by Elan Pharmaceuticals, San Diego, California. The views expressed here do not necessarily reflect those of Elan. NR 38 TC 21 Z9 21 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD JAN PY 2009 VL 29 IS 1 BP 121 EP 136 DI 10.1111/j.1539-6924.2008.01135.x PG 16 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 387WX UT WOS:000261983400009 PM 18826414 ER PT J AU Thomas, HJ Ahmad, T Rajaguru, C Barnardo, M Warren, BF Jewell, DP AF Thomas, Harry J. Ahmad, Tariq Rajaguru, Chandima Barnardo, Martin Warren, Bryan F. Jewell, Derek P. TI Contribution of histological, serological, and genetic factors to the clinical heterogeneity of adult-onset coeliac disease SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Coeliac disease; HLA-DQ antigens ID RISK VARIANTS; PRIMARY-CARE; HLA; SEVERITY; GLUTEN; DOSAGE; DQB1-ASTERISK-0201; SUSCEPTIBILITY; HETERODIMER; FAMILIES AB Objective. Although the factors predisposing to coeliac disease (CD) are largely understood, it remains unclear what determines the clinical heterogeneity of the disease. The aim of this study was to explore the contribution of histological, serological, and genetic factors to disease presentation. Material and methods. The study was designed as a retrospective chart review of 384 unrelated Caucasian patients diagnosed with CD after the age of 16 at a single UK centre. Results. We found that 8.8% of IgA-competent CD patients were endomysial antibody (EMA)-negative. Compared with the EMA-positive group, EMA-negative CD patients had a lower prevalence of iron deficiency (52.0% versus 72.6%, p = 0.03) and Marsh IIIb-c lesions (66.7% versus 85.3%, p = 0.03). Histological severity at diagnosis correlated with anaemia (p<0.01), folate deficiency (p<0.01), and iron deficiency (p = 0.05), but no other laboratory or clinical features. Compared with human leucocyte antigen (HLA)-DQ2.5-positive patients, those carrying HLA-DQ2.2 were similar in terms of all the characteristics we considered, whereas those carrying HLA-DQ8 had a lower frequency of EMA positivity (62.5% versus 92.6%, p<0.01). The proportion of EMA-positive patients increased with frequency of the HLA-DQB1*0201 allele (76.7% versus 92.3% versus 96.4% for 0 versus 1 versus 2 alleles, p<0.01); no other evidence of a gene-dose effect of HLADQB1*0201 was observed. Conclusions. Histological severity at diagnosis of CD is associated with anaemia and some micronutrient deficiencies, but no other clinical features. The proportion of EMA-positive patients is higher amongst those carrying HLA-DQ2 than in those carrying HLA-DQ8, and is highest in HLA-DQ2 homozygotes. We found no correlation between frequency of the HLA-DQ alleles encoding HLA-DQ2.5 and CD severity. C1 [Thomas, Harry J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ahmad, Tariq] Peninsula Med Sch, Plymouth, Devon, England. [Rajaguru, Chandima; Warren, Bryan F.] John Radcliffe Hosp, Dept Cellular Pathol, Oxford OX3 9DU, England. [Barnardo, Martin] Churchill Hosp, Oxford Transplant Ctr, Oxford OX3 7LJ, England. [Jewell, Derek P.] John Radcliffe Hosp, Gastroenterol Unit, Oxford OX3 9DU, England. RP Thomas, HJ (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM harry.thomas@doctors.org.uk FU University of Oxford FX The project was supported by the Gastroenterology Research Fund of Professor Jewell administered by the University of Oxford. We express our gratitude to Rosemary Kershaw and Diana Butler for secretarial assistance. NR 33 TC 12 Z9 13 U1 1 U2 4 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PY 2009 VL 44 IS 9 BP 1076 EP 1083 DI 10.1080/00365520903100473 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 503AW UT WOS:000270504600008 PM 19593686 ER PT J AU Jang, JS Choi, SR Qureshi, W Kim, MC Kim, SJ Jeung, JS Han, SY Noh, MH Lee, JH Lee, SW Baek, YH Kim, SH Choi, PJ AF Jang, Jin Seok Choi, Seok Reyol Qureshi, Waqar Kim, Min Chan Kim, Su Jin Jeung, Jin Sook Han, Sang Young Noh, Myung Hwan Lee, Jong Hoon Lee, Seung Wook Baek, Yang Hyun Kim, Sung Hyun Choi, Phil Jo TI Long-term outcomes of endoscopic submucosal dissection in gastric neoplastic lesions at a single institution in South Korea SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Curability; disease-free survival rate; endoscopic submucosal dissection; local recurrence; resectability ID LYMPH-NODE METASTASIS; MUCOSAL RESECTION; DIATHERMIC KNIFE; CANCER; STOMACH; TUMORS AB Objective. Although endoscopic treatment for early gastric cancer (EGC) is an accepted therapy in South Korea and Japan, long-term outcomes remain unknown. We evaluated the clinical outcome of endoscopic submucosal dissection (ESD) for gastric dysplasia and EGC. Material and methods. A total of 402 patients with gastric dysplasia and EGC were treated with ESD at a single hospital from January 2004 to December 2007. The patients underwent ESD and then received periodic endoscopic follow-up and metastatic surveys for 9-49 months (median 30 months). Resectability (en bloc or piecemeal resection), curability (complete or incomplete), local recurrence, and disease-free survival rates were estimated. Results. There were 107 patients with low-grade dysplasia (LGD), 97 with high-grade dysplasia (HGD) and 198 with EGC. In EGC patients, en bloc resection was achieved in 89.7% (177/198), the complete resection rate was 87.9% (174/198), and the local recurrence rate was 5.1% (10/198). Tumor size > 20 mm was significantly associated with local recurrence (odds ratio 6.45; 95% CI 1.20-20.11; p=0.001). There were significant correlations between the incidences of a piecemeal or incomplete resection and that of local recurrence (odds ratio 5.23; 95% CI 1.02-18.34; p=0.001; and odds ratio 6.99; 95% CI 1.22-21.65; p=0.002, respectively). The 3-year cancer-free survival rate was 94.9%. Conclusions. Curative treatment with successful en bloc resection can reduce the local recurrence of gastric neoplastic lesions after ESD. Clinical outcome may be excellent, although longer follow-up studies are warranted. C1 [Kim, Min Chan] Univ Coll Med, Dong A Med Ctr, Dept Gen Surg, Pusan, South Korea. [Kim, Su Jin; Jeung, Jin Sook] Univ Coll Med, Dong A Med Ctr, Dept Pathol, Pusan, South Korea. [Choi, Phil Jo] Univ Coll Med, Dong A Med Ctr, Dept Cardiac Surg, Pusan, South Korea. [Qureshi, Waqar] Baylor Coll Med, Houston, TX 77030 USA. [Qureshi, Waqar] Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX USA. [Jang, Jin Seok; Choi, Seok Reyol; Han, Sang Young; Noh, Myung Hwan; Lee, Jong Hoon; Lee, Seung Wook; Baek, Yang Hyun; Kim, Sung Hyun] Univ Coll Med, Dong A Med Ctr, Dept Internal Med, Pusan, South Korea. RP Choi, SR (reprint author), Univ Coll Med Busan, Dong A Med Ctr, Pusan, South Korea. EM sychoi@dau.ac.kr FU Dong-A University FX This study was supported by research funds from Dong-A University. NR 25 TC 25 Z9 27 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PY 2009 VL 44 IS 11 BP 1315 EP 1322 DI 10.3109/00365520903254304 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 528YX UT WOS:000272484000007 PM 19891582 ER PT J AU Jang, JS Choi, SR Graham, DY Kwon, HC Kim, MC Jeong, JS Won, JJ Han, SY Noh, MH Lee, JH Lee, SW Baek, YH Kim, MJ Jeong, DS Kim, SK AF Jang, Jin Seok Choi, Seok Reyol Graham, David Y. Kwon, Hyuk-Chan Kim, Min Chan Jeong, Jin Sook Won, Jong Jin Han, Sang Young Noh, Myung Hwan Lee, Jong Hoon Lee, Seung Wook Baek, Yang Hyun Kim, Min Ji Jeong, Dong Seong Kim, Seul Ki TI Risk factors for immediate and delayed bleeding associated with endoscopic submucosal dissection of gastric neoplastic lesions SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Endoscopic submucosal dissection; gastric neoplastic lesion; immediate and delayed bleeding; risk factors ID MUCOSAL RESECTION; CANCER; ULCER; TUMORS AB Objective. Endoscopic submucosal dissection (ESD) of gastric neoplasia has been reported to have a higher bleeding rate than conventional endoscopic mucosal resection (EMR). The aim of this study was to identify the risk factors for bleeding associated with ESD. Material and methods. The records of consecutive patients who underwent ESD for gastric adenoma/early gastric cancer were reviewed. Potential risk factors included patient age, lesion size, gross findings, location, and histology of the tumor. The primary end-point was the incidence of immediate or delayed bleeding related to ESD. Results. A total of 144 patients were studied; bleeding occurred in 32 cases (22.2%) with immediate bleeding in 29 cases. Delayed bleeding (3 cases) occurred at day 2 (2 patients) and at day 7 in 1 patient. In all cases of immediate bleeding, immediate hemostatic therapy was successful. The histology of tumor was the only factor that was statistically significantly associated with bleeding (adjusted hazard ratio 6.770, 95% confidence interval 1.830-25.048, p=0.004). Conclusions. The only factor that correlated with an increased risk of bleeding with ESD was the presence of gastric malignancy. We found no factor that would, prospectively, be amenable to prevention of bleeding. C1 [Jang, Jin Seok; Choi, Seok Reyol; Won, Jong Jin; Han, Sang Young; Noh, Myung Hwan; Lee, Jong Hoon; Lee, Seung Wook; Baek, Yang Hyun; Kim, Min Ji; Jeong, Dong Seong; Kim, Seul Ki] Univ Coll Med, Dong A Med Ctr, Dept Internal Med, Pusan, South Korea. [Graham, David Y.] Baylor Coll Med, Houston, TX 77030 USA. [Graham, David Y.] Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX USA. [Kwon, Hyuk-Chan] Univ Coll Med, Dong A Med Ctr, Dept Hematooncol, Pusan, South Korea. [Kim, Min Chan] Univ Coll Med, Dong A Med Ctr, Dept Gen Surg, Pusan, South Korea. [Jeong, Jin Sook] Univ Coll Med, Dong A Med Ctr, Dept Pathol, Pusan, South Korea. RP Choi, SR (reprint author), Univ Coll Med Busan, Dong A Med Ctr, Pusan, South Korea. EM sychoi@dau.ac.kr NR 20 TC 23 Z9 25 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PY 2009 VL 44 IS 11 BP 1370 EP 1376 DI 10.3109/00365520903194609 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 528YX UT WOS:000272484000014 PM 19891589 ER PT J AU Jespersen, S Sogaard, OS Fine, MJ Ostergaard, L AF Jespersen, Sanne Sogaard, Ole Schmeltz Fine, Michael J. Ostergaard, Lars TI The relationship between diagnostic tests and case characteristics in Legionnaires' disease SO SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID URINARY ANTIGEN TEST; LEGIONELLA INFECTION; CLINICAL SEVERITY; LARGE OUTBREAK; SENSITIVITY; PNEUMONIA AB In this retrospective study of 332 cases of Legionnaires' disease (LD) in 4 Danish counties between 1995 and 2005 we aimed to compare the sensitivity of culture, PCR, 'urinary antigen testing, and serology to the mode of acquisition, serogroup, and severity of disease. Furthermore, we analyzed time to diagnosis. Laboratory confirmed cases of LD were found through the national Danish surveillance system and departments of clinical microbiology. In our study PCR was more sensitive (79.2%) than urinary antigen testing (70.4%), serology (54.8%), and culture (39.9%) (p<0.001). The sensitivity of Legionella urinary antigen test was higher among travel-associated cases (90.2%) compared to non-travel-associated cases (65.8%) and hospital acquired cases (45.7%) (p <0.001). Overall, the most common species and serogroup identified was L. pneumophila serogroup 1 (64.3% (110/171)). Community acquired cases with serogroup 1 were diagnosed earlier (mean 5 cl, IQR: 4-9 d) than community acquired cases with other species or serogroups (mean 10.5 d, IQR: 5-19.5) (p < 0. 00 1). In conclusion, the urinary antigen test, PCR, and culture were conducive to the diagnosis of Legionella infection, and ordering of all 3 tests is recommended to ensure a definite and rapid diagnosis of Legionella. C1 [Jespersen, Sanne; Sogaard, Ole Schmeltz; Ostergaard, Lars] Aarhus Univ Hosp, Dept Infect Dis, Skejby, Denmark. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Fine, Michael J.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Med, Div Gen Med, Philadelphia, PA USA. RP Jespersen, S (reprint author), Aarhus Univ Hosp, Dept Infect Dis, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark. EM sannejespersen@hotmail.com RI Sogaard, Ole/P-6058-2016 FU Beckettforiden FX We acknowledge Statens Serum Institute and especially Soren Anker Uldum for making the microbiological data available to us. We thank Henrik C. Schonheyder for suggestions with the manuscript. The study was financially supported by Beckettforiden. NR 14 TC 7 Z9 9 U1 1 U2 3 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0036-5548 J9 SCAND J INFECT DIS JI Scand. J. Infect. Dis. PY 2009 VL 41 IS 6-7 BP 425 EP 432 DI 10.1080/00365540902946536 PG 8 WC Infectious Diseases SC Infectious Diseases GA 478JF UT WOS:000268583000005 PM 19424933 ER PT J AU Corrales-Medina, VE Fatemi, O Serpa, J Valayam, J Bozkurt, B Madjid, M Musher, DM AF Corrales-Medina, Vicente E. Fatemi, Omid Serpa, Jose Valayam, Josemon Bozkurt, Biykem Madjid, Mohammad Musher, Daniel M. TI The association between Staphylococcus aureus bacteremia and acute myocardial infarction SO SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID RECENT RESPIRATORY-INFECTION; ACUTE CORONARY SYNDROME; CARDIOVASCULAR-DISEASE; HEART-DISEASE; RISK; PREVENTION; INFLUENZA; VACCINATION; PNEUMONIA AB We evaluated a possible association between S. aureus bacteremia (SAB) and the occurrence of myocardial infarction (MI) in 588 patients using the self-controlled case series method. SAB increased the risk for MI 35-fold in the 2 d after recognition of this infection (IRR = 35.3; CI 16.7-74.7). C1 [Corrales-Medina, Vicente E.; Valayam, Josemon; Musher, Daniel M.] Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Houston, TX 77030 USA. [Bozkurt, Biykem] Michael E DeBakey Vet Affairs Med Ctr, Cardiol Sect, Houston, TX 77030 USA. [Corrales-Medina, Vicente E.; Fatemi, Omid; Serpa, Jose; Bozkurt, Biykem; Madjid, Mohammad; Musher, Daniel M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Musher, Daniel M.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Madjid, Mohammad] Univ Texas Hlth Sci Ctr, Texas Heart Inst, Houston, TX USA. RP Corrales-Medina, VE (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Room 4B-370, Houston, TX 77030 USA. EM vfmedina@bcm.edu OI Corrales-Medina, Vicente/0000-0002-9691-491X FU VA Menit Review Program FX This study was funded in part by the VA Menit Review Program (D.M.M). NR 23 TC 11 Z9 11 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0036-5548 J9 SCAND J INFECT DIS JI Scand. J. Infect. Dis. PY 2009 VL 41 IS 6-7 BP 511 EP 514 DI 10.1080/00365540902913460 PG 4 WC Infectious Diseases SC Infectious Diseases GA 478JF UT WOS:000268583000018 PM 19396667 ER PT J AU Minces, LR Ho, KS Veldkamp, PJ Clancy, CJ AF Minces, Lucio R. Ho, Ken S. Veldkamp, Peter J. Clancy, Cornelius J. TI Candida rugosa: a distinctive emerging cause of candidaemia. A case report and review of the literature SO SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID BLOOD-STREAM INFECTIONS; UNITED-STATES; FUNGEMIA; SURVEILLANCE; RESISTANCE; HOSPITALS; MASTITIS; PATHOGEN; OUTBREAK; ALBICANS AB Candida rugosa is a rare cause of candidaemia, but important to recognize because of frequent azole-resistance and its association with catheters and total parenteral nutrition. Recommended therapy is an echinocandin or amphotericin, and catheter discontinuation. Fluconazole might be substituted based on susceptibility testing and a clinical response to initial therapy. C1 [Minces, Lucio R.; Ho, Ken S.; Veldkamp, Peter J.; Clancy, Cornelius J.] Univ Pittsburgh, Dept Med, Med Ctr, Div Infect Dis, Pittsburgh, PA 15213 USA. [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Minces, LR (reprint author), Univ Pittsburgh, Dept Internal Med, Med Ctr, Div Infect Dis, 3601 5th Ave,Suite 3A, Pittsburgh, PA 15213 USA. EM mincesL2@upmc.edu NR 18 TC 12 Z9 12 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0036-5548 J9 SCAND J INFECT DIS JI Scand. J. Infect. Dis. PY 2009 VL 41 IS 11-12 BP 892 EP 897 DI 10.3109/00365540903161531 PG 6 WC Infectious Diseases SC Infectious Diseases GA 535MZ UT WOS:000272974600017 PM 19922077 ER PT J AU Potkin, SG Turner, JA Brown, GG McCarthy, G Greve, DN Glover, GH Manoach, DS Belger, A Diaz, M Wible, CG Ford, JM Mathalon, DH Gollub, R Lauriello, J O'Leary, D van Erp, TGM Toga, AW Preda, A Lim, KO AF Potkin, S. G. Turner, J. A. Brown, G. G. McCarthy, G. Greve, D. N. Glover, G. H. Manoach, D. S. Belger, A. Diaz, M. Wible, C. G. Ford, J. M. Mathalon, D. H. Gollub, R. Lauriello, J. O'Leary, D. van Erp, T. G. M. Toga, A. W. Preda, A. Lim, K. O. CA FBIRN TI Working memory and DLPFC inefficiency in schizophrenia: The FBIRN study SO SCHIZOPHRENIA BULLETIN LA English DT Article DE fMRI; schizophrenia; working memory; dorsolateral prefrontal cortex; cortical inefficiency ID DORSOLATERAL PREFRONTAL CORTEX; BASAL GANGLIA; FUNCTIONAL MRI; NAIVE PATIENTS; GRAY-MATTER; FMRI; PERFORMANCE; DYSFUNCTION; ACTIVATION; DEFICITS AB Background: The Functional Imaging Biomedical Informatics Network is a consortium developing methods for multisite functional imaging studies. Both prefrontal hyper- or hypoactivity in chronic schizophrenia have been found in previous studies of working memory. Methods: In this functional magnetic resonance imaging (fMRI) study of working memory, 128 subjects with chronic schizophrenia and 128 age- and gender-matched controls were recruited from 10 universities around the United States. Subjects performed the Sternberg Item Recognition Paradigm 1,2 with memory loads of 1, 3, or 5 items. A region of interest analysis examined the mean BOLD signal change in an atlas-based demarcation of the dorsolateral prefrontal cortex (DLPFC), in both groups, during both the encoding and retrieval phases of the experiment over the various memory loads. Results: Subjects with schizophrenia performed slightly but significantly worse than the healthy volunteers and showed a greater decrease in accuracy and increase in reaction time with increasing memory load. The mean BOLD signal in the DLPFC was significantly greater in the schizophrenic group than the healthy group, particularly in the intermediate load condition. A secondary analysis matched subjects for mean accuracy and found the same BOLD signal hyperresponse in schizophrenics. Conclusions: The increase in BOLD signal change from minimal to moderate memory loads was greater in the schizophrenic subjects than in controls. This effect remained when age, gender, run, hemisphere, and performance were considered, consistent with inefficient DLPFC function during working memory. These findings from a large multisite sample support the concept not of hyper- or hypofrontality in schizophrenia, but rather DLPFC inefficiency that may be manifested in either direction depending on task demands. This redirects the focus of research from direction of difference to neural mechanisms of inefficiency. C1 [Potkin, S. G.; Turner, J. A.; Preda, A.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92617 USA. [Brown, G. G.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92161 USA. [McCarthy, G.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Greve, D. N.; Manoach, D. S.; Gollub, R.] Massachusetts Gen Hosp, Dept Psychiat, Neuroimaging Div, Charlestown, MA 02129 USA. [Glover, G. H.] Stanford Univ, Lucas Imaging Ctr, Palo Alto, CA 94304 USA. [Belger, A.] Univ N Carolina, Chapel Hill, NC USA. [Belger, A.; Diaz, M.] Duke Univ, Med Ctr, Brain Imaging & Anal Ctr, Durham, NC 27710 USA. [Wible, C. G.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Wible, C. G.] Brigham Womans Hosp, Brockton VAMC, Boston, MA 02115 USA. [Lauriello, J.] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Ford, J. M.; Mathalon, D. H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lauriello, J.] Mind Res Network, Albuquerque, NM 87131 USA. [O'Leary, D.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [van Erp, T. G. M.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Toga, A. W.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Lim, K. O.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. RP Potkin, SG (reprint author), Univ Calif Irvine, Dept Psychiat & Human Behav, 5251 Calif Ave,Suite 240, Irvine, CA 92617 USA. EM sgpotkin@uci.edu RI Potkin, Steven/A-2021-2013; Turner, Jessica/H-7282-2015; OI Gollub, Randy L./0000-0002-9434-4044; Potkin, Steven/0000-0003-1028-1013; Preda, Adrian /0000-0003-3373-2438; Turner, Jessica/0000-0003-0076-8434; Belger, Aysenil/0000-0003-2687-1966; Mathalon, Daniel/0000-0001-6090-4974 FU National Center for Research Resources at the National Institutes of Health [U24-RR021992] FX U24-RR021992 to the Functional Imaging Biomedical Informatics Research Network ( FBIRN, http://www.fbirn.org) that is funded by the National Center for Research Resources at the National Institutes of Health. NR 66 TC 137 Z9 141 U1 3 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2009 VL 35 IS 1 BP 19 EP 31 DI 10.1093/schbul/sbn162 PG 13 WC Psychiatry SC Psychiatry GA 383OK UT WOS:000261682700007 PM 19042912 ER PT J AU Brown, GG McCarthy, G Bischoff-Grethe, A Ozyurt, B Greve, D Potkin, SG Turner, JA Notestine, R Calhoun, VD Ford, JM Mathalon, D Manoach, DS Gadde, S Glover, GH Wible, CG Belger, A Gollub, RL Lauriello, J O'Leary, D Lim, KO AF Brown, Gregory G. McCarthy, Gregory Bischoff-Grethe, Amanda Ozyurt, Burak Greve, Doug Potkin, Steven G. Turner, Jessica A. Notestine, Randy Calhoun, Vince D. Ford, Judy M. Mathalon, Daniel Manoach, Dara S. Gadde, Syam Glover, Gary H. Wible, Cynthia G. Belger, Aysenil Gollub, Randy L. Lauriello, John O'Leary, Daniel Lim, Kelvin O. TI Brain-Performance Correlates of Working Memory Retrieval in Schizophrenia: A Cognitive Modeling Approach SO SCHIZOPHRENIA BULLETIN LA English DT Article ID DORSOLATERAL PREFRONTAL CORTEX; FUNCTIONAL MRI; LEXICAL DECISION; YOUNG-ADULTS; FMRI; ACTIVATION; DYSFUNCTION; DEFICITS; TASK; FAMILIARITY AB Correlations of cognitive functioning with brain activation during a sternberg item recognition paradigm (SIRP) were investigated in patients with schizophrenia and in healthy controls studied at 8 sites. To measure memory scanning times, 4 response time models were fit to SIRP data. The best fitting model assumed exhaustive serial memory scanning followed by self-terminating memory search and involved one intercept parameter to represent SIRP processes not contributing directly to memory scanning. Patients displayed significantly longer response times with increasing memory load and differed on the memory scanning, memory search, and intercept parameters of the best fitting probability model. Groups differed in the correlation between the memory scanning parameter and linear brain response to increasing memory load within left inferior and left middle frontal gyrus, bilateral caudate, and right precuneus. The pattern of findings in these regions indicated that high scanning capacity was associated with high neural capacity among healthy subjects but that scanning speed was uncoupled from brain response to increasing memory load among schizophrenia patients. Group differences in correlation of the best fitting model's scanning parameter with a quadratic trend in brain response to increasing memory load suggested inefficient or disordered patterns of neural inhibition among individuals with schizophrenia, especially in the left perirhinal and entorhinal cortices. The results show at both cognitive and neural levels that disordered memory scanning contributes to deficient SIRP performance among schizophrenia patients. C1 [Brown, Gregory G.; Bischoff-Grethe, Amanda; Ozyurt, Burak; Notestine, Randy] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Brown, Gregory G.] VA San Diego Healthcare Syst, Psychol Serv, San Diego, CA USA. [McCarthy, Gregory] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Greve, Doug; Manoach, Dara S.; Gollub, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Potkin, Steven G.; Turner, Jessica A.] Univ Calif Irvine, Dept Psychiat, Irvine, CA 92717 USA. [Calhoun, Vince D.] Univ New Mexico, Mind Res Network, Albuquerque, NM 87131 USA. [Ford, Judy M.; Mathalon, Daniel] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Gadde, Syam] Duke Univ, Dept Psychiat, Durham, NC 27706 USA. [Glover, Gary H.] Stanford Univ, Radiol Sci Lab, Stanford, CA 94305 USA. [Wible, Cynthia G.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Belger, Aysenil] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Lauriello, John] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [O'Leary, Daniel] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. Univ Minnesota, Minneapolis VA Med Ctr, Dept Psychiat, Minneapolis, MN 55455 USA. RP Brown, GG (reprint author), Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. EM gbrown@ucsd.edu RI Potkin, Steven/A-2021-2013; Calhoun, Vince/H-7146-2013; Turner, Jessica/H-7282-2015; OI Mathalon, Daniel/0000-0001-6090-4974; Gollub, Randy L./0000-0002-9434-4044; Potkin, Steven/0000-0003-1028-1013; Calhoun, Vince/0000-0001-9058-0747; Turner, Jessica/0000-0003-0076-8434; Belger, Aysenil/0000-0003-2687-1966 FU National Center for Research Resources to the Function Biomedical Informatics Research Network [1 U24 RR021992]; Department of Veterans Affairs Mental Illness Research Education and Clinical Center FX National Center for Research Resources to the Function Biomedical Informatics Research Network ( National Institutes of Health grant 1 U24 RR021992); Department of Veterans Affairs Mental Illness Research Education and Clinical Center grant to the Desert Pacific Healthcare System. NR 60 TC 12 Z9 12 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2009 VL 35 IS 1 BP 32 EP 46 DI 10.1093/schbul/sbn149 PG 15 WC Psychiatry SC Psychiatry GA 383OK UT WOS:000261682700008 PM 19023127 ER PT J AU Wible, CG Lee, K Molina, I Hashimoto, R Preus, AP Roach, BJ Ford, JM Mathalon, DH McCarthey, G Turner, JA Potkin, SG O'Leary, D Belger, A Diaz, M Voyvodic, J Brown, GG Notestine, R Greve, D Lauriello, J AF Wible, C. G. Lee, K. Molina, I. Hashimoto, R. Preus, A. P. Roach, B. J. Ford, J. M. Mathalon, D. H. McCarthey, G. Turner, J. A. Potkin, S. G. O'Leary, D. Belger, A. Diaz, M. Voyvodic, J. Brown, G. G. Notestine, R. Greve, D. Lauriello, J. CA FBRIN TI fMRI Activity Correlated With Auditory Hallucinations During Performance of a Working Memory Task: Data From the FBIRN Consortium Study SO SCHIZOPHRENIA BULLETIN LA English DT Article ID VERBAL HALLUCINATIONS; PREFRONTAL CORTEX; SCHIZOPHRENIA; ANATOMY; BRAIN; PSYCHOSIS AB Introduction: Auditory hallucinations are a hallmark symptom of schizophrenia. The neural basis of auditory hallucinations was examined using data from a working memory task. Data were acquired within a multisite consortium and this unique dataset provided the opportunity to analyze data from a large number of subjects who had been tested on the same procedures across sites. We hypothesized that regions involved in verbal working memory and language processing would show activity that was associated with levels of hallucinations during a condition where subjects were rehearsing the stimuli. Methods: Data from the Sternberg Item Recognition Paradigm, a working memory task, were acquired during functional magnetic resonance imaging procedures. The data were collected and preprocessed by the functional imaging biomedical informatics research network consortium. Schizophrenic subjects were split into nonhallucinating and hallucinating subgroups and activity during the probe condition (in which subjects rehearsed stimuli) was examined. Levels of activation from contrast images for the probe phase (collapsed over levels of memory load) of the working memory task were also correlated with levels of auditory hallucinations from the Scale for the Assessment of Positive Symptoms scores. Results: Patients with auditory hallucinations (relative to nonhallucinating subjects) showed decreased activity during the probe condition in verbal working memory/language processing regions, including the superior temporal and inferior parietal regions. These regions also showed associations between activity and levels of hallucinations in a correlation analysis. Discussion: The association between activation and hallucinations scores in the left hemisphere language/working memory regions replicates the findings of previous studies and provides converging evidence for the association between superior temporal abnormalities and auditory hallucinations. C1 [Wible, C. G.; Molina, I.; Preus, A. P.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Wible, C. G.; Molina, I.; Preus, A. P.] Brockton VAMC, Boston, MA 02115 USA. [Lee, K.] Kangwon Natl Univ, Sch Med, Dept Psychiat, Kangwon Do, South Korea. [Hashimoto, R.] Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. [Roach, B. J.; Ford, J. M.; Mathalon, D. H.] Yale Univ, Dept Psychiat, West Haven, CT USA. [Roach, B. J.; Ford, J. M.; Mathalon, D. H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [McCarthey, G.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Turner, J. A.; Potkin, S. G.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [O'Leary, D.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Belger, A.; Diaz, M.; Voyvodic, J.] Duke Univ, Med Ctr, Dept Brain Imaging & Anal Ctr, Durham, NC USA. [Brown, G. G.; Notestine, R.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Greve, D.] Massachusetts Gen Hosp, Dept Psychiat, Neuroimaging Div, Charlestown, MA USA. [Lauriello, J.] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. RP Wible, CG (reprint author), Harvard Univ, Sch Med, 940 Belmont St,116A, Brockton, MA 02301 USA. EM cindy@bwh.harvard.edu RI Potkin, Steven/A-2021-2013; Turner, Jessica/H-7282-2015; OI Turner, Jessica/0000-0003-0076-8434; Roach, Brian/0000-0002-3264-1465; Belger, Aysenil/0000-0003-2687-1966; Mathalon, Daniel/0000-0001-6090-4974; Potkin, Steven/0000-0003-1028-1013 FU Biomedical Informatics Research Network [U24RR021992]; National Institute of Mental Health [1 R01 MH067080-01A2]; Harvard Neuro-Discovery Center FX Biomedical Informatics Research Network (U24RR021992); National Institute of Mental Health (1 R01 MH067080-01A2 to C. G. W.); Harvard Neuro-Discovery Center (formally HCNR). NR 25 TC 18 Z9 19 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2009 VL 35 IS 1 BP 47 EP 57 DI 10.1093/schbul/sbn142 PG 11 WC Psychiatry SC Psychiatry GA 383OK UT WOS:000261682700009 PM 18990710 ER PT J AU Ford, JM Roach, BJ Jorgensen, KW Turner, JA Brown, GG Notestine, R Bischoff-Grethe, A Greve, D Wible, C Lauriello, J Belger, A Mueller, BA Calhoun, V Preda, A Keator, D O'Leary, DS Lim, KO Glover, G Potkin, SG Mathalon, DH AF Ford, Judith M. Roach, Brian J. Jorgensen, Kasper W. Turner, Jessica A. Brown, Gregory G. Notestine, Randy Bischoff-Grethe, Amanda Greve, Douglas Wible, Cynthia Lauriello, John Belger, Aysenil Mueller, Bryon A. Calhoun, Vincent Preda, Adrian Keator, David O'Leary, Daniel S. Lim, Kelvin O. Glover, Gary Potkin, Steven G. Mathalon, Daniel H. CA FBRIN TI Tuning in to the Voices: A Multisite fMRI Study of Auditory Hallucinations SO SCHIZOPHRENIA BULLETIN LA English DT Article ID COROLLARY DISCHARGE DYSFUNCTION; SCHIZOPHRENIA; ACTIVATION; PERCEPTION; THINKING; SPEECH; CORTEX; BRAIN; GYRUS AB Introduction: Auditory hallucinations or voices are experienced by 75% of people diagnosed with schizophrenia. We presumed that auditory cortex of schizophrenia patients who experience hallucinations is tonically "tuned" to internal auditory channels, at the cost of processing external sounds, both speech and nonspeech. Accordingly, we predicted that patients who hallucinate would show less auditory cortical activation to external acoustic stimuli than patients who did not. Methods: At 9 Functional Imaging Biomedical Informatics Research Network (FBIRN) sites, whole-brain images from 106 patients and 111 healthy comparison subjects were collected while subjects performed an auditory target detection task. Data were processed with the FBIRN processing stream. A region of interest analysis extracted activation values from primary (BA41) and secondary auditory cortex (BA42), auditory association cortex (BA22), and middle temporal gyrus (BA21). Patients were sorted into hallucinators (n = 66) and nonhallucinators (n = 40) based on symptom ratings done during the previous week. Results: Hallucinators had less activation to probe tones in left primary auditory cortex (BA41) than nonhallucinators. This effect was not seen on the right. Discussion: Although "voices" are the anticipated sensory experience, it appears that even primary auditory cortex is "turned on" and "tuned in" to process internal acoustic information at the cost of processing external sounds. Although this study was not designed to probe cortical competition for auditory resources, we were able to take advantage of the data and find significant effects, perhaps because of the power afforded by such a large sample. C1 [Ford, Judith M.; Roach, Brian J.; Jorgensen, Kasper W.; Calhoun, Vincent; Mathalon, Daniel H.] Yale Univ, West Haven, CT 06520 USA. [Ford, Judith M.; Roach, Brian J.; Jorgensen, Kasper W.; Mathalon, Daniel H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ford, Judith M.; Roach, Brian J.; Mathalon, Daniel H.] San Francisco VA Med Ctr, San Francisco, CA USA. [Turner, Jessica A.; Preda, Adrian; Keator, David; Potkin, Steven G.] Univ Calif Irvine, Irvine, CA USA. [Brown, Gregory G.; Notestine, Randy; Bischoff-Grethe, Amanda] Univ Calif San Diego, San Diego, CA 92103 USA. [Greve, Douglas] Massachusetts Gen Hosp, Charlestown, MA USA. [Wible, Cynthia] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lauriello, John; Calhoun, Vincent] Univ New Mexico, Albuquerque, NM 87131 USA. [Belger, Aysenil] Univ N Carolina, Durham, NC USA. [Mueller, Bryon A.; O'Leary, Daniel S.] Univ Iowa, Iowa City, IA USA. [Lim, Kelvin O.] Univ Minnesota, Minneapolis, MN USA. [Glover, Gary] Stanford Univ, Stanford, CA 94305 USA. RP Ford, JM (reprint author), Yale Univ, West Haven, CT 06520 USA. EM judith.ford@yale.edu RI Potkin, Steven/A-2021-2013; Calhoun, Vince/H-7146-2013; Preda, Adrian /K-8889-2013; Turner, Jessica/H-7282-2015; OI Calhoun, Vince/0000-0001-9058-0747; Preda, Adrian /0000-0003-3373-2438; Turner, Jessica/0000-0003-0076-8434; Roach, Brian/0000-0002-3264-1465; Belger, Aysenil/0000-0003-2687-1966; Mathalon, Daniel/0000-0001-6090-4974; Potkin, Steven/0000-0003-1028-1013 FU Biomedical Informatics Research Network [U24RR021992] FX Biomedical Informatics Research Network (U24RR021992). NR 21 TC 52 Z9 52 U1 2 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2009 VL 35 IS 1 BP 58 EP 66 DI 10.1093/schbul/sbn140 PG 9 WC Psychiatry SC Psychiatry GA 383OK UT WOS:000261682700010 PM 18987102 ER PT J AU Kim, DI Mathalon, DH Ford, JM Mannell, M Turner, JA Brown, GG Belger, A Gollub, R Lauriello, J Wible, C O'Leary, D Lim, K Toga, A Potkin, SG Birn, F Calhoun, VD AF Kim, Dae Il Mathalon, D. H. Ford, J. M. Mannell, M. Turner, J. A. Brown, G. G. Belger, A. Gollub, R. Lauriello, J. Wible, C. O'Leary, D. Lim, K. Toga, A. Potkin, S. G. Birn, F. Calhoun, V. D. TI Auditory Oddball Deficits in Schizophrenia: An Independent Component Analysis of the fMRI Multisite Function BIRN Study SO SCHIZOPHRENIA BULLETIN LA English DT Article ID WORKING-MEMORY PERFORMANCE; PREFRONTAL CORTEX FUNCTION; RESTING-STATE NETWORKS; STATISTICAL LIMITATIONS; EFFECTIVE CONNECTIVITY; SELECTIVE DEFICITS; INTEGRATIVE THEORY; BRAIN-FUNCTION; NAIVE PATIENTS; DEFAULT MODE AB Deficits in the connectivity between brain regions have been suggested to play a major role in the pathophysiology of schizophrenia. A functional magnetic resonance imaging (fMRI) analysis of schizophrenia was implemented using independent component analysis (ICA) to identify multiple temporally cohesive, spatially distributed regions of brain activity that represent functionally connected networks. We hypothesized that functional connectivity differences would be seen in auditory networks comprised of regions such as superior temporal gyrus as well as executive networks that consisted of frontal-parietal areas. Eight networks were found to be implicated in schizophrenia during the auditory oddball paradigm. These included a bilateral temporal network containing the superior and middle temporal gyrus; a default-mode network comprised of the posterior cingulate, precuneus, and middle frontal gyrus; and multiple dorsal lateral prefrontal cortex networks that constituted various levels of between-group differences. Highly task-related sensory networks were also found. These results indicate that patients with schizophrenia show functional connectivity differences in networks related to auditory processing, executive control, and baseline functional activity. Overall, these findings support the idea that the cognitive deficits associated with schizophrenia are widespread and that a functional connectivity approach can help elucidate the neural correlates of this disorder. C1 [Kim, Dae Il; Mannell, M.; Calhoun, V. D.] Mind Res Network, Albuquerque, NM 87131 USA. [Mathalon, D. H.; Ford, J. M.; Calhoun, V. D.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Turner, J. A.; Potkin, S. G.; Birn, F.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92697 USA. [Brown, G. G.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92161 USA. [Belger, A.] Duke Univ, Med Ctr, Brain Imaging & Anal Ctr, Durham, NC 27710 USA. [Gollub, R.] Massachusetts Gen Hosp, Dept Psychiat, Neuroimaging Div, Charlestown, MA 02129 USA. [Lauriello, J.] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Wible, C.] Brigham Womans Hosp, Dept Radiol, Boston, MA 02115 USA. [O'Leary, D.; Lim, K.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Toga, A.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Calhoun, V. D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. RP Kim, DI (reprint author), Mind Res Network Inst, Albuquerque, NM 87131 USA. EM dkim@mrn.org RI Potkin, Steven/A-2021-2013; Calhoun, Vince/H-7146-2013; Turner, Jessica/H-7282-2015; OI Calhoun, Vince/0000-0001-9058-0747; Turner, Jessica/0000-0003-0076-8434; Belger, Aysenil/0000-0003-2687-1966; Mathalon, Daniel/0000-0001-6090-4974; Gollub, Randy L./0000-0002-9434-4044; Potkin, Steven/0000-0003-1028-1013 FU National Institutes of Health [000840]; NCRR [U24-RR021992] FX National Institutes of Health (1 R01 EB #000840); NCRR (U24-RR021992). NR 58 TC 74 Z9 74 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2009 VL 35 IS 1 BP 67 EP 81 DI 10.1093/schbul/sbn133 PG 15 WC Psychiatry SC Psychiatry GA 383OK UT WOS:000261682700011 PM 19074498 ER PT J AU Segall, JM Turner, JA van Erp, TGM White, T Bockholt, HJ Gollub, RL Ho, BC Magnotta, V Jung, RE McCarley, RW Schulz, SC Lauriello, J Clark, VP Voyvodic, JT Diaz, MT Calhoun, VD AF Segall, Judith M. Turner, Jessica A. van Erp, Theo G. M. White, Tonya Bockholt, H. Jeremy Gollub, Randy L. Ho, Beng C. Magnotta, Vince Jung, Rex E. McCarley, Robert W. Schulz, S. Charles Lauriello, John Clark, Vince P. Voyvodic, James T. Diaz, Michele T. Calhoun, Vince D. TI Voxel-based Morphometric Multisite Collaborative Study on Schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article ID GRAY-MATTER DIFFERENCES; ADULT HUMAN BRAINS; MULTICENTER FMRI; SEX-DIFFERENCES; FILTER SIZE; MRI; METAANALYSIS; VARIABILITY; NEUROANATOMY; FEASIBILITY AB Regional gray matter (GM) abnormalities are well known to exist in patients with chronic schizophrenia. Voxel-based morphometry (VBM) has been previously used on structural magnetic resonance images (MRI) data to characterize these abnormalities. Two multisite schizophrenia studies, the Functional Biomedical Informatics Research Network and the Mind Clinical Imaging Consortium, which include 9 data collection sites, are evaluating the efficacy of pooling structural imaging data across imaging centers. Such a pooling of data could yield the increased statistical power needed to elucidate effects that may not be seen with smaller samples. VBM analyses were performed to evaluate the consistency of patient versus control gray matter concentration (GMC) differences across the study sites, as well as the effects of combining multisite data. Integration of data from both studies yielded a large sample of 503 subjects, including 266 controls and 237 patients diagnosed with schizophrenia, schizoaffective or schizophreniform disorder. The data were analyzed using the combined sample, as well as analyzing each of the 2 multisite studies separately. A consistent pattern of reduced relative GMC in schizophrenia patients compared with controls was found across all study sites. Imaging center-specific effects were evaluated using a region of interest analysis. Overall, the findings support the use of VBM in combined multisite studies. This analysis of schizophrenics and controls from around the United States provides continued supporting evidence for GM deficits in the temporal lobes, anterior cingulate, and frontal regions in patients with schizophrenia spectrum disorders. C1 [Segall, Judith M.; Bockholt, H. Jeremy; Jung, Rex E.; Clark, Vince P.; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM 87131 USA. [Turner, Jessica A.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [van Erp, Theo G. M.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [White, Tonya; Schulz, S. Charles] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Gollub, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Ho, Beng C.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Magnotta, Vince] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. [McCarley, Robert W.] VAMC, Dept Psychiat, Brockton, MA USA. [McCarley, Robert W.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. [Lauriello, John] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Voyvodic, James T.; Diaz, Michele T.] Duke Univ, Brain Imaging & Anal Ctr, Durham, NC USA. [Calhoun, Vince D.] Univ New Mexico, Dept ECE, Albuquerque, NM 87131 USA. [Calhoun, Vince D.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. RP Calhoun, VD (reprint author), Mind Res Network, 1101 Yale Blvd NE, Albuquerque, NM 87131 USA. EM vcalhoun@unm.edu RI Turner, Jessica/H-7282-2015; Ho, Beng-Choon/D-6959-2011; Calhoun, Vince/H-7146-2013; McCarley, Robert/N-5562-2014; Clark, Vincent/B-3343-2010 OI Turner, Jessica/0000-0003-0076-8434; Gollub, Randy L./0000-0002-9434-4044; Ho, Beng-Choon/0000-0003-3976-1555; Calhoun, Vince/0000-0001-9058-0747; McCarley, Robert/0000-0001-5705-7495; Clark, Vincent/0000-0002-9151-2102 FU NIH [U24-RR021992, U24-RR021382]; DOE [DE-FG02-99ER62764] FX NIH U24-RR021992 to the Functional Biomedical Informatics Research Network (FBIRN, http://www.fbirn.org), and NIH U24-RR021382 to the Morphometry BIRN, by the National Center for Research Resources; and DOE Grant No. DE-FG02-99ER62764. NR 49 TC 67 Z9 68 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2009 VL 35 IS 1 BP 82 EP 95 DI 10.1093/schbul/sbn150 PG 14 WC Psychiatry SC Psychiatry GA 383OK UT WOS:000261682700012 PM 18997157 ER PT J AU Barch, DM Carter, CS Arnsten, A Buchanan, RW Cohen, JD Geyer, M Green, MF Krystal, JH Nuechterlein, K Robbins, T Silverstein, S Smith, EE Strauss, M Wykes, T Heinssen, R AF Barch, Deanna M. Carter, Cameron S. Arnsten, Amy Buchanan, Robert W. Cohen, Jonathan D. Geyer, Mark Green, Michael F. Krystal, John H. Nuechterlein, Keith Robbins, Trevor Silverstein, Steven Smith, Edward E. Strauss, Milton Wykes, Til Heinssen, Robert TI Selecting Paradigms From Cognitive Neuroscience for Translation into Use in Clinical Trials: Proceedings of the Third CNTRICS Meeting SO SCHIZOPHRENIA BULLETIN LA English DT Article ID IMPROVE COGNITION; SCHIZOPHRENIA; TARGETS; ENHANCEMENT; RECEPTORS; DEFICITS; AGONISTS; TASKS; SIZE AB This overview describes the goals and objectives of the third conference conducted as part of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. This third conference was focused on selecting specific paradigms from cognitive neuroscience that measured the constructs identified in the first CNTRICS meeting, with the goal of facilitating the translation of these paradigms into use in clinical trials contexts. To identify such paradigms, we had an open nomination process in which the field was asked to nominate potentially relevant paradigms and to provide information on several domains relevant to selecting the most promising tasks for each construct (eg, construct validity, neural bases, psychometrics, availability of animal models). Our goal was to identify 1-2 promising tasks for each of the 11 constructs identified at the first CNTRICS meeting. In this overview article, we describe the on-line survey used to generate nominations for promising tasks, the criteria that were used to select the tasks, the rationale behind the criteria, and the ways in which breakout groups worked together to identify the most promising tasks from among those nominated. This article serves as an introduction to the set of 6 articles included in this special issue that provide information about the specific tasks discussed and selected for the constructs from each of 6 broad domains (working memory, executive control, attention, long-term memory, perception, and social cognition). C1 [Barch, Deanna M.] Washington Univ, St Louis, MO 63130 USA. [Carter, Cameron S.] Univ Calif Davis, Davis, CA 95616 USA. [Arnsten, Amy; Krystal, John H.] Yale Univ, New Haven, CT USA. [Buchanan, Robert W.] Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. [Cohen, Jonathan D.] Princeton Univ, Princeton, NJ 08544 USA. [Geyer, Mark] Univ Calif San Diego, San Diego, CA 92103 USA. [Green, Michael F.] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA USA. [Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Nuechterlein, Keith] Univ Calif Los Angeles, Los Angeles, CA USA. [Robbins, Trevor] Univ Cambridge, Cambridge, England. [Silverstein, Steven] Univ Med & Dent New Jersey, Rutgers, NJ USA. [Smith, Edward E.] Columbia Univ, New York, NY USA. [Strauss, Milton] Univ New Mexico, Albuquerque, NM USA. [Wykes, Til] Kings Coll London, Inst Psychiat, London, England. [Heinssen, Robert] NIMH, Bethesda, MD 20892 USA. RP Barch, DM (reprint author), Washington Univ, St Louis, MO 63130 USA. EM dbarch@artsci.wustl.edu RI Wykes, Til/B-7894-2008; Wykes, Til/B-3812-2011; Barch, Deanna/G-8638-2013 OI Wykes, Til/0000-0002-5881-8003; FU National Institute of Mental Health (NIMH); Robert Wood Johnson Foundation; National Alliance for Research on Schizophrenia and Depression (NARSAD); McDonnell Foundation; National Institute of Drugs and Alcohol; US Veteran's Administration VISN 22 Mental Illness Research, Education, and Clinical Center; Janssen; Pfizer; GSK Inc FX We would also like to thank Jody Conrad, Carol Cox, and Deb Tussing, whose efforts have been invaluable in the CNTRICS process. Financial Disclosures: Carter receives funding from the National Institute of Mental Health (NIMH), the Robert Wood Johnson Foundation, and National Alliance for Research on Schizophrenia and Depression (NARSAD). Dr Carter has served as a consultant for Pfizer, Eli Lilly, and Roche. Barch receives funding from the NIMH, the McDonnell Foundation, and NARSAD. Dr Buchanan is currently a Data Safety and Management Board (DSMB) member for Pfizer and in the past has served as a DSMB member for Wyeth. He has served as a consultant for: Pfizer, Roche, Memory, GlaxoSmithKline, Astra-Zeneca, Solvay, Sanofi-Aventis, and Organon and has received study medications from Janssen and Ortho-McNeil Neurologics. Dr Geyer has received consulting compensation from Abbott, Acadia, Addex, Amgen, AstraZeneca, Bristol-Myers Squibb, Jazz, Organon, Nura, San Diego Instruments, Serono, and Wyeth-Ayerst. Dr Geyer also has research grant support from National Institute of Drugs and Alcohol, NIMH, and the US Veteran's Administration VISN 22 Mental Illness Research, Education, and Clinical Center. Dr Green received funding form the NIMH and serves as a consultant to Amgen, Acadia, Astellas, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Eli Lilly, Lundbeck, Memory Pharmaceuticals, Otsuka Pharmaceutical, Sanofi-Aventis Pharmaceuticals, and Solvay. Dr Krystal receives research funding from the NIMH and has served as an advisor or consultant for AstraZeneca Pharmaceuticals; LP Bristol-Myers Squibb; Cypress Bioscience, Inc; Eli Lilly and Co; Forest Laboratories; GlaxoSmithKline; HoustonPharma; Lohocla Research Corporation; Merz Pharmaceuticals; Organon Pharmaceuticals; Pfizer Pharmaceuticals; Tetragenex Pharmaceuticals; and Transcept Pharmaceuticals, Inc. Dr Nuechterlein has received research funding from the NIMH and from Janssen, L. P., and has served as a consultant for Janssen, L. P. Dr Robbins is a stockholder in CeNeS and has share options in Cambridge Cognition. He has served as a consultant to Eli Lilly, GSK, Wyeth, and Allon and has received research funding from Pfizer, GSK Inc and received speaking honoraria from Merck, Sharp and Dohme, Lundbeck, Cephalon, and Cortex. Dr Silverstein Medical Research Institute, Janssen, and AstraZeneca. Dr Strauss, Dr Heinssen, Dr Smith, and Dr Wykes reported no biomedical financial interests or conflicts of interest. Dr Cohen receives research funding from the NIMH. NR 17 TC 73 Z9 74 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2009 VL 35 IS 1 BP 109 EP 114 DI 10.1093/schbul/sbn163 PG 6 WC Psychiatry SC Psychiatry GA 383OK UT WOS:000261682700014 PM 19023126 ER PT J AU Green, MF Butler, PD Chen, Y Geyer, MA Silverstein, S Wynn, JK Yoon, JH Zemon, V AF Green, Michael F. Butler, Pamela D. Chen, Yue Geyer, Mark A. Silverstein, Steven Wynn, Jonathan K. Yoon, Jong H. Zemon, Vance TI Perception Measurement in Clinical Trials of Schizophrenia: Promising Paradigms From CNTRICS SO SCHIZOPHRENIA BULLETIN LA English DT Review ID LATERAL GENICULATE-NUCLEUS; EVENT-RELATED POTENTIALS; PRIMARY VISUAL-CORTEX; MACAQUE V1 NEURONS; MISMATCH NEGATIVITY GENERATION; PREPULSE INHIBITION DEFICITS; SENSORIMOTOR GATING DEFICITS; CONTOUR INTEGRATION DEFICITS; AUDITORY SENSORY MEMORY; RETINAL GANGLION-CELLS AB The third meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) focused on selecting promising measures for each of the cognitive constructs selected in the first CNTRICS meeting. In the domain of perception, the 2 constructs of interest were gain control and visual integration. CNTRICS received 5 task nominations for gain control and three task nominations for visual integration. The breakout group for perception evaluated the degree to which each of these tasks met prespecified criteria. For gain control, the breakout group for perception believed that 2 of the tasks (prepulse inhibition of startle and mismatch negativity) were already mature and in the process of being incorporated into multisite clinical trials. However, the breakout group recommended that steady-state visual-evoked potentials be combined with contrast sensitivity to magnocellular vs parvocellular biased stimuli and that this combined task and the contrast-contrast effect task be recommended for translation for use in clinical trial contexts in schizophrenia research. For visual integration, the breakout group recommended the Contour Integration and Coherent Motion tasks for translation for use in clinical trials. This manuscript describes the ways in which each of these tasks met the criteria used by the breakout group to evaluate and recommend tasks for further development. C1 [Green, Michael F.; Wynn, Jonathan K.] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA 90095 USA. [Green, Michael F.; Wynn, Jonathan K.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Butler, Pamela D.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. [Butler, Pamela D.] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Butler, Pamela D.] NYU, Cognit Neurosci Program, New York, NY USA. [Chen, Yue] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. [Geyer, Mark A.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Silverstein, Steven] Univ Behav HealthCare, Piscataway, NJ USA. [Silverstein, Steven] Robert Wood Johnson Med Sch, Piscataway, NJ USA. [Yoon, Jong H.] Univ Calif Davis, Dept Psychiat, Davis, CA 95616 USA. [Zemon, Vance] Yeshiva Univ, Ferkauf Grad Sch Psychol, Bronx, NY USA. RP Green, MF (reprint author), Univ Calif Los Angeles, Semel Inst, Los Angeles, CA 90095 USA. EM mgreen@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU National Institute of Mental Health (NIMH); Department of Veterans Affairs (VA) [MH43292, MH66374, MH61824]; National Institute of Drug Abuse (NIDA) [DA02925]; US Veteran's Administration VISN 22 Mental Illness Research, Education, and Clinical Center; Stanley Medical Research Institute; Janssen; AstraZeneca FX National Institute of Mental Health (NIMH) and the Department of Veterans Affairs (VA) to M. F. G. MH43292 and J.K.W.; NIMH to P. D. B., MH66374 Y.C., MH61824 and J.H.Y.; consulting compensation from Abbott, Acadia, Addex, Amgen, AstraZeneca, Bristol-Myers Squibb, Jazz, Organon, Nura, San Diego Instruments, Serono, and Wyeth-Ayerst to M. A. G.; MH52885 research grant support from National Institute of Drug Abuse (NIDA DA02925, NIMH, and the US Veteran's Administration VISN 22 Mental Illness Research, Education, and Clinical Center to M. A. G.; NIMH, NARSAD, Stanley Medical Research Institute, Janssen, and AstraZeneca to S. S. M. F. G. serves as a consultant to Amgen, Acadia, Astellas, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Eli Lilly, Lundbeck, Memory Pharmaceuticals, Otsuka Pharmaceutical, Sanofi-Aventis Pharmaceuticals, and Solvay. NR 172 TC 62 Z9 62 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2009 VL 35 IS 1 BP 163 EP 181 DI 10.1093/schbul/sbn156 PG 19 WC Psychiatry SC Psychiatry GA 383OK UT WOS:000261682700018 PM 19023123 ER PT J AU Fitzsimmons, J Kubicki, M Smith, K Bushell, G Estepar, RSJ Westin, CF Nestor, PG Niznikiewicz, MA Kikinis, R McCarley, RW Shenton, ME AF Fitzsimmons, J. Kubicki, M. Smith, K. Bushell, G. Estepar, R. San Jose Westin, C. -F. Nestor, P. G. Niznikiewicz, M. A. Kikinis, R. McCarley, R. W. Shenton, M. E. TI Diffusion tractography of the fornix in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Diffusion tensor imaging; Fractional anisotropy; Fornix; Schizophrenia ID WORKING-MEMORY DEFICITS; FRONTAL-CORTEX CONNECTIONS; WHITE-MATTER INTEGRITY; DT-MRI DATA; TEMPORAL-LOBE; HUMAN BRAIN; CINGULUM ABNORMALITIES; ONSET SCHIZOPHRENIA; HIPPOCAMPAL VOLUME; PREFRONTAL CORTEX AB Background: White matter fiber tracts, especially those interconnecting the frontal and temporal lobes, are likely implicated in pathophysiology of schizophrenia. Very few studies, however. have focused on the fornix, a compact bundle of white matter fibers, projecting from the hippocampus to the septum, anterior nucleus of the thalamus and the mamillary bodies. Diffusion Tenser Imaging (DTI), and a new post-processing method, fiber tractography, provides a unique opportunity to visualize and to quantify entire trajectories of fiber bundles, such as the fornix, in vivo. We applied these techniques to quantify fornix diffusion anisotropy in schizophrenia. Methods: DTI images were used to evaluate the left and the right fornix in 36 male patients diagnosed with chronic schizophrenia and 35 male healthy individuals. group matched on age, parental socioeconomic status, and handedness. Regions of interest were drawn manually, blind to group membership, to guide tractography, and fractional anisotropy (FA), a measure of fiber integrity, was calculated and averaged over the entire tract for each subject. The Doors and People test (DPT) was used to evaluate visual and verbal memory, combined recall and combined recognition. Results: Analysis of variance was performed and findings demonstrated a difference between patients with schizophrenia and controls for fornix FA (p=0.006). Protected post-hoc independent sample t-tests demonstrated a bilateral FA decrease in schizophrenia, compared with control subjects (left side: p=0.048; right side p=0.006). Higher fornix FA was statistically significantly correlated with DPT and measures of combined visual memory (r=0.554, p=0.026), combined verbal memory (r=0.647, p=0.007), combined recall (r=0.516, p=0.041), and combined recognition (r=0.710, p=0.002) for the control group. No such statistically significant correlations were found in the patient group. Conclusions: Our findings show the utility of applying DTI and tractography to study white matter fiber tracts in vivo in schizophrenia. Specifically, we observed a bilateral disruption in fornix integrity in schizophrenia, thus broadening our understanding of the pathophysiology of this disease. (c) 2008 Elsevier B.V. All rights reserved. C1 [Fitzsimmons, J.; Kubicki, M.; Smith, K.; Bushell, G.; Shenton, M. E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat,Psychiat Neuroimaging Lab, Boston, MA 02215 USA. [Kubicki, M.; Nestor, P. G.; Niznikiewicz, M. A.; McCarley, R. W.; Shenton, M. E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Boston, MA 02215 USA. [Estepar, R. San Jose; Westin, C. -F.; Kikinis, R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Math Imaging,Dept Radiol, Boston, MA 02215 USA. [Westin, C. -F.; Shenton, M. E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Surg Planning Lab,Dept Radiol,MRI Div, Boston, MA 02215 USA. RP Fitzsimmons, J (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat,Psychiat Neuroimaging Lab, 1249 Boylston St,3rd Floor, Boston, MA 02215 USA. EM jfitzsimmons@bwh.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU National Institute of Health [K05 MH070047, R01 MH 50740, R01 MH 40799, R01 MH 074794, P50 MH 080272]; National Alliance for Medical Image Computing (NAMIC); National Institutes of Health through the NIH Roadmap for Medical Research [U54 EB005149] FX The authors would like to thank Nancy Maxwell and Jennifer Goodrich for administrative support: Marek Kubicki, M.D.. Ph.D., and Martha Shenton, Ph.D. for personal support; and Georgia Bushell, B.A., Kate Smith, B.A. and Usman Khan, B.A. for their support as research assistants. Additionally, we gratefully acknowledge the support of the National Institute of Health (K05 MH070047 and R01 MH 50740 to MES, ROI MH 40799 to RWM and R01 MH 074794 to CFW, P50 MH 080272 to RWM, MES), the Department ofVeterans Affairs Merit Awards (MES, RWM), and the VA Schizophrenia Center Grant (RWM/MES). This work is also part of the National Alliance for Medical Image Computing (NAMIC), funded by the National Institutes of Health through the NIH Roadmap for Medical Research. Grant U54 EB005149 (MK, RK, MES). NR 84 TC 55 Z9 56 U1 3 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 JAN PY 2009 VL 107 IS 1 BP 39 EP 46 DI 10.1016/j.schres.2008.10.022 PG 8 WC Psychiatry SC Psychiatry GA 404KW UT WOS:000263151500005 PM 19046624 ER PT J AU Kee, KS Horan, WR Salovey, P Kern, RS Sergi, MJ Fiske, AP Lee, JH Subotnik, KL Nuechterlein, K Sugar, CA Green, MF AF Kee, Kimmy S. Horan, William R. Salovey, Peter Kern, Robert S. Sergi, Mark J. Fiske, Alan P. Lee, Junghee Subotnik, Kenneth L. Nuechterlein, Keith Sugar, Catherine A. Green, Michael F. TI Emotional intelligence in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Emotional intelligence; Emotion processing; Social cognition ID FACIAL-AFFECT RECOGNITION; SOCIAL COGNITION; BEHAVIOR; PERFORMANCE; MEDIATOR; PSYCHOPATHOLOGY; SYMPTOMATOLOGY; NEUROSCIENCE; PERSONALITY; PERCEPTION AB Background: Deficits in emotion perception have been extensively documented in schizophrenia and are associated with poor psychosocial functioning. However, little is known about other aspects of emotion processing that are critical for adaptive functioning. The current study assessed schizophrenia patients' performance on a theoretically-based, well-validated, multidimensional measure of emotional intelligence, the Mayer-Salovey-Caruso Emotional Intelligence Test (Mayer, J.D., Salovey, P., Caruso, D.R., 2002. Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT): User's Manual. Multi-Health Systems, Inc., Toronto, Ontario). Methods: 50 schizophrenia outpatients and 39 non-psychiatric controls completed the MSCEIT, a performance measure comprised of subtests that assess four components (branches) of emotional intelligence: Identifying, Using, Understanding, and Managing Emotions. Among patients, associations between MSCEIT scores and measures of clinical symptoms as well as functional outcome were evaluated. Results: The MSCEIT demonstrated good psychometric properties in both groups. Schizophrenia patients performed significantly worse than controls on the total MSCEIT score, and on three of the four subtests: Identifying, Understanding, and Managing Emotions. Among patients, lower MSCEIT scores significantly correlated with higher negative and disorganized symptoms, as well as worse community functioning. Conclusions: The MSCEIT is a useful tool for investigating emotion processing in schizophrenia. Individuals with schizophrenia demonstrate deficits across multiple domains of emotion processing. These deficits have significant links with clinical symptoms of schizophrenia and with how patients function in their daily lives. Further research is required to understand the links between emotional intelligence, clinical symptoms, and functional outcome in schizophrenia. (c) 2008 Elsevier B.V. All rights reserved. C1 [Kee, Kimmy S.; Horan, William R.; Kern, Robert S.; Sergi, Mark J.; Lee, Junghee; Green, Michael F.] VA Greater Angeles Healthcare Syst, VISN22, MIRECC, Los Angeles, CA 90073 USA. [Kee, Kimmy S.] Calif State Univ Channel Islands, Psychol Program, Camarillo, CA USA. [Kee, Kimmy S.; Horan, William R.; Kern, Robert S.; Lee, Junghee; Subotnik, Kenneth L.; Nuechterlein, Keith; Green, Michael F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Salovey, Peter] Yale Univ, Yale Coll Deans Off, New Haven, CT 06520 USA. [Salovey, Peter] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Sergi, Mark J.] Calif State Univ Northridge, Dept Psychol, Northridge, CA 91330 USA. [Fiske, Alan P.] Univ Calif Los Angeles, Dept Anthropol, Ctr Culture Brain & Dev, Los Angeles, CA 90024 USA. [Fiske, Alan P.] Univ Calif Los Angeles, Ctr Behav Evolut & Culture, Los Angeles, CA 90024 USA. [Nuechterlein, Keith] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. RP Kee, KS (reprint author), VA Greater Angeles Healthcare Syst, VISN22, MIRECC, 11301 Wilshire Blvd,MIRECC 210A,Bldg 210, Los Angeles, CA 90073 USA. EM kee@ucla.edu RI Lee, Junghee/C-5226-2014 OI Lee, Junghee/0000-0001-9567-8700 FU National Institute of Mental Health Center [P50 MH 66586] FX Funding for this project was supported by the National Institute of Mental Health Center Grant P50 MH 66586 (K. Nuechterlein, P.I.) The authors wish to thank Mike DeGroot, Robin Kite, Jeff Nishii, and Samantha Swain for their assistance in data collection and data management. NR 67 TC 45 Z9 49 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2009 VL 107 IS 1 BP 61 EP 68 DI 10.1016/j.schres.2008.08.016 PG 8 WC Psychiatry SC Psychiatry GA 404KW UT WOS:000263151500008 PM 18805674 ER PT J AU Gutierrez, PM Osman, A AF Gutierrez, Peter M. Osman, Augustine TI Getting the Best Return on Your Screening Investment: An Analysis of the Suicidal Ideation Questionnaire and Reynolds Adolescent Depression Scale SO SCHOOL PSYCHOLOGY REVIEW LA English DT Article ID PREVENTION PROGRAMS; BEHAVIOR; SCHOOL; YOUTH; ISSUES; RECOMMENDATIONS; INTERVIEW; VALIDITY; CHILDREN AB Data from 64 adolescent inpatients admitted for serious suicidal ideation, 50 adolescent inpatients admitted following a suicide attempt, and 56 randomly selected high school control participants were used to evaluate the sensitivity, specificity, positive predictive value, and negative predictive value of the Suicidal Ideation Questionnaire (SIQ) and the Reynolds Adolescent Depression Scale-2nd Edition (RADS-2). The purpose of the study was to provide information necessary for selecting assessment tools to use in large-scale screenings of high school students for suicide risk. The hypothesis that a combination of mean scores on the two measures and critical item scores would provide the best clinical utility was partially supported. The SIQ was found to be very useful in discriminating between the study groups, whereas the RADS-2 did not perform as expected. The fewest false negatives would result from relying on RADS-2 scale scores >= 63 and SIQ scale scores >= 14. However, the parsimonious and hence most cost-effective approach would be to rely on SIQ scale scores >= 14 in combination with SIQ critical Items 2, 3, and 4 for screening purposes. C1 [Gutierrez, Peter M.] Denver VA Med Ctr, MIRECC, Denver, CO 80220 USA. [Osman, Augustine] Univ Texas San Antonio, San Antonio, TX USA. RP Gutierrez, PM (reprint author), Denver VA Med Ctr, MIRECC, 1055 Clermont St, Denver, CO 80220 USA. EM peter.gutierrez@va.gov NR 39 TC 12 Z9 12 U1 2 U2 6 PU NATL ASSOC SCHOOL PSYCHOLOGISTS PI BETHESDA PA 4340 EAST WEST HWY, STE 402, BETHESDA, MD 20814 USA SN 0279-6015 J9 SCHOOL PSYCHOL REV JI Sch. Psychol. Rev. PY 2009 VL 38 IS 2 BP 200 EP 217 PG 18 WC Psychology, Educational SC Psychology GA 462MV UT WOS:000267358400004 ER PT J AU Kutner, NG Johansen, KL AF Kutner, Nancy G. Johansen, Kirsten L. TI Targeting Inactivity, Falls and Mobility Deficits SO SEMINARS IN DIALYSIS LA English DT Editorial Material ID HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; WOMENS HEALTH; FRAILTY; OLDER; INTERVENTIONS; PHENOTYPE; MORTALITY; EXERCISE; TIME C1 [Kutner, Nancy G.] Emory Univ, Dept Rehabil Med, Atlanta, GA 30322 USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. RP Kutner, NG (reprint author), Emory Univ, Dept Rehabil Med, 1441 Clifton Rd NE, Atlanta, GA 30322 USA. EM nkutner@emory.edu NR 20 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD JAN-FEB PY 2009 VL 22 IS 1 BP 34 EP 36 DI 10.1111/j.1525-139X.2008.00509.x PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 408WT UT WOS:000263467000010 ER PT J AU Bernt, KM Armstrong, SA AF Bernt, Kathrin M. Armstrong, Scott A. TI Leukemia Stem Cells and Human Acute Lymphoblastic Leukemia SO SEMINARS IN HEMATOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; HEPATOCELLULAR-CARCINOMA CELLS; PRIMITIVE HEMATOPOIETIC-CELL; CANCER STEM/PROGENITOR CELLS; TUMOR-INITIATING CELLS; PROGENITOR/STEM CELLS; THERAPEUTIC TARGET; SIDE POPULATION; IDENTIFICATION; INVOLVEMENT C1 [Armstrong, Scott A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Armstrong, SA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM Scott.Armstrong@childrens.harvard.edu RI Bernt, Kathrin/L-1826-2016 OI Bernt, Kathrin/0000-0002-5400-0482 FU NCI NIH HHS [P01 CA068484, T32 CA009172] NR 44 TC 16 Z9 16 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 2009 VL 46 IS 1 BP 33 EP 38 DI 10.1053/j.seminhematol.2008.09.010 PG 6 WC Hematology SC Hematology GA 393BI UT WOS:000262345500005 PM 19100366 ER PT J AU Bhan, I Thadhani, R AF Bhan, Ishir Thadhani, Ravi TI Vitamin D Therapy for Chronic Kidney Disease SO SEMINARS IN NEPHROLOGY LA English DT Review DE Chronic kidney disease; vitamin D; hyperparathyroidism; survival; hemodialysis ID STAGE RENAL-DISEASE; CATHELICIDIN ANTIMICROBIAL PEPTIDE; SUBTOTALLY NEPHRECTOMIZED RATS; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; 1,25-DIHYDROXYVITAMIN D-3; HEMODIALYSIS-PATIENTS; D-RECEPTOR; VASCULAR CALCIFICATION; PARATHYROID-HORMONE C1 [Bhan, Ishir; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. [Thadhani, Ravi] Massachusetts Gen Hosp, Ctr D Receptor Activat Res CeDAR, Boston, MA 02114 USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Dept Med, Renal Unit, Bulfinch 127,55 Fruit St, Boston, MA 02114 USA. EM rthadhani@partners.org FU Abbott Laboratories FX R. Thadhani has received grant support from Abbott Laboratories, and speaking honoraria from Abbott Laboratories and Genzyme. NR 79 TC 7 Z9 7 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD JAN PY 2009 VL 29 IS 1 BP 85 EP 93 DI 10.1016/j.semnephrol.2008.10.010 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 394BV UT WOS:000262421100011 PM 19121478 ER PT J AU Montezuma, SR Vavvas, D Miller, JW AF Montezuma, Sandra R. Vavvas, Demetrios Miller, Joan W. TI Review of the Ocular Angiogenesis Animal Models SO SEMINARS IN OPHTHALMOLOGY LA English DT Review DE angiogenesis; choroidal neovascularization (CNV); corneal neovascularization; subretinal neovascularization (SRN); Basic Fibroblast Growth Factor (bFGF); Vascular Endothelial Growth Factor (VEGF); fluorescein angiography (FA); BALB C and C57BL-6 mice; knockout or knock-in transgenic mice ID ENDOTHELIAL GROWTH-FACTOR; EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; OXYGEN-INDUCED RETINOPATHY; EXPERIMENTAL SUBRETINAL NEOVASCULARIZATION; EXPERIMENTAL PRERETINAL NEOVASCULARIZATION; ARGON-LASER PHOTOCOAGULATION; VASCULAR-PERMEABILITY FACTOR; CORNEAL NEOVASCULARIZATION; RETINAL NEOVASCULARIZATION; PROLIFERATIVE RETINOPATHY AB Increasing interest in developing reliable and reproducible models to study angiogenesis has emerged due to recent advances in the treatment of eye disease with pathologic angiogenesis. This review provides a summary of the principal ocular animal models for angiogenesis. Models of anterior segment neovascularization include the corneal micropocket assay, used to study the influence of specific molecules/proteins in angiogenesis, and corneal chemical and suture induced injury, which mimic more closely the complex nature of the human disease. Angiogenesis models of the posterior segment include the well-known laser-induced injury of the choroid/Bruch's membrane, as well as the oxygen induced retinopathy and models of injections of pro-angiogenic/inflammatory molecules. In addition, knockout or knock-in transgenic mice provide powerful tools in studying the role of specific proteins in angiogenesis. C1 [Montezuma, Sandra R.; Vavvas, Demetrios; Miller, Joan W.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv,Dept Ophthalmol, Boston, MA 02114 USA. RP Montezuma, SR (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM sandra_montezuma@meei.harvard.edu OI Vavvas, Demetrios/0000-0002-8622-6478 NR 85 TC 29 Z9 29 U1 0 U2 3 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 2 BP 52 EP 61 DI 10.1080/08820530902800017 PG 10 WC Ophthalmology SC Ophthalmology GA V18RA UT WOS:000208020700003 PM 19373687 ER PT J AU Leiderman, YI Miller, JW AF Leiderman, Yannek I. Miller, Joan W. TI Proliferative Vitreoretinopathy: Pathobiology and Therapeutic Targets SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE vitreoretinopathy; proliferative/etiology/physiopathology/therapy; intercellular signaling peptides and proteins; retinal detachment ID PIGMENT EPITHELIAL-CELLS; ENDOTHELIAL GROWTH-FACTOR; MATRICELLULAR PROTEINS THROMBOSPONDIN-1; MONOCYTE CHEMOATTRACTANT PROTEIN-1; RHEGMATOGENOUS RETINAL-DETACHMENT; AVASCULAR EPIRETINAL MEMBRANES; NECROSIS-FACTOR RECEPTORS; DIABETIC-RETINOPATHY; FACTOR-ALPHA; IN-VITRO AB The cell biology and molecular mediators of proliferative vitreoretinopathy continue to be elucidated. The purpose of this review is to summarize contemporary findings in the visual and neurosciences relevant to the pathophysiology of proliferative vitreoretinopathy, with an emphasis on the biologic mediators that represent potential therapeutic targets. C1 [Leiderman, Yannek I.; Miller, Joan W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA 02114 USA. RP Leiderman, YI (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Yannek_Leiderman@meei.harvard.edu FU Heed Ophthalmic Foundation FX The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. Dr. Leiderman is a recipient of the Heed Ophthalmic Foundation fellowship. NR 89 TC 19 Z9 27 U1 0 U2 7 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 2 BP 62 EP 69 DI 10.1080/08820530902800082 PG 8 WC Ophthalmology SC Ophthalmology GA V18RA UT WOS:000208020700004 PM 19373688 ER PT J AU Lin, KL Hirose, T Kroll, AJ Lou, PL Ryan, EA AF Lin, Kristie L. Hirose, Tatsuo Kroll, Arnold J. Lou, Peter L. Ryan, Edward A. TI Prospects for Treatment of Pediatric Vitreoretinal Diseases with Vascular Endothelial Growth Factor Inhibition SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE intravitreal avastin; retinopathy of prematurity; coats' disease; familial exudative vitreoretinopathy; retinopathy of incontinentia pigmenti; pediatric vitreoretinopathy; anti-angiogenesis; VEGF; VEGF Inhibition; anti-VEGF and infants ID FAMILIAL EXUDATIVE VITREORETINOPATHY; INTRAVITREAL BEVACIZUMAB; ADVANCED RETINOPATHY; PREMATURITY; ANGIOGENESIS; VEGF; NEOVASCULARIZATION; INJECTION; THERAPY; AVASTIN AB While angiogenesis inhibitors are already widely used to treat retinal disease in adults, only limited reports are currently available for the use of anti-VEGF in pediatric vitreoretinal diseases such as retinopathy of prematurity, Coats' disease, familial exudative vitreoretinopathy and retinopathy of incontinentia pigmenti. The limited trials of anti-VEGF therapy for pediatric vitreoretinal diseases are promising, although more extensive controlled trials will be needed to confirm their safety and efficacy. This paper will examine the current evidence for use of anti-VEGF therapy in a number of pediatric vitreoretinal disorders and describe a case of anti-VEGF therapy in retinopathy of incontinentia pigmenti. C1 [Lin, Kristie L.; Hirose, Tatsuo; Kroll, Arnold J.; Lou, Peter L.; Ryan, Edward A.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Lin, KL (reprint author), 0 Longfellow Pl, Boston, MA 02114 USA. EM Kristie.Lin@gmail.com NR 36 TC 10 Z9 13 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 2 BP 70 EP 76 DI 10.1080/08820530902800108 PG 7 WC Ophthalmology SC Ophthalmology GA V18RA UT WOS:000208020700005 PM 19373689 ER PT J AU Jardeleza, MSR Miller, JW AF Jardeleza, Maria Stephanie R. Miller, Joan W. TI Review of Anti-VEGF Therapy in Proliferative Diabetic Retinopathy SO SEMINARS IN OPHTHALMOLOGY LA English DT Review DE proliferative diabetic retinopathy; anti-VEGF treatment; vascular endothelial growth factor ID ENDOTHELIAL GROWTH-FACTOR; INTRAVITREAL BEVACIZUMAB AVASTIN; OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; PANRETINAL PHOTOCOAGULATION; RETINAL NEOVASCULARIZATION; IRIS NEOVASCULARIZATION; PREOPERATIVE ADJUNCT; NONHUMAN PRIMATE; FACTOR-A AB Proliferative diabetic retinopathy (PDR) is a visually significant complication of diabetes mellitus. Pan-retinal photocoagulation (PRP) remains the standard treatment of choice. However, adverse effects of and clinical barriers to PRP have led to exploration of alternative and adjunctive therapeutic strategies in the treatment of proliferative disease. Inhibition of ocular vascular endothelial growth factor (VEGF) has emerged as a promising treatment modality for PDR. This review summarizes results from published studies using intravitreal anti-VEGF agents singly and in combination with standard therapeutic regimens in the treatment of proliferative diabetic retinopathy. C1 [Jardeleza, Maria Stephanie R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, Boston, MA 02114 USA. RP Jardeleza, MSR (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, 243 Charles St,12th Flr, Boston, MA 02114 USA. EM Stephanie_Jardeleza@meei.harvard.edu NR 66 TC 40 Z9 40 U1 0 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 2 BP 87 EP 92 DI 10.1080/08820530902800330 PG 6 WC Ophthalmology SC Ophthalmology GA V18RA UT WOS:000208020700008 PM 19373692 ER PT J AU Silva, PS Sun, JK Aiello, LP AF Silva, Paolo S. Sun, Jennifer K. Aiello, Lloyd Paul TI Role of Steroids in the Management of Diabetic Macular Edema and Proliferative Diabetic Retinopathy SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE diabetic retinopathy; diabetic macular edema; corticosteroids; triamcinolone acetonide ID INTRAVITREAL TRIAMCINOLONE ACETONIDE; RANDOMIZED CLINICAL-TRIAL; OPTICAL COHERENCE TOMOGRAPHY; LASER PHOTOCOAGULATION; PANRETINAL PHOTOCOAGULATION; GRID PHOTOCOAGULATION; VASCULAR-PERMEABILITY; ANGIOSTATIC STEROIDS; ADJUNCTIVE TREATMENT; ANECORTAVE ACETATE AB Diabetic retinopathy is the most common microvascular complication of diabetes. Early clinical trials have established the efficacy and safety of laser in the treatment of proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). Despite timely and appropriate use of laser, some patients continue to experience visual loss. The pathogenesis of PDR and DME is multifactorial involving both angiogenic and inflammatory processes. Recent trials have shown that the anti-inflammatory and anti-angiogenic properties of corticosteroids may provide benefit in treating PDR and DME. The exact role of steroids in the treatment for diabetic retinopathy and macular edema remains to be fully elucidated. C1 [Aiello, Lloyd Paul] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Joslin Diabet Ctr, Sect Eye Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Aiello, LP (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM Paoloantonio.Silva@joslin.harvard.edu NR 63 TC 17 Z9 20 U1 0 U2 0 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 2 BP 93 EP 99 DI 10.1080/08820530902800355 PG 7 WC Ophthalmology SC Ophthalmology GA V18RA UT WOS:000208020700009 PM 19373693 ER PT J AU Wu, HJ Chen, TC AF Wu, Huijuan Chen, Teresa C. TI The Effects of Intravitreal Ophthalmic Medications on Intraocular Pressure SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE intraocular pressure; Injections; Vitreous body; pegaptanib; ranibizumab; bevacizumab; Triamcinolone acetonide; Antiviral Agents; Antibiotics Macugen; Lucentis; Avastin ID TRIAMCINOLONE ACETONIDE INJECTION; RANDOMIZED CLINICAL-TRIAL; MACULAR DEGENERATION; BEVACIZUMAB AVASTIN; TRABECULAR MESHWORK; OCULAR HYPERTENSION; CYTOMEGALOVIRUS RETINITIS; CIDOFOVIR HPMPC; AQUEOUS-HUMOR; RANIBIZUMAB AB Ophthalmic medications are often given as intravitreal injection. Antimicrobials, antivirals, corticosteroids and anti- vascular endothelial growth factor agents are the main classes which can be administered through intravitreal injections. Possible complications of intravitreal injection include intraocular pressure changes, especially intraocular pressure elevations. This review discusses both injection-related intraocular pressure elevations which can occur immediately after injection of any kind of medication and drug specific-related intraocular pressure changes which may be detected days or even months after the injection. C1 [Wu, Huijuan; Chen, Teresa C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Serv,Dept Ophthalmol, Boston, MA 02114 USA. [Wu, Huijuan] Peking Univ, Dept Ophthalmol, Peoples Hosp, Beijing 100871, Peoples R China. RP Chen, TC (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Teresa_Chen@meei.harvard.edu NR 68 TC 12 Z9 12 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 2 BP 100 EP 105 DI 10.1080/08820530902800397 PG 6 WC Ophthalmology SC Ophthalmology GA V18RA UT WOS:000208020700010 PM 19373694 ER PT J AU Anchala, AR Pasquale, LR AF Anchala, Anupama R. Pasquale, Louis R. TI Neovascular Glaucoma: A Historical Perspective on Modulating Angiogenesis SO SEMINARS IN OPHTHALMOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PROLIFERATIVE DIABETIC-RETINOPATHY; PANRETINAL PHOTO-COAGULATION; RUBEOSIS IRIDIS; FILTERING SURGERY; ANGLE NEOVASCULARIZATION; INTRAVITREAL BEVACIZUMAB; IRIS NEOVASCULARIZATION; FILTRATION SURGERY; AQUEOUS-HUMOR C1 [Anchala, Anupama R.; Pasquale, Louis R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Pasquale, LR (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Louis_Pasquale@meei.harvard.edu NR 38 TC 1 Z9 2 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 2 BP 106 EP 112 DI 10.1080/08820530902800959 PG 7 WC Ophthalmology SC Ophthalmology GA V18RA UT WOS:000208020700011 PM 19373695 ER PT J AU Shazly, TA Latina, MA AF Shazly, Tarek A. Latina, Mark A. TI Neovascular Glaucoma: Etiology, Diagnosis and Prognosis SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE neovascular glaucoma; rubeotic glaucoma; neovascularization; retinal ischemia; vascular endothelial growth factor (VEGF); proliferative diabetic retinopathy; central retinal vein occlusion ID IRIDOCORNEAL ENDOTHELIAL SYNDROME; RETINAL VASCULAR OCCLUSION; CAROTID-CAVERNOUS FISTULA; OCULAR NEOVASCULARIZATION; RUBEOSIS IRIDIS; IRIS NEOVASCULARIZATION; FILTERING SURGERY; VEIN OCCLUSION; OBSTRUCTION; ARTERY AB Neovascular glaucoma (NVG) is a severe form of glaucoma with devastating visual outcome attributed to new blood vessels obstructing aqueous humor outflow, usually secondary to widespread posterior segment ischemia. Invasion of the anterior chamber by a fibrovascular membrane initially obstructs aqueous outflow in an open-angle fashion and later contracts to produce secondary synechial angle-closure glaucoma. The full blown picture of NVG is characteristized by iris neovascularization, a closed anterior chamber angle, and extremely high intraocular pressure (IOP) with severe ocular pain and usually poor vision. C1 [Shazly, Tarek A.] Assiut Univ Hosp, Dept Ophthalmol, Assiut, Egypt. [Shazly, Tarek A.; Latina, Mark A.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Latina, Mark A.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. RP Shazly, TA (reprint author), 20 Pondmeadow Dr,Suite 203, Reading, MA 01867 USA. EM Ophth_inventor@yahoo.com OI A Shazly, Tarek/0000-0002-4561-1871 NR 44 TC 20 Z9 25 U1 0 U2 7 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 2 BP 113 EP 121 DI 10.1080/08820530902800801 PG 9 WC Ophthalmology SC Ophthalmology GA V18RA UT WOS:000208020700012 PM 19373696 ER PT J AU Jue, A AF Jue, Andrea TI Angiogenesis: Trabeculectomy and Bevacizumab SO SEMINARS IN OPHTHALMOLOGY LA English DT Article ID INTRAVITREAL BEVACIZUMAB; MITOMYCIN-C; NEOVASCULAR GLAUCOMA; FILTERING SURGERY; FLUOROURACIL; 5-FLUOROURACIL; ANTIBODY; BLEB AB The use of bevacizumab for the treatment of proliferative diabetic retinopathy, neovascular glaucoma, neovascular age related macular degeneration, and cystoid macular edema has been extensively reported upon. From the published case reports available, bevacizumab may be a useful adjunct to the trabeculectomy procedure. C1 Massachusetts Eye & Ear Infirm, Fellows Course 2009, Boston, MA 02114 USA. RP Jue, A (reprint author), Massachusetts Eye & Ear Infirm, Fellows Course 2009, Boston, MA 02114 USA. NR 25 TC 9 Z9 9 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 2 BP 122 EP 125 DI 10.1080/08820530902801015 PG 4 WC Ophthalmology SC Ophthalmology GA V18RA UT WOS:000208020700013 PM 19373697 ER PT J AU Adamis, AP Miller, JW AF Adamis, Anthony P. Miller, Joan W. TI Untitled SO SEMINARS IN OPHTHALMOLOGY LA English DT Editorial Material C1 [Adamis, Anthony P.] Jerini Ophthalm Inc, New York, NY USA. [Miller, Joan W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Adamis, AP (reprint author), Jerini Ophthalm Inc, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 3 BP 128 EP 129 DI 10.1080/08820530902800116 PG 2 WC Ophthalmology SC Ophthalmology GA V18RB UT WOS:000208020800002 PM 19437346 ER PT J AU Mauro, J Foster, CS AF Mauro, John Foster, C. Stephen TI Pterygia: Pathogenesis and the Role of Subconjunctival Bevacizumab in Treatment SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE pterygium; subconjunctival bevacizumab; anti-VEGF therapy ID ENDOTHELIAL GROWTH-FACTOR; BLUE MOUNTAINS EYE; CORNEAL NEOVASCULARIZATION; MATRIX METALLOPROTEINASES; CONJUNCTIVAL AUTOGRAFT; RECURRENT PTERYGIUM; EPITHELIAL-CELLS; ANGIOGENESIS; EXPRESSION; AVASTIN AB Apterygium is a very common conjunctival degenerative condition. It has been well established that there are different factors that are interrelated and involved in the growth of pterygia. Historically described more as a degenerative process, inflammation and fibrovascular proliferation have proven to be very important factors. Many studies have shown VEGF to be increased in the pathogenesis of pterygia. There are a variety of options for the management of pterygium. The over expression of VEGF in pterygium tissue led us to develop anti-angiogenic/anti-VEGF therapy which could induce regression of blood vessels and hence retard progression of pterygium. The role of angiogenesis and of VEGF in ocular pathology is established including in corneal neovascularization, specifically in pterygial tissue. Evidence suggests that local bevacizumab may be effective in treatment of ocular surface neovascularization. Currently, data in the use of subconjunctival bevacizumab in the treatment of pterygia are not conclusive. New anti-angiogenic therapies will hopefully focus more on facilitating delivery into tissue, increasing the duration of effect while continuing to minimize adverse side effects. C1 [Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA 02142 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Foster, CS (reprint author), Massachusetts Eye Res & Surg Inst, 5 Cambridge Ctr,8th Floor, Cambridge, MA 02142 USA. EM fosters@uveitis.org NR 55 TC 28 Z9 31 U1 0 U2 2 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 3 BP 130 EP 134 DI 10.1080/08820530902801106 PG 5 WC Ophthalmology SC Ophthalmology GA V18RB UT WOS:000208020800003 PM 19437347 ER PT J AU Patel, SP Dana, R AF Patel, Sangita P. Dana, Reza TI Corneal Lymphangiogenesis: Implications in Immunity SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE cornea; lymphangiogenesis; corneal neovascularization; corneal transplantation AB The lymphatic system is a network of vessels throughout the body that serves to return lymphatic fluid to the systemic blood circulation and serves as the immune system's highway in the afferent limb of the immune response. This paper reviews the basics of structure, function and development of the lymphatic system. The emphasis is on understanding the role of lymphatics in the cornea as related to angiogenesis and the clinical setting of corneal transplant rejection. The lymphatic system has two main functions: to drain excess extracellular fluid from capillary beds to return to the systemic blood circulation and to capture antigen for presentation to the immune system in the lymphoid compartment (e.g. nodes) connected in parallel to the lymphatic system. The normal cornea is devoid of lymphatic vessels and blood vessels, thus allowing for its unique immune privileged status. Abnormal blood vessel growth into the cornea has been studied for many years, but the study of lymphatic vessels has been hampered until the recent discovery of lymphatic-specific markers. Subsequent studies of vascularized corneas support the presence of lymphatic vessels in the cornea. The growth of new lymphatic (lymphangiogenesis) and blood (hemangiogenesis) vessels in the cornea is closely related to the abrogation of the immune privileged status of the cornea. This review summarizes our current understanding of the parallel development of hemangiogenesis and lymphangiogenesis as related to the mechanisms of immune rejection of corneal transplants. C1 [Patel, Sangita P.; Dana, Reza] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Cornea Refract Surg Serv, Boston, MA 02114 USA. RP Patel, SP (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Cornea Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM sangita-patel@meei.harvard.edu OI Patel, Sangita/0000-0001-6969-490X NR 21 TC 17 Z9 22 U1 0 U2 0 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 3 BP 135 EP 138 DI 10.1080/08820530902801320 PG 4 WC Ophthalmology SC Ophthalmology GA V18RB UT WOS:000208020800004 PM 19437348 ER PT J AU Lim, P Fuchsluger, TA Jurkunas, UV AF Lim, Pauline Fuchsluger, Thomas A. Jurkunas, Ula V. TI Limbal Stem Cell Deficiency and Corneal Neovascularization SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE limbal stem cell deficiency; corneal neovascularization; stem cell transplantation; stem cells; cultivated limbal epithelium stem cell; cultivated oral mucosal epithelium AB The corneal limbus harbors corneal epithelial stem cells and contributes to the unique microenvironment of the stem cell niche. Corneal conditions, such as infections, tumors, immunological disorders, trauma, and chemical burns, often lead to the deficiency of the corneal stem cells, and subsequent vision loss. One key feature of limbal stem cell deficiency is corneal neovascularization. There is a delicate balance between pro-angiogenic and anti-angiogenic factors that, in a normal cornea, maintain an avascular state. A pro-angiogenic shift in this balance can occur due to various mechanisms, such as inflammation, gene mutations, physical breach in the limbal barrier, and decreased production of anti-angiogenic molecules. Currently available treatment options for limbal stem cell deficiency include allogeneic and autologous limbal transplants, and more recently, transplantation of alternative sources of epithelium, such as cultivated corneal and oral mucosal stem cells. Further studies are needed to investigate the combination of limbal and stem cell transplantation and concurrent anti-angiogenic therapy. C1 [Lim, Pauline; Jurkunas, Ula V.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Fuchsluger, Thomas A.; Jurkunas, Ula V.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Jurkunas, UV (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM ula_jurkunas@meei.harvard.edu NR 99 TC 29 Z9 30 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 3 BP 139 EP 148 DI 10.1080/08820530902801478 PG 10 WC Ophthalmology SC Ophthalmology GA V18RB UT WOS:000208020800005 PM 19437349 ER PT J AU Lim, M Jacobs, DS Rosenthal, P Carrasquillo, KG AF Lim, Mira Jacobs, Deborah S. Rosenthal, Perry Carrasquillo, Karen G. TI The Boston Ocular Surface Prosthesis as a Novel Drug Delivery System for Bevacizumab SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE corneal neovascularization; bevacizumab; scleral lens AB Corneal neovascularization causes deterioration of visual acuity and increases surface irregularities. Various techniques have been employed to help control the progression of corneal neovascularization; bevacizumab is a medication that targets the specific pathway of corneal neovascularization. The Boston Ocular Surface Prosthesis (BOSP) is a large diameter contact lens that aids in maintaining corneal surface integrity and may serve as a delivery system for topical bevacizumab. This paper reviews five patients who were treated with topical bevacizumab in their BOSP. All patients demonstrated improvement in their visual acuity and clinical exam. No adverse reactions were noted. C1 [Lim, Mira] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Jacobs, Deborah S.; Rosenthal, Perry; Carrasquillo, Karen G.] Boston Fdn Sight, Boston, MA USA. RP Lim, M (reprint author), 243 Charles St, Boston, MA 02114 USA. EM mira_lim@meei.harvard.edu NR 32 TC 6 Z9 6 U1 0 U2 4 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 3 BP 149 EP 155 DI 10.1080/08820530902802013 PG 7 WC Ophthalmology SC Ophthalmology GA V18RB UT WOS:000208020800006 PM 19437350 ER PT J AU Ciolino, JB Dohlman, CH Kohane, DS AF Ciolino, Joseph B. Dohlman, Claes H. Kohane, Daniel S. TI Contact Lenses for Drug Delivery SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE contact lens; drug delivery; hydrogel; polymer AB The majority of ocular medications are delivered to the eye topically, often in the form of a solution, or eye drop. Contact lenses could potentially also be used to deliver medications to the eye. Recently, progress has been made in developing a drug-eluting contact lens. Different designs have been proposed and several offer the hope of expanding the therapeutic armamentarium for eye care providers. C1 [Kohane, Daniel S.] Harvard Univ, Childrens Hosp, Lab Biomat & Drug Delivery, Dept Anesthesiol,Div Crit Care Med,Sch Med, Boston, MA 02115 USA. [Ciolino, Joseph B.; Dohlman, Claes H.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Kohane, DS (reprint author), Harvard Univ, Childrens Hosp, Lab Biomat & Drug Delivery, Dept Anesthesiol,Div Crit Care Med,Sch Med, Boston, MA 02115 USA. EM daniel.kohane@childrens.harvard.edu FU NIGMS [GM073626]; CIMIT/J&J Young Investigator Award; Massachusetts Eye and Ear Infirmary FX This research was funded by NIGMS GM073626, CIMIT/J&J Young Investigator Award, and by the Boston KPro Fund, Massachusetts Eye and Ear Infirmary. NR 35 TC 28 Z9 28 U1 1 U2 6 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 3 BP 156 EP 160 DI 10.1080/08820530902802161 PG 5 WC Ophthalmology SC Ophthalmology GA V18RB UT WOS:000208020800007 PM 19437351 ER PT J AU Ciralsky, J Colby, K AF Ciralsky, Jessica Colby, Kathryn TI Conjunctival Melanomas: Can the Cancer Stem Cell Hypothesis be Applied? SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE conjunctival melanoma; cancer stem cell hypothesis AB Conjunctival melanoma patients often follow an unpredictable course with significant rates of recurrence and metastases despite optimal treatment. Can we better understand conjunctival melanomas by applying the cancer stem cell hypothesis? The cancer stem cell hypothesis posits that cancers exist as a hierarchical system where cancer stem cells generate and maintain tumors. Targeting cancer stem cells may be the key to future treatments. Directed treatments need to focus on key differences between cancer stem cells and normal tissue stem cells. These directed treatments may lead to curative therapies and decrease the number of recurrences and metastases. C1 [Ciralsky, Jessica; Colby, Kathryn] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Ciralsky, J (reprint author), Massachusetts Eye & Ear Infirm, Cornea Dept, 243 Charles St, Boston, MA 02114 USA. EM Jessica_Ciralsky@meei.harvard.edu NR 31 TC 1 Z9 1 U1 1 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 3 BP 161 EP 165 DI 10.1080/08820530902802351 PG 5 WC Ophthalmology SC Ophthalmology GA V18RB UT WOS:000208020800008 PM 19437352 ER PT J AU Bhat, P Jakobiec, FA Folberg, R AF Bhat, Pooja Jakobiec, Frederick A. Folberg, Robert TI Comparison of Tumor-Associated Vasculatures in Uveal and Cutaneous Melanomas SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE tumor microcirculation; vasculogenic mimicry; tumor-associated vasculatures; uveal melanoma microcirculation AB Much attention has been focused on the role of angiogenesis in tumor growth and dissemination. Alternative forms of tumor-associated microcirculation exist and were first demonstrated by light microscopic histological techniques such as PAS-positive patterns in uveal melanomas. Since then several advances have been made in unraveling the true nature of these patterns, and have been documented in other tumors such as cutaneous melanomas and hepatic melanomatous metastases. These patterns, termed as "vasculogenic mimicry," are distinctly different from endothelial cell-lined blood vessels and may contribute significantly as an alternative supply to the tumors' overall microcirculation. The molecular events that regulate the formation of these patterns in tumors, their constituent nature and the ability to demonstrate these patterns by non-invasive techniques provide further opportunities for enhanced detection, early prognostication and the development of targeted therapies. C1 [Bhat, Pooja; Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Dept Ophthalmol, Boston, MA 02114 USA. [Folberg, Robert] Oakland Univ, William Beaumont Sch Med, Dept Biomed Sci, Rochester, MI 48063 USA. [Folberg, Robert] Oakland Univ, William Beaumont Sch Med, Dept Pathol, Rochester, MI 48063 USA. RP Bhat, P (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Dept Ophthalmol, 243 Charles St,Suite 321,3rd Floor, Boston, MA 02114 USA. EM poojavbhat@yahoo.co.uk NR 51 TC 5 Z9 5 U1 0 U2 0 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 3 BP 166 EP 171 DI 10.1080/08820530902805305 PG 6 WC Ophthalmology SC Ophthalmology GA V18RB UT WOS:000208020800009 PM 19437353 ER PT J AU Lo, K Mihm, M Fay, A AF Lo, Kristine Mihm, Martin Fay, Aaron TI Current Theories on the Pathogenesis of Infantile Hemangioma SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE capillary hemangioma; infantile hemangioma; placenta theory; progenitor cell theory; extrinsic factor; metastatic theory AB Infantile hemangiomas are the most common tumors of infancy and although the natural history and progression of these lesions are well described, their origin remains unclear. Considerable progress has been achieved in the past two decades towards understanding the etiology of these lesions. New investigations have produced sophisticated hypotheses on the origin of these tumors and their behavior. These include suggestions of placental origin, intrinsic defect or somatic endothelial mutation, and extrinsic factors creating a conducive milieu for growth. While no current hypothesis explains all the characteristics of infantile hemangiomas, continued research targeting pathophysiology will ultimately lead to new treatment options. C1 [Lo, Kristine; Fay, Aaron] Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg Div, Boston, MA 02114 USA. [Lo, Kristine; Fay, Aaron] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Mihm, Martin] Massachusetts Gen Hosp, Dept Dermatopathol, Boston, MA 02114 USA. RP Fay, A (reprint author), Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg Div, 243 Charles St, Boston, MA 02114 USA. EM Aaron_Fay@meei.harvard.edu NR 41 TC 23 Z9 28 U1 0 U2 3 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 3 BP 172 EP 177 DI 10.1080/08820530902805438 PG 6 WC Ophthalmology SC Ophthalmology GA V18RB UT WOS:000208020800010 PM 19437354 ER PT J AU Nguyen, J Fay, A AF Nguyen, John Fay, Aaron TI Pharmacologic Therapy for Periocular Infantile Hemangiomas: A Review of the Literature SO SEMINARS IN OPHTHALMOLOGY LA English DT Review DE capillary hemangioma; infantile hemangioma; corticosteroids; interferon alpha; propranolol; imiquimod; cyclophosphamide; vincristine AB Infantile hemangiomas are common vascular tumors of childhood with a propensity for the head and neck. In the periocular region, they can cause functional and cosmetic deformity. The proliferation and involution of hemangiomas are controlled by complex interactions of molecular, cellular, and hormonal regulators. There is no single uniformly safe and effective treatment option. Various modalities, including local and systemic pharmacologic agents, lasers, surgery and embolization, are employed to halt growth and to induce regression. This article will review the rapidly evolving field of pharmacologic treatment of infantile hemangiomas. C1 [Nguyen, John; Fay, Aaron] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Fay, A (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Aaron_Fay@meei.harvard.edu NR 78 TC 36 Z9 43 U1 0 U2 2 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 3 BP 178 EP 184 DI 10.1080/08820530902805602 PG 7 WC Ophthalmology SC Ophthalmology GA V18RB UT WOS:000208020800011 PM 19437355 ER PT J AU Cohen, AB Lessell, S AF Cohen, Adam B. Lessell, Simmons TI Angiogenesis and Pituitary Tumors SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE angiogenesis; pituitary tumor; pituitary adenoma AB Pituitary adenomas often first manifest through visual symptoms. They are typically slow-growing and histologically benign tumors, but can become clinically destructive, invade adjacent structures, and recur after treatment. Unlike many other tumors that become aggressive and appear to depend upon angiogenesis in the process, pituitary adenomas tend to do so through non-angiogenic means. This article examines the role of angiogenesis in pituitary adenomas. C1 [Cohen, Adam B.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Neuroophthalmol, Boston, MA 02114 USA. [Cohen, Adam B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lessell, Simmons] Harvard Univ, Sch Med, Massachusetts Eye & Ear Hosp, Boston, MA USA. RP Cohen, AB (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Neuroophthalmol, 243 Charles St, Boston, MA 02114 USA. EM abcohen@partners.org NR 22 TC 10 Z9 10 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 3 BP 185 EP 189 DI 10.1080/08820530902805651 PG 5 WC Ophthalmology SC Ophthalmology GA V18RB UT WOS:000208020800012 PM 19437356 ER PT J AU Mitchell, EB Cestari, DM AF Mitchell, Ellen Browne Cestari, Dean M. TI Giant Cell Arteritis and Angiogenesis: A Review SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE giant cell arteritis; angiogenesis; vasculitis AB Giant cell arteritis is a vasculitis of large and medium sized arteries with variable clinical presentations. Arteritic anterior ischemic optic neuropathy is the most common cause of visual loss from giant cell arteritis and the ischemia related to this process is presumed to be secondary to luminal stenosis from intimal hyperplasia. This process has been found to be initiated and promoted by various inflammatory and pro-angiogenic factors. C1 [Mitchell, Ellen Browne; Cestari, Dean M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Mitchell, EB (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM elbrowne@gmail.com NR 26 TC 3 Z9 3 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2009 VL 24 IS 3 BP 190 EP 193 DI 10.1080/08820530902805776 PG 4 WC Ophthalmology SC Ophthalmology GA V18RB UT WOS:000208020800013 PM 19437357 ER PT J AU Pitetti, JL Torre, D Conne, B Papaioannou, MD Cederroth, CR Xuan, S Kahn, R Parada, LF Vassalli, JD Efstratiadis, A Nef, S AF Pitetti, J. L. Torre, D. Conne, B. Papaioannou, M. D. Cederroth, C. R. Xuan, S. Kahn, R. Parada, L. F. Vassalli, J. D. Efstratiadis, A. Nef, S. TI Insulin Receptor and IGF1R Are Not Required for Oocyte Growth, Differentiation, and Maturation in Mice SO SEXUAL DEVELOPMENT LA English DT Article DE Differentiation; Fertility; Growth; Igf1r; Insr; Maturation; Mouse; Oozyte ID FACTOR-I; PLASMINOGEN-ACTIVATOR; TARGETED DISRUPTION; OVARIAN-FOLLICLE; MOUSE OOCYTES; EXPRESSION; CELLS; GENE; REPRODUCTION; INHIBITOR AB In mammals, insulin and insulin-like growth factors (IGFs: IGF1 and IGF2) act through 2 structurally related receptors, the insulin receptor (INSR) and the type 1 IGF receptor (IGF1R), both of which are expressed in developing oocytes. IGF1 plays an important role in female reproduction, and female Igf1 knockout mice fail to ovulate and are infertile. On the other hand, little is known about the in vivo role of the insulin signaling pathway in oocytes during follicular development, although exposure to insulin or IGF1 in vitro improves oocyte maturation. To further address the significance of insulin/IGF signaling, we used conditional mutant mice and ablated the function of the genes encoding INSR, IGF1R, or both receptors specifically in developing mouse oocytes. Our genetic evidence showed unexpectedly that the female reproductive functions are not affected when Insr, Igf1r or both Insr; Igf1r are ablated in oocytes, as the female mice are fertile and exhibit normal estrous cyclicity, oocyte development and maturation, parturition frequency, and litter size. In view of these novel observations indicating that the insulin/IGF signaling is not essential in oocytes, the IGF1-dependent female fertility is re-evaluated and discussed. Copyright (C) 2009 S. Karger AG, Basel C1 [Pitetti, J. L.; Torre, D.; Conne, B.; Papaioannou, M. D.; Cederroth, C. R.; Vassalli, J. D.; Nef, S.] Univ Geneva, Dept Genet Med & Dev, Sch Med, CH-1211 Geneva 4, Switzerland. [Xuan, S.; Efstratiadis, A.] Columbia Univ, Dept Genet & Dev, Med Ctr, New York, NY USA. [Kahn, R.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kahn, R.] Harvard Univ, Sch Med, Boston, MA USA. [Parada, L. F.] Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA. RP Nef, S (reprint author), Univ Geneva, Dept Genet Med & Dev, Sch Med, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland. EM serge.nef@unige.ch RI Cederroth, Christopher/B-9932-2011; Parada, luis/B-9400-2014; OI Cederroth, Christopher/0000-0001-7267-5136 FU Swiss National Science Foundation [3100A0-119862, 3100A0-108245]; Ernst & Lucie Schmidheiny Foundation FX The authors wish to thank Francoise Kuhne and Virginie Godino for technical assistance. This work was supported by grants to S. N. from the Swiss National Science Foundation (3100A0-119862 and 3100A0-108245). C. R. C is funded by a grant from the Ernst & Lucie Schmidheiny Foundation. NR 46 TC 7 Z9 7 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-5425 J9 SEX DEV JI Sex. Dev. PY 2009 VL 3 IS 5 BP 264 EP 272 DI 10.1159/000252813 PG 9 WC Developmental Biology SC Developmental Biology GA 530NZ UT WOS:000272600900005 PM 19851056 ER PT J AU Li, YH Xiang, M Vodovotz, Y Billiar, TR Wilson, MA Fan, J AF Li, Yuehua Xiang, Meng Vodovotz, Yoram Billiar, Timothy R. Wilson, Mark A. Fan, Jie TI ROLE OF HMGB1-TLR2 SIGNALING IN HEMORRHAGIC SHOCK-AUGMENTED ICAM-1 EXPRESSION IN LUNG ENDOTHELIAL CELLS SO SHOCK LA English DT Meeting Abstract CT 13th Congress of the European-Shock-Society CY SEP 24-26, 2009 CL Lisbon, PORTUGAL SP European Shock Soc C1 [Li, Yuehua; Xiang, Meng; Vodovotz, Yoram; Billiar, Timothy R.; Wilson, Mark A.; Fan, Jie] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15240 USA. [Wilson, Mark A.; Fan, Jie] VA Pittsburgh Healthcare Syst, Res & Dev, Pittsburgh, PA 15240 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PY 2009 VL 32 BP 10 EP 10 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 486UV UT WOS:000269226200041 ER PT J AU Sumi, Y Chen, Y Yao, Y Woehrle, T Junger, WG AF Sumi, Y. Chen, Y. Yao, Y. Woehrle, T. Junger, W. G. TI PURINERGIC RECEPTORS MODULATE ADRENERGIC SIGNALING RESPONSES OF VASCULAR TISSUES SO SHOCK LA English DT Meeting Abstract CT 32nd Annual Conference on Shock CY JUN 06-09, 2009 CL San Antonio, TX SP Shock Soc C1 [Sumi, Y.; Chen, Y.; Yao, Y.; Woehrle, T.; Junger, W. G.] Harvard Univ, Dept Surg, BIDMC, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PY 2009 VL 31 BP 33 EP 33 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 463ND UT WOS:000267438000101 ER PT J AU Woehrle, T Yip, L Sumi, Y Yao, Y Chen, Y Junger, WG AF Woehrle, T. Yip, L. Sumi, Y. Yao, Y. Chen, Y. Junger, W. G. TI THE RESPONSE OF T CELLS TO HYPERTONIC SALINE INVOLVES P2X1, P2X5, AND P2Y14 RECEPTORS SO SHOCK LA English DT Meeting Abstract CT 32nd Annual Conference on Shock CY JUN 06-09, 2009 CL San Antonio, TX SP Shock Soc C1 [Woehrle, T.; Sumi, Y.; Yao, Y.; Chen, Y.; Junger, W. G.] Harvard Univ, Sch Med, Dept Surg, BIDMC, Boston, MA 02215 USA. [Yip, L.] Stanford Univ, Dept Med, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PY 2009 VL 31 BP 57 EP 57 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 463ND UT WOS:000267438000167 ER PT J AU Chen, Y Yao, Y Sumi, Y Woehrle, T Junger, WG AF Chen, Y. Yao, Y. Sumi, Y. Woehrle, T. Junger, W. G. TI ATP RELEASE AND P2 RECEPTORS ARE INVOLVED IN FC gamma R ACTIVATION OF PMN SO SHOCK LA English DT Meeting Abstract CT 32nd Annual Conference on Shock CY JUN 06-09, 2009 CL San Antonio, TX SP Shock Soc C1 [Chen, Y.; Yao, Y.; Sumi, Y.; Woehrle, T.; Junger, W. G.] Harvard Univ, Sch Med, BIDMC, Dept Surg, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PY 2009 VL 31 BP 66 EP 67 PG 2 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 463ND UT WOS:000267438000195 ER PT J AU Cho, SD Holcomb, JB Tieu, BH Englehart, MS Morris, MS Karahan, ZA Underwood, SA Muller, PJ Prince, MD Medina, L Sondeen, J Shults, C Duggan, M Tabbara, M Alam, HB Schreiber, MA AF Cho, S. David Holcomb, John B. Tieu, Brandon H. Englehart, Michael S. Morris, Melanie S. Karahan, Z. Ayhan Underwood, Samantha A. Muller, Patrick J. Prince, M. Dale Medina, Leticia Sondeen, Jill Shults, Christian Duggan, Michael Tabbara, Malek Alam, Hasan B. Schreiber, Martin A. TI REPRODUCIBILITY OF AN ANIMAL MODEL SIMULATING COMPLEX COMBAT-RELATED INJURY IN A MULTIPLE-INSTITUTION FORMAT SO SHOCK LA English DT Article DE Resuscitation; trauma; preclinical trial; shock; femur fracture; multicenter; swine; coagulopathy ID UNCONTROLLED HEMORRHAGIC-SHOCK; FRESH-FROZEN PLASMA; PROTHROMBIN TIME; LACTATED RINGERS; NORMAL SALINE; EARLY COAGULOPATHY; ACUTE TRAUMA; SWINE MODEL; BLOOD-LOSS; RESUSCITATION AB We developed a complex combat-relevant model of abdominal and extremity trauma, hemorrhagic shock, hypothermia, and acidosis. We then simulated injury, preoperative, and operative phases. We hypothesized that this model is reproducible and useful for randomized multicenter preclinical trials. Yorkshire swine were anesthetized, intubated, and instrumented. They then underwent femur fracture, 60% total blood volume hemorrhage, a 30-min shock period, induced hypothermia to 33 degrees C, and hemorrhage volume replacement with 3:1 isotonic sodium chloride solution (NS) at each of three centers. Hemodynamic parameters were measured continuously. Thromboelastography, arterial blood gas, and laboratory values were collected at baseline, after the shock period, and after NS replacement. Thirty-seven animals were used for model development. Eight (21%) died before completion of the study period. Twenty-nine survivors were included in the analysis. MAP (+/- SEM) after the shock period was 32 +/- 2 mmHg and was similar between centers (P = 0.4). Mean pH, base deficit, and lactate levels were 7.29 +/- 0.02, 8.20 +/- 0.65 mmol/L, and 5.29 +/- 0.44 mmol/L, respectively, after NS replacement. These were similar between centers (P > 0.05). Prothrombin time values increased significantly over time at all centers, reflecting a progressive coagulopathy (P < 0.02). Thromboelastography maximum amplitude values were similar among centers (P > 0.05) and demonstrated progressively weakened platelet interaction over time (P < 0.03). Hematocrit was similar after controlled hemorrhage (P = 0.15) and dilution (P = 0.9). The pH, lactate, base deficit, and coagulation tests reflect a severely injured state. A complex porcine model of polytrauma and shock can be used for multi-institutional study with excellent reproducibility. A consistent severe injury profile was achieved, after which experimental interventions can be applied. This is the first report of a reproducible multicenter trauma and resuscitation-related animal model. C1 [Cho, S. David; Tieu, Brandon H.; Englehart, Michael S.; Morris, Melanie S.; Karahan, Z. Ayhan; Underwood, Samantha A.; Muller, Patrick J.; Schreiber, Martin A.] Oregon Hlth & Sci Univ, Div Trauma & Crit Care, Portland, OR 97239 USA. [Holcomb, John B.; Prince, M. Dale; Medina, Leticia; Sondeen, Jill] USA, Inst Surg Res, Houston, TX USA. [Shults, Christian; Duggan, Michael; Tabbara, Malek; Alam, Hasan B.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Cho, SD (reprint author), Oregon Hlth & Sci Univ, Div Trauma & Crit Care, 3181 SW Sam Jackson Pk Rd,L611, Portland, OR 97239 USA. EM chos@ohsu.edu OI Tabbara, Malek/0000-0003-1046-7803 NR 42 TC 40 Z9 41 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD JAN PY 2009 VL 31 IS 1 BP 87 EP 96 DI 10.1097/SHK.0b013e3181777ffb PG 10 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 385LO UT WOS:000261815900012 PM 18497710 ER PT J AU Vierling-Claassen, D Kopell, N AF Vierling-Claassen, Dorea Kopell, Nancy TI The Dynamics of a Periodically Forced Cortical Microcircuit, With an Application to Schizophrenia SO SIAM JOURNAL ON APPLIED DYNAMICAL SYSTEMS LA English DT Article DE discrete map; schizophrenia; inhibition; excitation; periodic drive; forced oscillator; cortex; auditory; gamma; beta ID RAT SOMATOSENSORY CORTEX; INHIBITORY NEURONS; IN-VITRO; GAMMA; OSCILLATIONS; NETWORKS; SYNAPSES; RANGE; SYNCHRONIZATION; CURRENTS AB Synchronous neural activity in the brain in the "gamma" and "beta" frequency bands (15-70 Hz) is thought to be important for sensory processing and is altered in schizophrenia. In a previous study, gamma/beta click-train auditory stimuli were used to probe cortical oscillatory activity in control and schizophrenic subjects. We found that control subjects exhibited preferential 40 Hz responses to both 20 and 40 Hz stimulations, while schizophrenic subjects had enhanced 20 Hz responses to the same stimuli [D. Vierling-Claassen, P. Siekmeier, S. Stufflebeam, and N. Kopell, J. Neurophysiol., 99 (2008), pp. 2656-2671]. High-dimensional computational network models constructed previously, which were based on evidence of altered inhibition in schizophrenia, numerically generated the entrainment behaviors observed experimentally. However, questions regarding the dynamic origin of model behaviors remained. It was not clear that the 20 Hz response to 40 Hz drive in the schizophrenic network was robust to parameter changes, which would be necessary for the predicted mechanism to explain data from a heterogeneous subject population. In the schizophrenic network we observed 30 Hz drive responses with a frequency component below 30 Hz, for which no analogue appeared in experimental data, and wondered if these were dynamically distinct from the modeled 20 Hz response to 40 Hz drive. We also wished to explore the role of background noise in model behavior. To address these questions, we consider a system of two mutually coupled oscillators representative of neural cells, driven periodically in the gamma/beta frequency band. We show that there is a one-parameter family of discontinuous discrete maps, whose dynamics clarifies issues of robustness, classifies entrainment patterns, and provides insight into the role of excitatory noise. C1 [Vierling-Claassen, Dorea] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Kopell, Nancy] Boston Univ, Dept Math & Stat, Ctr BioDynam, Boston, MA 02215 USA. RP Vierling-Claassen, D (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, 149 13th St, Charlestown, MA 02129 USA. EM dorea@nmr.mgh.harvard.edu; nk@math.bu.edu FU NSF Award [DMS-0211505]; Burroughs Wellcome Fund Award [1001749] FX This work was supported by NSF Award DMS-0211505 and Burroughs Wellcome Fund Award 1001749. NR 30 TC 4 Z9 4 U1 1 U2 3 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 1536-0040 J9 SIAM J APPL DYN SYST JI SIAM J. Appl. Dyn. Syst. PY 2009 VL 8 IS 2 BP 710 EP 733 DI 10.1137/080738052 PG 24 WC Mathematics, Applied; Physics, Mathematical SC Mathematics; Physics GA 467MW UT WOS:000267744000009 ER PT B AU Patel, S Mancinelli, C Bonato, P Healey, J Moy, M AF Patel, Shyamal Mancinelli, Chiara Bonato, Paolo Healey, Jennifer Moy, Marilyn BE Lo, B Mitcheson, P TI Using Wearable Sensors to Monitor Physical Activities of Patients with COPD: A Comparison of Classifier Performance SO SIXTH INTERNATIONAL WORKSHOP ON WEARABLE AND IMPLANTABLE BODY SENSOR NETWORKS, PROCEEDINGS LA English DT Proceedings Paper CT 6th International Workshop on Wearable and Implantable Body Sensor Networks CY JUN 03-05, 2009 CL Berkeley, CA DE wearable sensors; classification; COPD ID DISEASE; BURDEN AB Chronic obstructive pulmonary disease (COPD) is a major public health problem. Early detection and treatment of an exacerbation in the outpatient setting are important to prevent worsening of clinical status and need for emergency room care or hospital admission. In this study we use accelerometers to capture motion data; and heart rate and respiration rate to capture physiological responses from patients with COPD as they perform a range of Activities of Daily Living (ADL) and physical exercises. We present a comparative analysis of classification performance of a set of different classification techniques and factors that affect classification performance for activity recognition based on accelerometer data. This is the first step towards building a wearable sensor monitoring system for tracking changes in physiological responses of patients with COPD with respect to their physical activity level. C1 [Patel, Shyamal; Mancinelli, Chiara; Bonato, Paolo] Spaulding Rehabil Hosp, HMS, Dept PM&R, Boston, MA USA. [Healey, Jennifer] Intel Digital Hlth Grp, Boston, MA USA. [Moy, Marilyn] VA Boston Healthcare Syst, Boston, MA USA. RP Patel, S (reprint author), Spaulding Rehabil Hosp, HMS, Dept PM&R, Boston, MA USA. EM spatel19@partners.org; cmancinelli@partners.org; pbonato@partners.org; jennifer.healey@intel.com; marilyn.moy@va.gov NR 15 TC 12 Z9 12 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 978-0-7695-3644-6 PY 2009 BP 234 EP + DI 10.1109/P3644.52 PG 2 WC Computer Science, Information Systems; Engineering, Electrical & Electronic; Remote Sensing SC Computer Science; Engineering; Remote Sensing GA BNX27 UT WOS:000275810500040 ER PT J AU Ouellette, H AF Ouellette, Hugue TI The year in review: recent advances in musculoskeletal science SO SKELETAL RADIOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. RP Ouellette, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. EM haouellette@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD JAN PY 2009 VL 38 IS 1 BP 93 EP 95 DI 10.1007/s00256-008-0618-1 PG 3 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 376MM UT WOS:000261187700015 ER PT S AU Kronenberg, HM McMahon, AP Tabin, CJ AF Kronenberg, Henry M. McMahon, Andrew P. Tabin, Clifford J. BE Pourquie, O TI Growth Factors and Chondrogenesis SO SKELETAL SYSTEM SE Cold Spring Harbor Monograph Series LA English DT Article; Book Chapter ID HORMONE-RELATED PEPTIDE; ENDOCHONDRAL BONE-FORMATION; SYNOVIAL JOINT FORMATION; INDIAN-HEDGEHOG; PARATHYROID-HORMONE; CHONDROCYTE PROLIFERATION; TGF-BETA; OSTEOBLAST DIFFERENTIATION; CARTILAGE DEVELOPMENT; TARGETED DISRUPTION C1 [Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Tabin, Clifford J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [McMahon, Andrew P.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [McMahon, Andrew P.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 144 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LABORATORY PRESS PI PLAINVIEW PA 10 SKYLINE DRIVE, PLAINVIEW, NY 11803-2500 USA SN 0270-1847 BN 978-0-87969-825-6 J9 COLD SPRING HARB MON JI Cold Spring Harbor Monogr. Ser. PY 2009 VL 53 BP 171 EP 203 PG 33 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BOL51 UT WOS:000276946900006 ER PT J AU Kroshinsky, D Lin, JY Johnson, RA AF Kroshinsky, Daniela Lin, Jennifer Y. Johnson, Richard Allen BE Hall, JC Hall, BJ TI INFECTIONS IN ORGAN TRANSPLANT PATIENTS SO SKIN INFECTIONS: DIAGNOSIS AND TREATMENT LA English DT Article; Book Chapter ID VARICELLA-ZOSTER-VIRUS; HERPES-SIMPLEX-VIRUS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; RENAL-ALLOGRAFT RECIPIENTS; IMIQUIMOD 5-PERCENT CREAM; SOLID-ORGAN; LIVER-TRANSPLANTATION; SKIN DISEASES; LYMPHOPROLIFERATIVE DISORDER; CYTOMEGALOVIRUS-INFECTION C1 [Kroshinsky, Daniela; Johnson, Richard Allen] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lin, Jennifer Y.] Harvard Univ, Sch Med, Dept Dermatol, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kroshinsky, D (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 57 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-89729-7 PY 2009 BP 195 EP 205 PG 11 WC Dermatology; Infectious Diseases SC Dermatology; Infectious Diseases GA BCH85 UT WOS:000310222400017 ER PT J AU Pace-Schott, EF Milad, MR Orr, SP Rauch, SL Stickgold, R Pitman, RK AF Pace-Schott, Edward F. Milad, Mohammed R. Orr, Scott P. Rauch, Scott L. Stickgold, Robert Pitman, Roger K. TI Sleep Promotes Generalization of Extinction of Conditioned Fear SO SLEEP LA English DT Article DE Fear conditioning; extinction; generalization; human; emotional memory ID POSTTRAUMATIC-STRESS-DISORDER; EYE-MOVEMENT SLEEP; VENTROMEDIAL PREFRONTAL CORTEX; REM-SLEEP; DEPRIVATION IMPAIRS; DECLARATIVE MEMORY; EMOTIONAL MEMORY; COCAINE USERS; HUMANS; RECALL AB Study Objective: To examine the effects of sleep on fear conditioning, extinction, extinction recall, and generalization of extinction recall in healthy humans. Design: During the Conditioning phase, a mild, 0.5-sec shock followed conditioned stimuli (CS+s), which consisted of 2 differently colored lamps. A third lamp color was interspersed but never reinforced (CS-). Immediately after Conditioning, one CS+ was extinguished (CS+E) by presentation without shocks (Extinction phase). The other CS+ went unextinguished (CS+U). Twelve hours later, following continuous normal daytime waking (Wake group, N = 27) or an equal interval containing a normal night's sleep (Sleep group, N = 26), conditioned responses (CRs) to all CSs were measured (Extinction Recall phase). It was hypothesized that the Sleep versus Wake group would show greater extinction recall and/or generalization of extinction recall from the CS+E to the CS+U. Setting: Academic medical center. Subjects: Paid normal volunteers. Measurements and Results: Square-root transformed skin conductance response (SCR) measured conditioned responding. During Extinction Recall, the Group (Wake or Sleep) x CS+ Type (CS+E or CS+U) interaction was significant (P = 0.04). SCRs to the CS+E did not differ between groups, whereas SCRs to the CS+U were significantly smaller in the Sleep group. Additionally, SCRs were significantly larger to the CS+U than CS+E in the Wake but not the Sleep group. Conclusions: After sleep, extinction memory generalized from an extinguished conditioned stimulus to a similarly conditioned but unextinguished stimulus. Clinically, adequate sleep may promote generalization of extinction memory from specific stimuli treated during exposure therapy to similar stimuli later encountered in vivo. C1 [Pace-Schott, Edward F.; Stickgold, Robert] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Psychiat,Ctr Sleep & Cognit, Boston, MA 02215 USA. [Pace-Schott, Edward F.; Milad, Mohammed R.; Orr, Scott P.; Pitman, Roger K.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,Psychophysiol Lab, Charlestown, MA USA. [Orr, Scott P.] Vet Affairs Med Ctr, Res Serv, Manchester, NH USA. [Rauch, Scott L.] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. RP Pace-Schott, EF (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Psychiat,Ctr Sleep & Cognit, Feldberg 864,E Campus,330 Brookline Ave, Boston, MA 02215 USA. EM epacesch@bidmc.harvard.edu FU NIDA [RO IDA 11744] FX Work was performed at Massachusetts General Hospital, Charlestown, MA. EPS is supported by NIDA grant RO IDA 11744 to Robert T. Malison. We thank Heike Croteau for laboratory NR 66 TC 75 Z9 75 U1 2 U2 13 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD JAN 1 PY 2009 VL 32 IS 1 BP 19 EP 26 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 389FC UT WOS:000262075600007 PM 19189775 ER PT J AU Bianchi, MT Cash, SS Mietus, JE Peng, C Thomas, RJ AF Bianchi, M. T. Cash, S. S. Mietus, J. E. Peng, C. Thomas, R. J. TI QUANTIFYING CONVENTIONAL AND ECG-SPECTROGRAPHIC SLEEP ARCHITECTURE WITH MARKOV STATE TRANSITION MODELS SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Bianchi, M. T.; Thomas, R. J.] BIDMC, Sleep Disorders Ctr, Boston, MA USA. [Cash, S. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mietus, J. E.; Peng, C.] BIDMC, Div Interdisciplinary Med & Biotechnol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 0060 BP A20 EP A20 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000062 ER PT J AU Brown, RE McKenna, JT Winston, S Yanagawa, Y McCarley, RW AF Brown, R. E. McKenna, J. T. Winston, S. Yanagawa, Y. McCarley, R. W. TI LONG-LASTING PLATEAU POTENTIALS AND CARBACHOL SUPPRESSION OF OREXIN EXCITATION IN GABAERGIC VENTRAL TEGMENTAL NUCLEUS OF GUDDEN NEURONS: IMPLICATIONS FOR THETA BURST FIRING SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Brown, R. E.; McKenna, J. T.; Winston, S.; McCarley, R. W.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Div Sleep Med, Brockton, MA 02401 USA. [Yanagawa, Y.] Gunma Univ, Grad Sch Med, Dept Genet & Behav Neurosci, Maebashi, Gumma 371, Japan. [Yanagawa, Y.] SORST, Maebashi, Gumma, Japan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 0032 BP A11 EP A11 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000034 ER PT J AU Chakravorty, S Oslin, D Witte, LM Cardillo, C Kuna, ST AF Chakravorty, S. Oslin, D. Witte, L. M. Cardillo, C. Kuna, S. T. TI SLEEP QUALITY IN RECENTLY SOBER ALCOHOLICS SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Chakravorty, S.; Oslin, D.; Witte, L. M.; Cardillo, C.; Kuna, S. T.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Chakravorty, S.; Oslin, D.; Kuna, S. T.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 1119 BP A365 EP A365 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542001466 ER PT J AU Chami, HA Resnick, HE Quan, SF Gottlieb, DJ AF Chami, H. A. Resnick, H. E. Quan, S. F. Gottlieb, D. J. TI REVERSE CAUSALITY IN THE ASSOCIATION OF SLEEP-DISORDERED BREATHING AND CARDIOVASCULAR DISEASE SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Chami, H. A.; Gottlieb, D. J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Chami, H. A.; Gottlieb, D. J.] VA Boston Hlth Care Syst, Pulm Sect, W Roxbury, MA USA. [Resnick, H. E.] Amer Assoc Homes & Serv Aging, Inst Future Aging Serv, Washington, DC USA. [Resnick, H. E.] Georgetown Univ, Dept Med, Washington, DC USA. [Quan, S. F.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. [Quan, S. F.] Univ Arizona, Arizona Resp Ctr, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 503 BP A166 EP A166 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000505 ER PT J AU Chen, L Bolortuya, Y Winston, S Basheer, R McCarley, RW AF Chen, L. Bolortuya, Y. Winston, S. Basheer, R. McCarley, R. W. TI SUPPRESSION OF OREXIN NEUROTRANSMISSION IN LOCUS COERULEUS FACILITATES REM SLEEP OCCURRENCE SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Chen, L.; Bolortuya, Y.; Winston, S.; Basheer, R.; McCarley, R. W.] VA Boston Healthcare Syst, Res Serv, Brockton, MA USA. [Chen, L.; Bolortuya, Y.; Winston, S.; Basheer, R.; McCarley, R. W.] Harvard Univ, Sch Med, Dept Psychiat, Brockton, MA 02401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 1210 BP A396 EP A396 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542001556 ER PT J AU Christie, M Strecker, R Bolortuya, Y Kalinchuk, A Basheer, R McCarley, R AF Christie, M. Strecker, R. Bolortuya, Y. Kalinchuk, A. Basheer, R. McCarley, R. TI NITRIC-OXIDE DONOR MICRODIALYSIS IN THE BASAL FOREBRAIN PRODUCES IMPAIRMENTS IN THE RAT-PSYCHOMOTOR VIGILANCE TASK THAT ARE REVERSED BY AN ADENOSINE AIR ANTAGONIST SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 VA Boston Healthcare Syst, Brockton, MA USA. Harvard Univ, Sch Med, Brockton, MA 02401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 108 BP A36 EP A37 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000110 ER PT J AU DaSilva, JK Madan, V Lei, Y Laitman, BM Mann, GL Gehrman, PR Tejani-Butt, S Ross, RJ Morrison, AR AF DaSilva, J. K. Madan, V Lei, Y. Laitman, B. M. Mann, G. L. Gehrman, P. R. Tejani-Butt, S. Ross, R. J. Morrison, A. R. TI FEAR-CONDITIONED ALTERATIONS IN REM PHASIC ACTIVITY MEASURED BY MUSCLE TWITCHES IN STRESS-SENSITIVE WISTAR-KYOTO (WKY) VERSUS WISTAR (WIS) RATS SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [DaSilva, J. K.; Lei, Y.; Tejani-Butt, S.] Univ Sci Philadelphia, Dept Pharmaceut Sci, Philadelphia, PA USA. [Madan, V; Laitman, B. M.; Mann, G. L.; Ross, R. J.; Morrison, A. R.] Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA. [Gehrman, P. R.; Ross, R. J.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Ross, R. J.] Philadelphia VA Med Ctr, Behav Hlth Serv, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 0068 BP A22 EP A22 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000070 ER PT J AU Fiorentino, L Martin, JL Josephson, K Jouldjian, S Alessi, CA AF Fiorentino, L. Martin, J. L. Josephson, K. Jouldjian, S. Alessi, C. A. TI SLEEP DISTURBANCE AMONG OLDER ADULTS RESIDING IN ASSISTED LIVING FACILITIES SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Fiorentino, L.] Univ Calif Los Angeles, Semel Inst Neurosci & Behav, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA USA. [Fiorentino, L.; Martin, J. L.; Josephson, K.; Jouldjian, S.; Alessi, C. A.] Vet Adm Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, North Hills, CA USA. [Martin, J. L.; Alessi, C. A.] Univ Calif Los Angeles, David Geffen Sch Med, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 0359 BP A119 EP A119 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000361 ER PT J AU Fiorentino, L Martin, JL Josephson, K Jouldjian, S Alessi, CA AF Fiorentino, L. Martin, J. L. Josephson, K. Jouldjian, S. Alessi, C. A. TI SLEEP DISTURBANCE PREDICTS DEPRESSIVE SYMPTOMS AND FUNCTIONAL DECLINE AMONG OLDER RESIDENTS IN ASSISTED LIVING FACILITIES SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Fiorentino, L.] Univ Calif Los Angeles, Semel Inst Neurosci & Behav, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA USA. [Fiorentino, L.; Martin, J. L.; Josephson, K.; Jouldjian, S.; Alessi, C. A.] Vet Adm Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, North Hills, CA USA. [Martin, J. L.; Alessi, C. A.] Univ Calif Los Angeles, David Geffen Sch Med, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 345 BP A114 EP A115 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000347 ER PT J AU Kalinchuk, A Porkka-Heiskanen, T McCarley, RW Basheer, R AF Kalinchuk, A. Porkka-Heiskanen, T. McCarley, R. W. Basheer, R. TI UNIQUE NEURONAL PRODUCTION OF INDUCIBLE NITRIC OXIDE SYNTHASE AND NITRIC OXIDE IN THE BASAL FOREBRAIN AS A MECHANISM OF HOMEOSTATIC SLEEP CONTROL SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Kalinchuk, A.; McCarley, R. W.; Basheer, R.] Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Porkka-Heiskanen, T.] Univ Helsinki, Inst Biomed, Helsinki, Finland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 06 BP A2 EP A2 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000008 ER PT J AU Kim, T Ramesh, V Kalinchuk, AV Messing, RO Choi, D Dworak, M McCarley, RW Basheer, R AF Kim, T. Ramesh, V Kalinchuk, A., V Messing, R. O. Choi, D. Dworak, M. McCarley, R. W. Basheer, R. TI COMPENSATORY CHANGES IN NUCLEOSIDE TRANSPORTERS AND SLEEP-WAKE PATTERN IN TYPE 1 EQUILIBRATIVE NUCLEOSIDE TRANSPORTER KNOCKOUT MICE SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Kim, T.; Kalinchuk, A., V; Dworak, M.; McCarley, R. W.; Basheer, R.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, W Roxbury, MA USA. [Ramesh, V] Univ Louisville, Sch Med, Dept Pediat, Louisville, KY 40292 USA. [Messing, R. O.] Univ Calif San Francisco, Earnest Gallo Clin & Res Ctr, San Francisco, CA 94143 USA. [Choi, D.] Mayo Clin, Coll Med, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 476 BP A157 EP A158 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000478 ER PT J AU Kim, Y Chen, L Basheer, R McCarley, RW Strecker, RE AF Kim, Y. Chen, L. Basheer, R. McCarley, R. W. Strecker, R. E. TI ADAPTIVE PATTERN OF CHANGES IN CINGULATE CORTEX BETA-ADRENERGIC RECEPTOR MRNA LEVEL DURING CHRONIC SLEEP RESTRICTION IN RATS SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Kim, Y.; Chen, L.; Basheer, R.; McCarley, R. W.; Strecker, R. E.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. [Kim, Y.; Chen, L.; Basheer, R.; McCarley, R. W.; Strecker, R. E.] VA Boston Healthcare Syst, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 0026 BP A9 EP A9 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000028 ER PT J AU Kocsis, B McKenna, JT Brown, RE McCarley, RW Strecker, RE AF Kocsis, B. McKenna, J. T. Brown, R. E. McCarley, R. W. Strecker, R. E. TI PARABRACHIAL (PB) AND BASAL FOREBRAIN (BF) UNIT ACTIVITY DURING HYPERCARBIA INDUCED AROUSALS FROM SLEEP IN RATS SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [McKenna, J. T.; Brown, R. E.; McCarley, R. W.; Strecker, R. E.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. [McKenna, J. T.; Brown, R. E.; McCarley, R. W.; Strecker, R. E.] VA Boston Healthcare Syst, Brockton, MA USA. [Kocsis, B.] Harvard Univ, Sch Med, Boston, MA USA. [Kocsis, B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 0657 BP A214 EP A215 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542001007 ER PT J AU Kosenko, P Lyamin, O Belyaev, E Kibalnikov, A Lapierre, J Mukhametov, L Siegel, J AF Kosenko, P. Lyamin, O. Belyaev, E. Kibalnikov, A. Lapierre, J. Mukhametov, L. Siegel, J. TI SELECTIVE REM SLEEP DEPRIVATION OF THE NORTHERN FUR SEAL ON LAND SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Kosenko, P.; Lyamin, O.; Belyaev, E.; Mukhametov, L.] Utrish Dolphinarium Ltd, Moscow, Russia. [Lyamin, O.; Lapierre, J.; Siegel, J.] Dept Psychiat, North Hills, CA USA. [Lyamin, O.; Lapierre, J.; Siegel, J.] VA GLAHS Sepulveda, North Hills, CA USA. [Lyamin, O.; Kibalnikov, A.] Russian Acad Sci, So Sci Ctr, Rostov Na Donu, Russia. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 04 BP A2 EP A2 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000006 ER PT J AU Laitman, BM DaSilva, JK Tejani-Butt, S Ross, RJ Morrison, AR AF Laitman, B. M. DaSilva, J. K. Tejani-Butt, S. Ross, R. J. Morrison, A. R. TI REM HEART RATE CHANGES IN WISTAR-KYOTO (WKY) VERSUS WISTAR (WIS) RATS SUGGEST NOREPINEPHRINE (NE) SURGES AS A POSSIBLE CAUSE OF REM FRAGMENTATION SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Laitman, B. M.; Ross, R. J.; Morrison, A. R.] Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. [DaSilva, J. K.; Tejani-Butt, S.] Univ Sci Philadelphia, Philadelphia, PA USA. [Ross, R. J.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Ross, R. J.] Philadelphia VA Med Ctr, Behav Hlth Serv, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 0036 BP A12 EP A12 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000038 ER PT J AU Martin, J Fiorentino, L Jouldjian, S Josephson, KR Alessi, CA AF Martin, J. Fiorentino, L. Jouldjian, S. Josephson, K. R. Alessi, C. A. TI DOES POOR SLEEP AMONG OLDER ADULTS DURING INPATIENT POST-ACUTE REHABILITATION PREDICT PERSISTENT SLEEP DISTURBANCE? SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Martin, J.; Jouldjian, S.; Alessi, C. A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Martin, J.; Fiorentino, L.; Josephson, K. R.; Alessi, C. A.] VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 0366 BP A121 EP A122 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000368 ER PT J AU McKenna, JT Franciosi, S Winston, S Yanagawa, Y McCarley, RW Brown, RE AF McKenna, J. T. Franciosi, S. Winston, S. Yanagawa, Y. McCarley, R. W. Brown, R. E. TI NEUROANATOMICAL INVESTIGATION OF BRAINSTEM PROJECTIONS TO THE MEDIAL MAMMILLARY BODY: POSSIBLE IMPLICATIONS FOR THE MODULATION OF THETA RHYTHM SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [McKenna, J. T.; Franciosi, S.; Winston, S.; McCarley, R. W.; Brown, R. E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA 02401 USA. [Yanagawa, Y.] Gunma Univ, Grad Sch Med, Dept Genet & Behav Neurosci, Maebashi, Gumma 371, Japan. [Yanagawa, Y.] SORST, Maebashi, Gumma, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 0030 BP A10 EP A10 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000032 ER PT J AU Medalie, L Thomas, RJ Thomas, N Kwong, K AF Medalie, L. Thomas, R. J. Thomas, N. Kwong, K. TI SLEEP DEPRIVATION AND FRAGMENTATION EFFECTS ON ANTERIOR CINGULATE FUNCTION - A FMRI STUDY SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Medalie, L.; Thomas, R. J.; Thomas, N.] Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm Crit Care & Sleep, Boston, MA 02215 USA. [Medalie, L.; Thomas, R. J.; Kwong, K.] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 483 BP A159 EP A160 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000485 ER PT J AU Plante, DT Winkelman, JW Afkarian, M Keenan, H Gusella, JF Thadhani, R AF Plante, D. T. Winkelman, J. W. Afkarian, M. Keenan, H. Gusella, J. F. Thadhani, R. TI PRELIMINARY EVIDENCE OF ASSOCIATION BETWEEN SINGLE NUCLEOTIDE POLYMORPHISMS ASSOCIATED WITH PERIODIC LIMB MOVEMENTS OF SLEEP AND RESTLESS LEGS SYNDROME AND MORTALITY IN END-STAGE RENAL DISEASE SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Plante, D. T.; Winkelman, J. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Sleep Med, Boston, MA 02115 USA. [Afkarian, M.; Thadhani, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA 02115 USA. [Keenan, H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Clin Invest, Boston, MA 02115 USA. [Gusella, J. F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 0911 BP A297 EP A297 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542001258 ER PT J AU Qiu, M Ramalingan, V Fuller, P Lu, J AF Qiu, M. Ramalingan, V Fuller, P. Lu, J. TI BASAL GANGLIA CONTROL OF AROUSAL SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 BIDMC, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 0065 BP A21 EP A21 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000067 ER PT J AU Ross, RJ Gehrman, P Cook, JM Harb, GC Gamble, GM AF Ross, R. J. Gehrman, P. Cook, J. M. Harb, G. C. Gamble, G. M. TI RANDOMIZED CONTROLLED TRIAL OF IMAGERY REHEARSAL FOR POSTTRAUMATIC NIGHTMARES IN VIETNAM VETERANS SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Ross, R. J.; Gehrman, P.; Harb, G. C.; Gamble, G. M.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Ross, R. J.; Gehrman, P.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Cook, J. M.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 1066 BP A348 EP A348 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542001413 ER PT J AU Saboisky, JP Nandedkar, S Eckert, DJ Jordan, AS David, WS Ali, M White, DP Nicholas, CL Trinder, JA Malhotra, A AF Saboisky, J. P. Nandedkar, S. Eckert, D. J. Jordan, A. S. David, W. S. Ali, M. White, D. P. Nicholas, C. L. Trinder, J. A. Malhotra, A. TI FEASIBILITY OF SELECTIVE MUSCLE FIBER DENSITY EXAMINATION IN THE GENIOGLOSSUS SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Saboisky, J. P.; Eckert, D. J.; Jordan, A. S.; White, D. P.; Malhotra, A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Sleep Disorders Program,Div Sleep Med, Boston, MA 02115 USA. [David, W. S.; Ali, M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Nicholas, C. L.; Trinder, J. A.] Univ Melbourne, Dept Psychol, Melbourne, Vic, Australia. [Nandedkar, S.] Cardinal Hlth, Hopewell Jct, NY USA. RI Saboisky, Julian/P-5782-2014 OI Saboisky, Julian/0000-0002-9450-6023 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 0044 BP A15 EP A15 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000046 ER PT J AU Solet, J Buxton, OM Carballeira, A Ellenbogen, JM AF Solet, J. Buxton, O. M. Carballeira, A. Ellenbogen, J. M. TI SOUND SLEEP: AROUSAL THRESHOLDS AND SLEEP DISRUPTION FROM COMMON HOSPITAL NOISES SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Solet, J.] Cambridge Hlth Alliance, Psychiat, Cambridge, MA USA. [Solet, J.; Buxton, O. M.; Ellenbogen, J. M.] Harvard Univ, Sch Med, Boston, MA USA. [Buxton, O. M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Carballeira, A.] Cavanaugh Tocci Associates, Sudbury, MA USA. [Ellenbogen, J. M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 444 BP A147 EP A147 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000446 ER PT J AU Thomas, RJ Greve, DN Fischl, BR Yang, R Dayno, JM Rippon, GA AF Thomas, R. J. Greve, D. N. Fischl, B. R. Yang, R. Dayno, J. M. Rippon, G. A. TI A FUNCTIONAL NEUROIMAGING STUDY OF THE EFFECTS OF ARMODAFINIL ON CORTICAL ACTIVITY AND WORKING MEMORY IN PATIENTS WITH RESIDUAL EXCESSIVE SLEEPINESS ASSOCIATED WITH OBSTRUCTIVE SLEEP APNEA SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Thomas, R. J.] Beth Israel Deaconess Med Ctr, KB Pulm Off 023, Boston, MA 02215 USA. [Greve, D. N.] Massachusetts Gen Hosp, NMR Ctr, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Yang, R.; Dayno, J. M.; Rippon, G. A.] Cephalon Inc, Frazer, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2009 VL 32 MA 579 BP A190 EP A190 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000581 ER PT J AU van de Riet, WAC Grezes, J de Gelder, B AF van de Riet, Wim A. C. Grezes, Julie de Gelder, Beatrice TI Specific and common brain regions involved in the perception of faces and bodies and the representation of their emotional expressions SO SOCIAL NEUROSCIENCE LA English DT Review ID SUPERIOR TEMPORAL SULCUS; HUMAN EXTRASTRIATE CORTEX; PRIMARY SOMATOSENSORY CORTEX; BILATERAL AMYGDALA DAMAGE; MONKEY CAUDATE NEURONS; VOXEL PATTERN-ANALYSIS; FACIAL EXPRESSIONS; VISUAL-CORTEX; INTERINDIVIDUAL VARIABILITY; INTERSUBJECT VARIABILITY AB Many studies provide support for the role of the fusiform gyrus in face recognition and its sensitivity to emotional expressions. Recently, category-specific representation was also observed for neutral human bodies in the middle temporal/middle occipital gyrus (extrastriate body area) but it is not clear whether this area is also sensitive to emotional bodily expressions. Besides these areas, other regions that process the affective information carried by the face and the body may be common and/or specific to the face or the body. To clarify these issues we performed a systematic comparison of how the whole brain processes faces and bodies and how their affective information is represented. Participants categorized emotional facial and bodily expressions while brain activity was measured using functional magnetic resonance imaging. Our results show that, first, the amygdala and the fusiform gyrus are sensitive to recognition of facial and bodily fear signals. Secondly, the extrastriate body area-area V5/MT is specifically involved in processing bodies without being sensitive to the emotion displayed. Thirdly, other important areas such as the superior temporal sulcus, the parietal lobe and subcortical structures represent selectively facial and bodily expressions. Finally, some face/body differences in activation are a function of the emotion expressed. C1 [de Gelder, Beatrice] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [van de Riet, Wim A. C.; de Gelder, Beatrice] Tilburg Univ, Dept Psychol, Cognit & Affect Neurosci Lab, Tilburg, Netherlands. [van de Riet, Wim A. C.; de Gelder, Beatrice] FC Donders Ctr Cognit Neuroimaging, Nijmegen, Netherlands. [Grezes, Julie] Coll France, CNRS, LPPA, Paris, France. RP de Gelder, B (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Room 409,Bldg 36,1st St, Charlestown, MA 02129 USA. EM degelder@nmr.mgh.harvard.edu RI Grezes, Julie/E-5060-2016 FU Human Frontier Science Program [HFSP-RGP0054/2004-C] FX We are grateful to I. Toni for advice on the design of the study, M. Barth for advice on the scanning parameters, P. Gaalman, R. Scheeringa and R. B. Mars for technical assistance, H. K. M. Meeren for assistance with the stimulus presentation programming, S. van der Goor and R. A. Otte for their assistance with the stimulus preparation and with the validation of the stimuli, S. Pichon for advice on the fMRI analysis, and R. Righart, J. Van den Stock and B. M. C. Stienen for comments on the manuscript. The authors were partly supported by Human Frontier Science Program HFSP-RGP0054/2004-C. NR 114 TC 56 Z9 56 U1 3 U2 15 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1747-0919 J9 SOC NEUROSCI-UK JI Soc. Neurosci. PY 2009 VL 4 IS 2 BP 101 EP 120 AR PII 909175842 DI 10.1080/17470910701865367 PG 20 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 416YE UT WOS:000264040600001 PM 19255912 ER PT J AU Ganis, G Keenan, JP AF Ganis, Giorgio Keenan, Julian Paul TI The cognitive neuroscience of deception SO SOCIAL NEUROSCIENCE LA English DT Article C1 [Ganis, Giorgio] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Ganis, Giorgio] Harvard Univ, Sch Med, Boston, MA USA. [Ganis, Giorgio] Harvard Univ, Cambridge, MA 02138 USA. [Keenan, Julian Paul] Montclair State Univ, Montclair, NJ USA. RP Ganis, G (reprint author), Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. EM ganis@nmr.mgh.harvard.edu OI Ganis, Giorgio/0000-0001-6175-2618 NR 14 TC 15 Z9 15 U1 0 U2 3 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1747-0919 J9 SOC NEUROSCI JI Soc. Neurosci. PY 2009 VL 4 IS 6 BP 465 EP 472 AR PII 915178102 DI 10.1080/17470910802507660 PG 8 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 498KE UT WOS:000270137900001 PM 19787548 ER PT J AU Ganis, G Morris, RR Kosslyn, SM AF Ganis, Giorgio Morris, Robert R. Kosslyn, Stephen M. TI Neural processes underlying self- and other-related lies: An individual difference approach using fMRI SO SOCIAL NEUROSCIENCE LA English DT Article ID FUNCTIONAL MAGNETIC-RESONANCE; ANTERIOR CINGULATE; EPISODIC MEMORY; BRAIN ACTIVITY; DECEPTION; TASK; INFORMATION; PERFORMANCE; ACTIVATION; RETRIEVAL AB Two hypotheses were tested using a novel individual differences approach, which identifies rate-limiting brain regions, that is, brain regions in which variations in neural activity predict variations in behavioral performance. The first hypothesis is that the rate-limiting regions that support the production of lies about oneself (self-related) are partially distinct from those underlying the production of lies about other individuals (other-related). The second hypothesis is that a cingulate-insular-prefrontal network found to be rate-limiting for interference tasks is involved in both types of lies. The results confirmed both hypotheses and supported the utility of this individual differences approach in the study of deception in particular, as well in the study of complex cognitive phenomena more generally. C1 [Ganis, Giorgio] Harvard Univ, Sch Med, Martinos Ctr, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Ganis, Giorgio] Harvard Univ, Sch Med, Boston, MA USA. [Morris, Robert R.] MIT, Cambridge, MA 02139 USA. [Ganis, Giorgio; Kosslyn, Stephen M.] Harvard Univ, Cambridge, MA 02138 USA. [Kosslyn, Stephen M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ganis, G (reprint author), Harvard Univ, Sch Med, Martinos Ctr, Massachusetts Gen Hosp, Bldg 149, Charlestown, MA 02129 USA. EM ganis@nmr.mgh.harvard.edu OI Ganis, Giorgio/0000-0001-6175-2618 FU National Science Foundation [BCS-0322611] FX This material is based partially upon work supported by the National Science Foundation under Grant BCS-0322611. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation. The authors wish to thank Haline Schendan, Julian P. Keenan, and Mark D. Happel for helpful discussion, and Jonathan Weiss for help with stimulus design and implementation. NR 57 TC 21 Z9 25 U1 3 U2 8 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1747-0919 J9 SOC NEUROSCI JI Soc. Neurosci. PY 2009 VL 4 IS 6 BP 539 EP 553 AR PII 904259965 DI 10.1080/17470910801928271 PG 15 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 498KE UT WOS:000270137900007 PM 18925536 ER PT J AU Bove, R Valeggia, C AF Bove, Riley Valeggia, Claudia TI Polygyny and women's health in sub-Saharan Africa SO SOCIAL SCIENCE & MEDICINE LA English DT Review DE Polygyny; HIV; Sub-Saharan Africa; Women's health; Mental health; Fertility; Sexually transmitted infections (STIs); Review ID MALE SEXUAL-BEHAVIOR; CHILD SURVIVAL; REPRODUCTIVE HEALTH; RISK-FACTORS; WEST-AFRICA; RURAL MALI; FERTILITY; MARRIAGE; NIGERIA; HIV AB In this paper we review the literature on the association between polygyny and women's health in sub-Saharan Africa. We argue that polygyny is an example of "co-operative conflict" within households, with likely implications for the vulnerability of polygynous women to illness, and for their access to treatment. We begin with a review of polygyny and then examine vulnerability to sexually transmitted infections (STIs, including HIV) and differential reproductive outcomes. Polygyny is associated with an accelerated transmission of STIs, both because it permits a multiplication of sexual partners and because it correlates with low rates of condom use, poor communication between spouses, and age and power imbalances among other factors. Female fertility is affected by the interplay between marital rank, household status, and cultural norms in polygynous marriages. Finally, we present areas which have received only cursory attention: mental health and a premature, "social" menopause. Although data are scarce, polygyny seems to be associated with higher levels of anxiety and depression, particularly around stressful life events. It is our hope that the examples reviewed here will help build a framework for mixed method quality research, which in turn can inform decision makers on more appropriate, context-dependent health policies. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Bove, Riley] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Valeggia, Claudia] Univ Penn, Dept Anthropol, Philadelphia, PA 19104 USA. RP Bove, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM riley_bove@post.harvard.edu; valeggia@sas.upenn.edu NR 104 TC 26 Z9 27 U1 7 U2 31 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD JAN PY 2009 VL 68 IS 1 BP 21 EP 29 DI 10.1016/j.socscimed.2008.09.045 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 399JL UT WOS:000262796100004 PM 18952335 ER PT J AU Haghgooie, R Doyle, PS AF Haghgooie, Ramin Doyle, Patrick S. TI Directed self-assembly of field-responsive fluids in confined geometries SO SOFT MATTER LA English DT Article ID COLLOIDAL CRYSTALLIZATION; MICROCHANNELS; MOLECULES; CRYSTALS; DYNAMICS AB We present an investigation into the important physical principles associated with the self-assembly of magnetorheological (MR) fluids in the microfluidic setting. We concentrate on the role of channel topology in influencing the resulting microstructure. In particular, using Brownian dynamics simulations, we show how a variety of geometrically-simple confining microchannels can be used to strongly control the lattice type and orientation in self-assembled MR fluids. Additionally, we demonstrate how topographical features can be used to dictate the order (or disorder) of the steady-state structure. We highlight the similarities and differences between our three-dimensional microchannel system and the structures and dynamics observed in two-dimensional confined systems. Furthermore, we present an example of the introduction of local magnetic field inhomogeneity and its strong influence over the resulting self-assembled MR fluid structure. C1 [Haghgooie, Ramin] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Doyle, Patrick S.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Haghgooie, R (reprint author), Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. EM rhaghgooie@partners.org; pdoyle@mit.edu FU NSF NIRT [CTS-0304128]; Singapore-MIT Alliance; MIT-MGH FX P. Doyle gratefully acknowledges the support of NSF NIRT Grant No. CTS-0304128 and Singapore-MIT Alliance (SMA-II, CPE Program) for this project. R. Haghgooie gratefully acknowledges the MIT-MGH Postdoctoral Fellowship in Translational Research for financial support. NR 36 TC 3 Z9 3 U1 2 U2 9 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1744-683X J9 SOFT MATTER JI Soft Matter PY 2009 VL 5 IS 6 BP 1192 EP 1197 DI 10.1039/b807389a PG 6 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Multidisciplinary; Polymer Science SC Chemistry; Materials Science; Physics; Polymer Science GA 417SX UT WOS:000264099800009 ER PT J AU Hsu, WC AF Hsu, William C. TI Consequences of Delaying Progression to Optimal Therapy in Patients with Type 2 Diabetes Not Achieving Glycemic Goals SO SOUTHERN MEDICAL JOURNAL LA English DT Review DE hemoglobin Alc; modem insulin analogues; type 2 diabetes ID INTENSIVE INSULIN THERAPY; MICROVASCULAR COMPLICATIONS; DOSE-RESPONSE; CARDIOVASCULAR-DISEASE; SULFONYLUREA DRUGS; PIOGLITAZONE HYDROCHLORIDE; MYOCARDIAL-INFARCTION; COMBINATION THERAPY; CLINICAL-TRIALS; GLUCOSE CONTROL AB As a result of the progressive nature of diabetes, glycemic control deteriorates with time, and the risk of associated complications increases. To delay the onset of complications, effective anti-hyperglycemia therapy should be initiated as soon as possible after diagnosis. Insulin is the most efficacious therapy for diabetes, but its administration is often delayed. This delay, which adversely affects patients' long-term prognosis, steins partly from clinical inertia and psychological factors affecting both patients and physicians, and part]),, from a treatment paradigm that advocates the sequential addition of oral interventions before eventual insulin initiation. Starting insulin therapy sooner can help to minimize complications, and modern insulin formulations, used in a well-designed treatment regimen with modern delivery devices, can help patients take advantage of this effect, with minimal hypoglycemia and weight gain. C1 [Hsu, William C.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Hsu, William C.] Joslin Clin, Boston, MA 02215 USA. RP Hsu, WC (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM william.hsu@joslin.harvard.edu NR 101 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD JAN PY 2009 VL 102 IS 1 BP 67 EP 76 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 396TU UT WOS:000262614900019 PM 19077788 ER PT J AU Alexander, MS Biering-Sorensen, F Bodner, D Brackett, NL Cardenas, D Charlifue, S Creasey, G Dietz, V Ditunno, J Donovan, W Elliott, SL Estores, I Graves, DE Green, B Gousse, A Jackson, AB Kennelly, M Karlsson, AK Krassioukov, A Krogh, K Linsenmeyer, T Marino, R Mathias, CJ Perkash, I Sheel, AW Shilero, G Schurch, B Sonksen, J Stiens, S Wecht, J Wuermser, LA Wyndaele, JJ AF Alexander, M. S. Biering-Sorensen, F. Bodner, D. Brackett, N. L. Cardenas, D. Charlifue, S. Creasey, G. Dietz, V. Ditunno, J. Donovan, W. Elliott, S. L. Estores, I. Graves, D. E. Green, B. Gousse, A. Jackson, A. B. Kennelly, M. Karlsson, A-K Krassioukov, A. Krogh, K. Linsenmeyer, T. Marino, R. Mathias, C. J. Perkash, I. Sheel, A. W. Shilero, G. Schurch, B. Sonksen, J. Stiens, S. Wecht, J. Wuermser, L. A. Wyndaele, J-J TI International standards to document remaining autonomic function after spinal cord injury SO SPINAL CORD LA English DT Review DE autonomic nervous system; spinal cord injury; human; international standards ID URINARY-TRACT FUNCTION; FEMALE SEXUAL FUNCTION; DATA SET; BRAIN ACTIVATION; NERVOUS-SYSTEM; DYSFUNCTION; PATHWAYS; HYPERRESPONSIVENESS; DYSREFLEXIA; AROUSAL AB Study design: Experts opinions consensus. Objective: To develop a common strategy to document remaining autonomic neurologic function following spinal cord injury (SCI). Background and Rationale: The impact of a specific SCI on a person's neurologic function is generally described through use of the International Standards for the Neurological Classification of SCI. These standards document the remaining motor and sensory function that a person may have; however, they do not provide information about the status of a person's autonomic function. Methods: Based on this deficiency, the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS) commissioned a group of international experts to develop a common strategy to document the remaining autonomic neurologic function. Results: Four subgroups were commissioned: bladder, bowel, sexual function and general autonomic function. On-line communication was followed by numerous face to face meetings. The information was then presented in a summary format at a course on Measurement in Spinal Cord Injury, held on June 24, 2006. Subsequent to this it was revised online by the committee members, posted on the websites of both ASIA and ISCoS for comment and re-revised through webcasts. Topics include an overview of autonomic anatomy, classification of cardiovascular, respiratory, sudomotor and thermoregulatory function, bladder, bowel and sexual function. Conclusion: This document describes a new system to document the impact of SCI on autonomic function. Based upon current knowledge of the neuroanatomy of autonomic function this paper provides a framework with which to communicate the effects of specific spinal cord injuries on cardiovascular, broncho-pulmonary, sudomotor, bladder, bowel and sexual function. C1 [Krassioukov, A.] Univ British Columbia, Dept Med, ICORD, Vancouver, BC V6T 1Z4, Canada. [Alexander, M. S.; Jackson, A. B.] Univ Alabama, Birmingham, AL USA. [Biering-Sorensen, F.] Rigshosp, DK-2100 Copenhagen, Denmark. [Biering-Sorensen, F.] Univ Copenhagen, Copenhagen, Denmark. [Bodner, D.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Brackett, N. L.; Cardenas, D.; Gousse, A.] Univ Miami, Miami, FL USA. [Charlifue, S.] Craig Hosp, Englewood, CO USA. [Creasey, G.; Perkash, I.] Stanford Univ, Palo Alto, CA 94304 USA. [Dietz, V.; Schurch, B.] Univ Hosp Balgrist, Zurich, Switzerland. [Ditunno, J.; Marino, R.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Estores, I.] James A Haley VA Hosp, Tampa, FL USA. [Donovan, W.; Graves, D. E.] Baylor Coll Med, Houston, TX 77030 USA. [Green, B.] Shepherd Ctr, Atlanta, GA USA. [Kennelly, M.] Carolinas Healthcare, McKay Urol, Charlotte, NC USA. [Karlsson, A-K] Sahlgrens Univ Hosp, S-41345 Gothenburg, Sweden. [Krogh, K.] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Linsenmeyer, T.] Kessler Inst Rehabil, W Orange, NJ USA. [Mathias, C. J.] Imperial Coll Sch Med, St Marys Hosp, London, England. [Shilero, G.; Wecht, J.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Sonksen, J.] Univ Copenhagen, Herlev Hosp, Copenhagen, Denmark. [Stiens, S.] Vet Affairs Puget Sound Hlth Care, Seattle, WA USA. [Wuermser, L. A.] Mayo Clin, Rochester, MS USA. [Wyndaele, J-J] Univ Antwerp, Univ Antwerp Hosp, B-2020 Antwerp, Belgium. RP Krassioukov, A (reprint author), Univ British Columbia, Dept Med, ICORD, 6270 Univ Blvd, Vancouver, BC V6T 1Z4, Canada. EM krassioukov@icord.org OI Marino, Ralph/0000-0003-2670-4113 NR 42 TC 84 Z9 93 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD JAN PY 2009 VL 47 IS 1 BP 36 EP 43 DI 10.1038/sc.2008.121 PG 8 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 392IS UT WOS:000262297000003 PM 18957962 ER PT J AU Paxinos, O Ghanayem, AJ Zindrick, MR Voronov, LI Havey, RM Carandang, G Hadjipavlou, A Patwardhan, AG AF Paxinos, Odysseas Ghanayem, Alexander J. Zindrick, Michael R. Voronov, Leonard I. Havey, Robert M. Carandang, Gerard Hadjipavlou, Alexander Patwardhan, Avinash G. TI Anterior Cervical Discectomy and Fusion With a Locked Plate and Wedged Graft Effectively Stabilizes Flexion-Distraction Stage-3 Injury in the Lower Cervical Spine A Biomechanical Study SO SPINE LA English DT Article DE cervical spine; flexion-distraction injury; trauma; facet dislocation; ACDF; preload; follower load ID BONE-MINERAL DENSITY; HUMAN CADAVERIC MODEL; FACET DISLOCATION; FRACTURE-DISLOCATIONS; FIXATION; REDUCTION; MANAGEMENT; CASPAR; SCREWS; LOAD AB Study Design. An in vitro three-dimensional (3D) flexibility test of human C3-C7 cervical spine specimens. Objective. To test the hypothesis that anterior cervical fusion with a wedged graft and a locked plate can effectively stabilize the cervical spine after complete anterior and posterior segmental ligamentous release. Summary of Background Data. Distraction-flexion Stage 3 injuries of the lower cervical spine (bilateral facet dislocations) are usually reduced under awake cranial traction. When the magnetic resonance imaging reveals a traumatic disc prolapse, anterior cervical discectomy and fusion (ACDF) is usually recommended. Most authors advise combining ACDF with posterior instrumentation to address the insufficiency of the posterior elements. However, there is clinical evidence that ACDF with a locked plate alone suffices for the treatment of these injuries, especially in young patients. Still, there are no biomechanical studies on the effect of a locked plate on the complete anterior and posterior ligamentous-deficient young cervical spine under physiologic preload. Methods. Eight fresh frozen human lower cervical spines (C3-C7) from young donors (age, 44.5 years; range, 21-63 years) were used. A 3D flexibility test was conducted using a moment of 0.8 Nm without preload. Flexion-extension was additionally tested using a moment of 1.5 Nm under 0 and 150 N follower preload. Spines were tested first intact, then after complete C5-C6 discectomy with posterior longitudinal ligament resection and ACDF with a wedged bone graft and a rigid locked plate, and finally after complete release of the supraspinous, interspinous, and intertransverse ligaments; the facet capsules; and ligamentum flavum. Results. When tested under 0.8 Nm moment without preload, complete posterior and anterior ligamentous release did not significantly increase the ROM of the ACDF construct in flexion-extension (P > 0.025), lateral bending (P > 0.025), and axial rotation (P > 0.025). When tested under 1.5 Nm moment with or without a compressive preload, the complete posterior and anterior ligamentous release did not significantly affect the ROM of the ACDF construct (P > 0.01). The application of preload significantly reduced the motion at the C5-C6 ACDF construct with ligamentous disruption in comparison with the motion in the absence of a preload (P < 0.01). Conclusion. Anterior cervical fusion with a wedged graft and a rigid constrained (locked) plate can effectively stabilize the nonosteoporotic cervical spine after complete posterior element injury when excessive ROM is prevented (for example, by the use of postoperative external immobilization). Even when the construct is subjected to higher moments, adequate stability can be achieved when physiologic preload is present. Osteoporosis and lack of sufficient preload due to poor neuromuscular control may affect long-term screw stability, and additional external immobilization may be needed until fusion matures. C1 [Paxinos, Odysseas; Ghanayem, Alexander J.; Zindrick, Michael R.; Voronov, Leonard I.; Havey, Robert M.; Patwardhan, Avinash G.] Loyola Univ, Dept Orthopaed Surg & Rehabil, Med Ctr, Maywood, IL 60153 USA. [Paxinos, Odysseas; Voronov, Leonard I.; Havey, Robert M.; Carandang, Gerard; Patwardhan, Avinash G.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Zindrick, Michael R.] Hinsdale Orthopaed Associates, Hinsdale, IL USA. [Hadjipavlou, Alexander] Univ Crete, Iraklion, Greece. RP Patwardhan, AG (reprint author), Loyola Univ, Dept Orthopaed Surg & Rehabil, Med Ctr, 2160 S 1st Ave, Maywood, IL 60153 USA. EM apatwar@lumc.edu NR 46 TC 10 Z9 15 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD JAN 1 PY 2009 VL 34 IS 1 BP E9 EP E15 DI 10.1097/BRS.0b013e318188386a PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 405YV UT WOS:000263261000019 PM 19127153 ER PT J AU Phillips, FM Tzermiadianos, MN Voronov, LI Havey, RM Carandang, G Renner, SM Rosler, DM Ochoa, JA Patwardhan, AG AF Phillips, Frank M. Tzermiadianos, Michael N. Voronov, Leonard I. Havey, Robert M. Carandang, Gerard Renner, Susan M. Rosler, David M. Ochoa, Jorge A. Patwardhan, Avinash G. TI Effect of the Total Facet Arthroplasty System after complete laminectomy-facetectomy on the biomechanics of implanted and adjacent segments SO SPINE JOURNAL LA English DT Review DE Lumbar spine; Facetectomy; Facet arthroplasty; ROM; Quality of motion ID LUMBAR SPINE; HYPOTHESIS; KINEMATICS; FUSION AB BACKGROUND CONTEXT: Lumbar fusion is traditionally used to restore stability after wide surgical decompression for spinal stenosis. The Total Facet Arthroplasty System (TFAS) is a motion-restoring implant suggested as an alternative to rigid fixation after complete facetectomy. PURPOSE: To investigate the effect of TFAS on the kinematics of the implanted and adjacent lumbar segments. STUDY DESIGN: Biomechanical in vitro study. METHODS: Nine human lumbar spines (L1 to sacrum) were tested in flexion-extension (+8 to -6 Nm), lateral bending (+/- 6 Nm), and axial rotation (+/- 5 Nm). Flexion-extension was tested under 400 N follower preload. Specimens were tested intact, after complete L3 laminectomy with L3-L4 facetectomy, after L3-L4 pedicle screw fixation, and after L3-L4 TFAS implantation. Range of motion (ROM) was assessed in all tested directions. Neutral zone and stiffness in flexion and extension were calculated to assess quality of motion. RESULTS: Complete laminectomy-facetectomy increased L3-L4 ROM compared with intact in flexion-extension (8.7 +/- 2.0 degrees to 12.2 +/- 3.2 degrees, p<.05) lateral bending (9.0 +/- 2.5 degrees to 12.6 +/- 3.2 degrees, p=.09), and axial rotation (3.8 +/- 2.7 degrees to 7.8 +/- 4.5 degrees p<.05). Pedicle screw fixation decreased ROM compared with intact, resulting in 1.7 +/- 0.5 degrees flexion-extension (p<.05), 3.3 +/- 1.4 degrees lateral bending (p<.05), and 1.8 +/- 0.6 degrees axial rotation (p=.09). TFAS restored intact ROM (p>.05) resulting in 7.9 +/- 2.1 degrees flexion-extension, 10.1 +/- 3.0 degrees lateral bending, and 4.7 +/- 1.6 degrees axial rotation. Fusion significantly increased the normalized ROM at all remaining lumbar segments, whereas TFAS implantation resulted in near-normal distribution of normalized ROM at the implanted and remaining lumbar segments. Flexion and extension stiffness in the high-flexibility zone decreased after facetectomy (p<.05) and increased after simulated fusion (p<.05). TFAS restored quality of motion parameters (load-displacement curves) to intact (p>.05). The quality of motion parameters for the whole lumbar spine mimicked L3-L4 segmental results. CONCLUSIONS: TEAS restored range and quality of motion at the operated segment to intact values and restored near-normal motion at the adjacent segments. (C) 2009 Elsevier Inc. All rights reserved. C1 [Patwardhan, Avinash G.] Loyola Univ, Med Ctr, Dept Orthoped Surg, Maywood, IL 60153 USA. [Phillips, Frank M.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Carandang, Gerard; Renner, Susan M.; Patwardhan, Avinash G.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Rosler, David M.; Ochoa, Jorge A.] Archus Orthoped Inc, Redmond, WA USA. RP Patwardhan, AG (reprint author), Loyola Univ, Med Ctr, Dept Orthoped Surg, 2160 S 1st Ave, Maywood, IL 60153 USA. EM apatwar@lumc.edu OI Ochoa, Jorge/0000-0003-1992-8143 FU Archus Orthopedics Inc. FX This study was funded by Archus Orthopedics Inc., a commercial entity. NR 13 TC 20 Z9 22 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 J9 SPINE J JI Spine Journal PD JAN PY 2009 VL 9 IS 1 BP 96 EP 102 DI 10.1016/j.spinee.2008.01.010 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 393MX UT WOS:000262378500012 PM 18440280 ER PT J AU Engler, D Li, Y AF Engler, David Li, Yi TI Survival Analysis with High-Dimensional Covariates: An Application in Microarray Studies SO STATISTICAL APPLICATIONS IN GENETICS AND MOLECULAR BIOLOGY LA English DT Article DE survival analysis; microarray; elastic net; variable selection ID PROPORTIONAL HAZARDS MODEL; FAILURE TIME MODEL; VARIABLE SELECTION; CENSORED-DATA; ADAPTIVE LASSO; REGRESSION AB Use of microarray technology often leads to high-dimensional and low-sample size (HDLSS) data settings. A variety of approaches have been proposed for variable selection in this context. However, only a small number of these have been adapted for time-to-event data where censoring is present. Among standard variable selection methods shown both to have good predictive accuracy and to be computationally efficient is the elastic net penalization approach. In this paper, adaptations of the elastic net approach are presented for variable selection both under the Cox proportional hazards model and under an accelerated failure time (AFT) model. Assessment of the two methods is conducted through simulation studies and through analysis of microarray data obtained from a set of patients with diffuse large B-cell lymphoma where time to survival is of interest. The approaches are shown to match or exceed the predictive performance of a Cox-based and an AFT-based variable selection method. The methods are moreover shown to be much more computationally efficient than their respective Cox- and AFT-based counterparts. C1 [Engler, David] Brigham Young Univ, Provo, UT 84602 USA. [Li, Yi] Harvard Univ, Cambridge, MA 02138 USA. [Li, Yi] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Engler, D (reprint author), Brigham Young Univ, Provo, UT 84602 USA. EM engler@byu.edu; yili@jimmy.harvard.edu NR 35 TC 11 Z9 11 U1 3 U2 6 PU BERKELEY ELECTRONIC PRESS PI BERKELEY PA 2809 TELEGRAPH AVENUE, STE 202, BERKELEY, CA 94705 USA SN 1544-6115 J9 STAT APPL GENET MOL JI Stat. Appl. Genet. Mol. Biol. PY 2009 VL 8 IS 1 AR 14 DI 10.2202/1544-6115.1423 PG 24 WC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Mathematics GA 408NB UT WOS:000263440600014 ER PT J AU Varas, F Stadtfeld, M De Andres-Aguayo, L Maherali, N di Tullio, A Pantano, L Notredame, C Hochedlinger, K Graf, T AF Varas, Florencio Stadtfeld, Matthias De Andres-Aguayo, Luisa Maherali, Nimet di Tullio, Alessandro Pantano, Lorena Notredame, Cedric Hochedlinger, Konrad Graf, Thomas TI Fibroblast-Derived Induced Pluripotent Stem Cells Show No Common Retroviral Vector Insertions SO STEM CELLS LA English DT Article DE Induced pluripotent stem cells; Retroviral insertions; Cellular reprogramming; Retroviral tagged mouse genes; Insertional mutagenesis ID DEFINED FACTORS; GENERATION; MUTAGENESIS; INDUCTION; PATHWAYS; DNA AB Several laboratories have reported the reprogramming of mouse and human fibroblasts into pluripotent cells, using retroviruses carrying the Oct4, Sox2, Klf4, and c-Myc transcription factor genes. In these experiments the frequency of reprogramming was lower than 0.1% of the infected cells, raising the possibility that additional events are required to induce reprogramming, such as activation of genes triggered by retroviral insertions. We have therefore determined by ligation-mediated polymerase chain reaction (LM-PCR) the retroviral insertion sites in six induced pluripotent stem (iPS) cell clones derived from mouse fibroblasts. Seventy-nine insertion sites were assigned to a single mouse genome location. Thirty-five of these mapped to gene transcription units, whereas 29 insertions landed within 10 kilobases of transcription start sites. No common insertion site was detected among the iPS clones studied. Moreover, bioinformatics analyses revealed no enrichment of a specific gene function, network, or pathway among genes targeted by retroviral insertions. We conclude that Oct4, Sox2, Klf4, and c-Myc are sufficient to promote fibroblast-to-iPS cell reprogramming and propose that the observed low reprogramming frequencies may have alternative explanations. STEM CELLS 2009; 27: 300-306 C1 [Pantano, Lorena; Notredame, Cedric; Graf, Thomas] Ctr Genom Regulat, Bioinformat Program, Barcelona 08003, Spain. [Pantano, Lorena; Notredame, Cedric] Pompeu Fabra Univ, Barcelona, Spain. [Stadtfeld, Matthias; Maherali, Nimet; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Harvard Stem Cell Inst, Boston, MA USA. [Stadtfeld, Matthias; Maherali, Nimet; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Harvard Stem Cell Inst, Boston, MA USA. RP Graf, T (reprint author), Ctr Genom Regulat, Bioinformat Program, C Dr Aiguader 88, Barcelona 08003, Spain. EM khochedlinger@helix.mgh.harvard.edu; thomas.graf@crg.es RI Graf, Thomas/B-4252-2015; Notredame, Cedric/G-3868-2010; OI Graf, Thomas/0000-0003-2774-4117; Notredame, Cedric/0000-0003-1461-0988; Stadtfeld, Matthias/0000-0002-5852-9906 FU Center for Genomic Regulation and ICREA; Fondo de Investigacion Sanitaria-ISCIII; NIH; Harvard Stem Cell Institute; Schering postdoctoral fellowship FX This work was funded by Center for Genomic Regulation and ICREA (to T. G.), as well as by a grant from Fondo de Investigacion Sanitaria-ISCIII (to F. V.). Work was also supported by an NIH Director's Innovator Award and the Harvard Stem Cell Institute (to K. H.). M. S. was supported by a Schering postdoctoral fellowship. NR 21 TC 34 Z9 37 U1 1 U2 3 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 PY 2009 VL 27 IS 2 BP 300 EP 306 DI 10.1634/stemcells.2008-0696 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 412IW UT WOS:000263719500005 PM 19008347 ER PT J AU Sommer, CA Stadtfeld, M Murphy, GJ Hochedlinger, K Kotton, DN Mostoslavsky, G AF Sommer, Cesar A. Stadtfeld, Matthias Murphy, George J. Hochedlinger, Konrad Kotton, Darrell N. Mostoslavsky, Gustavo TI Induced Pluripotent Stem Cell Generation Using a Single Lentiviral Stem Cell Cassette SO STEM CELLS LA English DT Article DE Induced pluripotent stem cells; Stem cell; Reprogramming; Single lentiviral vector; Stem cell cassette ID SOMATIC-CELLS; MOUSE; FIBROBLASTS; EXPRESSION; DIFFERENTIATION; VECTORS; SYSTEM; STATE; MAPS AB Induced pluripotent stem (iPS) cells can be generated using retroviral vectors expressing Oct4, Klf4, Sox2, and cMyc. Most prior studies have required multiple retroviral vectors for reprogramming, resulting in high numbers of genomic integrations in iPS cells and limiting their use for therapeutic applications. Here we describe the use of a single lentiviral vector expressing a "stem cell cassette'' composed of the four transcription factors and a combination of 2A peptide and internal ribosome entry site technology, generating iPS cells from postnatal. broblasts. iPS cells generated in this manner display embryonic stem cell-like morphology, express stem cell markers, and exhibit in vivo pluripotency, as evidenced by their ability to differentiate in teratoma assays and their robust contribution to mouse chimeras. Combining all factors into a single transcript achieves the most efficient reprogramming system to date and allows derivation of iPS cells with a single viral integration. The use of a single lentiviral vector for reprogramming represents a powerful laboratory tool and a significant step toward the application of iPS technology for clinical purposes. STEM CELLS 2009; 27: 543-549 C1 [Mostoslavsky, Gustavo] Boston Univ, Sch Med, Dept Med, Gastroenterol Sect, Boston, MA 02118 USA. [Kotton, Darrell N.] Boston Univ, Ctr Pulm, Boston, MA USA. [Stadtfeld, Matthias; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Stadtfeld, Matthias; Hochedlinger, Konrad] Ctr Regenerat Med, Boston, MA USA. [Murphy, George J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Mostoslavsky, G (reprint author), Boston Univ, Sch Med, Dept Med, Gastroenterol Sect, 650 Albany St X-513, Boston, MA 02118 USA. EM gmostosl@bu.edu RI Sommer, Cesar /H-9187-2013; OI Murphy, George/0000-0003-3464-793X; Kotton, Darrell/0000-0002-9604-8476; Stadtfeld, Matthias/0000-0002-5852-9906 FU NIH Director's Innovator Award; Harvard Stem Cell Institute; Kimmel Foundation; V Foundation; NIH [P01-HL047049-16A1] FX We are grateful to Raul Mostoslavsky for critical reading of the manuscript and technical advice. We thank Alejandro Balazs and Wellington Cardoso for insightful discussions, Andreia Gianotti Sommer and Constantina Christodoulou for technical support, and Linda Neville for administrative assistance. Support to K. H. came from the NIH Director's Innovator Award, the Harvard Stem Cell Institute, the Kimmel Foundation, and the V Foundation. Support to D.N.K. came from NIH Grant P01-HL047049-16A1. NR 24 TC 309 Z9 326 U1 2 U2 39 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 PY 2009 VL 27 IS 3 BP 543 EP 549 DI 10.1634/stemcells.2008-1075 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 426KJ UT WOS:000264706900006 PM 19096035 ER PT J AU Qiu, JH Takagi, Y Harada, J Topalkara, K Wang, YM Sims, JR Zheng, GG Huang, P Ling, Y Scadden, DT Moskowitz, MA Cheng, T AF Qiu, Jianhua Takagi, Yasushi Harada, Jun Topalkara, Kamil Wang, Yumei Sims, John R. Zheng, Guoguang Huang, Paulina Ling, Yun Scadden, David T. Moskowitz, Michael A. Cheng, Tao TI p27(Kip1) Constrains Proliferation of Neural Progenitor Cells in Adult Brain Under Homeostatic and Ischemic Conditions SO STEM CELLS LA English DT Article DE Neural progenitor cells; Cell cycle; p27; Ischemia; Adult brain ID STEM-CELLS; DENTATE GYRUS; SUBVENTRICULAR ZONE; CYCLE INHIBITORS; MICE LACKING; G(1) PHASE; NEUROGENESIS; QUIESCENCE; INJURY; FGF-2 AB Cell cycle inhibition of neural stem and progenitor cells is critical for maintaining the stability of central nervous system in adults, but it may represent a significant hurdle for neural regeneration after injury. We have previously demonstrated that the cyclin-dependent kinase inhibitor (CKI) p21(cip1/waf1) (p21) maintains the quiescence of neural stem-like cells under cerebral ischemia, as similarly shown for the hematopoietic stem cells. Here, we report the distinct role of another CKI member, p27 kip1 (p27) in neural progenitor cells (NPCs) from adult brain (subventricular zone and hippocampal subgranular zone) under both homeostatic and ischemic conditions. The basal level of NPC proliferation in the p27-/- mice was higher than that in p27+/+ mice. Upon ischemia, the overall proliferation of NPCs continued to be higher in p27-/- mice than that in p27+/+ mice. Moreover, the increase of NPC proliferation in p27-/- mice remained until 2 weeks after ischemia, whereas it resumed back to the basal level in p27+/+ mice. As a result, newly generated neuronal cells in the granular layer of p27-/- brain were more abundant compared with p27+/+ controls. These new data demonstrate that p27 functions as a distinct inhibitor for NPC proliferation under homeostatic as well as ischemic conditions. STEM CELLS 2009;27:920-927 C1 [Huang, Paulina; Ling, Yun; Cheng, Tao] Univ Pittsburgh, Sch Med, Dept Radiat Oncol, Pittsburgh, PA USA. [Qiu, Jianhua; Takagi, Yasushi; Harada, Jun; Topalkara, Kamil; Wang, Yumei; Sims, John R.; Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Sch Med,Dept Radiol & Neurol, Boston, MA 02129 USA. [Zheng, Guoguang; Cheng, Tao] Peking Union Med Coll, State Key Lab Expt Hematol, Tianjin, Peoples R China. [Zheng, Guoguang; Cheng, Tao] Chinese Acad Med Sci, Inst Hematol, Tianjin, Peoples R China. [Zheng, Guoguang; Cheng, Tao] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China. [Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Ctr Regenerat Med, Sch Med,Harvard Stem Cell Inst, Boston, MA 02129 USA. [Huang, Paulina; Ling, Yun; Cheng, Tao] Univ Pittsburgh, Inst Canc, Canc Stem Cell Program, Pittsburgh, PA USA. RP Qiu, JH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Sch Med,Dept Radiol & Neurol, Boston, MA 02129 USA. EM jqiu@partners.org; chengt588@gmail.com FU American Heart Association [N0335154]; NIH [P50 NS10828, K08 NS049241, P30 NS045776]; Massachusetts General Hospital Neuroscience Center Core Facility [HL070561]; Ministry of Education, Science Research Funds of Tianjin [07JCZDJC10600]; Natural Science Foundation of China [30825017] FX This work was supported by American Heart Association (N0335154 to J.Q.), NIH (Grants P50 NS10828 to M.A.M., K08 NS049241 to J. R. S), NIH (Grant P30 NS045776) (Massachusetts General Hospital Neuroscience Center Core Facility), HL070561, ChangJiang Scholarship from the Ministry of Education, Science Research Funds of Tianjin (07JCZDJC10600) and Outstanding Young Scholar Award (30825017) from the Natural Science Foundation of China (to T.C.). We thank Masaki Nishimura and Igor Bagayev for their excellent technical assistance. NR 42 TC 26 Z9 26 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2009 VL 27 IS 4 BP 920 EP 927 DI 10.1002/stem.1 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 438AX UT WOS:000265529400020 PM 19353520 ER PT J AU Fliedner, TM Chao, NJ Bader, JL Boettger, A Case, C Chute, J Confer, DL Ganser, A Gorin, NC Gourmelon, P Graessle, DH Krawisz, R Meineke, V Niederwieser, D Port, M Powles, R Sirohi, B Weinstock, DM Wiley, A Coleman, CN AF Fliedner, Theodor M. Chao, Nelson J. Bader, Judith L. Boettger, Axel Case, Cullen, Jr. Chute, John Confer, Dennis L. Ganser, Arnold Gorin, Norbert-Claude Gourmelon, Patrick Graessle, Dieter H. Krawisz, Robert Meineke, Viktor Niederwieser, Dietger Port, Matthias Powles, Ray Sirohi, Bhawna Weinstock, David M. Wiley, Albert Coleman, C. Norman TI Stem Cells, Multiorgan Failure in Radiation Emergency Medical Preparedness: A US/European Consultation Workshop SO STEM CELLS LA English DT Article DE Hemopoietic growth factor; Irradiation; Stem cell transplantation; Stem cell-microenvironment interactions ID HEMATOPOIETIC STEM; NUCLEAR EVENTS; HUMAN EMBRYO; NICHE; BLOOD; MANAGEMENT; EXPOSURE; CONSEQUENCES; RESPONSES; SEVERITY AB The concern of the public regarding terrorist actions involving nuclear emergencies resulted in the reopening of the discussion regarding the best ways to cope with the inevitable health impairments. Medical experts from the US and from Europe considered it of importance to harmonize at an international level the diagnostic and therapeutic approaches regarding the radiation-induced health impairments. The present contribution is the result of the first U.S./European Consultation Workshop addressing approaches to radiation emergency preparedness and assistance, which was held recently at Ulm University, Ulm, Germany. Discussions dealt with the assessment of the extent of damage after total body exposure and, in particular, the quantity and quality of the damage to the hematopoietic stem cell pool. Secondly, the pathogenesis of the multiorgan failure was considered because of the organ-to-organ interactions. Thirdly, approaches were considered to harmonize the "triage-methods'' used on an international level using the "Response Category'' approach as developed for the European Communities. These discussions lead to the conclusion that there is a strong need for continuing education of physicians, nurses, and support personnel to address the issues posed by the management of patients suffering from radiation syndromes. Finally, the discussions expressed the need for more international cooperation in research and development of more refined methods to treat patients with any type of radiation syndromes. STEM CELLS 2009;27:1205-1211 C1 [Chao, Nelson J.; Chute, John] Duke Univ, Div Cellular Therapy, Dept Med, RadCCORE Radiat Countermeasures Ctr Res Excellenc, Durham, NC 27710 USA. [Fliedner, Theodor M.; Graessle, Dieter H.] Univ Ulm, Radiat Med Res Grp, D-89069 Ulm, Germany. [Bader, Judith L.; Coleman, C. Norman] NCI, NIH, Bethesda, MD 20892 USA. [Bader, Judith L.; Coleman, C. Norman] Off Assistant Secretary Preparedness & Response, Dept Hlth & Human Serv, Washington, DC USA. [Boettger, Axel] Fed Minist Environm Nat Protect & Nucl Safety, Dept Radiat Protect, Bonn, Germany. [Case, Cullen, Jr.; Confer, Dennis L.] NMDP, Minneapolis, MN USA. [Ganser, Arnold; Port, Matthias] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, D-3000 Hannover, Germany. [Gorin, Norbert-Claude] Hosp St Antoine, Dept Hematol & Cell Therapy, Paris, France. [Gourmelon, Patrick] IRSN, Fontenay Aux Roses, France. [Krawisz, Robert] Amer Soc Blood & Marrow Transplantat, Arlington Hts, IL USA. [Meineke, Viktor] Bundeswehr Inst Radiobiol, Munich, Germany. [Niederwieser, Dietger] Univ Leipzig, Dept Hematol & Oncol, Leipzig, Germany. [Powles, Ray] Parkside Oncol Clin, London, England. [Sirohi, Bhawna] Addenbrookes Hosp, Dept Med Oncol, Cambridge, England. [Weinstock, David M.] DFCI, Div Hematol Neoplasia, Boston, MA USA. [Wiley, Albert] Radiat Emergency Assistance Ctr Training Site, Oak Ridge, TN USA. RP Chao, NJ (reprint author), Duke Univ, Div Cellular Therapy, Dept Med, RadCCORE Radiat Countermeasures Ctr Res Excellenc, 2400 Pratt St,Suite 9100, Durham, NC 27710 USA. EM Chao0002@mc.duke.edu RI Port, Matthias/D-5230-2011 FU NIAID NIH HHS [U19 AI067798, U19 AI067798-07] NR 38 TC 23 Z9 23 U1 0 U2 3 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 PY 2009 VL 27 IS 5 BP 1205 EP 1211 DI 10.1002/stem.16 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 447GL UT WOS:000266179500023 PM 19418462 ER PT J AU Herve, D Godin, O Dufouil, C Viswanathan, A Jouvent, E Pachai, C Guichard, JP Bousser, MG Dichgans, M Chabriat, H AF Herve, Dominique Godin, Ophelia Dufouil, Carole Viswanathan, Anand Jouvent, Eric Pachai, Chahin Guichard, Jean-Pierre Bousser, Marie-Germaine Dichgans, Martin Chabriat, Hugues TI Three-Dimensional MRI Analysis of Individual Volume of Lacunes in CADASIL SO STROKE LA English DT Article DE CADASIL; cerebral lacunes; MRI ID AUTOSOMAL-DOMINANT ARTERIOPATHY; SUBCORTICAL INFARCTS; LEUKOENCEPHALOPATHY; ARTERIES; LESIONS AB Background and Purpose-Three-dimensional MRI segmentation may be useful to better understand the physiopathology of lacunar infarctions. Using this technique, the distribution of lacunar infarctions volumes has been recently reported in patients with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Whether the volume of each lacune (individual lacunar volume [ILV]) is associated with the patients' other MRI lesions or vascular risk factors has never been investigated. The purpose of this study was to study the impact of age, vascular risk factors, and MRI markers on the ILV in a large cohort of patients with CADASIL. Methods-Of 113 patients with CADASIL, 1568 lacunes were detected and ILV was estimated after automatic segmentation on 3-dimensional T1-weighted imaging. Relationships between ILV and age, blood pressure, cholesterol, diabetes, white matter hyperintensities load, number of cerebral microbleeds, apparent diffusion coefficient, brain parenchymal fraction, and mean and median of distribution of lacunes volumes at the patient level were investigated. We used random effect models to take into account intraindividual correlations. Results-The ILV varied from 4.28 to 1619 mm(3). ILV was not significantly correlated with age, vascular risk factors, or different MRI markers (white matter hyperintensity volume, cerebral microbleed number, mean apparent diffusion coefficient or brain parenchymal fraction). In contrast, ILV was positively correlated with the patients' mean and median of lacunar volume distribution (P=0.0001). Conclusions-These results suggest that the ILV is not related to the associated cerebral lesions or to vascular risk factors in CADASIL, but that an individual predisposition may explain predominating small or predominating large lacunes among patients. Local anatomic factors or genetic factors may be involved in these variations. (Stroke. 2009;40:124-128.) C1 [Herve, Dominique; Jouvent, Eric; Bousser, Marie-Germaine; Chabriat, Hugues] Univ Paris 07, Hop Lariboisiere, Dept Neurol, F-75010 Paris, France. [Godin, Ophelia; Dufouil, Carole] Hop La Pitie Salpetriere, INSERM, U708, Paris, France. [Viswanathan, Anand] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Viswanathan, Anand] Massachusetts Gen Hosp, Clin Trials Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Jouvent, Eric; Chabriat, Hugues] Fac Med Lariboisiere, INSERM, U740, Paris, France. [Pachai, Chahin] Bioimaging Technol Inc, Lyon, France. [Guichard, Jean-Pierre] Univ Paris 07, Hop Lariboisiere, Dept Neuroradiol, F-75010 Paris, France. [Dichgans, Martin] Univ Munich, Klinikum Grosshadern, Dept Neurol, Munich, Germany. RP Chabriat, H (reprint author), Univ Paris 07, Hop Lariboisiere, Dept Neurol, 2 Rue Ambroise Pare, F-75010 Paris, France. EM hugues.chabriat@lrb.aphp.fr RI Dufouil, Carole/J-4968-2012; Jouvent, Eric/B-4320-2014; Chabriat, Hugues/G-5699-2010 OI Jouvent, Eric/0000-0001-7797-2236; Chabriat, Hugues/0000-0001-8436-6074 FU NINDS NIH HHS [T32 NS048005, T32 NS048005-08] NR 20 TC 10 Z9 12 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2009 VL 40 IS 1 BP 124 EP 128 DI 10.1161/STROKEAHA.108.520825 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 388ZN UT WOS:000262059400023 PM 18948610 ER PT J AU Goldmakher, GV Camargo, ECS Furie, KL Singhal, AB Roccatagliata, L Halpern, EF Chou, MJ Biagini, T Smith, WS Harris, GJ Dillon, WP Gonzalez, RG Koroshetz, WJ Lev, MH AF Goldmakher, Gregory V. Camargo, Erica C. S. Furie, Karen L. Singhal, Aneesh B. Roccatagliata, Luca Halpern, Elkan F. Chou, Maggie J. Biagini, Trese Smith, Wade S. Harris, Gordon J. Dillon, William P. Gonzalez, R. Gilberto Koroshetz, Walter J. Lev, Michael H. TI Hyperdense Basilar Artery Sign on Unenhanced CT Predicts Thrombus and Outcome in Acute Posterior Circulation Stroke SO STROKE LA English DT Article DE acute stroke; brain imaging; computed tomography; prognosis; vertebrobasilar ID ACUTE ISCHEMIC-STROKE; INTRAARTERIAL THROMBOLYSIS; CEREBRAL-ARTERY; ANGIOGRAPHY; OCCLUSION; TRIAL AB Background and Purpose-In acute stroke patients, the presence of a hyperdense middle cerebral artery sign on unenhanced CT is a specific but insensitive indicator of acute thrombosis. Our purpose was to determine whether the hyperdense basilar artery (HDBA) sign has utility in detecting thrombosis and predicting outcome in patients presenting with signs and symptoms of posterior circulation stroke. Methods-Unenhanced CT scans obtained within 24 hours of symptom onset in 95 patients with suspected posterior circulation stroke were reviewed. Three neuroimagers blinded to clinical outcome and results of the concurrent CT angiography (which served as the reference standard) rated presence of HDBA sign on a 5-point scale for level of certainty (1=definitely absent; 5=definitely present). Receiver operating characteristic curve analysis was performed. Short-term outcome was measured by discharge National Institute of Health Stroke Scale (NIHSS) scores; long-term outcome was measured by 6-month modified Rankin score (dichotomized, poor outcome defined as modified Rankin score >2). The following variables were correlated with short-term and long-term outcome by univariate analysis: HDBA sign, age, sex, time from stroke onset to imaging, admission NIHSS, history of stroke/TIA, atrial fibrillation, coronary artery disease, hypertension, diabetes, hypercholesterolemia, tobacco use, and thrombolysis. Variables showing correlation with P<0.1 were included in multiple regression analysis. Results-Using a level of certainty cutoff score of >= 4 (probable, definite), HDBA sign had 71% sensitivity, 98% specificity, 94% accuracy, 83% positive predictive value, and 95% negative predictive value for basilar artery occlusion. In univariate analysis, factors significantly correlated with discharge NIHSS were: admission NIHSS (P<0.0001; r=0.77), HDBA sign (P=0.01), and diabetes (P=0.02). Factors showing significant correlation or association with poor long-term outcome were age (P=0.02), admission NIHSS (P=0.007), HDBA sign (P=0.02), and history of stroke or TIA (P=0.007). The odds ratio of HDBA sign for predicting poor long-term outcome was 5.3 (95% CI, 1.1-33.3). In multiple regression analysis, the only independent predictors of discharge NIHSS were admission NIHSS (P<0.0001) and HDBA sign (P=0.004). Significant independent predictors of poor long-term outcome were age (P=0.02), admission NIHSS (P=0.008), history of stroke/TIA (P=0.03), and HDBA sign (P=0.05). Conclusion-In patients presenting with a high pretest probability of posterior circulation stroke based on clinical symptoms, the presence of the HDBA sign on unenhanced CT is a strong predictor of basilar artery thrombosis, and both short- and long-term outcome. (Stroke. 2009;40;134-139.) C1 [Camargo, Erica C. S.] Massachusetts Gen Hosp, Dept Neurol, MGH Stroke Res Ctr, Boston, MA 02114 USA. [Goldmakher, Gregory V.; Roccatagliata, Luca; Halpern, Elkan F.; Harris, Gordon J.; Gonzalez, R. Gilberto; Lev, Michael H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Biagini, Trese; Smith, Wade S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Dillon, William P.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. RP Goldmakher, GV (reprint author), Massachusetts Gen Hosp, Dept Neurol, MGH Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM ecamargo@partners.org FU National Institutes of Health [AHRQ RO1 HS11392] FX This work was supported by National Institutes of Health grant AHRQ RO1 HS11392 (PI-Karen Furie, MD). NR 16 TC 45 Z9 48 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2009 VL 40 IS 1 BP 134 EP 139 DI 10.1161/STROKEAHA.108.516690 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 388ZN UT WOS:000262059400025 PM 19038918 ER PT J AU Ay, H Arsava, EM Johnston, SC Vangel, M Schwamm, LH Furie, KL Koroshetz, WJ Sorensen, AG AF Ay, Hakan Arsava, E. Murat Johnston, S. Claiborne Vangel, Mark Schwamm, Lee H. Furie, Karen L. Koroshetz, Walter J. Sorensen, A. Gregory TI Clinical- and Imaging-Based Prediction of Stroke Risk After Transient Ischemic Attack The CIP Model SO STROKE LA English DT Article DE diffusion-weighted imaging; stroke risk; transient ischemic attack ID DIFFUSION-WEIGHTED MRI; MINOR STROKE; TIA PATIENTS; ABCD SCORE; EMERGENCY; PREVALENCE; LESIONS; VALIDATION AB Background and Purpose-Predictive instruments based on clinical features for early stroke risk after transient ischemic attack suffer from limited specificity. We sought to combine imaging and clinical features to improve predictions for 7-day stroke risk after transient ischemic attack. Methods-We studied 601 consecutive patients with transient ischemic attack who had MRI within 24 hours of symptom onset. A logistic regression model was developed using stroke within 7 days as the response criterion and diffusion-weighted imaging findings and dichotomized ABCD(2) score (ABCD(2) >= 4) as covariates. Results-Subsequent stroke occurred in 25 patients (5.2%). Dichotomized ABCD(2) score and acute infarct on diffusion-weighted imaging were each independent predictors of stroke risk. The 7-day risk was 0.0% with no predictor, 2.0% with ABCD(2) score >= 4 alone, 4.9% with acute infarct on diffusion-weighted imaging alone, and 14.9% with both predictors (an automated calculator is available at http://cip. martinos. org). Adding imaging increased the area under the receiver operating characteristic curve from 0.66 (95% CI, 0.57 to 0.76) using the ABCD(2) score to 0.81 (95% CI, 0.74 to 0.88; P = 0.003). The sensitivity of 80% on the receiver operating characteristic curve corresponded to a specificity of 73% for the CIP model and 47% for the ABCD(2) score. Conclusions-Combining acute imaging findings with clinical transient ischemic attack features causes a dramatic boost in the accuracy of predictions with clinical features alone for early risk of stroke after transient ischemic attack. If validated in relevant clinical settings, risk stratification by the CIP model may assist in early implementation of therapeutic measures and effective use of hospital resources. (Stroke. 2009; 40: 181-186.) C1 [Ay, Hakan; Schwamm, Lee H.; Furie, Karen L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, Charlestown, MA 02129 USA. [Ay, Hakan; Arsava, E. Murat; Vangel, Mark; Sorensen, A. Gregory] Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA 02129 USA. [Johnston, S. Claiborne] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Johnston, S. Claiborne] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Koroshetz, Walter J.] NINDS, NIH, Bethesda, MD USA. RP Ay, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM hay@partners.org RI Arsava, Ethem Murat/I-9197-2013; OI Arsava, Ethem Murat/0000-0002-6527-4139; Schwamm, Lee/0000-0003-0592-9145 FU NIH [R01-NS38477-04, P41-RR14075]; [USPHSNS38477] FX This work was supported by USPHSNS38477 and NIH grants R01-NS38477-04 and P41-RR14075. NR 34 TC 78 Z9 91 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2009 VL 40 IS 1 BP 181 EP 186 DI 10.1161/STROKEAHA.108.521476 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 388ZN UT WOS:000262059400032 PM 18948609 ER PT J AU Sandman, E Bierer, M Marable, D Quinlan, J Kane, M AF Sandman, E. Bierer, M. Marable, D. Quinlan, J. Kane, M. TI Buprenorphine Treatment in Primary Care SO SUBSTANCE ABUSE LA English DT Meeting Abstract C1 [Sandman, E.; Bierer, M.; Marable, D.; Quinlan, J.; Kane, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PY 2009 VL 30 IS 2 BP 209 EP 210 PG 2 WC Substance Abuse SC Substance Abuse GA 668WZ UT WOS:000283306600045 ER PT J AU Kamholz, B Gulliver, SB Helstrom, A Morissette, S AF Kamholz, Barbara W. Gulliver, Suzy Bird Helstrom, Amy Morissette, Sandra B. TI Implications of Participant Self-Selection for Generalizability: Who Participates in Smoking Laboratory Research? SO SUBSTANCE USE & MISUSE LA English DT Article DE smoking cessation; generalizability; participant eligibility ID CESSATION TREATMENT; EXCLUSION CRITERIA; ADOLESCENT SMOKING; CIGARETTE-SMOKING; CLINICAL-TRIAL; NON-JOINERS; SMOKERS; ATTRITION; PROGRAM; DEPENDENCE AB The generalizability of data from laboratory smoking studies using volunteer samples is debatable. We tracked potential participants from first contact with research staff through screening to study completion. We found that a minority of individuals were ultimately enrolled in the study. Failure to enroll was as often a function of participant lack of attendance at the laboratory as a function of ineligibility. With some exceptions, groups of potential participants were similar regarding demographic characteristics and substance use history. These findings support the generalizability of the sample and highlight the importance of documenting details of study eligibility and participation. The study's limitations are noted. C1 [Kamholz, Barbara W.] Boston Univ, Mood Disorders Clin, Boston, MA 02215 USA. [Kamholz, Barbara W.] VA Boston Healthcare Syst, Mental Hlth Outpatient Serv, Boston, MA USA. [Gulliver, Suzy Bird] Texas A&M Univ, Coll Med, College Stn, TX 77843 USA. [Gulliver, Suzy Bird] Vet Integrated Serv Network, Ctr Excellence Res Returning War Vet 17, Waco, TX USA. [Helstrom, Amy] Boston Univ, Sch Med, Boston, MA 02215 USA. [Morissette, Sandra B.] VA Boston Healthcare System, Integrated Primary Care Mental Hlth Program, Boston, MA USA. [Morissette, Sandra B.] VA Boston Healthcare System, Cognit Behav Therapy Anxiety Disorders Clin, Boston, MA USA. RP Kamholz, B (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B, 150 S Huntington Ave, Jamaica Plain, MA 02130 USA. EM barbara.kamholz2@va.gov NR 43 TC 2 Z9 2 U1 4 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2009 VL 44 IS 3 BP 343 EP 356 AR PII 908657700 DI 10.1080/10826080802345051 PG 14 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 406JW UT WOS:000263291800004 PM 19212926 ER PT J AU Primack, BA Kraemer, KL Fine, MJ Dalton, MA AF Primack, Brian A. Kraemer, Kevin L. Fine, Michael J. Dalton, Madeline A. TI Media Exposure and Marijuana and Alcohol Use Among Adolescents SO SUBSTANCE USE & MISUSE LA English DT Article DE alcohol; marijuana; mass media; entertainment media; adolescence; music; movies; television; video games; books ID RATED VIDEO GAMES; CANNABIS USE; SMOKING INITIATION; CIGARETTE-SMOKING; RISK; ASSOCIATION; TELEVISION; DRINKING; HEALTH; MUSIC AB We aimed to determine which media exposures are most strongly associated with marijuana and alcohol use among adolescents. In 2004, we surveyed 1,211 students at a large high school in suburban Pittsburgh regarding substance use, exposure to entertainment media, and covariates. Of the respondents, 52% were female, 8% were non-White, 27% reported smoking marijuana, and 60% reported using alcohol. They reported average exposure to 8.6 hr of media daily. In adjusted models, exposure to music was independently associated with marijuana use, but exposure to movies was independently associated with alcohol use. Implications, limitations, and suggestions for further research are discussed. C1 [Primack, Brian A.; Kraemer, Kevin L.; Fine, Michael J.] Univ Pittsburgh, Ctr Res Hlth Care, Sch Med, Pittsburgh, PA 15213 USA. [Primack, Brian A.; Kraemer, Kevin L.; Fine, Michael J.] Univ Pittsburgh, Div Gen Internal Med, Dept Med, Sch Med, Pittsburgh, PA 15213 USA. [Primack, Brian A.] Univ Pittsburgh, Div Adolescent Med, Dept Pediat, Sch Med, Pittsburgh, PA 15213 USA. [Fine, Michael J.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Fine, Michael J.] VA Hlth Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Dalton, Madeline A.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pediat, Hanover, NH 03756 USA. [Dalton, Madeline A.] Dartmouth Med Sch, Community Hlth Res Program, Hood Ctr Children & Families, Hanover, NH USA. RP Primack, BA (reprint author), Univ Pittsburgh, Ctr Res Hlth Care, Sch Med, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM bprimack@pitt.edu FU NCI NIH HHS [K07 CA114315, K07 CA114315-03]; NIAID NIH HHS [K24 AI001769] NR 58 TC 13 Z9 13 U1 3 U2 24 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2009 VL 44 IS 5 BP 722 EP 739 AR PII 909746983 DI 10.1080/10826080802490097 PG 18 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 434WK UT WOS:000265304600009 PM 19306219 ER PT J AU Harris, AHS Bryson, CL Sun, HL Blough, D Bradley, KA AF Harris, Alex H. S. Bryson, Chris L. Sun, Haili Blough, David Bradley, Katharine A. TI Alcohol Screening Scores Predict Risk of Subsequent Fractures SO SUBSTANCE USE & MISUSE LA English DT Article DE alcohol misuse; alcohol screening; fractures; risk factors; clinical markers ID PRIMARY-CARE PATIENTS; BONE-MINERAL DENSITY; HIP FRACTURE; HEALTH-STATUS; SELF-REPORTS; MEN; CONSUMPTION; OSTEOPOROSIS; MORTALITY; WOMEN AB The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C; 0-12 points) was included on health surveys in a cohort (if 32,622 general medicine outpatients from seven US Department of Veterans Affairs (VA) hospitals. Cox proportional hazards models were used to estimate the risk of fracture (mean follow-up = 1.6 years) by AUDIT-C category After adjusting for confounders, AUDIT-C scores of 8-9 and 10-12 were associated with significantly increased risks for subsequent fractures, HR (95% CI) = 1.37 (1.03 to 1.83) and 1.79 (1.38 to 2.33) respectively. These results can be used to provide feedback to patients linking their alcohol screening scores to medical outcomes-a critical component of evidence-based brief counseling for alcohol misuse. The study's limitations are noted. C1 [Harris, Alex H. S.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat MC152, Menlo Pk, CA 94025 USA. [Bryson, Chris L.; Sun, Haili; Blough, David; Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Harris, AHS (reprint author), VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat MC152, 795 Willow Rd, Menlo Pk, CA 94025 USA. EM Alexander.Harris2@va.gov NR 39 TC 20 Z9 20 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2009 VL 44 IS 8 BP 1055 EP 1069 DI 10.1080/10826080802485972 PG 15 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 478JA UT WOS:000268582500001 PM 19544147 ER PT J AU Miller, CS Woodson, J Howell, RT Shields, AL AF Miller, Christopher S. Woodson, Joshua Howell, Ryan T. Shields, Alan L. TI Assessing the Reliability of Scores Produced by the Substance Abuse Subtle Screening Inventory SO SUBSTANCE USE & MISUSE LA English DT Article DE The Substance Abuse Subtle Screening Inventory (SASSI); substance abuse scales; reliability induction; reliability generalization; meta-analysis ID PSYCHOMETRIC PROPERTIES; PSYCHOLOGY; ALCOHOL; SCALES; DISORDERS; JOURNALS AB The Substance Abuse Subtle Screening Inventory (SASSI) is a 10 scale indirect screening instrument used to detect substance use disorders. The current meta-analytic study described reliability reporting practices across 48 studies involving the SASSI. Reliability generalization methods were then employed to evaluate typical score reliability for the screening measure. Results showed approximately 73% of studies did not report reliability estimates. Analysis of data from the remaining studies revealed adequate reliability for the total scale (alpha = .87) and face valid, scales (FVA alpha = .88 and FVOD alpha = .92), but substantially lower reliability estimates for the indirect scales (range of alpha = .23-65). The study's findings underscore the need for improved reliability reporting for the SASSI and suggest cautious use of the measure, especially its indirect scales, as an indicator of problematic substance use/abuse in clinical settings. C1 [Miller, Christopher S.] VA Puget Sound Hlth Care Syst, Ctr Polytrauma Care, Seattle, WA 98101 USA. [Woodson, Joshua] E Tennessee State Univ, Johnson City, TN 37614 USA. [Howell, Ryan T.] San Francisco State Univ, San Francisco, CA 94132 USA. [Shields, Alan L.] Harvard Univ, E Tennessee State Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. [Miller, Christopher S.; Shields, Alan L.] PRO Consulting, Pittsburgh, PA USA. RP Miller, CS (reprint author), VA Puget Sound Hlth Care Syst, Ctr Polytrauma Care, 1600 S Columbian Way, Seattle, WA 98101 USA. EM Christopher.Miller7@va.gov NR 40 TC 3 Z9 3 U1 3 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2009 VL 44 IS 8 BP 1090 EP 1100 DI 10.1080/10826080802486772 PG 11 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 478JA UT WOS:000268582500003 PM 19544146 ER PT J AU Stuart, GL O'Farrell, TJ Temple, JR AF Stuart, Gregory L. O'Farrell, Timothy J. Temple, Jeff R. TI Review of the Association Between Treatment for Substance Misuse and Reductions in Intimate Partner Violence SO SUBSTANCE USE & MISUSE LA English DT Review DE intimate partner violence; substance misuse; treatment; behavioral couples therapy ID MALE ALCOHOLIC PATIENTS; BEHAVIORAL COUPLES THERAPY; DOMESTIC VIOLENCE; MARITAL VIOLENCE; PHYSICAL AGGRESSION; ABUSE TREATMENT; RISK-FACTORS; INTERVENTION PROGRAMS; HUSBAND VIOLENCE; NEWLYWED COUPLES AB A substantial body of research supports a strong cross-sectional and longitudinal association between substance misuse and perpetration of intimate partner violence (W). This article briefly addresses the theoretical connection between substance use and intimate partner violence and research on the association between substance misuse and IPV Studies examining the effect of individual and couples-based addiction treatments on IPV are reviewed. The implications of this work and future directions for research are. discussed. C1 [Stuart, Gregory L.] Univ Tennessee, Dept Psychol, Knoxville, TN 37996 USA. [O'Farrell, Timothy J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [O'Farrell, Timothy J.] VA Boston Healthcare Syst, Boston, MA USA. [Temple, Jeff R.] Univ Texas Med Branch Galveston, Galveston, TX USA. RP Stuart, GL (reprint author), Univ Tennessee, Dept Psychol, Austin Peay Bldg, Knoxville, TN 37996 USA. EM gstuart@utk.edu RI Temple, Jeff/A-7666-2009 OI Temple, Jeff/0000-0003-3193-0510 FU National Institute on Alcohol Abuse and Alcoholism [R01AA016315, R01AA014193]; National Institute oil Alcohol Abuse and Alcoholism [R01AA14700, R01AA12834]; National Institute on Drug Abuse [R01DA15156]; Department of Veterans Affairs; Building Interdisciplinary Research Careers in Women's Health Program-BIRCWH [K12HD052023]; National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Child Health and Human Development (NICHD); Office of the Director (OD); National Institutes of Health FX Dr. Stuart is supported, in part, by grants R01AA016315 and R01AA014193 from the National Institute on Alcohol Abuse and Alcoholism. Dr. O'Farrell is supported by grants from the National Institute oil Alcohol Abuse and Alcoholism (R01AA14700, R01AA12834), the National Institute on Drug Abuse (R01DA15156), and by the Department of Veterans Affairs. Dr. Temple is supported by a research career development award (K12HD052023: Building Interdisciplinary Research Careers in Women's Health Program-BIRCWH) from the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Child Health and Human Development (NICHD), and the Office of the Director (OD), National Institutes of Health. NR 120 TC 51 Z9 53 U1 5 U2 16 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2009 VL 44 IS 9-10 BP 1298 EP 1317 DI 10.1080/10826080902961385 PG 20 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 506MH UT WOS:000270778400007 PM 19938919 ER PT J AU Temple, JR Stuart, GL O'Farrell, TJ AF Temple, Jeff R. Stuart, Gregory L. O'Farrell, Timothy J. TI Prevention of Intimate Partner Violence in Substance-Using Populations SO SUBSTANCE USE & MISUSE LA English DT Article DE intimate partner violence; substance misuse; prevention ID MALE ALCOHOLIC PATIENTS; TARGETING LICENSED PREMISES; BEHAVIORAL COUPLES THERAPY; DATING VIOLENCE; DOMESTIC VIOLENCE; MARITAL VIOLENCE; ABUSE TREATMENT; AGGRESSION; WOMEN; DRINKING AB Although the prevention of intimate partner violence is a major public health priority for the United States, little is known about how to prevent this form of violence. The strong cross-sectional and longitudinal association between substance misuse and partner violence suggests that substance-misusing populations may be an ideal audience for implementing partner violence prevention programs. This approach is reviewed from the perspective of universal, selective, and indicated prevention programs. C1 [Temple, Jeff R.] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA. [Stuart, Gregory L.] Univ Tennessee, Knoxville, TN USA. [O'Farrell, Timothy J.] Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Temple, JR (reprint author), Univ Texas Med Branch, Dept Obstet & Gynecol, 301 Univ Blvd, Galveston, TX 77555 USA. EM jetemple@utmb.edu RI Temple, Jeff/A-7666-2009 OI Temple, Jeff/0000-0003-3193-0510 FU Building Interdisciplinary Research Careers in Women's Health Program - BIRCWH [KI2HD052023]; National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Child Health and Human Development (NICHD); Office of the Director (OD); National Institutes of Health; National Institute on Alcohol Abuse and Alcoholism [R01AA016315, R01AA014193, R01AA14700, R01AA12834]; National Institute on Drug Abuse [R01DA15156]; Department of Veterans Affairs FX Dr. Temple is supported by a research career development award (KI2HD052023: Building Interdisciplinary Research Careers in Women's Health Program - BIRCWH) from the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Child Health and Human Development (NICHD), and the Office of the Director (OD), National Institutes of Health. Dr. Stuart is Supported,, in part, by grants R01AA016315 and R01AA014193 from the National Institute on Alcohol Abuse and Alcoholism. Dr. O'Farrell is supported by grants from the National Institute on Alcohol Abuse and Alcoholism (R01AA14700, R01AA12834), the National Institute on Drug Abuse (R01DA15156), and by the Department of Veterans Affairs. NR 67 TC 9 Z9 9 U1 3 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2009 VL 44 IS 9-10 BP 1318 EP 1328 DI 10.1080/10826080902961377 PG 11 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 506MH UT WOS:000270778400008 PM 19938920 ER PT J AU Wagner, KD Brief, DJ Vielhauer, MJ Sussman, S Keane, TM Malow, R AF Wagner, Karla D. Brief, Deborah J. Vielhauer, Melanie J. Sussman, Steve Keane, Terence M. Malow, Robert TI The Potential for PTSD, Substance Use, and HIV Risk Behavior among Adolescents Exposed to Hurricane Katrina SO SUBSTANCE USE & MISUSE LA English DT Article DE adolescents; natural disaster; post-traumatic stress disorders; HIV; substance use ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; NATIONAL-COMORBIDITY-SURVEY; NATURAL DISASTER; PSYCHIATRIC COMORBIDITY; MAJOR DEPRESSION; TRAUMATIC EVENTS; COMMUNITY SAMPLE; MENTAL-ILLNESS; UNITED-STATES AB Adverse psychosocial outcomes can be anticipated among youth exposed to Hurricane Katrina. Adolescents are particularly vulnerable to the consequences of this natural disaster and may suffer lasting consequences in the form of psychological morbidity and the development of negative health behaviors due to their exposure. We review existing literature on the effects of exposure to natural disasters and similar traumas on youth and, where data on youth are unavailable, on adults. The effect of natural disasters is discussed in terms of risk for three negative health outcomes that are of particular concern due to their potential to cause long-term morbidity: post-traumatic stress disorder, substance use disorder, and HIV-risk behavior. Where available, data from studies of the effects of Hurricane Katrina are included. C1 [Malow, Robert] Florida Int Univ, Miami, FL 33199 USA. [Brief, Deborah J.; Vielhauer, Melanie J.; Keane, Terence M.] VA Boston Healthcare Syst, Boston, MA USA. [Brief, Deborah J.; Vielhauer, Melanie J.; Keane, Terence M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Wagner, Karla D.; Sussman, Steve] Univ So Calif, Inst Hlth Promot & Dis Prevent Res, Alhambra, CA USA. RP Malow, R (reprint author), Florida Int Univ, Dept Publ Hlth, AIDS Prevent Program, Biscayne Bay Campus,ACI 278, N Miami, FL 33181 USA. EM r.malow@bellsouth.net FU National Institute on Drug Abuse [R03-DA 21982]; National Center for PTSD FX This work was supported, in part, by a grant from the National Institute on Drug Abuse (Grant # R03-DA 21982) and by the National Center for PTSD. NR 78 TC 11 Z9 12 U1 6 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2009 VL 44 IS 12 BP 1749 EP 1767 DI 10.3109/10826080902963472 PG 19 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 523RU UT WOS:000272093000008 PM 19895305 ER PT J AU Katzburg, JR Yano, EM Washington, DL Farmer, MM Yee, EFT Fu, S Trowell-Harris, I Sherman, SE AF Katzburg, Judith R. Yano, Elizabeth M. Washington, Donna L. Farmer, Melissa M. Yee, Ellen F. T. Fu, Steven Trowell-Harris, Irene Sherman, Scott E. TI Combining Women's Preferences and Expert Advice to Design a Tailored Smoking Cessation Program SO SUBSTANCE USE & MISUSE LA English DT Article DE women veterans; smoking cessation; tailored; consumer focus; expert panel ID VA HEALTH-CARE; GENDER-DIFFERENCES; FEMALE VETERANS; QUIT-SMOKING; TOBACCO; PREDICTORS; THERAPY; INTERVENTION; PREVENTION; DEPENDENCE AB We designed a patient-centered smoking cessation program for women in 2004/2005, incorporating women's preferences and expert opinion. Our four-step process included: (1) concept-development focus groups; (2) an expert panel; (3) concept-testing focus groups, and (4) a pilot study. Data analyses occurred in 2004-2007. The new program offered options: the traditional Veterans Health Administration (VA) male-dominated program was the least selected option in the pilot study. Patients can be effectively involved in program development. The study's implications and limitations are noted. This research (conducted in Los Angeles, California) was funded by the American Legacy Foundation with additional VA support. C1 [Katzburg, Judith R.; Sherman, Scott E.] Vet Affairs Greater Los Angeles HSR & D Ctr Excel, Sepulveda, CA USA. [Katzburg, Judith R.] Univ Calif Los Angeles, Johnson & Johnson Hlth Care Inst, Anderson Sch Management, Los Angeles, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Yano, Elizabeth M.] Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, VA HSR&D, Los Angeles, CA USA. [Washington, Donna L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Yee, Ellen F. T.] New Mexico Vet Affairs Healthcare Syst, Womens Hlth Clin Albuquerque, Albuquerque, NM USA. [Yee, Ellen F. T.] Univ New Mexico, Albuquerque, NM 87131 USA. [Fu, Steven] Minneapolis Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Fu, Steven] Univ Minnesota, Sch Med, TTURC, Minneapolis, MN 55455 USA. [Trowell-Harris, Irene] Ctr Women Vet, Dept VA, Washington, DC USA. [Sherman, Scott E.] NYU, Sch Med, Geriatr Med Sect, New York, NY USA. [Sherman, Scott E.] Vet Affairs New York Harbor Healthcare Sys, New York, NY USA. RP Katzburg, JR (reprint author), Vet Affairs Greater Los Angeles HSR & D Ctr Excel, Sepulveda, CA USA. EM jkatzbur@ucla.edu OI Sherman, Scott/0000-0003-1752-7303 FU Veterans Affairs Greater Los Angeles Healthcare System; VA HSRD Center [012]; American Legacy Foundation; Agency for Healthcare Research FX We gratefully acknowledge the contributions of the following agencies: Veterans Affairs Greater Los Angeles Healthcare System and the VA HSR&D Center for the Study of Healthcare Provider Behavior for additional resources and support (Project # 012), American Legacy Foundation for funding this research project, and the Agency for Healthcare Research and Quality for funding Dr. Katzburg's postdoctoral fellowship which provided support during part of this project. NR 35 TC 6 Z9 6 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2009 VL 44 IS 14 BP 2114 EP 2127 DI 10.3109/10826080902858433 PG 14 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 545PO UT WOS:000273748500010 PM 20001698 ER PT J AU Warshaw, AL Sarr, MG AF Warshaw, Andrew L. Sarr, Michael G. TI Ethics editorial note SO SURGERY LA English DT Editorial Material C1 [Warshaw, Andrew L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,White 506, Boston, MA 02114 USA. EM swilliams7@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JAN PY 2009 VL 145 IS 1 BP 5 EP 5 DI 10.1016/j.surg.2008.09.001 PG 1 WC Surgery SC Surgery GA 386SX UT WOS:000261904000002 ER PT J AU Tohamy, AE Eid, GM AF Tohamy, Aley Eldin Eid, George M. TI Laparoscopic reduction of small bowel intussusception in a 33-week pregnant gastric bypass patient: surgical technique and review of literature SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Article DE Intussusception; Gastric bypass; Pregnancy; Laparoscopy ID RETROGRADE INTUSSUSCEPTION; PREOPERATIVE DIAGNOSIS; ADULT INTUSSUSCEPTION; OBSTRUCTION; MANAGEMENT; PAIN C1 [Tohamy, Aley Eldin; Eid, George M.] Univ Pittsburgh, Med Ctr, Div Minimally Invas Surg, Pittsburgh, PA USA. [Eid, George M.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Eid, GM (reprint author), Magee Womens Hosp, 300 Halket St, Pittsburgh, PA 15213 USA. EM eidgm@upmc.edu NR 22 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-7289 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD JAN-FEB PY 2009 VL 5 IS 1 BP 111 EP 115 DI 10.1016/j.soard.2008.09.008 PG 5 WC Surgery SC Surgery GA 400UW UT WOS:000262895700023 PM 19161938 ER PT B AU Hunt, JL AF Hunt, Jennifer L. BE Khan, A TI Application of Molecular Diagnosis Techniques in the Diagnosis and Management of Endocrine Tumors SO SURGICAL PATHOLOGY OF ENDOCRINE AND NEUROENDOCRINE TUMORS SE Current Clinical Pathology LA English DT Article; Book Chapter DE Papillary carcinoma; Follicular carcinoma; Medullary carcinoma; Multiple endocrine neoplasia syndrome; BRAF mutation; RAS mutation; RET/PTC translocation; RET mutation; Parathyroid adenoma; Parathyroid carcinoma; Hyperparathyroidisim-jaw tumor syndrome; HRPT2 gene; Pituitary adenoma; Carney complex; McCune-Albright syndrome; Adrenal cortical adenoma; Adrenal cortical carcinoma; Beckwith-Wiedemann syndrome; Li-Fraumeni syndrome; Pheochromocytoma; Von Hippel-Lindau syndrome; Neurofibromatosis; Familial paragangliomatosis syndrome ID PAPILLARY THYROID-CARCINOMA; GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS; SECRETING PITUITARY-ADENOMAS; INTERACTING PROTEIN GENE; POORLY DIFFERENTIATED CARCINOMAS; BECKWITH-WIEDEMANN-SYNDROME; RAS ONCOGENE MUTATIONS; BRAF V600E MUTATION; PAX8-PPAR-GAMMA REARRANGEMENT; PARATHYROID CARCINOMA AB Molecular alterations in endocrine tumors can be related to genetic syndromes or can be somatic mutations that are restricted to tumor tissues. Tumors associated with genetic syndromes have been described for all endocrine organs and include medullary thyroid carcinoma, parathyroid tumors, pituitary adenomas, adrenal cortical tumors, and pheochromocytomas. The endocrine syndromes are discussed in detail, with particular attention to mutational analysis. In terms of somatic mutations. the most advanced understanding is for thyroid and parathyroid lesions, where established markers are making their way slowly into clinical practice. Somatic mutations for endocrine tumors are also discussed, with an emphasis on testing that has clinical diagnostic and therapeutic implications. C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Hunt, JL (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, WRN225,55 Fruit St, Boston, MA 02114 USA. EM huntj2@ccf.org NR 131 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-395-4 J9 CURR CLIN PATHOL PY 2009 BP 221 EP 234 DI 10.1007/978-1-60327-396-1_18 D2 10.1007/978-1-60327-396-1 PG 14 WC Endocrinology & Metabolism; Pathology; Surgery SC Endocrinology & Metabolism; Pathology; Surgery GA BLT83 UT WOS:000270996100018 ER PT B AU Marvizon, JC AF Marvizon, Juan Carlos BE Malcangio, M TI Opioidergic Transmission in the Dorsal Horn SO SYNAPTIC PLASTICITY IN PAIN LA English DT Article; Book Chapter ID RAT SPINAL-CORD; ENKEPHALIN-LIKE MATERIAL; FOOTSHOCK-INDUCED ANALGESIA; PRIMARY AFFERENT-FIBERS; PROTEIN-COUPLED RECEPTOR; CENTRAL-NERVOUS-SYSTEM; ROOT GANGLION NEURONS; SUBSTANCE-P RELEASE; METHYL-D-ASPARTATE; ANGIOTENSIN CONVERTING ENZYME AB The potent analgesia produced by opiate drugs is induced, at least in part, in the spinal cord. The three "classical" opioid receptors, mu, delta and kappa, are found in dorsal horn neurons and primary afferent terminals. Dorsal horn neurons expressing opioid receptors are mostly excitatory, and their inhibition by opioids decreases pain intensity. In primary afferents, opioid receptors inhibit the release of the pro-nociceptive neuropeptides substance P and CGRP. The spinal cord also contains "atypical" opioid receptors: the nociceptin receptor, the opioid growth factor receptor and toll-like receptors, which modulate pain in ways still not well understood. Enkephalins and dynorphins are the main opioid peptides in the dorsal horn, and are expressed by different neuronal Populations. Endorphins are not found in the dorsal horn, and recent Studies question whether endomorphins are indeed endogenous. Enkephalins and dynorphins are highly susceptible to peptidase degradation, which has prompted the use of peptidase inhibitors as analgesics. Endogenous peptidase inhibitors with analgesic properties have also been found. Opioid release in the spinal cord is inhibited by several neurotransmitter receptors, including adrenergic alpha(2C) receptors, serotonin 5-HT1A receptors and NMDA receptors. Spinal opioid release appears to be driven by signals originating in both in primary afferents and supraspinally. Pain modality appears to determine whether pain induces spinal opioid release through local or supraspinal circuits. Some forms of stress-induced analgesia are also mediated by spinal opioid release. This involves a circuit originating in the dorsal raphe nucleus involved in the fear/anxiety response. Spinal opioids also mediate the analgesia induced by acupuncture. C1 [Marvizon, Juan Carlos] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis,Ctr Neurobiol Stress, Los Angeles, CA 90095 USA. [Marvizon, Juan Carlos] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Marvizon, JC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis,Ctr Neurobiol Stress, Los Angeles, CA 90095 USA. EM marvizon@ucla.edu NR 232 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0225-2 PY 2009 BP 139 EP 173 DI 10.1007/978-1-4419-0226-9_7 D2 10.1007/978-1-4419-0226-9 PG 35 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BKW58 UT WOS:000269476100007 ER PT J AU Younker, TD Conlay, LA Searle, NS Khan, M Raty, SR Afifi, S Martin, D Zimmerman, B Epps, JL Rinehardt, P Stock, MC Zell, C AF Younker, T. Dirk Conlay, Lydia A. Searle, Nancy S. Khan, Myrna Raty, Sally R. Afifi, Sheriff Martin, Donna Zimmerman, Brian Epps, Jerry L. Rinehardt, Paige Stock, M. Christine Zell, Christopher TI Performance Outcomes in Anesthesiology Residents Completing Categorical (Anesthesia) or Advanced (Nonspecific) Internship Training SO TEACHING AND LEARNING IN MEDICINE LA English DT Article AB Background: The internship or first year (PGY 1) of anesthesiology training may be categorical (within anesthesiology), or obtained in more diverse settings. Revisions recently proposed in the training requirements incorporated the PGY 1 into the existing curriculum. Purposes: We studied whether this change improved measurable outcomes. Methods: There were 518 residents studied retrospectively from four institutions that offered entry following both "Categorical" and "Other" internships. Thus the training in clinical anesthesia was identical. Results: No differences were observed in percentile scores on the Anesthesiology In-Service Training Examination during clinical anesthesia training, the receipt of awards, board certification or time to certification, or in reports of unsatisfactory performance to the American Board of Anesthesiology. "Categorical" residents were more frequently appointed chief resident. Conclusions: Easily accessible performance measures may function as valuable aids in decision making, particularly when significant changes in curricula are contemplated. Data do not support the proposed changes in anesthesiology. C1 [Conlay, Lydia A.] Baylor Coll Med, Michael E Debakey Vet Affairs Med Ctr, Dept Anesthesiol, Houston, TX 77030 USA. [Searle, Nancy S.] Baylor Coll Med, Off Curriculum, Houston, TX 77030 USA. [Khan, Myrna] Houston Ctr Stat Anal, Houston, TX USA. [Afifi, Sheriff; Stock, M. Christine] Northwestern Univ, Feinberg Sch Med, Dept Anesthesiol, Chicago, IL 60611 USA. [Martin, Donna; Zimmerman, Brian] Advocate Illinois Mason Med Ctr, Dept Anesthesiol, Chicago, IL USA. [Epps, Jerry L.; Rinehardt, Paige] Univ Tennessee, Med Ctr, Dept Anesthesiol, Knoxville, TN USA. [Zell, Christopher] NW Med Fac Fdn, Chicago, IL USA. RP Conlay, LA (reprint author), Baylor Coll Med, Michael E Debakey Vet Affairs Med Ctr, Dept Anesthesiol, 2002 Holcombe Blvd 145, Houston, TX 77030 USA. EM lconlay@bcm.edu NR 7 TC 0 Z9 0 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1040-1334 J9 TEACH LEARN MED JI Teach. Learn. Med. PY 2009 VL 21 IS 1 BP 20 EP 23 DI 10.1080/10401330802573878 PG 4 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 425OB UT WOS:000264645900004 PM 19130382 ER PT J AU Sung, AD Collins, ME Smith, AK Sanders, AM Quinn, MA Block, SD Arnold, RM AF Sung, Anthony D. Collins, Molly E. Smith, Alexander K. Sanders, Aimee M. Quinn, Mariah A. Block, Susan D. Arnold, Robert M. TI Crying: Experiences and Attitudes of Third-Year Medical Students and Interns SO TEACHING AND LEARNING IN MEDICINE LA English DT Article ID RESIDENTS; BURNOUT; PATIENT; STRESS; PROFESSIONALISM; ENVIRONMENT; DEPRESSION; CURRICULUM; PHYSICIANS; EDUCATION AB Background: The medical socialization process is emotionally stressful for trainees; anecdotally, crying is a frequent response. Purposes: To understand the experiences and attitudes related to crying among 3rd-year medical students and interns. Methods: Web-based survey distributed to all 3rd-year medical students and interns at two medical schools and affiliated internal medicine residency programs. Results: Participation rates were 208/307 (68%) students and 93/126 (74%) interns. Sixty-nine percent of students and 74% of interns self-reported crying for reasons related to medicine. For both, the most common cause was "burnout." Although there were no significant differences in crying between students and interns (p = .38), twice as many women cried as men (93% vs. 44%, p < .001). Seventy-three percent of students and 68% of interns thought discussion of physicians' crying was inadequate. Conclusions: Crying is common among medical students and interns, especially women. Many consider it unprofessional to cry in front of patients and colleagues. Trainees want more discussions of crying. C1 [Sanders, Aimee M.; Arnold, Robert M.] Univ Pittsburgh, Div Gen Internal Med, Med Ctr, Pittsburgh, PA 15213 USA. [Block, Susan D.] Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Quinn, Mariah A.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Smith, Alexander K.] Beth Israel Deaconess Med Ctr, Div Gen Internal Med & Primary Care, Boston, MA 02215 USA. [Sung, Anthony D.; Collins, Molly E.] Harvard Univ, Sch Med, Boston, MA USA. RP Arnold, RM (reprint author), Univ Pittsburgh, Div Gen Internal Med, Med Ctr, 932 Montefiore Univ Hosp,200 Lothrop St, Pittsburgh, PA 15213 USA. EM rabob+@pitt.edu FU Death in America Faculty Scholars Program; Greenwall Foundation; Ladies Hospital Aid Society of Western Pennsylvania; International Union Against Cancer (UICC); Jewish Health Care Foundation; LAS Trust Foundation; National Research Service [5 T32 HP11001-19.] FX An abstract for this article was presented at the 2007 annual meeting of the Society of General Internal Medicine. Robert M. Arnold was supported by the Project on Death in America Faculty Scholars Program, the Greenwall Foundation, Ladies Hospital Aid Society of Western Pennsylvania, the International Union Against Cancer (UICC) Yamagiwa-Yoshida Memorial International Cancer Study Grant Fellowship, the Jewish Health Care Foundation, and the LAS Trust Foundation. Alexander K. Smith is supported by an institutional National Research Service Award, #5 T32 HP11001-19. These funders have had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the article. NR 45 TC 9 Z9 9 U1 1 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1040-1334 EI 1532-8015 J9 TEACH LEARN MED JI Teach. Learn. Med. PY 2009 VL 21 IS 3 BP 180 EP 187 DI 10.1080/10401330903014111 PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 575MM UT WOS:000276071200002 PM 20183336 ER PT J AU Braunwald, E AF Braunwald, Eugene TI THE THROMBOLYSIS IN MYOCARDIAL INFARCTION (TIMI) STUDY GROUP EXPERIENCE SO TERAPEVTICHESKII ARKHIV LA Russian DT Review DE review; myocardial infarctoin; thrombolysis ID ACUTE CORONARY SYNDROMES; ORAL ANTIPLATELET THERAPY; ST-ELEVATION MI; NATRIURETIC PEPTIDE; RISK SCORE; TROPONIN-I; CONSERVATIVE STRATEGIES; RANDOMIZED-TRIAL; PROGNOSTIC VALUE; ISCHEMIC EVENTS AB The article presents the history of development of various methods of reperfusion therapy in myocardial infarction. The method of intracoronary thrombolysis was developed and used in Russia in 1976. In 1984 the TIMI Study Group initiated large-scale long-term trial of thrombolytic therapy in myocardial infarction and unstable angina pectoris. Some basic results of the study are outlined. C1 [Braunwald, Eugene] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Braunwald, Eugene] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 36 TC 0 Z9 0 U1 0 U2 0 PU IZDATELSTVO MEDITSINA PI MOSCOW PA PETROVERIGSKII PER 6-8, K-142 MOSCOW, RUSSIA SN 0040-3660 J9 TERAPEVT ARKH JI Ter. Arkhiv PY 2009 VL 81 IS 5 BP 78 EP + PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 462NP UT WOS:000267361100015 PM 19537593 ER PT J AU Dougherty, DD Rauch, SL Greenberg, BD AF Dougherty, Darin D. Rauch, Scott L. Greenberg, Benjamin D. BE Stein, DJ Hollander, E Rothbaum, BO TI Pathophysiology of Obsessive-Compulsive Disorders SO TEXTBOOK OF ANXIETY DISORDERS, 2ND EDITION LA English DT Article; Book Chapter ID POSITRON-EMISSION-TOMOGRAPHY; DEXAMETHASONE SUPPRESSION TEST; CORTICOTROPIN-RELEASING-FACTOR; FAMILY-BASED ASSOCIATION; SEROTONIN TRANSPORTER AVAILABILITY; AUTOSOMAL-DOMINANT TRANSMISSION; POSTTRAUMATIC-STRESS-DISORDER; DOPAMINE AGONIST QUINPIROLE; BASAL GANGLIA VOLUMES; ACUTE RHEUMATIC-FEVER C1 [Dougherty, Darin D.; Rauch, Scott L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, OCD Inst, Boston, MA 02114 USA. [Rauch, Scott L.] McLean Hosp, Belmont, MA 02178 USA. [Greenberg, Benjamin D.] Brown Univ, Butler Hosp, Warren Alpert Med Sch, Providence, RI 02912 USA. RP Dougherty, DD (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 257 TC 0 Z9 0 U1 6 U2 6 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-254-2 PY 2009 BP 287 EP 309 PG 23 WC Psychiatry; Psychology SC Psychiatry; Psychology GA BCF28 UT WOS:000310050600019 ER PT J AU Pollack, MH Smoller, JW Otto, MW Hoge, E Simon, N AF Pollack, Mark H. Smoller, Jordan W. Otto, Michael W. Hoge, Elizabeth Simon, Naomi BE Stein, DJ Hollander, E Rothbaum, BO TI Phenomenology of Panic Disorder SO TEXTBOOK OF ANXIETY DISORDERS, 2ND EDITION LA English DT Article; Book Chapter ID NATIONAL-COMORBIDITY-SURVEY; EPIDEMIOLOGIC CATCHMENT-AREA; CORONARY-HEART-DISEASE; DIAGNOSTIC INTERVIEW CIDI; WORLD-HEALTH-ORGANIZATION; BIPOLAR-I DISORDER; QUALITY-OF-LIFE; ANXIETY DISORDERS; SUICIDAL IDEATION; PRIMARY-CARE C1 [Pollack, Mark H.; Simon, Naomi] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Pollack, Mark H.; Smoller, Jordan W.; Hoge, Elizabeth; Simon, Naomi] Harvard Univ, Sch Med, Boston, MA USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Otto, Michael W.] Boston Univ, Boston, MA 02215 USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. NR 115 TC 0 Z9 0 U1 2 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-254-2 PY 2009 BP 367 EP 379 PG 13 WC Psychiatry; Psychology SC Psychiatry; Psychology GA BCF28 UT WOS:000310050600023 ER PT J AU Yehuda, R Sarapas, C AF Yehuda, Rachel Sarapas, Casey BE Stein, DJ Hollander, E Rothbaum, BO TI Pathogenesis of Posttraumatic Stress Disorder and Acute Stress Disorder SO TEXTBOOK OF ANXIETY DISORDERS, 2ND EDITION LA English DT Article; Book Chapter ID CHILDHOOD SEXUAL-ABUSE; CORTICOTROPIN-RELEASING-FACTOR; NEUROPEPTIDE-Y CONCENTRATIONS; NATIONAL COMORBIDITY SURVEY; MAJOR DEPRESSIVE DISORDER; VEHICLE ACCIDENT VICTIMS; VIETNAM COMBAT VETERANS; URINARY CORTISOL-LEVELS; DELAYED-ONSET PTSD; TRAUMA EXPOSURE C1 James J Peters Vet Affairs Med Ctr, Mt Sinai Sch Med, Traumat Stress Studies Div, Bronx, NY USA. RP Yehuda, R (reprint author), James J Peters Vet Affairs Med Ctr, Mt Sinai Sch Med, Traumat Stress Studies Div, Bronx, NY USA. NR 147 TC 0 Z9 0 U1 1 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-254-2 PY 2009 BP 567 EP 581 PG 15 WC Psychiatry; Psychology SC Psychiatry; Psychology GA BCF28 UT WOS:000310050600033 ER PT J AU Back, SE Waldrop, AE Brady, KT AF Back, Sudie E. Waldrop, Angela E. Brady, Kathleen T. BE Stein, DJ Hollander, E Rothbaum, BO TI Anxiety in the Context of Substance Abuse SO TEXTBOOK OF ANXIETY DISORDERS, 2ND EDITION LA English DT Article; Book Chapter ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL-COMORBIDITY-SURVEY; PLACEBO-CONTROLLED TRIAL; COCAINE-DEPENDENT INDIVIDUALS; ALCOHOL-USE DISORDERS; PROSPECTIVE FOLLOW-UP; DSM-IV DISORDERS; PSYCHIATRIC-DISORDERS; PANIC DISORDER; GENERALIZED ANXIETY C1 [Back, Sudie E.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, Charleston, SC 29425 USA. [Waldrop, Angela E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Waldrop, Angela E.] San Francisco VA Med Ctr, PTSD Clin Team, San Francisco, CA USA. RP Back, SE (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, 171 Ashley Ave, Charleston, SC 29425 USA. NR 105 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-254-2 PY 2009 BP 665 EP 679 PG 15 WC Psychiatry; Psychology SC Psychiatry; Psychology GA BCF28 UT WOS:000310050600038 ER PT B AU Lin, HY AF Lin, Herbert Y. BE Singh, AK Williams, GH TI Erythropoiesis: The Roles of Erythropoietin and Iron SO TEXTBOOK OF NEPHRO-ENDOCRINOLOGY LA English DT Article; Book Chapter ID REGULATED EIF-2-ALPHA KINASE; GENE-EXPRESSION; SIGNAL-TRANSDUCTION; STEM-CELLS; JUVENILE HEMOCHROMATOSIS; LINEAGE COMMITMENT; MOLECULAR CONTROL; YOLK-SAC; RECEPTOR; HEPCIDIN C1 Massachusetts Gen Hosp, Dept Med, Ctr Syst Biol, Program Membrane Biol,Div Nephrol, Boston, MA 02114 USA. RP Lin, HY (reprint author), Massachusetts Gen Hosp, Dept Med, Ctr Syst Biol, Program Membrane Biol,Div Nephrol, Boston, MA 02114 USA. NR 69 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092046-7; 978-0-12-373870-7 PY 2009 BP 19 EP 26 DI 10.1016/B978-0-12-373870-7.00002-8 PG 8 WC Endocrinology & Metabolism; Gastroenterology & Hepatology SC Endocrinology & Metabolism; Gastroenterology & Hepatology GA BA4PI UT WOS:000336096500003 ER PT B AU Juppner, H Portale, AA AF Jueppner, Harald Portale, Anthony A. BE Singh, AK Williams, GH TI Endocrine Regulation of Phosphate Homeostasis SO TEXTBOOK OF NEPHRO-ENDOCRINOLOGY LA English DT Article; Book Chapter ID FIBROBLAST GROWTH FACTOR-23; DOMINANT HYPOPHOSPHATEMIC RICKETS; PSEUDOHYPOPARATHYROIDISM TYPE-IB; FAMILIAL TUMORAL CALCINOSIS; MCCUNE-ALBRIGHT-SYNDROME; STIMULATORY G-PROTEIN; VITAMIN-D METABOLISM; MATRIX EXTRACELLULAR PHOSPHOGLYCOPROTEIN; TRANSPORTER MESSENGER-RNA; COTRANSPORTER NPT2 GENE C1 [Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Portale, Anthony A.] Univ Calif San Francisco, Dept Pediat, Div Pediat Nephrol, San Francisco, CA 94143 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 221 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092046-7; 978-0-12-373870-7 PY 2009 BP 105 EP 126 DI 10.1016/B978-0-12-373870-7.00009-0 PG 22 WC Endocrinology & Metabolism; Gastroenterology & Hepatology SC Endocrinology & Metabolism; Gastroenterology & Hepatology GA BA4PI UT WOS:000336096500010 ER EF