FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Lin, PH Martin, L Matsuura, JH Wellons, E Bush, RL Terramani, TT Chen, CY Lumsden, AB AF Lin, PH Martin, L Matsuura, JH Wellons, E Bush, RL Terramani, TT Chen, CY Lumsden, AB TI Intraaortic stabilization of the AneuRx stent-graft system: A useful adjunct to minimize device migration SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE stent-grafts-abdominal aortic aneurysm; interventional procedure ID ABDOMINAL AORTIC-ANEURYSMS; ENDOVASCULAR REPAIR AB The deployment of a Medtronic AneuRx stent-graft system for endovascular abdominal aortic aneurysm repair requires a series of precise maneuvers that include positioning the primary delivery catheter in the infrarenal aorta, retracting the graft-covering sheath, and withdrawing the stainless steel runners. The last step allows the stent-graft to fully expand and attach to the non-aneurysmal aorta and iliac arteries. Such maneuvers may cause the stent-graft to move caudally if the device is placed in a severely angulated aortic neck. We describe a simple, coaxial, stabilization technique utilizing the contralateral introducer sheath which minimizes potential caudal migration of the stent-graft in angulated aortic necks during runner withdrawal. C1 Baylor Coll Med, Houston VAMC, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, Houston, TX 77030 USA. Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. Med Coll Georgia, Atlanta Med Ctr, Dept Surg, Atlanta, GA USA. RP Lin, PH (reprint author), Baylor Coll Med, Houston VAMC, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, 2002 Holcomb Blvd 112, Houston, TX 77030 USA. NR 5 TC 1 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD JAN-FEB PY 2003 VL 26 IS 1 BP 73 EP 75 DI 10.1007/s00270-002-2624-3 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 649DV UT WOS:000181192400012 PM 12491021 ER PT B AU Hemler, ME Yang, X Kovalenko, OV Song, H Kazarov, AR Kolesnikova, TV Stipp, CS AF Hemler, ME Yang, X Kovalenko, OV Song, H Kazarov, AR Kolesnikova, TV Stipp, CS BE Reutter, W Schuppan, D Tauber, R Zeitz, M TI Tetraspanin functions and microdomain organization SO CELL ADHESION MOLECULES IN HEALTH AND DISEASE SE FALK SYMPOSIUM LA English DT Proceedings Paper CT FALK Workshop on Cell Adhesion Molecules in Health and Disease CY JAN 23-24, 2003 CL Berlin, GERMANY SP FALK ID CELL-SURFACE; MAJOR CD9; PROTEINS; INTEGRIN; CD81; PALMITOYLATION; COMPLEXES; LINK; ASSOCIATION; MORPHOLOGY C1 Harvard Univ, Sch Med, Dept Pathol, Dana Farber Canc Inst, Cambridge, MA 02115 USA. RP Hemler, ME (reprint author), Harvard Univ, Sch Med, Dept Pathol, Dana Farber Canc Inst, Room D-1430,44 Binney St, Cambridge, MA 02115 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8786-4 J9 FALK SYMP PY 2003 BP 26 EP 35 PG 10 WC Cell Biology; Gastroenterology & Hepatology SC Cell Biology; Gastroenterology & Hepatology GA BAM94 UT WOS:000222892000002 ER PT J AU Goldmann, WH AF Goldmann, WH TI Examination of actin polymerization and viscosity induced by cations and ionic strength when cross-linked by alpha-actinin (vol 26, pg 541, 2002) SO CELL BIOLOGY INTERNATIONAL LA English DT Correction C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Charlestown, MA 02129 USA. RP Goldmann, WH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Bldg 149 13th St, Charlestown, MA 02129 USA. RI Goldmann, Wolfgang/H-5572-2013 NR 1 TC 5 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 2003 VL 27 IS 4 BP 391 EP 391 DI 10.1016/S1065-6995(03)00021-0 PG 1 WC Cell Biology SC Cell Biology GA 672FF UT WOS:000182510000012 ER PT J AU Goldmann, WH AF Goldmann, WH TI The coupling of vinculin to the cytoskeleton is not essential for mechano-chemical signalling in F9 cells (vol 26, pg 279, 2002) SO CELL BIOLOGY INTERNATIONAL LA English DT Correction C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Charlestown, MA 02129 USA. RP Goldmann, WH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Bldg 149 13th St, Charlestown, MA 02129 USA. RI Goldmann, Wolfgang/H-5572-2013 NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 2003 VL 27 IS 4 BP 393 EP 393 DI 10.1016/S1065-6995(03)00022-2 PG 1 WC Cell Biology SC Cell Biology GA 672FF UT WOS:000182510000013 ER PT J AU Furmanczyk, PS Quinn, LS AF Furmanczyk, PS Quinn, LS TI Interleukin-15 increases myosin accretion in human skeletal myogenic cultures SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE Interleukin-15; insulin-like growth factor-I; skeletal muscle; cytokines; anabolism; hypertrophy; atrophy; myoblasts; myotubes; muscle fibers ID GROWTH-FACTOR-I; SATELLITE CELL-ACTIVITY; MUSCLE HYPERTROPHY; BODY-COMPOSITION; DIFFERENTIATION; EXPRESSION; HORMONE; OVEREXPRESSION; PROLIFERATION; CACHEXIA AB Interleukin-15 (IL-15) has been shown to have anabolic effects on skeletal muscle in rodent studies conducted in vitro and in vivo. The mechanism of IL-15 action on muscle appears to be distinct from that of the well-characterized muscle anabolic factor insulin-like growth factor-I (IGF-I). IL-15 action has not been investigated in a human culture system nor in detail in primary skeletal myogenic cells. The purpose of this study was to compare the effects of IL-15 and IGF-I in primary human skeletal myogenic cells. Accretion of a major myofibrillar protein, myosin heavy chain (MHC), was used as a measure of muscle anabolism. We found that both growth factors induced increases in MHC accretion in primary human skeletal myogenic cultures; however, IL-15 and IGF-I actions were temporally distinct. IL-15 was more effective at stimulating MHC accretion when added to cultures after differentiation of myoblasts had occurred. In contrast, IGF-I was more effective at stimulating MHC accretion when added to cultures prior to differentiation of myoblasts. These results using a human system support recent findings from rodent models which indicate that the primary mode of IGF-I action on skeletal muscle anabolism is through stimulation of myogenic precursor cells, whereas the primary target of IL-15 action is the differentiated muscle fiber. Further, since clinical and experimental studies have shown IGF-I is not effective in preventing skeletal muscle wasting, the distinct mode of action of IL-15 suggests it may be of potential usefulness in the treatment of muscle wasting disorders. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Washington, Dept Med, Div Gerontol & Geriat Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Amer Lake Div 151, Tacoma, WA 98493 USA. RP Quinn, LS (reprint author), Univ Washington, Dept Med, Div Gerontol & Geriat Med, Seattle, WA 98195 USA. NR 27 TC 41 Z9 42 U1 0 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 2003 VL 27 IS 10 BP 845 EP 851 DI 10.1016/S1065-6995(03)00172-0 PG 7 WC Cell Biology SC Cell Biology GA 737JC UT WOS:000186225800007 PM 14499665 ER PT J AU Daley, GQ AF Daley, George Q. TI Gleevec Resistance Lessons for Target-Directed Drug Development SO CELL CYCLE LA English DT Article DE BCR/ABL; Chronic Myeloid Leukemia; Gleevec; STI-571; Imatinib; Autoinhibition; Tyrosine kinase C1 [Daley, George Q.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Div Pediat Hematol Oncol,Childrens Hosp, Boston, MA 02115 USA. [Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM daley@wi.mit.edu NR 10 TC 11 Z9 13 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2003 VL 2 IS 3 BP 190 EP 191 DI 10.4161/cc.2.3.401 PG 2 WC Cell Biology SC Cell Biology GA V43OO UT WOS:000209690900009 PM 12734421 ER PT J AU Matsui, T Nagoshi, T Rosenzweig, A AF Matsui, Takashi Nagoshi, Tomohisa Rosenzweig, Anthony TI Akt and PI 3-Kinase Signaling in Cardiomyocyte Hypertrophy and Survival SO CELL CYCLE LA English DT Article DE Cardiac; Signal transduction; Kinase; Apoptosis; Growth; Hypertrophy AB In many systems, activation of the "protein and lipid kinase" phosphoinositide 3-kinase (PI 3-kinase) and its downstream serine-threonine kinase effector, Akt (or Protein Kinase B), provide a potent stimulus for cell proliferation, growth, and survival. In the heart, constrained by the limited proliferative capacity of cardiomyocytes, this pathway plays a key role in regulating cardiomyocyte growth and survival, with little effect on proliferation. Simultaneously, PI 3-kinase and Akt are important modulators of metabolic substrate utilization and cardiomyocyte function. Thus, the convergent signaling pathways controlling so many clinically important phenotypes of the cardiomyocyte suggest it holds promise as a therapeutic target in a variety of cardiac diseases. However, the similar role of PI 3-kinase/Akt signaling in neoplasia suggests the difficulty of activating this pathway in the heart without invoking adverse consequences elsewhere. Here we review evidence regarding the role of PI 3-kinase/Akt in controlling cardiomyocyte growth and survival, and discuss the implications for therapeutic strategies. C1 [Matsui, Takashi; Nagoshi, Tomohisa; Rosenzweig, Anthony] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Cardiovasc Gene Therapy,CVRC & Cardiol Di, Boston, MA USA. RP Rosenzweig, A (reprint author), Massachusetts Gen Hosp, Program Cardiovasc Gene Therapy, 114 16th St,Rm 2600, Charlestown, MA 02129 USA. EM arosen-zweig@partners.org FU NIH [HL-59521, HL-61557, HL-04250] FX This work is supported in part by grants from the NIH [HL-59521 and HL-61557 (AR), HL-04250 (TM)]. Dr Rosenzweig is an Established Investigator of the American Heart Association. NR 40 TC 121 Z9 128 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2003 VL 2 IS 3 BP 220 EP 223 DI 10.4161/cc.2.3.381 PG 4 WC Cell Biology SC Cell Biology GA V43OO UT WOS:000209690900016 PM 12734428 ER PT J AU D'Andrea, AD AF D'Andrea, Alan D. TI The Fanconi Anemia/BRCA Signaling Pathway Disruption in Cisplatin-Sensitive Ovarian Cancers SO CELL CYCLE LA English DT Article DE cisplatin; Fanconi anemia; gene methylation; ovarian cancer; BRCA2 AB Ovarian tumors often exhibit chromosome instability and hypersensitivity to the chemotherapeutic agent cisplatin. Recently, we have shown that this cellular phenotype may result from an acquired disruption of the Fanconi Anemia/BRCA (FA/BRCA) signaling pathway. Disruption results from methylation and silencing of one of the FA genes (FANCF), leading to cisplatin sensitivity. Restoration of this pathway is associated with demethylation of FANCF, leading to acquired cisplatinum resistance. The serial inactivation and reactivation of the FA/BRCA pathway has important implications for the diagnosis and treatment of ovarian cancers and related cancers. C1 [D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu NR 12 TC 46 Z9 48 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2003 VL 2 IS 4 BP 290 EP 292 DI 10.4161/cc.2.4.413 PG 3 WC Cell Biology SC Cell Biology GA V43OS UT WOS:000209691300009 PM 12851475 ER PT J AU Armstrong, SA Korsmeyer, SJ AF Armstrong, Scott A. Korsmeyer, Stanley J. TI Comparison of Human Genomics and Genetic Models of Cancer to Identify Novel Therapeutic Targets SO CELL CYCLE LA English DT Article DE MLL; FLT3; leukemia; microarray; mouse models; tyrosine kinase C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. Howard Hughes Med Inst, Ashburn, VA USA. RP Korsmeyer, SJ (reprint author), Dana Farber Canc Inst, One Jimmy Fund Way, Boston, MA 02115 USA. EM Stanley_Korsmeyer@dfci.harvard.edu NR 9 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2003 VL 2 IS 5 BP 408 EP 409 DI 10.4161/cc.2.5.486 PG 2 WC Cell Biology SC Cell Biology GA V43OT UT WOS:000209691400003 PM 12963826 ER PT J AU Pardee, AB AF Pardee, Arthur B. TI Normal Cells Arrest Cancer Cells in G(2) SO CELL CYCLE LA English DT Editorial Material DE cell cycle; cancer; SV40; 3T3; contact inhibition; G(2) phase C1 [Pardee, Arthur B.] Dana Farber Canc Inst, SM 936A,44 Binney St, Boston, MA 02115 USA. RP Pardee, AB (reprint author), Dana Farber Canc Inst, SM 936A,44 Binney St, Boston, MA 02115 USA. EM Arthur_Pardee@dfci.har-vard.edu NR 3 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2003 VL 2 IS 5 BP 454 EP 454 DI 10.4161/cc.2.5.487 PG 1 WC Cell Biology SC Cell Biology GA V43OT UT WOS:000209691400019 PM 12963842 ER PT J AU Lamb, J Ewen, ME AF Lamb, Justin Ewen, Mark E. TI Cyclin D1 and Molecular Chaperones Implications for Tumorigenesis SO CELL CYCLE LA English DT Article DE cyclin D1; C/EBP beta; chaperones; cell growth; tumorigenisis; functional genomics; transcriptional profiling AB We recently investigated the mechanisms of cyclin D1 action in human cancer using global analyses of gene expression. With an experimentally-determined expression signature for cyclin D1 overexpression, gene expression data from human tumors, and a novel data-mining method, we were able to reveal a previously unappreciated and apparently predominant functional interdependency between cyclin D1 and C/EBP beta. Many of the genes we found to be affected by cyclin D1 overexpression are recognized as molecular chaperones or their regulators. Might this provide insights to the role of the cyclin D1-C/EBP beta axis in carcinogenesis? C1 [Lamb, Justin] MIT Ctr Genome Res, Whitehead Inst, Howard Hughes Med Inst, Cambridge, MA USA. [Ewen, Mark E.] Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. [Ewen, Mark E.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Ewen, Mark E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ewen, ME (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM mark_ewen@dfci.harvard.edu NR 30 TC 26 Z9 27 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2003 VL 2 IS 6 BP 525 EP 527 DI 10.4161/cc.2.6.584 PG 3 WC Cell Biology SC Cell Biology GA V43PC UT WOS:000209692300008 PM 14504466 ER PT J AU Omer, A Duvivier-Kali, VF Weir, GC AF Omer, A Duvivier-Kali, VF Weir, GC TI Factors affecting the biocompatibility and stability of alginate microcapsules in rats SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 6th International Congress of the Cell-Transplant-Society CY MAR 02-05, 2003 CL ATLANTA, GEORGIA SP Cell Transplant Soc C1 Joslin Diabet Ctr, Sect Islet Transplantat, Boston, MA 02215 USA. Joslin Diabet Ctr, Sect Cell Biol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2003 VL 12 IS 2 BP 157 EP 158 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 680CM UT WOS:000182958800042 ER PT J AU Duvivier-Kali, VF Omer, A Lopez-Avalos, MD O'Neil, JJ Weir, GC AF Duvivier-Kali, VF Omer, A Lopez-Avalos, MD O'Neil, JJ Weir, GC TI Role of beta cell loss and antibody response on the survival of microencapsulated adult pig islets SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 6th International Congress of the Cell-Transplant-Society CY MAR 02-05, 2003 CL ATLANTA, GEORGIA SP Cell Transplant Soc C1 Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2003 VL 12 IS 2 BP 161 EP 161 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 680CM UT WOS:000182958800048 ER PT J AU Duvivier-Kali, VF Fernandes, J Hollister-Lock, J Su, S Omer, A Feng, S Mulligan, R Lee, JS Weir, GC AF Duvivier-Kali, VF Fernandes, J Hollister-Lock, J Su, S Omer, A Feng, S Mulligan, R Lee, JS Weir, GC TI Transfection of rat islets by CTLA4 and TGF-beta using adeno- and lentivirus vectors. In vitro and in vivo results SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 6th International Congress of the Cell-Transplant-Society CY MAR 02-05, 2003 CL ATLANTA, GEORGIA SP Cell Transplant Soc C1 Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2003 VL 12 IS 2 BP 164 EP 164 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 680CM UT WOS:000182958800054 ER PT J AU O'Neil, JJ Bonner-Weir, S Tchipashvili, V Chandra, G Yelverton, T Omer, A Xu, G Alm, YB Weir, GC AF O'Neil, JJ Bonner-Weir, S Tchipashvili, V Chandra, G Yelverton, T Omer, A Xu, G Alm, YB Weir, GC TI The theoretical and actual characterization of clinical islet preparations SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 6th International Congress of the Cell-Transplant-Society CY MAR 02-05, 2003 CL ATLANTA, GEORGIA SP Cell Transplant Soc C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2003 VL 12 IS 2 BP 168 EP 168 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 680CM UT WOS:000182958800061 ER PT J AU Papas, KK Colton, CK Qipo, A Wu, HY Auchincloss, H Weir, GC Koulmanda, M AF Papas, KK Colton, CK Qipo, A Wu, HY Auchincloss, H Weir, GC Koulmanda, M TI Islet quality assay based on oxygen consumption rate and DNA measurements predicts graft function in mice SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 6th International Congress of the Cell-Transplant-Society CY MAR 02-05, 2003 CL ATLANTA, GEORGIA SP Cell Transplant Soc C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Islet Transplantat Lab, Boston, MA 02114 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2003 VL 12 IS 2 BP 176 EP 176 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 680CM UT WOS:000182958800079 ER PT J AU Omer, A Duvivier-Kali, VF Ashenbach, W Tchipashvili, V Goodyear, L Weir, GC AF Omer, A Duvivier-Kali, VF Ashenbach, W Tchipashvili, V Goodyear, L Weir, GC TI Rats with islet transplants are vulnerable to exercise-induced hypoglycemia SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 6th International Congress of the Cell-Transplant-Society CY MAR 02-05, 2003 CL ATLANTA, GEORGIA SP Cell Transplant Soc C1 Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Joslin Diabet Ctr, Metab Sect, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2003 VL 12 IS 2 BP 180 EP 180 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 680CM UT WOS:000182958800086 ER PT J AU Macklis, JD AF Macklis, JD TI Activation of endogenous neural precursors/stem cells in situ: Induction of neurogenesis in neocortex of adult mice SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 13th Meeting of the Network of European CNS Transplantation and Restoration (NECTAR) CY DEC 12-14, 2002 CL AMSTERDAM, NETHERLANDS C1 Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Massachusetts Gen Hosp, MGH HMS Ctr Nervous Syst Repair, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2003 VL 12 IS 3 BP 326 EP 326 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 680CN UT WOS:000182958900056 ER PT J AU O'Neil, JJ Tchipashvili, V Parent, RJ Ugochukwu, O Chandra, G Koulmanda, M Ko, D Kawai, T AF O'Neil, JJ Tchipashvili, V Parent, RJ Ugochukwu, O Chandra, G Koulmanda, M Ko, D Kawai, T TI A simple and cost-effective method for the isolation of islets from nonhuman primates SO CELL TRANSPLANTATION LA English DT Article DE nonhuman primate; islet isolation; assessment; transplantation ID LONG-TERM SURVIVAL; HUMANIZED ANTI-CD154; CYNOMOLGUS MONKEYS; METABOLIC FUNCTION; DIABETES-MELLITUS; PANCREATIC-ISLETS; RHESUS-MONKEYS; TRANSPLANTATION; MODEL; ALLOGRAFTS AB Recent advances in islet cell transplantation have led to insulin independence in a majority of islet transplant recipients. However, there exists a need to overcome the shortage of donor tissue and the necessity for lifelong immumosuppression. Preclinical studies in large animal models are necessary to evaluate the safety and efficacy of alternative approaches for clinical islet transplantation. The nonhuman primate serves as an appropriate animal model for such investigations; however, a major impediment in performing such preclinical research has been the difficulty in isolating islets of sufficient quantity and quality. The current study describes a simple and cost-effective method to isolate nonhuman primate islets to support preclinical islet transplantation research. The results of islet isolations from 54 cynomolgus monkeys and 4 baboons are reported. The pancreas was infused with Liberase HI and subjected to static digestion. The digested tissue was shaken, filtered through a mesh screen, applied to a discontinuous gradient, and centrifuged in much the same manner as with conventional rodent islet isolations. Islets were collected from the two interfaces, washed, and transplanted. Following purification, cynomolgus monkey islet isolation yields were 50,100 +/- 3120 IE total or 8760 +/- 420 IE/g pancreas with the percent purity and viability of 90.8 +/- 0.9 and 90.7 +/- 0.7, respectively. Total insulin content of the isolated islets was 405 +/- 53 mug insulin with DNA content being and 976 +/- 117 mug DNA, corresponding to a ratio of 0.57 mug insulin/ mug DNA. STZ-induced diabetes was reversed in both mouse and nonhuman primate recipients, which possessed significant levels of c-peptide following transplantation and well-granulated islet grafts. The technique yields sufficient numbers of pure and viable islets to support preclinical research to develop improved strategies to prevent the immune destruction of the transplanted islet graft. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP O'Neil, JJ (reprint author), Johnson & Johnson Consumer Prod Inc, 199 Grandview Rd, Skillman, NJ 08558 USA. EM jjoneil@cpcus.jnj.com FU NIDDK NIH HHS [DK-36836] NR 25 TC 15 Z9 16 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2003 VL 12 IS 8 BP 883 EP 890 PG 8 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 762VA UT WOS:000188001800008 PM 14763508 ER PT J AU Engelman, A AF Engelman, A TI The roles of cellular factors in retroviral integration SO CELLULAR FACTORS INVOLVED IN EARLY STEPS OF RETROVIRAL REPLICATON SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; RNA-POLYMERASE-III; EFFICIENT CONCERTED INTEGRATION; DEPENDENT PROTEIN-KINASE; I-HYPERSENSITIVE SITES; HIV TYPE-1 INTEGRATION; VIRAL-DNA ENDS; PREINTEGRATION COMPLEXES; CDNA INTEGRATION; NUCLEOCAPSID PROTEIN AB A key early step in the retroviral life cycle is the integration of reverse-transcribed viral cDNA into a chromosome of an infected cell. The key protein player in retroviral integration is the viral integrase, which enters the cell as part of the virus. Although purified integrase protein is necessary and sufficient to perform the basic catalytic DNA breakage and joining steps of retroviral integration, a variety of normal cellular proteins have been implicated as playing important roles in establishing the integrated provirus in cells. This chapter reviews the roles of host cell factors that function during integrase catalysis, during the repair of the resulting DNA recombination intermediate, and by potentially guiding viral preintegration complexes to their chromosomal locations for cDNA integration. The potential to interfere with proper integration by blocking either integrase catalysis or the function of cellular integration cofactors is also discussed. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI-39394, AI-28691, AI-45313] NR 110 TC 29 Z9 29 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2003 VL 281 BP 209 EP 238 PG 30 WC Immunology; Microbiology SC Immunology; Microbiology GA BX56E UT WOS:000185676400006 PM 12932079 ER PT S AU Daly, C Dube, C Rollins, BJ AF Daly, C Dube, C Rollins, BJ BE Murphy, PM Horuk, R TI Chemokine influences on adaptive immunity and malignancies of the immune system SO CHEMOKINE ROLES IN IMMUNOREGULATION AND DISEASE SE ERNST SCHERING RESEARCH FOUNDATION WORKSHOP LA English DT Proceedings Paper CT Workshop on Chemokine Roles in Immunoregulation and Disease CY 2002 CL NAPA VALLEY, CA SP Ernst Schering Res Fdn ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NEUTROPHIL-ACTIVATING PROPERTIES; DENDRITIC CELL MATURATION; SMOOTH-MUSCLE CELLS; HUMAN-BREAST-CANCER; TRANSGENIC MICE; KNOCKOUT MICE; GROWTH-FACTOR; MACROPHAGE INFILTRATION C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Daly, C (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 68 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0947-6075 BN 3-540-40221-7 J9 E SCHERING RES FDN W PY 2003 VL 45 BP 11 EP 30 PG 20 WC Immunology SC Immunology GA BY41H UT WOS:000189198200002 ER PT S AU Kazemi, H AF Kazemi, H BE Pequignot, JM Gonzalez, C Nurse, CA Prabhakar, NR Dalmaz, Y TI CO2/H+ signal transduction and central ventilatory control SO CHEMORECEPTION: FROM CELLULAR SIGNALLING TO FUNCTIONAL PLASTICITY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 15th International Symposium on Arterial Chemoreception CY NOV 18-22, 2002 CL LYON, FRANCE SP CNRS, INSERM, Univ Claude Bernard Lyon I, Inst Rech Int Serv, Reg Rhone Alpes, Ville Lyon, Conseil Gen Rhone ID CHOLINE-ACETYLTRANSFERASE GENE; CENTRAL RESPIRATORY CONTROL; INSITU HYBRIDIZATION; ACETYLCHOLINE; PERTURBATIONS C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kazemi, H (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47868-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 536 BP 401 EP 406 PG 6 WC Cell Biology; Medicine, Research & Experimental; Physiology SC Cell Biology; Research & Experimental Medicine; Physiology GA BY34Y UT WOS:000188998400051 PM 14635693 ER PT S AU Chen, J Dinger, B Jung, R Stensaas, L Fidone, S AF Chen, J Dinger, B Jung, R Stensaas, L Fidone, S BE Pequignot, JM Gonzalez, C Nurse, CA Prabhakar, NR Dalmaz, Y TI Altered expression of vascular endothelial growth factor and FLK-1 receptor in chronically hypoxic rat carotid body SO CHEMORECEPTION: FROM CELLULAR SIGNALLING TO FUNCTIONAL PLASTICITY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 15th International Symposium on Arterial Chemoreception CY NOV 18-22, 2002 CL LYON, FRANCE SP CNRS, INSERM, Univ Claude Bernard Lyon I, Inst Rech Int Serv, Reg Rhone Alpes, Ville Lyon, Conseil Gen Rhone ID FEATURES; BODIES; LUNGS; CELLS C1 Univ Utah, Sch Med, Dept Physiol, Salt Lake City, UT 84112 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Chen, J (reprint author), Univ Utah, Sch Med, Dept Physiol, Salt Lake City, UT 84112 USA. FU NINDS NIH HHS [NS 12636, NS 07938] NR 19 TC 7 Z9 7 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47868-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 536 BP 583 EP 591 PG 9 WC Cell Biology; Medicine, Research & Experimental; Physiology SC Cell Biology; Research & Experimental Medicine; Physiology GA BY34Y UT WOS:000188998400074 PM 14635716 ER PT J AU Wells, MJ Wilkie, DJ Brown, MA Corless, IB Farber, SJ Judge, MKM Shannon, SE AF Wells, MJ Wilkie, DJ Brown, MA Corless, IB Farber, SJ Judge, MKM Shannon, SE TI Technology survey of nursing programs - Implications for electronic end-of-life teaching tool development SO CIN-COMPUTERS INFORMATICS NURSING LA English DT Article DE end-of-life care; nursing education; computer hardware and software; infrastructure ID INFORMATION TECHNOLOGY; EDUCATION; COMPUTER; MULTIMEDIA; CLASSROOM AB From an online survey of current technological capabilities of US undergraduate nursing programs, we found almost universal use of Microsoft Windows-based computers and Microsoft Office Suite software. Netscape and Microsoft Internet Explorer were the most popular browsers for Internet access. The survey also assessed faculty preferences for end-of-life care teaching materials and found that nurse educators preferred simple easy-to-use tools provided on CD-ROM or the Internet, with instructions provided via CD-ROM, the Internet, and demonstration workshops. Our findings have numerous implications for the development of electronic teaching materials for nursing. C1 Univ Washington, Sch Nursing, Seattle, WA 98195 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Massachusetts Gen Hosp, MGH Inst Hlth Profess, Boston, MA 02114 USA. RP Wilkie, DJ (reprint author), Univ Washington, Sch Nursing, Box 357266, Seattle, WA 98195 USA. OI Corless, Inge/0000-0003-0438-2037 NR 40 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1538-2931 J9 CIN-COMPUT INFORM NU JI CIN-Comput. Inform. Nurs. PD JAN-FEB PY 2003 VL 21 IS 1 BP 29 EP 36 DI 10.1097/00024665-200301000-00011 PG 8 WC Computer Science, Interdisciplinary Applications; Medical Informatics; Nursing SC Computer Science; Medical Informatics; Nursing GA 641QN UT WOS:000180757000004 PM 12544152 ER PT J AU Suggs, J Wang, C Li, GA AF Suggs, J Wang, C Li, GA TI The effect of graft stiffness on knee joint biomechanics after ACL reconstruction - a 3D computational simulation SO CLINICAL BIOMECHANICS LA English DT Article DE anterior cruciate ligament; knee; biomechanics; computational model; kinematics ID ANTERIOR CRUCIATE LIGAMENT; PATELLAR TENDON GRAFT; TERM FOLLOW-UP; 3-DIMENSIONAL MODEL; GRACILIS TENDONS; IN-VITRO; FIXATION; TENSION; SEMITENDINOSUS; QUADRICEPS AB Objective. The objective was to determine the effect of varying graft stiffness and initial graft tension on knee kinematics and graft tension after anterior cruciate ligament reconstruction. Design. A 3D computational knee model was used. Background. Many factors influencing the biomechanical outcome of anterior cruciate ligament reconstruction have been investigated. However, there are no reports on the effect of variations in graft stiffness on knee behavior. Methods. A 3D computational knee model was used to simulate anterior cruciate ligament reconstruction using three different grafts with stiffnesses similar to the anterior cruciate ligament (graft 1), a 10mm bone-patellar tendon-bone graft (graft 2), and a 14mm bone-patellar tendon-bone graft (graft 3). The initial graft tension was set to 0 or 40 N with the knee at 30degrees of flexion. A 134 N anterior tibial drawer load and a 400 N quadriceps load were applied to the knee, and kinematics and graft tension were calculated. Results. When fixed with no initial tension, graft I was found to under-constrain the knee, while graft 2 slightly over-constrained the knee, and graft 3 over-constrained the knee when compared to the intact knee. When an initial graft tension of 40 N was used, all of the reconstructed knees were more constrained than when an initial tension of 0 N was used. Conclusions. This study suggests that graft stiffness has a direct impact on knee biomechanics after anterior cruciate ligament reconstruction. An optimal anterior cruciate ligament reconstruction can be achieved if the anterior cruciate ligament is replaced by a graft with similar structural stiffness. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Beth Israel Deaconess Med Ctr,Orthopaed Biomec La, Boston, MA 02215 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, GA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Beth Israel Deaconess Med Ctr,Orthopaed Biomec La, 330 Brookline Ave,RN 115, Boston, MA 02215 USA. NR 45 TC 35 Z9 45 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD JAN PY 2003 VL 18 IS 1 BP 35 EP 43 AR PII S0268-0033(02)00137-7 DI 10.1016/S0268-0033(02)00137-7 PG 9 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA 653WX UT WOS:000181461000006 PM 12527245 ER PT J AU Come, SE Buzdar, AU Arteaga, CL Brodie, AM Davidson, NE Dowsett, M Ingle, JN Johnston, SRD Lee, AV Osborne, CK Pritchard, KI Vogel, VG Winer, EP Hart, CS AF Come, SE Buzdar, AU Arteaga, CL Brodie, AM Davidson, NE Dowsett, M Ingle, JN Johnston, SRD Lee, AV Osborne, CK Pritchard, KI Vogel, VG Winer, EP Hart, CS TI Second International Conference on Recent Advances and Future Directions in Endocrine Manipulation of Breast Cancer: Summary consensus statement SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Hematol Oncol Unit, Boston, MA 02215 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37232 USA. Univ Maryland, Sch Med, Dept Pharmacol, Baltimore, MD 21202 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. Acad Dept Biochem, Royal Marsden Hosp, London SW3 6JJ, England. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Royal Marsden Hosp, London SW3 6JJ, England. Inst Canc Res, Dept Med, London SW3 6JJ, England. Baylor Breast Ctr, Baylor Coll Med, Houston, TX 77030 USA. Toronto Sunnybrook Reg Canc Ctr, Clin Trials & Epidemiol, Toronto, ON M4N 3M5, Canada. UPCI Breast Program, Magee Womens Hosp, Pittsburgh, PA 15213 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. InforMED, Narberth, PA 19072 USA. RP Come, SE (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Hematol Oncol Unit, 330 Brookline Ave, Boston, MA 02215 USA. NR 0 TC 3 Z9 4 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN PY 2003 VL 9 IS 1 SU S BP 443S EP 446S PN 2 PG 4 WC Oncology SC Oncology GA 637QY UT WOS:000180525000001 PM 12538498 ER PT J AU Ligibel, JA Winer, EP AF Ligibel, JA Winer, EP TI Clinical differences among the aromatase inhibitors SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 2nd International Conference on Recent Advances and Future Directions in Endocrine Manipulation of Breast Cancer CY JUN 28-29, 2002 CL CAMBRIDGE, MASSACHUSETTS ID ADVANCED BREAST-CANCER; FIRST-LINE THERAPY; POSTMENOPAUSAL WOMEN; PHASE-III; MEGESTROL-ACETATE; RANDOMIZED TRIAL; DOUBLE-BLIND; LETROZOLE; TAMOXIFEN; ANASTROZOLE AB In the United States, three third-generation aromatase inhibitors are available commercially: anastrozole, letrozole, and exemestane. Anastrozole and letrozole are nonsteroidal agents, whereas exemestane is a steroid. The three agents differ in terms of structure and metabolic products and in the degree to which they suppress aromatase activity. The clinical significance of these differences is unclear. All three of the agents have been found to be equivalent or superior to megesterol acetate as a second-line therapy for metastatic breast cancer. In the first-line setting, large Phase III trials have demonstrated that anastrozole and letrozole are equivalent or superior to tamoxifen in women with metastatic disease. Multiple trials with widely varying study designs have been launched in the adjuvant setting comparing the aromatase inhibitors to tamoxifen. Early results from the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial suggest a small but statistically significant improvement in disease-free survival for anastrozole compared with tamoxifen, but further follow-up is needed. This article explores the efficacy and tolerability of the aromatase inhibitors in both the metastatic and the adjuvant settings. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Winer, EP (reprint author), 44 Binney St, Boston, MA 02115 USA. NR 30 TC 8 Z9 8 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN PY 2003 VL 9 IS 1 SU S BP 473S EP 479S PN 2 PG 7 WC Oncology SC Oncology GA 637QY UT WOS:000180525000006 PM 12538503 ER PT J AU Lyon, GM Zurita, S Casquero, J Holgado, W Guevara, J Brandt, ME Douglas, S Shutt, K Warnock, DW Hajjeh, RA AF Lyon, GM Zurita, S Casquero, J Holgado, W Guevara, J Brandt, ME Douglas, S Shutt, K Warnock, DW Hajjeh, RA CA Sporotrichosis Peru Investigation TI Population-based surveillance and a case-control study of risk factors for endemic lymphocutaneous sporotrichosis in Peru SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 14th Congress of the International-Society-for-Animal-and-Human-Mycoses CY MAY 08-12, 2000 CL BUENOS AIRES, ARGENTINA SP Int Soc Anim Human Mycoses ID FELINE SPOROTRICHOSIS; CUTANEOUS SPOROTRICHOSIS; SYSTEMIC MYCOSES; UNITED-STATES; SPHAGNUM MOSS; TRANSMISSION; OUTBREAK; EPIDEMIOLOGY; INFECTIONS; WORKERS AB Population-based surveillance and a case-control study were conducted in Abancay, Peru, to estimate the burden of disease and to determine risk factors for sporadic lymphocutaneous sporotrichosis (LS). Laboratory records from local hospitals were reviewed for the years of 1997 and 1998, and prospective surveillance was conducted for the period of September 1998 through September 1999. A case-control study was conducted with 2 matched control subjects per case patient. The mean annual incidence was 98 cases per 100,000 persons. Children had an incidence 3 times higher than that for adults and were more likely to have LS lesions on the face and neck. Identified risk factors included owning a cat, playing in crop fields, having a dirt floor in the house, working mainly outdoors, and having a ceiling made of raw wood or conditions associated with a lower socioeconomic status. Decreased environmental exposure, such wearing protective clothing during construction activities for adults or limiting contact with cats and soil for children, and improvements in living spaces may decrease the incidence of LS. C1 Ctr Dis Control & Prevent, Epidem Intelligence Serv, Epidemiol Program Off, Atlanta, GA USA. Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA USA. Ctr Dis Control & Prevent, Biostat & Informat Management Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Atlanta, GA USA. Minist Salud, Inst Nacl Salud, Lima, Peru. Ctr Med Santa Teresa, Abancay, Peru. Direcc Salud Apurimac, Abancay, Peru. RP Lyon, GM (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 55 Fruit St,J-504, Boston, MA 02114 USA. OI Shutt, Kathleen/0000-0003-3376-6152 NR 37 TC 25 Z9 27 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2003 VL 36 IS 1 BP 34 EP 39 DI 10.1086/345437 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 627DM UT WOS:000179916500010 PM 12491199 ER PT J AU Yazdanpanah, Y Goldie, SJ Paltiel, AD Losina, E Coudeville, L Weinstein, MC Gerard, Y Kimmel, AD Zhang, H Salamon, R Mouton, Y Freedberg, KA AF Yazdanpanah, Y Goldie, SJ Paltiel, AD Losina, E Coudeville, L Weinstein, MC Gerard, Y Kimmel, AD Zhang, H Salamon, R Mouton, Y Freedberg, KA TI Prevention of human immunodeficiency virus-related opportunistic infections in France: A cost-effectiveness analysis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID MYCOBACTERIUM-AVIUM COMPLEX; ACTIVE ANTIRETROVIRAL THERAPY; DRUG-RESISTANCE; FLUCONAZOLE PROPHYLAXIS; FUNGAL-INFECTIONS; RANDOMIZED TRIAL; HIV-1 INFECTION; PLUS INDINAVIR; VIRAL LOAD; AIDS AB A simulation model of human immunodeficiency virus (HIV) disease, which incorporated French data on the progression of HIV disease in the absence of antiretroviral therapy and on cost, was used to determine the clinical impact and cost-effectiveness of different strategies for the prevention of opportunistic infections in French patients who receive highly active antiretroviral therapy (HAART). Compared with use of no prophylaxis, use of trimethoprim-sulfamethoxazole (TMP-SMZ) increased per-person lifetime costs from 185,600 to 187,900 and quality-adjusted life expectancy from 112.2 to 113.7 months, for an incremental cost-effectiveness ratio of 18,700 per quality-adjusted life-year (/QALY) gained. Compared with use of TMP-SMZ alone, use of TMP-SMZ plus azithromycin cost 23,900/QALY gained; adding fluconazole cost an additional 54,500/QALY gained. All strategies that included oral ganciclovir had cost-effectiveness ratios that exceeded 100,000/QALY gained. In the era of HAART, on the basis of French data, prophylaxis against Pneumocystis carinii pneumonia, toxoplasmic encephalitis, and Mycobacterium avium complex bacteremia is cost-effective. Prophylaxis against fungal and cytomegalovirus infections is less cost-effective than are other therapeutic options for HIV disease and should remain of lower priority. C1 Ctr Hosp Tourcoing, Fac Med Lille, Serv Univ Malad Infect & Voyageur, F-59208 Tourcoing, France. Inst Pasteur, Ctr Immunol & Biol Parasitaire, CNRS, URA 362,Lab Rech Econ & Sociales, F-59019 Lille, France. Univ Bordeaux 2, INSERM, U330, F-33076 Bordeaux, France. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Risk Anal, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Div Gen Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Partners AIDS Res Ctr, Boston, MA USA. Yale Univ, Sch Med, Dept Epidemiol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Publ Hlth, New Haven, CT 06510 USA. RP Yazdanpanah, Y (reprint author), Ctr Hosp Tourcoing, Fac Med Lille, Serv Univ Malad Infect & Voyageur, 135 Rue President Coty,BP 619, F-59208 Tourcoing, France. FU NIAID NIH HHS [R01 AI042006, AI-42006]; ODCDC CDC HHS [U64/CCU114927, U64/CCU119525] NR 45 TC 19 Z9 19 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2003 VL 36 IS 1 BP 86 EP 96 DI 10.1086/344902 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 627DM UT WOS:000179916500018 PM 12491207 ER PT J AU Chiodo, CP Jupiter, JB Alvarez, G Chandler, HP AF Chiodo, CP Jupiter, JB Alvarez, G Chandler, HP TI Oblique osteotomy for multiplanar correction of malunions of the femoral shaft SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID FRACTURES; ANTEVERSION; FIXATION; FEMUR; DEFORMITY; NONUNIONS; TRAUMA; PLATE AB Between 1990 and 1996, six patients had oblique femoral osteotomies for symptomatic posttraumatic femoral malunions. In each patient, an oblique osteotomy was done that allowed for correction in the coronal, transverse, and sagittal planes. Fixation was achieved with lag screws supplemented by a neutralization plate. The average followup was 49 months (range, 18-99 months). All osteotomies; healed at an average of 2.9 months (range, 2.5-4.0 months). Postoperatively, all patients had full range of motion in the ipsilateral hip and knee and could bear full weight without pain. Radiographically, the average deformity measured on anteroposterior radiographs improved from 21.6degrees to 4.2degrees varus. The average deformity on lateral radiographs improved from 22.5degrees to 7.0degrees antecurvatum. In all patients, the leg lengths were within 0.5 cm of each other and axial alignment was within 10degrees of the contralateral limb. The use of an oblique osteotomy is a simple and predictable method of correcting complex posttraumatic femoral malunions and provides excellent surgical and clinical results. C1 Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Chiodo, CP (reprint author), Brigham & Womens Hosp, Dept Orthopaed Surg, 75 Francis St, Boston, MA 02115 USA. NR 46 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2003 IS 406 BP 185 EP 194 DI 10.1097/01.blo.0000038042.63743.d6 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 634EG UT WOS:000180326600028 PM 12579018 ER PT J AU Tondo, L Isacsson, G Baldessarini, RJ AF Tondo, L Isacsson, G Baldessarini, RJ TI Suicidal behaviour in bipolar disorder - Risk and prevention SO CNS DRUGS LA English DT Review ID COMPARATIVE PROPHYLACTIC EFFICACY; MANIC-DEPRESSIVE PATIENTS; LITHIUM TREATMENT; MOOD DISORDERS; FOLLOW-UP; ELECTROCONVULSIVE-THERAPY; GENERAL-PRACTITIONERS; PSYCHIATRIC-DISORDERS; MAINTENANCE TREATMENT; AFFECTIVE-ILLNESS AB Bipolar (manic-depressive) disorder is a common and severe illness. It is also potentially fatal as a result of accidents and increased mortality associated with comorbid substance use and medical illnesses, but its highest lethality results from suicide. Suicide rates, averaging 0.4% per year in men and women diagnosed with bipolar disorder, are >20-fold higher than in the general population. Suicidal acts often occur early in the illness course and in association with severe depressive and dysphoric-agitated mixed phases of illness, especially following repeated, severe depressions. Systematic consideration of risk and protective factors enhances assessment of potentially suicidal patients. Short-term interventions employed empirically to manage acute suicidality include close clinical supervision, rapid hospitalisation and use of electroconvulsive treatment. Several plausible therapeutic interventions have limited evidence of long-term effectiveness against mortality risks associated with any psychiatric disorder, including antidepressant, antimanic, antipsychotic and electroconvulsive, as well as psychosocial, treatments. However, in bipolar disorder and other major affective disorders, lithium maintenance treatment is a notable exception, with strong and consistent evidence that it reduces suicidal risk. The growing range of drugs being introduced to treat acute and long-term phases of bipolar disorder, including antiepileptic drugs, atypical antipsychotics and relatively safe, modern antidepressants, require research assessment for their ability to limit premature mortality from suicide and other causes. For now, however, more can be done to improve treatment in major affective illnesses by application of current knowledge in a systematic fashion, with close and sustained clinical follow-up of patients at risk, hopefully with a resulting reduction of mortality rates. C1 Univ Cagliari, Dept Psychol, Ctr Lucio Bini Stanley Med, Res Inst,Res Ctr, Cagliari, Sardinia, Italy. Harvard Univ, Sch Med, Dept Psychiat, Bipolar & Psychot Disorders Program, Belmont, MA 02178 USA. Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorder Res, Belmont, MA USA. Huddinge Univ Hosp, Karolinska Inst, Neurotec Inst, Div Psychiat, Stockholm, Sweden. RP Tondo, L (reprint author), McLean Hosp, Bipolar Disorder Res Unit, 115 Mill St,N Belknap 3, Belmont, MA 02478 USA. NR 189 TC 231 Z9 237 U1 7 U2 19 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2003 VL 17 IS 7 BP 491 EP 511 DI 10.2165/00023210-200317070-00003 PG 21 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 688TV UT WOS:000183453200003 PM 12751919 ER PT J AU Camargo, CA Spooner, C Rowe, BH AF Camargo, Carlos A., Jr. Spooner, Carol Rowe, Brian H. TI Continuous versus intermittent beta-agonists for acute asthma SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review DE Acute Disease; Administration, Inhalation; Adrenergic beta-Agonists [administration & dosage]; Anti-Asthmatic Agents [administration & dosage]; Asthma [drug therapy]; Emergencies; Randomized Controlled Trials as Topic; Humans AB Background Patients with acute asthma treated in the emergency department are frequently treated with intermittent inhaled beta-agonists delivered by nebulisation. The use of continuous beta-agonist (CBA) via nebulisation in the emergency setting may offer additional benefits in acute asthma. Objectives To determine the efficacy (e.g., reductions in admission, improvement in pulmonary functions) and risks (e.g., adverse events, effects on vital signs) of continuous versus intermittent inhaled beta-agonists for the treatment of patients with acute asthma managed in the emergency department. Search methods Randomised controlled trials were identified from the Cochrane Airways Group Specialised Register of trials. In addition, primary authors and content experts were contacted to identify eligible studies. Bibliographies from included studies, known reviews and texts were also searched. The search is considered updated to February 2011. Selection criteria Only randomised controlled trials (RCTs) were eligible for inclusion. Studies were included if patients presented with acute asthma and were treated with either continuous or intermittent inhaled beta-agonists early in the ED treatment. "Continuous" nebulisation was defined as truly continuous aerosol delivery of beta-agonist medication (e.g., using a commercially available large-volume nebuliser, or a small-volume nebuliser with infusion pump) or sufficiently frequent nebulisations that medication delivery was effectively continuous (i.e., 1 nebulisation every 15 minutes or >4 nebulisations per hour). Studies also needed to report either pulmonary function or admission results. Two reviewers independently selected potentially relevant articles and two additional reviewers independently selected articles for inclusion. Methodological quality was independently assessed by two reviewers. Data collection and analysis Data were extracted independently by two reviewers if the authors were unable to verify the validity of information. Missing data were obtained from authors or calculated from other data presented in the paper. The data were analysed using the Cochrane Review Manager (Version 4.1). Relative risks (RR), weighted mean differences (WMD) and standardized mean differences (SMD) are reported with corresponding 95% confidence intervals (CI); both peak expiratory flow rates (PEFR) and forced expiratory volume in one second (FEU-1) data are reported. Main results 165 trials were reviewed and eight were included; a total of 461 patients have been studied (229 with CBA; 232 with intermittent beta-agonists). Overall, admission to hospital was reduced with CBA compared to intermittent beta-agonists (RR: 0.68; 95% CI: 0.5 to 0.9); patients with severe airway obstruction at presentation appeared to benefit most from this intervention (RR: 0.64; 95% CI: 0.5 to 0.9). Patients receiving CBA demonstrated small but statistically significant improvements in pulmonary function tests when all studies were pooled. Patients receiving CBA had greater improvements in % predicted FEU-1 (SMD: 0.3; 95% CI: 0.03 to 0.5) and PEFR (SMD: 0.33; 95% CI: 0.1 to 0.5); this effect was observed by 2-3 hours. Continuous treatment was generally well tolerated, with no clinically important differences observed in pulse rate (WMD:-2.87; 95% CI:-6.0 to 0.3) or blood pressure (WMD:-1.75; 95% CI:-5.6 to 2.1) between the treatment groups. Tremor was equally common in both groups (OR: 0.81; 95% CI: 0.5 to 1.3) and potassium concentration was unchanged (WMD: 0.02; 95% CI:-0.2 to 0.2). Authors' conclusions Current evidence supports the use of CBA in patients with severe acute asthma who present to the emergency department to increase their pulmonary functions and reduce hospitalisation. Moreover, CBA treatment appears to be safe and well tolerated in patients who receive it. C1 [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. [Spooner, Carol] 1G1 52 Walter Mackenzie Hlth Ctr, Div Emergency Med, Edmonton, AB, Canada. [Rowe, Brian H.] Univ Alberta, Dept Emergency Med, Edmonton, AB, Canada. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org FU Division of Emergency Medicine, University of Alberta, Edmonton, Canada; National Institute of Health, Bethesda, USA [NIH HL-03533]; Canada Institute of Health Research, Ottawa, Canada; Garfield Weston Foundation, UK FX Internal sources; Division of Emergency Medicine, University of Alberta, Edmonton, Canada.; External sources; National Institute of Health (CAC; NIH HL-03533), Bethesda, USA.; Canada Institute of Health Research (BHR), Ottawa, Canada.; Garfield Weston Foundation, UK. NR 36 TC 45 Z9 45 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2003 IS 4 AR CD001115 DI 10.1002/14651858.CD001115 PG 39 WC Medicine, General & Internal SC General & Internal Medicine GA V46YH UT WOS:000209919000019 ER PT J AU Edmonds, M Camargo, CA Pollack, CV Rowe, BH AF Edmonds, Marcia Camargo, Carlos A. Pollack, Charles V. Rowe, Brian H. TI Early use of inhaled corticosteroids in the emergency department treatment of acute asthma SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review DE * Emergency Service; Hospital; Acute Disease; Administration; Inhalation; Adrenal Cortex Hormones [* administration & dosage]; Anti-Asthmatic Agents [* administration & dosage]; Asthma [* drug therapy]; Randomized Controlled Trials as Topic; Adult; Child; Humans AB Background Systemic corticosteroid therapy is central to the management of acute asthma. The use of ICS may also be beneficial in this setting. Objectives To determine the benefit of ICS for the treatment of patients with acute asthma managed in the emergency department (ED). Search methods Randomised controlled trials (RCTs) were identified from the Cochrane Airways Group register. Bibliographies from included studies, known reviews, and texts also were searched. The search is considered updated to February of 2005. Selection criteria Only RCTs or quasi-randomised trials were eligible for inclusion. Studies were included if patients presented with acute asthma to the ED or its equivalent, and were treated with ICS or placebo, in addition to standard therapy. Two reviewers independently selected potentially relevant articles, and then independently selected articles for inclusion. Methodological quality was independently assessed by two reviewers. Data collection and analysis Data were extracted independently by two reviewers if the authors were unable to verify the validity of extracted information. Missing data were obtained from the authors or calculated from other data presented in the paper. Main results Ten trials were selected for inclusion. In the included trials, (5 adult, 5 paediatric), a total of 587 patients were studied (294 ICS, 293 non-ICS treated). Patients treated with ICS were less likely to be admitted to hospital (OR: 0.32; 95% CI: 0.18, 0.54). This benefit was evident in the subgroup of patients not receiving concomitant systemic steroids (CS) (OR 0.27; 95% CI: 0.14, 0.52). Patients receiving concomitant CS showed a similar, but non-significant, trend towards reduced admissions compared to placebo treatment (OR 0.45; 95% CI: 0.2, 1.1). Patients receiving ICS also demonstrated small, significant improvements in peak expiratory flows (PEFR WMD: 7%; 95% CI: 4, 11%) and forced expiratory volumes (FEV1WMD: 6%; 95% CI: 2, 10%). The treatment was well tolerated, with few reported adverse side effects. A secondary analysis compared ICS alone vs CS alone; in the seven trials included, there was significant heterogeneity between the study results for admission rates which precluded meaningful pooling of the study results. Authors' conclusions Inhaled steroids reduced admission rates in patients with acute asthma, but it is unclear if there is a benefit of ICS when used in addition to systemic corticosteroids. There is insufficient evidence that ICS therapy results in clinically important changes in pulmonary function or clinical scores when used in acute asthma. Similarly, there is insufficient evidence that ICS alone is as effective as CS. Further research is needed to clarify if there is a benefit of ICS when used in addition to CS. C1 [Edmonds, Marcia] Schulich Sch Med & Dent, 800 Commissioners Rd E1-102, London, ON N6A 5W9, Canada. [Camargo, Carlos A.] Massachusetts Gen Hosp, EMNet Coordinating Ctr, Boston, MA 02114 USA. [Pollack, Charles V.] Penn Hosp, Dept Emergency Med, Philadelphia, PA 19107 USA. [Rowe, Brian H.] Univ Alberta, Dept Emergency Med, Edmonton, AB, Canada. RP Edmonds, M (reprint author), Schulich Sch Med & Dent, 800 Commissioners Rd E1-102, London, ON N6A 5W9, Canada. EM medmonds@ualberta.ca FU National Institutes of Health Bethesda, USA [HL-03533]; Canadian Insitutes of Health Research (CIHR), Canada FX National Institutes of Health (HL-03533) Bethesda, MD (Dr. CA Camargo, Jr), USA.; Canadian Insitutes of Health Research (CIHR), Canada. NR 71 TC 47 Z9 48 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2003 IS 3 AR CD002308 DI 10.1002/14651858.CD002308 PG 59 WC Medicine, General & Internal SC General & Internal Medicine GA V46YG UT WOS:000209918900046 ER PT S AU Park, BH Pierce, M Cense, B de Boer, JF AF Park, BH Pierce, M Cense, B de Boer, JF BE Tuchin, VV Izatt, JA Fujimoto, JG TI Real-time multi-functional optical coherence tomography SO COHERENCE DOMAIN OPTICAL METHODS AND OPTICAL COHERENCE TOMOGRAPHY IN BIOMEDICINE VII SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Coherence Domain Optical Methods and Optical Coherence Tomography in Biomedical VII CY JAN 27-29, 2003 CL SAN JOSE, CA SP SPIE ID VIVO HUMAN SKIN; BIOLOGICAL TISSUE; DOPPLER TOMOGRAPHY; BLOOD-FLOW; SPEED; VELOCITY; BIREFRINGENCE AB We demonstrate real-time acquisition, processing, and display of tissue structure, birefringence, and blood flow in a multi-functional optical coherence tomography (MF-OCT) system. This is accomplished by efficient data processing of the phase-resolved inteference patterns without dedicated hardware or extensive modification to the high-speed fiber-based OCT system. The system acquires images of 2048 depth scans per second, covering an area of 5 mm in width x 1.2 mm in depth with real-time display updating images in a rolling manner K times each second. C1 Harvard Univ, Sch Med, Wellman Labs Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Park, BH (reprint author), Harvard Univ, Sch Med, Wellman Labs Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 24 TC 0 Z9 0 U1 1 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 0-8194-4756-0 J9 P SOC PHOTO-OPT INS PY 2003 VL 4956 BP 179 EP 186 DI 10.1117/12.478971 PG 8 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BX31X UT WOS:000184939000028 ER PT S AU Pierce, MC Sheridan, RL Park, BH Cense, B de Boer, JF AF Pierce, MC Sheridan, RL Park, BH Cense, B de Boer, JF BE Tuchin, VV Izatt, JA Fujimoto, JG TI Burn depth determination in human skin using polarization-sensitive optical coherence tomography SO COHERENCE DOMAIN OPTICAL METHODS AND OPTICAL COHERENCE TOMOGRAPHY IN BIOMEDICINE VII SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Coherence Domain Optical Methods and Optical Coherence Tomography in Biomedical VII CY JAN 27-29, 2003 CL SAN JOSE, CA SP SPIE DE biomedical imaging; birefringence; collagen ID BIREFRINGENCE; TISSUE; ULTRASOUND; PERFUSION; DIAGNOSIS; AID AB Accurate evaluation of the depth of injury in burn victims is of considerable practical value to the surgeon, both for initial determination of resuscitation fluid requirements, and in deciding whether excision and closure of the wound is necessary. Currently, burn depth is most accurately evaluated by visual inspection, though decisions concerning treatment may not be possible for a number of days post-injury. As part of our ongoing efforts to provide an objective, quantitative method for burn depth determination, we present here the results of a study using polarization-sensitive optical coherence tomography (PS-OCT) to detect and measure thermally induced changes in collagen birefringence in skin excised from burn patients. We find that PS-OCT is capable of imaging and quantifying significantly reduced birefringence in burned human skin. C1 Harvard Univ, Sch Med, Wellman Labs Photomed, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Pierce, MC (reprint author), Harvard Univ, Sch Med, Wellman Labs Photomed, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 25 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4756-0 J9 P SOC PHOTO-OPT INS PY 2003 VL 4956 BP 263 EP 270 DI 10.1117/12.478966 PG 8 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BX31X UT WOS:000184939000038 ER PT J AU Kilzieh, N Wood, AE Erdmann, J Raskind, M Tapp, A AF Kilzieh, N Wood, AE Erdmann, J Raskind, M Tapp, A TI Depression in Kraepelinian schizophrenia SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID POST-PSYCHOTIC DEPRESSION; SYMPTOMS; REPLICATION; DISORDERS; EXTENSION; RELAPSE AB In order to improve our understanding of depression in chronic schizophrenia, depressive symptoms were assessed in institutionalized, so called Kraepelinian, patients with schizophrenia (N = 43). The patients had been ill and dependent on others for at least 5 years. Depressive symptoms as measured by the Hamilton Depression (HAM-D) scale were less prevalent in this population compared to published data on non-Kraepelinian patients. Only 5% of our Kraepelinian patients had a HAM-D score greater than or equal to 16. There was also a low prevalence of core depressive symptoms (depressed mood, suicidal ideation, and guilt). The relationship of depression to other dimensions of schizophrenia was explored. Depression had a modest positive correlation (r = 0.44) with general psychopathology as measured by the Brief Psychiatric Rating Scale (BPRS), but not with positive symptoms as measured by BPRS positive subscale or negative symptoms as measured by the Scale for the Assessment of Negative Symptoms (SANS). Depression also showed a modest positive correlation (r =.48) using the Simpson-Angus Rating Scale (SAS) for extrapyramidal symptoms (EPS). These results indicate that in Kraepelinian schizophrenia, depression is not prevalent, even though patients are severely ill both in symptom and functioning domains. The results of our analysis support that Kraepelinian schizophrenia is a distinct subtype, and raise questions regarding the boundary between schizoaffective disorder and non-Kraepelinian schizophrenia. Finally, the low rate of depression observed revives the notion that preservation of core functional abilities is important for a depressive reaction to evolve in schizophrenia. Copyright 2003, Elsevier Science (USA). All rights reserved. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Kilzieh, N (reprint author), VA Puget Sound Hlth Care Syst, Mental Hlth Serv 116M, Amer Lake Div, Tacoma, WA 98493 USA. NR 27 TC 11 Z9 12 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JAN-FEB PY 2003 VL 44 IS 1 BP 1 EP 6 DI 10.1053/comp.2003.50002 PG 6 WC Psychiatry SC Psychiatry GA 632TN UT WOS:000180239100001 PM 12524629 ER PT J AU Papakostas, GI Petersen, T Mischoulon, D Hughes, ME Spector, AR Alpert, JE Fava, M Nierenberg, AA AF Papakostas, GI Petersen, T Mischoulon, D Hughes, ME Spector, AR Alpert, JE Fava, M Nierenberg, AA TI Functioning and interpersonal relationships as predictors of response in treatment-resistant depression SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID STRESSFUL LIFE EVENTS; DELIBERATE SELF-HARM; MAJOR DEPRESSION; RECOVERY; SERTRALINE; IMIPRAMINE AB The purpose of this study was to examine whether occupational functioning or the quality of interpersonal relationships is predictive of clinical response to a 6-week open trial of nortriptyline (NT) in patients with treatment-resistant depression (TRD). Ninetytwo subjects with TRD were treated openly with NT for 6 weeks. The longitudinal interval follow-up evaluation (LIFE) scale was administered at baseline. A logistic regression was performed using occupational functioning and interpersonal relationships (over the past month and over the past 5 years) as predictors of treatment response. Unpaired ttests were performed to examine mean composite LIFE score values between responders and nonresponders. The composite scores that were statistically significant were used as single predictors of treatment status in separate logistic regression equations. Better occupational function over the past 5 years predicted better response to treatment with NT in patients with TRD. Beyond a history of nonresponse to antidepressants, long-term occupational function may be a predictor of outcome in the treatment of TRD. Copyright 2003, Elsevier Science (USA), All rights reserved. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R29 MH46952] NR 36 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JAN-FEB PY 2003 VL 44 IS 1 BP 44 EP 50 DI 10.1053/comp.2003.50012 PG 7 WC Psychiatry SC Psychiatry GA 632TN UT WOS:000180239100007 PM 12524635 ER PT B AU Kaazempur-Mofrad, MR Younis, HF Karcher, H Lin, JW Golji, J Isasi, AG Tan, JS Chan, RC Kamm, RD AF Kaazempur-Mofrad, MR Younis, HF Karcher, H Lin, JW Golji, J Isasi, AG Tan, JS Chan, RC Kamm, RD BE Bathe, KJ TI Biological simulations at all scales: from cardiovascular hemodynamics to protein molecular mechanics SO COMPUTATIONAL FLUID AND SOLID MECHANICS 2003, VOLS 1 AND 2, PROCEEDINGS LA English DT Proceedings Paper CT 2nd MIT Conference on Computational Fluid and Solid Mechanics CY JUN 17-20, 2003 CL MIT, CAMBRIDGE, MA SP GM, HP, Compaq, Daimler Chrysler, Hyundai, Ford, MSC Software, Sgi, ESI Grp, Boeing, CINI, Texas Instruments, Fluent Inc, CFX, CFD Soc Canada, SIAM, Michelin, IACMAG, Adinan, Mecalog, Star CD, ALCAN, ANSYS Inc HO MIT DE computational simulation; multi-scale biological phenomena AB Computational simulations provide a powerful tool for understanding the complex biological systems at all scales. A wide range of examples is presented here to show the extensive role of computational simulation in the development of biological sciences. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Kamm, RD (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 5 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 0-08-044046-0 PY 2003 BP 8 EP 12 PG 5 WC Mechanics SC Mechanics GA BX31V UT WOS:000184938200002 ER PT B AU Lees, S AF Lees, S BE Bathe, KJ TI Structure modification of collagen associated with mineral and water content SO COMPUTATIONAL FLUID AND SOLID MECHANICS 2003, VOLS 1 AND 2, PROCEEDINGS LA English DT Proceedings Paper CT 2nd MIT Conference on Computational Fluid and Solid Mechanics CY JUN 17-20, 2003 CL MIT, CAMBRIDGE, MA SP GM, HP, Compaq, Daimler Chrysler, Hyundai, Ford, MSC Software, Sgi, ESI Grp, Boeing, CINI, Texas Instruments, Fluent Inc, CFX, CFD Soc Canada, SIAM, Michelin, IACMAG, Adinan, Mecalog, Star CD, ALCAN, ANSYS Inc HO MIT DE collagen; lateral spacing; constant mass; mineral; fibrils AB It is well known that the lateral spacing between collagen molecules varies as the inverse wet density. It has been shown recently that the lateral spacing is linearly dependent on the inverse wet density whether the tissue is wet or dry. The slope of the wet tissue plot is positive while that at for dry tissue is negative. An explanation is offered that relates these various observations to the deposition of mineral in hard tissues. C1 Forsyth Inst, Dept Bioengn, Boston, MA 02115 USA. RP Lees, S (reprint author), Forsyth Inst, Dept Bioengn, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 0-08-044046-0 PY 2003 BP 1759 EP 1761 PG 3 WC Mechanics SC Mechanics GA BX31V UT WOS:000184938200426 ER PT S AU Rae, A Jackson, D Ramanan, P Flanz, J Leyman, D AF Rae, A Jackson, D Ramanan, P Flanz, J Leyman, D BE Anderson, S Felici, M Littlewood, B TI Critical feature analysis of a radiotherapy machine SO COMPUTER SAFETY, RELIABILITY, AND SECURITY, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 22nd International Conference on Computer Safety, Reliability and Security CY SEP 23-26, 2003 CL EDINBURGH, SCOTLAND SP British Comp Soc, DIRC, European Asoc Cognit Ergonom, ENCRESS, Gesell Informatik, IEE, Int Federat Automat Control, IFIG WG10 4, IFIG WG13 5, ISA EUNET, Austrian Comp Soc, Safety Critical Syst Club, Software Reliabil & Metr Club AB The software implementation of the emergency shutdown feature in a major radiotherapy system was analyzed, using a directed form of code review based on module dependences. Dependences between modules are labelled by particular assumptions; this allows one to trace through the code, and identify those fragments responsible for critical features. An 'assumption tree' is constructed in parallel, showing the assumptions which each module makes about others. The root of the assumption tree is the critical feature of interest, and its leaves represent assumptions which, if not valid, might cause the critical feature to fail. The analysis revealed some unexpected assumptions that motivated improvements to the code. C1 Univ Queensland, St Lucia, Qld, Australia. MIT, Lab Comp Sci, Cambridge, MA USA. Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA USA. Ion Beam Applicat, Louvain, Belgium. RP Rae, A (reprint author), Univ Queensland, St Lucia, Qld, Australia. NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-20126-2 J9 LECT NOTES COMPUT SC PY 2003 VL 2788 BP 221 EP 234 PG 14 WC Computer Science, Software Engineering; Computer Science, Theory & Methods SC Computer Science GA BY02P UT WOS:000187294900018 ER PT S AU Chan, RC Ferencik, M Wu, T Hoffmann, U Brady, TJ Achenbach, S AF Chan, RC Ferencik, M Wu, T Hoffmann, U Brady, TJ Achenbach, S BE Murray, A TI Evaluation of arterial wall Imaging with 16-slice multi-detector computed tomography SO COMPUTERS IN CARDIOLOGY 2003, VOL 30 SE COMPUTERS IN CARDIOLOGY LA English DT Proceedings Paper CT 30th Annual Meeting on Computers in Cardiology CY SEP 21-24, 2003 CL Thessaloniki Chalkidiki, GREECE SP European Soc Cardiol, Natl Inst Hlth ID PLAQUES AB We have characterized the performance of 16-slice cardiac MDCT for assessment of coronary disease burden and lesion composition under optimal conditions. Morphology measurements with MDCT were accurate and reproducible. Detection of lipid-containing regions was possible with sensitivities greater than or equal to 88% and specificity of 96% for regions greater than or equal to1.5mm in size with greater than or equal to 30% lipid. Estimation of lipid pool dimension is difficult and lipid pool CT densities cannot be used directly to determine the %lipid content due to noise and blurring. These results represent the best-case performance of MDCT and help to guide interpretation of images obtained in vivo. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Cardiac MR&CT Program, Boston, MA 02114 USA. RP Chan, RC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Cardiac MR&CT Program, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0276-6574 BN 0-7803-8170-X J9 COMPUT CARDIOL PY 2003 VL 30 BP 661 EP 664 DI 10.1109/CIC.2003.1291242 PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Cardiovascular System & Cardiology; Computer Science; Engineering GA BY90P UT WOS:000189491900168 ER PT J AU Bartlett, JD Zhou, ZJ Skobe, Z Dobeck, JM Tryggvason, K AF Bartlett, JD Zhou, ZJ Skobe, Z Dobeck, JM Tryggvason, K TI Delayed tooth eruption in membrane type-1 matrix metalloproteinase deficient mice SO CONNECTIVE TISSUE RESEARCH LA English DT Article; Proceedings Paper CT 7th International Conference on the Chemistry and Biology of Mineralized Tissues CY NOV 04-09, 2001 CL PONTE VEDRA, FLORIDA DE biomineralization; dental enamel; dentin; development; matrix metalloproteinase ID RNA TISSUE DISTRIBUTION; GELATINASE-A MMP-2; AMELOGENIN HYDROLYSIS; INTERGLOBULAR DOMAIN; GEL ELECTROPHORESIS; MOLECULAR-CLONING; DEVELOPING ENAMEL; PROGELATINASE-A; PORCINE DENTIN; MT1-MMP AB Membrane-type I matrix metalloproteinase (MT1-MMP) is expressed highly in mineralizing tissues including bones and teeth. Mice deficient in MT1-MMP (-/-) display severe defects in skeletal development including dwarfism, osteopenia, and craniofacial abnormalities. Death occurs in these mice by about 3 weeks of age. Since MT1-MMP is expressed by the ameloblasts of the enamel organ and by the odontoblasts of the dental papilla, we asked if the developing teeth were adversely affected in the knockout animals. Molars from MT1-MMP -/- mice and controls were examined by histological, X-ray, and SEM analysis at 4, 18-20, and 25 days of postnatal development. At 4 days of development the molars from the -/- mice appeared histologically normal. At 18-20 days of development, the first molars of the -/- mice had apparently normal tooth crowns with normal dentin and enamel; however, the roots were truncated and the teeth had not yet erupted. In contrast to the -/- mice, the first molars of the 18-20-day control animals had erupted. SEM analysis of a -/- first molar and incisor revealed a normal enamel prism pattern. However, X-ray analysis demonstrated that tooth eruption was delayed by approximately 5 days and that the tooth roots were abnormally short in the knockout animals. Since MT1-MMP-deficient mice have been demonstrated to display a generalized increase in bone resorption, these data suggest that inefficient growth of bone surrounding the tooth root complex causes a delay in tooth eruption. C1 Forsyth Inst, Harvard Forsyth Dept Oral Biol, Dept Cytokine Biol, Boston, MA 02115 USA. Karolinska Inst, Dept Med Biochem & Biophys, Div Matrix Biol, Stockholm, Sweden. Forsyth Inst, Biostruct Core Facil, Boston, MA 02115 USA. RP Bartlett, JD (reprint author), Forsyth Inst, Harvard Forsyth Dept Oral Biol, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM jbartlett@forsyth.org RI Zhou, Zhongjun/C-4476-2009 FU NIDCR NIH HHS [P01 DE013237, DE13237] NR 37 TC 5 Z9 5 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PY 2003 VL 44 SU 1 BP 300 EP 304 DI 10.1080/03008200390181816 PG 5 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA 660AD UT WOS:000181811000050 PM 12952213 ER PT J AU Sedeek, KA Takeuchi, M Suchodolski, K Kacmarek, RM AF Sedeek, KA Takeuchi, M Suchodolski, K Kacmarek, RM TI Determinants of tidal volume during high-frequency oscillation SO CRITICAL CARE MEDICINE LA English DT Article DE high-frequency oscillation; tidal volume; frequency; inspiratory to expiratory ratio; lung injury; acute respiratory distress syndrome ID RESPIRATORY-DISTRESS-SYNDROME; VENTILATION; TRIAL AB Objective. High-frequency oscillation has been proposed for use in adult acute respiratory distress syndrome. However, limited data are available on the effect of pressure amplitude and rate (Hz) on tidal volumes delivered during high-frequency oscillation in adults. Design. Prospective, animal model, lung injury study. Setting. Large-animal laboratory of a university-affiliated medical center. Subjects. Nine sheep (29.2 +/- 2.4 kg). Interventions. Severe lung injury was induced by repeated saline lung lavage. After stabilization, high-frequency oscillation was initiated at a mean airway pressure equal to the point of maximum curvature on the deflation limb of the pressure-volume curve (26 +/- 1.9 cm H2O). Tidal volume at all combinations of rates of 4, 6, 8, and 10 Hz, pressure amplitudes of 30, 40, 50, and 60 cm H2O, and inspiratory/expiratory ratios of 1:1 and 1:2 (using the Sensormedics 3100B oscillator) were measured. Flow was measured by a pneumotachometer, amplified and digitized at 1000 Hz. Three breaths were analyzed at each setting. Measurements and Main Results. At both inspiratory/expiratory ratios, tidal volume was directly proportional to pressure amplitude and inversely proportional to frequency. During an inspiratory/expiratory ratio of 1:1, at 60 cm H2O pressure amplitude and 4 Hz, a tidal volume of 129.1 +/- 34.8 mL (4.4 +/- 1.2 mL/kg) was delivered. Conclusions. At low rates and high-pressure amplitudes in this model, tidal volumes approaching conventional mechanical ventilation can be delivered during high-frequency oscillation. C1 Massachusetts Gen Hosp, Dept Anesthesia Resp Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Resp Care, Resp Care Ellison 401, Boston, MA 02114 USA. NR 16 TC 42 Z9 43 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2003 VL 31 IS 1 BP 227 EP 231 DI 10.1097/01.CCM.0000044504.43673.B0 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 640XU UT WOS:000180714800035 PM 12545020 ER PT J AU Yusuf, RZ Duan, Z Lamendola, DE Penson, RT Seiden, MV AF Yusuf, R. Z. Duan, Z. Lamendola, D. E. Penson, R. T. Seiden, M. V. TI Paclitaxel Resistance: Molecular Mechanisms and Pharmacologic Manipulation SO CURRENT CANCER DRUG TARGETS LA English DT Article DE paclitaxel; drug resistance; reversal of drug resistance; in vivo drug resistance assays; MDR; Pgp; beta-tubulin; cytokine. AB It has been approximately ten years since the Food and Drug Administration (FDA) approved paclitaxel for the treatment of platinum resistant epithelial ovarian carcinoma. Since the approval, the drug has found therapeutic applications in a variety of schedules and in a wide variety of epithelial malignancies. Its novel mechanism of action provided the hope that it would demonstrate anti-neoplastic activity in multidrug resistant tumor cells. Unfortunately, as with other chemotherapeutic drugs, resistance is commonly seen. Laboratory investigation has defined a wide variety of resistance mechanisms including overexpression of multidrug resistance (MDR-1) gene, molecular changes in the target molecule (beta- tubulin), changes in apoptotic regulatory and mitosis checkpoint proteins, and more recently changes in lipid composition and potentially the overexpression of interleukin 6 (IL- 6). This review describes the in vitro molecular data that define and support the various mechanisms of resistance and critically evaluates the evidence for the participation of these mechanisms in clinically relevant paclitaxel resistance. This review also explores pharmacologic attempts to modulate paclitaxel resistance, principally through inhibition of the MDR-1 drug efflux pump. Future avenues for drug resistance research and its pharmacologic manipulation in the clinic are discussed. C1 [Yusuf, R. Z.; Duan, Z.; Lamendola, D. E.; Penson, R. T.; Seiden, M. V.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Cox 640,100 Blossom St, Boston, MA 02114 USA. EM mseiden@partners.org NR 185 TC 156 Z9 170 U1 2 U2 17 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 EI 1873-5576 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PY 2003 VL 3 IS 1 BP 1 EP 19 DI 10.2174/1568009033333754 PG 19 WC Oncology SC Oncology GA V33XY UT WOS:000209052700001 PM 12570657 ER PT J AU Jagadeesh, D Syngal, S AF Jagadeesh, D Syngal, S TI Genetic testing for hereditary nonpolyposis colorectal cancer SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; MICROSATELLITE INSTABILITY; BETHESDA GUIDELINES; COLON-CANCER; MLH1; MSH2; HNPCC; MUTATIONS; CARRIERS; RISK AB Colorectal cancer remains a major cause of morbidity and mortality in United States. While most newly diagnosed cases are sporadic, a small percent of colorectal cancers are due to hereditary cancer syndromes, of which hereditary nonpolyposis colorectal cancer (HNPCC) is the most common. HNPCC is caused by mutations resulting in defective DNA mismatch repair gene function. Advances in molecular technology have enabled us to use genetic testing for HNPCC genes to identify high-risk families. Over the past several years, genetic testing for HNPCC has evolved from a research endeavor to a clinical test that often is an integral part of providing care for high-risk families. This article reviews the available genetic tests, genetic testing recommendations, interpretation of test results, and the clinical impact of genetic testing for HNPCC. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 1 Jimmy Fund Way,SM 209, Boston, MA 02115 USA. NR 33 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD JAN PY 2003 VL 19 IS 1 BP 57 EP 63 DI 10.1097/00001574-200301000-00010 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 626GH UT WOS:000179863100010 PM 15699895 ER PT J AU Clark, JJ Smith, FO Arceci, RJ AF Clark, JJ Smith, FO Arceci, RJ TI Update in childhood acute myeloid leukemia: recent developments in the molecular basis of disease and novel therapies SO CURRENT OPINION IN HEMATOLOGY LA English DT Review ID ACUTE PROMYELOCYTIC LEUKEMIA; BONE-MARROW TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; INTERNAL TANDEM DUPLICATION; TRANS-RETINOIC ACID; TYROSINE KINASE INHIBITOR; CHILDRENS CANCER GROUP; ENDOTHELIAL GROWTH-FACTOR; ARSENIC TRIOXIDE AS2O3; FACTOR FUSION PROTEIN AB Childhood acute myeloid leukemia is a heterogeneous group of disorders that remains challenging to treat. There are multiple common genetic alterations in childhood acute myeloid leukemia. These include chromosomal translocations affecting RUNX1-CBFbeta, RARalpha, and MLL. There are known activating mutations in the genes for the receptor tyrosine kinases FLT3, KIT, and FMS. As these abnormalities are better understood, they are providing important insights into the pathogenesis of disease as well as information about prognosis. Although intensive chemotherapy remains the mainstay of acute myeloid leukemia therapy, long-term cure rates with chemotherapy alone remain approximately 50%, creating an urgent need for better therapies. Multiple avenues are being explored in the design of new treatments for pediatric acute myeloid leukemia. Targeted therapies include targeted antibody therapy; inhibitors of FLT3, KIT, and farnesyltransferase; diphtheria toxin conjugated to the granulocyte-macrophage colony-stimulating factor; and antisense oligonucleotides. Another area of interest is chromatin remodeling and differentiation therapy, including agents such as all-trans retinoic acid, arsenic trioxide, and inhibitors of DNA methylation and histone deacetylation. There are also ongoing trials of antiangiogenesis agents. Another avenue for novel therapies is immunotherapy with agents such as interleukin-2 and tumor vaccines. This article reviews recent advances in understanding of the molecular basis for childhood acute myeloid leukemia and the design of novel therapies for the treatment of childhood acute myeloid leukemia. (C) 2003 Lippincott Williams Wilkins, Inc. C1 Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Boston, MA 02115 USA. Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Cincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Dept Pediat, Baltimore, MD USA. RP Clark, JJ (reprint author), Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, 44 Binney St, Boston, MA 02115 USA. NR 138 TC 15 Z9 18 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JAN PY 2003 VL 10 IS 1 BP 31 EP 39 DI 10.1097/00062752-200301000-00006 PG 9 WC Hematology SC Hematology GA 624TX UT WOS:000179778600006 PM 12483109 ER PT J AU Gricks, CS Gribben, JG AF Gricks, CS Gribben, JG TI Cytotoxic T cell reponses against immunoglobulin in malignant and normal B cells: Implications for tumor immunity and autoimmunity SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID VARIABLE-REGION GENE; CLASS-I MOLECULES; CHRONIC LYMPHOCYTIC-LEUKEMIA; MELANOMA-REACTIVE CTL; NON-HODGKINS-LYMPHOMA; MYELIN BASIC-PROTEIN; PROTECTIVE IMMUNITY; ANTIGENIC PEPTIDE; PERIPHERAL-BLOOD; MULTIPLE-MYELOMA AB There is compelling evidence in murine model systems and from human clinical trials that immunotherapy approaches can induce immune responses against tumors. The idiotypic determinants (Id) of the rearranged immunoglobulin proteins of malignant B cells were the First tumor-specific antigens to be recognized and provide a target of an immune mediated response against malignant B cells. Id was thought of as not only tumor-specific but also patient-specific since every patient's malignant B cell clone expresses a unique sequence that is determined by the third complementary determinant regions (CDRIII) of the Id. Although CD4(+) T cell responses against Id have been demonstrated, the role of CD8(+) T lymphocytes in induction of responses against Id has remained elusive. The requirements for peptides to bind to HI,A molecules and elicit T cell responses have been studied extensively and are best characterized for HLA class I molecules that elicit CD8(+) cytotoxic T lymphocyte (CTL) responses. We applied a bioinformatics approach to the immunoglobulin sequences of malignant and normal B cells. We identified and characterized epitopes recognized by CTLs within these sequences and could generate CTL responses against Id determinants of both normal B cells and malignant B cell. Class II binding immunoglobulin derived sequences had weak binding affinity but were capable in some cases of inducing CTL mediated immune response. More surprisingly, these sequences were not derived from unique sequences within the CDRIII region but were more often from framework region sequences that were often shared among patients and were also found in the immunoglobulin sequences of normal B cells. It was possible to increase binding affinity by single amino acid substitutions at the residues responsible for binding to HLA class I molecules. These "heteroclitic" peptides resulted in generation of T cells with increased ability to kill targets expressing not only the altered peptides, but also the native sequences from which these peptides had been derived. These findings have implications not only for tumor immunity, but also for regulation of B cell dependent autoimmune responses. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Gribben, JG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, 44 Binney St, Boston, MA 02115 USA. NR 97 TC 12 Z9 13 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2003 VL 9 IS 23 BP 1889 EP 1903 DI 10.2174/1381612033454333 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 713HG UT WOS:000184851000008 PM 12871193 ER PT J AU Petersen, TJ Alpert, JE Papakostas, GI Bernstein, EM Freed, R Smith, MM Fava, M AF Petersen, TJ Alpert, JE Papakostas, GI Bernstein, EM Freed, R Smith, MM Fava, M TI Early-onset depression and the emotional and behavioral characteristics of offspring SO DEPRESSION AND ANXIETY LA English DT Article DE depressive disorder; child of impaired parents; child behavior; affective symptoms ID PROSPECTIVE-LONGITUDINAL-COMMUNITY; CONTROLLED FAMILY HISTORY; MAJOR DEPRESSION; PSYCHIATRIC-DISORDERS; MENTAL-DISORDERS; PANIC DISORDER; HIGH-RISK; PARENTS; CHILDREN; PROBANDS AB We compared the emotional and behavioral characteristics of offspring of parents with early-onset depression and the offspring of parents with late-onset depression. Forty-three parents who met criteria for major depressive disorder (MDD) completed the Achenbach Child Behavior Checklist-Parent Report Version (CBCL) for a birth child (n = 43, age range 6-17 years). Parents were classified as having either early SD onset (< 19 years) or late-onset (greater than or equal to 19 years) MDD based on responses gathered during the SCID-P interview. Unpaired t-tests were used to compare the two offspring groups on CBCL clinical and competency scales. Chi-square analyses and unpaired t-tests were used to compare the two parent groups on demographic and clinical features. Offspring of parents with early-onset depression scored significantly higher on the majority of the CBCL clinical scale scores when compared with offspring of parents with late-onset depression, rated as exhibiting higher levels of the characteristics measured. withdrawn, anxious/depressed, social problems, thought problems, attention problems, delinquent behavior, and aggressive behavior. Additionally, this group bad a significantly higher total T score (a global measure of psychopathology) and significantly lower social functioning. Children of parents with early-onset depression may be at higher risk for behavioral and emotional problems than offspring of parents with late-onset depression. This finding may be significant in uncovering sources of vulnerability and formulating intervention strategies for offspring of depressed parents. (C) 2003 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Petersen, TJ (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X NR 28 TC 2 Z9 2 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2003 VL 18 IS 2 BP 104 EP 108 DI 10.1002/da.10118 PG 5 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 726HJ UT WOS:000185592600008 PM 12964178 ER PT J AU Kenney, AM Cole, MD Rowitch, DH AF Kenney, AM Cole, MD Rowitch, DH TI Nmyc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors SO DEVELOPMENT LA English DT Article DE cerebellum; sonic hedgehog; proliferation; cyclopamine; medulloblastoma; Nmyc; neural precursor; TRRAP; mouse ID CELL-CYCLE PROGRESSION; IMMEDIATE EARLY GENES; C-MYC EXPRESSION; N-MYC; EMBRYONIC LETHALITY; INHIBITS DIFFERENTIATION; ESSENTIAL COFACTOR; PROTEIN-KINASE; NERVOUS-SYSTEM; GROWTH-FACTOR AB Hedgehog pathway activation is required for expansion of specific neuronal precursor populations during development and is etiologic in the human cerebellar tumor, medulloblastoma. We report that sonic hedgehog (Shh) signaling upregulates expression of the protooncogene Nmyc in cultured cerebellar granule neuron precursors (CGNPs) in the absence of new protein synthesis. The temporal-spatial expression pattern of Nmyc, but not other Myc family members, precisely coincides with regions of hedgehog proliferative activity in the developing cerebellum and is observed in medulloblastomas of Patched (Ptch) heterozygous mice. Overexpression of Nmyc promotes cell-autonomous G(1) cyclin upregulation and CGNP proliferation independent of Shh signaling. Furthermore, Myc antagonism in vitro significantly decreases proliferative effects of Shh in cultured CGNPs. Together, these findings identify Nmyc as a direct target of the Shh pathway that functions to regulate cell cycle progression in cerebellar granule neuron precursors. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. RP Rowitch, DH (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. FU NINDS NIH HHS [R01 NS4051, R21 NS41764-01] NR 88 TC 331 Z9 340 U1 3 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JAN PY 2003 VL 130 IS 1 BP 15 EP 28 DI 10.1242/dev.00182 PG 14 WC Developmental Biology SC Developmental Biology GA 637WZ UT WOS:000180537900003 PM 12441288 ER PT J AU Wallis, D Hamblen, M Zhou, Y Venken, KJT Schumacher, A Grimes, HL Zoghbi, HY Orkin, SH Bellen, HJ AF Wallis, D Hamblen, M Zhou, Y Venken, KJT Schumacher, A Grimes, HL Zoghbi, HY Orkin, SH Bellen, HJ TI The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival SO DEVELOPMENT LA English DT Article DE Gfi1; Gfi1b; senseless; PAG-3; inner ear hair cell; basic helix-loop-helix (bHLH); deafness; mouse ID PERIPHERAL NERVOUS-SYSTEM; NEUROENDOCRINE DIFFERENTIATION; IL-2-INDEPENDENT GROWTH; SENSORY EPITHELIA; GENE; DROSOPHILA; EXPRESSION; MATH1; MASH1; CNS AB Gfi1 was first identified as causing interleukin 2-independent growth in T cells and lymphomagenesis in mice. Much work has shown that Gfi1 and Gfi1b, a second mouse homolog, play pivotal roles in blood cell lineage differentiation. However, neither Gfi1 nor Gfi1b has been implicated in nervous system development, even though their invertebrate homologues, senseless in Drosophila and pag-3 in C elegans are expressed and required in the nervous system. We show that Gfi1 mRNA is expressed in many areas that give rise to neuronal cells during embryonic development in mouse, and that Gfi1 protein has a more restricted expression pattern. By E12.5 Gfi1 mRNA is expressed in both the CNS and PNS as well as in many sensory epithelia including the developing inner ear epithelia. At later developmental stages, Gfi1 expression in the ear is refined to the hair cells and neurons throughout the inner ear. Gfi1 protein is expressed in a more restricted pattern in specialized sensory cells of the PNS, including the eye, presumptive Merkel cells, the lung and hair cells of the inner ear. Gfi1 mutant mice display behavioral defects that are consistent with inner ear anomalies, as they are ataxic, circle, display head tilting behavior and do not respond to noise. They have a unique inner ear phenotype in that the vestibular and cochlear hair cells are differentiafly affected. Although Gfi1-deficient mice initially specify inner ear hair cells, these hair cells are disorganized in both the vestibule and cochlea. The outer hair cells of the cochlea are improperly innervated and express neuronal markers that are not normally expressed in these cells. Furthermore, Gfil mutant mice lose all cochlear hair cells just prior to and soon after birth through apoptosis. Finally, by five months of age there is also a dramatic reduction in the number of cochlear neurons. Hence, Gfil is expressed in the developing nervous system, is required for inner ear hair cell differentiation, and its loss causes programmed cell death. C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Div Hematol Oncol,Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA. Univ Louisville, Inst Cellular Therapeut, Louisville, KY 40202 USA. Univ Louisville, Dept Surg, Louisville, KY 40202 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Bellen, HJ (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. EM hbellen@bcm.tmc.edu RI Venken, Koen/B-9909-2013 OI Venken, Koen/0000-0003-0741-4698 FU NICHD NIH HHS [HD 24064]; NIDCD NIH HHS [F32 DC 5109] NR 54 TC 140 Z9 147 U1 1 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD JAN PY 2003 VL 130 IS 1 BP 221 EP 232 DI 10.1242/dev.00190 PG 12 WC Developmental Biology SC Developmental Biology GA 637WZ UT WOS:000180537900020 PM 12441305 ER PT J AU Omer, A Duvivier-Kali, VF Trivedi, N Wilmot, K Bonner-Weir, S Weir, GC AF Omer, A Duvivier-Kali, VF Trivedi, N Wilmot, K Bonner-Weir, S Weir, GC TI Survival and maturation of microencapsulated porcine neonatal pancreatic cell clusters transplanted into immunocompetent diabetic mice SO DIABETES LA English DT Article ID ISLET TRANSPLANTATION; ENDOCRINE PANCREAS; NUDE-MICE; DIFFERENTIATION; XENOGRAFTS; MASS; IMMUNOSUPPRESSION; PROLIFERATION; PROTECTION; REJECTION AB Differentiation and maturation of porcine neonatal pancreatic cell clusters (NPCCs) microencapsulated in barium alginate were assessed after transplantation into immunocompetent mice. Microencapsulated NPCCs were transplanted into the peritoneal cavity of streptozocin-induced diabetic B6AF1 mice (n = 32). The microcapsules were removed at 2, 6, and 20 weeks and examined for cellular overgrowth, insulin content, and insulin secretory responses to glucose and glucose with theophylline. The differentiation, maturation, and proliferation of the beta-cells in the NPCCs were assessed by immunohistochemistry. Blood glucose levels were normalized in 81% of the animals that received a transplant and remained normal until termination of the experiments at 20 weeks. Hyperglycemic blood glucose levels after explantation of the capsules confirmed the function of the encapsulated NPCCs. Insulin content of the encapsulated NPCCs was increased 10-fold at 20 weeks after transplantation compared with pretransplantation levels. A 3.2-fold increase of the ratio of the beta-cell area to the total cellular area was observed at 20 weeks, demonstrating the maturation of NPCCs into beta-cells. In conclusion, NPCCs encapsulated with simple barium alginate can differentiate into beta-cells and reverse high blood glucose levels in immunocompetent mice without immunosuppression for >20 weeks. C1 Harvard Univ, Sect Islet Transplantat & Cell Biol, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Weir, GC (reprint author), Harvard Univ, Sect Islet Transplantat & Cell Biol, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [P01 DK 53087, DK 36836, R01 DK 50657] NR 26 TC 78 Z9 83 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2003 VL 52 IS 1 BP 69 EP 75 DI 10.2337/diabetes.52.1.69 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 631FK UT WOS:000180157300010 PM 12502495 ER PT J AU Butler, AE Janson, J Bonner-Weir, S Ritzel, R Rizza, RA Butler, PC AF Butler, AE Janson, J Bonner-Weir, S Ritzel, R Rizza, RA Butler, PC TI beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes SO DIABETES LA English DT Article ID ISLET AMYLOID POLYPEPTIDE; INSULIN-SECRETION; B-CELLS; COMPENSATORY GROWTH; PANCREATIC-ISLETS; GENE-EXPRESSION; MACACA-NIGRA; A-CELLS; MELLITUS; GLUCOSE AB Type 2 diabetes is characterized by impaired insulin secretion. Some but not all studies suggest that a decrease in beta-cell mass contributes to this. We examined pancreatic tissue from 124 autopsies: 91 obese cases (BMI >27 kg/m(2); 41 with type 2 diabetes, 15 with impaired fasting glucose [IFG], and 35 nondiabetic subjects) and 33 lean cases (13111 <25 kg/m(2); 16 type 2 diabetic and 17 nondiabetic subjects). We measured relative beta-cell volume, frequency of beta-cell apoptosis and replication, and new islet formation from exocrine ducts (neogenesis). Relative beta-cell volume was increased in obese versus lean nondiabetic cases (P = 0.05) through the mechanism of increased neogenesis (P < 0.05). Obese humans with IFG and type 2 diabetes had a 40% (P < 0.05) and 63% (P < 0.01) deficit and lean cases of type 2 diabetes had a 41% deficit (P < 0.05) in relative R-cell volume compared with nondiabetic obese and lean cases, respectively. The frequency of beta-cell replication was very low in all cases and no different among groups. Neogenesis, while increased with obesity, was comparable in obese type 2 diabetic, IFG, or nondiabetic subjects and in lean type 2 diabetic or nondiabetic subjects. However, the frequency of beta-cell apoptosis was increased 10-fold in lean and 3-fold in obese cases of type 2 diabetes compared with their respective nondiabetic control group (P < 0.05). We conclude that beta-cell mass is decreased in type 2 diabetes and that the mechanism underlying this is increased beta-cell apoptosis. Since the major defect leading to a decrease in beta-cell mass in type 2 diabetes is increased apoptosis, while new islet formation and beta-cell replication are normal, therapeutic approaches designed to arrest apoptosis could be a significant new development in the management of type 2 diabetes, because this approach might actually reverse the disease to a degree rather than just palliate glycemia. C1 Univ So Calif, Div Endocrinol & Diabet, Keck Sch Med, Los Angeles, CA 90033 USA. Karolinska Inst, Stockholm, Sweden. Joslin Diabet Ctr, Boston, MA 02215 USA. Mayo Clin, Div Endocrinol, Rochester, MN USA. RP Butler, PC (reprint author), Univ So Calif, Div Endocrinol & Diabet, Keck Sch Med, 1333 San Pablo St,BMT-B11, Los Angeles, CA 90033 USA. FU NIDDK NIH HHS [DK29953, DK44523, DK59579] NR 54 TC 2026 Z9 2167 U1 27 U2 151 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2003 VL 52 IS 1 BP 102 EP 110 DI 10.2337/diabetes.52.1.102 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 631FK UT WOS:000180157300014 PM 12502499 ER PT J AU Nieves, DJ Cnop, M Retzlaff, B Walden, CE Brunzell, JD Knopp, RH Kahn, SE AF Nieves, DJ Cnop, M Retzlaff, B Walden, CE Brunzell, JD Knopp, RH Kahn, SE TI The atherogenic lipoprotein profile associated with obesity and insulin resistance is largely attributable to intra-abdominal fat SO DIABETES LA English DT Article ID CORONARY-ARTERY-DISEASE; ADIPOSE-TISSUE DISTRIBUTION; IMPAIRED GLUCOSE-TOLERANCE; HEPATIC LIPASE ACTIVITY; WEIGHT-LOSS; OLDER MEN; REGIONAL ADIPOSITY; INTRAABDOMINAL FAT; LIPID-METABOLISM; VISCERAL FAT AB Obesity and insulin resistance are both associated with an atherogenic lipoprotein profile. We examined the effect of insulin sensitivity and central adiposity on lipoproteins in 196 individuals (75 men and 121 women) with an average age of 52.7 years. Subjects were subdivided into three groups based on BMI and their insulin sensitivity index (S-I): lean insulin sensitive (n = 65), lean insulin resistant (n = 73), and obese insulin resistant (n = 58). This categorization revealed that both obesity and insulin resistance determined the lipoprotein profile. In addition, the insulin-resistant groups had increased central adiposity. Increasing intra-abdominal fat (IAF) area, quantified by computed tomography scan and decreasing SI, were important determinants of an atherogenic profile, marked by increased triglycerides, LDL cholesterol, and apolipoprotein B and decreased HDL cholesterol and LDL buoyancy (Rf). Density gradient ultracentrifugation (DGUC) revealed that in subjects who had more IAF and were more insulin resistant, the cholesterol content was increased in VLDL, intermediate-density lipoprotein (IDL), and dense LDL fractions whereas it was reduced in HDL fractions. Multiple linear regression analysis of the relation between the cholesterol content of each DGUC fraction as the dependent variable and IAF and S, as independent variables revealed that the cholesterol concentration in the fractions corresponding to VLDL, IDL, dense LDL, and HDL was associated with IAF, and that S, additionally contributed independently to VLDL, but not to IDL, LDL, or HDL. Thus an atherogenic lipoprotein profile appears to be the result primarily of an increase in IAF, perhaps via insulin resistance. C1 VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA 98108 USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, 151,1660 S Columbian Way, Seattle, WA 98108 USA. OI Kahn, Steven/0000-0001-7307-9002 FU NCRR NIH HHS [RR-37]; NHLBI NIH HHS [HL-30086]; NIDDK NIH HHS [DK-02456, DK-02654, DK-17047, DK-35816] NR 65 TC 147 Z9 160 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2003 VL 52 IS 1 BP 172 EP 179 DI 10.2337/diabetes.52.1.172 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 631FK UT WOS:000180157300024 PM 12502509 ER PT J AU Goldhaber-Fiebert, JD Goldhaber-Fiebert, SN Tristan, ML Nathan, DM AF Goldhaber-Fiebert, JD Goldhaber-Fiebert, SN Tristan, ML Nathan, DM TI Randomized controlled community-based nutrition and exercise intervention improves glycemia and cardiovascular risk factors in type 2 diabetic patients in rural Costa Rica SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; BLOOD-PRESSURE; LIPID-LEVELS; COMPLICATIONS; MELLITUS; DIET; CHOLESTEROL; PREVALENCE; MANAGEMENT; METFORMIN AB OBJECTIVE - The prevalence of type 2 diabetes, especially in developing countries, has grown over the past decades. We performed a controlled clinical study to determine whether a community-based, group-centered public health intervention addressing nutrition and exercise can ameliorate glycemic control and associated cardiovascular risk factors in type 2 diabetic patients in rural Costa Rica. RESEARCH DESIGN AND METHODS - A total of 75 adults with type 2 diabetes, mean age 59 years, were randomly assigned to the intervention group or the control group. All participants received basic diabetes education. The subjects in the intervention group participated in 11 weekly nutrition classes (90 min each session). Subjects for whom exercise was deemed safe also participated in triweekly walking groups (60 min each session). Glycosylated hemoglobin, fasting plasma glucose, total cholesterol, triglycerides, HDL and LDL cholesterol, height, weight, BMI, and blood pressure were measured at baseline and the end of the study (after 12 weeks). RESULTS - The intervention group lost 1.0 +/- 2.2 kg compared with a weight gain in the control group of 0.4 +/- 2.3 kg (P = 0.028). Fasting plasma glucose decreased 19 +/- 55 mg/dl in the intervention group and increased 16 78 mg/dl in the control group (P = 0.048). Glycosylated hemoglobin decreased 1.8 +/- 2.3% in the intervention group and 0.4 +/- 2.3% in the control group (P = 0.028). CONCLUSIONS - Glycemic control of type 2 diabetic patients can be improved through community-based, group-centered public health interventions addressing nutrition and exercise. This pilot study provides an economically feasible model for programs that aim to improve the health status of people with type 2 diabetes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, Boston, MA USA. Int Hlth Cent Amer Inst, San Jose, Costa Rica. RP Goldhaber-Fiebert, SN (reprint author), Walter Bradford Cannon Soc, Tosteson Med Educ Ctr, Room 229,260 Longwood Ave, Boston, MA 02115 USA. NR 23 TC 80 Z9 86 U1 1 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2003 VL 26 IS 1 BP 24 EP 29 DI 10.2337/diacare.26.1.24 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UK UT WOS:000185504900004 PM 12502654 ER PT J AU Parchman, ML Arambula-Solomon, TG Noel, PH Larme, AC Pugh, JA AF Parchman, ML Arambula-Solomon, TG Noel, PH Larme, AC Pugh, JA TI Stage of change advancement for diabetes self-management behaviors and glucose control SO DIABETES EDUCATOR LA English DT Article ID PATIENT EDUCATION RESEARCH; REGULAR EXERCISE; IMPACT; NIDDM AB PURPOSE this study was conducted to evaluate whether patients with type 2 diabetes who participated in diabetes education advanced through stages of change for self-management behaviors and to determine if movement was related to glucose control. METHODS A cohort of 428 patients with type 2 diabetes participated in a traditional diabetes education program in a large urban center in the Southwest. The sample was predominantly female with less than a high school education, a mean age of 52 years, and a mean duration of diabetes of 7 years. Two interviews were conducted approximately 9 months apart, at 1 to 4 weeks before the educational program and at 6 months after completing it. Blood specimens were collected at each interview to measure hemoglobin A1C (A1C) levels. RESULTS Most of the patients advanced 1 or more stages of change for at least 1 self-management behavior. Those with diabetes for less than 2 years were significantly more likely to advance at least 1 stage of change for diet and exercise than those with diabetes for more than 2 years. Such advancement was significantly associated with a decline in A1C. CONCLUSIONS Patients with type 2 diabetes who participated in diabetes education advanced through stages of change for self-care behaviors. The intervention was more effective for those with a shorter duration of diabetes. C1 Univ Texas, Hlth Sci Ctr, Dept Family & Community Med, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, VERDICT Ctr, S Texas Vet Hlth Care Syst,Audie L Murphy Div, San Antonio, TX 78285 USA. RP Parchman, ML (reprint author), Diabet Educator, 367 W Chicago Ave, Chicago, IL 60610 USA. OI Pugh, Jacqueline/0000-0003-4933-141X; Parchman, Michael/0000-0001-7129-2889 FU PHS HHS [3015941485] NR 18 TC 18 Z9 19 U1 0 U2 3 PU AMER ASSOC DIABETES EDUCATORS PI CHICAGO PA STE 1240, 444 NORTH MICHIGAN AVE, CHICAGO, IL 60611-3901 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD JAN-FEB PY 2003 VL 29 IS 1 BP 128 EP 134 DI 10.1177/014572170302900117 PG 7 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 643UZ UT WOS:000180880400011 PM 12632691 ER PT J AU Falsetti, D Charron-Prochownik, D Sereika, S Kitutu, J Peterson, K Becker, D Jacober, S Mansfield, J White, NH AF Falsetti, D Charron-Prochownik, D Sereika, S Kitutu, J Peterson, K Becker, D Jacober, S Mansfield, J White, NH TI Condom use, pregnancy, and STDs in adolescent females with and without type 1 diabetes SO DIABETES EDUCATOR LA English DT Article ID WOMEN AB PURPOSE the purpose of this secondary analysis was to describe and compare adolescent females with and without diabetes in terms of use of condoms, pregnancy outcomes, and sexually transmitted disease (STD) outcomes. METHODS Data from a multisite, case-controlled, telephone survey study were used in a secondary analysis to evaluate the parameters stated in the purpose. RESULTS The 87 females with type 1 diabetes and 45 nondiabetic females who participated were 16 to 22 years old. Most were in high school Caucasian and lived with their parents No demographic differences were noted between the groups. Of those sexually active, for both groups, the most common contraceptive method was male condoms. Four females with diabetes and 2 without diabetes reported an unplanned pregnancy. Three females with diabetes reported an STD infection (chlamydia or trichomonas). Five females with diabetes and 4 nondiabetic females bad abnormal pap tests. CONCLUSIONS Adolescent females with and without diabetes engaged in less than optimally protected sexual activity, which increased their risk for unplanned pregnancies and STD infections. Further and short-term research is needed of the incidence treatment and long-term complications of STDs in adolescent females with diabetes. C1 Univ Pittsburgh, Sch Nursing, Dept Hlth Promot & Dev, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Serv Adm, Pittsburgh, PA 15260 USA. Childrens Hosp Pittsburgh, Dept Endocrinol, Pittsburgh, PA 15213 USA. Wayne State Univ, Sch Med, Dept Endocrinol, Detroit, MI 48202 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. St Louis Childrens Hosp, Dept Endocrinol, St Louis, MO 63178 USA. RP Charron-Prochownik, D (reprint author), Diabet Educator, 367 W Chicago Ave, Chicago, IL 60610 USA. FU NINR NIH HHS [5P30NR03924] NR 25 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC DIABETES EDUCATORS PI CHICAGO PA STE 1240, 444 NORTH MICHIGAN AVE, CHICAGO, IL 60611-3901 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD JAN-FEB PY 2003 VL 29 IS 1 BP 135 EP 143 DI 10.1177/014572170302900118 PG 9 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 643UZ UT WOS:000180880400012 PM 12632692 ER PT J AU Welch, G Weinger, K Anderson, B Polonsky, WH AF Welch, G Weinger, K Anderson, B Polonsky, WH TI Responsiveness of the problem areas in diabetes (PAID) questionnaire SO DIABETIC MEDICINE LA English DT Article DE diabetes mellitus; emotional distress; PAID; validity; responsiveness ID GLYCEMIC CONTROL; INTENSIVE TREATMENT; SCALE; INTERVENTION; VALIDATION; EDUCATION; DISTRESS; CARE AB Aim Responsiveness (sensitivity to change over time) is a key psychometric quality for an outcome measure. We examined the responsiveness of the Problem Areas In Diabetes (PAID) questionnaire, a measure of diabetes-specific emotional distress. Methods PAID data were obtained from seven diabetes intervention studies following a literature search that included both published papers and conference abstracts. To estimate responsiveness we used two indices: (i) a statistical test (the dependent t -test), and (ii) a commonly used effect size index (Cohen's d). Results Mean patient PAID scores improved from baseline to follow-up for all seven studies. Specifically, t -statistics ranged from t = 8.5 (P < 0.001) to t = 2.1 (P < 0.06). Effect size results ranged from 0.32 (i.e. small) for a disease management intervention to 0.65 (i.e. moderate) for an intensive medical/educational intervention. Conclusions Despite the pilot nature of the studies, the pattern of findings provided strong support for the responsiveness of the PAID. Information on responsiveness helps clinical researchers select measures, accurately estimate sample size to ensure adequate statistical power, and prioritize outcomes to be assessed. C1 Joslin Diabet Ctr, Behav & Mental Hlth Res Div, Boston, MA 02115 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Welch, G (reprint author), Joslin Diabet Ctr, Behav & Mental Hlth Res Div, Boston, MA 02115 USA. NR 25 TC 104 Z9 108 U1 3 U2 8 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD JAN PY 2003 VL 20 IS 1 BP 69 EP 72 DI 10.1046/j.1464-5491.2003.00832.x PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 632XT UT WOS:000180250700011 PM 12519323 ER PT J AU Vidal, J Verchere, CB Andrikopoulos, S Wang, F Hull, RL Cnop, M Olin, KL LeBoeuf, RC O'Brien, KD Chait, A Kahn, SE AF Vidal, J Verchere, CB Andrikopoulos, S Wang, F Hull, RL Cnop, M Olin, KL LeBoeuf, RC O'Brien, KD Chait, A Kahn, SE TI The effect of apolipoprotein E deficiency on islet amyloid deposition in human islet amyloid polypeptide transgenic mice SO DIABETOLOGIA LA English DT Article DE islet amyloid; islet amyloid polypeptide; amylin; apolipoprotein E; diabetes; Alzheimer's disease ID BETA-PEPTIDE DEPOSITION; DEPENDENT DIABETES-MELLITUS; ONSET ALZHEIMER-DISEASE; MOUSE MODEL; CYNOMOLGUS MONKEYS; PRECURSOR PROTEIN; E GENOTYPE; HYPERCHOLESTEROLEMIA; ATHEROSCLEROSIS; HYPERGLYCEMIA AB Aims/hypothesis. Islet amyloid deposits are present in over 85% of Type 2 diabetic patients and have been suggested to be pathogenic. The mechanism that converts islet amyloid polypeptide (IAPP), the unique component of these deposits, into amyloid fibrils in vivo is not known. The amino acid sequence of IAPP is critical but insufficient for beta-pleated sheet formation. As apolipoprotein E (apoE), another component of islet amyloid deposits, plays a critical role in amyloid formation in Alzheimer's disease, we hypothesised that apoE could play an important role in islet amyloid formation. Methods. Transgenic mice expressing the human form of IAPP (hIAPP(+/0)) were crossbred with apoE deficient (apoE(-/-)) mice and followed for 12 months, at which time the prevalence and severity of islet amyloid, as well as plasma glucose, hIAPP, immunoreactive insulin (IRI) and lipid concentrations were measured. Results. The prevalence and severity of islet amyloid after one year of follow up were comparable among hIAPP(+/0) mice that were apoE(+/+), apoE(+/-) or apoE(-/-). Differences in glucose tolerance, lipid abnormalities or changes in pancreatic content or plasma concentrations of hIAPP and/or IRI did not account for these findings. Conclusion/interpretation. Our data shows that, unlike in the localized amyloidosis in the brain characteristic of Alzheimer's disease, apoE is not critical for islet amyloid formation in a transgenic mouse model of Type 2 diabetes mellitus. These results indicate that the mechanisms of localised amyloid formation probably vary among different amyloid-associated disorders. Therefore, therapeutic strategies targeting apoE might not apply equally to patients with different amyloid associated diseases. C1 Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. Univ Washington, Dept Nutr Sci, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Cardiol, Seattle, WA USA. RP Kahn, SE (reprint author), Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. OI Kahn, Steven/0000-0001-7307-9002; Hull, Rebecca/0000-0001-9690-4087 FU NHLBI NIH HHS [HL-30086, HL-52848]; NIA NIH HHS [AG10917]; NIDDK NIH HHS [DK-50703, DK-02456, DK-17047] NR 43 TC 20 Z9 21 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2003 VL 46 IS 1 BP 71 EP 79 DI 10.1007/s00125-002-0984-5 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 654PX UT WOS:000181506200010 PM 12637985 ER PT B AU Garber, AM AF Garber, AM GP OECD OECD TI Comparing health care systems from the disease-specific perspective SO DISEASE-BASED COMPARISON OF HEALTH SYSTEMS: WHAT IS BEST AND AT WHAT COST? LA English DT Proceedings Paper CT Workshop on Disease Based Comparison of Health Systems CY JUN 20-21, 2002 CL PARIS, FRANCE SP Natl Inst Aging U S, Natl Board Hlth & Welfare Japan AB The McKinsey Health Care Productivity study sought to learn about system factors that might influence health care productivity by comparing the costs and outcomes of care in Germany, the United Kingdom, and the United States in the management of four specific conditions: breast cancer, lung cancer, cholelithiasis, and diabetes mellitus. The study assessed productivity in the management of these conditions by measuring the levels of inputs used, rather than expenditures on inputs. The US health care system, despite its much greater expenditures, tended to be more productive than Germany and the UK, except in diabetes care, where the UK experienced better outcomes at lower Costs than in the US Several system features may have been responsible for these performance findings. The OECD Ageing-Related Diseases project is leading to similar insights in a range of conditions. C1 Stanford Univ, US Dept Vet Affairs, Stanford, CA 94305 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU ORGANIZATION ECONOMIC COOPERATION & DEVELOPMENT PI PARIS PA 2, RUE ANDRE PASCAL, CEDEX 16, 75775 PARIS, FRANCE BN 92-64-09981-6 PY 2003 BP 95 EP 103 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA BX11X UT WOS:000184328200005 ER PT J AU Etminan, M Gill, S Samii, A AF Etminan, M Gill, S Samii, A TI Comparison of the risk of adverse events with pramipexole and ropinirole in patients with Parkinson's disease - A meta-analysis SO DRUG SAFETY LA English DT Article ID DOUBLE-BLIND; DOPAMINE AGONIST; MOTOR FLUCTUATIONS; D-2 AGONIST; PLACEBO; MULTICENTER; SAFETY; LEVODOPA; EFFICACY; TRIALS AB Background: Pramipexole and ropinirole are relatively new dopamine agonists, both of which have proven efficacy in the treatment of Parkinson's disease. There is, however, uncertainty regarding differences in the adverse event profiles associated with each drug. Objective: To compare the adverse events of pramipexole and ropinirole as. reported in the peer-reviewed medical literature. Methods: We systematically reviewed the medical literature to identify randomised controlled trials of pramipexole and ropinirole used in the management of Parkinson's disease. Computerised databases (including Medline, Embase, the Cochrane Library, and the International Pharmaceutical Abstracts) were used to identify pertinent articles for inclusion in this study. Trials that compared the dopamine agonists to either levodopa or placebo were included. Analysis: Adverse events with these drugs included dizziness, nausea, hypotension, hallucinations, and somnolence. We made two separate analyses. In the first analysis, we estimated the pooled relative risk (RR) of adverse events with either pramipexole or ropinirole as compared with levodopa. In the second analysis, the pooled RRs of adverse events with pramipexole and ropinirole were compared with placebo. We used the random-effects model of DerSimonian and Laird to estimate the RRs and their corresponding 95% CIs. We tested for study heterogeneity using Q statistics. Results: There was no significant difference in the risk of dizziness, nausea, or hypotension with either drug individually or in combination when compared with levodopa. The risk of hypotension was approximately four times higher with ropinirole than pramipexole when each drug was individually compared with placebo (6.46 [95% CI 1.47-28.28] for ropinirole, and 1.65 [0.88-3.08] for pramipexole). The pooled RR (for pramipexole and ropinirole combined) of hallucinations was 1.92 (95% CI 1.08-3.43) when compared with levodopa. Relative to placebo, pramipexole had a significantly higher risk of hallucinations than ropinirole (pramipexole 5.2 [95% CI 1.97-13.72] vs ropinirole 2.75 [95% CI 0.55-13.73]). There was no significant difference in the risk of somnolence between the two drugs when each was individually compared with levodopa. When compared with placebo, the pooled RR (pramipexole and ropinirole combined) of somnolence was 3.16 (95% CI 1.62-6.13). Relative to placebo, the risk of somnolence was 2.01 (95% CI 2.17-3.16) with pramipexole and 5.73 (95% CI 2.34-14.01) with ropinirole. Conclusions: Use of ropinirole seems to be associated with a higher risk of hypotension and somnolence than use of pramipexole when compared with placebo. Use of pramipexole seems to be associated with a higher risk of hallucinations than use of ropinirole when compared with placebo. C1 Univ Toronto, Baycrest Ctr Geriatr Care, Kunin Lunenfeld Appl Res Unit, Dept Clin Epidemiol, Toronto, ON, Canada. Washington Univ, Dept Neurol, Seattle, WA USA. RP Samii, A (reprint author), VA Puget Sound Hlth Care Syst, Dept Neurol, Mailstop 127,1660 S Columbian Way, Seattle, WA 98108 USA. NR 25 TC 47 Z9 50 U1 0 U2 8 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2003 VL 26 IS 6 BP 439 EP 444 DI 10.2165/00002018-200326060-00005 PG 6 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 679BF UT WOS:000182900600005 PM 12688834 ER PT J AU Messmore, HL Jeske, WP Wehrmacher, WH Walenga, JM AF Messmore, HL Jeske, WP Wehrmacher, WH Walenga, JM TI Benefit-risk assessment of treatments for heparin-induced thrombocytopenia SO DRUG SAFETY LA English DT Review ID SYNTHETIC THROMBIN INHIBITOR; PLATELET-AGGREGATION TEST; MOLECULAR-WEIGHT HEPARIN; CARDIOPULMONARY BYPASS; RECOMBINANT HIRUDIN; R-HIRUDIN; ARGATROBAN ANTICOAGULATION; ANTITHROMBOTIC AGENTS; CLINICAL USEFULNESS; ARTERIAL-OCCLUSION AB Patients with heparin-induced thrombocytopenia (HIT) are at high risk of thrombosis and should be treated with alternative anticoagulant therapy to reduce complications. The current treatment of choice is one of the approved direct thrombin inhibitors, argatroban or lepirudin. These drugs have been proven to be safe and effective in multicentre clinical trials where dosage regimens have been established for prophylaxis and treatment of thrombosis. Argatroban has also been tested and approved for use in invasive cardiology procedures in the HIT patient. Dosage regimens for other clinical uses, such as cardiac surgery, have not yet been established for either drug. The safety and effectiveness of the thrombin inhibitors is dependent on their use according to established guidelines. Other treatment options that may be effective for the patient with HIT include dextran, plasmapheresis, intravenous gammaglobulin and aspirin (acetylsalicylic acid). Although used historically, these options have not been tested in rigorous clinical trials. For life- and limb-threatening thrombosis, thrombolytic agents and/or surgery may provide benefit. Because the risk of bleeding is high from these procedures, they should be performed only by an experienced practitioner. Several studies have shown that patients with HIT requiring continued anticoagulation are best managed with a warfarin derivative initiated while under full anticoagulation with a thrombin inhibitor. There is a risk of skin necrosis and bleeding if guidelines for dose administration and monitoring of warfarin are not followed. Subsequent use of heparin or a low molecular weight heparin after resolution of the clinical episode of HIT can be hazardous, particularly within the first 3 months. If laboratory testing is negative, heparin may be cautiously reinstituted for short-term use (1-2 hours) with monitoring for platelet count decrease and thromboembolism. The pregnant patient with HIT requiring anticoagulation represents a particular challenge, where there is no drug of choice at present. Although today there are realistic treatment options for the patient with HIT, the morbidity and mortality associated with this disease have not been eliminated. Awareness and early treatment of HIT remain important components of the clinical care for patients exposed to heparins. Future therapeutic developments based on a better understanding of the pathophysiology of HIT may further improve clinical outcomes. Despite some limitations, the current treatment options for patients with HIT provide unparalleled benefit compared with the treatment options available only a few years ago. C1 Loyola Univ, Med Ctr, Cardiovasc Inst, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Med, Hines, IL 60141 USA. Loyola Univ, Med Ctr, Dept Cardiovasc Thorac Surg, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Physiol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Med, Maywood, IL 60153 USA. RP Walenga, JM (reprint author), Loyola Univ, Med Ctr, Cardiovasc Inst, Bldg 110,Room 5226, Maywood, IL 60153 USA. NR 112 TC 24 Z9 24 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2003 VL 26 IS 9 BP 625 EP 641 DI 10.2165/00002018-200326090-00003 PG 17 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 702YZ UT WOS:000184253800003 PM 12814331 ER PT J AU Thorner, AR Rosenberg, ES AF Thorner, AR Rosenberg, ES TI Early versus delayed antiretroviral therapy in patients with HIV infection - A review of the current guidelines from an immunological perspective SO DRUGS LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD4 CELL COUNT; PNEUMOCYSTIS-CARINII PNEUMONIA; PROTEASE INHIBITOR THERAPY; STEVENS-JOHNSON-SYNDROME; BONE-MINERAL LOSS; VIRAL-LOAD; SECONDARY PROPHYLAXIS; LACTIC-ACIDOSIS; RNA LEVELS AB The development and implementation of highly active antiretroviral therapy (HAART) for the treatment of the human immunodeficiency virus has revolutionised the care of patients with this disease. Despite the positive impact that antiretroviral therapy has had on the lives of, individuals with HIV infection, the adverse. effects, potential long-term toxicities, complexity of regimens, development of drug resistance and cost have made decisions about when. to initiate. HAART difficult. The benefits and risks of antiretroviral therapy vary considerably among patients at different stages of disease, mainly as a result of the irreversible destruction of the immune system that occurs as HIV infection progresses. In acute HIV infection, the primary aim of treatment is preservation and reconstitution of HIV-specific immune function. In symptomatic or late-stage disease, the goal is control of viral replication with resulting improvement in non-HIV-specific immunity, which leads to decreased morbidity and increased survival. The most controversial decision involves when to start therapy in persons with asymptomatic chronic HIV, where the benefits are less well established and may be outweighed by the drawbacks, depending on the individual patient. In all patients, the advantages and disadvantages must be considered carefully, and the readiness and ability of the individual to adhere to a complex multidrug regimen needs to be assessed before the initiation of therapy. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Microbiol Lab, Boston, MA 02114 USA. Partners AIDS Res Ctr, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rosenberg, ES (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,GRJ 529, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI40873] NR 112 TC 11 Z9 11 U1 0 U2 3 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2003 VL 63 IS 13 BP 1325 EP 1337 DI 10.2165/00003495-200363130-00001 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 696UT UT WOS:000183906500001 PM 12825959 ER PT J AU Wilens, TE AF Wilens, TE TI Drug therapy for adults with attention-deficit hyperactivity disorder SO DRUGS LA English DT Review ID MINIMAL BRAIN-DYSFUNCTION; AGE-DEPENDENT DECLINE; OPEN-LABEL TRIAL; DEFICIT/HYPERACTIVITY DISORDER; RESIDUAL TYPE; DOUBLE-BLIND; TRICYCLIC ANTIDEPRESSANTS; PSYCHIATRIC COMORBIDITY; ORAL METHYLPHENIDATE; DOPAMINE TRANSPORTER AB Practitioners are increasingly called upon to diagnose and treat attention deficit hyperactivity disorder (ADHD) in adults. Although the use of pharmacotherapy in children with ADHD is well studied, the use of drugs for the treatment of adults with ADHD remains less well established. A systematic review of the literature identified 15 studies (n = 482 patients) of stimulants, and 27 studies of nonstimulant medications (n = 1179 subjects) including antidepressants, norepinephrine reuptake inhibitors, antihypertensive agents, amino acids and wake-promoting agents for the treatment of ADHD in adults. Controlled clinical trials in adults showed that stimulants, antidepressants and norepinephrine reuptake inhibitors demonstrated significant short-term improvements in ADHD symptoms compared with placebo. The two longer term trials with methylphenidate in adults confirmed the ongoing effectiveness and tolerability of stimulants. The response to amphetamine and methylphenidate appears to be dose-dependent. Methylphenidate and amphetamine had an immediate onset of action, whereas responses to pemoline, antidepressants and norepinephrine reuptake inhibitors appeared delayed. Controlled data on nicotinic/cholinergic compounds appear promising. Considerable variability was found in the diagnostic criteria for ADHD in adults, drug dosages and response rates between the various studies. Under controlled conditions, the aggregate literature comprised mainly of short-term studies, shows that stimulants, norepinephrine reuptake inhibitors and specific antidepressants had clinically and statistically significant beneficial effects in the treatment of ADHD in adults. Cholinergic agents appear promising. Further studies are necessary to evaluate the long-term effectiveness and tolerability of various agents, functional and neuropsychological outcomes, and the use of various agents in specific subgroups of adults with ADHD. C1 Massachusetts Gen Hosp, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. FU NIDA NIH HHS [DA11929] NR 127 TC 53 Z9 54 U1 8 U2 10 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2003 VL 63 IS 22 BP 2395 EP 2411 DI 10.2165/00003495-200363220-00002 PG 17 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 743GA UT WOS:000186563000002 PM 14609347 ER PT J AU Soares, CN Poitras, JR Prouty, J AF Soares, CN Poitras, JR Prouty, J TI Effect of reproductive hormones and selective estrogen receptor modulators on mood during menopause SO DRUGS & AGING LA English DT Review ID QUALITY-OF-LIFE; PREMENSTRUAL DYSPHORIC DISORDER; HEALTHY POSTMENOPAUSAL WOMEN; CENTRAL-NERVOUS-SYSTEM; REPLACEMENT THERAPY; HOT FLASHES; BREAST-CANCER; DOUBLE-BLIND; TRANSDERMAL ESTRADIOL; DEPRESSIVE SYMPTOMS AB Periods of intense hormonal fluctuations have been associated with heightened prevalence and exacerbation of underlying psychiatric illness, particularly the occurrence of premenstrual dysphoria, puerperal depression and depressive symptoms during perimenopause. It has been speculated that sex steroids such as estrogens, progestogens, testosterone and dehydroepiandrosterone (DHEA) exert a significant modulation of brain functioning, possibly through interactions with various neurotransmitter systems. It is therefore intuitive that abrupt alterations of these hormones would interfere with mood and behaviour. On the other hand, accumulating data suggest that hormonal interventions may also promote relief or even remission of depressive symptoms, as already demonstrated in studies with patients experiencing postpartum depression and perimenopausal depressive disorders. The extent to which perimenopause, alone, may increase the risk for depression is unclear. However, existing data strongly suggest that some women are particularly vulnerable to developing significant physical and psychological disturbances when entering perimenopause. This article reviews the effect of sex hormones and selective estrogen receptor modulators (SERMs) on mood among peri- and postmenopausal women. There are preliminary, though promising, data on the use of estradiol (particularly transdermal estradiol) to alleviate depression during perimencipause, use of a combination of estrogens and selective serotonin reuptake inhibitors for depression during the postmenopausal period, and the use of testosterone to improve psychological well-being and increase libido among women with induced menopause. Further studies would help to better delineate the usage of hormones as an antidepressant strategy (monotherapy or augmenting treatment) for peri- and postmenopausal women. A brief review of some nonhormonal interventions for the treatment of menopause-related symptoms that may significantly affect a woman's quality of life is also presented. There are some preliminary data suggesting the efficacy of antidepressants for the treatment of hot flushes; existing data on diet supplements and herbal products have shown more mixed results. C1 Harvard Univ, Sch Med, MGH Ctr Womens Mental Hlth, Boston, MA USA. RP Soares, CN (reprint author), Massachusetts Gen Hosp, MGH Ctr Womens Mental Hlth, 15 Parkman St,WACC 812, Boston, MA 02114 USA. NR 118 TC 45 Z9 47 U1 0 U2 3 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2003 VL 20 IS 2 BP 85 EP 100 DI 10.2165/00002512-200320020-00001 PG 16 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 647PK UT WOS:000181102000001 PM 12534310 ER PT J AU Smith, MR AF Smith, MR TI Bisphosphonates to prevent osteoporosis in men receiving androgen deprivation therapy for prostate cancer SO DRUGS & AGING LA English DT Article ID BONE-MINERAL DENSITY; X-RAY ABSORPTIOMETRY; SEX STEROID-LEVELS; OLDER MEN; INTRAVENOUS PAMIDRONATE; HORMONE AGONISTS; VITAMIN-D; AROMATASE DEFICIENCY; RANCHO BERNARDO; ELDERLY MEN AB Osteoporosis is an important complication of androgen deprivation therapy for prostate cancer. Androgen deprivation therapy either by bilateral orchiectomies or treatment with a gonadotropin-releasing hormone agonist decreases bone mineral density (BMD) and increases the risk of fracture. Dietary factors and lifestyle may contribute to bone loss. There are limited prospective data about treatment or prevention of osteoporosis in men with prostate cancer and many recommendations are based on studies of postmenopausal osteoporosis. Lifestyle modification including smoking cessation, moderation of alcohol consumption, and regular weight bearing exercise should be encouraged. Supplemental calcium and vitamin D are recommended. Additional treatment may be warranted for men with osteoporosis, fractures, or high rates of bone loss during androgen deprivation therapy. Recent studies have evaluated the efficacy of bisphosphonates to prevent bone loss during androgen deprivation therapy. Pamidronate (pamidronic acid), a second-generation bisphosphonate, prevents bone loss in the hip and spine during androgen deprivation therapy. Zoledronic acid, a more potent third-generation bisphosphonate, not only prevents bone loss but also increases BMD in the hip and spine. Alendronate (alendronic acid) is approved for the treatment of osteoporosis in men although its efficacy and that of other oral bisphosphonates has not been evaluated in men receiving androgen deprivation therapy. Additional prospective studies are needed to evaluate the long-term effects of bisphosphonates on fracture risk and disease-related outcomes. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 63 TC 29 Z9 30 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2003 VL 20 IS 3 BP 175 EP 183 DI 10.2165/00002512-200320030-00002 PG 9 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 652CX UT WOS:000181363200002 PM 12578398 ER PT J AU Basile, JN AF Basile, JN TI Systolic blood pressure elevation - It's where the action is SO DRUGS & AGING LA English DT Editorial Material ID HYPERTENSION C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Primary Care Program, Charleston, SC 29403 USA. Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Div Gen Internal Med Geriatr, Charleston, SC 29403 USA. RP Basile, JN (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Primary Care Program, 1090 Bee St, Charleston, SC 29403 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2003 VL 20 IS 4 BP 287 EP 288 DI 10.2165/00002512-200320040-00007 PG 2 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 665XJ UT WOS:000182146300005 PM 12641484 ER PT J AU Mendez, MF Lim, GTH AF Mendez, MF Lim, GTH TI Seizures in elderly patients with dementia - Epidemiology and management SO DRUGS & AGING LA English DT Review ID ONSET ALZHEIMERS-DISEASE; UNITED-STATES POPULATION; NEWLY-DIAGNOSED EPILEPSY; UNPROVOKED SEIZURES; ANTIEPILEPTIC DRUGS; COGNITIVE FUNCTION; CLINICAL-FEATURES; PRESENILIN-1 MUTATION; STATUS EPILEPTICUS; PREDICTIVE MODEL AB Epileptic seizures occur in patients with dementia at a higher prevalence than among healthy elderly individuals. The incidence of seizures among patients with dementia varies with the aetiology of the dementing illness. In patients with Alzheimer's disease (the most common form of dementia), approximately 10-22% have at least one unprovoked seizure. Seizures usually occur in later stages of Alzheimer's disease, on average, greater than or equal to6 years into the course of the disease. Seizures in Alzheimer's disease are more likely to occur with early-onset disease, particularly if there is a familial presenilin I mutation. The incidence of seizures in other dementing diseases is less clear. There are special considerations regarding the management of seizures in the elderly with dementia. First, the presence of cognitive impairment may impede an accurate diagnosis of seizures. Clinicians may also mistake seizure manifestations for symptoms of the underlying dementia. Second, since most dementia patients are elderly, there are pharmacokinetic changes with aging that affect the use of antiepileptic drugs. Third, antiepileptic drugs have potential cognitive adverse effects that may worsen dementia. Although few studies are available, extrapolations from research in young people and elderly patients without dementia provide several recommendations for the management of seizures in patients with dementia: exclude symptomatic causes of seizures before committing to antiepileptic drug therapy; treat after a first seizure if there is evidence of focal neurological involvement or a risk of recurrent seizures; use antiepileptic drugs with minimal cognitive adverse effects, such as carbamazepine, valproic acid, gabapentin and lamotrigine; and use the lowest possible dosage and monitor antiepileptic drug levels, where possible. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA 90073 USA. RP Mendez, MF (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Neurol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 100 TC 89 Z9 91 U1 1 U2 7 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2003 VL 20 IS 11 BP 791 EP 803 DI 10.2165/00002512-200320110-00001 PG 13 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 725JE UT WOS:000185539700001 PM 12964886 ER PT J AU Fukuhara, H Todo, T AF Fukuhara, H Todo, T TI New generation, conditionally replicating herpes simplex virus G47 Delta as a potential backbone vector for expressing foreign proteins SO DRUGS OF THE FUTURE LA English DT Review ID ONCOLYTIC VIRAL THERAPY; TYPE-1 MUTANT G207; CLASS-I MOLECULES; GENE-THERAPY; ANTITUMOR IMMUNITY; COLORECTAL-CANCER; ANTIGEN PRESENTATION; SAFETY EVALUATION; MALIGNANT GLIOMA; TUMOR-THERAPY AB The use of replication-competent viruses that can selectively replicate, spread in situ and lyse malignant cells is an attractive strategy for treating cancer. G207 is a multimutated, conditionally replicating HSV-1 vector, and recent clinical trials in recurrent malignant glioma patients showed its safety when inoculated into human brain tumors. Whereas G207 has been shown to be effective in various types of cancer in animal models, its replication capability in tumor cells is considerably attenuated compared with wild-type HSV-1. In order to improve the antitumor efficacy, we have recently constructed a new generation vector, G47Delta, by creating an additional deletion in the alpha47 gene of G207. G47Delta showed enhanced tumor cell killing and increased major histocompatibility complex class I expression in infected human cells. This paper reviews the circumstances that led to the development of G47Delta and the features of the vector that may be suitable as a backbone for expressing foreign molecules. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurosurg Lab, Charlestown, MA 02129 USA. RP Todo, T (reprint author), Tokyo Univ Hosp, Dept Neurosurg, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. NR 58 TC 1 Z9 1 U1 0 U2 0 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0377-8282 J9 DRUG FUTURE JI Drug Future PD JAN PY 2003 VL 28 IS 1 BP 43 EP 49 DI 10.1358/dof.2003.028.01.856924 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 657TV UT WOS:000181683200006 ER PT J AU Sachs, G Shin, JM Pratha, V Hogan, D AF Sachs, G Shin, JM Pratha, V Hogan, D TI Synthesis or rupture: Duration of acid inhibition by proton pump inhibitors SO DRUGS OF TODAY LA English DT Article; Proceedings Paper CT Symposium on Acid-Related Disease CY OCT, 2002 CL GENEVA, SWITZERLAND ID SECRETION; OMEPRAZOLE; LANSOPRAZOLE; REVERSAL; E3810 AB Insight has been gained into the relationship between the structure of proton pump inhibitors (PPIs), their binding, and their suppression of acid secretion. PPIs accumulate in the acidic space of the secreting parietal cell, where then their active forms create disulfide bonds with key cysteines of the H+, K+-ATPase. Studies in humans on the half-lives of recovery of acid secretion have found that while lansoprazole showed a half-life of less than 15 h, and both omeprazole and rabeprazole showed one of less than 30 h, for pantoprazole the half-life was approximately 46 h. This difference in duration of inhibition with PPIs may be related to variations in proton pump inhibitor dwell time. A study in rats suggests that the recovery of gastric pump activity after treatment with omeprazole, esomeprazole, lansoprazole and rabeprazole is likely due to both reversal of binding by disulfide-reducing agents and to pump synthesis. However, for pantoprazole, reversal of acid inhibition is probably due mainly to de novo pump synthesis and not loss of binding. This profile is likely related to the unique binding of pantoprazole to cysteine 822, a binding site which is buried deep within the membrane domain of the pump and may therefore be inaccessible to reducing agents. Although clinical data supporting these findings are limited, prolonged binding of pantoprazole may confer a longer duration of action in comparison with other PPIS. (C) 2003 Prous Science. Ail rights reserved. C1 Univ Calif Los Angeles, Membrane Biol Lab, W Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP Sachs, G (reprint author), Univ Calif Los Angeles, Membrane Biol Lab, W Los Angeles VA Med Ctr, 11301 Wilshire Blvd,Bldg 113,Rm 324, Los Angeles, CA 90073 USA. NR 9 TC 13 Z9 13 U1 1 U2 2 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0025-7656 J9 DRUGS TODAY JI Drugs Today PY 2003 VL 39 SU A BP 11 EP 14 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 663RT UT WOS:000182019900003 PM 12712216 ER PT J AU Canning, J Takai, Y Tilly, JL AF Canning, J Takai, Y Tilly, JL TI Evidence for genetic modifiers of ovarian follicular endowment and development from studies of five inbred mouse strains SO ENDOCRINOLOGY LA English DT Article ID OOCYTE APOPTOSIS; CELL-DEATH; BCL-2; EXPRESSION; DISRUPTION; DEFICIENCY; MICE AB The laboratory mouse is the model of choice for genetic studies in mammals due to the availability of many genetically defined inbred strains and inbred congenic strains, as well as the ability to study the effects of over-expression (transgenics) or inactivation (knockouts) of a given gene on cells or tissues. During our studies using these technologies to uncover the importance of various genes to apoptosis in the ovary, we observed that the size of the primordial oocyte reserve was affected by mouse strain in the absence of any other genetic manipulation. To determine if genetic modifiers of oocyte endowment truly exist, herein we examined follicle numbers in one outbred (CD-1) and several inbred (129/Sv, DBA/2, C57BL/6, FVB, AKR/J) strains of mice at day 4 (neonatal) and day 42 (young adult) postpartum. In neonatal life, ovaries of AKR/J females had the lowest total number of follicles, whereas 129/Sv females possessed the highest total number of follicles (P<0.05 for AKR/J versus 129/Sv). There were more primordial follicles in 129/Sv compared with DBA/2 (P<0.05), C57BL/6 (P<0.05), FVB (P<0.05) or AKR/J (P<0.05) females, and in CD-1 compared with AKR/J (P< 0.05) females. Although no significant strain-dependent differences in primary follicle numbers were noted, C57BL/6 females had the fewest number of small preantral follicles (P<0.05 versus all other strains). Evaluation of ovaries at 42 days of age revealed the persistence of strain-dependent differences in early follicle growth patterns, although the total numbers of follicles were comparable. Of interest, marked strain-dependent differences in the rate of primordial follicle growth activation, as well as in the rate of follicle loss (atresia), between days 4 and 42 were observed. These results indicate that genetic modifiers play a major role in follicle endowment, development and atresia in the mouse ovary. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, VBK113-GYN,55 Fruit St, Boston, MA 02114 USA. FU NIA NIH HHS [R01-AG12279] NR 13 TC 36 Z9 36 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2003 VL 144 IS 1 BP 9 EP 12 DI 10.1210/en.2002-220988 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 631PL UT WOS:000180176100004 PM 12488324 ER PT J AU Takai, Y Canning, J Perez, GI Pru, JK Schlezinger, JJ Sherr, DH Kolesnick, RN Yuan, JY Flavell, RA Korsmeyer, SJ Tilly, JL AF Takai, Y Canning, J Perez, GI Pru, JK Schlezinger, JJ Sherr, DH Kolesnick, RN Yuan, JY Flavell, RA Korsmeyer, SJ Tilly, JL TI Bax, caspase-2, and caspase-3 are required for ovarian follicle loss caused by 4-vinylcyclohexene diepoxide exposure of female mice in vivo SO ENDOCRINOLOGY LA English DT Article ID ARYL-HYDROCARBON RECEPTOR; PROGRAMMED CELL-DEATH; INDUCED OVOTOXICITY; OOCYTE APOPTOSIS; FAMILY MEMBERS; DEFICIENT MICE; EXPRESSION; GENE; BCL-2; MOUSE AB The industrial chemical, 4-vinylcyclohexene diepoxide (VCD), kills oocytes within immature follicles in the ovaries of mice and rats and is considered a potential occupational health hazard. It has been reported that VCD-induced follicle loss occurs via a cell death process involving elevated expression of Bax, a proapoptotic Bcl-2 family member, and increased caspase-3-like activity. We have previously shown that oocytes lacking acid sphingomyelinase (ASMase; an enzyme that generates the proapoptotic stress sensor ceramide), the aromatic hydrocarbon receptor (Ahr), Bax, or caspase-2 are resistant to apoptosis induced by other chemical toxicants. Therefore, this study was designed to investigate the functional importance of ASMase, Ahr, Bax, and caspase-2 as well as the related executioner enzyme caspase-3 to VCD-induced ovotoxicity in mice using gene knockout technology. For each gene mutant mouse line, wild-type and homozygous-null female siblings derived from heterozygous matings were given once-daily ip injections of either vehicle (sesame oil) or VCD (80 mg/kg body weight) for 15 d (three or four mice per treatment group per genotype). Ovaries were collected 24 h after the final injection and analyzed for the total number of nonatretic primordial and primary follicles remaining per ovary. No differences in the extent of primordial or primary follicle destruction resulting from VCD exposure were observed in wild-type vs. ASMase- or Ahr-deficient mice. By contrast, the extent of VCD-induced primordial follicle depletion in Bax-deficient mice (45 +/- 11%) was significantly (P < 0.05) lower than that in wild-type females (85 +/- 2%). The extent of primary follicle loss in bax-null mice exposed to VCD (3 +/- 22%) was also significantly (P < 0.05) lower than that in their wild-type sisters (86 +/- 4%). In caspase-2-deficient mice, significantly (P < 0.05) fewer oocyte-containing primary follicles were destroyed by VCD (17 +/- 19%) vs. wild-type controls (71 +/- 6%); however, no significant difference in the extent of VCD-induced primordial follicle destruction was observed in caspase-2-null vs. wild-type females. Finally, in caspase-3-deficient mice, significantly (P < 0.05) fewer oocyte-containing primary follicles were destroyed by VCD (33 +/- 3%) vs. wild-type controls (71 +/- 2%); however, no significant difference in the extent of VCD-induced primordial follicle destruction was observed in caspase-3-null vs. wild-type females. We conclude that Bax, caspase-2, and caspase-3, but not ASMase or Ahr, are functionally important in VCD-induced follicle loss. However, as a loss of Bax, caspase-2, or caspase-3 function conveyed only partial protection from the ovotoxic effects of VCD, other cell death pathways that either function independently of Bax, caspase-2, and caspase-3 or are not apoptotic in nature are also involved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Environm Hlth, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02118 USA. Mem Sloan Kettering Canc Ctr, Lab Signal Transduct, New York, NY 10021 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06510 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, VBK113-GYN,55 Fruit St, Boston, MA 02114 USA. FU NIEHS NIH HHS [R01-ES-06999, F32-ES-11941, R01-ES-08430] NR 33 TC 42 Z9 47 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2003 VL 144 IS 1 BP 69 EP 74 DI 10.1210/en.2002.220814 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 631PL UT WOS:000180176100011 PM 12488331 ER PT J AU Koski, G AF Koski, G TI Ethical issues in antiepileptic trials: Old issues in a new world SO EPILEPSIA LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA 02114 USA. RP Koski, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2003 VL 44 SU 7 BP 16 EP 18 DI 10.1046/j.1528-1157.44.s7.8.x PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 722JQ UT WOS:000185372300004 PM 12919334 ER PT J AU Thiele, EA AF Thiele, EA TI Assessing the efficacy of antiepileptic treatments: The ketogenic diet SO EPILEPSIA LA English DT Article DE ketogenic diet; pediatric epilepsy ID INTRACTABLE SEIZURE DISORDERS; EPILEPSY; COMPLICATIONS; EXPERIENCE AB Purpose: To evaluate the evidence for determining if the ketogenic diet is an effective treatment for epilepsy. Methods: A literature review of published data over the past 80 years concerning the ketogenic diet was performed, focusing on efficacy, tolerability, age of patient population, as well as study design. Results: There have been several studies involving prospective and retrospective studies showing the ketogenic diet to be a very efficacious treatment in epilepsy, particularly epilepsy in childhood. However, no Class 1 studies have been published concerning the efficacy of the ketogenic diet. Conclusions: The ketogenic diet appears to be a very effective treatment for epilepsy, particularly in childhood. It would be beneficial to have Class 1 studies available to help better define the role of the diet both in children and adults. C1 Massachusetts Gen Hosp, Dept Neurol, Pediat Epilepsy Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Pediat Epilepsy Serv, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp Children, Pediat Epilepsy Serv, 55 Fruit St VBK 830, Boston, MA 02115 USA. NR 25 TC 40 Z9 42 U1 1 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2003 VL 44 SU 7 BP 26 EP 29 DI 10.1046/j.1528-1157.44.s7.4.x PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 722JQ UT WOS:000185372300006 PM 12919336 ER PT J AU He, Z Rask-Madsen, C King, GL AF He, Z Rask-Madsen, C King, GL TI Managing heart disease - Mechanisms of cardiovascular complications in diabetes and potential new pharmacological therapies SO EUROPEAN HEART JOURNAL SUPPLEMENTS LA English DT Review DE cardiovascular complications; diabetes; hyperglycaemia; insulin resistance; therapy ID PROTEIN-KINASE-C; GLYCATION END-PRODUCTS; NITRIC-OXIDE SYNTHASE; GROWTH-FACTOR-BETA; ENDOTHELIN-1 GENE-EXPRESSION; VITAMIN-E SUPPLEMENTATION; SMOOTH-MUSCLE CELLS; INSULIN-RESISTANCE; IN-VIVO; VASCULAR COMPLICATIONS AB A reasonable body of information is becoming available that will help us to understand some of the cellular and molecular abnormalities in cardiac and arteries in diabetic and insulinresistant states. Rational therapeutic efforts to improve the actions of insulin, specifically in cardiovascular tissues, are needed. Similarly, specific interventions to prevent vascular complications induced by hyperglycaemia, even if euglycaemia is not achieved, are also feasible. (Eur Heart J Supplements 2003; 5 (SuppI B): 1351-1357) (C) 2003 The European Society of Cardiology C1 Joslin Diabet Ctr, Sect Vasc Cell Biol & Complicat, Boston, MA 02215 USA. RP King, GL (reprint author), Joslin Diabet Ctr, Sect Vasc Cell Biol, 1 Joslin Pl,Room 4504, Boston, MA 02215 USA. NR 108 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1520-765X J9 EUR HEART J SUPPL JI Eur. Heart J. Suppl. PD JAN PY 2003 VL 5 IS B BP B51 EP B57 DI 10.1016/S1520-765X(03)90041-1 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 637FF UT WOS:000180500300008 ER PT J AU Minneci, P Deans, K Natanson, C Eichacker, PQ AF Minneci, P Deans, K Natanson, C Eichacker, PQ TI Increasing the efficacy of anti-inflammatory agents used in the treatment of sepsis SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Review ID TUMOR-NECROSIS-FACTOR; INTERLEUKIN-1 RECEPTOR ANTAGONIST; PLACEBO-CONTROLLED TRIAL; CONTROLLED MULTICENTER TRIAL; HIGH-DOSE METHYLPREDNISOLONE; HUMAN SEPTIC SHOCK; DOUBLE-BLIND; FACTOR-ALPHA; MONOCLONAL-ANTIBODY; ESCHERICHIA-COLI AB Excessive production of inflammatory mediators during invasive infection plays a key role in the pathogenesis of septic shock. In an attempt to improve survival of patients with this lethal syndrome, agents were developed to selectively inhibit mediators in this inflammatory response. Despite promising preclinical results, several different mediator-specific anti-inflammatory agents failed to demonstrate significant benefit in patients. There was, however, a significant difference in mortality between preclinical and clinical trials. The median control mortality in preclinical trials, performed almost uniformly in highly lethal sepsis models, was 88%. In clinical trials however, the median control mortality rate was much lower, at 41%. A recent meta-regression analysis of these preclinical and clinical trials in combination with prospective confirmatory studies demonstrated that risk of death as assessed by control group mortality rate significantly altered the treatment effect of these agents in both humans and animals. While anti-inflammatory agents were very beneficial in groups with high control mortality rates, they were ineffective or harmful in groups with low control mortality rates. Thus, variation in the risk of death due to sepsis provides a basis for the marked difference in the efficacy of these anti-inflammatory agents in preclinical and clinical trials over the last decade. In contrast to mediator-specific anti-inflammatory agents, glucocorticoids and activated protein C have recently demonstrated significant beneficial effects in individual clinical trials. However, glucocorticoids were studied only in patients with vasopressor-dependent septic shock, which is associated with a high control mortality rate (i.e. 61%) similar to the level at which mediator-specific agents would have been expected to be markedly beneficial. Furthermore, consistent with earlier findings for mediator-specific anti-inflammatory agents, analysis of the activated protein C study also demonstrated a relationship between risk of death and effect of treatment. Developing better methods to define high-risk septic populations for treatment with anti-inflammatory agents will increase the efficacy of this therapeutic approach and minimize its potential for harm. C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Minneci, P (reprint author), NIH, Dept Crit Care Med, Bldg 10,Room 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. NR 83 TC 16 Z9 18 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD JAN PY 2003 VL 22 IS 1 BP 1 EP 9 DI 10.1007/s10096-002-0857-3 PG 9 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 655ET UT WOS:000181538900001 PM 12582737 ER PT J AU Xu, YY Sen, J AF Xu, YY Sen, J TI beta-Catenin expression in thymocytes accelerates thymic involution SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE beta-catenin; thymic involution; aging ID AGE-RELATED-CHANGES; BONE-MARROW CELLS; MICE; CAPACITY AB Age-related thymic involution in mammals is accompanied by decreased generation of naive T cells without significant reduction in the number of peripheral T cells. This leads to inefficient immune responses and inadequate combating of infections and other challenges to the immune system in older mammals. The molecular mechanisms that underlie this phenomenon are not known. In this report we show that expression of beta-catenin in thymocytes enhances thymic involution. The effect of beta-catenin expression is seen in all the thymic sub-populations, suggesting that an age-related developmental process is accelerated. We also show that, as in normal mice, thymic involution does not lead to a drastic reduction in splenic T cells in beta-catenin-transgenic mice. This study identifies beta-catenin expression in thymocytes as a molecular target of age-related thymic involution. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sen, J (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 19 TC 16 Z9 16 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2003 VL 33 IS 1 BP 12 EP 18 DI 10.1002/immu.200390002 PG 7 WC Immunology SC Immunology GA 639HU UT WOS:000180623100002 PM 12594827 ER PT J AU Subrahmanyam, G Rudd, CE Schneider, H AF Subrahmanyam, G Rudd, CE Schneider, H TI Association of T cell antigen CD7 with type II phosphatidylinositol-4 kinase, a key component in pathways of inositol phosphate turnover SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD7; phosphatidylinositol 3-kinase phosphatidylinositol 4-kinase ID SIGNAL-TRANSDUCTION; PHOSPHOINOSITIDE KINASES; PROTEIN-KINASE; CROSS-LINKING; 4-KINASE; 3-KINASE; LYMPHOCYTES; PHOSPHORYLATION; REQUIREMENT; EXPRESSION AB CD7 is a 40-kDa glycoprotein that is expressed on prothymocytes and persists during T cell differentiation. CD7 has been demonstrated to generate, like other costimulatory molecules, intracellular signals that modulate T cell function. However, although it binds to phosphatidylinositol 3-kinase (PI 3-kinase), the signaling events mediated by CD7 are not completely understood. In this context, phosphatidylinositol 4-kinase (PI 4-kinase) is a key enzyme involved in a variety of events, from the modeling of the actin cytoskeleton to the activation of protein kinase C. In this study, we show for the first time that PI 4-kinase of 55 kDa can associate with CD7. The enzyme activity was insensitive to wortmannin, but was inhibited by adenosine, a characteristic for type II PI 4-kinase. Together, our findings demonstrate that type II PI 4-kinases are integral components of the CD7 signaling pathway and may play a role of CD7 in co-stimulation and thymic differentiation. C1 Univ London Imperial Coll Sci Technol & Med, Dept Haematol, Fac Med, Hammersmith Hosp, London W12 ONN, England. Indian Inst Technol, Ctr Biotechnol, Bombay 400076, Maharashtra, India. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Schneider, H (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Haematol, Fac Med, Hammersmith Hosp, London W12 ONN, England. NR 44 TC 11 Z9 11 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2003 VL 33 IS 1 BP 46 EP 52 DI 10.1002/immu.200390006 PG 7 WC Immunology SC Immunology GA 639HU UT WOS:000180623100006 PM 12594831 ER PT J AU Miserocchi, E Modorati, G Azzolini, C Foster, CS Brancato, R AF Miserocchi, E Modorati, G Azzolini, C Foster, CS Brancato, R TI Herpes simplex virus type 2 acute retinal necrosis in an immunocompetent patient SO EUROPEAN JOURNAL OF OPHTHALMOLOGY LA English DT Article DE acute retinal necrosis; cytomegalovirus; herpes simplex virus; herpes zoster virus; retinitis; retinal detachment; vitrectomy AB PURPOSE. To report a case of acute retinal necrosis caused by herpes simplex virus 2 in an otherwise healthy patient. CASE REPORT. A 45-year-old man presented with one month's history of decreased vision in the right eye. He had previously received a course of intravenous gancyclovir because of a clinical suspicion of cytomegalovirus retinitis. The patient's ocular history was remarkable for a similar episode in the left eye thirty years earlier, resulting in important visual impairment. System and laboratory investigations were unremarkable. Ocular examination showed severe anterior granulomatous uveitis, vitreous haze, areas of necrosis and retinal exudates. The anterior chamber tap disclosed the presence of HSV type 2, and oral steroids and acyclovir were instituted. Two weeks after the patient had been discharged, a retinal detachment occurred in the right eye, necessitating surgical repair. The presence of HSV type 2 was confirmed in the vitreous. Visual acuity recovered completely after surgery and the patient was placed on a maintenance dose of oral acyclovir CONCLUSIONS. HSV type 2 is a rare cause of acute retinal necrosis in healthy patients. Bilateral involvement can occur in the fellow eye, even with a long delay. Acute retinal necrosis is a severe ocular inflammatory syndrome associated with a very poor visual outcome. It is caused by VZV, HSV type 1 and, less commonly, by HSV type 2. The disease can affect healthy patients and cause bilateral involvement in the fellow eye, even with a long delay. C1 Univ Milan, Hosp San Raffaele, Dept Ophthalmol & Visual Sci, I-20132 Milan, Italy. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Immunol & Uveitis Serv, Boston, MA 02115 USA. RP Brancato, R (reprint author), Univ Milan, Hosp San Raffaele, Dept Ophthalmol & Visual Sci, Via Olgettina 60, I-20132 Milan, Italy. OI Azzolini, Claudio/0000-0002-1334-0974 NR 6 TC 4 Z9 8 U1 1 U2 2 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1120-6721 J9 EUR J OPHTHALMOL JI Eur. J. Ophthalmol. PD JAN-FEB PY 2003 VL 13 IS 1 BP 99 EP 102 PG 4 WC Ophthalmology SC Ophthalmology GA 650KH UT WOS:000181262200018 PM 12635685 ER PT J AU Kang, K Lee, YS Kim, NH Kim, DE Park, SH AF Kang, K Lee, YS Kim, NH Kim, DE Park, SH TI Associated ischemic lesions in intracranial hemorrhage: MRI study SO EUROPEAN NEUROLOGY LA English DT Article DE intracranial hemorrhage; magnetic resonance imaging; lacunar infarction; cerebral infarction; leukoaraiosis ID INTRACEREBRAL HEMATOMAS; LEUKOARAIOSIS; ABNORMALITIES; STROKE AB Cerebral small-vessel disease is an important cause of a hemorrhagic stroke (HS) or a certain type of ischemic stroke (IS). Using magnetic resonance imaging, the frequency and the pattern of ischemic lesions between an HS group and an IS group were compared. Sixty-eight patients with HS and 104 patients with IS as a control group were enrolled in this study. The rate of grade 2 and 3 periventricular white matter lesions (WML) in the HS group was similar to that in the IS group. However, grade 2 and 3 lacunes (LAC) were more frequent in the HS group. These results show that the incidence of concomitant silent LAC is different from that of WML in HS patients. This suggests that the pathophysiology of WML and that of LAC is different and that the pathophysiology of HS is closely associated with that of LAC. Copyright (C) 2003 S. Karger AG, Basel. C1 Seoul Municipal Boramae Hosp, Dept Neurol, Seoul 156707, South Korea. Seoul Natl Univ Hosp, Dept Neurol, Seoul 110744, South Korea. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. RP Lee, YS (reprint author), Seoul Municipal Boramae Hosp, Dept Neurol, Sindaebang 2 Dong 395, Seoul 156707, South Korea. RI Park, Seong Ho/J-5488-2012; Lee, Yong Seok/J-5587-2012 NR 14 TC 2 Z9 2 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0014-3022 J9 EUR NEUROL JI Eur. Neurol. PY 2003 VL 49 IS 2 BP 94 EP 97 DI 10.1159/000068507 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 651KC UT WOS:000181318200006 PM 12584417 ER PT J AU Ntziachristos, V Bremer, C Weissleder, R AF Ntziachristos, V Bremer, C Weissleder, R TI Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging SO EUROPEAN RADIOLOGY LA English DT Review DE near infrared; in vivo; molecular imaging; fluorescence ID RESOLVED OPTICAL TOMOGRAPHY; IN-VIVO; CONTRAST AGENTS; TURBID MEDIA; CATHEPSIN-B; MAGNETIC-RESONANCE; BREAST-CANCER; HUMAN SKIN; MICROSCOPY; TUMORS AB A recent development in biomedical imaging is the non-invasive mapping of molecular events in intact tissues using fluorescence. Underpinning to this development is the discovery of bio-compatible, specific fluorescent probes and proteins and the development of highly sensitive imaging technologies for in vivo fluorescent detection. Of particular interest are fluorochromes that emit in the near infrared (NIR), a spectral window, whereas hemoglobin and water absorb minimally so as to allow photons to penetrate for several centimetres in tissue. In this review article we concentrate on optical imaging technologies used for non-invasive imaging of the distribution of such probes. We illuminate the advantages and limitations of simple photographic methods and turn our attention to fluorescence-mediated molecular tomography (FMT), a technique that can three-dimensionally image gene expression by resolving fluorescence activation in deep tissues. We describe theoretical specifics, and we provide insight into its in vivo capacity and the sensitivity achieved. Finally, we discuss its clinical feasibility. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Ntziachristos, V (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St 5406, Charlestown, MA 02129 USA. NR 66 TC 535 Z9 546 U1 23 U2 230 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD JAN PY 2003 VL 13 IS 1 BP 195 EP 208 DI 10.1007/s00330-002-1524-x PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 643YK UT WOS:000180891000028 PM 12541130 ER PT J AU Shiomi, T Okada, Y Foronjy, R Schiltz, J Jaenish, R Krane, S D'Armiento, J AF Shiomi, T Okada, Y Foronjy, R Schiltz, J Jaenish, R Krane, S D'Armiento, J TI Emphysematous changes are caused by degradation of type III collagen in transgenic mice expressing MMP-1 SO EXPERIMENTAL LUNG RESEARCH LA English DT Article DE collagen; collagenase; emphysema; transgenic mice ID OBSTRUCTIVE PULMONARY-DISEASE; LUNGS; TISSUE; LOCALIZATION; PARENCHYMA; ELASTIN; SITE; IV AB Disruption of the extracellular matrix is believed to play an important role in the pathogenesis of emphysema. Prior studies have demonstrated that transgenic mice expressing the human tissue collagenase, matrix metalloproteinase 1 (MMP-1), develop emphysema. MMP-1 is a protease with substrate specificity for fibillar collagen. Type I and III collagens, which are the most abundant proteins within the lungs, are the primary substrates for MMP-1. To assess if type I collagen was indeed the site of action for MMP-1 in these transgenic mice, hybrid mice were generated by crossing the MMP-1 transgenic mice with mice that had degradation-resistant type I collagen. The hybrid mice demonstrated an identical emphysematous phenotype as the MMP-1 transgenic mice, indicating that the degradation of type I collagen was not essential to the development of emphysema in these mice. Immunohistochemical studies in control mice demonstrated that collagen fibers in the alveolar walls and ducts of the normal mouse lungs consist mainly of type III collagen. In the transgenic and hybrid mice, the emphysematous changes, which developed, were associated with a marked decrease in type III collagen in these alveolar structures. These results indicate that MMP-1. C1 Columbia Univ, Dept Med, Div Mol Med & Pulm Med, New York, NY USA. MIT, Whitehead Inst, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Keio Univ, Sch Med, Dept Pathol, Tokyo 160, Japan. RP Shiomi, T (reprint author), Dept Med, 630 W 168th St,P&S 9-449, New York, NY 10032 USA. RI Okada, Yasunori/B-5550-2014; OI Okada, Yasunori/0000-0001-9208-4755; Shiomi, Takayuki/0000-0002-4250-1204 FU NIA NIH HHS [R01 AG16994-0] NR 29 TC 26 Z9 27 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD JAN-FEB PY 2003 VL 29 IS 1 BP 1 EP 15 DI 10.1080/01902140390116526 PG 15 WC Respiratory System SC Respiratory System GA 630PK UT WOS:000180116900001 PM 12652812 ER PT J AU El-Armouche, A Rau, T Zolk, O Ditz, D Pamminger, T Zimmermann, WH Jackel, E Harding, SE Boknik, P Neumann, J Eschenhagen, T AF El-Armouche, A Rau, T Zolk, O Ditz, D Pamminger, T Zimmermann, WH Jackel, E Harding, SE Boknik, P Neumann, J Eschenhagen, T TI Evidence for protein phosphatase inhibitor-1 playing an amplifier role in beta-adrenergic signaling in cardiac myocytes SO FASEB JOURNAL LA English DT Article DE adenoviral gene transfer; gene expression; heart failure; beta-adrenergic signaling; phospholamban ID RABBIT SKELETAL-MUSCLE; HUMAN HEART-FAILURE; GLYCOGEN-SYNTHASE; FAILING HEARTS; PHOSPHORYLATION; RAT; PHOSPHOLAMBAN; EXPRESSION; ISOPROTERENOL; STIMULATION AB The protein phosphatase inhibitor-1 (PPI-1) inhibits phosphatase type-1 (PP1) only when phosphorylated by protein kinase A and could play a pivotal role in the phosphorylation/dephosphorylation balance. Rat cardiac PPI-1 was cloned by reverse transcriptase-polymerase chain reaction, expressed in Eschericia coli, evaluated in phosphatase assays, and used to generate an antiserum. An adenovirus was constructed encoding PPI-1 and green fluorescent protein (GFP) under separate cytomegalovirus promotors (AdPPI-1/GFP). A GFP-only virus (AdGFP) served as control. Engineered heart tissue (EHT) from neonatal rat cardiomyocytes and adult rat cardiac myocytes (ARCMs) were used as model systems. PPI-1 expression was determined in human ventricular samples by Northern blots. Compared with AdGFP, AdPPI-1/GFP-infected neonatal rat cardiomyocytes displayed a 73% reduction in PP1 activity. EHTs infected with AdPPI-1/GFP exhibited a fivefold increase in isoprenaline sensitivity. AdPPI-1/GFP-infected ARCMs displayed enhanced cell shortening as well as enhanced phospholamban phosphorylation when stimulated with 1 nM isoprenaline. PPI-1 mRNA levels were reduced by 57+/-12% in failing hearts with dilated and ischemic cardiomyopathy (n=8 each) compared with nonfailing hearts (n=8). In summary, increased PPI-1 expression enhances myocyte sensitivity to isoprenaline, indicating that PPI-1 acts as an amplifier in beta-adrenergic signaling. Decreased PPI-1 in failing human hearts could participate in desensitization of the cAMP pathway. C1 Univ Hamburg, Hosp Eppendorf, Inst Expt & Klin Pharmakol & Toxikol, D-20246 Hamburg, Germany. Univ Erlangen Nurnberg, Inst Expt & Klin Pharmakol & Toxikol, Erlangen, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ London Imperial Coll Sci Technol & Med, Sch Med, NHLI, London, England. Univ Munster, Inst Pharmakol & Toxikol, D-4400 Munster, Germany. RP Eschenhagen, T (reprint author), Univ Hamburg, Hosp Eppendorf, Inst Expt & Klin Pharmakol & Toxikol, Martinistr 52, D-20246 Hamburg, Germany. EM t.eschenhagen@uke.uni-hamburg.de RI Zimmermann, Wolfram-Hubertus/I-6838-2012; OI Zimmermann, Wolfram-Hubertus/0000-0003-1190-4040; Zolk, Oliver/0000-0002-8220-3834 NR 38 TC 75 Z9 76 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 2003 VL 17 IS 1 BP 437 EP + DI 10.1096/fj.02-0057fje PG 23 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 653TT UT WOS:000181453700021 PM 12514122 ER PT J AU Henderson, JA Smith, JJ AF Henderson, JA Smith, JJ TI Financial conflict of interest in medical research: Overview and analysis of institutional controls SO FOOD AND DRUG LAW JOURNAL LA English DT Article ID POLICIES C1 Ctr Integrat Med & Innovat Technol, Regulatory Affairs Program, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Ctr Integrat Med & Innovat Technol, Boston, MA USA. RP Henderson, JA (reprint author), Ctr Integrat Med & Innovat Technol, Regulatory Affairs Program, Boston, MA USA. NR 4 TC 2 Z9 2 U1 0 U2 1 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2003 VL 58 IS 2 BP 251 EP 267 PG 17 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 703NB UT WOS:000184285000008 PM 12866557 ER PT J AU Wang, SS Smith, JJ AF Wang, SS Smith, JJ TI Potential legal barriers to increasing CMS/FDA collaboration: The law of trade secrets and related considerations SO FOOD AND DRUG LAW JOURNAL LA English DT Article ID MEDICAL DEVICES; DRUG C1 Duke Univ, Ctr Med, Dept Internal Med, Durham, NC 27706 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Ctr Integrat Med & Innovat Technol, Boston, MA USA. RP Wang, SS (reprint author), Duke Univ, Ctr Med, Dept Internal Med, Durham, NC 27706 USA. NR 21 TC 3 Z9 3 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2003 VL 58 IS 4 BP 613 EP 627 PG 15 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 778DQ UT WOS:000189224200005 PM 15027453 ER PT J AU Green, P Byun, J Mendez, A Driscoll, W Crowley, J Hyman, B Heinecke, J AF Green, P Byun, J Mendez, A Driscoll, W Crowley, J Hyman, B Heinecke, J TI Increased myeloperoxidase expression in Alzheimer's disease: Implications for amyloid oxidation and aggregation. SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Miami, Sch Med, Dept Med, Coral Gables, FL 33124 USA. Washington Univ, St Louis, MO 63130 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2003 VL 35 SU 1 MA 486 BP S156 EP S157 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900509 ER PT J AU Hensley, K Brown, R Cudkowicz, M Fedynyshyn, J Floyd, R Gabbita, P Mou, SY Pye, Q Mhatre, M Stewart, C West, M Williamson, K AF Hensley, K Brown, R Cudkowicz, M Fedynyshyn, J Floyd, R Gabbita, P Mou, SY Pye, Q Mhatre, M Stewart, C West, M Williamson, K TI Dysfunctional cytokine networks in amyotrophic lateral sclerosis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. BioRad Labs, Hercules, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2003 VL 35 SU 1 MA 489 BP S157 EP S157 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900512 ER PT J AU Yang, HY Tartier, L McCarey, Y Held, K AF Yang, HY Tartier, L McCarey, Y Held, K TI Role of calcium, MAPKs and bcl-2 in thiol-induced apoptosis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne CY NOV 20-24, 2003 CL SEATTLE, WASHINGTON SP Soc Free Rad Biol & Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2003 VL 35 SU 1 MA 399 BP S126 EP S126 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 744XV UT WOS:000186658900421 ER PT J AU Best, CA Laposata, M AF Best, CA Laposata, M TI Fatty acid ethyl esters: Toxic non-oxidative metabolites of ethanol and markers of ethanol intake SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Review DE fatty acid ethyl esters; FAEE; ethanol; biomarker; alcohol; review ID CARBOHYDRATE-DEFICIENT TRANSFERRIN; GLUTATHIONE-S-TRANSFERASE; FETAL ALCOHOL SYNDROME; WHITE BLOOD-CELLS; ADIPOSE-TISSUE; UNITED-STATES; PANCREATIC INJURY; PROTEIN-SYNTHESIS; LIVER-MICROSOMES; HEPG2 CELLS AB This report describes the biochemistry of fatty acid ethyl esters (FAEE), non-oxidative metabolites of ethanol, and their clinical significance. We review information regarding the enzymes responsible for FAEE synthesis and degradation, and the mechanisms involved with the intracellular and extracellular transport of FAEE and FAEE-mediated cytotoxicity. Also a summary of reports on the emerging clinical significance and diagnostic utility of FAEE as short and long-term markers of alcohol consumption, and the methodological aspects of FAEE assessment is included. C1 Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Room 235,Gray Bldg,55 Fruit St, Boston, MA 02114 USA. EM mlaposata@partners.org NR 100 TC 42 Z9 45 U1 1 U2 7 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN PY 2003 VL 8 BP E202 EP E217 DI 10.2741/931 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 633DQ UT WOS:000180266400066 PM 12456329 ER PT J AU Sarkar, S Hobson, AR Hughes, A Growcott, J Woolf, CJ Thompson, DG Aziz, Q AF Sarkar, S Hobson, AR Hughes, A Growcott, J Woolf, CJ Thompson, DG Aziz, Q TI The prostaglandin E2 receptor-1 (EP-1) mediates acid-induced visceral pain hypersensitivity in humans SO GASTROENTEROLOGY LA English DT Article ID RAT SPINAL-CORD; CONSCIOUS MICE; PHARMACOLOGICAL ANALYSIS; E(2)-INDUCED ALLODYNIA; CENTRAL SENSITIZATION; POLYMODAL RECEPTORS; UNANESTHETIZED RATS; INFLAMMATORY PAIN; CHEST PAIN; HYPERALGESIA AB Background & Aims: Central sensitization, an activity-dependent increase in spinal cord neuronal excitability, has been shown to contribute to esophageal pain hypersensitivity. Prostaglandin E2 (PGE(2)) is a mediator in both peripheral and central sensitization, in part via the prostaglandin E2 receptor-1 (EP-1), and may be a potential target for treating visceral pain. The purpose of this study was to determine whether acid-induced pain hypersensitivity within the non-acid-exposed esophagus (secondary hyperalgesia) is mediated by PGE(2) activation of the EP-1 receptor. Methods: Twelve healthy male subjects participated in a randomized, placebo-controlled crossover study. Upper esophageal pain thresholds (PTs) to electrical stimulation were determined, and either the EP-1 antagonist ZD6416 or a placebo was orally administered. One-hour after dosing, acid or saline (0.15 mol/L) was infused into the lower esophagus for 30 minutes. Upper esophageal PT was monitored for 120 minutes after infusion. Results: Except in 1 subject (who was excluded), the pH in the upper esophagus remained above 5 throughout all studies. In 8 subjects, ZD6416 attenuated the reduction in PT in the upper esophagus normally induced by acid infusion into the lower esophagus (area under curve [AUC]: -11.9 +/- 2.5 and 6.4 +/- 6.7 for placebo and ZD6416, respectively; P < 0.01). After saline infusion, the effects of ZD6416 and placebo were similar (AUC: 9.9 +/- 6 and 4.1 +/- 2, respectively; P = 0.8). Three subjects had no reduction in PT to acid infusion with placebo and were excluded at post hoc analysis. Conclusions: The attenuation of secondary esophageal hyperalgesia by ZD6416 suggests that PGE(2), via the EP-1 receptor, contributes to human visceral pain hypersensitivity. C1 Univ Manchester, Hope Hosp, Dept GI Sci, Salford M6 8HD, Lancs, England. AstraZeneca, Alderley Pk, England. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Aziz, Q (reprint author), Univ Manchester, Hope Hosp, Dept GI Sci, Clin Sci Bldg, Salford M6 8HD, Lancs, England. OI hughes, andrew/0000-0002-8690-4056 NR 61 TC 84 Z9 86 U1 2 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2003 VL 124 IS 1 BP 18 EP 25 DI 10.1053/gast.2003.50022 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 631GP UT WOS:000180160000005 PM 12512025 ER PT J AU Dienstag, JL Goldin, RD Heathcote, EJ Hann, HWL Woessner, M Stephenson, SL Gardner, S Gray, DF Schiff, ER AF Dienstag, JL Goldin, RD Heathcote, EJ Hann, HWL Woessner, M Stephenson, SL Gardner, S Gray, DF Schiff, ER TI Histological outcome during long-term lamivudine therapy SO GASTROENTEROLOGY LA English DT Article ID CHRONIC HEPATITIS-B; FIBROSIS; INFECTION; TRIAL AB Background & Aims: One year of lamivudine for chronic hepatitis B results in histologic improvement. We aimed to assess the histological impact of longer-term treatment. Methods: Sets of 3 liver biopsies, from 63 patients before and after I year of randomized lamivudine treatment and after 2 years of further open-label treatment, were assigned Histologic Activity Index scores under code. Results: At the end of year 1, 36/63 (57%) showed greater than or equal to2 point improvement and 24/63 (38%) no change in necroinflammatory activity; after 2 additional years of lamivudine, 38/63 (60%) remained stable and 12/63 (19%) continued to improve. Worsening occurred in similar proportions of patients with and without YMDD (tyrosine, methionine, aspartate, aspartate) variants. After all 3 years of lamivudine treatment, 35/63 (56%) of patients showed improvement, 21/63 (33%) no change, and 7/63 (11%) worsening. Those without, compared with those with, YMDD variants were more likely to improve (17/22 [77%] vs. 18/41 [44%]) and less likely to deteriorate (1/22 [5%] vs. 6/41 [15%]). Patients with YMDD variants for >2 years were least likely to improve (8/22 [36%]). Bridging fibrosis improved by greater than or equal to1 level in 12/19 (63%), and cirrhosis improved (score of 4 to less than or equal to3) in 8/11 (73%). Only 1/52 [2%]) showed progression to cirrhosis, and 3/34 (9%) showed progression to bridging fibrosis (all with YMDD variants). Conclusions: Three years of lamivudine therapy reduces necroinflammatory activity and reverses fibrosis (including cirrhosis) in most patients. The emergence of YMDD variants blunts histologic responses; therefore, extended-duration YMDD variants may require additional therapies to maintain the histological benefit of treatment. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ London Imperial Coll Sci Technol & Med, Sch Med, St Marys Hosp, London, England. Univ Hlth Network, Toronto Western Hosp, Toronto, ON, Canada. Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA. GlaxoSmith Res & Dev, Greenford, Middx, England. GlaxoSmithKline Res & Dev, Res Triangle Pk, NC USA. Univ Miami, Med Ctr, Ctr Liver, Miami, FL 33152 USA. RP Dienstag, JL (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. NR 25 TC 485 Z9 532 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2003 VL 124 IS 1 BP 105 EP 117 DI 10.1053/gast.2003.50013 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 631GP UT WOS:000180160000015 PM 12512035 ER PT J AU Hunt, GC Smith, PP Faigel, DO AF Hunt, GC Smith, PP Faigel, DO TI Yield of tissue sampling for submucosal lesions evaluated by EUS SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Digestive Disease Week/102nd Annual Meeting of the American-Gastroenterological-Association CY MAY 20-23, 2001 CL ATLANTA, GEORGIA SP Amer Gastroenterol Assoc ID ENDOSCOPIC MUCOSAL RESECTION; COLORECTAL TUMORS; ULTRASOUND PROBE; DIAGNOSIS; INVASION AB Background: Evaluation of submucosal nodules or large gastric folds is a common indication for EUS. Establishing a tissue diagnosis is challenging because the yield of forceps biopsies is low. The aim of this study was to determine the diagnostic yield of EUS-guided endoscopic submucosal-mucosal resection and forceps biopsy for submucosal nodules and large gastric folds. Methods: Patients who underwent EUS from March 1997 through January 2002 for evaluation of submucosal nodules or large gastric folds were identified, and the procedure and pathology reports reviewed. Patients were included who underwent endoscopic submucosal-mucosal resection (n = 45) or large-capacity ("jumbo") biopsy (n = 36) of submucosal lesions (arising from third endosonographic layer) or large gastric folds. Endoscopic submucosal-mucosal resection was performed with an electrosurgical snare or with a cap-fitted endoscopic mucosal resection device. Results: Sixty-six patients (62% men; mean age, 61 years; range 27-80 years) underwent 69 EUS procedures to obtain tissue samples of subepithelial lesions. Diagnostic yields were as follows: endoscopic submucosal-mucosal resection 40/45 (89%; 95% CI [80%, 98%]), jumbo biopsy 15/36 (42%; 95% CI [26%, 58%]) (p < 0.001 by two-tailed Fisher exact test). There were 9 complications: 7 instances of bleeding (6 endoscopic submucosal-mucosal resection, 1 jumbo biopsy), 3 requiring hospitalization (2 endoscopic submucosal-mucosal resection, 1 jumbo biopsy) and 2 requiring transfusion; 1 chest pain and odynophagia (esophageal endoscopic submucosal-mucosal resection); and 1 oversedation (requiring administration of reversal agents). Conclusions: For submucosal lesions and large gastric folds, endoscopic submucosal-mucosal resection has a better diagnostic yield than the jumbo biopsy, but may have a higher complication rate. C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Faigel, DO (reprint author), Oregon Hlth Sci Univ, Phys Pavil,Suite 310,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. NR 20 TC 65 Z9 70 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JAN PY 2003 VL 57 IS 1 BP 68 EP 72 DI 10.1067/mge.2003.34 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 634JQ UT WOS:000180336600012 PM 12518134 ER PT J AU Kontos, N Freudenreich, O Querques, J Norris, E AF Kontos, N Freudenreich, O Querques, J Norris, E TI The consultation psychiatrist as effective physician SO GENERAL HOSPITAL PSYCHIATRY LA English DT Editorial Material DE C-L psychiatry; practice; opinion ID DEPRESSION AB The two fundamental tasks of the consultation psychiatrist, diagnosis and treatment, can sometimes seem at odds with the consultee's desired plan or outcome. While implicitly recognized, this fact is rarely explicitly taught to residents or addressed in the literature. The authors proffer three principles of inpatient consultation psychiatry aimed at dealing with tensions that can arise over issues of; 1) diagnosis (Principle I: Do not be afraid to refute notions of psychopathology); 2) medication (Principle II: Do not be afraid to discontinue unnecessary psychotropics); and 3) responsibility (Principle III: Do not be afraid to "sign off" when necessary). These principles emphasize the medical model, the status of the psychiatrist as a medical expert, and the importance of defining one's professional limits. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Sch Med, Cambridge Hlth Allilance, Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02129 USA. Emory Univ, Emory Univ Hosp, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. RP Kontos, N (reprint author), Harvard Univ, Sch Med, Cambridge Hlth Allilance, Dept Psychiat, Cambridge, MA 02138 USA. NR 6 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2003 VL 25 IS 1 BP 20 EP 23 DI 10.1016/S0163-8343(02)00251-7 PG 4 WC Psychiatry SC Psychiatry GA 648CR UT WOS:000181132700004 PM 12583923 ER PT J AU Chang, S Khoo, CM Naylor, ML Maser, RS DePinho, RA AF Chang, S Khoo, CM Naylor, ML Maser, RS DePinho, RA TI Telomere-based crisis: functional differences between telomerase activation and ALT in tumor progression SO GENES & DEVELOPMENT LA English DT Article DE telomere; telomerase; metastasis; ALT (alternative lengthening of telomeres); chromosomal instability; SKY ID MAMMARY EPITHELIAL-CELLS; HUMAN FIBROBLASTS; LIFE-SPAN; CHROMOSOMAL INSTABILITY; ALTERNATIVE MECHANISM; REVERSE-TRANSCRIPTASE; CELLULAR SENESCENCE; CATALYTIC SUBUNIT; IMMORTAL CELLS; DEFICIENT MICE AB Telomerase activation is a common feature of most advanced human cancers and is postulated to restore genomic stability to a level permissive for cell viability and tumor progression. Here, we used genetically defined transformed mouse embryonic fibroblast (MEF) cultures derived from late generation mTerc(-/-)Ink4a/Arf(-/-) mice to explore more directly how telomere-based crisis relates to the evolution of cancer cell genomes and to tumor biology. An exhaustive serial analysis of cytogenetic profiles over extensive passage in culture revealed that the emergence of chromosomal fusions (including dicentrics) coincided with onset of deletions and complex nonreciprocal translocations (NRTs), whereas mTerc-transduced cultures maintained intact chromosomes and stable genomes. Despite a high degree of telomere dysfunction and genomic instability, transformed late passage mTerc(-/-)Ink4a/Arf(-/-) cultures retained the capacity to form subcutaneous tumors in immunocompromised mice. However, even moderate levels of telomere dysfunction completely abrogated the capacity of these cells to form lung metastases after, tail-vein injection, whereas InTerc reconstitution alone conferred robust metastatic activity in these cells. Finally, serial subcutaneous tumor formation using late passage transformed mTerc(-/-)Ink4a/Arf(-/-) cultures revealed clear evidence of telomerase-independent alternative lengthening of telomeres (ALT). Significantly, despite a marked increase in telomere reserve, cells derived from the ALT+ subcutaneous tumors were unable to generate lung metastases, indicating in vivo functional differences in these principal mechanisms of telomere maintenance. Together, these results are consistent with the model that although telomere dysfunction provokes chromosomal aberrations that initiate carcinogenesis, telomerase-mediated telomere maintenance enables such initiated cells to efficiently achieve a fully malignant endpoint, including metastasis. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RI Maser, Richard/B-2970-2012 FU NIA NIH HHS [1KO8AG01019-01, K08 AG001019] NR 72 TC 145 Z9 160 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 1 PY 2003 VL 17 IS 1 BP 88 EP 100 DI 10.1101/gad.1029903 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 633JT UT WOS:000180280700009 PM 12514102 ER PT J AU Almasy, L Cupples, LA Daw, EW Levy, D Thomas, D Rice, JP Santangelo, S MacCluer, JW AF Almasy, L Cupples, LA Daw, EW Levy, D Thomas, D Rice, JP Santangelo, S MacCluer, JW TI Genetic analysis workshop 13: Introduction to workshop summaries SO GENETIC EPIDEMIOLOGY LA English DT Editorial Material C1 SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Harvard Univ, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA USA. RP Almasy, L (reprint author), SW Fdn Biomed Res, Dept Genet, POB 760549, San Antonio, TX 78245 USA. OI Cupples, L. Adrienne/0000-0003-0273-7965 FU NIGMS NIH HHS [GM31575] NR 5 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2003 VL 25 SU 1 BP S1 EP S4 DI 10.1002/gepi.10278 PG 4 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 751GP UT WOS:000187044700001 PM 14635163 ER PT J AU Goldin, LR Camp, NJ Keen, KJ Martin, LJ Moslehi, R Ghosh, S North, KE Wyszynski, DF Blacker, D AF Goldin, LR Camp, NJ Keen, KJ Martin, LJ Moslehi, R Ghosh, S North, KE Wyszynski, DF Blacker, D TI Analysis of metabolic syndrome phenotypes in Framingham Heart Study families from Genetic Analysis Workshop 13 SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 13th Genetic Analysis Workshop CY NOV 11-14, 2002 CL NEW ORLEANS, LA DE metabolic syndrome; longitudinal measures; linkage methods; susceptibility genes ID QUANTITATIVE-TRAIT LOCI; MULTILOCUS LINKAGE ANALYSIS; BODY-MASS INDEX; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; BLOOD-PRESSURE; OBESITY; HYPERTENSION; RISK AB Twelve teams of investigators constituted a group which analyzed phenotypes related to metabolic syndrome, making use of the available longitudinal measurements from the family component of the Framingham Heart Study or the simulated data, as distributed by Genetic Analysis Workshop 13 (GAW13). Body mass index, obesity, lipid abnormalities, glucose, or combinations of these traits were analyzed by this group. A wide variety of approaches were taken to construct phenotypes from the longitudinal measurements, including considering single or multiple cross-sectional time points, single ages, minimum values, maximum values, means, other lifetime values, ever/never dichotomy, or age at onset of some threshold value. Approaches also differed in the family structures utilized (sib pairs to full extended pedigrees), the genetic data considered (two-point or multipoint), and the statistics calculated (model-free and parametric), and led to a diverse set of analyses being performed. Inferences were made about heritability, and attempts were made to map underlying genes. Over 40 genome-wide linkage analyses were conducted. Despite the broad range of approaches, several regions of the genome were repeatedly identified across multiple analyses. Published 2003 Wiley-Liss, Inc dagger. C1 NCI, DCEG, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Univ Utah, Sch Med, Dept Med Informat, Div Genet Epidemiol, Salt Lake City, UT USA. Case Western Reserve Univ, Dept Epidemiol, Cleveland, OH 44106 USA. Cincinnati Childrens Hosp Med Ctr, Ctr Biostat & Epidemiol, Cincinnati, OH USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Indian Stat Inst, Appl Stat Unit, Kolkata 700035, W Bengal, India. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. Boston Univ, Sch Med, Dept Med, Genet Program, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Goldin, LR (reprint author), NCI, DCEG, Genet Epidemiol Branch, 6120 Execut Blvd,MSC 7236, Bethesda, MD 20892 USA. EM goldinl@mail.nih.gov RI Keen, Kevin/D-5628-2013; Martin, Lisa/E-2425-2016 OI Keen, Kevin/0000-0001-5695-0505; Martin, Lisa/0000-0001-8702-9946 NR 56 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2003 VL 25 SU 1 BP S78 EP S89 DI 10.1002/gepi.10288 PG 12 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 751GP UT WOS:000187044700011 PM 14635173 ER PT J AU Asha, H Nagy, I Kovacs, G Stetson, D Ando, I Dearolf, CR AF Asha, H Nagy, I Kovacs, G Stetson, D Ando, I Dearolf, CR TI Analysis of Ras-induced overproliferation in Drosophila hemocytes SO GENETICS LA English DT Article ID DEPENDENT KINASE INHIBITOR; PROMOTES CELLULAR GROWTH; ABERRANT CRYPT FOCI; SIGNAL-TRANSDUCTION; FATE DETERMINATION; EXPRESSION; PROTEIN; MELANOGASTER; GENE; TRANSFORMATION AB We use the Drosophila melanogaster larval hematopoietic system as an in vivo model for the genetic and functional genomic analysis of oncogenic cell overproliferation. Ras regulates cell proliferation and differentiation in multicellular eukaryotes. To further elucidate the role of activated Ras in cell overproliferation, we generated a collagen promoter-Ga14 strain to ovcrexpress Ras(V12) in Drosophila hemocytes. Activated Ras causes a dramatic increase in the number of circulating larval hemocytes (blood cells), which is caused by cellular overproliferation. This phenotype is mediated by the Raf/MAPK pathway. The mutant hemocytes retain the ability to phagocytose bacteria as well as to differentiate into lamellocytes. Microarray analysis of hemocytes overexpressing Rasv(V12) vs. Ras(+) identified 279 transcripts that are differentially expressed threefold or more in hemocytes expressing activated Ras. This work demonstrates that it will be feasible to combine genetic and functional genomic approaches in the Drosophila hematopoietic system to systematically identify oncogene-specific downstream targets. C1 Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Hungarian Acad Sci, Biol Res Ctr, Genet Inst, H-6701 Szeged, Hungary. RP Dearolf, CR (reprint author), Massachusetts Gen Hosp, Dept Pediat, Jackson 1402,55 Fruit St, Boston, MA 02114 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 57 TC 151 Z9 157 U1 0 U2 4 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JAN PY 2003 VL 163 IS 1 BP 203 EP 215 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 646MW UT WOS:000181039700018 PM 12586708 ER PT J AU Liberfarb, RM Levy, HP Rose, PS Wilkin, DJ Davis, J Balog, JZ Griffith, AJ Szymko-Bennett, YM Johnston, JJ Francomano, CA AF Liberfarb, RM Levy, HP Rose, PS Wilkin, DJ Davis, J Balog, JZ Griffith, AJ Szymko-Bennett, YM Johnston, JJ Francomano, CA TI The Stickler syndrome: Genotype/phenotype correlation in 10 families with Stickler syndrome resulting from seven mutations in the type II collagen gene locus COL2A1 SO GENETICS IN MEDICINE LA English DT Article DE Stickler syndrome; genotype/phenotype correlation; prevalence of clinical features ID PROGRESSIVE ARTHRO-OPHTHALMOPATHY; PREMATURE TERMINATION CODONS; MITRAL-VALVE PROLAPSE; PROCOLLAGEN GENE; SYNDROME ARTHROOPHTHALMOPATHY; IMPEDANCE AUDIOMETRY; STOP CODON; LINKAGE; COL11A1; MANIFESTATIONS AB Purpose: To evaluate a cohort of clinically diagnosed Stickler patients in which the causative COL2A1 mutation has been identified, determine the prevalence of clinical features in this group as a whole and as a function of age, and look for genotype/phenotype correlations. Methods: Review of medical records, clinical evaluations, and mutational analyses of clinically diagnosed Stickler patients. Results: Patients with seven defined COL2A1 mutations had similar phenotypes, though both inter- and intrafamilial variability were apparent and extensive. The prevalence of certain clinical features was a function of age. Conclusion: Although the molecular determination of a COL2A1 mutation can predict the occurrence of Stickler syndrome, the variability observed in the families described here makes it difficult to predict the severity of the phenotype on the basis of genotype. C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Microarray Core Facil, Los Angeles, CA 90048 USA. Mayo Clin & Mayo Grad Sch Med, Dept Orthoped Surg, Rochester, MN 55901 USA. Johns Hopkins Univ, Sch Med, Dept Internal Med, Baltimore, MD USA. RP Liberfarb, RM (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Warren 801,55 Fruit St, Boston, MA 02114 USA. FU NIDCD NIH HHS [Z01 DC000060-01] NR 55 TC 29 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JAN-FEB PY 2003 VL 5 IS 1 BP 21 EP 27 DI 10.1097/01.GIM.0000048704.65405.D8 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 740EV UT WOS:000186390700004 PM 12544472 ER PT J AU Blackshaw, S Kuo, WP Park, PJ Tsujikawa, M Gunnersen, JM Scott, HS Boon, WM Tan, SS Cepko, CL AF Blackshaw, S Kuo, WP Park, PJ Tsujikawa, M Gunnersen, JM Scott, HS Boon, WM Tan, SS Cepko, CL TI MicroSAGE is highly representative and reproducible but reveals major differences in gene expression among samples obtained from similar tissues SO GENOME BIOLOGY LA English DT Article ID SERIAL ANALYSIS; MICROARRAY ANALYSIS; MOUSE-BRAIN; RAT RETINA; RNA; CELL; MICE; PROFILES; DISEASE; SAGE AB Background: Serial analysis of gene expression using small amounts of starting material (microSAGE) has not yet been conclusively shown to be representative, reproducible or accurate. Results: We show that microSAGE is highly representative, reproducible and accurate, but that pronounced differences in gene expression are seen between tissue samples taken from different individuals. Conclusions: MicroSAGE is a reliable method of comprehensively profiling differences in gene expression among samples, but care should be taken in generalizing results obtained from libraries constructed from tissue obtained from different individuals and/or processed or stored differently. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp Informat Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Decis Syst Grp, Boston, MA 02115 USA. Harvard Univ, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Univ Melbourne, Brain Dev Lab, Howard Florey Inst, Parkville, Vic 3010, Australia. RP Cepko, CL (reprint author), Harvard Univ, Sch Med, Dept Genet, 200 Longwood Ave, Boston, MA 02115 USA. RI Scott, Hamish/B-2122-2009 OI Scott, Hamish/0000-0002-5813-631X FU NEI NIH HHS [EY0976]; NLM NIH HHS [5T15 LM07092-07, T15 LM007092] NR 56 TC 33 Z9 35 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2003 VL 4 IS 3 AR R17 DI 10.1186/gb-2003-4-3-r17 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 675KU UT WOS:000182694200006 PM 12620102 ER PT J AU Griffin, RS Mills, CD Costigan, M Woolf, CJ AF Griffin, RS Mills, CD Costigan, M Woolf, CJ TI Exploiting microarrays to reveal differential gene expression in the nervous system SO GENOME BIOLOGY LA English DT Editorial Material ID SINGLE CELLS; BRAIN; MICE; IDENTIFICATION; PROFILE; NEURONS; NETWORK; CORTEX; CDNA AB Microarrays have been used in a wide variety of experimental systems, but realizing their full potential is contingent on sophisticated and rigorous experimental design and data analysis. This article highlights what is needed to get the most out of microarrays in terms of accurately and effectively revealing differential gene expression and regulation in the nervous system. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. FU NICHD NIH HHS [HD38533]; NINDS NIH HHS [F32 NS045459, NS3825, NS39518, NS45459, R01 NS039518, R37 NS039518] NR 32 TC 15 Z9 17 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2003 VL 4 IS 2 AR 105 DI 10.1186/gb-2003-4-2-105 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 675KH UT WOS:000182693100002 PM 12620110 ER PT J AU Cabarrocas, J Savidge, TC Liblau, RS AF Cabarrocas, J Savidge, TC Liblau, RS TI Role of enteric glial cells in inflammatory bowel disease SO GLIA LA English DT Review DE enteric glial cells; digestive tract; T-cell; autoimmunity; immune response ID BLOOD-BRAIN-BARRIER; NITRIC-OXIDE SYNTHASE; FIBRILLARY ACIDIC PROTEIN; NEURON-SPECIFIC ENOLASE; ADULT TRANSGENIC MICE; RAT MYENTERIC PLEXUS; NERVOUS-SYSTEM; CROHNS-DISEASE; GUINEA-PIG; ENDOTHELIAL-CELLS AB Enteric glial cells (EGCs) represent an extensive but relatively poorly described cell population within the gastrointestinal tract. Accumulating data suggest that EGCs represent the morphological and. functional equivalent of CNS astrocytes within the enteric nervous system (ENS). The EGC network has trophic and protective functions toward enteric neurons and is fully implicated in the integration and the modulation of neuronal activities. Moreover, EGCs seem to be active elements of the ENS during intestinal inflammatory and immune responses, sharing with astrocytes the ability to act as antigen-presenting cells and interacting with the mucosal immune system via the expression of cytokines and cytokine receptors. Transgenic mouse systems have demonstrated that specific ablation of EGC by chemical ablation or autoimmune T-cell targeting induces an intestinal pathology that shows similarities to the early intestinal immunopathology of Crohn's disease. EGCs may also share with astrocytes the ability to regulate tissue integrity, thereby postulating that similar interactions to those observed for the blood-brain barrier may also be partly responsible for regulating mucosal and vascular permeability in the gastrointestinal tract. Disruption of the EGC network in Crohn's disease patients may represent one possible cause for the enhanced mucosal permeability state and vascular dysfunction that are thought to favor mucosal inflammation. (C) 2003 Wiley-Liss, Inc. C1 Hop La Pitie Salpetriere, INSERM, U546, Paris, France. Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. CHU Toulouse, Immunol Lab, Toulouse, France. RP Liblau, RS (reprint author), Hop Rangueil, Immunol Lab, F-31403 Toulouse, France. NR 122 TC 98 Z9 99 U1 5 U2 14 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0894-1491 J9 GLIA JI Glia PD JAN PY 2003 VL 41 IS 1 BP 81 EP 93 DI 10.1002/glia.10169 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 631FX UT WOS:000180158400009 PM 12465048 ER PT S AU Coyle, JT Tsai, G Goff, D AF Coyle, JT Tsai, G Goff, D BE Moghaddam, B Wolf, M TI Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophrenia SO GLUTAMATE AND DISORDERS OF COGNITION AND MOTIVATION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Glutamate and Disorders of Cognition and Motivation CY APR 13-15, 2003 CL NEW HAVEN, CONNECTICUT SP Acad Sci, Natl Inst Ment Mental, Eli Lilly & Co DE NMDA receptor; schizophrenia; glycine modulatory site; glycine; D-serine; D-cycloserine; negative symptoms; GlyT1 ID D-ASPARTATE RECEPTOR; PREFRONTAL CORTEX; D-CYCLOSERINE; D-SERINE; GLYCINE TRANSPORT; NEGATIVE SYMPTOMS; NERVOUS-SYSTEM; MESSENGER-RNA; KETAMINE; NEURONS AB Numerous clinical studies demonstrate that subanesthetic doses of dissociative anesthetics, which are noncompetitive antagonists at the NMDA receptor, replicate in normal subjects the cognitive impairments, negative symptoms, and brain functional abnormalities of schizophrenia. Postmortem and genetic studies have identified several abnormalities associated with schizophrenia that would interfere with the activation of the glycine modulatory site on the NMDA receptor. Placebo-controlled clinical trials with agents that directly or indirectly activate the glycine modulatory site consistently reduce negative symptoms and frequently improve cognition in patients with chronic schizophrenia who are receiving concurrent typical antipsychotics. Thus, there is convincing evidence that hypofunction of a subset of NMDA receptors may contribute to the symptomatic features of schizophrenia. C1 McLean Hosp, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Coyle, JT (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. EM joseph_coyle@hms.harvard.edu FU NIMH NIH HHS [MH-572901] NR 53 TC 250 Z9 254 U1 2 U2 11 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-476-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1003 BP 318 EP 327 DI 10.1196/annals.1300.020 PG 10 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BY31Q UT WOS:000188893500025 PM 14684455 ER PT S AU Sattin, A Pekary, AE Lloyd, RL Paulson, M Meyerhoff, JA Hinkle, PM Faull, K AF Sattin, A Pekary, AE Lloyd, RL Paulson, M Meyerhoff, JA Hinkle, PM Faull, K BE Moghaddam, B Wolf, M TI TRH and related peptides - Homeostatic regulators of glutamate transmission? SO GLUTAMATE AND DISORDERS OF COGNITION AND MOTIVATION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Glutamate and Disorders of Cognition and Motivation CY APR 13-15, 2003 CL NEW HAVEN, CONNECTICUT SP Acad Sci, Natl Inst Ment Mental, Eli Lilly & Co DE TRH; glutamate transmission; colocalization ID RAT-BRAIN; MECHANISM; RECEPTORS C1 Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Calif State Univ Los Angeles, Dept Psychiat, Los Angeles, CA USA. Calif State Univ Los Angeles, Dept Med, Los Angeles, CA USA. Calif State Univ Los Angeles, Brain Res Inst, Los Angeles, CA USA. Univ Minnesota, Dept Psychol, Duluth, MN USA. Walter Reed Army Inst Res, Silver Spring, MD USA. Univ Rochester, Dept Pharmacol, Rochester, NY USA. RP Sattin, A (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, POB 84122, Los Angeles, CA 90073 USA. EM asattin@ucla.edu NR 10 TC 2 Z9 2 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-476-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1003 BP 458 EP 460 DI 10.1196/annals.1300.053 PG 3 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BY31Q UT WOS:000188893500058 PM 14684488 ER PT J AU Baltatzis, S Romero-Rangel, T Foster, CS AF Baltatzis, S Romero-Rangel, T Foster, CS TI Sectorial keratitis and uveitis: differential diagnosis SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID KERATOUVEITIS AB Purpose: The purpose of this study was to examine the importance of considering the differential diagnosis for patients with sectorial keratitis and uveitis by case summary and literature review. Methods: A retrospective review of patients with sectorial keratitis and uveitis seen at the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary and a summary of the diagnoses of cases with similar ocular findings that have been reported in the literature. Results: Data on six patients with sectorial keratitis and uveitis were reviewed. Four patients were female and two were male, ages 21-50 years. All were eventually diagnosed with herpes simplex viral stromal sectorial keratitis. The corneal infiltrates were most common in the superior corneal quadrants, located in the posterior corneal layers. Anterior non-granulomatous uveitis was present in all cases. One case had bilateral ocular involvement. Five of the six patients responded to topical steroids and antiviral treatment. Immunomodulation with methotrexate, cyclosporine, and systemic prednisone was required in one patient. Glaucoma was a complication in six of the seven eyes. Five patients developed corneal scarring, localized in the anterior and midstroma. Conclusion: The differential diagnosis of sectorial keratitis and uveitis is limited. The entities included in the differential are diverse; some of them threaten not only vision but also life. It is important for the ophthalmologist to be familiar with these entities, in order to pursue pertinent diagnostic investigations and arrive at an accurate diagnosis and institute appropriate management. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. NR 20 TC 2 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD JAN PY 2003 VL 241 IS 1 BP 2 EP 7 DI 10.1007/s00417-002-0569-5 PG 6 WC Ophthalmology SC Ophthalmology GA 647ZE UT WOS:000181123300001 PM 12545285 ER PT J AU Suh-Burgmann, E Sivret, J Duska, LR Del Carmen, M Seiden, MV AF Suh-Burgmann, E Sivret, J Duska, LR Del Carmen, M Seiden, MV TI Long-term administration of intravaginal dehydroepiandrosterone on regression of low-grade cervical dysplasia - A pilot study SO GYNECOLOGIC AND OBSTETRIC INVESTIGATION LA English DT Article DE chemoprevention; dehydroepiandrosterone; neoplasia; preinvasive cervical disease; cervix; dysplasia ID ORAL DEHYDROEPIANDROSTERONE; INTRAEPITHELIAL NEOPLASIA; POSTMENOPAUSAL WOMEN; NATURAL-HISTORY; UTERINE CERVIX; T-CELLS; INHIBITION; MICE; EXPRESSION; MANAGEMENT AB Although many dysplastic cervical lesions regress spontaneously, treatment is common due to concern for progression. Lesions persist or progress in women whose immune systems are unable to clear infection by human papillomavirus (HPV). Dehydroepiandrosterone (DHEA) is an adrenal steroid that has both immune modulatory and tumor inhibitory activity. A pilot study was conducted to examine the feasibility, safety and potential efficacy of intravaginal DHEA in women with low-grade cervical dysplasia. Twelve women with low-grade dysplasia, confirmed by colposcopic exam, were given 150 mg of intravaginal micronized DHEA daily for up to 6 months. Follow-up evaluations of the cervix were done at 3 and 6 months of use. DHEA, DHEA-S, androstenedione and testosterone levels were also measured. By the end of the study period, 10 of the 12 women (83%) had no evidence of dysplasia; the remaining 2 had normal colposcopic exams but cytology showing atypical cells of undetermined significance. There were no serious side effects. Androstenedione levels were elevated at 3 months, whereas testosterone levels were unchanged over the course of treatment. The results suggest that intravaginal DHEA is safe and well tolerated and may promote regression of low-grade cervical lesions. Further study is needed to establish efficacy. Copyright (C) 2003 S. Karger AG, Basel. C1 Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Suh-Burgmann, E (reprint author), Kaiser Permanente Med Ctr, Div Gynecol Oncol, 2238 Geary,5th Floor, San Francisco, CA 94115 USA. EM Betty.Suh-Burgmann@kp.org NR 35 TC 11 Z9 11 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-7346 J9 GYNECOL OBSTET INVES JI Gynecol.Obstet.Invest. PY 2003 VL 55 IS 1 BP 25 EP 31 DI 10.1159/000068953 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 656NP UT WOS:000181614100005 PM 12624548 ER PT J AU Garner, EIO Meyerovitz, M Goldstein, DP Berkowitz, RS AF Garner, EIO Meyerovitz, M Goldstein, DP Berkowitz, RS TI Successful term pregnancy after selective arterial embolization of symptomatic arteriovenous malformation in the setting of gestational trophoblastic tumor SO GYNECOLOGIC ONCOLOGY LA English DT Article DE gestational trophoblastic disease; transcatheter arterial embolization AB Background. Patients with arteriovenous malformations (AVMs) are at risk for significant vaginal hemorrhage, and are traditionally managed surgically. In the patient desiring future fertility, conservative management via selective arterial embolization is a reasonable option. Only a few cases have been previously reported of successful pregnancy after this procedure in the setting of gestational trophoblastic disease (GTD). Case. A 31-year-old gravida 1 para 0 was treated for persistent gestational trophoblastic tumor after a complete mole in 1997. She presented with heavy vaginal bleeding, and arteriogram demonstrated a large uterine AVM. The patient underwent selective uterine artery embolization with complete resolution of bleeding, as well as arteriographic cessation of flow through the AVM. After two first-trimester spontaneous abortions, the patient successfully completed a normal pregnancy, resulting in the force ps-assisted delivery of a healthy female infant. Conclusion. Successful term pregnancy can occur after selective uterine artery embolization in women hemorrhaging from symptomatic GTD-associated AVM. (C) 2002 Elsevier Science (USA). C1 Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol,New England Trophoblast Dis Ctr, Donald P Goldsmith MD Trophoblast Dis Registry, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol,New England Trophoblast Dis Ctr, Donald P Goldsmith MD Trophoblast Dis Registry, 75 Francis St, Boston, MA 02115 USA. NR 12 TC 23 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2003 VL 88 IS 1 BP 69 EP 72 DI 10.1006/gyno.2002.6861 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 629QQ UT WOS:000180060700014 PM 12504631 ER PT J AU Karlan, BY Boyd, J Strong, L Fountain, J Beller, U AF Karlan, BY Boyd, J Strong, L Fountain, J Beller, U TI Discussion: Hereditary ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 8th International Forum on Ovarian Cancer CY 1999 CL STOCKHOLM, SWEDEN C1 Univ Calif Los Angeles, Cedars Sinai Med Ctr, Los Angeles, CA 90024 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Ctr, Boston, MA USA. NCI, Bethesda, MD 20892 USA. Shaare Zedek Med Ctr, Jerusalem, Israel. RP Karlan, BY (reprint author), Univ Calif Los Angeles, Cedars Sinai Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2003 VL 88 IS 1 BP S11 EP S13 DI 10.1006/gyno.2002.6675 PN 2 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 641ZM UT WOS:000180777000004 ER PT J AU Kaye, S Gershensen, D Hung, MC Seiden, M AF Kaye, S Gershensen, D Hung, MC Seiden, M TI Discussion: Molecular therapeutics and pharmacogenomics SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 8th International Forum on Ovarian Cancer CY 1999 CL STOCKHOLM, SWEDEN ID OVARIAN-CANCER CELLS; HUMAN BREAST; RECEPTOR; REPAIR C1 Royal Marsden Hosp, London SW3 6JJ, England. MD Anderson Canc Ctr, Houston, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kaye, S (reprint author), Royal Marsden Hosp, London SW3 6JJ, England. NR 13 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2003 VL 88 IS 1 BP S93 EP S96 DI 10.1006/gyno.2002.6693 PN 2 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 641ZM UT WOS:000180777000022 ER PT J AU Huffman, JC Perlis, RH AF Huffman, JC Perlis, RH TI The development of new antidepressants: Focus on duloxetine and escitalopram SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID MAJOR DEPRESSIVE DISORDER; IN-VITRO; REUPTAKE INHIBITORS; SEROTONIN; CITALOPRAM; TRIAL; SSRIS; VENLAFAXINE; ENANTIOMERS; FLUOXETINE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, 15 Parkman St,Wang 812, Boston, MA 02114 USA. NR 31 TC 2 Z9 2 U1 1 U2 2 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JAN-FEB PY 2003 VL 11 IS 1 BP 30 EP 36 PG 7 WC Psychiatry SC Psychiatry GA 655WM UT WOS:000181575700004 PM 12866739 ER PT J AU Lowe, HC Mino, M Mark, EJ Mac Neill, BD Palacios, IF Houser, SL AF Lowe, HC Mino, M Mark, EJ Mac Neill, BD Palacios, IF Houser, SL TI Histopathology of coronary in-stent restenosis following gamma brachytherapy SO HEART LA English DT Article ID TISSUE AB The histopathology of in-stent restenosis (ISR) following y brachytherapy is described. Such histology has not been reported previously. An 82 year old man presented with recurrent ISR three months after brachytherapy to an area of ISR within a native circumflex vessel. The recurrent ISR was treated with directional coronary atherectomy; the histopathology of this directional coronary atherectomy specimen is discussed. These histopathological examinations showed abundant extracellular matrix material. Surprisingly, there was a relatively small cellular (myofibroblastic) component, with an absence of endothelial cells and little evidence of active proliferation. ISR after 7 brachytherapy may be a pathologically distinct entity. C1 Massachusetts Gen Hosp, Div Cardiol, Cardiac Catheterizat Labs, Boston, MA 02144 USA. Harvard Univ, Sch Med, Boston, MA 02144 USA. RP Palacios, IF (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiac Catheterizat Labs, 55 Fruit St,Bullfinch 105, Boston, MA 02144 USA. NR 9 TC 3 Z9 4 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD JAN PY 2003 VL 89 IS 1 BP 11 EP 13 DI 10.1136/heart.89.1.11 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 630EP UT WOS:000180094800007 PM 12482781 ER PT J AU Agnihotri, AK Recanati, MA White, JK Titus, J Fischer, JI Schon, J Torchiana, DF AF Agnihotri, AK Recanati, MA White, JK Titus, J Fischer, JI Schon, J Torchiana, DF TI Continuous addition of adenosine with a micropump system improves warm whole blood cardioplegia SO HEART SURGERY FORUM LA English DT Article; Proceedings Paper CT 7th Annual Outcomes Meeting CY MAY 21-25, 2003 CL KEY WEST, FLORIDA ID POTASSIUM CARDIOPLEGIA; MYOCARDIAL PROTECTION; CARDIAC-ARREST; HEART; MECHANISM; RECEPTOR; FLOW; REPERFUSION; METABOLISM AB Background: Micropump additive systems allow for continuous modification of cardioplegia composition during heart surgery. Although the use of such systems in warm heart surgery is theoretically desirable, the role of the systems has been clinically limited by coronary vasoreactivity with higher potassium concentration and unreliable mechanical arrest at lower potassium concentration. Adenosine, a potent coronary vasodilator and arresting agent, has the potential to reduce the potassium concentration required for arrest and to improve distribution of cardioplegia. However, clinical use of adenosine has been limited by a short half-life in blood and difficulty in titrating the dose. This study tested the hypothesis that continuous addition of adenosine with an in-line linear micropump system would facilitate whole blood hyperkalemic perfusion for cardiac surgery. Methods: Canine hearts (n=9) were randomized to 20 minutes of arrest with whole blood cardioplegia or cardioplegia with adenosine at either low (0.5 muM) or high (8 muM) concentration. Potassium was supplemented at an arresting dose (24 mEq/L) for 5 minutes and then at a maintenance dose (6 mEq/L) for an additional 15 minutes. Coronary flow was held constant (4 mL/kg per minute), and aortic root pressure was measured. Myocardial performance was assessed by measurement of the end-diastolic pressure to stroke volume relationship at constant afterload. Myocardial tissue perfusion was evaluated with colored microspheres. Results: During the initial period of high-concentration potassium arrest, coronary resistance rose progressively regardless of adenosine addition. Coronary resistance remained elevated during the period of low potassium perfusion, except when high-concentration adenosine was added. With addition of 8 M adenosine, coronary resistance returned to baseline, and left ventricular endocardial perfusion was augmented. Electromechanical quiescence improved with adenosine perfusion and was complete with high-dose adenosine addition. Function was preserved in all hearts. Conclusion: Use of a modern micropump system allowed for continuous addition of adenosine and potassium to whole blood cardioplegia. Adenosine minimized potassium-induced coronary vasoconstriction and improved endocardial perfusion and mechanical quiescence. These findings supported addition of adenosine to the perfusate during warm whole blood cardioplegia. C1 Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, Boston, MA 02114 USA. RP Agnihotri, AK (reprint author), Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, Edwards Res Bldg 109,55 Fruit St, Boston, MA 02114 USA. NR 38 TC 0 Z9 0 U1 0 U2 0 PU FORUM MULTIMEDIA PUBLISHING, LLC PI CHARLOTTESVILLE PA 375 GREENBRIER DR, CHARLOTTESVILLE, VA 22901 USA SN 1098-3511 J9 HEART SURG FORUM JI Heart Surg. Forum PY 2003 VL 6 IS 4 BP 264 EP 272 PG 9 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 712ZW UT WOS:000184830300021 PM 12928212 ER PT J AU Kathiresan, S MacGillivray, TE Lewandrowski, K Servoss, SJ Lewandrowski, E Januzzi, JL AF Kathiresan, S MacGillivray, TE Lewandrowski, K Servoss, SJ Lewandrowski, E Januzzi, JL TI Off-pump coronary bypass grafting is associated with less myocardial injury than coronary bypass surgery with cardiopulmonary bypass SO HEART SURGERY FORUM LA English DT Article ID CARDIAC TROPONIN-T; ON-PUMP; REVASCULARIZATION; OPERATION; RELEASE; HEART AB Background: Excessive myocardial necrosis following coronary artery bypass grafting is associated with adverse outcome. The present study was designed to assess the extent of myocardial injury after conventional coronary artery bypass grafting with cardiopulmonary bypass (ONCAB) compared with off-pump coronary artery bypass (OPCAB). Methods: Measurements of serum cardiac troponin T (TnT) were obtained in 137 consecutive, unselected patients who underwent coronary artery bypass grafting. Serial blood sampling was performed at 3 time intervals after surgery: immediately postoperatively, 6 to 12 hours postoperatively, and 18 to 24 hours postoperatively. Results: ONCAB patients totaled 122, and OPCAB patients numbered 15. Ten patients in the ONCAB group suffered perioperative complications, compared with no patients in the OPCAB group. At each time point examined, OPCAB patients exhibited significantly less release of TnT than ONCAB patients ( immediately postoperative TnT, 1.99+/-4.75 ng/mL versus 0.20+/-0.32 ng/mL, P =.004; 6- to 12- hour TnT, 2.28+/-3.66 ng/mL versus 0.37+/-0.32 ng/mL, P=.001; and 18- to 24-hour TnT 1.59+/-3.49 ng/mL versus 0.30+/-0.32 ng/mL, P=.01). When ONCAB patients with perioperative ischemic complications were excluded, the differences between the 2 groups remained. The OPCAB patients still demonstrated less TnT release, typically 5- to 6-fold less than for ONCAB patients. Conclusions: The nearly 6-fold reduction of postoperative TnT associated with OPCAB suggests that off-pump surgery may offer superior cardioprotection than coronary artery bypass grafting with conventional cardiopulmonary bypass. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Surg Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Chem Labs, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bulfinch 019,55 Fruit St, Boston, MA 02114 USA. EM JJanuzzi@Partners.org NR 16 TC 8 Z9 8 U1 0 U2 0 PU FORUM MULTIMEDIA PUBLISHING, LLC PI CHARLOTTESVILLE PA 375 GREENBRIER DR, CHARLOTTESVILLE, VA 22901 USA SN 1098-3511 J9 HEART SURG FORUM JI Heart Surg. Forum PY 2003 VL 6 IS 6 BP E174 EP E178 PG 5 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 855UA UT WOS:000223998900022 PM 14722006 ER PT J AU Recanati, MA White, JK Titus, J Agnihotri, AK Torchiana, DF AF Recanati, MA White, JK Titus, J Agnihotri, AK Torchiana, DF TI Endoscopic multivessel coronary artery bypass grafting using automated device for proximal anastomosis SO HEART SURGERY FORUM LA English DT Article ID CARDIAC-SURGERY; ROBOTIC SYSTEM; BEATING HEART AB Background: The use of computer-enhanced telemanipulation robots in cardiothoracic surgery can reduce the need for open surgical access and enable closed-chest, endoscopic procedures, but these procedures have been limited to anterior target vessels. The feasibility of fully endoscopic multivessel, coronary artery bypass grafting (CABG) was examined. Methods: Fully endoscopic, multivessel CABG solely through surgical ports was performed on 23 dogs weighing 75 to 85 pounds. A proximal anastomosis was made with the Symmetry bypass system aortic connector. The aorta was cross clamped, and cardioplegia solution was administered through the vein graft into the ascending aorta. Results: Eighteen of 23 procedures yielded successful proximal anastomoses and 1 to 3 distal anastomoses. Conclusion: Endoscopic anastomosis to the ascending aorta is feasible with the Symmetry bypass connector. Antegrade cardioplegia and aortic root venting can then be easily accomplished. This approach simplifies closed chest cardioplegic arrest for multivessel CABG. C1 Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, Boston, MA 02114 USA. RP Torchiana, DF (reprint author), Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, Bullfinch 209,55 Fruit St, Boston, MA 02114 USA. EM Dtorchiana@partners.org NR 16 TC 0 Z9 0 U1 0 U2 0 PU FORUM MULTIMEDIA PUBLISHING, LLC PI CHARLOTTESVILLE PA 375 GREENBRIER DR, CHARLOTTESVILLE, VA 22901 USA SN 1098-3511 J9 HEART SURG FORUM JI Heart Surg. Forum PY 2003 VL 6 IS 6 BP E80 EP E84 PG 5 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 855UA UT WOS:000223998900001 PM 14721988 ER PT B AU El-Zimaity, H AF El-Zimaity, H BE Hunt, RH Tytgat, GNJ TI Multifocal Atrophic Gastritis (MAG) does not exist: new finding based on sectioning the entire stomach SO HELICOBACTER PYLORI: BASIC MECHANISMS TO CLINICAL CURE 2002 LA English DT Proceedings Paper CT 5th Symposium on Helicobacter Pylori - Basic Mechanisms to Clinical Care CY NOV 10-13, 2002 CL Maui, HI SP AXCAN PHARMA ID HELICOBACTER-PYLORI INFECTION; DUODENAL-ULCER DISEASE; INTESTINAL METAPLASIA; PEPTIC-ULCER; CANCER; CARCINOMA; MUCOSA; OMEPRAZOLE; RISK; ACQUISITION C1 VA Med Ctr, Gastrointestinal Mucosa Pathol Lab, Houston, TX 77030 USA. RP El-Zimaity, H (reprint author), VA Med Ctr, Gastrointestinal Mucosa Pathol Lab, GI 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 51 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8790-2 PY 2003 BP 133 EP 142 PG 10 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA BAN62 UT WOS:000222982900013 ER PT S AU Daley, GQ AF Daley, GQ BE Orlic, D Brummendorf, TH Fibbe, W Sharkis, S Kanz, L TI From embryos to embryoid bodies - Generating blood from embryonic stem cells SO HEMATOPOIETIC STEM CELLS 2002: GENETICS AND FUNCTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Symposium on Hematopoietic Stem Cells CY SEP 19-21, 2002 CL UNIV TUBINGEN, TUBINGEN, GERMANY SP Amgen Europe, Kirin Japan HO UNIV TUBINGEN DE embryonic stem cells; embryoid bodies; in vitro differentiation; HoxB4; therapeutic cloning ID MURINE YOLK-SAC; CHRONIC MYELOGENOUS LEUKEMIA; COLONY-FORMING CELLS; IN-VITRO; HEMATOPOIETIC-CELLS; ES CELLS; DEFINITIVE HEMATOPOIESIS; COMMON PRECURSOR; DEVELOPING MOUSE; B-LYMPHOCYTES AB Differentiation of embryonic stem (ES) cells in vitro yields abundant hematopoietic progenitors, but achieving stable hematopoietic engraftment of irradiated mice has proven difficult, begging the question of whether ES cells give rise to hematopoietic stem cells in vitro, and limiting the application of ES cells as experimental and therapeutic models. We have employed a number of hematopoietic regulatory genes to probe the nature and developmental potential of ES-derived blood precursors. The chronic myeloid leukemia-associated BCR/ABL oncoprotein transforms a novel class of ES-derived embryonic hematopoietic stem cell that represents a common progenitor of primitive erythropoiesis and definitive lymphoid-myeloid blood development. Expression of the homeobox gene HoxB4 generated normal, nonleukemic hematopoietic progenitors that enabled long-term, multilineage hematopoietic engraftment in primary and secondary mouse recipients. We have used these repopulating hematopoietic stem cells to model therapeutic transplantation from ES cells. We treated an immunodeficient Rag2(-/-) mouse by therapeutic cloning, that is, isogenic ES cell generation by somatic cell nuclear transfer, gene correction, and cell replacement therapy. Comparable approaches with human ES cells are being developed to lay the foundation for cellular therapies in patients with a variety of bone marrow diseases. C1 Whitehead Inst, Cambridge, MA 02142 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA. FU NCI NIH HHS [CA86991, CA76418]; NHLBI NIH HHS [HL71265]; NIDDK NIH HHS [DK59279] NR 57 TC 46 Z9 49 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-466-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 996 BP 122 EP 131 PG 10 WC Cell Biology; Hematology; Multidisciplinary Sciences SC Cell Biology; Hematology; Science & Technology - Other Topics GA BW93G UT WOS:000183697800015 PM 12799290 ER PT S AU Ishikawa, F Drake, CJ Yang, S Fleming, PA Minamiguchi, H Visconti, RP Crosby, CV Argraves, WS Harada, M Key, LL Livingston, AG Wingard, JR Ogawa, M AF Ishikawa, F Drake, CJ Yang, S Fleming, PA Minamiguchi, H Visconti, RP Crosby, CV Argraves, WS Harada, M Key, LL Livingston, AG Wingard, JR Ogawa, M BE Orlic, D Brummendorf, TH Fibbe, W Sharkis, S Kanz, L TI Transplanted human cord blood cells give rise to hepatocytes in engrafted mice SO HEMATOPOIETIC STEM CELLS 2002: GENETICS AND FUNCTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Symposium on Hematopoietic Stem Cells CY SEP 19-21, 2002 CL UNIV TUBINGEN, TUBINGEN, GERMANY SP Amgen Europe, Kirin Japan HO UNIV TUBINGEN DE hepatocytes; cord blood; transdifferentiation; production; stem cells ID BONE-MARROW CELLS; STEM-CELL; C-KIT; LIVER; DIFFERENTIATE; ANTIBODY; FUSION; TUMORS AB Recent studies suggest-that rodent hepatocytes may be derived from hematopoietic stem cells. In the current study, the potential hematopoietic origin of hepatocytes was addressed using xenogeneic transplantation of human cord blood cells. CD34(+) or CD45(+) human cord blood cells were transplanted into "conditioned" newborn NOD/SCID/beta2-microglobulin(null) mice. At 4 to 5 months post-transplantation, livers of the recipient mice were cryosectioned and examined for evidence of human hepatocyte engraftment using RT-PCR to detect human albumin mRNA, immunohistochemistry to detect human hepatocytic proteins, and fluorescence in situ hybridization (FISH) to detect the presence of human centromeric DNA. Analysis of the bone marrow of transplanted mice revealed that 21.0-45.9% of the cells were human CD45(+) cells. FISH analysis of frozen sections of transplanted mouse liver revealed the presence of engrafted cells positive for human centromeric DNA. That engrafted human cells functioned as hepatocytes was indicated by the expression of human albumin mRNA, as judged by RT-PCR. FISH analysis with human and mouse centromeric DNA probes excluded spontaneous cell fusion as the cause for the generation of human hepatocytes. Human cord blood cells can give rise to hepatocytes in a xenogeneic transplantation model. This model will be useful to further characterize the cord blood progenitors of hepatocytes. C1 Dept Vet Affairs Med Ctr, Charleston, SC USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Kyushu Univ, Grad Sch Med, Dept Med & Biosystemat Sci, Fukuoka 812, Japan. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Cell Biol & Anat, Charleston, SC 29425 USA. Univ Florida, Dept Hematol Oncol, Gainesville, FL USA. RP Ogawa, M (reprint author), Ralph H Johnson Vet Affairs Med Ctr, 109 Bee St, Charleston, SC 29401 USA. RI 石川, 文彦/L-4488-2014 FU NCI NIH HHS [P01-CA78582]; NHLBI NIH HHS [R01-HL52813, R01-HL57375]; NIDDK NIH HHS [R01-DK54197] NR 20 TC 99 Z9 103 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-466-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 996 BP 174 EP 185 PG 12 WC Cell Biology; Hematology; Multidisciplinary Sciences SC Cell Biology; Hematology; Science & Technology - Other Topics GA BW93G UT WOS:000183697800020 PM 12799295 ER PT J AU Houser, CR Esclapez, M AF Houser, CR Esclapez, M TI Downregulation of the alpha 5 subunit of the GABA(A) receptor in the pilocarpine model of temporal lobe epilepsy SO HIPPOCAMPUS LA English DT Article DE GABA; hippocampus; plasticity; immunohistochemistry; in situ hybridization ID GAMMA-AMINOBUTYRIC-ACID; SPONTANEOUS RECURRENT SEIZURES; MESSENGER-RNA EXPRESSION; CEREBELLAR GRANULE CELLS; CA1 PYRAMIDAL CELLS; ADULT-RAT BRAIN; A RECEPTOR; DENTATE GYRUS; IMMUNOCYTOCHEMICAL DISTRIBUTION; PHARMACOLOGICAL PROPERTIES AB Specific subunits of gamma-aminobutyric acid (GABA)(A) receptors may be regulated differentially in animal models of temporal lobe epilepsy during the chronic stage. Although several subunits may be upregulated, other subunits may be downregulated in the hippocampal formation. The alpha5 subunit is of particular interest because of its relatively selective localization in the hippocampus and its potential role in tonic inhibition. In normal rats, immunolabeling of the alpha5 subunit was high in the dendritic layers of CA1 and CA2 and moderate in these regions of CA3. in chronic pilocarpine-treated rats displaying recurrent seizures, alpha5 subunit-labeling was substantially decreased in CA1 and nearly absent in CA2. Only slight decreases in immunolabeling were evident in CA3. In situ hybridization studies demonstrated that the alpha5 subunit mRNA was also strongly decreased in stratum pyramidale of CA1 and CA2. Thus, the alterations in localization of the alpha5 subunit peptide and its mRNA were highly correlated. The large decreases in labeling of the alpha5 subunit did not appear to be related to loss of pyramidal neurons in CA1 or CA2 since these neurons were generally preserved in pilocarpine-treated animals. No comparable decreases in labeling of the alpha2 subunit of the GABA(A) receptor were detected. These findings indicate that the alpha5 subunit of the GABA(A) receptor is capable of substantial and prolonged downregulation in remaining pyramidal neurons in a model of temporal lobe epilepsy. The results raise the possibility that presumptive extrasynaptic GABA(A) receptor subunits, such as the alpha5 subunit, may be regulated differently than synaptically located subunits, such as the alpha2 subunit, within the same brain regions in some pathological conditions. (C) 2003 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Inst Brain Res, Los Angeles, CA 90095 USA. Fac Sci Luminy, INSERM, INMED, U29, Marseille, France. VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. RP Houser, CR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, 73-235 CHS, Los Angeles, CA 90095 USA. RI Esclapez, Monique/O-6509-2016 OI Esclapez, Monique/0000-0002-8558-1363 FU BLRD VA [I01 BX000404]; NINDS NIH HHS [NS35985] NR 66 TC 74 Z9 78 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2003 VL 13 IS 5 BP 633 EP 645 DI 10.1002/hipo.10108 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 706FZ UT WOS:000184444100008 PM 12921352 ER PT J AU Granholm, AC Sanders, L Seo, H Lin, L Ford, K Isacson, O AF Granholm, AC Sanders, L Seo, H Lin, L Ford, K Isacson, O TI Estrogen alters amyloid precursor protein as well as dendritic and cholinergic markers in a mouse model of Down syndrome SO HIPPOCAMPUS LA English DT Article DE amyloid precursor protein; amyloid beta-peptide; acetylcholine; hippocampus; cortex; neurodegeneration; Alzheimer's disease; Down syndrome; dementia; microtubule-associated proteins ID NERVE GROWTH-FACTOR; RADIAL-ARM MAZE; ALZHEIMERS-DISEASE; TS65DN MICE; REPLACEMENT THERAPY; REFERENCE MEMORY; NUCLEUS BASALIS; MESSENGER-RNA; ANIMAL-MODEL; IN-VIVO AB Individuals with Down syndrome (DS) develop the pathological hallmarks of Alzheimer's disease at an early age, later followed by memory decline and dementia. Women with DS are twice as likely to undergo early menopause, and levels of estradiol correlate with onset of cognitive decline in these women. We have demonstrated that a mouse model of DS, mice with segmental trisomy of chromosome 16 (Ts65Dn), develop a significant deficit in both reference and working memory as young adults (6-10 months of age), coupled with phenotypic loss of cholinergic neurons in the basal forebrain and altered growth factor levels. In the present study we examined cholinergic and dendritic markers in the hippocampal formation and levels of the amyloid precursor protein (APP) in different brain regions of Ts65Dn mice treated with estradiol for 60 days. The density of the dendritic marker Map2 was significantly decreased in the hippocampal formation of middle-aged trisomic mice (9-15 months old), and the density of cholinergic neurites (acetylcholinesterase [AChE] histochemistry) was also decreased in specific layers of the hippocampus. Treatment with 17beta-estradiol alleviated the decreases in Map2 and AChE staining, but had no effect on full-length APP levels in the hippocampus. In contrast, a main effect of treatment on APP levels in the striatum was noted, with significant elevations observed in controls and trisomics. These findings demonstrate that estrogen can alleviate deficits in cholinergic and dendritic elements in the hippocampal formation and further strengthens the rationale to explore estrogen replacement therapy in women with DS. (C) 2003 Wiley-Liss, Inc. C1 Med Univ S Carolina, Dept Physiol & Neurosci, Ctr Aging, Charleston, SC 29425 USA. Univ Colorado, Dept Basic Sci, Denver, CO 80202 USA. Harvard Univ, Sch Med, McLean Hosp, Program Neurosci,Neuroregenerat Lab, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Finch Univ Hlth Sci Chicago Med Sch, Dept Pharmacol, N Chicago, IL 60064 USA. RP Granholm, AC (reprint author), Med Univ S Carolina, Dept Physiol & Neurosci, Ctr Aging, 171 Ashley Ave, Charleston, SC 29425 USA. EM granholm@musc.edu FU NIA NIH HHS [AG12122, R01 AG012122] NR 85 TC 34 Z9 35 U1 2 U2 10 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2003 VL 13 IS 8 BP 905 EP 914 DI 10.1002/hipo.10130 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 762KP UT WOS:000187971100004 PM 14750653 ER PT J AU Marttila, R Haataja, R Ramet, M Lofgren, J Hallman, M AF Marttila, R Haataja, R Ramet, M Lofgren, J Hallman, M TI Surfactant protein B polymorphism and respiratory distress syndrome in premature twins SO HUMAN GENETICS LA English DT Article ID SP-A GENE; ASSOCIATION; BIRTH; 2ND-BORN; OUTCOMES; INFANTS; LOCUS AB Recent evidence suggests that the susceptibility to respiratory distress syndrome (RDS) is partly explained by genetic variation in the surfactant proteins (SP) SP-A and SP-B. The present study was designed to evaluate the concordance difference method and candidate gene analysis, in parallel, for the investigation of genetic susceptibility to RDS. We studied 100 same-sex twin pairs with established RDS in at least one twin. The difference in RDS concordance rates between the monozygotic (MZ) and dizygotic (DZ) twin pairs as evidence of a genetic influence was evaluated, and the SP-A and SP-B genes were investigated for potential associations with the susceptibility to RDS. The concordance rates of RDS were 54 and 44% in the MZ and DZ pairs, respectively. The concordance difference of 10% was not significant [95% confidence interval (CI) -0.1 to +0.3, P = 0.32], suggesting a low hereditary impact. However, the SP-B Ile131Thr polymorphism was associated with RDS. The threonine allele was associated with an increased risk of RDS [odds ratio (OR) 2.2, 95% CI 1.4-3.5, P = 0.0014]. This was particularly apparent in first-born male infants (OR 6.2, 95% CI 2.4-16.3, P < 0.001). The degree of prematurity (< 32 weeks OR 2.0, 95% CI 1.1-3.7, P = 0.021) and birth order (second-born OR 3.1, 95% CI 1.3-7.4, P = 0.009) were the clinical variables affecting the risk of RDS. An association between the SP-B Ile131Thr polymorphism and RDS was found. The threonine allele was associated with the risk of RDS, particularly in the first-born twin infants. The concordance difference between MZ and DZ twin pairs underestimates the genetic impact on the risk of RDS. The traditional twin concordance study is insufficient to evaluate genetic predisposition to RDS or other diseases that are confounded by the birth order or multiple pregnancy in itself. C1 Oulu Univ, Dept Paediat, FIN-90014 Oulu, Finland. Oulu Univ, Bioctr, FIN-90014 Oulu, Finland. Cent Hosp So Ostrobothnia, Seinajoki, Finland. Harvard Univ, Sch Med, MassGen Hosp Children, Lab Dev Immunol, Boston, MA 02115 USA. RP Hallman, M (reprint author), Oulu Univ, Dept Paediat, POB 5000, FIN-90014 Oulu, Finland. NR 24 TC 29 Z9 37 U1 1 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JAN PY 2003 VL 112 IS 1 BP 18 EP 23 DI 10.1007/s00439-002-0835-y PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 638CM UT WOS:000180552400003 PM 12483294 ER PT J AU Stram, DO Haiman, CA Hirschhorn, JN Altshuler, D Kolonel, LN Henderson, BE Pike, MC AF Stram, DO Haiman, CA Hirschhorn, JN Altshuler, D Kolonel, LN Henderson, BE Pike, MC TI Choosing haplotype-tagging SNPS based on unphased genotype data using a preliminary sample of unrelated subjects with an example from the multiethnic cohort study SO HUMAN HEREDITY LA English DT Article DE haplotypes; case-control studies; linkage disequilibrium; candidate gene analysis; htSNP ID LINKAGE DISEQUILIBRIUM; LOGISTIC-REGRESSION; HUMAN GENOME; FREQUENCIES; ASSOCIATION; ALGORITHM; INFERENCE; TRAITS; BLOCKS AB We describe an approach for picking haplotype-tagging single nucleotide polymorphisms (htSNPs) that is presently being taken in two large nested case-control studies within a multiethnic cohort (MEC), which are engaged in a search for associations between risk of prostate and breast cancer and common genetic variations in candidate genes. Based on a preliminary sample of 70 control subjects chosen at random from each of the 5 ethnic groups in the MEC we estimate haplotype frequencies using a variant of the Excoffier-Slatkin E-M algorithm after genotyping a high density of SNPs selected every 3-5 kb in and surrounding a candidate gene. In order to evaluate the performance of a candidate set of htSNPS (which will be genotyped in the much larger case-control sample) we treat the haplotype frequencies estimate above as known, and carry out a formal calculation of the uncertainty of the number of copies of common haplotypes carried by an individual, summarizing this calculation as a coefficient of determination, R-h(2). A candidate date set of htSNPS of a given size is chosen so as to maximize the minimum value of R-h(2) over the common haploh types, h. Copyright (C) 2003 S. Karger AG, Basel. C1 Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90033 USA. MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Univ Hawaii, Canc Res Ctr, Honolulu, HI 96822 USA. RP Stram, DO (reprint author), Univ So Calif, Dept Prevent Med, Keck Sch Med, 1540 Alcazar St,Suite 220, Los Angeles, CA 90033 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NCI NIH HHS [CA63464]; NIGMS NIH HHS [GM58897] NR 20 TC 322 Z9 333 U1 0 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2003 VL 55 IS 1 BP 27 EP 36 DI 10.1159/000071807 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 712NT UT WOS:000184804300004 PM 12890923 ER PT J AU Stram, DO Pearce, CL Bretsky, P Freedman, M Hirschhorn, JN Altshuler, D Kolonel, LN Henderson, BE Thomas, DC AF Stram, DO Pearce, CL Bretsky, P Freedman, M Hirschhorn, JN Altshuler, D Kolonel, LN Henderson, BE Thomas, DC TI Modeling and E-M estimation of haplotype-specific relative risks from genotype data for a case-control study of unrelated individuals SO HUMAN HEREDITY LA English DT Article DE haplotypes; case-control studies; linkage disequilibrium; candidate gene analysis; htSNP ID MULTIETHNIC COHORT; DISEASE; TRAITS; ASSOCIATIONS; FREQUENCIES; LIKELIHOOD; ALGORITHM; LOCUS; TESTS; GENE AB The US National Cancer Institute has recently sponsored the formation of a Cohort Consortium (http://2002.cancer.gov/scpgenes.htm) to facilitate the pooling of data on very large numbers of people, concerning the effects of genes and environment on cancer incidence. One likely goal of these efforts will be generate a large population-based case-control series for which a number of candidate genes will be investigated using SNP haplotype as well as genotype analysis. The goal of this paper is to outline the issues involved in choosing a method of estimating haplotype-specific risk estimates for such data that is technically appropriate and yet attractive to epidemiologists who are already comfortable with odds ratios and logistic regression. Our interest is to develop and evaluate extensions of methods, based on haplotype imputation, that have been recently described (Schaid et al., Am J Hum Genet, 2002, and Zaykin et al., Hum Hered, 2002) as providing score tests of the null hypothesis of no effect of SNP haplotypes upon risk, which may be used for more complex tasks, such as providing confidence intervals, and tests of equivalence of haplotype-specific risks in two or more separate populations. In order to do so we (1) develop a cohort approach towards odds ratio analysis by expanding the E-M algorithm to provide maximum likelihood estimates of haplotype-specific odds ratios as well as genotype frequencies; (2) show how to correct the cohort approach, to give essentially unbiased estimates for population-based or nested case-control studies by incorporating the probability of selection as a case or control into the likelihood, based on a simplified model of case and control selection, and (3) finally, in an example data set (CYP17 and breast cancer, from the Multiethnic Cohort Study) we compare likelihood-based confidence interval estimates from the two methods with each other, and with the use of the single-imputation approach of Zaykin et al. applied under both null and alternative hypotheses. We conclude that so long as haplotypes are well predicted by SNP genotypes (we use the R-h(2) criteria of Stram et al. [1]) the differences h between the three methods are very small and in particular that the single imputation method may be expected to work extremely well. Copyright (C) 2003 S. Karger AG, Basel. C1 Univ So Calif, Dept Prevent Med, Los Angeles, CA 90033 USA. MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Genet, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Endocrinol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA USA. Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. RP Stram, DO (reprint author), Univ So Calif, Dept Prevent Med, 1540 Alcazar St,Suite 220, Los Angeles, CA 90033 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NCI NIH HHS [CA63464]; NIGMS NIH HHS [GM58897] NR 25 TC 203 Z9 207 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2003 VL 55 IS 4 BP 179 EP 190 DI 10.1159/000073202 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 739DA UT WOS:000186325900004 PM 14566096 ER PT J AU Azocar, J Clavijo, OP Yunis, EJ AF Azocar, J Clavijo, OP Yunis, EJ TI MHC class II genes in HCV viral clearance of hepatitis C infected Hispanic patients SO HUMAN IMMUNOLOGY LA English DT Article DE HCV; MHC; HLA; Hispanics; Puerto Rican ID VIRUS-INFECTION; PCR AMPLIFICATION; IMMUNE-RESPONSES; ALLELES; SUSCEPTIBILITY; ASSOCIATION; GENOTYPE; THERAPY AB The frequency of class 11 human leukocyte antigen (HLA) alleles in 112 infected patients of Hispanic ancestry with serology positive for hepatitis C virus (HCV) was investigated. Our studies failed to demonstrate significant association between class 11 HLA alleles and the outcome of HCV infection: chronic viremia versus spontaneous viral clearance. Our results suggest that the genes responsible for the outcome are unknown, so far, and those HLA associations reported in several ethnic groups may represent genetic markers in non-random association with the responsible genes involved in determining viral clearance or chronic viremia following HCV infection. (C) American Society for Histocompatibility and Immunogenetics, 2003. Published by Elsevier Science Inc. C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Northgate Med, Springfield, MA USA. RP Yunis, EJ (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL59838, HL29583] NR 24 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD JAN PY 2003 VL 64 IS 1 BP 99 EP 102 AR PII S0198-8859(02)00722-X DI 10.1016/S0198-8859(02)00722-X PG 4 WC Immunology SC Immunology GA 636EU UT WOS:000180442200011 PM 12507819 ER PT J AU Blacker, D Bertram, L Saunders, AJ Moscarillo, TJ Albert, MS Wiener, H Perry, RT Collins, JS Harrell, LE Go, RCP Mahoney, A Beaty, T Fallin, MD Avramopoulos, D Chase, GA Folstein, MF McInnis, MG Bassett, SS Doheny, KJ Pugh, EW Tanzi, RE AF Blacker, D Bertram, L Saunders, AJ Moscarillo, TJ Albert, MS Wiener, H Perry, RT Collins, JS Harrell, LE Go, RCP Mahoney, A Beaty, T Fallin, MD Avramopoulos, D Chase, GA Folstein, MF McInnis, MG Bassett, SS Doheny, KJ Pugh, EW Tanzi, RE CA NIMH Genetics Initiative Alzheime TI Results of a high-resolution genome screen of 437 Alzheimer's Disease families SO HUMAN MOLECULAR GENETICS LA English DT Article ID APOLIPOPROTEIN-E GENOTYPE; SUSCEPTIBILITY LOCUS; LINKAGE ANALYSIS; GENETIC-LINKAGE; COMPLEX TRAITS; TYPE-4 ALLELE; ONSET; ASSOCIATION; ALPHA-2-MACROGLOBULIN; HEALTH AB Alzheimer's disease (AD) is a devastating neurodegenerative disorder of late life with complex inheritance. Mutations in three known genes lead to the rare early-onset autosomal dominant form of AD, while a common polymorphism (epsilon4) in the gene encoding apolipoprotein E (APOE) is a risk factor for more typical late-onset (>60 years) AD. A recent study concluded that there are up to four additional genes with an equal or greater contribution to the disease. We performed a 9 cM genome screen of 437 families with AD, the full National Institute of Mental Health (NIMH) sample, which has been carefully ascertained, evaluated and followed by our group over the last decade. Performing standard parametric and non-parametric linkage analyses, we observed a 'highly significant' linkage peak by Lander and Kruglyak criteria on chromosome 19q13, which probably represents APOE. Twelve additional locations-on 1q23, 3p26, 4q32, 5p14, 6p21, 6q27, 9q22, 10q24, 11q25, 14q22, 15q26 and 21q22--met criteria for 'suggestive' linkage [i.e. two-point lod score (TLS) greater than or equal to1.9 and/or multipoint lod score (MLS) greater than or equal to2.2] in at least one of our analyses. Although some of these will surely prove to be false positives, these linkage signals should provide a valuable framework for future studies aimed at identifying additional susceptibility genes for late-onset AD. C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ Alabama, Birmingham, AL USA. Johns Hopkins Univ, Baltimore, MD USA. Ctr Inherited Dis Res, Baltimore, MD USA. RP Tanzi, RE (reprint author), Ctr Aging Genet & Neurodegenerat, Genet & Aging Res Unit, MGH E,114 16th St, Charlestown, MA 02129 USA. RI McInnis, Melvin/F-6963-2012; Avramopoulos, Dimitrios/J-4392-2012; Bertram, Lars/K-3889-2015 OI McInnis, Melvin/0000-0002-0375-6247; Bertram, Lars/0000-0002-0108-124X FU NHGRI NIH HHS [N01-HG-65403]; NIMH NIH HHS [U01 MH46290, U01 MH46281, U01 MH46373] NR 50 TC 265 Z9 277 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN PY 2003 VL 12 IS 1 BP 23 EP 32 DI 10.1093/hmg/ddg007 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 631HA UT WOS:000180161000003 PM 12490529 ER PT J AU Johnson, FK Durante, W Peyton, KJ Johnson, RA AF Johnson, FK Durante, W Peyton, KJ Johnson, RA TI Heme oxygenase inhibitor restores arteriolar nitric oxide function in Dahl rats SO HYPERTENSION LA English DT Article DE acetylcholine; nitric oxide; hypertension, sodium-dependent; rats, Dahl; endothelium ID SALT-SENSITIVE HYPERTENSION; CARBON-MONOXIDE; ANGIOTENSIN-II; L-ARGININE; VASODILATION; HEMOPROTEIN; EXPRESSION; SYNTHASE AB Vascular tissues express heme oxygenase (HO), which metabolizes heme to form carbon monoxide (CO). CO relaxes vascular smooth muscle but inhibits nitric oxide (NO) formation. Decreased NO synthesis may contribute to salt-induced hypertension in Dahl salt-sensitive (DS) rats. The current study examines the hypothesis that elevated levels of endogenous CO contribute to NO dysfunction in salt-induced hypertensive DS rats. Male DS rats were placed on high-salt (8% NaCl, HS) or low-salt (0.3% NaCl, LS) diets for 4 weeks. With respect to the LS group, the HS group's blood pressure and carboxyhemoglobin levels were elevated, and abdominal aortas showed 6-fold higher HO-1 protein levels. Experiments used isolated pressurized first-order gracilis muscle arterioles superfused with oxygenated modified Krebs buffer. An inhibitor of NO synthase, Nomega-nitro-L-arginine methyl ester (L-NAME), caused concentration-dependent vasoconstriction in both groups, with attenuated responses in HS arterioles. HS arterioles also showed attenuated vasodilatory responses to an endothelium-dependent vasodilator, acetylcholine. Acute pretreatment with an inhibitor of HO, chromium mesoporphyrin, enhanced vascular responses to L-NAME and acetylcholine in both groups but abolished the differences between HS and LS arterioles. These data show that HO-1 protein levels and CO production are increased in HS rats. Arteriolar responses to L-NAME and acetylcholine are impaired in HS rats compared with LS animals, and this difference can be abolished by an inhibitor of endogenous CO production. These results suggest that elevated levels of endogenous CO contribute to arteriolar NO dysfunction in DS rats with salt-induced hypertension. C1 Tulane Univ, Hlth Sci Ctr, Dept Physiol, New Orleans, LA 70112 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. Baylor Coll Med, Houston VA Med Ctr, Houston, TX 77030 USA. RP Johnson, FK (reprint author), Tulane Univ, Hlth Sci Ctr, Dept Physiol, 1430 Tulane Ave,SL39, New Orleans, LA 70112 USA. FU NCRR NIH HHS [P20 RR017659]; NHLBI NIH HHS [1R01HL64577, R01 HL59976] NR 38 TC 40 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 2003 VL 41 IS 1 BP 149 EP 155 DI 10.1161/01.HYP.0000046923.52222.58 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 634XD UT WOS:000180367000025 PM 12511545 ER PT J AU Bush, RK Stave, GM AF Bush, RK Stave, GM TI Laboratory animal allergy: An update SO ILAR JOURNAL LA English DT Article DE allergens; allergy; animal allergy; asthma; laboratory animal allergy; laboratory animals; occupational health ID GUINEA-PIG; OCCUPATIONAL ALLERGY; UNIVERSITY EMPLOYEES; LIPOCALIN PROTEINS; RABBIT ALLERGENS; MOUSE ALLERGENS; IMMUNE-RESPONSE; DOG ALLERGENS; RAT FUR; SENSITIZATION AB Allergic reactions are among the most common conditions affecting the health of workers involved in the care and use of research animals. Between 11 and 44% of the individuals working with laboratory animals report work-related allergic symptoms. Of those who become symptomatic, 4 to 22% may eventually develop occupational asthma that can persist even after exposure ceases. Allergic symptoms consist of rashes where animals are in contact with the skin, nasal congestion and sneezing, itchy eyes, and asthma (cough, wheezing, and chest tightness). The generation of immunoglobulin E (IgE) antibodies is a prerequisite for the production of allergic symptoms. The mechanism by which IgE antibodies develop is becoming clearer. The propensity to produce IgE is genetically determined, and pre-existing allergy may be a risk factor for the development of laboratory animal allergy (LAA). However, exposure to animal allergens is the major risk factor for the development of LAA. Techniques to measure the airborne concentration of laboratory animal allergens have been developed. Research on animal allergens themselves indicates that many of the mouse and rat urinary proteins belong to a family of proteins called lipocalins, which share sequence homology with antigens of the parasitic agent that causes schistosomiasis. The fact that parasite infections also trigger I-E antibody responses may account for the development of LAA in persons who have never had any previous allergy. The prevention of LAA should be a major goal of an effective health and safety program in the animal research facility, and it can be accomplished by education and training of employees, reduction of exposure (including the use of personal protective gear), and changes in facility design. Medical surveillance programs can also play a role in improving health of individuals working with laboratory research animals. Early recognition of symptoms and evidence of sensitization can lead to interventions to reduce exposure and thereby avoid the long-term health consequences of LAA. C1 William S Middleton Mem Vet Adm Med Ctr, Allergy Sect, Madison, WI USA. Univ Wisconsin, Madison, WI 53706 USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Duke Univ, Med Ctr, Div Environm & Occupat Med, Durham, NC 27706 USA. RP Bush, RK (reprint author), William S Middleton Mem Vet Adm Med Ctr, Allergy Sect, Madison, WI USA. NR 75 TC 41 Z9 44 U1 0 U2 1 PU INST LABORATORY ANIMAL RESEARCH, NATL RES COUNCIL PI WASHINGTON PA 500 FIFTH ST, N W, WASHINGTON, DC 20001 USA SN 1084-2020 J9 ILAR J JI ILAR J. PY 2003 VL 44 IS 1 BP 28 EP 51 PG 24 WC Veterinary Sciences SC Veterinary Sciences GA 752WL UT WOS:000187199100005 PM 12473829 ER PT S AU Ippolito, GC Pelkonen, J Nitschke, L Rajewsky, K Schroeder, HW AF Ippolito, GC Pelkonen, J Nitschke, L Rajewsky, K Schroeder, HW BE Chiorazzi, N Lahita, RG Capra, JD Ferrarini, M Zabriskie, JB TI Antibody repertoire in a mouse with a simplified D-H locus: The D-limited mouse SO IMMUNE MECHANISMS AND DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Immune Mechanisms and Disease CY APR 14-17, 2002 CL ST GEORGES, W IND ASSOC ST SP Henry Kunkel Soc, NY Acad Sci DE antibody; repertoire; CDR3 ID REGION; SPECIFICITIES; DIVERSITY; GENES C1 Univ Alabama, Div Dev & Clin Immunol, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Wurzburg, Inst Virol & Immunbiol, D-97078 Wurzburg, Germany. Univ Kuopio, Dept Clin Microbiol, FIN-70211 Kuopio, Finland. RP Schroeder, HW (reprint author), Univ Alabama, Div Dev & Clin Immunol, Dept Med, WTI 378,1530 3rd Ave S, Birmingham, AL 35294 USA. FU FIC NIH HHS [F06 TW002130, TW02130]; NIAID NIH HHS [R01 AI047322, AI 07051, AI42732, T32 AI007051]; NICHD NIH HHS [R01 HD036292, HD36292] NR 7 TC 6 Z9 6 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-434-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 987 BP 262 EP 265 PG 4 WC Cell Biology; Immunology; Multidisciplinary Sciences SC Cell Biology; Immunology; Science & Technology - Other Topics GA BW84D UT WOS:000183319000032 PM 12727649 ER PT J AU Jung, D Bassing, CH Fugmann, SD Cheng, HL Schatz, DG Alt, FW AF Jung, D Bassing, CH Fugmann, SD Cheng, HL Schatz, DG Alt, FW TI Extrachromosomal recombination substrates recapitulate beyond 12/23 restricted V(D)J recombination in nonlymphoid cells SO IMMUNITY LA English DT Article ID VARIABLE REGION GENES; SIGNAL SEQUENCE; SOMATIC RECOMBINATION; JOINING SIGNALS; CHAIN GENES; PROTEINS; REARRANGEMENT; SEGMENTS; RAG-2; DNA AB V(D)J recombination occurs efficiently only between gene segments flanked by recombination signals (RSs) containing 12 and 23 base pair spacers (the 12/23 rule). A further limitation "beyond the 12/23 rule" (B12/23) exists at the TCRbeta locus and ensures Dbeta usage. Herein, we show that extrachromosomal V(D)J recombination substrates recapitulate B12/23 restriction in nonlymphoid cells. We further demonstrate that the Vbeta coding flank, the 12-RS heptamer/nonamer, and the 23-RS spacer each can significantly influence B12/23 restriction. Finally, purified core RAG1 and RAG2 proteins (together with HMG2) also reproduce B12/23 restriction in a cell-free system. Our findings indicate that B12/23 restriction of V(D)J recombination is cemented at the level of interactions between the RAG proteins and TCRbeta RS sequences. C1 Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA USA. Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06510 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RI Schatz, David/A-6748-2013 OI Schatz, David/0000-0002-5669-1176 FU NIAID NIH HHS [AI 32524, AI 20047] NR 53 TC 50 Z9 50 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 2003 VL 18 IS 1 BP 65 EP 74 DI 10.1016/S1074-7613(02)00507-1 PG 10 WC Immunology SC Immunology GA 643KN UT WOS:000180860600007 PM 12530976 ER PT J AU Wu, C Bassing, CH Jung, D Woodman, BB Foy, D Alt, FW AF Wu, C Bassing, CH Jung, D Woodman, BB Foy, D Alt, FW TI Dramatically increased rearrangement and peripheral representation of V beta 14 driven by the 3 ' D beta 1 recombination signal sequence SO IMMUNITY LA English DT Article ID T-CELL-RECEPTOR; GENE SEGMENT USAGE; V(D)J RECOMBINATION; BETA LOCUS; INCREASED SUSCEPTIBILITY; MEDIATE RECOMBINATION; SOMATIC RECOMBINATION; ALLELIC EXCLUSION; B-LYMPHOCYTES; CHAIN GENES AB V(D)J recombination is targeted by short recombination signal (RS) sequences that are relatively conserved but exhibit natural sequence variations. To evaluate the potential of RS sequence variations to determine the primary and peripheral TCRbeta repertoire, we generated mice containing specific replacement of the endogenous Vbeta14 RS with the 3'Dbeta1 RS (Vbeta14/3'DbetadRS). These mice exhibited a dramatic increase in Vbeta14(+) thymocyte numbers at the expense of thymocytes expressing other Vbetas. In addition, the percentage of peripheral Vbeta14(+) cip T lymphocytes was similarly increased. Strikingly, this altered Vbeta repertoire resulted predominantly from a higher relative level of primary Vbeta14/3'DORS rearrangement to DbetaJbeta complexes, despite the ability of the 3'Dbeta1 RS to break B12/23 restriction and allow direct rearrangement of Vbeta14/3'DbetaRS to Jbeta segments. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Ctr Blood Res, Boston, MA 02115 USA. FU NIAID NIH HHS [AI 20047] NR 48 TC 37 Z9 38 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 2003 VL 18 IS 1 BP 75 EP 85 DI 10.1016/S1074-7613(02)00515-0 PG 11 WC Immunology SC Immunology GA 643KN UT WOS:000180860600008 PM 12530977 ER PT J AU Hock, H Hamblen, MJ Rooke, HM Traver, D Bronson, RT Cameron, S Orkin, SH AF Hock, H Hamblen, MJ Rooke, HM Traver, D Bronson, RT Cameron, S Orkin, SH TI Intrinsic requirement for zinc finger transcription factor Gfi-1 in neutrophil differentiation SO IMMUNITY LA English DT Article ID BINDING-PROTEIN-EPSILON; ALPHA C/EBP-ALPHA; CELL-DIFFERENTIATION; DEFICIENT MICE; BONE-MARROW; PU.1; EXPRESSION; IDENTIFICATION; LINEAGES; MOUSE AB We report essential roles of zinc finger transcription factor Gfi-1 in myeloid development. Gene-targeted Gfi-1(-/-) mice lack normal neutrophils and are highly susceptible to abscess formation by gram-positive bacteria. Arrested, morphologically atypical, Gr1(+)Mac1(+) myeloid cells expand with age in the bone marrow. RNAs encoding primary but not secondary or tertiary neutrophil (granulocyte) granule proteins are expressed. The atypical Gr1(+)Mac1(+) cell population shares characteristics of both the neutrophil and macrophage lineages and exhibits phagocytosis and respiratory burst activity. Reexpression of Gfi-1 in sorted Gfi-1(-/-) progenitors ex vivo rescues neutrophil differentiation in response to G-CSF. Thus, Gfi-1 not only promotes differentiation of neutrophils but also antagonizes traits of the alternate monocyte/macrophage program. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Tufts Univ, Sch Med & Vet Med, Dept Pathol, Boston, MA 02111 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. NR 38 TC 207 Z9 213 U1 1 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 2003 VL 18 IS 1 BP 109 EP 120 DI 10.1016/S1074-7613(02)00501-0 PG 12 WC Immunology SC Immunology GA 643KN UT WOS:000180860600011 PM 12530980 ER PT J AU Fleuridor, R Wilson, B Hou, R Landay, A Kessler, H Al-Harthi, L AF Fleuridor, R Wilson, B Hou, R Landay, A Kessler, H Al-Harthi, L TI CD1d-restricted natural killer T cells are potent targets for human immunodeficiency virus infection SO IMMUNOLOGY LA English DT Article ID NKT CELLS; ALPHA-GALACTOSYLCERAMIDE; ANTITUMOR-ACTIVITY; GENE-EXPRESSION; ACTIVATION; MICE; LYMPHOCYTES; IMMUNITY; CD4; RECOGNITION AB Invariant human natural killer T cells (NKT) express a restricted T-cell receptor (TCR) Valpha24Vbeta11 repertoire. These cells share both phenotypic and functional similarities between NK and T cells. Given the emerging role of NKT cells as critical cells in bridging the gap between innate and adaptive immunity, we examined their susceptibility to productive human immunodeficiency virus (HIV) infection by T-tropic, M-tropic, and primary isolates of HIV. We generated three human NKT cell clones (CA5, CA29, and CA31). Phenotypic characterization of these Valpha24(+) Vbeta11(+) clones indicated that they were predominately positive for CD4, CD161, HLA-DR, CD38, CD45RO, and CD95 expression. The NKT cell clones expressed significantly more surface CCR5 molecules/cell and lower CXCR4 molecules/cell than phytohaemagglutinin-stimulated peripheral blood mononuclear cells (PBMC). Consistent with the surface expression of CCR5 and CXCR4, the NKT clones were also selectively susceptible to HIV M-tropic, T-tropic, and primary isolate infection, as evaluated by both HIV p24 enzyme-linked immunosorbent assay and intracellular staining of HIV proteins. The amount of p24 production was dependent on the NKT clone studied and the HIV strain used. Clones CA29 and CA31 were also susceptible to HIV IIIB infection. The virions produced by these clones were able to productively infect PHA-stimulated PBMCs with the same kinetics as for primary infection of CD4(+) blast. Collectively, this data demonstrates that NKT cells can be a target for productive HIV infection but with a lag in the time to peak p24 production. C1 Rush Presbyterian St Lukes Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA. Rush Presbyterian St Lukes Med Ctr, Div Infect Dis, Chicago, IL 60612 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Al-Harthi, L (reprint author), Rush Presbyterian St Lukes Med Ctr, Dept Immunol Microbiol, W Congress Pkwy,Rm 1577 JSC, Chicago, IL 60612 USA. FU PHS HHS [R01 A YS051] NR 40 TC 35 Z9 39 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JAN PY 2003 VL 108 IS 1 BP 3 EP 9 DI 10.1046/j.1365-2567.2003.01560.x PG 7 WC Immunology SC Immunology GA 634RL UT WOS:000180354400002 PM 12519296 ER PT S AU Wucherpfennig, KW AF Wucherpfennig, KW BE Sanjeevi, CB Eisenbarth, GS TI MHC-Linked susceptibility to type 1 diabetes a structural perspective SO IMMUNOLOGY OF DIABETES II: PATHOGENESIS FROM MOUSE TO MAN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th International Congress of the Immunology-of-Diabetes-Society and American-Diabetes-Association Research Symposium CY OCT 03-06, 2002 CL COPPER MT, COLORADO SP Amer Diabetes Assoc, Immunol Diabetes Soc DE type 1 diabetes; susceptibility; MHC class II; humans; NOD mice; pathogenesis; SDS; DQ8; I-A(g7) ID CLASS-II MHC; A BETA-CHAIN; PEPTIDE BINDING; HUMAN THYMUS; NOD MOUSE; MICE; INSULIN; MOLECULES; MELLITUS; I-A(G7) AB The MHC represents the most important susceptibility locus for type 1 diabetes, and the MHC class II alleles that encode DQ8 and DQ2 in humans and I-A(g7) in NOD mice represent critical elements. Even though these genetic facts have been known for a number of years, the biochemical and structural features of these MHC class 11 molecules have only been elucidated recently. We expressed DQ8 and I-Ag7 as soluble proteins and observed significant structural and functional similarities between these human and murine MHC molecules. It had been postulated that I-Ag7 and DQ8 are poor peptide binders, based on the observation that the subunits dissociate in the presence of SDS, a denaturing detergent. We observed that both DQ8 and I-Ag7 form stable, long-lived complexes with a number of different peptides, indicating that they are not unstable in the absence of detergent. DQ8 and I-Ag7 were found to bind similar sets of peptides, which included peptides that had been identified as immunodominant T cell epitopes of insulin and GAD 65 in NOD mice. The insulin B (9-23) peptide formed long-lived complexes with DQ8 and was thus chosen for crystallization of the complex. No defect in the peptide binding groove was evident in the crystal structure and the insulin peptide was deeply anchored in the binding site. The structure demonstrated significant similarities between DQ8 and I-A(g7), indicating that similar antigen presentation events are relevant in the NOD mouse model and the human disease. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [P01AI45757, R01AI42316] NR 31 TC 14 Z9 14 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-460-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1005 BP 119 EP 127 DI 10.1196/annals.1288.013 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Immunology; Multidisciplinary Sciences SC Endocrinology & Metabolism; Genetics & Heredity; Immunology; Science & Technology - Other Topics GA BY06K UT WOS:000187496100012 PM 14679046 ER PT J AU Bates, DW Yu, T Black, E Sands, KE Schwartz, JS Hibberd, PL Graman, PS Lanken, PN Kahn, KL Snydman, DR Parsonnet, J Moore, R Platt, R AF Bates, DW Yu, T Black, E Sands, KE Schwartz, JS Hibberd, PL Graman, PS Lanken, PN Kahn, KL Snydman, DR Parsonnet, J Moore, R Platt, R TI Resource utilization among patients with sepsis syndrome SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID INFLAMMATORY RESPONSE SYNDROME; CRITICALLY ILL PATIENTS; INTENSIVE-CARE UNIT; SEPTIC SHOCK; ATTRIBUTABLE MORTALITY; EXCESS LENGTH; COSTS; STAY; EPIDEMIOLOGY; MORBIDITIES AB OBJECTIVE: To assess the resource utilization associated with sepsis syndrome in academic medical centers. DESIGN: Prospective cohort study. SETTING: Eight academic, tertiary-care centers. PATIENTS: Stratified random sample of 1,028 adult admissions with sepsis syndrome and all 248,761 other adult admissions between January 1993 and April 1994. The main outcome measures were length of stay (LOS) in total and after onset of sepsis syndrome (post-onset LOS) and total hospital charges. RESULTS:The mean LOS for patients with sepsis was 27.7 +/- 0.9 days (median, 20 days), with sepsis onset occurring after a mean of 8.1 +/- 0.4 days (median, 3 days). For all patients without sepsis, the LOS was 7.2 +/- 0.03 days (median, 4 days). In multiple linear regression models, the mean for patients with sepsis syndrome was 18.2 days, which was 11.0 days longer than the mean for all other patients (P < .0001), whereas the mean difference in total charges was $43,000 (both P < .0001). These differences were greater for patients with nosocomial as compared with community acquired sepsis, although the groups were similar after adjusting for pre-onset LOS. Eight independent correlates of increased post onset LOS and 12 correlates of total charges were identified. CONCLUSIONS: These data quantify the resource utilization associated with sepsis syndrome, and demonstrate that resource utilization is high in this group. Additional investigation is required to determine how much of the excess post-onset LOS and charges are attributable to sepsis syndrome rather than the underlying medical conditions. C1 Brigham & Womens Hosp, Dept Med, Div Gen Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA USA. Univ Penn, Leonard Davis Inst, Philadelphia, PA USA. Univ Penn, Dept Med, Div Gen Internal Med, Philadelphia, PA USA. Univ Penn, Dept Med, Pulm & Crit Care Div, Philadelphia, PA USA. Univ Rochester, Sch Med, Dept Med, Div Gen Internal Med, Rochester, NY USA. Univ Rochester, Sch Med, Dept Med, Infect Dis Unit, Rochester, NY USA. Calif State Univ Los Angeles, Div Infect Dis, Los Angeles, CA USA. Tufts Univ, Sch Med, Boston, MA USA. Tufts Univ New England Med Ctr, Dept Med & Pathol, Div Infect Dis, Boston, MA USA. Dartmouth Hitchcock Med Ctr, Infect Dis Sect, Lebanon, NH USA. Johns Hopkins Univ Hosp, Div Infect Dis, Baltimore, MD USA. RP Bates, DW (reprint author), Brigham & Womens Hosp, Dept Med, Div Gen Med, 75 Francis St, Boston, MA 02115 USA. RI Snydman, David/O-3889-2014 OI Snydman, David/0000-0003-0119-3978 NR 20 TC 14 Z9 16 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JAN PY 2003 VL 24 IS 1 BP 62 EP 70 DI 10.1086/502117 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 636HE UT WOS:000180447900012 PM 12558238 ER PT S AU Golland, P Fischl, B AF Golland, P Fischl, B BE Taylor, C Noble, JA TI Permutation tests for classification: Towards statistical significance in image-based studies SO INFORMATION PROCESSING IN MEDICAL IMAGING, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Article; Proceedings Paper CT 18th International Conference on Information Processing in Medical Imaging CY JUL 20-25, 2003 CL ST MARTINS COLL, AMBLESIDE, ENGLAND SP Philips Med Syst, Image Metr, iMorphics, Mirada Solut HO ST MARTINS COLL ID HUMAN CEREBRAL-CORTEX; COORDINATE SYSTEM; CORTICAL SURFACE; BRAIN AB Estimating statistical significance of detected differences between two groups of medical scans is a challenging problem due to the high dimensionality of the data and the relatively small number of training examples. In this paper, we demonstrate a non-parametric technique for estimation of statistical significance in the context of discriminative analysis (i.e., training a classifier function to label new examples into one of two groups). Our approach adopts permutation tests, first developed in classical statistics for hypothesis testing, to estimate how likely we are to obtain the observed classification performance, as measured by testing on a hold-out set or cross-validation, by chance. We demonstrate the method on examples of both structural and functional neuroimaging studies. C1 MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP MIT, Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM polina@ai.mit.edu; fischl@nmr.mgh.harvard.edu NR 19 TC 81 Z9 81 U1 0 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-40560-7 J9 LECT NOTES COMPUT SC PY 2003 VL 2732 BP 330 EP 341 PG 12 WC Computer Science, Information Systems; Computer Science, Theory & Methods; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BX52Q UT WOS:000185604900028 ER PT J AU Iparraguirre, A Weninger, W AF Iparraguirre, A Weninger, W TI Visualizing T cell migration in vivo SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Review DE adhesion molecules; chemokines; lymphocytes; microscopy; trafficking ID HIGH ENDOTHELIAL VENULES; SELECTIN GLYCOPROTEIN LIGAND-1; LYMPHOCYTE-ASSOCIATED ANTIGEN; THYMUS-EXPRESSED CHEMOKINE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; LEUKOCYTE ADHESION MOLECULE-1; MUCOSAL IMMUNE-SYSTEM; SPLENIC WHITE PULP; P-SELECTIN; DENDRITIC CELLS AB Ever since the realization that T lymphocytes are key players in the defense against pathogens and tumors, a major aim of immunologists has been to understand the relationship between the functional and migratory properties of antigen-specific T cells. The current paradigm proposes that T cells follow organ-specific trafficking pathways to exit from blood into the extravascular compartment. T cell homing is regulated at the level of adhesion molecules and chemokine receptors, whose expression is linked tightly to the differentiation state of the cell. Naive T lymphocytes follow relatively uniform recirculation routes through secondary lymphoid organs, the molecular cues of which are fairly well understood. As effector and memory T cells must be capable of reaching virtually any site in the body, their migratory behavior is considerably more heterogeneous. During the past few years, innovative approaches for tracking T cells in vivo have emerged. Here, we review recent technical developments in experimental methods for the visualization of T cells both at the population and single cell level in vivo, and discuss what these methods have taught us about T cell trafficking. Copyright (C) 2003 S. Karger AG, Basel. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Weninger, W (reprint author), Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA. OI Weninger, Wolfgang/0000-0003-3133-8699 NR 159 TC 16 Z9 16 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PY 2003 VL 132 IS 4 BP 277 EP 293 DI 10.1159/000074896 PG 17 WC Allergy; Immunology SC Allergy; Immunology GA 760CW UT WOS:000187794600001 PM 14707460 ER PT J AU Hammer, MB Faldowski, RA Ulmer, HG Frueh, BC Huber, MG Arana, GW AF Hammer, MB Faldowski, RA Ulmer, HG Frueh, BC Huber, MG Arana, GW TI Adjunctive risperidone treatment in post-traumatic stress disorder: a preliminary controlled trial of effects on comorbid psychotic symptoms SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE risperidone; post-traumatic stress disorder; psychosis ID AUDITORY HALLUCINATIONS; COMBAT VETERANS; DOUBLE-BLIND; PTSD; SCHIZOPHRENIA; OLANZAPINE; PLACEBO; MULTICENTER; SERTRALINE; SEVERITY AB Positive and negative symptoms of psychosis may be common in patients with chronic post-traumatic stress disorder (PTSD), but few studies have investigated the use of antipsychotic agents in these patients. This preliminary study examined the potential efficacy of risperidone in treating psychotic symptoms associated with chronic PTSD. In a 5-week, prospective, randomized, double-blind, placebo-controlled trial, adjunctive risperidone treatment was assessed in 40 combat veterans with chronic PTSD and comorbid psychotic features. Most patients were receiving antidepressants and some other psychotics with doses of concurrent medications held constant for at least 1 month prior to and during the study. Thirty-seven patients completed at least 1 week of treatment with risperidone or placebo. The Positive and Negative Syndrome Scale (PANSS) and the Clinician Administered PTSD Scale (CAPS) were used to assess symptoms. The PANSS was the primary outcome measure. At treatment endpoint, risperidone-treated patients showed a significantly greater decrease from baseline, albeit modest, in psychotic symptoms (PANSS total scores) than placebo-treated patients (P<0.05). CAPS ratings declined significantly in both groups but did not differ significantly between groups. However, CAPS re-experiencing subscale scores had greater improvement in the risperidone-treated patients at week 5 (P<0.05, completer analysis) with a trend towards greater improvement versus placebo a endpoint (P<0.1, LOCF). Risperidone was well tolerated with minimal extrapyramidal symptoms. These preliminary results support studying the potential efficacy of risperidone for treating global psychotic symptoms associated with chronic PTSD with a suggestion that core re-experiencing symptoms may also be responsive. Further research using randomized, controlled trial designs in larger patient groups are needed to define more adequately the role of risperidone and other atypical agents in PTSD. (C) 2003 Lippincott Williams Wilkins. C1 Ralph H Johnson VA Med Ctr 116, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Hammer, MB (reprint author), Ralph H Johnson VA Med Ctr 116, 109 Bee St, Charleston, SC 29401 USA. EM hamnermb@musc.edu NR 34 TC 12 Z9 13 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-1315 EI 1473-5857 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD JAN PY 2003 VL 18 IS 1 BP 1 EP 8 DI 10.1097/01.yic.0000050744.67514.6d PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 636ZZ UT WOS:000180488300001 ER PT J AU Haffajee, AD Arguello, EI Ximenez-Fyvie, LA Socransky, SS AF Haffajee, AD Arguello, EI Ximenez-Fyvie, LA Socransky, SS TI Controlling the plaque biofilm SO INTERNATIONAL DENTAL JOURNAL LA English DT Article; Proceedings Paper CT Can Tooth Brushing Damage Your Health Symposium CY JUN, 2003 CL Berlin, GERMANY DE periodontal diseases; supragingival plaque removal; supragingival plaque; subgingival plaque; periodontal therapy; periodontal pathogens; oral hygiene ID NON-SURGICAL TREATMENT; SUPRAGINGIVAL PLAQUE; PERIODONTAL-DISEASE; MICROBIOLOGICAL PARAMETERS; SUBGINGIVAL MICROBIOTA; PATHOGENS; EFFICACY; REMOVAL; POCKETS AB Aim: To examine the effect of supragingival plaque removal in conjunction with different periodontal therapies on subgingival plaque composition in different subject populations. Method: Four different studies are presented which examined the effect of repeated removal of supragingival plaque performed by professionals or by tooth brushing on subgingival plaque composition. The studies were performed in different populations including chronic periodontitis, periodontal maintenance and refractory subjects. For all studies, each subject was examined for clinical parameters at up to 168 sites and subgingival plaque samples were taken from the mesial aspect of each tooth and examined for their content of specific bacterial species using checkerboard DNA-DNA hybridisation techniques. Results: Repeated supragingival plaque removal used in conjunction with scaling and root planing only or combined with other periodontal therapies resulted in improvements in clinical parameters as well as significant decreases in the counts of subgingival species, including those associated with periodontal disease aetiology. Meticulous tooth brushing provided similar clinical and microbial improvements. Conclusions: Meticulous removal of supragingival plaque has beneficial effects on clinical parameters of periodontal disease and on the nature of the microbiota. that colonises both above and below the gingival margin and appropriately has been a major focus in the prevention and control of dental diseases, particularly periodontal disease. C1 Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, Boston, MA USA. EM ahaffajee@forsyth.org FU NIDCR NIH HHS [DE-13232, DE-12108, DE-12861] NR 24 TC 28 Z9 31 U1 0 U2 7 PU F D I WORLD DENTAL PRESS LTD PI LOWESTOFT PA 5 BATTERY GREEN RD, LOWESTOFT NR32 1 DE, SUFFOLK, ENGLAND SN 0020-6539 J9 INT DENT J JI Int. Dent. J. PY 2003 VL 53 IS 3 SU S BP 191 EP 199 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 911GL UT WOS:000227990500004 PM 12875308 ER PT J AU Jones, JA Orner, MB Spiro, A Kressin, NR AF Jones, JA Orner, MB Spiro, A Kressin, NR TI Tooth loss and dentures: patients' perspectives SO INTERNATIONAL DENTAL JOURNAL LA English DT Article; Proceedings Paper CT Symposium on Patient-Centric Prosthodontics CY 2003 CL Sydney, AUSTRALIA DE outcomes; validity; dental; oral; dentures; quality of life; veterans ID QUALITY-OF-LIFE; ORAL-HEALTH; UNITED-STATES; VETERANS; CARE; ADULTS; IMPACT; NEED AB Objective: Despite dramatic improvements in tooth retention around the world, a substantial proportion of older adults have lost natural teeth and many wear removable partial and complete dentures. Problems associated with tooth loss and denture wearing remain important in the context of global ageing. The purpose of this paper is to examine the effects of tooth loss and denture wearing on their day-to-day lives from the patient perspective. Design: Cross-sectional study. Setting: Greater Boston area, USA. Participants: Community-dwelling older men. Methods: Brief examination and survey. Main outcome measures: Self-reported oral health measures including the single-item self-rating of oral health, the Oral Health Impact Profile (OHIP), the Geriatric Oral Health Assessment Index (GOHAI), Oral-Health-related Quality of Life (OHQOL) and a newly-developed short-form instrument (the DELTA). Results: Men with >= 25 teeth had better self-rated oral health by all measures. The new, brief DELTA differentiates between dentition/denture groupings as well as or better than existing instruments. Over 80% of men with ! 25 teeth rated their oral health as excellent, very good or good, compared with 70% of men with no teeth (and dentures) and 54% of men with 1-24 teeth. Avoidance of certain foods discriminates well between dentition groups. To a lesser extent, difficulty with relaxation, pain and distress, and avoidance of going out are associated with tooth loss and/or denture wearing. C1 Edith Nourse Rogers Mem Vet Adm Hosp, CHQOER, Bedford, MA 01730 USA. Boston Univ, Goldman Sch Dent Med, Dept Gen Dent, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA 02215 USA. Boston Univ, VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. RP Jones, JA (reprint author), Boston Univ, Sch Dent Med, Dept Gen Dent, Rm 612A,100 E Newton St, Boston, MA 02118 USA. EM judjones@bu.edu FU NIDCR NIH HHS [K24 DE00419] NR 35 TC 33 Z9 36 U1 2 U2 7 PU F D I WORLD DENTAL PRESS LTD PI LOWESTOFT PA 5 BATTERY GREEN RD, LOWESTOFT NR32 1 DE, SUFFOLK, ENGLAND SN 0020-6539 J9 INT DENT J JI Int. Dent. J. PY 2003 VL 53 IS 5 SU S BP 327 EP 334 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 911GM UT WOS:000227990600002 PM 14562938 ER PT J AU Mizoguchi, A Mizoguchi, E de Jong, YP Takedatsu, H Preffer, FI Terhorst, C Bhan, AK AF Mizoguchi, A Mizoguchi, E de Jong, YP Takedatsu, H Preffer, FI Terhorst, C Bhan, AK TI Role of the CD5 molecule on TCR gamma delta T cell-mediated immune functions: development of germinal centers and chronic intestinal inflammation SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CD4; immune deficiency; inflammatory bowel disease; regulatory; TCR beta knockout mice ID ALPHA MUTANT MICE; BOWEL-DISEASE; B-CELLS; INTRAEPITHELIAL LYMPHOCYTES; ANTIGEN RECEPTOR; AUTOANTIBODY PRODUCTION; SIGNAL-TRANSDUCTION; NEGATIVE REGULATION; SURFACE LIGAND; DEFICIENT MICE AB Although CD4(+) T cells form a major subset of TCRalphabeta T cells, only a small number of TCRgammadelta T cells express CD4. Factors contributing to the down-regulation of CD4(+) TCRgammadelta T cells have not been identified. The CD5 molecule is expressed on most TCRgammadelta T cells in the spleen, whereas only a few intestinal intraepithelial TCRgammadelta T cells express this molecule in wild-type mice and TCRbeta mutant (beta(-/-)) mice. Unexpectedly, in the present studies, the lack of CD5 led to a remarkable increase of a CD4(+) TCRgammadelta T cell subset in CD5(-/-)beta(-/-) mice. The CD4(+) TCRgammadelta T cells were also detectable in MHC II(-/-)CD5(-/-)beta(-/-) triple-mutant mice. This CD4(+) TCRgammadelta T cell subset provided help in Mycobacterium-induced germinal center (GC) formation and showed a T-h-like cytokine profile. In contrast, CD5(+) TCRgammadelta T cells suppressed the CD4(+) TCRgammadelta T cell-mediated GC formation, presumably by eliminating this CD4(+) subset. Unlike intraepithelial gammadelta T cells, >30% of TCRgammadelta T cells in the colonic lamina propria (LP) expressed CD5. The lack of CD5 also led to increased numbers of CD4(+) TCRgammadelta T cells in the colonic LP and increased susceptibility to development of chronic colitis in beta(-/-) mice. Cell transfer studies suggest that CD5(+) TCRgammadelta T cells are capable of selectively eliminating CD4(+) TCRgammadelta T cells in the intestine. The CD4(+) TCRgammadelta T cells possess immune functions similar to CD4(+) TCRalphabeta T cells. C1 Massachusetts Gen Hosp, Immunopathol Unit, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Immunol, Boston, MA 02115 USA. RP Mizoguchi, A (reprint author), Massachusetts Gen Hosp, Immunopathol Unit, Dept Pathol, Warren 501,55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK43351, DK47677] NR 62 TC 14 Z9 14 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JAN PY 2003 VL 15 IS 1 BP 97 EP 108 DI 10.1093/intimm/dxg006 PG 12 WC Immunology SC Immunology GA 640MU UT WOS:000180693200011 PM 12502730 ER PT J AU Niaura, RS Stroud, LR Todaro, J Ward, KD Spiro, A Aldwin, C Landsberg, L Weiss, ST AF Niaura, RS Stroud, LR Todaro, J Ward, KD Spiro, A Aldwin, C Landsberg, L Weiss, ST TI Associations between repression, general maladjustment, body weight, and body shape in older males: The normative aging study SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE body mass index; waist-hip ratio; repression; maladjustment; personality; body shape ID MIDDLE-AGED MEN; CORONARY HEART-DISEASE; ADIPOSE-TISSUE DISTRIBUTION; CARDIOVASCULAR RISK-FACTORS; REGIONAL FAT DISTRIBUTION; DEFENSIVE COPING STYLES; STRESS-INDUCED CORTISOL; PSYCHIATRIC ILL-HEALTH; METABOLIC SYNDROME-X; PSYCHOSOCIAL FACTORS AB We examined relationships between repression, general maladjustment, body mass index (BMI), and waist-to-hip ratio (WHR). The participants were 1,081 healthy older men from the Normative Aging Study. Repression and General Maladjustment Scales of the Minnesota Multiphasic Personality Inventory were composite measures of personality. Repression was associated with lower BMI and WHR, and maladjustment with higher BMI and WHR. However, associations between WHR and personality dimensions were no longer significant when controlling for BMI, but associations between BMI and personality dimensions remained significant when controlling for WHR. These effects were explained by differing relationships between WHR, repression, and maladjustment for normal weight, overweight, and obese individuals. Specifically, associations between repression, maladjustment, and body shape were significant for normal weight and overweight individuals, but not for obese individuals. Health behaviors including smoking did not mediate relationships between repression, maladjustment, and body shape, but might be considered in future studies as mechanisms underlying links between personality and body shape. C1 Brown Med Sch, Ctr Behav & Prevent Med, Providence, RI 02903 USA. Miriam Hosp, Ctr Behav & Prevent Med, Providence, RI USA. Univ Memphis, Ctr Community Hlth, Memphis, TN 38152 USA. Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Normat Aging Study, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Univ Calif Davis, Dept Human & Community Dev, Davis, CA 95616 USA. Northwestern Univ, Feinberg Sch Med, Dept Med, Evanston, IL 60208 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Niaura, RS (reprint author), Brown Med Sch, Ctr Behav & Prevent Med, Coro W Suite 500,1 Hoppin St, Providence, RI 02903 USA. FU NHLBI NIH HHS [HL37871, HL48363, HL32318]; NIA NIH HHS [AG02287] NR 77 TC 4 Z9 4 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PY 2003 VL 10 IS 3 BP 221 EP 238 DI 10.1207/S15327558IJBM1003_03 PG 18 WC Psychology, Clinical SC Psychology GA 717JN UT WOS:000185085500003 PM 14525718 ER PT J AU Adams, DS AF Adams, DS TI Teaching critical thinking in a developmental biology course at an American liberal arts college SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE critical thinking; developmental biology lectures; loss-of-function; gain-of-function AB We all expect our students to learn facts and concepts, but more importantly, we want them to learn how to evaluate new information from an educated and skeptical perspective; that is, we want them to become critical thinkers. For many of us who are scientists and teachers, critical thought is either intuitive or we learned it so long ago that it is not at all obvious how to pass on the skills to our students. Explicitly discussing the logic that underlies the experimental basis of developmental biology is an easy and very successful way to teach critical thinking skills. Here, I describe some simple changes to a lecture course that turn the practice of critical thinking into the centerpiece of the learning process. My starting point is the "Evidence and Antibodies" sidelight in Gilbert's Developmental Biology (2000), which I use as an introduction to the ideas of correlation, necessity and sufficiency, and to the kinds of experiments required to gather each type of evidence: observation ("show it"), loss of function ("block it") and gain of function ("move it"). Thereafter, every experiment can be understood quickly by the class and discussed intelligently with a common vocabulary. Both verbal and written reinforcement of these ideas dramatically improve the students' ability to evaluate new information. In particular, they are able to evaluate claims about cause and effect; they become experts at distinguishing between correlation and causation. Because the intellectual techniques are so powerful and the logic so satisfying, the students come to view the critical assessment of knowledge as a fun puzzle and the rigorous thinking behind formulating a question as an exciting challenge. C1 Smith Coll, Dept Biol Sci, Northampton, MA 01063 USA. RP Adams, DS (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. NR 3 TC 2 Z9 2 U1 0 U2 6 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2003 VL 47 IS 2-3 SI SI BP 145 EP 151 PG 7 WC Developmental Biology SC Developmental Biology GA 664QF UT WOS:000182071200010 PM 12705662 ER PT J AU Solomon, CS Leitner, JW Goalstone, ML AF Solomon, CS Leitner, JW Goalstone, ML TI Dominant negative alpha-subunit of farnesyl- and geranylgeranyl-transferase I inhibits insulin-induced differentiation of 3T3-L1 pre-adipocytes SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE 3T3-L1 adipocytes; DN FTase alpha-subunit; farnesyltransferase; geranylgeranyltransferase; obesity; type 2 diabetes ID ACTIVATED PROTEIN-KINASE; SMOOTH-MUSCLE CELLS; GENE-EXPRESSION; GROWTH-FACTOR; FARNESYLTRANSFERASE; HYPERINSULINEMIA; ADIPOGENESIS; RAS; PHOSPHORYLATION; PREADIPOCYTES AB OBJECTIVE: To investigate whether the expression of a dominant negative (DN) farnesyl- and geranygeranyl-transferase I (FTase /GGTase 1) alpha-subunit in 3T3-L1 pre-adipocytes can inhibit insulin's ability to induce differentiation, DESIGN: 3T3-L1 pre-adipocytes were stably transfected with vector alone or vector expressing a mutated DN FTase/GGTase I alpha-subunit (S60A)(S62A) and incubated in serum-free medium in the absence and presence of insulin. MEASUREMENTS: Various assays were performed to determine the effect of DN FTase/GGTase I alpha-subunit expression in 3T3-L1 pre-adipocyte on insulin-induced DNA synthesis, cell count, phosphorylation of the FTase/GGTase I alpha-subunit, FTase and GGTase I activity, amounts of prenylated p21 Ras and RhoA, phosphorylation of MAP kinase and Akt, and differentiation to mature fat cells. RESULTS: Expression of DN FTase/GGTase I alpha-subunit inhibited insulin's ability to increase DNA synthesis, cell count, FTase and GGTase I activity, amounts of prenylated p21 Ras and RhoA, and magnitude of phosphorylation of MAP kinase, Expression of DN FTase/GGTase I alpha-subunit in 3T3-L1 pre-adipocytes was without effect on insulin-induced Akt phosphorylation. CONCLUSION: Expression of DN FTase/GGTase I alpha-subunit inhibits insulin-induced differentiation of 3T3-L1 pre-adipocytes to mature adipocytes, and thus could indicate potential therapeutic avenues to assuage the deleterious effects of obesity and type 2 diabetes. C1 Denver VA Med Ctr, Res Serv, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. RP Goalstone, ML (reprint author), Denver VA Med Ctr, Res Serv, 111H,1055 Clermont St, Denver, CO 80220 USA. NR 36 TC 11 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD JAN PY 2003 VL 27 IS 1 BP 40 EP 47 DI 10.1038/sj.ijo.0802189 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 636XP UT WOS:000180482800006 PM 12532152 ER PT J AU Nambiar, PR Girnun, G Lillo, NA Guda, K Whiteley, HE Rosenberg, DW AF Nambiar, PR Girnun, G Lillo, NA Guda, K Whiteley, HE Rosenberg, DW TI Preliminary analysis of azoxymethane induced colon tumors in inbred mice commonly used as transgenic/knockout progenitors SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE mouse; colon; carcinogenesis; azoxymethane; beta-catenin; genetic susceptibility ID ABERRANT CRYPT FOCI; BETA-CATENIN GENE; MOUSE COLON; MURINE COLON; CARCINOGENESIS; NEOPLASMS; 1,2-DIMETHYLHYDRAZINE; IDENTIFICATION; TUMORIGENESIS; MECHANISMS AB Azoxymethane (AOM) is a colon carcinogen that is used to study the pathogenesis of sporadic colorectal cancer. We have evaluated differential susceptibility to AOM in inbred mice used as progenitors of recombinant/transgenic lines. In experiment 1, male FVB/N, 129/SvJ, C57Bl/6J mice were treated i.p. with 10 mg/kg AOM once per week for 4 weeks and sacrificed after 20 weeks. Only AOM-treated FVB/N mice developed tumors (3.6 tumors/mouse) in distal colon. In experiment 2, A/J, AKR/J, Balb/CJ mice were treated with AOM for 6 weeks and sacrificed after 24 weeks. AOM-treated A/J and Balb/CJ mice developed 9.2 and 1 tumor/mouse, respectively. Despite these differences, tumors had similar morphology regardless of strain. Immunohistochemistry with B-catenin resulted in marked nuclear and cytoplasmic staining of tumor cells in FVB/N. However, fainter and heterogeneous B-catenin staining was observed in A/J tumors, suggesting distinct pathways of tumorigenesis in different strains. Irrespective of cytological features of malignancy, tumor cells rarely breached the muscularis mucosa and showed no evidence of distant metastasis. Lack of invasiveness and metastasis in even the most sensitive strains provides a model system for studying the potential role of 'metastasis genes' in imparting a malignant phenotype. C1 Univ Connecticut, Ctr Hlth, Ctr Mol Med, Farmington, CT 06030 USA. Univ Connecticut, Dept Pathobiol, Storrs, CT 06269 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Rosenberg, DW (reprint author), Univ Connecticut, Ctr Hlth, Ctr Mol Med, 263 Farmington Ave, Farmington, CT 06030 USA. RI guda, kishore/E-3389-2010 FU NCI NIH HHS [CA81428-01]; PHS HHS [E10547] NR 36 TC 58 Z9 60 U1 0 U2 6 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JAN PY 2003 VL 22 IS 1 BP 145 EP 150 PG 6 WC Oncology SC Oncology GA 626KH UT WOS:000179871000019 PM 12469197 ER PT J AU Willett, CG Safran, H Abrams, RA Regine, WF Rich, TA AF Willett, CG Safran, H Abrams, RA Regine, WF Rich, TA CA Gastrointestinal Comm Radiation TI Clinical research in pancreatic cancer: The Radiation Therapy Oncology Group Trials SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE radiation therapy oncology group; pancreatic cancer; radiotherapy; adjuvant treatment ID ADJUVANT COMBINED RADIATION; FARNESYLTRANSFERASE INHIBITORS; PHASE-I; DUCTAL ADENOCARCINOMA; CONCURRENT RADIATION; CURATIVE RESECTION; RANDOMIZED TRIAL; RECTAL-CANCER; SURVIVAL; CHEMOTHERAPY AB Purpose: To summarize the clinical research activities of the Radiation Therapy Oncology Group program in the treatment of patients with locally advanced, as well as resected, pancreatic cancer. Methods and Materials: Phase 11 and III clinical trials are underway, examining novel cytotoxic and targeted agents with irradiation (RT) for patients with locally advanced and resected pancreatic cancer. Results: A Phase H study incorporating concurrent paclitaxel with external beam radiotherapy in the locally advanced setting has been completed and recently analyzed. This experience has served as the foundation of a Phase H study using concurrent paclitaxel and gemcitabine with RT followed by R115777, a farnesyltransferase inhibitor, as maintenance therapy. In the adjuvant treatment of pancreatic cancer, an Intergroup Phase III trial has compared ''conventional" postoperative chemoirradiation (5-fluorouracil before, after, and during RT) and gemcitabine before and after RT (with 5-fluorouracil during RT). This study has recently closed, meeting its accrual goal. The successor study will evaluate the use of gemcitabine given concurrently with RT, as well as in a maintenance schedule. Conclusion: This report summarizes current and future Radiation Therapy Oncology Group clinical trials in the treatment of patients with localized pancreatic cancer. (C) 2003 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Brown Univ, Dept Med Oncol, Providence, RI 02912 USA. Johns Hopkins Oncol Ctr, Dept Radiat Oncol, Baltimore, MD USA. Univ Kentucky, Dept Radiat Oncol, Lexington, KY USA. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. RP Willett, CG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. NR 52 TC 18 Z9 20 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2003 VL 56 IS 4 SU S BP 31 EP 37 DI 10.1016/S0360-3016(03)00446-2 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 699AC UT WOS:000184032900006 PM 12826249 ER PT J AU Cheng, GC Chen, MH Whittington, R Malkowicz, SB Schnall, MD Tomaszewski, JE D'Amico, AV AF Cheng, GC Chen, MH Whittington, R Malkowicz, SB Schnall, MD Tomaszewski, JE D'Amico, AV TI Clinical utility of endorectal MRI in determining PSA outcome for patients with biopsy Gleason score 7, PSA <= 10, and clinically localized prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostatic neoplasms; prostate-specific antigen; MRI ID RADIOTHERAPY AB Purpose: Although the optimal management for patients with high-grade clinically localized prostate cancer is undefined, radical prostatectomy (RP) or external beam radiotherapy (EBRT) is performed. The clinical utility of the pretreatment prostrate-specific antigen (PSA) level (less than or equal to10 and >10 ng/mL) and endorectal MRI (erMRI) stage (T3 vs. T2) to stratify PSA outcome after RP in these patients was evaluated. Methods and Materials: erMRI was performed in 147 men with biopsy Gleason score greater than or equal to7 and 1992 AJCC clinical Stage T1c or T2a disease before PP. Enumerations of the biopsy and prostatectomy Gleason scores, pathologic stage, and margin status were performed for each pretreatment group on the basis of erMRI findings and PSA level. Comparisons were made using a chi-square metric. The median follow-up was 4.5 years (range 1-10 years). Comparisons of the actuarial freedom from PSA failure (bNED) were made using the log-rank test. Results: erMRI Stage T2 and T3 disease was found in 132 and 15 patients, respectively. On stratification by PSA level, patients with erMRI T3 disease had similar bNED outcomes (p = 0.46), regardless of the PSA level. The 3-year bNED rate was 82%, 64%, and 25% (p <0.0001) for Group 1 (erMRI T2 and PSA less than or equal to10 ng/mL), Group 2 (erMRI T2 and PSA >10 ng/mL), and Group 3 (erMRI T3 with any PSA level), respectively. The rates of prostatectomy T3 disease, biopsy and prostatectomy Gleason score 8-10, and positive surgical margins were significantly higher (p less than or equal to0.007) in Group 3, followed by Group 2 and were lowest in Group 1. When considering only the patients with biopsy Gleason score 7 (n = 110), the 3-year bNED rate was 83 %, 63 %, and 28 % (p trend <0.0001) for Groups 1, 2, and 3, respectively. Conclusion: In the setting of biopsy Gleason score greater than or equal to7, PSA less than or equal to10 ng/mL, and clinically localized disease, local therapy alone may be adequate for patients with erMRI T2 disease. On the other hand, these data suggest that more aggressive therapy may be warranted in patients with erMRI T3 disease. Given the survival benefit established for patients with locally advanced prostate cancer treated with EBRT and androgen suppression therapy compared with EBRT alone, erMRI staging may help identify patients with high biopsy Gleason score and clinically localized disease who may benefit most from treatment with EBRT and hormonal therapy as opposed to EBRT alone. (C) 2003 Elsevier Science Inc. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Urol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. RP Cheng, GC (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. NR 12 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2003 VL 55 IS 1 BP 64 EP 70 AR PII S0360-3016(02)03820-8 DI 10.1016/S0360-3016(02)03820-8 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 647BD UT WOS:000181070600010 PM 12504037 ER PT J AU Breitner, J AF Breitner, J TI Nixon's law: for AD risk factors, "timing is everything" SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PUBLISHING CO PI NEW YORK PA 536 BROADWAY, NEW YORK, NY 10012 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PY 2003 VL 15 SU 2 BP 109 EP 109 PG 1 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 831QJ UT WOS:000222209400258 ER PT J AU Sano, M AF Sano, M TI Practical strategies for identifying minority elders: Focus on Alzheimer's disease trials SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Meeting Abstract C1 Bronx Vet Adm Med Ctr, Dept Psychiat, Mt Sinai Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PUBLISHING CO PI NEW YORK PA 536 BROADWAY, NEW YORK, NY 10012 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PY 2003 VL 15 SU 2 BP 154 EP 154 PG 1 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 831QJ UT WOS:000222209400376 ER PT J AU Rapp, MA Mohs, RC Sano, M Wysocki, M Kesar, R Ware, K Marin, D Haroutunian, V Grossman, HZ AF Rapp, MA Mohs, RC Sano, M Wysocki, M Kesar, R Ware, K Marin, D Haroutunian, V Grossman, HZ TI Predictors of longitudinal change in cognition in very old nursing home residents SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Meeting Abstract C1 Mt Sinai Sch Med, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PUBLISHING CO PI NEW YORK PA 536 BROADWAY, NEW YORK, NY 10012 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PY 2003 VL 15 SU 2 BP 281 EP 282 PG 2 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 831QJ UT WOS:000222209400652 ER PT J AU Rapp, MA Mohs, RC Sano, M Wysocki, M Ware, K Kesar, R Marin, D Grossman, HZ Haroutunian, V AF Rapp, MA Mohs, RC Sano, M Wysocki, M Ware, K Kesar, R Marin, D Grossman, HZ Haroutunian, V TI Orientation deficits precede rapid cognitive decline in nursing home residents with Alzheimer's disease SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Meeting Abstract C1 Mt Sinai Sch Med, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PUBLISHING CO PI NEW YORK PA 536 BROADWAY, NEW YORK, NY 10012 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PY 2003 VL 15 SU 2 BP 281 EP 281 PG 1 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 831QJ UT WOS:000222209400651 ER PT J AU Raskind, M Peskind, E Kershaw, P Mahableshwarkar, AR AF Raskind, M Peskind, E Kershaw, P Mahableshwarkar, AR TI Long-term cognitive response to galantamine in patients with mild-to-moderate Alzheimer's disease: A continuance analysis SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Janssen Pharmaceutica Prod LP, Titusville, NJ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PUBLISHING CO PI NEW YORK PA 536 BROADWAY, NEW YORK, NY 10012 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PY 2003 VL 15 SU 2 BP 282 EP 282 PG 1 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 831QJ UT WOS:000222209400653 ER PT J AU Mistry, R Gokhman, I Bastani, R Gould, R Jimenez, EE Lavretsky, H Maxwell, A McDermott, C Rosansky, J Van Stone, W Jarvik, L AF Mistry, R Gokhman, I Bastani, R Gould, R Jimenez, EE Lavretsky, H Maxwell, A McDermott, C Rosansky, J Van Stone, W Jarvik, L TI Measuring medical burden in older veterans enrolled in UPBEAT, a psychogeriatric treatment program: A pilot study SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RI Lavretsky, Helen/M-5711-2015 OI Lavretsky, Helen/0000-0001-9990-5085 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PUBLISHING CO PI NEW YORK PA 536 BROADWAY, NEW YORK, NY 10012 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PY 2003 VL 15 SU 2 BP 310 EP 310 PG 1 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 831QJ UT WOS:000222209400709 ER PT S AU Gensure, R Carter, PH Gardella, TJ AF Gensure, R Carter, PH Gardella, TJ BE Ijzerman, AP TI Inverse agonism and the PTH/PTHrP receptor SO INVERSE AGONISM SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 10th Symposium on Inverse Agonism CY OCT 02-05, 2002 CL S AGARO, SPAIN SP Estere Fdn DE parathyroid hormone; PTH/PTHrP receptor; inverse agonist; photoaffinity cross-linking ID PHOTOAFFINITY CROSS-LINKING; HORMONE; CONTACT AB The PTH/PTHrP receptor (PPR) is a family B G protein-coupled receptor that plays a vital role in calcium homeostasis and skeletal development. We are using photoaffinity cross-linking methods to explore how inverse agonists interact with constitutively active mutant PPRs. The analog [parabenzoyl-phenylalanine (Bpa)(2)]PTHrP(I - 36) is a selective inverse agonist for PPR-H223R (altered in transmembrane domain (TMD) 2), while [D-Bpa(12)]PTHrP(5-36) is an inverse agonist for both PPR-H223R and PPR-T410P (altered in TMD 6). In each ligand, the photolabile Bpa group is the key determinant of inverse agonism. The [Bpa(2)]PTHrP(I - 36) analog cross-linked to two sites in PPR-H223R: a primary site near the extracellular end of TMD 6 and a secondary site within TMD 4, extracellular loop 2 or TMD 5. Mutational studies revealed that the intensity of cross-linking to TMD 6, relative to TMD 4/5, increased as receptor signaling activity increased. Our preliminary mapping studies with [D-Bpa(12)]PTHrP(5-36) indicate that this analog cross-links to a different site, possibly near the boundary of TMD I and the N-terminal domain. Thus, there appear to be two different mechanisms by which inverse agonism can be achieved in constitutively active PPRs. The studies also reveal conformational differences between active and inactive state PPRs, at least in the vicinity of residue 2 of the ligand. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Gardella, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. NR 8 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 SN 0531-5131 BN 0-444-51032-X J9 INT CONGR SER PY 2003 VL 1249 BP 225 EP 233 DI 10.1016/S05313-5131(03)00602-2 PG 9 WC Cell Biology; Pharmacology & Pharmacy SC Cell Biology; Pharmacology & Pharmacy GA BX83U UT WOS:000186622400019 ER PT J AU Kato, T Chang, JH Azar, DT AF Kato, T Chang, JH Azar, DT TI Expression of type XVIII collagen during healing of corneal incisions and keratectomy wounds SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ANGIOGENESIS INHIBITOR ENDOSTATIN; ENDOGENOUS INHIBITOR; GELATINASE-A; TUMOR-GROWTH; DOMAIN; MOUSE; ALPHA-1(XVIII); LOCALIZATION; MEMBRANE; FORMS AB PURPOSE. To determine the distribution of type XVIII Collagen in mouse ocular tissues and to investigate the expression of type XVIII Collagen during healing of corneal incisions and keratectomy wounds. METHODS. Immunohistochemical analysis of type XVIII Collagen was performed in mouse ocular tissue, with polyclonal antibodies to the hinge domain. For wound-healing experiments, excimer laser keratectomy and single linear incisions were performed on mouse corneas. The corneas were harvested at various time points after wounding and processed for immunohistochemistry, in situ hybridization, competitive reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analysis. RESULTS. In the unwounded mouse cornea, type XVIII collagen was expressed by the corneal epithelial cells. Type XVIII collagen was immumolocalized to the mouse corneal epithelium, epithelial basement membrane, Descemet's membrane, ciliary epithelium, lens capsule, retinal inner limiting membrane, and Bruch's membrane. In the early stages of wound healing after excimer laser keratectomy (days 3 and 7), type XVIII collagen staining of the epithelial basement membrane was absent, whereas its localization to Descemet's membrane was unchanged. After linear corneal incisions, however, type XVIII Collagen was clearly seen in the stroma and in the epithelial basement membrane. Type XVIII collagen immunolocalization to the subepithelial stromal wound region peaked at I week after wounding, and its mRNA showed a corresponding temporal increase in expression within the same region after linear corneal incisions. CONCLUSIONS. The results suggest that type XVIII Collagen is broadly expressed in ocular tissues and that it may have a role in wound healing, especially after incisional corneal wounds. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. RP Azar, DT (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY 10101] NR 22 TC 28 Z9 32 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2003 VL 44 IS 1 BP 78 EP 85 DI 10.1167/iovs.01-1257 PG 8 WC Ophthalmology SC Ophthalmology GA 631EZ UT WOS:000180156300013 PM 12506058 ER PT J AU Argueso, P Tisdale, A Mandel, U Letko, E Foster, CS Gipson, IK AF Argueso, P Tisdale, A Mandel, U Letko, E Foster, CS Gipson, IK TI The cell-layer- and cell-type-specific distribution of GalNAc-transferases in the ocular surface epithelia is altered during keratinization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE; ALPHA-D-GALACTOSAMINE; O-LINKED GLYCOSYLATION; UDP-GALNAC; 3 MEMBERS; CDNA CLONING; MUCIN GENES; DRY-EYE; EXPRESSION; FAMILY AB PURPOSE. It has been hypothesized that the biosynthesis of O-linked glycans on proteins, particularly on the highly O-glycosylated mucins, by the corneal and conjunctival epithelium is necessary for the protection and maintenance of a healthy ocular surface. The initial step in O-glycosylation is the enzymatic addition of N-acetyl galactosamine (GalNAc) to serine and threonine residues by a large family of polypeptide GalNAc-transferases (GalNAc-Ts). The purpose of this study was to determine the cellular distribution of GalNAc-Ts in the normal ocular surface epithelia and to compare their distribution with that in pathologically keratinized conjunctival epithelia. METHODS. Five conjunctival biopsy specimens and 5 corneas from normal individuals, and 14 conjunctival specimens from patients with ocular cicatricial pemphigoid (OCP) were used. Based on the histologic characteristics of their epithelia, OCP specimens were divided into two groups: less advanced, non-keratinized (n = 6), and late-stage, keratinized (n = 8). Five monoclonal antibodies raised against the GalNAc-T1, -T2, -T3, -T4, and -T6 isoenzymes, were used for immunofluorescence microscopic localization according to standard protocols. RESULTS. Immunohistochemical studies revealed the presence of GalNAc-T2, -T3, and -T4 isoforms within the stratified epithelium of the cornea and the conjunctiva. The GalNAc-T4 isoenzyme was found in the apical cell layers, whereas GalNAc-T2 was found in the supranuclear region of the basal cell layers of both cornea and conjunctiva. GalNAc-T3 was distributed throughout the entire ocular surface epithelium, whereas GalNAc-T1 was found in scattered cells in conjunctiva only. Binding of antibody to GalNAc-T6 was restricted exclusively to conjunctival goblet cells. There were distinct alterations in expression patterns of GalNAc-T2, -T6, and -T1 in nonkeratinized OCP epithelia compared with normal epithelia. Both GalNAc-T2 and -T6 were expressed in the apical stratified epithelia, and T1 was detected in all cell layers in five of six biopsy specimens. By comparison with nonkeratinized OCP epithelia, a marked reduction in the binding of GalNAc-T antibody was observed in the late-stage keratinized conjunctival epithelia of patients with OCP. In all samples, apical GalNAc-T2 was absent, and GalNAc-T6 was entirely absent. Only one of eight samples was positive for GalNAc-T1. CONCLUSIONS. The presence of GalNAc-T isoenzymes in the human corneal and conjunctival epithelia is cell-layer and cell-type specific. The increased distribution of GalNAc-Ts observed in early stages of the keratinization process in patients with OCP suggests a compensatory attempt of the ocular surface epithelium to synthesize mucin-type O-glycans to maintain a wet-surface phenotype. This early increase in isoenzymes in nonkeratinized OCP epithelia is reduced as keratinization proceeds in the disease. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA. Univ Copenhagen, Sch Dent, Fac Hlth Sci, Dept Oral Diag, Copenhagen, Denmark. Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA 02114 USA. RP Gipson, IK (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA. FU NEI NIH HHS [R01 EY 03306] NR 31 TC 35 Z9 35 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2003 VL 44 IS 1 BP 86 EP 92 DI 10.1167/iovs.02-0181 PG 7 WC Ophthalmology SC Ophthalmology GA 631EZ UT WOS:000180156300014 PM 12506059 ER PT J AU Joussen, AM Poulaki, V Mitsiades, N Stechschulte, SU Kirchhof, B Dartt, DA Fong, GH Rudge, J Wiegand, SJ Yancopoulos, GD Adamis, AP AF Joussen, AM Poulaki, V Mitsiades, N Stechschulte, SU Kirchhof, B Dartt, DA Fong, GH Rudge, J Wiegand, SJ Yancopoulos, GD Adamis, AP TI VEGF-dependent conjunctivalization of the corneal surface SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; GOBLET CELLS; NEOVASCULARIZATION; EXPRESSION; FLT-1; TRANSDIFFERENTIATION; MIGRATION; RECEPTOR AB PURPOSE. To investigate the mechanisms governing corneal neovascularization and the appearance of goblet cells in a murine model of limbal insufficiency. METHODS. The spatial and time-dependent relationship between corneal neovascularization and goblet cell density was analyzed in corneal flatmounts. Immunohistochemical detection of the vascular endothelial growth factor (VEGF) receptor Flt-1 (VEGFR1) was performed in paraffin-embedded sections. A transgenic mouse that expresses the reporter gene lacZ targeted to the Flt-1 locus through homologous recombination was used to analyze corneal expression of Flt-1. The presence of soluble and membranous goblet cell Flt-1 mRNA and protein content was assessed with Northern and Western blot analyses, respectively. Finally, systemic adenoviral expression of a soluble Flt-1/Fc construct was used to study the effect of inhibition of VEGF bioactivity on the appearance of goblet cells and neovascularization. RESULTS. Corneal neovascularization preceded the appearance of goblet cells, although both processes overlapped temporally. Flt-1 was abundant in the conjunctiva-like epithelium covering the cornea, as well as in the goblet cells, invading leukocytes, and vasculature. A similar expression pattern was observed in the transgenic mice expressing the lacZ gene downstream from the Flt-1 promoter. Isolated human and rat goblet cells in culture expressed Flt-1 mRNA and protein, as did freshly isolated human conjunctiva. The systemic inhibition of VEGF bioactivity potently suppressed both corneal neovasculatization (8.3% +/- 8.1% vs. 41.1% +/- 15.3% corneal area; P < 0.001) and corneal goblet cell density (1.6% +/- 2.5% vs. 12.2% +/- 2.4% corneal area; P < 0.001). CONCLUSIONS. Two important features of corneal conjunctivalization, the appearance of goblet cells and neovascularization, are regulated by VEGF. Both processes are probably mediated, in part, through the Flt-1 receptor. Taken together, these data indicate that an anti-VEGF therapeutic approach may limit the visual loss associated with conjunctivalization of the corneal surface. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Adult Oncol, Boston, MA USA. Univ Cologne, Ctr Ophthalmol, Dept Vitreoretinal Surg, Cologne, Germany. Univ Cologne, Ctr Mol Med, Cologne, Germany. Univ Connecticut, Ctr Hlth, Ctr Vasc Biol, Farmington, CT USA. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. RP Adamis, AP (reprint author), Eyetech Res Ctr, 42 Cummings Pk, Woburn, MA 01801 USA. FU NEI NIH HHS [R01 EY 11627] NR 16 TC 52 Z9 56 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2003 VL 44 IS 1 BP 117 EP 123 DI 10.1137/iovs.01-1277 PG 7 WC Ophthalmology SC Ophthalmology GA 631EZ UT WOS:000180156300018 PM 12506063 ER PT J AU Kure, T Chang, JH Kato, T Hernandez-Quintela, E Ye, HQ Lu, PCS Matrisian, LM Gatinel, D Shapiro, S Gosheh, F Azar, DT AF Kure, T Chang, JH Kato, T Hernandez-Quintela, E Ye, HQ Lu, PCS Matrisian, LM Gatinel, D Shapiro, S Gosheh, F Azar, DT TI Corneal neovascularization after excimer keratectomy wounds in matrilysin-deficient mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MATRIX METALLOPROTEINASES; BASEMENT-MEMBRANE; ENDOTHELIAL-CELLS; GELATINASE-B; EPITHELIAL-CELLS; CLEAVAGE SITES; GROWTH-FACTOR; ANGIOGENESIS; EXPRESSION; IDENTIFICATION AB PURPOSE. Matrilysin, matrix metalloproteinase (MMP)-7, is upregulated in the corneal epithelium during wound heating after excimer keratectomy wounds. The purpose of this study was to determine the role of matrilysin in maintaining corneal avascularity during wound healing. METHODS. Matrilysin-deficient mice (n = 17) and their age-matched wild-type littermates (n = 18) were treated with 193 run argon-fluoride excimer keratectomy (experiment I). The percentage of corneal surface occupied by neovasculatization was measured with a computer image-analysis program adjusted for parallax. In another experiment (experiment II), epithelial closure was monitored with slit lamp biomicroscopy and fluorescein staining, and corneal neovascularization was confirmed by india ink perfusion, electron microscopy, and immunolocalization of CD31 and type IV Collagen. Corneal micropocket assays were performed to compare the area of corneal neovascularization in matrilysin-deficient mice and wild-type littermates (experiment III). To determine whether the differences in corneal neovascularization were related to differences in angiogenic factors, the levels of basic fibroblast growth factor (bFGF) were compared with those of vascular endothelial growth factor (VEGF) in matrilysin-deficient and wild-type mouse corneas (experiment IV). RESULTS. The percentages of the corneal surface occupied by neovascularization after excimer laser keratectomy in the matrilysin-deficient mice measured 21.3% +/- 5.2% and 18.7% +/- 5.8% at days 3 and 7, respectively, compared with 5.3% +/- 2.4% and 5.5% +/- 3.4% in the wild-type littermates at days 3 (P < 0.01) and 7, respectively (P < 0.05; experiment I). No significant differences in the rates of epithelial closure of corneal wounds were observed between matrilysin-deficient and wildtype mice after wounding. Corneal neovascularization in the matrilysin-deficient mice was confirmed by india ink present in the corneal stromal blood vessels (extending from the limbus to the wound), immunohistochemical staining, and electron microscopy. Gram, Giemsa, calcofluor white, and acridine orange stains and electron microscopy showed no evidence of corneal infection (experiment II). The area of corneal neovascularization in matrilysin-deficient mice was not significantly different from that of wild-type littermates after implantation of bFGF pellets (0.91 +/- 0.55 mm(2) and 0.77 +/- 0.34 mm(2), respectively; experiment III). The levels of bFGF and VEGF (VEGF, VEGF-B, and VEGF-C) in corneal epithelial cells were not elevated in matrilysin-deficient mice compared with the wild-type mice (experiment IV). CONCLUSIONS. Matrilysin may play an important role in maintaining corneal avascularity during wound healing. The differences in corneal neovascularization between matrilysin-deficient mice and wild-type littermates seem unrelated to the bFGF and VEGF levels in the corneal epithelium. C1 Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Vanderbilt Univ, Dept Cell Biol, Nashville, TN 37232 USA. Univ Paris, Rothschild Fdn, F-75252 Paris, France. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY 10101] NR 35 TC 33 Z9 34 U1 1 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2003 VL 44 IS 1 BP 137 EP 144 DI 10.1167/iovs.01-1058 PG 8 WC Ophthalmology SC Ophthalmology GA 631EZ UT WOS:000180156300021 PM 12506066 ER PT J AU Stempel, D Sandusky, H Lampi, K Cilluffo, M Horwitz, J Braun, J Goodglick, L Gordon, LK AF Stempel, D Sandusky, H Lampi, K Cilluffo, M Horwitz, J Braun, J Goodglick, L Gordon, LK TI Beta B1-crystallin: Identification of a candidate ciliary body uveitis antigen SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; ALPHA-B-CRYSTALLIN; ULCERATIVE-COLITIS; ANTERIOR UVEITIS; EPITHELIAL-CELLS; CROHNS-DISEASE; EXTRALENTICULAR EXPRESSION; DIFFERENTIAL EXPRESSION; PANCA ANTIBODIES AB PURPOSE. Perineuclear anti-neutrophil cytoplasmic antibody (pANCA), a marker antibody present in 12% of patients with anterior uveitis, recognizes cytoplasmic antigens in the nonpigmented ciliary body epithelium, a probable site of immunologic reactivity in this inflammatory disease. In this study, a recombinantly isolated pANCA monoclonal antibody was used to identify the corresponding antigenic target(s) in the ciliary body. METHODS. Proteins from microdissected eye bank ocular ciliary body tissue were used to identify the corresponding ANCA antigen. Parallel two-dimensional protein gels were used for simultaneous identification of candidate antigenic protein spots by Western blot analysis and as a source of material for proteomic analysis. Multiple independent methods including Western blot analysis, confocal microscopy, and RT-PCR were used to provide additional characterization of the candidate protein. RESULTS. Proteomic analysis suggested that beta B1 (betaB1)-crystallin is the primary ciliary body antigen. The presence of betaB1-crystallin in the human ciliary body was confirmed by Western blot with a betaB1 specific anti-peptide antibody. Confocal microscopy revealed colocalization of the antigenic reactivity of both anti-betaB1 antibody and monoclonal pANCA. RTPCR confirmed the presence of betaB1-crystallin RNA in the ciliary body tissues. CONCLUSIONS. This study identified betaB1-crystallin as a new cytoplasmic ciliary body antigenic target of a marker autoantibody associated with uveitis. This characterization of betaB1-crystallin outside the lens raises questions about its extralenticular expression, intracellular role, and potential target of inflammation in uveitis. C1 Univ Calif Los Angeles, Dept Ophthalmol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA. Oregon Hlth Sci Univ, Dept Oral Mol Biol, Portland, OR USA. W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA USA. RP Gordon, LK (reprint author), Jules Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA. FU NEI NIH HHS [R29 EY012239-05, EY 12239, EY 00360, EY 13708, R29 EY012239, R03 EY013708] NR 53 TC 15 Z9 16 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2003 VL 44 IS 1 BP 203 EP 209 DI 10.1167/iovs.01-1261 PG 7 WC Ophthalmology SC Ophthalmology GA 631EZ UT WOS:000180156300031 PM 12506076 ER PT J AU Carrasquillo, KG Ricker, JA Rigas, IK Miller, JW Gragoudas, ES Adamis, AP AF Carrasquillo, KG Ricker, JA Rigas, IK Miller, JW Gragoudas, ES Adamis, AP TI Controlled delivery of the anti-VEGF aptamer EYE001 with poly(lactic-co-glycolic) acid microspheres SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; DRUG-DELIVERY; POLY(LACTIDE-CO-GLYCOLIDE) MICROSPHERES; BIODEGRADABLE POLYMER; MACULAR DEGENERATION; PLASMID DNA; IN-VITRO; RELEASE; STABILITY AB PURPOSE. To develop a controlled-drug delivery system for the long-term inhibition of vascular endothelial growth factor (VEGF) and its mediated responses. METHODS. Poly(lactic-co-glycolic)acid (PLGA) microspheres containing anti-VEGF RNA aptamer (EYE001) formulations in the solid-state were developed by an oil-in-oil solvent evaporation process. In vitro experiments were performed to characterize the release profiles. Stability and bioactivity of the released drug were assayed by monitoring the RNA aptamer's ability to inhibit VEGF-induced cell proliferation in human umbilical vein endothelial cells (HUVECs). Cell proliferation experiments were conducted with aptamer aliquots collected after short-, mid-, and long-term release time points. To investigate the feasibility of this polymer device as a potential transscleral delivery device, an in vitro apparatus was developed to assess polymer hydration and degradation through rabbit sclera and subsequent delivery through it. RESULTS. PLGA microspheres were able to deliver EYE001 in a sustained manner, with an average rate of 2 mug/d over a period of 20 days. Solid-state stabilization of the aptamer with disaccharide trehalose before lyophilization and encapsulation in PLGA rendered the drug more stable after release. Cell proliferation experiments demonstrated that the bioactivity of the aptamer was preserved after release, as indicated by inhibition of endothelial cell proliferation after incubation with VEGF. Microspheres packed into a sealed chamber and placed onto the "orbital" part of a rabbit sclera for a period of 6 days became hydrated and started to degrade, as shown by scanning electron microscopy (SEM). As a result, the aptamer was delivered from the microspheres through the sclera, as determined spectrophotometrically. CONCLUSIONS. The loading of aptamer-containing microspheres into a device and placing it on the orbital surface of the sclera was assessed and shown to be feasible. RNA aptamer EYE001 encapsulated in PLGA was delivered over a period of 20 days with retained activity. This method represents a promising approach for the transscleral delivery of drugs and the treatment of choroidal and retinal diseases. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Angiogenesis & Retina Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Draper Labs, Elect Microscopy Lab, Cambridge, MA USA. RP Adamis, AP (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Angiogenesis & Retina Res Lab, 325 Cambridge St, Boston, MA 02114 USA. FU NEI NIH HHS [EY 11627, EY 12611] NR 56 TC 97 Z9 99 U1 2 U2 11 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2003 VL 44 IS 1 BP 290 EP 299 DI 10.1167/iovs.01-1156 PG 10 WC Ophthalmology SC Ophthalmology GA 631EZ UT WOS:000180156300042 PM 12506087 ER PT J AU Nurnberg, HG Hensley, PL Gelenberg, AJ Fava, M Lauriello, J Paine, S AF Nurnberg, HG Hensley, PL Gelenberg, AJ Fava, M Lauriello, J Paine, S TI Treatment of antidepressant-associated sexual dysfunction with sildenafil - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; SPINAL-CORD INJURY; ERECTILE DYSFUNCTION; ORAL SILDENAFIL; PRIMARY-CARE; RADICAL PROSTATECTOMY; DEPRESSIVE SYMPTOMS; INTERNATIONAL INDEX; SUSTAINED-RELEASE; MEN AB Context Sexual dysfunction is a common adverse effect of antidepressants that frequently results in treatment noncompliance. Objective To assess the efficacy of sildenafil citrate in men with sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants. Design, Setting, and Patients Prospective, parallel-group, randomized, double-blind, placebo-controlled trial conducted between November 1, 2000, and January 1, 2001, at 3 US university medical centers among 90 male outpatients (mean [SD] age, 45 [8] years) with major depression in remission and sexual dysfunction associated with SRI antidepressant treatment. Intervention Patients were randomly assigned to take sildenafil (n=45) or placebo (n=45) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks. Main Outcome Measures The primary outcome measure was score on the Clinical Global Impression-Sexual Function (CGI-SF); secondary measures were scores on the International index of Erectile Function, Arizona Sexual Experience Scale, Massachusetts General Hospital-Sexual Functioning Questionnaire, and Hamilton Rating Scale for Depression (HAM-D). Results Among the 90 randomized patients, 93% (83/89) of patients treated per protocol took at least 1 dose of study drug and 85% (76/89) completed week 6 end-point assessments with last observation carried forward analyses. At a CGI-SF score of 2 or lower, 54.5% (24/44) of sildenafil compared with 4.4% (2/45) of placebo patients were much or very much improved (P<.001). Erectile function, arousal, ejaculation, orgasm, and overall satisfaction domain measures improved significantly in sildenafil compared with placebo patients. Mean depression scores remained consistent with remission (HAM-D score &LE;10) in both groups for the study duration. Conclusion In our study, sildenafil effectively improved erectile function and other aspects of sexual function in men with sexual dysfunction associated with the use of SRI antidepressants. These improvements may allow patients to maintain adherence with effective antidepressant treatment. C1 Univ New Mexico, Sch Med, Dept Psychiat, Hlth Sci Ctr, Albuquerque, NM 87131 USA. Arizona Hlth Sci Ctr, Dept Psychiat, Tucson, AZ 85724 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nurnberg, HG (reprint author), Univ New Mexico, Sch Med, Dept Psychiat, Hlth Sci Ctr, 2400 Tucker NE, Albuquerque, NM 87131 USA. NR 71 TC 114 Z9 117 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 1 PY 2003 VL 289 IS 1 BP 56 EP 64 DI 10.1001/jama.289.1.56 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 630XL UT WOS:000180136600026 PM 12503977 ER PT J AU Otto, MW Reilly-Harrington, N Sachs, GS AF Otto, MW Reilly-Harrington, N Sachs, GS TI Psychoeducational and cognitive-behavioral strategies in the management of bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Review DE psychosocial strategy; psychoeducational strategy; cognitive-behavioral therapy; bipolar disorder; medication adherence ID LIFE EVENTS; ENDOGENOUS-DEPRESSION; PHARMACOLOGICAL TREATMENT; PANIC DISORDER; I DISORDER; THERAPY; RELAPSE; SLEEP; PHARMACOTHERAPY; METAANALYSIS AB Despite advances in the pharmacologic treatment of bipolar disorder, it is clear that additional strategies are needed to provide patients with longer-term mood stability. Recent years have witnessed the development of a number of psychosocial strategies for bipolar disorder that are design as adjuncts to ongoing pharmacotherapy. In this article we describe psychoeducational and cognitive-behavioral approaches to the management of bipolar disorder, with emphasis on broader treatment packages that can be offered by cognitive-behavior therapists working in specialty bipolar clinics, as well as specific strategies that can be integrated into standard pharmacotherapy for the disorder. A growing body of evidence documents the potential value of these interventions, and large-scale studies are underway, including the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), which will provide outcome on these interventions from the perspective of large, multicenter trials. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Cognit Behav Therapy Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Otto, MW (reprint author), Massachusetts Gen Hosp, Cognit Behav Therapy Program, WACC-812,15 Parkman St, Boston, MA 02114 USA. NR 63 TC 44 Z9 47 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JAN PY 2003 VL 73 IS 1-2 BP 171 EP 181 AR PII S0165-0327(01)00460-8 DI 10.1016/S0165-0327(01)00460-8 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 638VX UT WOS:000180593900019 PM 12507750 ER PT J AU Xu, J Fei, ZW Yu, YM Xu, WY Rhodes, A Tompkins, RG Schulz, JT AF Xu, J Fei, ZW Yu, YM Xu, WY Rhodes, A Tompkins, RG Schulz, JT TI In vivo rabbit hindquarter model for assessment of regional burn hypermetabolism SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE burn injury; phenylalanine kinetics ID MUSCLE PROTEIN-SYNTHESIS; METABOLISM; LEUCINE; INVIVO; INJURY; RAT AB Severe burn injury evokes hypermetabolism. and muscle wasting, despite nominally adequate nutrition. Although there is much information on whole organism and isolated tissue metabolism after burn injury, data examining regional burn hypermetabolism. in vivo are lacking. Using surgically implanted (general anesthesia) regional vascular catheters and primed constant infusion of L- [1-C-13] phenylalanine tracer, we have determined in vivo burn-induced alterations in rabbit hindquarter protein and energy metabolism. Burn injury evokes increased whole body resting energy expenditure and phenylalanine turnover, accompanied by significantly increased hindquarter proteolysis, creating a negative protein balance in burned rabbit hindquarter. Hindquarter oxygen consumption showed an increase after burn injury, but it did not reach statistical significance. Burn-induced changes in hindquarter protein turnover account for approximately one-third of the whole animal hypermetabolism. This model offers a system for regional manipulation of postburn hypermetabolism. C1 Massachusetts Gen Hosp, Burn & Trauma Serv, Shriners Burns Hosp, Boston, MA 02114 USA. RP Schulz, JT (reprint author), Dept Surg, Burn & Trauma Div, GRB 1302,55 Fruit St, Boston, MA 02114 USA. NR 29 TC 4 Z9 5 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JAN PY 2003 VL 94 IS 1 BP 135 EP 140 DI 10.1152/japplphysiol.00513.2002 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 625KM UT WOS:000179815700019 PM 12391055 ER PT J AU Edwards, RL Edwards, EH Edwards, AD AF Edwards, RL Edwards, EH Edwards, AD TI Observations of Theotima minutissimus (araneae, Ochyroceratidae), a parthenogenetic spider SO JOURNAL OF ARACHNOLOGY LA English DT Article DE parthenogenesis; spider; tropical rainforest; leaf litter; Wolbachia AB It has been suggested by several authorities that at least one species of spider of the genus Theotima, family Ochyroceratidae, occurring in tropical regions in South Africa, the Caribbean and Asia may be parthenogenetic. Theotima minutissimus is particularly abundant in the tropical rainforest leaf litter on El Yunque, Puerto Rico. While many hundreds of specimens have been collected over many years, none has been a male. To examine the possibility that this small species, +/- 0.9 mm body length, is parthenogenetic, live specimens were collected and maintained in the laboratory. A second generation spiderling, raised separately, produced viable progeny. C1 Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. RP Edwards, RL (reprint author), Box 505, Woods Hole, MA 02543 USA. NR 12 TC 16 Z9 20 U1 4 U2 10 PU AMER ARACHNOLOGICAL SOC PI COLLEGE PARK PA UNIV MARYLAND, DEPT ENTOMOLOGY, 4112 PLANT SCIENCES BLDG, COLLEGE PARK, MD 20742-4454 USA SN 0161-8202 EI 1937-2396 J9 J ARACHNOL JI J. Arachnol. PY 2003 VL 31 IS 2 BP 274 EP 277 DI 10.1636/0161-8202(2003)031[0274:OOTMAO]2.0.CO;2 PG 4 WC Entomology SC Entomology GA 732FB UT WOS:000185929200005 ER PT J AU Bhattacharyya, T Gale, D Dewire, P Totterman, S Gale, ME McLaughlin, S Einhorn, TA Felson, DT AF Bhattacharyya, T Gale, D Dewire, P Totterman, S Gale, ME McLaughlin, S Einhorn, TA Felson, DT TI The clinical importance of meniscal tears demonstrated by magnetic resonance imaging in osteoarthritis of the knee SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID CONTROLLED TRIAL; OSTEO-ARTHRITIS; BONE-MARROW; PAIN; HIP; THERAPY; AGE AB Background: Meniscal tears are frequently found during magnetic resonance imaging of osteoarthritic knees. However, the prevalence and clinical relevance of these tears have not been determined. This study was designed to investigate the relationship between meniscal tears and osteoarthritis and between such tears and pain in patients with osteoarthritis. Methods: Magnetic resonance imaging and plain radiography of the knee were performed in a group of 154 patients with clinical symptoms of knee osteoarthritis and a group of forty-nine age-matched asymptomatic controls. Pain scores (according to a 100-mm visual analog scale) and functional scores (according to the Western Ontario and McMaster University Osteoarthritis Index [WOMAC]) were determined for ninety-one of the patients with symptomatic osteoarthritis. Meniscal tears were defined as tears extending to an articular surface as seen on magnetic resonance imaging. Results: A medial or lateral meniscal tear was a very common finding in the asymptomatic subjects (prevalence, 76%) but was more common in the patients with symptomatic osteoarthritis (91%) (p < 0.005). In the group with symptomatic osteoarthritis, a higher Kellgren-Lawrence radiographic grade was correlated with a higher frequency of meniscal tears (r = 0.26, p < 0.001), and men had a higher prevalence of meniscal tears than did women (p < 0.01). However, there was no significant difference with regard to the pain or WOMAC score between the patients with and those without a medial or lateral meniscal tear in the osteoarthritic group (p = 0.8 to 0.9 for all comparisons). The power of the study was 80% to detect a difference in the WOMAC scores of 15 points and a difference in the scores on the visual analog scale of 16 mm. Conclusions: Meniscal tears are highly prevalent in both asymptomatic and clinically osteoarthritic knees of older individuals. However, osteoarthritic knees with a meniscal tear are not more painful than those without a tear, and the meniscal tears do not affect functional status. These data do not support the routine use of magnetic resonance imaging for the evaluation and management of meniscal tears in patients with osteoarthritis of the knee. Level of Evidence: Diagnostic study, Level 1-1 (testing of previously developed diagnostic criteria in series of consecutive patients [with universally applied reference "gold" standard]). See p. 2 for complete description of levels of evidence. C1 Boston Univ, Sch Med, Med Ctr,Clin Epidemiol Res & Training Unit, Arthrit Ctr, Boston, MA 02118 USA. Boston Univ, Med Ctr, Dept Orthopaed, Boston, MA 02118 USA. VA Boston Healthcare Syst, Dept Radiol, Boston, MA 02130 USA. RP Bhattacharyya, T (reprint author), Dept Orthopaed Surg, 720 Harrison Ave, Boston, MA 02118 USA. FU NIAMS NIH HHS [AR47785] NR 31 TC 187 Z9 192 U1 2 U2 15 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JAN PY 2003 VL 85A IS 1 BP 4 EP 9 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 631DT UT WOS:000180152900002 PM 12533565 ER PT J AU Muratoglu, OK Mark, A Vittetoe, DA Harris, WH Rubash, HE AF Muratoglu, OK Mark, A Vittetoe, DA Harris, WH Rubash, HE TI Polyethylene damage in total knees and use of highly crosslinked polyethylene SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID MOLECULAR-WEIGHT POLYETHYLENE; WEAR; ARTHROPLASTY; UHMWPE; REPLACEMENTS; OSTEOLYSIS; COMPONENTS; JOINT; STERILIZATION; PERFORMANCE C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, GRJ 1206, Boston, MA 02114 USA. NR 63 TC 25 Z9 26 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PY 2003 VL 85A SU 1 BP 7 EP 13 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 632HE UT WOS:000180217200003 ER PT J AU Mahomed, NN Barrett, JA Katz, JN Phillips, CB Losina, E Lew, RA Guadagnoli, E Harris, WH Poss, R Baron, JA AF Mahomed, NN Barrett, JA Katz, JN Phillips, CB Losina, E Lew, RA Guadagnoli, E Harris, WH Poss, R Baron, JA TI Rates and outcomes of primary and revision total hip replacement in the United States Medicare population SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID RACIAL-DIFFERENCES; ARTHROPLASTY; TRANSPLANTATION; DISLOCATION; OSTEOARTHRITIS; HEALTH AB Background: Information on the epidemiology of primary total hip replacement is limited, and we are not aware of any reports on the epidemiology of revision total hip replacement. The objective of this study was to characterize the rates and immediate postoperative outcomes of primary and revision total hip replacement in persons sixty-five years of age and older residing in the United States. Methods: We used Medicare claims submitted by hospitals, physicians, and outpatient facilities between July 1, 1995, and June 30, 1996, to identify individuals who had undergone elective primary total hip replacement for a reason other than a fracture (61,568 patients) or had had revision total hip replacement (13,483 patients). Annual incidence rates of primary and revision total hip replacement were calculated, and multivariate modeling was used to evaluate the association between patient characteristics and surgical rates. The rates of occurrence of five complications within ninety days postoperatively were also evaluated, and relationships between those outcomes and patient characteristics were assessed with use of multivariate models adjusted for hospital and surgeon volume. Results: The rates of primary total hip replacement were three to six times higher than the rates of revision total hip replacement. Women had higher rates than men, and whites had higher rates than blacks. The rates of primary and revision total hip replacement increased with age until the age of seventy-five to seventy-nine years and then declined. The rates of complications occurring within ninety days after primary total hip replacement were 1.0% for mortality, 0.9% for pulmonary embolus, 0.2% for wound infection, 4.6% for hospital readmission, and 3.1% for hip dislocation. The rates after revision total hip replacement were 2.6%, 0.8%, 0.95%, 10.0%, and 8.4%, respectively. Factors associated with an increased risk of an adverse outcome included increased age, gender (men were at higher risk than women), race (blacks were at higher risk than whites), a medical comorbidity, and a low income. Conclusions: Analysis of United States Medicare population data showed that the rates of total hip replacement increased with age up to the age of seventy-five to seventy-nine years and that blacks had a significantly lower rate of total hip replacement than whites. The overall rates of adverse outcomes were relatively low, but they were significantly higher after revision than after primary total hip replacement. Level of Evidence: Prognostic study, Level II-1 (retrospective study). See p. 2 for complete description of levels of evidence. C1 Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. Dartmouth Coll Sch Med, Dept Community & Family Med, Hanover, NH 03755 USA. Brigham & Womens Hosp, Robert Breck Multipurpose Arthrit & Musculoskelet, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Mahomed, NN (reprint author), Toronto Western Hosp, 399 Bathurst St,ECW 1-002, Toronto, ON M5T 2S8, Canada. FU AHRQ HHS [1R01 HS09775-01]; NIAMS NIH HHS [K24 AR02123, P01 AR36308] NR 28 TC 368 Z9 386 U1 5 U2 29 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JAN PY 2003 VL 85A IS 1 BP 27 EP 32 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 631DT UT WOS:000180152900005 PM 12533568 ER PT J AU Lonner, JH Mont, MA Sharkey, PF Siliski, JM Rajadhyaksha, AD Lotke, PA AF Lonner, JH Mont, MA Sharkey, PF Siliski, JM Rajadhyaksha, AD Lotke, PA TI Fate of the unrevised all-polyethylene patellar component in revision total knee arthroplasty SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article AB Background: During revision total knee arthroplasty, the alternatives for addressing the well-positioned and secure all-polyethylene patellar component with minimal or no wear include retention, revision, and resection. The purpose of the present study was to determine the intermediate-term fate of all-polyethylene patellar components that were left in situ at the time of revision tibiofemoral arthroplasty. Methods: We retrospectively reviewed the results of 202 revision total knee arthroplasties, performed at four centers, in which a well-fixed, well-positioned all-polyethylene patellar component with minimal wear was retained. Clinical evaluation was performed to identify the presence of anterior knee symptoms or patellar failures, and the Knee Society clinical scores were recorded. Results: Sixty-eight percent of the revision tibiofemoral components were from a different manufacturer than the retained patellar component. Twenty-one patients (twenty-one knees; 10%) reported anterior knee pain at a mean duration of follow-up of seven years (range, two to fourteen years). Eleven of the twenty-one knees with anterior knee pain had evidence of component loosening, excessive wear, or delamination either on follow-up radiographs or on direct inspection at the time of reoperation. In the other ten knees, the findings were attributable to osseous impingement on the femoral component or soft-tissue dysfunction (including soft-tissue impingement, subluxation, and scarring). Seventeen of the twenty-one patients with anterior knee pain underwent additional surgery to address the source of the pain. Failures due to loosening or wear occurred only in patients in whom the patellar component had been sterilized with gamma irradiation in air; these failures occurred at a mean 7.3 years after revision (eleven years after primary total knee arthroplasty). The likelihood of patellar component failure was significantly greater when the component had been gamma irradiated in air than when it had been sterilized with another method (p = 0.0008). The average knee score increased from 42 to 86 points, and the average function score increased from 46 to 70 points. Conclusions: Retaining a well-positioned, stable all-polyethylene patellar component at the time of revision tibiofemoral arthroplasty can be successful, provided that the polyethylene has not oxidized. Manufacturing mismatch is acceptable with most contemporary designs provided that the patellar component articulates appropriately with the femoral implant. Level of Evidence: Therapeutic study, Level IV (case series [no, or historical, control group]). See p. 2 for complete description of levels of evidence. C1 Penn Hosp, Booth Bartolozzi balderston Orthopaed, Philadelphia, PA 19107 USA. Sinai Hosp Baltimore, Inst Adv Orthopaed, Baltimore, MD 21215 USA. Thomas Jefferson Univ, Rothman Univ, Philadelphia, PA 19107 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lonner, JH (reprint author), Penn Hosp, Booth Bartolozzi balderston Orthopaed, 800 Spruce St, Philadelphia, PA 19107 USA. NR 13 TC 16 Z9 16 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JAN PY 2003 VL 85A IS 1 BP 56 EP 59 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 631DT UT WOS:000180152900009 PM 12533572 ER PT J AU Bozic, KJ Rosenberg, AG Huckman, RS Herndon, JH AF Bozic, KJ Rosenberg, AG Huckman, RS Herndon, JH TI Economic evaluation in orthopaedics SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Review ID QUALITY-OF-LIFE; COST-EFFECTIVENESS ANALYSIS; TOTAL JOINT ARTHROPLASTY; TOTAL HIP-ARTHROPLASTY; HEALTH-CARE; MEDICAL LITERATURE; USERS GUIDES; SURGICAL INTERVENTION; CLINICAL-PRACTICE; TECHNOLOGY C1 Rush Presbyterian St Lukes Med Ctr, Dept Orthopaed Surg, Chicago, IL 60612 USA. Harvard Univ, Sch Business, Dept Technol & Operat Management, Boston, MA 02163 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Bozic, KJ (reprint author), Rush Presbyterian St Lukes Med Ctr, Dept Orthopaed Surg, 1725 W Harrison St,Suite 1063, Chicago, IL 60612 USA. NR 82 TC 42 Z9 42 U1 4 U2 5 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JAN PY 2003 VL 85A IS 1 BP 129 EP 142 PG 14 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 631DT UT WOS:000180152900021 PM 12533584 ER PT J AU Heimbach, DM Warden, GD Luterman, A Jordan, MH Ozobia, N Ryan, CM Voigt, DW Hickerson, WL Saffle, JR DeClement, FA Sheridan, RL Dimick, AR AF Heimbach, DM Warden, GD Luterman, A Jordan, MH Ozobia, N Ryan, CM Voigt, DW Hickerson, WL Saffle, JR DeClement, FA Sheridan, RL Dimick, AR TI Multicenter postapproval clinical trial of Integra((R)) dermal regeneration template for burn treatment SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article ID INHALATION INJURY; ARTIFICIAL SKIN; FULL-THICKNESS; BODY-SURFACE; MORTALITY; EXPERIENCE; KERATINOCYTES; DETERMINANTS; PROBABILITY; EXCISION AB The safety and effectiveness of Integra(R) Dermal Regeneration Template was evaluated in a postapproval study involving 216 burn injury patients who were treated at 13 burn care facilities in the United States. The mean total body surface area burned was 36.5% (range, 1-95%). Integra(R) was applied to fresh, clean, surgically excised burn wounds. Within 2 to 3 weeks, the dermal layer regenerated, and a thin epidermal autograft was placed. The incidence of invasive infection at Integra(R) treated sites was 3.1% (95% confidence interval, 2.0-4.5%) and that of superficial infection 13.2% (95% confidence interval, 11.0-15.7%). Mean take rate of Integra(R) was 76.2%; the median take rate was 95%. The mean take rate of epidermal autograft was 87.7%; the median take rate was 98%. This postapproval study further supports the conclusion that Integra(R) is a safe and effective treatment modality in the hands of properly trained clinicians under conditions of routine clinical use at burn centers. C1 Univ Washington, Dept Surg, Seattle, WA 98195 USA. Shriners Burns Inst, Cincinnati, OH 45219 USA. Univ S Alabama, Dept Surg, Mobile, AL 36688 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Lions Burns Care Ctr, Las Vegas, NV USA. Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. St Elizabeths Reg Burn Ctr, Lincoln, NE USA. Univ Tennessee, Med Grp, Memphis, TN USA. Univ Utah, Hosp & Clin, Burn Trauma Unit, Salt Lake City, UT USA. St Agnes Burn Ctr, Philadelphia, PA USA. Shriners Hosp Children, Burn Inst, Boston Unit, Boston, MA USA. Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. RP Heimbach, DM (reprint author), Harborview Med Ctr, 325 9th Ave,Box 359796, Seattle, WA 98104 USA. NR 31 TC 100 Z9 103 U1 3 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD JAN-FEB PY 2003 VL 24 IS 1 BP 42 EP 48 DI 10.1097/01.BCR.0000045659.08820.00 PG 7 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 637XZ UT WOS:000180540200007 PM 12543990 ER PT J AU Danias, PG Tritos, NA Stuber, M Kissinger, KV Salton, CJ Manning, WJ AF Danias, PG Tritos, NA Stuber, M Kissinger, KV Salton, CJ Manning, WJ TI Cardiac structure and function in the obese: A Cardiovascular Magnetic Resonance Imaging Study SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE cardiovascular magnetic resonance (CMR); obesity; tagging ID LEFT-VENTRICULAR MASS; OBSTRUCTIVE SLEEP-APNEA; HEART-FAILURE; NONINVASIVE QUANTIFICATION; GENDER-DIFFERENCES; SYSTOLIC FUNCTION; BODY-SIZE; HYPERTROPHY; ECHOCARDIOGRAPHY; HYPERTENSION AB Background. Obesity is a major health problem in the Western world. Among obese subjects cardiac pathology is common, but conventional noninvasive imaging modalities are often suboptimal for detailed evaluation of cardiac structure and function. We investigated whether cardiovascular magnetic resonance imaging (CMR) can better characterize possible cardiac abnormalities associated with obesity, in the absence of other confounding comorbidifies. Methods. In this prospective cross-sectional study, CMR was used to quantify left and right ventricular volumes, ejection fraction, mass, cardiac output, and apical left ventricular rotation in 25 clinically healthy obese men and 25 age-matched lean controls. Results. Obese subjects had higher left ventricular mass (203 +/- 38 g vs. 163 +/- 22 g, p < 0.001), end-diastolic volume (176 +/- 29 mL vs. 156 +/- 25 mL; p < 0.05), and cardiac output (8.2 +/- 1.2 L/min vs. 6.4 +/- 1.3 L/min, p < 0.001). The obese also had increased right ventricular mass (105 +/- 25 g vs. 87 +/- 18 g, p < 0.005) and end-diastolic volume (179 +/- 36 mL vs. 155 +/- 28 mL, p < 0.05). When indexed for height, differences in left and right ventricular mass, and left ventricular end-diastolic volume remained significant. Apical left ventricular rotation and rotational velocity patterns were also different between obese and lean subjects. Conclusions. Obesity is independently associated with remodeling of the heart. Cardiovascular magnetic resonance imaging identifies subtle cardiac abnormalities and may be the preferred imaging technique to evaluate cardiac structure and function in the obese. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiol, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol,Dept Med, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Philips Med Syst, Best, Netherlands. RP Danias, PG (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiol, 330 Brookline Ave, Boston, MA 02215 USA. EM pdanias@bidmc.harvard.edu RI Stuber, Matthias/B-2949-2010 OI Stuber, Matthias/0000-0001-9843-2028 FU NCRR NIH HHS [RR 01032] NR 34 TC 28 Z9 28 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1097-6647 J9 J CARDIOV MAGN RESON JI J. Cardiov. Magn. Reson. PY 2003 VL 5 IS 3 BP 431 EP 438 DI 10.1081/JCMR-120022259 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 700EH UT WOS:000184099300002 PM 12882074 ER PT J AU Su, M West, CA Young, AJ He, CF Konerding, MA Mentzer, SJ AF Su, M West, CA Young, AJ He, CF Konerding, MA Mentzer, SJ TI Dynamic deformation of migratory efferent lymph-derived cells "trapped" in the inflammatory microcirculation SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID SCANNING ELECTRON-MICROSCOPY; KILLER-CELLS; VEILED CELLS; IN-VIVO; LYMPHOCYTES; SHEEP; NEUTROPHIL; LOCOMOTION; DEFORMABILITY; IMMUNOBLASTS AB The cellular immune response depends on the delivery of lymphocytes from the lymph node to the peripheral site of antigenic challenge. During their passage through the inflammatory microcirculaton, the migratory cells can become transiently immobilized or "trapped" in small caliber vessels. In this report, we used intravital microscopy and temporal area mapping to define the dynamic deformation of efferent lymph-derived mononuclear cells trapped in the systemic inflammatory microcirculation. Mononuclear cells obtained from the efferent lymph draining the oxazolone-stimulated microcirculation were labeled with fluorescent dye and reinjected into the feeding arterial circulation. Intravital video microscopy observed thousands of cells passing through the microcirculation; 35 cells were "trapped" in the oxazolone-stimulated microcirculation. Temporal area maps of the trapped cells demonstrated dramatic slowing and deformation. The cells were trapped in the microcirculation for a median of 8.90 sec (range 5-17 sec) prior to returning to the flow stream. During this period, the cells showed sustained movement associated with both antegrade locomotion (mean cell velocity=7.92 mum/sec; range 1.16-14.23 mum/sec) and dynamic elongation (median cell length-73.8 mum; range 58-144 mum). In contrast, efferent lymph-derived cells passing unimpeded through the microcirculation demonstrated rapid velocity (median velocity=216 mum/sec) and spherical geometry (median diameter = 14.6 mum). Further, the membrane surface area of the "trapped" cells, calculated based on digital image morphometry and corrosion cast scanning electron microscopy, suggested that the fractional excess membrane of the cells in the efferent lymph was significantly greater than previous estimates of membrane excess. These data indicate that transient immobilization of efferent lymph-derived mononuclear cells in the systemic inflammatory microcirculation is rare. When "trapping" does occur, the shape changes and sustained cell movement facilitated by excess cell membrane may contribute to the return of the "trapped cells" into the flow stream. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Immunophysiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Surg Res Lab, Boston, MA 02115 USA. Univ Mainz, Dept Anat, D-6500 Mainz, Germany. RP Mentzer, SJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Immunophysiol Lab, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL47078] NR 50 TC 6 Z9 6 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JAN PY 2003 VL 194 IS 1 BP 54 EP 62 DI 10.1002/jcp.10190 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 620XE UT WOS:000179558100006 PM 12447989 ER PT J AU Geller, DA Biederman, J Stewart, SE Mullin, B Farrell, C Wagner, KD Emslie, G Carpenter, D AF Geller, DA Biederman, J Stewart, SE Mullin, B Farrell, C Wagner, KD Emslie, G Carpenter, D TI Impact of Comorbidity on treatment response to paroxetine in pediatric obsessive-compulsive disorder: Is the use of exclusion criteria empirically supported in randomized clinical trials? SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DOUBLE-BLIND; CLOMIPRAMINE TREATMENT; MULTICENTER TRIAL; ADOLESCENTS; CHILDREN; CHILDHOOD; FLUVOXAMINE; DESIPRAMINE; RELIABILITY; FLUOXETINE AB Objective: To examine the influence of psychiatric comorbidity on response and relapse rates in children and adolescents treated with paroxetine for obsessive-compulsive disorder (OCD). Methods: Patients responding following 16 weeks of treatment (phase D were randomized to continued paroxetine or to placebo for 16 additional weeks (phase 11). OCD response (phase D and relapse (phase 11) criteria were based on the Clinical Global Impression Improvement Scale and the Children's Yale-Brown Obsessive Compulsive Scale. The presence of OCD and other psychiatric disorders was ascertained using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version interview. Results: At entry, 193 of 335 (57.6%) patients had at least one psychiatric disorder in addition to OCD, and 102 of 335 (30.4%) had multiple other disorders. Although the response rate to paroxetine in the overall population was high (71%), the response rates in patients with comorbid attention deficit hyperactivity disorder, tic disorder, or oppositional defiant disorder (56%, 53%, and 39%, respectively) were significantly less than in patients with OCD only (75%) (intent-to-treat population, last observation carried forward analysis, p < 0.05). Psychiatric comorbidity was associated with a greater rate of relapse in the total patient population (46% for one or more comorbid disorders [p = 0.04] and 56% for two or more comorbid disorders [p < 0.05] vs. 32% for no comorbidity). Conclusions: The results of these post hoc analyses show that comorbid illness adversely impacted response to pharmacotherapy with paroxetine in pediatric OCD and significantly increased risk of relapse following withdrawal from treatment. Continued paroxetine treatment reduced relapse rates in all groups compared with placebo, including those with comorbid illness. Because pediatric OCD is frequently comorbid with other psychiatric disorders, results of randomized, controlled pediatric OCD trials that use multiple exclusion criteria may not generalize to more naturalistic OCD samples. C1 Massachusetts Gen Hosp, Obsess Compuls Disorder Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Div Child & Adolescent Psychiat, Dallas, TX USA. Childrens Med Ctr, Dallas, TX 75235 USA. GlaxoSmithKline Pharmaceut, King Of Prussia, PA USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. RP Geller, DA (reprint author), Massachusetts Gen Hosp, Pediat Obsess Compuls Disorder Program, ACC725,15 Parkman St, Boston, MA 02114 USA. RI Stewart, Evelyn/K-6961-2014 NR 34 TC 90 Z9 90 U1 1 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PY 2003 VL 13 SU 1 BP S19 EP S29 PG 11 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 704HZ UT WOS:000184335400003 PM 12880497 ER PT J AU Schwaber, MJ Krasner, CN Gold, HS Venkataraman, L Avigan, DE Karchmer, AW Uhl, L AF Schwaber, MJ Krasner, CN Gold, HS Venkataraman, L Avigan, DE Karchmer, AW Uhl, L TI Detection of Staphylococcus aureus in peripheral blood stem cell cultures after sterilization of standard blood cultures SO JOURNAL OF CLINICAL APHERESIS LA English DT Article DE apheresis; Staphyloeoecus aureus; peripheral blood stem cells; blood cultures; bacteremia; endocarditis ID MICROBIAL-CONTAMINATION; BACTERIAL-CONTAMINATION AB We report central venous catheter (CVC)-associated Staphylococcus aureus bacteremia detected by apheresis product culture after sterilization of standard blood cultures. A 64-year-old man with non-Hodgkin's lymphoma underwent peripheral blood stem cell (PBSC) collection. Five days after placement of a CVC, inflammation was evident at the insertion site. The CVC was removed and cephalexin was begun. Discharge at the site contained neutrophils and gram-positive cocci in pairs and clusters. Cultures of the discharge, of blood drawn via the CVC, of the CVC tip and of the apheresis product collected that day grew methicillin-susceptible S. aureus (MSSA). Cephalexin was discontinued in favor of oxacillin. Three days after removal of the CVC, PBSC collections were resumed via a contralateral CVC. Three sets of standard blood cultures drawn the day the new CVC was placed and the following day were negative, yet apheresis product cultures from each of these days grew MSSA. PBSC collections were halted, the CVC was removed, and oxacillin was continued via a peripherally inserted central catheter. Transesophageal echocardiography after two weeks of therapy revealed thickened mitral leaflets and damage to the posterior leaflet. Transthoracic echocardiography 11 weeks preceding this study had demonstrated normal mitral valve anatomy and function. Oxacillin was continued for six weeks, after which PBSC collections were resumed. Pulsed-field gel electrophoresis of the MSSA isolates revealed a clonal pattern. Cultures of apheresis product may be more sensitive to the presence of bacteremia than standard blood cultures, and they should guide clinical decisions when the bacteria isolated are potential pathogens or suggest clinical infection. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Infect Dis, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol & Med Oncol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol & Oncol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Lab Med Transfus Med, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Uhl, L (reprint author), Beth Israel Deaconess Med Ctr, Div Lab Med Transfus Med, Dept Pathol, Yamins 309,330 Brookline Ave, Boston, MA 02215 USA. FU ODCDC CDC HHS [TO1/CCU-111438] NR 8 TC 0 Z9 0 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0733-2459 J9 J CLIN APHERESIS JI J. Clin. Apheresis PY 2003 VL 18 IS 1 BP 37 EP 39 DI 10.1002/jca.10046 PG 3 WC Hematology SC Hematology GA 674DM UT WOS:000182621800007 PM 12717792 ER PT J AU Krischer, JP Cuthbertson, DD Yu, LP Orban, T Maclaren, N Jackson, R Winter, WE Schatz, DA Palmer, JP Eisenbarth, GS AF Krischer, JP Cuthbertson, DD Yu, LP Orban, T Maclaren, N Jackson, R Winter, WE Schatz, DA Palmer, JP Eisenbarth, GS CA Diabetes Prev Trial-Type 1 Study G TI Screening strategies for the identification of multiple antibody-positive relatives of individuals with type 1 diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ISLET-CELL ANTIBODIES; INSULIN AUTOANTIBODIES; RISK ASSESSMENT; PREDICTION; MELLITUS; ASSAY; GAD65; IDDM; POPULATION; MICROASSAY AB The objective of this study was to determine the extent to which different screening strategies could identify a population of nondiabetic relatives of a proband with type 1 diabetes who had two or more immunologic markers from the group consisting of islet cell antibodies (ICA), micro insulin auto antibodies (MIAA), GAD65 autoantibodies (GAA), and ICA512 autoantibodies (ICA512AA). Relatives of subjects with type 1 diabetes were screened for ICA as part of the Diabetes Prevention Trial-Type 1. A total of 71,148 samples were also tested for GAA and ICA512AA. IAA results were available on 17,207 of these samples using a protein A/protein G MIAA assay as well. The study population was defined to be those in which all four antibodies were tested. There were 1010 (5.9%) relatives with a single autoantibody on initial screening and 394 (2.3%) with two or more autoantibodies. GAA was more sensitive than ICA [GAA, 91% (357 of 394); ICA, 82% (324 of 394)] in the detection of multiple antibody-positive individuals. The addition of ICA512AA to GAA as a screening test increased sensitivity to 97% (381 of 394), whereas adding ICA512AA to ICA as a screening test increased sensitivity to 93% (367 of 394). GAA and ICA identified somewhat nonoverlapping subgroups of multiple antibody-positive subjects. Thus, the substitution of GAA or ICA for the other failed to detect 8-17% of multiple antibody subjects. Higher ICA titers were associated with increased percentages of multiple antibody-positive subjects; 86% of subjects having Juvenile Diabetes Foundation titers of at least 160 were positive for two or more antibodies. A screening strategy combining GAA and ICA512AA resulted in a higher sensitivity than using any marker individually, although statistically it was not significantly higher than using GAA alone. Screening for any three antibodies guaranteed that all multiple antibody-positive subjects were detected. Screening for two antibodies at one time and testing for the remaining antibodies among those who are positive for one resulted in a sensitivity of 99% for GAA and ICA, 97% for GAA and MIAA or GAA and ICA512AA, 93% for ICA512AA and ICA, 92% for MIAA and ICA, and 73% for ICA512AA and MIAAA. From a laboratory perspective, screenings for GAA, ICA512AA, and MIAA are semiautomated tests with high throughput that, if used as initial screen, would identify at first testing 67% of the 2.3% of multiple antibody-positive relatives (100% if antibody-positive subjects are subsequently tested for ICA) as well as 4.7% of relatives with a single biochemical autoantibody, some of whom may convert to multiple autoantibody positivity on follow-up. Testing for ICA among relatives with one biochemical antibody would identify the remaining 33% of multiple antibody-positive relatives. Further follow-up and analysis of actual progression to diabetes will be essential to define actual diabetes risk in this large cohort. C1 Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Univ Colorado, Barbara Davis Ctr Childhood Diabet, Denver, CO 80262 USA. Cornell Univ, Weill Med Coll, Dept Pediat, New York, NY 10021 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Univ Florida, Dept Pathol & Lab Med, Gainesville, FL 32611 USA. Univ Florida, Dept Pediat, Gainesville, FL 32611 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Krischer, JP (reprint author), Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM jpkrischer@moffitt.usf.edu NR 24 TC 79 Z9 85 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2003 VL 88 IS 1 BP 103 EP 108 DI 10.1210/jc.2002-020760 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 636MK UT WOS:000180459700018 PM 12519837 ER PT J AU Leder, BZ LeBlanc, KM Schoenfeld, DA Eastell, R Finkelstein, JS AF Leder, BZ LeBlanc, KM Schoenfeld, DA Eastell, R Finkelstein, JS TI Differential effects of androgens and estrogens on bone turnover in normal men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID OSTEOBLAST-LIKE CELLS; SEX STEROID-LEVELS; AGED MALE-RATS; MINERAL DENSITY; AROMATASE DEFICIENCY; ELDERLY MEN; OLDER MEN; SERUM TESTOSTERONE; RANCHO BERNARDO; RECEPTOR GENE AB The physiologic role of androgens and estrogens in the maintenance of normal bone turnover in men is a fundamental issue in bone biology. To address this question, we randomized 70 men between the ages of 20 and 44 yr to receive one of three treatment regimens. Group 1 (n = 25) received a GnRH analog (goserelin acetate 3.6 mg by se injection every 4 wk) alone for 12 wk to suppress endogenous gonadal steroids to prepubertal levels. Group 2 (n = 22) received goserelin plus transdermal testosterone (Androderm 5 mg topically daily) to normalize circulating testosterone and estradiol levels. Group 3 (n = 23) received goserelin plus testosterone plus an aromatase inhibitor (anastrozole 1 mg orally daily) to induce selective estrogen deficiency. The selective effects of androgens and estrogens on skeletal homeostasis were then assessed by measuring changes in biochemical markers of bone turnover and analyzing the between-group differences. Bone resorption markers increased in both the hypogonadal group (group 1) and in the group with selective estrogen deficiency (group 3). Urinary deoxypyridinoline excretion increased more in group 1 than in group 3 (P = 0.023), suggesting a significant effect of androgens on bone resorption, whereas serum N-telopeptide levels increased more in group 3 than in group 2 (P = 0.037), suggesting a significant effect of estrogen on bone resorption. Bone formation markers initially declined in all groups and then increased in groups 1 and 3. The between-group comparisons were consistent for all formation markers. Bone formation markers increased more in group 1 than in group 2 (P = 0.001, 0.037, 0.005 for osteocalcin, carboxyterminal propeptide of type I procollagen, and amino-terminal propeptide of type I procollagen, respectively). Bone formation markers also increased more in group I than in group 3 but these differences were not statistically significant (P = 0.065 0.073, 0.099 for osteocalcin, carboxy-terminal propeptide of type I procollagen, and amino-terminal propeptide of type I procollagen, respectively). Taken together, these data suggest that both androgens and estrogens play independent and fundamental roles in regulating bone resorption in men. These data also suggest that androgens may play an important role in the regulation of bone formation in men. C1 Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Dept Med, Boston, MA 02114 USA. No Gen Hosp, Div Clin Sci, Sheffield S5 7AU, S Yorkshire, England. RP Leder, BZ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Bulfinch 327,Fruit St, Boston, MA 02114 USA. EM bzleder@partners.org RI Eastell, Richard/G-5851-2011 OI Eastell, Richard/0000-0002-0323-3366 FU NCRR NIH HHS [K23-RR16310, RR-1066]; NIAMS NIH HHS [F32-AR08574]; NIDDK NIH HHS [K24-DK02759] NR 41 TC 170 Z9 180 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2003 VL 88 IS 1 BP 204 EP 210 DI 10.1210/jc.2002-021036 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 636MK UT WOS:000180459700034 PM 12519853 ER PT J AU Schellhase, KG Koepsell, TD Weiss, NS Wagner, EH Reiber, GE AF Schellhase, KG Koepsell, TD Weiss, NS Wagner, EH Reiber, GE TI Glucose screening and the risk of complications in Type 2 diabetes mellitus SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE mass screening; diabetes mellitus; outcome assessment; case-control studies; diabetes mellitus/complications; diabetes mellitus/epidemiology ID COLORECTAL-CANCER; NIDDM; MORTALITY; BENEFITS; ADULTS AB It is unknown whether glucose screening for Type 2 diabetes mellitus (DM2) reduces the risk of diabetic complications. We conducted a case-control study using 303 cases with DM2 and at least one symptomatic microvascular diabetic complication, matched 1:1 to control subjects. All subjects' blood glucose tests for the decade before the first clinical suspicion of DM2 were categorized as screening or not based on the presence of symptoms suggestive of DM2. Approximately 90% of case subjects and control subjects had been screened for diabetes. After adjusting for multiple covariates in a logistic regression model, the odds ratio of developing a complication associated with screening was 0.87 (95% confidence interval 0.38-1.98), suggesting that screening may be associated with a modest reduction in the risk of certain diabetic complications. However, the confidence limits were wide and consistent with no true benefit. Further studies are needed to establish whether the small reduction we observed is genuine. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Univ Washington, Dept Family Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Sci, Seattle, WA 98195 USA. Univ Washington, Robert Wood Johnson Clin Scholars Program, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Sandy MacColl Inst Healthcare Innovat, Seattle, WA 98101 USA. Grp Hlth Cooperat Puget Sound, Seattle, WA 98101 USA. Vet Affairs Puget Sound Hlth Syst, Hlth Sci Res & Dev, Seattle, WA 98108 USA. RP Schellhase, KG (reprint author), Med Coll Wisconsin, Dept Family & Community Med, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. NR 25 TC 11 Z9 11 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JAN PY 2003 VL 56 IS 1 BP 75 EP 80 AR PII S0895-4356(02)00533-4 DI 10.1016/S0895-4356(02)00533-4 PG 6 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 646ZW UT WOS:000181067600010 PM 12589873 ER PT J AU Burstein, HJ Harris, LN Gelman, R Lester, SC Nunes, RA Kaelin, CM Parker, LM Ellisen, LW Kuter, I Gadd, MA Christian, RL Kennedy, PR Borges, VF Bunnell, CA Younger, J Smith, BL Winer, EP AF Burstein, HJ Harris, LN Gelman, R Lester, SC Nunes, RA Kaelin, CM Parker, LM Ellisen, LW Kuter, I Gadd, MA Christian, RL Kennedy, PR Borges, VF Bunnell, CA Younger, J Smith, BL Winer, EP TI Preoperative therapy with trastuzumab and paclitaxel followed by sequential adjuvant doxorubicin/cyclophosphamide for HER2 overexpressing stage II or III breast cancer: A pilot study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PRIMARY CHEMOTHERAPY; MONOCLONAL-ANTIBODY; DOXORUBICIN; CYCLOPHOSPHAMIDE; FLUOROURACIL; EFFICACY; TUMORS; SAFETY; WOMEN AB Purpose: Trastuzumab combined with chemotherapy improves outcomes for women with human epidermal growth factor receptor 2 (HER2) overexpressing advanced breast cancer. We conducted a pilot study of preoperative trastuzumab and paclitaxel, followed by surgery and adjuvant doxorubicin and cyclophosphamide chemotherapy in earlier stage breast cancer. Patients and Methods: Patients with HER2-positive (2+ or 3+ by immunohistochemistry) stage II or III breast cancer received preoperative trastuzumab (4 mg/kg x 1, then 2 mg/kg/wk x 11) in combination with paclitaxel (175 mg/m(2) every 3 weeks x 4). Patients received adjuvant doxorubicin and cyclophosphamide chemotherapy following definitive breast surgery. Clinical and pathologic response rates were determined after preoperative therapy. Left ventricular ejection fraction and circulating levels of HER2 extracellular domain were measured serially. Results: Preoperative trastuzumab and paclitaxel achieved clinical response in 75% and complete pathologic response in 18% of the 40 women on study. HER2 3+ tumors were more likely to respond than 2+ tumors (84% v 38%). No unexpected treatment-related noncardiac toxicity was encountered. Four patients developed grade 2 cardiotoxicity (asymptomatic declines in left ventricular ejection fraction). Baseline HER2 extracellular domain was elevated in 24% of patients and declined with preoperative therapy. Immunohistochemical analyses of posttherapy tumor specimens indicated varying patterns of HER2 expression following trastuzumab-based treatment. Conclusion: Preoperative trastuzumab and paclitaxel is active against HER2 overexpressing early-stage breast cancer and may be feasible as part of a sequential treatment program including anthracyclines. The observed changes in cardiac function merit further investigation. Correlative analyses of HER2 status may facilitate understanding of tumor response and resistance to targeted therapy. (C) 2003 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Faulkner Hosp, Dept Surg, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 21 TC 194 Z9 204 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2003 VL 21 IS 1 BP 46 EP 53 DI 10.1200/JCO.2003.03.124 PG 8 WC Oncology SC Oncology GA 685UF UT WOS:000183281100009 PM 12506169 ER PT J AU Adelstein, DJ Li, Y Adams, GL Wagner, H Kish, JA Ensley, JF Schuller, DE Forastiere, AA AF Adelstein, DJ Li, Y Adams, GL Wagner, H Kish, JA Ensley, JF Schuller, DE Forastiere, AA TI Intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROSPECTIVE RANDOMIZED TRIAL; STAGE-III; CHEMOTHERAPY; CARCINOMA; RADIOTHERAPY; CISPLATIN; INDUCTION; RADIOCHEMOTHERAPY; FRACTIONATION; OROPHARYNX AB Purpose : The Head and Neck Intergroup conducted a phase III randomized trial to test the benefit of adding chemotherapy to radiation in patients with unresectable squamous cell head and neck cancer. Patients and Methods: Eligible patients were randomly assigned between arm A (the control), single daily fractionated radiation (70 Gy at 2 Gy/d); arm B, identical radiation therapy with concurrent bolus cisplatin, given on days 1, 22, and 43; and arm C, a split course of single daily fractionated radiation and three cycles of concurrent infusional fluorouracil and bolus cisplatin chemotherapy, 30 Gy given with the first cycle and 30 to 40 Gy given with the third cycle. Surgical resection was encouraged if possible after the second chemotherapy cycle on arm C and, if necessary, as salvage therapy on all three treatment arms. Survival data were compared between each experimental arm and the control arm using a one-sided log-rank test. Results: Between 1992 and 1999, 295 patients were entered on this trial. This did not meet the accrual goal of 362 patients and resulted in premature study closure. Grade 3 or worse toxicity occurred in 52% of patients enrolled in arm A, compared with 89% enrolled in arm 8 (P < .0001) and 77% enrolled in arm C (P < .001). With a median follow-up of 41 months, the 3-year projected overall survival for patients enrolled in arm A is 23%, compared with 37% for arm B (P = .0 14) and 27% for arm C (P = not significant). Conclusion: The addition of concurrent high-dose, single-agent cisplatin to conventional single daily fractionated radiation significantly improves survival, although it also increases toxicity. The loss of efficacy resulting from split-course radiation was not offset by either multiagent chemotherapy or the possibility of midcourse surgery. (C) 2003 by American Society of Clinical Oncology. C1 Cleveland Clin Fdn, Dept Hematol & Med Oncol, Cleveland, OH 44195 USA. Arthur G James Canc Hosp, Columbus, OH USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Minnesota, Fairview Univ Med Ctr, Minneapolis, MN USA. H Lee Moffitt Canc Ctr, Tampa, FL USA. Henry Ford Hosp, Detroit, MI 48202 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Johns Hopkins Univ, Baltimore, MD USA. RP Adelstein, DJ (reprint author), Cleveland Clin Fdn, Dept Hematol & Med Oncol, 9500 Euclid Ave,Desk R35, Cleveland, OH 44195 USA. FU NCI NIH HHS [CA04919, CA04920, CA16116, CA21115, CA23318, CA58416, CA66636, CA73590]; VA [VA14028] NR 36 TC 766 Z9 787 U1 1 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2003 VL 21 IS 1 BP 92 EP 98 DI 10.1200/JCO.2003.01.008 PG 7 WC Oncology SC Oncology GA 685UF UT WOS:000183281100016 PM 12506176 ER PT J AU Biederman, J AF Biederman, J TI Pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD) decreases the risk for substance abuse: Findings from a longitudinal follow-up of youths with and without ADHD SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Long-Term Safety of Methylphenidate in the Treatment of ADHD CY JAN 18, 2003 CL BOSTON, MASSACHUSETTS ID DEFICIT HYPERACTIVITY DISORDER; PSYCHIATRIC COMORBIDITY; CONTROLLED FAMILY; CHILDREN; ADULTS; ADOLESCENTS; RELATIVES; PROBANDS; PATTERNS; CONDUCT AB Findings from a previously published longitudinal follow-up of adolescents with and without attention-deficit/hyperactivity disorder (ADHD) were reanalyzed to determine the extent to which pharmacotherapy for ADHD is associated with substance use disorders, including abuse and dependence. Using naturalistic data from 140 people with ADHD and 120 controls, researchers returned to previously accumulated data to determine whether exposure to stimulant therapy had increased rates of substance use disorder among ADHD patients. Findings included confirmation that, in fact, stimulant therapy protected medicated ADHD patients against substance use disorder, which occurred at rates that were 3 to 4 times greater among people with untreated ADHD. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WAC 725, Boston, MA 02114 USA. NR 26 TC 79 Z9 82 U1 6 U2 17 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2003 VL 64 SU 11 BP 3 EP 8 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 727RG UT WOS:000185671800001 PM 14529323 ER PT J AU Marder, SR AF Marder, SR TI Overview of partial compliance SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Teleconference on Partial Compliance: Need for Long Acting Atypical Antipsychotics CY MAR 27, 2002 CL ELECTR NETWORK ID SCHIZOPHRENIC-PATIENTS; MEDICATION ADHERENCE; ANTIPSYCHOTIC MEDICATION; PSYCHOTIC DISORDERS; RELAPSE; INPATIENTS; THERAPY; DRUG; NONCOMPLIANCE AB A substantial proportion of patients with psychiatric and nonpsychiatric chronic illnesses fail to take their medications as prescribed. A number of studies suggest that 50% or more of individuals with schizophrenia are noncompliant with medications at some time during their illness. In most cases, patients are partially compliant, taking only a portion of their prescribed medications. Noncompliance is probably the most important element contributing to relapse in schizophrenia. Factors contributing to the rate of noncompliance include medication side effects, the severity of psychotic symptoms, impaired cognition, and an inadequate understanding of the role of medication for preventing relapse. In addition, both patients and clinicians overestimate patients' compliance. Strategies for managing partial compliance include the treatment of medication side effects, the education of patients about their illness, and the use of long-acting antipsychotic formulations. C1 W LA VA Hlth Care Ctr, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. RP Marder, SR (reprint author), W LA VA Hlth Care Ctr, VA Greater Los Angeles Hlth Care Syst, MIRECC-210A,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 41 TC 61 Z9 62 U1 2 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2003 VL 64 SU 16 BP 3 EP 9 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 753YW UT WOS:000187276800001 PM 14680412 ER PT J AU Evins, AE AF Evins, AE TI Efficacy of newer anticonvulsant medications in bipolar spectrum mood disorders SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Using the Newer Anticonvulsants as Mood Stabilizers in Affective Disorders CY JUL 16, 2001 CL ELECTR NETWORK ID ACUTE MANIA; OPEN-LABEL; DOUBLE-BLIND; CASE SERIES; GABAPENTIN; LAMOTRIGINE; TOPIRAMATE; MONOTHERAPY; TIAGABINE; TRIAL AB Background: More treatment options for all phases of bipolar disorder are needed. While lithium, valproate, and carbamazepine remain the standard of care for treatment of bipolar disorder, many patients do not respond adequately to these treatments. Some new antiepileptic medications such as lamotrigine, gabapentin, topiramate, oxcarbazepine, tiagabine, and zonisamide are beginning to be used to treat bipolar disorder. Data Sources: Evidence for effectiveness of these novel antiepileptic drugs in treating acute mania and depression as well as in preventing the recurrence of mania and depression is reviewed. A MEDLINE search (1966-2001) was performed for clinical trials that were published in English using the keywords lamotrigine, gabapentin, topiramate, oxcarbazepine, tiagabine, and zonisamide, plus the terms bipolar disorder and mania. Evidence for effectiveness of monotherapy is presented first when it is available. Data from augmentation treatment studies and open case series in which standard ratings of symptoms were employed are presented when these are the only available data. Data Synthesis: Twenty-eight reports of the efficacy of novel antiepileptic medications in bipolar disorder are reviewed. Evidence is strongest for lamotrigine monotherapy in patients with bipolar depression, in some patients with rapid-cycling bipolar disorder, and as prophylaxis. Evidence for the efficacy of topiramate in acute and refractory mania is promising but comes predominantly from open trials. Although some very small studies have found that oxcarbazepine and zonisamide may have some effectiveness for treating mania, these data are very preliminary. Results are mixed from the 2 small open trials of tiagabine. Although gabapentin is widely used in bipolar disorder, controlled data do not support the use of gabapentin as an antimanic medication or mood stabilizer. Conclusion: More controlled trials are needed to assess the effectiveness of novel antiepileptic medications in bipolar disorder. C1 Massachusetts Gen Hosp, Dept Psychiat, Schizophrenia Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Evins, AE (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. NR 29 TC 33 Z9 36 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2003 VL 64 SU 8 BP 9 EP 14 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 706VA UT WOS:000184474700003 PM 12892536 ER PT J AU Faraone, SV Wilens, T AF Faraone, SV Wilens, T TI Does stimulant treatment lead to substance use disorders? SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Long-Term Safety of Methylphenidate in the Treatment of ADHD CY JAN 18, 2003 CL BOSTON, MASSACHUSETTS ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PRESCRIBED METHYLPHENIDATE; INTRANASAL ABUSE; ADHD AB The authors examine the relationship between the treatment of attention-deficit/hyperactivity disorder (ADHD) with stimulants and substance use disorders by reviewing their published meta-analysis of 6 studies and adding preliminary data from a seventh study. Despite some discrepancies among the findings of the 7 studies, the meta-analysis demonstrated that exposure to stimulant therapy for ADHD does not increase the risk for developing substance use disorders but is, in fact, protective against it. Stimulant treatment of ADHD appears to reduce the risk for substance use disorders by 50%, thus reducing the risk for substance use disorders in ADHD youth to levels well within the normal population risk. The implication of this finding is unquestionably one with enormous value both clinically and as a matter of public health. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Faraone, SV (reprint author), Massachusetts Gen Hosp, WRN 705,55 Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 16 TC 66 Z9 68 U1 1 U2 6 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2003 VL 64 SU 11 BP 9 EP 13 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 727RG UT WOS:000185671800002 PM 14529324 ER PT J AU Hughes, DH Kleespies, PM AF Hughes, DH Kleespies, PM TI Treating aggression in the psychiatric emergency service SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Management of Aggression Across the Life Cycle CY JUN 04, 2002 CL ELECTR NETWORK ID INTRAMUSCULAR HALOPERIDOL; PSYCHOTIC AGITATION; MENTAL DISORDER; DOUBLE-BLIND; DE-POINTES; SCHIZOPHRENIA; RISPERIDONE; LORAZEPAM; VIOLENCE; PATIENT AB Reports indicate that the severely mentally ill, those patients with schizophrenia or bipolar disorder, are at increased risk of being violent to others. They are also at increased risk of being victims of violence or homicide. This article discusses the state of knowledge concerning the 3 most common classes of drugs used to decrease agitation in the psychiatric emergency service setting: benzodiazepines, conventional antipsychotics, and atypical antipsychotics. The decision whether to use benzodiazepines alone versus benzodiazepines combined with an antipsychotic, and whether that antipsychotic should be a conventional or atypical antipsychotic, hinges on considerations of mental health history, need for synergistic sedating effects, and the side effect profiles of the various medications. C1 Boston Med Ctr, Solomon Carter Fuller Hlth Ctr, Boston, MA USA. VA Boston Healthcare Syst, Boston, MA USA. RP Hughes, DH (reprint author), 85 E Newton St, Boston, MA 02118 USA. NR 39 TC 23 Z9 25 U1 2 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2003 VL 64 SU 4 BP 10 EP 15 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 667UL UT WOS:000182252100002 PM 12672260 ER PT J AU Nierenberg, AA Petersen, TJ Alpert, JE AF Nierenberg, AA Petersen, TJ Alpert, JE TI Prevention of relapse and recurrence in depression: The role of long-term pharmacotherapy and psychotherapy SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID COGNITIVE-BEHAVIORAL TREATMENT; WELL-BEING THERAPY; RESIDUAL SYMPTOMS; MAJOR DEPRESSION; MAINTENANCE THERAPIES; REMISSION; UNIPOLAR; DISORDER; PLACEBO; CITALOPRAM AB Major depressive disorder is a chronic disorder, frequently characterized by relapses and recurrences. One of the major risk factors for additional episodes of depression is the presence of residual symptoms that persist after a depressive episode ends; these residual symptoms tend to progress to another depressive episode. Although relapse or recurrence may be prevented with long-term pharmacotherapy, this approach is recommended only for patients at high risk of relapse or recurrence. Patients not at high risk who are effectively treated to full remission have a substantially lower risk of developing another depressive episode. In addition, psychotherapy, alone or combined with medication, has been shown to be effective in preventing further episodes of depression. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 15 Parkman St,WACC 812, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 36 TC 45 Z9 48 U1 2 U2 8 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2003 VL 64 SU 15 BP 13 EP 17 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 751GF UT WOS:000187043900004 PM 14658986 ER PT J AU Cohen, LS AF Cohen, LS TI Gender-specific considerations in the treatment of mood disorders in women across the life cycle SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID PREMENSTRUAL DYSPHORIC DISORDER; ESTROGEN PLUS PROGESTIN; RANDOMIZED CONTROLLED-TRIAL; PHASE SERTRALINE TREATMENT; PLACEBO-CONTROLLED TRIAL; SEROTONIN REUPTAKE INHIBITORS; NATIONAL-COMORBIDITY-SURVEY; OLDER PREMENOPAUSAL WOMEN; HUMAN BREAST-MILK; LUTEAL-PHASE AB Major depressive disorder in women is a significant health concern. Rates of depression in women are approximately twice those seen in men. Observations of gender-based differences in prevalence, presentation, and treatment response in depression raise questions about the underlying causes of such differences. In addition, the specific factors that predict vulnerability to reproductive-associated mood disturbance, including premenstrual dysphoric disorder, postpartum depression, and perimenopausal mood disturbance, remain to be delineated. While a growing amount of controlled data is emerging that describes response to treatment in women who suffer from these disorders, further investigation is needed to identify subgroups of women who are most at risk for depression and to define the most effective treatments for these patients. C1 Harvard Univ, Sch Med, Boston, MA USA. RP Cohen, LS (reprint author), Massachusetts Gen Hosp, Perinatal Psychiat Clin Res Program, 15 Parkman St,WACC 815, Boston, MA 02114 USA. NR 141 TC 12 Z9 12 U1 3 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2003 VL 64 SU 15 BP 18 EP 29 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 751GF UT WOS:000187043900005 PM 14658987 ER PT J AU Mintzer, JE AF Mintzer, JE TI The search for better noncholinergic treatment options for Alzheimer's disease SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Teleconference on Noncholinergic Treatments for Alzheimers Disease CY NOV 25, 2002 CL ELECTR NETWORK ID PLACEBO-CONTROLLED-TRIAL; DOUBLE-BLIND; BEHAVIORAL DISTURBANCES; DEMENTIA; GINKGO; PSYCHOSIS; MEMANTINE; EFFICACY; MEMORY AB Alzheimer's disease is a biological process that involves the disruption of multiple neurochemical pathways. Current treatments for Alzheimer's disease focus on deficits in the cholinergic neurochemical pathway. While newer generation cholinergic agents have a more favorable side effect profile, only a limited, but consistent, degree of efficacy is seen. Treatments are emerging that focus on other areas of neurochemical activity such as oxidative damage, inflammation, glutamatergic neurotransmissions, and serotonergic and dopaminergic pathways. These treatments, supplemented with current cholinergic therapies, may help to ease patients' suffering and caregiver distress. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Mintzer, JE (reprint author), Med Univ S Carolina, 5900 Core Rd,Ste 203, Charleston, SC 29425 USA. NR 15 TC 4 Z9 5 U1 1 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2003 VL 64 SU 9 BP 18 EP 22 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 715ZQ UT WOS:000185004700004 PM 12934970 ER PT J AU Sachs, GS Rush, AJ AF Sachs, GS Rush, AJ TI Response, remission, and recovery in bipolar disorders: What are the realistic treatment goals? SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Roundtable Discussion on Bipolar Disorder - From Clinical Research to Therapeutic Intervention CY JUN 30, 2001 CL BERLIN, GERMANY ID LITHIUM; DISCONTINUATION; ILLNESS; MANIA; RISK AB Bipolar disorder presents particular challenges with regard to assessing response to therapy. Criteria for determining remission and recovery have been suggested for mood disorders, but the clinical usefulness of these terms in bipolar disorder is elusive. Formal psychological rating scales may be impractical in a routine medical practice setting. As an alternative, clinicians might probe for information about particular "signal events," such as sleep disturbances, that may herald mood fluctuations. The ultimate goal of bipolar management should be complete and sustained remission, whenever possible, although most patients will not achieve this status for any significant length of time. Furthermore, overaggressive management might entail pushing medication doses to intolerable levels. Individual treatment goals should always take into account patient acceptance of side effect burden, allowing for trade-offs between treatment effect and quality of life. Noncompliance with therapy, notoriously common among patients suffering from bipolar disorder, can stem from drug side effects, treatment ineffectiveness, or even treatment success if the patient misses the manic symptoms. Despite effective treatment, relapse is common. Realistic treatment goals should strive for sustained symptom abatement while maximizing patient quality of life from visit to visit. C1 Massachusetts Gen Hosp, Harvard Bipolar Res Program, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. RP Sachs, GS (reprint author), Massachusetts Gen Hosp, Harvard Bipolar Res Program, 50 Staniford St,5th Fl, Boston, MA 02114 USA. OI Rush, Augustus/0000-0003-2004-2382 NR 24 TC 26 Z9 28 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2003 VL 64 SU 6 BP 18 EP 22 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 677UU UT WOS:000182827000004 PM 12720476 ER PT J AU Fava, M AF Fava, M TI Depression with physical symptoms: Treating to remission SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID RANDOMIZED CONTROLLED TRIALS; MAJOR DEPRESSION; SOMATIC SYMPTOMS; PRIMARY-CARE; EFFICACY; ANTIDEPRESSANT; PAIN; FLUOXETINE; SEROTONIN; NONRESPONSE AB Depression is a recurrent, often chronic disease consisting of psychological and physical symptoms that are frequently undiagnosed or inadequately treated. While psychological symptoms have been shown to respond to current antidepressants, physical symptoms may not be as responsive. Treating both psychological and physical symptoms of depression may lead to a higher percentage of patients reaching remission. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, ACC 812,15 Parkman St, Boston, MA 02114 USA. EM mfava@partners.org NR 49 TC 26 Z9 26 U1 2 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2003 VL 64 SU 7 BP 24 EP 28 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 683PZ UT WOS:000183159400005 PM 12755649 ER PT J AU Fava, M AF Fava, M TI The role of the serotonergic and noradrenergic neurotransmitter systems in the treatment of psychological and physical symptoms of depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID MAJOR DEPRESSION; ANTIDEPRESSANT-TREATMENT; DIABETIC-NEUROPATHY; PAIN; NOREPINEPHRINE; DISORDERS; PATHOPHYSIOLOGY; TRANSPORTER; STRATEGIES; FLUOXETINE AB Major depressive disorder is a medical condition that includes abnormalities of affect and mood, cognition, and physical functioning. In particular, as many as 76% of patients suffering from depression are found to report somatic symptoms, including various types of pain such as headaches, stomach pain, back pain, and vague, poorly localized pain. Although the pathophysiology of depression is still unknown, there is significant evidence for abnormalities of the norepinephrine (NE) and serotonin (5-HT) neurotransmitter systems in depressive disorders. Interestingly, both 5-HT and NE also appear to exert analgesic effects via descending pain pathways and therefore play a modulating role in pain. There are many effective antidepressant treatments available. However, residual symptoms are relatively common, among both partial responders and responders without remission. A recent study from our group has shown that responders who have not achieved remission have significantly more somatic symptoms than remitters following 8 weeks of treatment with fluoxetine. These data may suggest that antidepressants that are particularly effective in the treatment of pain and painful physical symptoms may yield higher remission rates in major depressive disorder. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, ACC 812,15 Parkman St, Boston, MA 02114 USA. NR 34 TC 37 Z9 39 U1 2 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2003 VL 64 SU 13 BP 26 EP 29 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 736ZD UT WOS:000186202400005 PM 14552653 ER PT J AU Fava, M AF Fava, M TI Symptoms of fatigue and cognitive/executive dysfunction in major depressive disorder before and after antidepressant treatment SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Teleconference on Optimizing Wakefulness in Patients with Fatigue and Executive Dysfunction CY FEB 10, 2003 CL ELECTR NETWORK ID NEUROPSYCHOLOGICAL FUNCTION; HIPPOCAMPAL VOLUME; COGNITIVE FUNCTION; MEMORY IMPAIRMENT; DOUBLE-BLIND; FLUOXETINE; PERFORMANCE; RECURRENT; AUGMENTATION; COMMUNITY AB Patients with major depressive disorder commonly experience fatigue and cognitive/executive dysfunction. These problems may be symptoms of the depression and persist despite effective antidepressant treatment, or these problems may emerge as adverse effects of some antidepressant treatments. A number of augmentation strategies can be employed to manage fatigue or cognitive/executive dysfunction, but the efficacy of these augmentation strategies must be researched further. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,ACC 812, Boston, MA 02114 USA. NR 46 TC 40 Z9 42 U1 5 U2 7 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2003 VL 64 SU 14 BP 30 EP 34 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 747AG UT WOS:000186782400006 PM 14658933 ER PT J AU Nierenberg, AA Papakostas, GI Petersen, T Kelly, KE Iacoviello, BM Worthington, JJ Tedlow, J Alpert, JE Fava, M AF Nierenberg, AA Papakostas, GI Petersen, T Kelly, KE Iacoviello, BM Worthington, JJ Tedlow, J Alpert, JE Fava, M TI Nortriptyline for treatment-resistant depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; MONOAMINE-OXIDASE INHIBITORS; MAJOR DEPRESSION; DOUBLE-BLIND; TRICYCLIC ANTIDEPRESSANTS; REFRACTORY DEPRESSION; FLUOXETINE; EFFICACY; TRANYLCYPROMINE; METAANALYSIS AB Background: Up to 30% of patients with major depression fail to respond to an antidepressant trial, with most taking a selective serotonin reup-take inhibitor (SSRI) as initial treatment. While the tricyclic antidepressants might be effective for SSRI nonresponders, they have been relegated to third- and fourth-line treatment. This study assesses the efficacy of nortriptyline for patients with treatment-resistant major depression. Method: 92 patients with treatment-resistant DSM-III-R major depression, with resistance defined by at least 1, but no more than 5, well-documented adequate trials of antidepressants during the current episode, were treated openly with nortriptyline for 6 weeks. Patients were titrated up to full target doses of nortriptyline within 1 week, with target blood levels of 100 ng/mL. Response was defined as a 50% or greater decrease of baseline 17-item Hamilton Rating Scale for Depression score. We performed an intent-to-treat analysis with the last observation carried forward. Results: Approximately 40% of patients were responders (N = 39) and 12% were remitters (N = 11) after 6 weeks of nortriptyline. Over a third of patients were unable to complete the trial. Conclusion: Nortriptyline was effective for over a third of patients with treatment-resistant depression, and nortriptyline should be considered as potential treatment if patients fail to respond to other antidepressants. C1 Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Depress & Clin Res Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM anierenberg@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R29 MH46952] NR 42 TC 40 Z9 40 U1 3 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JAN PY 2003 VL 64 IS 1 BP 35 EP 39 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 641PQ UT WOS:000180754500007 PM 12590621 ER PT J AU Sachs, GS AF Sachs, GS TI Decision tree for the treatment of bipolar disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Using the Newer Anticonvulsants as Mood Stabilizers in Affective Disorders CY JUL 16, 2001 CL ELECTR NETWORK ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; ACUTE MANIA; LITHIUM-CARBONATE; ADJUNCTIVE THERAPY; MOOD STABILIZER; EFFICACY; DEPRESSION; OLANZAPINE; COMBINATION AB Clinicians managing patients with bipolar disorder confront a myriad of complex treatment decisions. This complexity limits the practicality of treatment guidelines, which attempt to be comprehensive. A user-friendly guide can, however, be constructed by considering only the most common early critical decision points likely to be encountered in the management of bipolar patients: new onset of an acute manic or mixed episode, interepisode treatment entry, and initial treatment for acute bipolar depression. Three general treatment principles, i.e., use proven treatments first, use a mood stabilizer in every phase of the illness, and use a multiphase treatment strategy to link current assessment with an appropriate treatment plan, can be applied to guide decision making at critical decision points that follow entry into clinical care. To guide the selection of appropriate therapeutic agents, a simple grading system can be used to evaluate the weight of evidence supporting use of various options. Multiple high-quality studies with positive results support the use of lithium, divalproex, carbamazepine, olanzapine, and haloperidol as initial intervention for acute mania; other agents with positive results in one double-blind mania trial are reasonable first-line alternatives. In the absence of high-quality evidence to guide treatment selection for nonacutely ill bipolar patients, guidelines recommend maintenance mood-stabilizer treatment. Standard antidepressant medications do not appear to add statistically significant benefit beyond that of mood stabilizers alone; lithium and lamotrigine have shown some benefit, and promising preliminary data have been presented on the antidepressant benefit of divalproex and topiramate as well. C1 Massachusetts Gen Hosp, Partners Bipolar Treatment Ctr, Boston, MA 02114 USA. RP Sachs, GS (reprint author), Partners Bipolar Treatment Ctr, 50 Staniford St,Suite 580, Boston, MA 02114 USA. NR 51 TC 24 Z9 28 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2003 VL 64 SU 8 BP 35 EP 40 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 706VA UT WOS:000184474700007 PM 12892540 ER PT J AU Doyle, AC Pollack, MH AF Doyle, AC Pollack, MH TI Establishment of remission criteria for anxiety disorders SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL-COMORBIDITY-SURVEY; QUALITY-OF-LIFE; PANIC DISORDER; LONGITUDINAL COURSE; MAJOR DEPRESSION; THERAPY; SERTRALINE; IMIPRAMINE; PREVALENCE AB Anxiety disorders such as generalized anxiety disorder, social anxiety disorder, panic disorder, and posttraumatic stress disorder are typically chronic conditions associated with high health care costs and are often accompanied by psychiatric comorbidity, including major depressive disorder, substance abuse, and other anxiety disorders. Anxiety disorders are associated with significant functional impairment in social, vocational, and familial spheres and with diminished overall quality of life. The following clinical overview provides informal guidelines for identifying remission in patients with an anxiety disorder. A systematic approach to treatment that includes patient education, encouragement of exposure, attention to relevant comorbidities, use of empirically proven pharmacotherapies, and psychosocial interventions of adequate intensity and duration will improve outcomes and move patients toward marked improvement and remission. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Anxiety & Traumat Stress Related Disorders, Boston, MA 02114 USA. RP Pollack, MH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Anxiety & Traumat Stress Related Disorders, WAC-812,15 Parkman St, Boston, MA 02114 USA. NR 30 TC 42 Z9 43 U1 2 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2003 VL 64 SU 15 BP 40 EP 45 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 751GF UT WOS:000187043900008 PM 14658990 ER PT J AU Marder, SR Conley, R Ereshefsky, L Kane, JM Turner, MS AF Marder, SR Conley, R Ereshefsky, L Kane, JM Turner, MS TI Clinical guidelines - Dosing and switching strategies for long-acting risperidone SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Teleconference on Partial Compliance: Need for Long Acting Atypical Antipsychotics CY MAR 27, 2002 CL ELECTR NETWORK C1 W Los Angeles Hlth Ctr, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Stobhill Gen Hosp, Glasgow G21 3UW, Lanark, Scotland. Zucker Hillside Hosp, N Shore Long Isl Jewish Hlth Syst, Dept Psychiat, Glen Oaks, NY USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Calif Clin Trials, Los Angeles, CA USA. San Antonio State Hosp, Clin Res Unit, Los Angeles, CA USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Marder, SR (reprint author), W Los Angeles Hlth Ctr, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. NR 4 TC 15 Z9 16 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2003 VL 64 SU 16 BP 41 EP 46 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 753YW UT WOS:000187276800007 PM 14680418 ER PT J AU Huang, LQ Max, M Margolskee, RF Su, H Masland, RH Euler, T AF Huang, LQ Max, M Margolskee, RF Su, H Masland, RH Euler, T TI G protein subunit G gamma 13 is coexpressed with G alpha o, G beta 3, and G beta 4 in retinal ON bipolar cells SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE mammalian retina; transgenic; signal transduction; single cell RT-PCR; gene expression profiling ID TASTE RECEPTOR-CELLS; MAMMALIAN RETINA; CARP RETINA; RAT RETINA; DIFFERENTIAL EXPRESSION; GLUTAMATE RECEPTORS; GANGLION-CELLS; AMACRINE CELLS; ROD; RESPONSES AB We investigated the expression of Ggamma13, a recently discovered G protein subunit, and a selection of Gbeta subunits in retinal bipolar cells, by using a transgenic mouse strain in which green fluorescent protein is strongly expressed in a single type of cone bipolar cell. The cells have ON morphology, and patch-clamp recordings in slices confirmed that they are of the physiological ON type. Immunohistochemistry showed that Ggamma13 is expressed in rod bipolar cells and ON cone bipolar cells, where it is colocalized in the dendrites with Galphao. ON and OFF cone bipolar cells and rod bipolar cells were identified among dissociated cells by their green fluorescence and/or distinct morphology. Hybridization of single-cell polymerase chain reaction products with cDNA probes for G protein subunits Gbeta1 to 5 showed that Gbeta3, Gbeta4, and Ggamma13 are coexpressed in ON bipolar cells but not present in OFF bipolar cells. Gbeta1, 2, and 5 are expressed in partially overlapping subpopulations of cone bipolar cells. Ggamma13 and Gbeta3 and/or Gbeta4, thus, seem selectively to participate in signal transduction by ON bipolar cells. (C) 2002 Wiley-Liss, Inc. C1 CUNY Mt Sinai Sch Med, Dept Physiol & Biophys, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Howard Hughes Med Inst, New York, NY 10029 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. Max Planck Inst Med Res, Dept Biomed Opt, D-69120 Heidelberg, Germany. RP Euler, T (reprint author), Max Planck Inst Met Res, Dept Biomed Opt, Jahnstr 29, D-69120 Heidelberg, Germany. FU NIDCD NIH HHS [DC03155, DC00310]; NIMH NIH HHS [MHS7241] NR 54 TC 81 Z9 83 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JAN 1 PY 2003 VL 455 IS 1 BP 1 EP 10 DI 10.1002/cne.10396 PG 10 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 622FF UT WOS:000179635300001 PM 12454992 ER PT J AU Mukherjee, S Tamayo, P Rogers, S Rifkin, R Engle, A Campbell, C Golub, TR Mesirov, JP AF Mukherjee, S Tamayo, P Rogers, S Rifkin, R Engle, A Campbell, C Golub, TR Mesirov, JP TI Estimating dataset size requirements for classifying DNA microarray data SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE gene expression profiling; molecular pattern recognition; DNA microarrays; microarray analysis; sample size estimation ID GENE-EXPRESSION; STATISTICAL-MECHANICS; CLASSIFICATION; PREDICTION; CARCINOMAS; DISCOVERY; CANCER; ERROR AB A statistical methodology for estimating dataset size requirements for classifying microarray data using learning curves is introduced. The goal is to use existing classification results to estimate dataset size requirements for future classification experiments and to evaluate the gain in accuracy and significance of classifiers built with additional data. The method is based on fitting inverse power-law models to construct empirical learning curves. It also includes a permutation test procedure to assess the statistical significance of classification performance for a given dataset size. This procedure is applied to several molecular classification problems representing a broad spectrum of levels of complexity. C1 MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. MIT, McGovern Inst, Cambridge, MA 02139 USA. MIT, CBCL, Cambridge, MA 02139 USA. Univ Bristol, Dept Engn Math, Bristol BS8 1TH, Avon, England. RP Room 201,Bldg E-25,45 Carleton St, Cambridge, MA 02139 USA. EM sayan@genome.wi.mit.edu OI Mukherjee, Sayan/0000-0002-6715-3920 NR 37 TC 117 Z9 120 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 EI 1557-8666 J9 J COMPUT BIOL JI J. Comput. Biol. PY 2003 VL 10 IS 2 BP 119 EP 142 DI 10.1089/106652703321825928 PG 24 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 680NX UT WOS:000182985200002 PM 12804087 ER PT J AU Kalluri, S Delgutte, B AF Kalluri, S Delgutte, B TI Mathematical models of cochlear nucleus onset neurons: I. Point neuron with many weak synaptic inputs SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Article DE integrate-and-fire model; coincidence detection; cochlear nucleus ID AUDITORY-NERVE FIBERS; DIFFERING SPONTANEOUS RATE; SINGLE UNIT-ACTIVITY; OCTOPUS CELLS; BUSHY CELLS; RESPONSE PROPERTIES; AMPLITUDE-MODULATION; HORSERADISH-PEROXIDASE; COMPUTATIONAL MODEL; REGULARITY ANALYSIS AB The cochlear nucleus ( CN) presents a unique opportunity for quantitatively studying input- output transformations by neurons because it gives rise to a variety of different response types from a relatively homogeneous input source, the auditory nerve ( AN). Particularly interesting among CN neurons are Onset ( On) neurons, which have a prominent response to the onset of sustained sounds followed by little or no response in the steady- state. On neurons contrast sharply with their AN inputs, which respond vigorously throughout stimuli. On neurons can entrain to stimuli ( firing once per cycle of a periodic stimulus) at up to 1000 Hz, unlike their AN inputs. To understand the mechanisms underlying these response patterns, we tested whether an integrate- to- threshold point- neuron model with a fixed refractory period can account for On discharge patterns for tones, systematically examining the effect of membrane time constant and the number and strength of the exclusively excitatory AN synaptic inputs. To produce both onset responses to high- frequency tone bursts and entrainment to a broad range of low- frequency tones, the model must have a short time constant (approximate to 0.125 ms) and a large number (> 100) of weak synaptic inputs, properties that are consistent with the electrical properties and anatomy of On- responding cells. With these parameters, the model acts like a coincidence detector with a threshold- like relationship between the instantaneous discharge rates of the output and the inputs. Onset responses to high- frequency tone bursts result because the threshold effect enhances the initial response of the AN inputs and suppresses their relatively lower sustained response. However, when the model entrains across a broad range of frequencies, it also produces short interspike intervals at the onset of high- frequency tone bursts, a response pattern not found in all types of On neurons. These results show a tradeoff, that may be a general property of many neurons, between following rapid stimulus fluctuations and responding without short interspike intervals at the onset of sustained stimuli. C1 Harvard Univ, MIT,Massachusetts Eye & Ear Infirm, Eaton Peabody Lab,Div Hlth Sci & Technol, Speech & Hearing Sci Program, Boston, MA 02114 USA. MIT, Elect Res Lab, Speech & Hearing Sci Program, Harvard Univ Massachusetts Inst Technol Div Hlth, Cambridge, MA 02139 USA. RP Kalluri, S (reprint author), Harvard Univ, MIT,Massachusetts Eye & Ear Infirm, Eaton Peabody Lab,Div Hlth Sci & Technol, Speech & Hearing Sci Program, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [T32 DC000038, DC-00038, R01 DC002258-08, R01 DC002258, DC-02258] NR 76 TC 18 Z9 18 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5313 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD JAN-FEB PY 2003 VL 14 IS 1 BP 71 EP 90 DI 10.1023/A:1021128418615 PG 20 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA 615LC UT WOS:000179245800005 PM 12435925 ER PT J AU Kalluri, S Delgutte, B AF Kalluri, S Delgutte, B TI Mathematical models of cochlear nucleus onset neurons: II. Model with dynamic spike-blocking state SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Article DE refractory period; state-dependent spike discharge; voltage-gated ion channels; cochlear nucleus ID AUDITORY-NERVE FIBERS; DIFFERING SPONTANEOUS RATE; OCTOPUS CELLS; HORSERADISH-PEROXIDASE; CENTRAL PROJECTIONS; RESPONSE PROPERTIES; ACTION-POTENTIALS; BUSHY CELLS; CAT; CURRENTS AB Onset ( On) neurons in the cochlear nucleus ( CN), characterized by their prominent response to the onset followed by little or no response to the steady- state of sustained stimuli, have a remarkable ability to entrain ( firing 1 spike per cycle of a periodic stimulus) to low- frequency tones up to 1000 Hz. In this article, we present a point- neuron model with independent, excitatory auditory- nerve ( AN) inputs that accounts for the ability of On neurons to both produce onset responses for high- frequency tone bursts and entrain to a wide range of low- frequency tones. With a fixed- duration spike- blocking state after a spike ( an absolute refractory period), the model produces entrainment to a broad range of low- frequency tones and an On response with short interspike intervals ( chopping) for high- frequency tone bursts. To produce On response patterns with no chopping, we introduce a novel, more complex, active membrane model in which the spike- blocking state is maintained until the instantaneous membrane voltage falls below a transition voltage. During the sustained depolarization for a high- frequency tone burst, the new model does not chop because it enters a spike- blocking state after the first spike and fails to leave this state until the membrane voltage returns toward rest at the end of the stimulus. The model entrains to low- frequency tones because the membrane voltage falls below the transition voltage on every cycle when the AN inputs are phase- locked. With the complex membrane model, On response patterns having moderate steady- state activity for high- frequency tone bursts ( On- L) are distinguished from those having no steady- state activity ( On- I) by requiring fewer AN inputs. Voltage- gated ion channels found in On- responding neurons of the CN may underlie the hypothesized dynamic spike- blocking state. These results provide a mechanistic rationale for distinguishing between the different physiological classes of CN On neurons. C1 Harvard Univ, MIT,Massachusetts Eye & Ear Infirm, Eaton Peabody Lab,Div Hlth Sci & Technol, Speech & Hearing Sci Program, Boston, MA 02114 USA. MIT, Elect Res Lab, Speech & Hearing Sci Program, Harvard Univ Massachusetts Inst Technol Div Hlth, Cambridge, MA 02139 USA. RP Kalluri, S (reprint author), Harvard Univ, MIT,Massachusetts Eye & Ear Infirm, Eaton Peabody Lab,Div Hlth Sci & Technol, Speech & Hearing Sci Program, 243 Charles St,, Boston, MA 02114 USA. FU NIDCD NIH HHS [T32 DC000038, DC-00038, R01 DC002258-08, R01 DC002258, DC-02258] NR 41 TC 13 Z9 13 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5313 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD JAN-FEB PY 2003 VL 14 IS 1 BP 91 EP 110 DI 10.1023/A:1021180419523 PG 20 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA 615LC UT WOS:000179245800006 PM 12435926 ER PT J AU Voldman, J Toner, M Gray, ML Schmidt, MA AF Voldman, J Toner, M Gray, ML Schmidt, MA TI Design and analysis of extruded quadrupolar dielectrophoretic traps SO JOURNAL OF ELECTROSTATICS LA English DT Article DE dielectrophoretic levitation; quadrupolar traps; cell analysis ID LIVING CELLS; FIELD; CAGES; ELECTROROTATION; MANIPULATION; LEVITATION; FLOW AB We present the design and experimental analysis of a dielectrophoretic trap composed of four microfabricated gold posts excited in a quadrupolar fashion. Using quantitative modeling tools, we have designed these extruded traps to attain strong holding against flow while being constrained by a set of system parameters. The extruded geometry consists of cylindrical electrodes in a trapezoidal arrangement and substrate-interconnect shunts. The traps can be individually electrically switched, are easily arrayable, and are amenable to batch fabrication. We have verified the predicted performance of the extruded traps by measuring holding of beads against flows and comparing to the model predictions. The results demonstrate that extruded quadrupolar traps exhibit strong particle confinement and that the modeling tools can be used for a priori design of dielectrophoresis-based single-particle traps. (C) 2002 Elsevier Science B.V. All rights reserved. C1 MIT, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. RP Voldman, J (reprint author), MIT, Dept Genet, Boston, MA 02115 USA. NR 24 TC 99 Z9 101 U1 2 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3886 J9 J ELECTROSTAT JI J. Electrost. PD JAN PY 2003 VL 57 IS 1 BP 69 EP 90 AR PII S0304-3886(02)00120-1 DI 10.1016/S0304-3886(02)00120-1 PG 22 WC Engineering, Electrical & Electronic SC Engineering GA 618UH UT WOS:000179435300007 ER PT J AU Thomsen, T Brown, DFM Nadel, ES AF Thomsen, T Brown, DFM Nadel, ES TI Abdominal pain in first trimester pregnancy SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID ECTOPIC PREGNANCY; HETEROTOPIC PREGNANCY; MANAGEMENT C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Emergency Med Residency, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, CLN-115, Boston, MA 02114 USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JAN PY 2003 VL 24 IS 1 BP 55 EP 58 DI 10.1016/S0736-4679(02)00666-2 PG 4 WC Emergency Medicine SC Emergency Medicine GA 638RY UT WOS:000180585200009 PM 12554040 ER PT J AU Pandol, SJ Gukovsky, I Satoh, A Lugea, A Gukovskaya, AS AF Pandol, SJ Gukovsky, I Satoh, A Lugea, A Gukovskaya, AS TI Emerging concepts for the mechanism of alcoholic pancreatitis from experimental models SO JOURNAL OF GASTROENTEROLOGY LA English DT Review DE alcohol; pancreatitis; cholecytokinin; fatty acid ethyl esters; nuclear factor-kappa B ID NF-KAPPA-B; ACID ETHYL-ESTERS; ACINAR-CELLS; STELLATE CELLS; NONOXIDATIVE METABOLITES; ETHANOL-METABOLISM; INHIBITORY FACTOR; GENE-EXPRESSION; ACTIVATION; RAT AB The pathophysiologic mechanisms that underlie acute and chronic pancreatitis arising from alcohol abuse are poorly understood. The reasons for this state of knowledge result historically from a lack of models for experimental investigation. Ethanol feeding alone, even at high doses, has minimal and inconsistent effects on morphologic findings in the pancreas in experimental animals. This experience, plus the fact that alcohol abuse causes pancreatic pathology in only a minority of patients, suggest that ethanol acts to sensitize the pancreas to the deleterious effects of other stimuli. In this article, we discuss findings to support this concept of ethanol as a sensitizing agent and experimental models developed that can be used to investigate the effects of ethanol on the pathologic processes of pancreatitis. These pathologic processes include inflammation, cell death, intrapancreatic digestive enzyme activation, and fibrosis. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, W Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. USC UCLA, Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA USA. RP Pandol, SJ (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, W Los Angeles Healthcare Ctr, Bldg 258,Room 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIAAA NIH HHS [P50 AA 11999]; NIDDK NIH HHS [DK 59936, DK 59508] NR 63 TC 21 Z9 24 U1 0 U2 0 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 0944-1174 J9 J GASTROENTEROL JI J. Gastroenterol. PY 2003 VL 38 IS 7 BP 623 EP 628 DI 10.1007/s00535-003-1134-7 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 706KH UT WOS:000184452500001 PM 12898353 ER PT J AU Hedrick, SC Chaney, EF Felker, B Liu, CF Hasenberg, N Heagerty, P Buchanan, J Bagala, R Greenberg, D Paden, G Fihn, SD Katon, W AF Hedrick, SC Chaney, EF Felker, B Liu, CF Hasenberg, N Heagerty, P Buchanan, J Bagala, R Greenberg, D Paden, G Fihn, SD Katon, W TI Effectiveness of collaborative care depression treatment in veterans' affairs primary care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE depressive disorder; primary health care; veterans ID RANDOMIZED CONTROLLED TRIAL; HEALTH-CARE; ANTIDEPRESSANT TREATMENT; IMPROVE TREATMENT; MAJOR DEPRESSION; MANAGEMENT; GUIDELINES; POPULATION; DISORDERS; SYMPTOMS AB OBJECTIVE: To compare collaborative care for treatment of depression in primary care with consult-liaison (CL) care. In collaborative care, a mental health team provided a treatment plan to the primary care provider, telephoned patients to support adherence to the plan, reviewed treatment results, and suggested modifications to the provider. In CL care, study clinicians informed the primary care provider of the diagnosis and facilitated referrals to psychiatry residents practicing in the primary care clinic. DESIGN: Patients were randomly assigned to treatment model by clinic firm. SETTING: VA primary care clinic. PARTICIPANTS: One hundred sixty-eight collaborative care and 186 CL patients who met criteria for major depression and/or dysthymia. MEASUREMENTS: Hopkins Symptom Checklist (SCL-20), Short Form (SF)-36, Sheehan Disability Scale. MAIN RESULTS: Collaborative care produced greater improvement than CL in depressive symptomatology from baseline to 3 months (SCL-20 change scores), but at 9 months there was no significant difference. The intervention increased the proportion of patients receiving prescriptions and cognitive behavioral therapy. Collaborative care produced significantly greater improvement on the Sheehan at 3 months. A greater proportion of collaborative care patients exhibited an improvement in SF-36 Mental Component Score of 5 points or more from baseline to 9 months. CONCLUSIONS: Collaborative care resulted in more rapid improvement in depression symptomatology, and a more rapid and sustained improvement in mental health status compared to the more standard model. Mounting evidence indicates that collaboration between primary care providers and mental health specialists can improve depression treatment and supports the necessary changes in clinic structure and incentives. C1 VA Puget Sound Hlth Care Syst, HSR&D 152, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. VA Puget Sound, Med Serv, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Sch Social Work, Seattle, WA 98195 USA. RP Hedrick, SC (reprint author), VA Puget Sound Hlth Care Syst, HSR&D 152, Hlth Serv Res & Dev Ctr Excellence, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 49 TC 120 Z9 120 U1 0 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2003 VL 18 IS 1 BP 9 EP 16 DI 10.1046/j.1525-1497.2003.11109.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 634QU UT WOS:000180352600002 PM 12534758 ER PT J AU Thomas, EJ Petersen, LA AF Thomas, EJ Petersen, LA TI Measuring errors and adverse events in health care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE medical error; adverse events; patient safety; measurement ID COMPLICATIONS SCREENING-PROGRAM; OF-MEDICINE REPORT; ADMINISTRATIVE DATA; DRUG EVENTS; QUALITY; CRITERIA; ANESTHESIA; VALIDATION; EXPLICIT; SYSTEMS AB In this paper, we identify 8 methods used to measure errors and adverse events in health care and discuss their strengths and weaknesses. We focus on the reliability and validity of each, as well as the ability to detect latent errors (or system errors) versus active errors and adverse events. We propose a general framework to help health care providers, researchers, and administrators choose the most appropriate methods to meet their patient safety measurement goals. C1 Univ Texas, Sch Med, Ctr Clin Res & Evidence Based Med, Div Gen Med, Houston, TX 77030 USA. Univ Texas, Sch Med, Dept Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. RP Thomas, EJ (reprint author), Univ Texas, Sch Med, Ctr Clin Res & Evidence Based Med, Div Gen Med, 6431 Fannin MSB 1-122, Houston, TX 77030 USA. NR 54 TC 171 Z9 177 U1 5 U2 14 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2003 VL 18 IS 1 BP 61 EP 67 DI 10.1046/j.1525-1497.2003.20147.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 634QU UT WOS:000180352600010 PM 12534766 ER PT J AU Carpenter, KM Watson, JM Raffety, B Chabal, C AF Carpenter, KM Watson, JM Raffety, B Chabal, C TI Teaching brief interventions for smoking cessation via an interactive computer-based tutorial SO JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article DE e-learning; motivational interviewing; smoking cessation ID PRIMARY-CARE; PHYSICIANS; PRACTITIONERS; PREVENTION; STRATEGIES; DENTISTS; SKILLS; ADVICE; STAGE AB Many current smokers do not plan on quitting any time soon. For these smokers, the immediate treatment goal is not a quit attempt, but an increase in readiness to stop smoking. In the present study we developed an interactive multimedia simulation and tutoring environment that teaches healthcare professionals to provide brief motivational interviewing-based smoking cessation interventions tailored to the patient's current readiness to change. This tutorial utilizes a cognitive science-derived learning approach that provides tailored feedback and lessons based on learners pre-existing knowledge, is highly interactive and allows learners to practice skills in simulated clinical situations. Results from two pilot studies indicate that healthcare professionals and students found the software easy and enjoyable to use and successfully learned MI-based strategies for smoking cessation. C1 Talaria Inc, Seattle, WA 98104 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. RP Carpenter, KM (reprint author), Talaria Inc, 821 2nd Ave,Suite 1150, Seattle, WA 98104 USA. FU NCI NIH HHS [R43 CA088569] NR 44 TC 8 Z9 8 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON EC2A 4PU, ENGLAND SN 1359-1053 J9 J HEALTH PSYCHOL JI J. Health Psychol. PD JAN PY 2003 VL 8 IS 1 BP 149 EP 160 DI 10.1177/1359105303008001450 PG 12 WC Psychology, Clinical SC Psychology GA 640GZ UT WOS:000180681500012 PM 22113907 ER PT J AU Mar, CM Chabal, C Anderson, RA Vore, AE AF Mar, CM Chabal, C Anderson, RA Vore, AE TI An interactive computer tutorial to teach pain assessment SO JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article DE communication skills; computer-assisted learning; nurse education; pain assessment; role-play ID ELDERLY PATIENTS; MANAGEMENT; LIFE; PHYSICS; CANCER; SKILLS; CARE; END AB Under-treated pain is a significant problem. Health care institutions are under increasing pressure from patients and accreditation bodies to improve staff training in pain management. Pain assessment, a necessary pre-cursor to good pain management, is a complex multi-step process requiring sophisticated understanding and superior communication skills. This article describes the development and usability testing of an interactive, Internet-deliverable, multimedia tutorial to teach best practice pain assessment. The software platform allowed non-programmers to create multimedia tutorials and included the capability to simulate role-plays. The tutorial was designed to actively engage and respond to the learner and to include skills practice. Twenty-five nurses took the tutorial and rated it positively on a usability questionnaire in terms of ease-of-use and learning method. C1 Talaria Inc, Seattle, WA 98104 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Talaria Inc, Seattle, WA USA. RP Mar, CM (reprint author), Talaria Inc, 821 2nd Ave,Suite 1150, Seattle, WA 98104 USA. NR 30 TC 1 Z9 1 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON EC2A 4PU, ENGLAND SN 1359-1053 J9 J HEALTH PSYCHOL JI J. Health Psychol. PD JAN PY 2003 VL 8 IS 1 BP 161 EP 173 DI 10.1177/1359105303008001454 PG 13 WC Psychology, Clinical SC Psychology GA 640GZ UT WOS:000180681500013 PM 22113908 ER PT J AU Ogino, S Wilson, RB AF Ogino, S Wilson, RB TI Genotype and haplotype distributions of MTHFR 677C > T and 1298A > C single nucleotide polymorphisms: a meta-analysis SO JOURNAL OF HUMAN GENETICS LA English DT Article DE MTHFR; 677C > T; 1298A > C; SNP; cis; haplotype; frequency; meta-analysis ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; NEURAL-TUBE DEFECTS; CORONARY-ARTERY DISEASE; RISK FACTOR; HOMOCYSTEINE LEVELS; COMMON MUTATION; PLASMA HOMOCYSTEINE; VASCULAR-DISEASE; ACUTE-LEUKEMIA; A1298C AB Common single nucleotide polymorphisms (SNPs; 677C>T and 1298A>C) in the methylenetetrahydrofolate reductase gene (MTHFR) decrease the activity of the enzyme, leading to hyperhomocysteinemia, particularly in folate-deficient states. We calculate herein the haplotype frequencies of the MTHFR 677 and 1298 polymorphisms in pooled general populations derived from published data. We selected 16 articles that provided reliable data on combined MTHFR genotypes in general populations (n = 5389). The combined data comprised the following totals for each genotype at nucleotide positions 677 and 1298: 838 CC/AA (i.e., 677CC/1298AA), 1225 CC/AC, 489 CC/CC, 1120 CT/AA, 1093 CT/AC, 8 CT/CC, 606 TT/AA, 10 TT/ AC, and 0 TT/CC. The estimated haplotype frequencies, and the fractional contribution of each, were 677C/1298A, 0.37; 677C/1298C, 0.31; 677T/1298A, 0.32; and 677T/1298C, 0.0023 to 0.0034. Thus, a vast majority of 677T alleles and 1298C alleles are associated with 1298A alleles and 677C alleles, respectively. There may be an increased frequency of the very rare cis 677T/1298C haplotype in some parts of the United Kingdom and Canada, possibly due to a founder effect. Further studies on both SNPs are needed to determine their exact role in various clinical settings. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Penn, Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Ogino, S (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St,Amory 3rd Floor, Boston, MA 02115 USA. NR 28 TC 86 Z9 94 U1 0 U2 8 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 1434-5161 J9 J HUM GENET JI J. Hum. Genet. PY 2003 VL 48 IS 1 BP 1 EP 7 DI 10.1007/s100380300000 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 641RB UT WOS:000180758700001 PM 12560871 ER PT J AU Pozdnyakova, O Guttormsen, HK Lalani, FN Carroll, MC Kasper, DL AF Pozdnyakova, O Guttormsen, HK Lalani, FN Carroll, MC Kasper, DL TI Impaired antibody response to group B streptococcal type III capsular polysaccharide in C3-and complement receptor 2-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MARGINAL ZONE MACROPHAGES; IMMUNE-RESPONSE; HUMORAL RESPONSE; MANNOSE RECEPTOR; GERMINAL-CENTERS; CELL-DEVELOPMENT; LYMPHOCYTES-B; LYMPH-NODE; ANTIGENS; C3 AB Group B Streptococcus (GBS) is the foremost bacterial cause of serious neonatal infections. Protective immunity to GBS is mediated by specific Abs to the organism's capsular polysaccharide Ags. To examine the role of complement in the humoral immune response to type III GBS capsular polysaccharide (III-PS), mice deficient in C3 or in CD21/CD35 (i.e., complement receptors 1 and 2; CR1/CR2) were immunized with III-PS. Mice deficient in C3 or Cr2 had an impaired primary immune response to HI-PS. The defective response was characterized by low IgM levels and the lack of an isotype switch from IgM to IgG Ab production. Compared with wild-type mice, C3- and Cr2-deficient mice exhibited decreased uptake of III-PS by follicular dendritic cells within the germinal centers and impaired localization of III-PS to the marginal zone B cells. Complement-dependent uptake of capsular polysaccharide by marginal zone B cells appears necessary for an effective immune response to III-PS. The normal immune response in wild-type mice may require localization of polysaccharide to marginal zone B cells with subsequent transfer of the Ag to follicular dendritic cells. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. RP Kasper, DL (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [1R01 AI36389, AI23339] NR 38 TC 60 Z9 61 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2003 VL 170 IS 1 BP 84 EP 90 PG 7 WC Immunology SC Immunology GA 630KT UT WOS:000180106600013 PM 12496386 ER PT J AU Yan, G Shi, LJ Penfornis, A Faustman, DL AF Yan, G Shi, LJ Penfornis, A Faustman, DL TI Impaired processing and presentation by MHC class II proteins in human diabetic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COMPLEX CLASS-II; INVARIANT CHAIN COMPLEXES; HLA-DR MOLECULES; INTRACELLULAR-TRANSPORT; DENDRITIC CELLS; PEPTIDE; ANTIGEN; COMPARTMENTS; BINDING; PHOSPHORYLATION AB The biochemical processing of and Ag presentation by MHC class II molecules were examined in B cell lines derived from pairs of identical twins discordant for type 1 diabetes. MHC class II defects detected exclusively in cells derived from the twins with autoimmunity included increased rates of transport to and subsequent turnover at the cell surface, inadequate glycosylation, and a reduced display at the cell surface of antigenic peptides. These defects appeared to be secondary to a decreased abundance of the p35 isoform of the invariant chain (Ii), a human-specific chaperone protein for MHC class II normally generated by use of an alternative translation start site. Stable transfection of diabetic B cell lines with an Ii p35 expression vector corrected the defects in MHC class II processing and peptide presentation. A defect in the expression of Ii p35 may thus result in impairment of Ag presentation by MHC class II molecules and thereby contribute to the development of type I diabetes in at-risk genotypes. C1 Massachusetts Gen Hosp, Immunobiol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Faustman, DL (reprint author), Massachusetts Gen Hosp E, Immunobiol Lab, Bldg 149,13th St,CNY-3601, Charlestown, MA 02129 USA. NR 30 TC 13 Z9 13 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2003 VL 170 IS 1 BP 620 EP 627 PG 8 WC Immunology SC Immunology GA 630KT UT WOS:000180106600078 PM 12496451 ER PT J AU Tierney, C Lathey, JL Christopherson, C Bettendorf, DM D'Aquila, RT Hammer, SM Katzenstein, DA AF Tierney, C Lathey, JL Christopherson, C Bettendorf, DM D'Aquila, RT Hammer, SM Katzenstein, DA CA AIDS Clin Trial Grp TI Prognostic value of baseline human immunodeficiency virus type 1 DNA measurement for disease progression in patients receiving nucleoside therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID BLOOD MONONUCLEAR-CELLS; HIV-INFECTED ADULTS; ANTIRETROVIRAL THERAPY; REPLICATION-COMPETENT; COMBINATION THERAPY; CUBIC MILLIMETER; T-CELLS; PLASMA; ASSAY; RNA AB Human immunodeficiency virus (HIV) type 1 DNA assay data were obtained at baseline from 111 HIV-1-positive subjects who were treated with nucleosides. Higher baseline DNA level, HIV-1 RNA level, and infectious titer were comparably associated with an increased hazard of disease progression (each P < .03). Only DNA level was significantly associated with survival (adjusted hazard ratio for 1 log(10) higher level, 3.99; 95% confidence interval, 1.44-11.09; P = .008). C1 Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. Roche Mol Syst, Alameda, CA USA. Stanford Univ, Dept Med, Palo Alto, CA 94304 USA. Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. RP Tierney, C (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, 651 Huntington Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [AI-46339, AI-46386, AI-27670, AI-29193, AI-36214, AI-42848, AI-48013] NR 16 TC 36 Z9 36 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2003 VL 187 IS 1 BP 144 EP 148 DI 10.1086/345870 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 625GZ UT WOS:000179809900021 PM 12508159 ER PT J AU Yano, K Brown, LF Lawler, J Miyakawa, T Detmar, M AF Yano, K Brown, LF Lawler, J Miyakawa, T Detmar, M TI Thrombospondin-1 plays a critical role in the induction of hair follicle involution and vascular regression during the catagen phase SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE TSP-1; angiogenesis; VEGF ID GROWTH; ANGIOGENESIS; SKIN; OVEREXPRESSION AB Hair growth is associated with pronounced vascular-endothelial-growth-factor-induced perifollicular angiogenesis, whereas the catagen regression phase is characterized by apoptosis-driven blood vessel regression. The biologic relevance of endogenous inhibitors of angiogenesis in the control of hair cycling, however, has remained unknown. We studied the expression and biologic role of the angiogenesis inhibitor thrombospondin-1 (TSP-1) during the induced adult hair follicle cycle in wild-type, TSP-1 deficient, and TSP-1 overexpressing transgenic mice. TSP-1 expression was absent from hair bulb and dermal papilla cells during early to mid-anagen but was highly upregulated throughout the catagen involution phase. In TSP-1 deficient mice, the follicle growth phase was significantly prolonged, associated with increased perifollicular vascularization and vascular proliferation. Conversely, hair follicle growth was delayed in K14/TSP-1 transgenic mice that expressed high levels of TSP-1 in outer root sheath keratinocytes, associated with reduced perifollicular vascularization. These effects were most probably mediated via its antiangiogenic effects because TSP-1 did not affect the growth of cultured murine vibrissae in the absence of a functional vascular system. These results identify a critical role of TSP-1 in the induction of anagen follicle involution, with potential implications for the therapeutic modulation of hair follicle growth. C1 Massachusetts Gen Hosp, Dept Dermatol, CBRC, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Hiroshima Univ, Dept Mol Biotechnol, Higashihiroshima 724, Japan. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Dept Dermatol, CBRC, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA91861, CA69184, CA86410]; NHLBI NIH HHS [HL68003] NR 23 TC 26 Z9 28 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2003 VL 120 IS 1 BP 14 EP 19 DI 10.1046/j.1523-1747.2003.12045.x PG 6 WC Dermatology SC Dermatology GA 635TP UT WOS:000180415700006 PM 12535193 ER PT J AU Beare, AHM O'Kane, S Krane, SM Ferguson, MWJ AF Beare, AHM O'Kane, S Krane, SM Ferguson, MWJ TI Severely impaired wound healing in the collagenase-resistant mouse SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE collagen; matrix metalloproteinases; tissue repair; transgenic mice; wound healing ID I COLLAGEN; INTERSTITIAL COLLAGENASE; MATRIX METALLOPROTEINASE-2; HUMAN-SKIN; EXPRESSION; GENE; CONTRACTION; FIBROBLASTS; CLEAVAGE; MICE AB Collagen in the skin undergoes dramatic reorganization during wound repair. Matrix metalloproteinases degrade and remodel the collagen in a tightly controlled process. The collagenase-resistant mouse, Col1a1(tm1Jae) , has been developed to produce collagen type I, which is resistant to degradation by human matrix metalloproteinase 1. These mice grow normally but develop thickened skin with age. We investigated the effect of this mutant collagen on wound repair. Incisional wounds were made on Col1a1(tm1Jae) homozygous mutant (Col1a1(r/r) ) and wild-type (Col1a1(+/+)) mice and these wounds were harvested at 1 and 6 h, 1, 2, 3, 7, 10, 14, and 70 d post wounding. Wound healing was severely delayed in Col1a1(r/r) wounds, with wounds remaining significantly wider than wild-type for the first 2 wk after injury. Reepithelialization of the Col1a1(r/r) wounds took 7 d longer than in the wild-type. The Col1a1(r/r) wounds had a prolonged early inflammatory response. Immunostaining for matrix metalloproteinases revealed significant upregulation of matrix metalloproteinase 13 in Col1a1(r/r) wounds, but minimal changes in other matrix metalloproteinases. There was no significant difference in scarring between Col1a1(r/r) and Col1a1(+/+) wounds after 70 d. C1 Univ Manchester, Sch Biol Sci, Div Immunol Microbiol & Dev, Manchester M13 9PT, Lancs, England. Univ Manchester, Sch Biol Sci, UK Ctr Tissue Engn, Manchester M13 9PT, Lancs, England. Harvard Med Sch, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. RP Ferguson, MWJ (reprint author), Univ Manchester, Sch Biol Sci, Div Immunol Microbiol & Dev, 3-239 Stopford Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England. NR 32 TC 38 Z9 40 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2003 VL 120 IS 1 BP 153 EP 163 DI 10.1046/j.1523-1747.2003.12019.x PG 11 WC Dermatology SC Dermatology GA 635TP UT WOS:000180415700025 PM 12535212 ER PT J AU Yin, L Schneider, H Rudd, CE AF Yin, L Schneider, H Rudd, CE TI Short cytoplasmic SDYMNM segment of CD28 is sufficient to convert CTLA-4 to a positive signaling receptor SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE coreceptor; phosphatidylinositol 3-kinase ID KINASE PHOSPHATIDYLINOSITOL 3-KINASE; JURKAT T-CELLS; COSTIMULATION; BINDING; EXPRESSION; ENDOCYTOSIS; STIMULATION; ACTIVATION; MUTATIONS; INTERACTS AB CD28 and cytotoxic T-lymphocyte antigen (CTLA)-4 are key coreceptors on the surface of T cells that have opposing effects on T cell activation. Although CD28 enhances proliferation, CTLA-4 markedly inhibits the activation process. These opposing roles are particularly surprising given the structural similarity of the cytoplasmic residues of the two receptors. These include the related CD28(SDYMNM) and CTLA-4(GVYVKM) Motifs' In this study, we have directly addressed whether these related motifs may play different roles in the activation process by swapping the CTLA-4(GVYVKM) motif with the CD28(SDYMNM) motif. Remarkably, stable transfectants of the T cell hybridoma DC27.10 showed that substitution of CTLA-4(GVYVKM) was sufficient to convert CTLA-4 from a negative signaling coreceptor to a positive CD28-like coreceptor. CD28(SDYMNM) is therefore sufficient to convey positive signals within CTLA-4. These results demonstrate that CD28(SYMNM) and CTLA-4(GVYVKM) motifs contain sufficient information to distinguish positive versus negative coreceptor signaling in T cells. C1 Univ London Imperial Coll Sci Technol & Med, Dept Haematol, Div Invest Sci, Fac Med, London W12 0NN, England. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rudd, CE (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Haematol, Div Invest Sci, Fac Med, Hammersmith Hosp Campus,Du Cane Rd, London W12 0NN, England. NR 27 TC 6 Z9 7 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JAN PY 2003 VL 73 IS 1 BP 178 EP 182 DI 10.1189/jlb.0702365 PG 5 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 636MY UT WOS:000180460900019 PM 12525576 ER PT J AU Rosenberger, TA Villacreses, NE Contreras, MA Bonventre, JV Rapoport, SI AF Rosenberger, TA Villacreses, NE Contreras, MA Bonventre, JV Rapoport, SI TI Brain lipid metabolism in the cPLA(2) knockout mouse SO JOURNAL OF LIPID RESEARCH LA English DT Article DE arachidonate; docosahexaenoate; phospholipase A(2); phospholipid; turnover; kinetics ID CYTOSOLIC PHOSPHOLIPASE A(2); PERFORMANCE LIQUID-CHROMATOGRAPHY; POLYUNSATURATED FATTY-ACIDS; CHRONIC LITHIUM TREATMENT; ACYL-COA SYNTHETASE; ARACHIDONIC-ACID; RAT-BRAIN; INTRACELLULAR CALCIUM; SIGNAL-TRANSDUCTION; TREATMENT DECREASES AB We examined brain phospholipid metabolism in mice in which the cytosolic phospholipase A(2) (cPLA(2) Type IV, 85 kDa) was knocked out (cPLA(2)(-/-) mice). Compared with controls, these mice demonstrated altered brain concentrations of several phospholipids, reduced esterified linoleate, arachidonate, and docosahexaenoate in choline glycerophospholipid, and reduced esterified arachidonate in phosphatidylinositol. Unanesthetized cPLA(2)(-/-) mice had reduced rates of incorporation of unlabeled arachidonate from plasma and from the brain arachidonoyl-CoA pool into ethanolamine glycerophospholipid and choline glycerophospholipid, but elevated rates into phosphatidylinositol. These differences corresponded to altered turnover and metabolic loss of esterified brain arachidonate. These results suggests that cPLA(2) is necessary to maintain normal brain concentrations of phospholipids and of their esterified polyunsaturated fatty acids. M Reduced esterified arachidonate and docosahexaenoate may account for the resistance of the cPLA(2)(-/-) mouse to middle cerebral artery occlusion, and should influence membrane fluidity, neuroinflammation, signal transduction, and other brain processes. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. RP Rosenberger, TA (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. NR 75 TC 43 Z9 45 U1 0 U2 3 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JAN PY 2003 VL 44 IS 1 BP 109 EP 117 DI 10.1194/jlr.M200298-JLR200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 636VT UT WOS:000180478500013 PM 12518029 ER PT J AU Tseng, WYI Wedeen, VJ Reese, TG Smith, RN Halpern, EF AF Tseng, WYI Wedeen, VJ Reese, TG Smith, RN Halpern, EF TI Diffusion tensor MRI of myocardial fibers and sheets: Correspondence with visible cut-face texture SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE MRI; diffusion tensor; myocardium; validation; architecture ID ORIENTATION; SHEAR; HEART; NMR AB Purpose: To test the hypothesis that the primary, secondary, and tertiary eigenvectors of the diffusion tensor (DT) measured with DT-MRI correspond to the fiber, sheet, and sheet normal directions, respectively, we compared DT-MRI data with the texture visible in the cut face of fresh bovine myocardium. Materials and Methods: DT-MRI and optical images obtained under identical conditions were compared objectively. Ink prints were made of the cut tissue, and the local orientations within these images were defined by analysis of local autocorrelations for regions matching DT-MRI pixels. Deviation angles between the cleavage orientations and the diffusion eigenvectors were analyzed in eight specimens sliced in three orthogonal planes. Results: Root mean-square (RMS) angular disparity was 11degrees between the first eigenvectors of the DT and the fiber direction 14degrees between the second eigenvector and the sheet direction, 14degrees between the third eigenvector and the sheet normal direction, and 15degrees between the tensor orientation in the imaging plane and the cleavage orientation of the cut face. Conclusion: the results support a parallel relationship between the eigenvectors of the DT and symmetry axes of the myocardial architecture. Specifically, the first, second, and third eigenvectors correspond to the fiber, sheet, and sheet normal directions, respectively. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr,Dept Radiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Natl Taiwan Univ, Coll Med, Ctr Optoelect Biomed, Taipei 10018, Taiwan. Natl Taiwan Univ Hosp, Dept Radiol, Taipei, Taiwan. RP Wedeen, VJ (reprint author), MGH NMR Ctr, Bldg 149,2nd Floor,13th St, Charlestown, MA 02129 USA. OI Tseng, Wen-Yih Isaac/0000-0002-2314-6868 FU NHLBI NIH HHS [1R01-HL56737]; NIMH NIH HHS [MH64044] NR 21 TC 95 Z9 98 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JAN PY 2003 VL 17 IS 1 BP 31 EP 42 DI 10.1002/jmri.10223 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 674VQ UT WOS:000182657900004 PM 12500272 ER PT J AU O'Farrell, TJ Fals-Stewart, W AF O'Farrell, TJ Fals-Stewart, W TI Alcohol abuse SO JOURNAL OF MARITAL AND FAMILY THERAPY LA English DT Review ID BEHAVIORAL MARITAL-THERAPY; RELAPSE PREVENTION SESSIONS; COMMUNITY-REINFORCEMENT APPROACH; COST-EFFECTIVENESS ANALYSES; FAMILY-THERAPY; COUPLES THERAPY; HEAVY DRINKERS; UNILATERAL INTERVENTION; DISULFIRAM TREATMENT; SIGNIFICANT OTHERS AB We reviewed 38 controlled studies of marital and family therapy (MFT) in alcoholism treatment. We conclude that, when the alcoholic is unwilling to seek help, MFT is effective in helping the family cope better and motivating alcoholics to enter treatment. Specifically, (a) Al-Anon-facilitation and referral help family members cope better; (b) Community Reinforcement and Family Training promotes treatment entry; and (c) the popular Johnson intervention apparently does not effectively promote treatment entry. Once the alcoholic enters treatment, MFT, particularly behavioral couples therapy (BCT), is clearly more effective than individual treatment at increasing abstinence and improving relationship functioning. BCT also reduces social costs, domestic violence, and emotional problems of the couple's children. Future studies need to specifically evaluate: MFT with women and with minority patients, mechanisms and processes of change, and transportability of evidence-based MFT approaches to clinical practice settings. C1 Harvard Univ, Sch Med, Dept Psychiat,VA Boston Healthcare Syst, Harvard Families & Addict Program,VAMC, Brockton, MA 02301 USA. SUNY Buffalo, Res Inst Addict, Buffalo, NY 14260 USA. RP O'Farrell, TJ (reprint author), Harvard Univ, Sch Med, Dept Psychiat,VA Boston Healthcare Syst, Harvard Families & Addict Program,VAMC, 116B1,940 Belmont St, Brockton, MA 02301 USA. NR 105 TC 41 Z9 41 U1 4 U2 7 PU AMER ASSOC MARRIAGE FAMILY THERAPY PI ALEXANDRIA PA 112 SOUTH ALFRED ST, ALEXANDRIA, VA 22314 USA SN 0194-472X J9 J MARITAL FAM THER JI J. Marital Fam. Ther. PD JAN PY 2003 VL 29 IS 1 BP 121 EP 146 DI 10.1111/j.1752-0606.2003.tb00387.x PG 26 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 636HB UT WOS:000180447600011 PM 12616803 ER PT J AU Erikson, JM Freeman, GL Chandrasekar, B AF Erikson, JM Freeman, GL Chandrasekar, B TI Ultrasound-targeted antisense oligonucleotide attenuates ischemia/reperfusion-induced myocardial tumor necrosis factor-alpha SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE antisense oligonucleotides; contrast; ultrasound; ischemia/reperfusion injury ID SONICATED DEXTROSE ALBUMIN; CONSCIOUS DOGS; INFARCTION; MICROBUBBLES; DESTRUCTION; INTERLEUKIN-6; EXPRESSION; CYTOKINE; ISCHEMIA; DELIVERY AB Ultrasound contrast agents are now emerging as effective vehicles for delivering therapeutic agents to target tissues. In the present study, we used ultrasound-targeted, contrast-bound antisense oligonucleotides to inhibit the expression of tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine with negative inotropic effects. We compared the efficacy of left ventricular vs. intravenous administration and determined the optimal time for delivery. WKY rats were treated with perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microspheres incubated with 100 mug of antisense oligonucleotide directed against TNF-alpha. Contrast was infused into either the superior vena cava or the left ventricular cavity along with simultaneous application of ultrasound. Twenty-four hours later, the animals underwent 15 min of ischemia and 2 h reperfusion. Control animals underwent sham operation only, ischemia/reperfusion only, or received PESDA only. A second group received treatment just prior to, or immediately after the onset of ischemia. At the end of the experimental period, hearts were removed and analyzed for TNF-alpha by northern and western blotting. While no TNF-alpha expression was detected in sham-operated animals, robust expression of TNF-alpha mRNA and protein was seen in controls treated with ultrasound and PESDA alone. In contrast, intravenous or left ventricular administration of antisense oligonucleotides significantly inhibited ischemia/reperfusion-induced TNF-alpha expression. Direct delivery into the left ventricular cavity was more effective than intravenous administration, and delivery just prior to ischemia was most effective in attenuating TNF-alpha expression. Furthermore, attenuation of TNF-alpha expression also significantly inhibited other post-ischemic inflammatory mediators including IL-1beta and intercellular adhesion molecule-1 (ICAM-1). Thus, ultrasound-targeted antisense oligonucleotides can effectively attenuate post-ischemic cytokine expression when delivered in a clinically relevant time frame, obviating the need for pretreatment. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Cardiol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Erikson, JM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Cardiol, 7703 Floyd Curl Dr,MC 7872, San Antonio, TX 78229 USA. EM erikson@uthscsa.edu FU NHLBI NIH HHS [HL68020] NR 32 TC 21 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JAN PY 2003 VL 35 IS 1 BP 119 EP 130 AR PII S0022-2828(02)00289-4 DI 10.1016/S0022-2828(02)00289-4 PG 12 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 650YZ UT WOS:000181293500012 PM 12623306 ER PT J AU Payton, S Cahill, CM Randall, JD Gullans, SR Rogers, JT AF Payton, S Cahill, CM Randall, JD Gullans, SR Rogers, JT TI Drug discovery targeted to the Alzheimer's APP mRNA 5 '-untranslated region - The action of paroxetine and dimercaptopropanol SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE APP 5 '-untranslated region; FDA preapproved drugs; paroxetine; dimercaptopropanol; Alzheimer's disease; therapeutics ID RESPONSIVE ELEMENT; PROTEIN-PRECURSOR; DISEASE; INTERLEUKIN-1; TRANSLATION; MICE; CHELATION; AGONISTS; MODEL AB We screened for drugs that specifically interact with the 5'-untranslated region of the mRNA encoding the Alzheimer's amyloid precursor protein (APP). Our goal was to use newly discovered APP 5' UTR directed compounds to limit amyloid-beta (Abeta)-peptide output in cell culture systems. The APP 5' UTR folds into a stable RNA secondary structure (Gibbs free energy: DeltaG = -54.9 kcal/mol) and is an important regulator of the amount of APP translated in response to IL-1 (Nilsson et al., 1998; Rogers et al., 1999) and iron (Rogers et al., 2002). Seventeen drug "hits" were identified from a library of 1,200 FDA preapproved drugs (Rogers et al., 2002). Six of the original 17 compounds were validated for their capacity to suppress reporter gene expression in stable neuroblastoma transfectants expressing the dicistronic reporter construct shown in Fig. 2. These six leads suppressed APP 5' UTR driven luciferase translation while causing no effect on the translation of dicistronic GFP gene translated from a viral IRES (negative control to ensure specificity during drug screens). In this report, we show that paroxetine (serotonin reuptake blocker) and dimercaptopropanol (Hg chelator) exerted significant effects on APP expression (steady-state levels of APP), whereas Azithromycin altered APP processing. None of these three compounds altered APLP-1 expression. In the future, we will identify further novel compounds that influence Abeta levels, either via translation inhibition or by changing the activity of proteins coupled between APP translation and APP processing. C1 Massachusetts Gen Hosp, Dept Psychiat, Genet & Aging Res Unit, Boston, MA 02129 USA. RP Rogers, JT (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Genet & Aging Res Unit, Boston, MA 02129 USA. NR 24 TC 38 Z9 39 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2003 VL 20 IS 3 BP 267 EP 275 DI 10.1385/JMN:20:3:267 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 726BT UT WOS:000185578800009 PM 14501007 ER PT J AU Singhal, AB Newstein, MC Budzik, R Cha, JH Rordorf, G Buonanno, FS Panzara, MA AF Singhal, AB Newstein, MC Budzik, R Cha, JH Rordorf, G Buonanno, FS Panzara, MA TI Diffusion-weighted magnetic resonance imaging abnormalities in Bartonella encephalopathy SO JOURNAL OF NEUROIMAGING LA English DT Article DE cat-scratch disease; encephalitis; diffusion MRI; thalamus; brain biopsy ID CAT-SCRATCH DISEASE; STATUS EPILEPTICUS; B-QUINTANA; MRI; ENCEPHALITIS; HENSELAE AB The authors describe 2 patients with new-onset, refractory status epilepticus and serological evidence for Bartonella infection. Brain magnetic resonance imaging (MRI) in patient 1 showed transient diffusion abnormalities in the posterior (pulvinar) thalami. In patient 2, brain MRI showed several enhancing cortical lesions, of which one lesion was bright on diffusion -weighted imaging (DWI). In patients with unexplained, refractory seizures, the presence of DWI abnormalities warrants a search for unusual infectious or inflammatory disorders, like Bartonella encephalitis. C1 Massachusetts Gen Hosp, Stroke Serv, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA. Biogen Inc, Boston, MA USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Stroke Serv, Dept Neurol, VBK-802, Boston, MA 02114 USA. EM asinghal@partners.org NR 9 TC 10 Z9 15 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD JAN PY 2003 VL 13 IS 1 BP 79 EP 82 DI 10.1177/1051228402239722 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 876BW UT WOS:000225471600011 PM 12593136 ER PT J AU Sperling, RA Bates, JF Chua, EF Cocchiarella, AJ Rentz, DM Rosen, BR Schacter, DL Albert, MS AF Sperling, RA Bates, JF Chua, EF Cocchiarella, AJ Rentz, DM Rosen, BR Schacter, DL Albert, MS TI FMRI studies of associative encoding in young and elderly controls and mild Alzheimer's disease SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; WORKING-MEMORY; FUNCTIONAL MRI; BRAIN; DECLINE; DYSFUNCTION; ACTIVATION; RISK; AD AB Objective: To examine alterations in patterns of brain activation seen in normal aging and in mild Alzheimer's disease by functional magnetic resonance imaging (fMRI) during an associative encoding task. Methods: 10 young controls, 10 elderly controls, and seven patients with mild Alzheimer's disease were studied using fMRI during a face-name association encoding task. The fMRI paradigm used a block design with three conditions: novel face-name pairs, repeated face-name pairs, and visual fixation. Results: The young and elderly controls differed primarily in the pattern of activation seen in prefrontal and parietal cortices: elderly controls showed significantly less activation in both superior and inferior prefrontal cortices but greater activation in parietal regions than younger controls during the encoding of novel face-name pairs. Compared with elderly controls, the Alzheimer patients showed significantly less activation in the hippocampal formation but greater activation in the medial parietal and posterior cingulate regions. Conclusions: The pattern of fMRI activation during the encoding of novel associations is differentially altered in the early stages of Alzheimer's disease compared with normal aging. C1 Brigham & Womens Hosp, Dept Neurol, Memory Disorders Unit, Boston, MA 02115 USA. Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Gerontol Res Unit, Boston, MA 02114 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Sperling, RA (reprint author), 221 Longwood Ave, Boston, MA 02115 USA. RI Chua, Elizabeth/B-3770-2010; OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [AG 08441, P01 AG 04953]; NIMH NIH HHS [MH 60941]; NINDS NIH HHS [K23 NS 02189] NR 30 TC 258 Z9 266 U1 4 U2 14 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JAN PY 2003 VL 74 IS 1 BP 44 EP 50 DI 10.1136/jnnp.74.1.44 PG 7 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 632DA UT WOS:000180207400012 PM 12486265 ER PT J AU Fisher, CM AF Fisher, CM TI Hypertensive cerebral hemorrhage. Demonstration of the source of bleeding SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Fisher, CM (reprint author), Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. NR 7 TC 26 Z9 28 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JAN PY 2003 VL 62 IS 1 BP 104 EP 107 PG 4 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 633GQ UT WOS:000180274800010 PM 12528822 ER PT J AU Zupan, LH Merfeld, DM AF Zupan, LH Merfeld, DM TI Neural processing of gravito-inertial cues in humans. IV. Influence of visual rotational cues during roll optokinetic stimuli SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID ANGULAR VESTIBULOOCULAR REFLEX; SPATIAL ORIENTATION; SEMICIRCULAR CANALS; POSTROTATORY NYSTAGMUS; ECCENTRIC ROTATION; VESTIBULAR SYSTEM; OCULAR RESPONSES; VIEWING DISTANCE; AFTER-NYSTAGMUS; SQUIRREL-MONKEY AB Sensory systems often provide ambiguous information. For example, otolith organs measure gravito-inertial force (GIF), the sum of gravitational force and inertial force due to linear acceleration. However, according to Einstein's equivalence principle, a change in gravitational force due to tilt is indistinguishable from a change in inertial force due to translation. Therefore the central nervous system (CNS) must use other sensory cues to distinguish tilt from translation. For example, the CNS might use dynamic visual cues indicating rotation to help determine the orientation of gravity (tilt). This, in turn, might influence the neural processes that estimate linear acceleration, since the CNS might estimate gravity and linear acceleration such that the difference between these estimates matches the measured GIF. Depending on specific sensory information inflow, inaccurate estimates of gravity and linear acceleration can occur. Specifically, we predict that illusory tilt caused by roll optokinetic cues should lead to a horizontal vestibuloocular reflex compensatory for an interaural estimate of linear acceleration, even in the absence of actual linear acceleration. To investigate these predictions, we measured eye movements binocularly using infrared video methods in 17 subjects during and after optokinetic stimulation about the subject's nasooccipital (roll) axis (60degrees/s, clockwise or counterclockwise). The optokinetic stimulation was applied for 60 s followed by 30 s in darkness. We simultaneously measured subjective roll tilt using a somatosensory bar. Each subject was tested in three different orientations: upright, pitched forward 10degrees, and pitched backward 10degrees. Five subjects reported significant subjective roll tilt (>10degrees) in directions consistent with the direction of the optokinetic stimulation. In addition to torsional optokinetic nystagmus and afternystagmus, we measured a horizontal nystagmus to the right during and following clockwise (CW) stimulation and to the left during and following counterclockwise (CCW) stimulation. These measurements match predictions that subjective tilt in the absence of real tilt should induce a nonzero estimate of interaural linear acceleration and, therefore, a horizontal eye response. Furthermore, as predicted, the horizontal response in the dark was larger for Tilters (n = 5) than for Non-Tilters (n = 12). C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol& Laryngol,Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. RP Zupan, LH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol& Laryngol,Jenks Vestibular Physiol Lab, Suite 421,243 Charles St, Boston, MA 02114 USA. EM lionel_zupan@meei.harvard.edu FU NIDCD NIH HHS [R01-DC-04158] NR 65 TC 36 Z9 37 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2003 VL 89 IS 1 BP 390 EP 400 DI 10.1152/jn.00513.2001 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 634FL UT WOS:000180329300036 PM 12522188 ER PT J AU Ellis, DZ Rabe, J Sweadner, KJ AF Ellis, DZ Rabe, J Sweadner, KJ TI Global loss of Na,K-ATPase and its nitric oxide-mediated regulation in a transgenic mouse model of amyotrophic lateral sclerosis SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Na,K-ATPase; SOD1; amyotrophic lateral sclerosis; neurodegeneration; spinal cord; nitric oxide ID CU/ZN SUPEROXIDE-DISMUTASE; CENTRAL-NERVOUS-SYSTEM; GLIAL GLUTAMATE TRANSPORTER; NA+-K+-ATPASE; RAT HIPPOCAMPUS; DIFFERENTIAL DISTRIBUTION; NITROSO-COMPOUNDS; OXIDATIVE DAMAGE; MESSENGER-RNAS; DOWNS-SYNDROME AB Na,K-ATPase plays a critical role in energy metabolism and ion fluxes. Its loss was investigated in the G93A mouse model of amyotrophic lateral sclerosis (ALS) in which the mutation of Cu/Zn superoxide dismutase (SOD1) is thought to lead to aberrant oxidative damage. Observed losses in spinal cord Na,K-ATPase activity exceeded all expectations. All three catalytic subunit isoforms (alpha1, alpha2, alpha3) were reduced, and the global alpha subunit loss affected not just neurons, glia, and myelinated axon tracts but even ependymal and pial membranes. Decreases in Na,K-ATPase activity were greater than losses of protein, and there were losses of Na,K-ATPase alpha, but not beta, subunits. Together, these observations are consistent with selective degradation of the alpha subunit after damage. Overexpression of normal SOD1 does not cause ALS-like symptoms, but it has other known pathological effects. In transgenic mice overexpressed normal human SOD1 had a smaller but still considerable effect on Na,K-ATPase. Furthermore, the nitric oxide-mediated regulatory pathway for Na,K-ATPase inhibition was undetectable in spinal cord tissue slices from mice overexpressing either mutant or normal human SOD1. Na,K-ATPase activity did not respond to nitric oxide donors, and the free radical-dependent step of the pathway could not be bypassed by the addition of the downstream protein kinase G activator, 8-Br-cGMP. The data demonstrate that Na,K-ATPase is vulnerable to aberrant SOD1 activity, making it a potential contributing factor in disease pathology. Moreover, the global cellular distribution of Na,K-ATPase loss indicates that SOD1 overexpression is far-reaching in its pathological effects. C1 Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA 02129 USA. RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, 149 13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [R01-NS27653] NR 71 TC 52 Z9 52 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 1 PY 2003 VL 23 IS 1 BP 43 EP 51 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 632BC UT WOS:000180202300009 PM 12514200 ER PT J AU Prevot, V Rio, C Cho, GJ Lomniczi, A Heger, S Neville, CM Rosenthal, NA Ojeda, SR Corfas, G AF Prevot, V Rio, C Cho, GJ Lomniczi, A Heger, S Neville, CM Rosenthal, NA Ojeda, SR Corfas, G TI Normal female sexual development requires neuregulin-erbB receptor signaling in hypothalamic astrocytes SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neuregulin; neuroendocrine; mammalian puberty; hypothalamus; astrocytes; neuron-glia interactions ID HORMONE-RELEASING HORMONE; GROWTH-FACTOR-ALPHA; CARDIAC DEVELOPMENT; GENE-EXPRESSION; NEUROENDOCRINE CONTROL; TRANSGENIC MICE; PUBERTY; NEURONS; NETWORK; LHRH AB The initiation of mammalian puberty requires the activation of hypothalamic neurons secreting the neuropeptide luteinizing hormone-releasing hormone (LHRH). It is thought that this activation is caused by changes in trans-synaptic input to LHRH neurons. More recently, it has been postulated that the pubertal increase in LHRH secretion in female animals also requires neuron-glia signaling mediated by growth factors of the epidermal growth factor (EGF) family and their astrocytic erbB receptors. Although it appears clear that functional astrocytic erbB1 receptors are necessary for the timely advent of puberty, the physiological contribution that erbB4 receptors may make to this process has not been established. To address this issue, we generated transgenic mice expressing a dominant-negative erbB4 receptor (DN-erbB4) under the control of the GFAP promoter, which targets transgene expression to astrocytes. DN-erbB4 expression is most abundant in hypothalamic astrocytes, where it blocks the ligand-dependent activation of glial erbB4 and erbB2 receptors, without affecting erbB1 (EGF) receptor signaling. Mice carrying the transgene exhibit delayed sexual maturation and a diminished reproductive capacity in early adulthood. These abnormalities are related to a deficiency in pituitary gonadotropin hormone secretion, caused by impaired release of LHRH, the hypothalamic neuropeptide that controls sexual development. In turn, the reduction in LHRH release is caused by the inability of hypothalamic astrocytes to respond to neuregulin (NRG) with production of prostaglandin E-2, which in wild-type animals mediates the stimulatory effect of astroglial erbB receptor activation on neuronal LHRH release. Thus, neuron-astroglia communication via NRG-erbB4/2 receptor signaling appears to be essential for the timely unfolding of the developmental program by which the brain controls mammalian sexual maturation. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Oregon Reg Primate Res Ctr, Div Neurosci, Beaverton, OR 97006 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Ojeda, SR (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Neurosci, 300 Longwood Ave, Boston, MA 02115 USA. RI Prevot, Vincent/E-5720-2016; OI Lomniczi, Alejandro/0000-0003-4535-0103; Prevot, Vincent/0000-0001-7185-3615 FU NCRR NIH HHS [RR00163]; NICHD NIH HHS [HD U54 HD18185, HD25123, P30-HD 18655]; NINDS NIH HHS [R01 NS35884] NR 41 TC 97 Z9 102 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 1 PY 2003 VL 23 IS 1 BP 230 EP 239 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 632BC UT WOS:000180202300029 PM 12514220 ER PT J AU Matejuk, A Buenafe, AC Dwyer, J Ito, A Silverman, M Zamora, A Subramanian, S Vandenbark, AA Offner, H AF Matejuk, A Buenafe, AC Dwyer, J Ito, A Silverman, M Zamora, A Subramanian, S Vandenbark, AA Offner, H TI Endogenous CD4+BV8S2-T cells from TG BV8S2+donors confer complete protection against spontaneous experimental encephalomyelitis (Sp-EAE) in TCR transgenic, RAG(-/-) mice SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE EAE; regulatory T cells; CD4+T cells; TCR transgenic mice ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; V-BETA-GENES; CHEMOKINE RECEPTORS; DIFFERENTIAL EXPRESSION; NOD MICE; DISEASE; DEFINES; REGION; RAT AB To investigate regulatory mechanisms which naturally prevent autoimmune diseases, we adopted the genetically restricted immunodeficient (RAG-1 (-/-)) myelin basic protein (MBP)-specific T cell receptor (TCR) double transgenic (T/R-) mouse model of spontaneous experimental autoimmune encephalomyelitis (Sp-EAE). Sp-EAE can be prevented after transfer of CD4+splenocytes from naive immunocompetent mice. RAG-1+ double transgenic (T/R+) mice do not develop Sp-EAE due to the presence of a very small population (about 2%) of non-Tg TCR specificities. In this study, CD4+BV8S2+ T cells that predominate in T/R+ mice, and three additional populations, CD4+BV8S2-, CD4-CD8-BV8S2+, and CD4-CD8+BV8S2+ T cells that expanded in T/R+ mice after immunization with MBP-Ac1-11 peptide, were studied for their ability to prevent Sp-EAE in T/R- mice. Only the CD4+BV8S2- T cell population conferred complete protection against Sp-EAE, similar to unfractionated splenocytes from non-Tg donors, whereas CD4-CD8-BV8S2+ and CD4+BV8S2+ T cells conferred partial protection. In contrast, CD4-CD8+BV8S2+ T cells had no significant protective effects. The highly protective CD4+BV8S2- subpopulation was CD25+, contained non-clonotypic T cells, and uniquely expressed the CCR4 chemokine receptor. Protected recipient T/R- mice had marked increases in CD4+CD25+ Treg-like cells, retention of the pathogenic T cell phenotype in the spleen, and markedly reduced inflammation in CNS tissue. Partially protective CD4+BV8S2+ and CD4- CD8-BV8S2+ subpopulations appeared to be mainly clonotypic T cells with altered functional properties. These three Sp-EAE protective T cell subpopulations possessed distinctive properties and induced a variety of effects in T/R- recipients, thus implicating differing mechanisms of protection. (C) 2002 Wiley-Liss, Inc. C1 Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Vet Affairs Med Ctr, Portland, OR USA. Polish Acad Sci, L Hirszfeld Inst Immunol & Expt Therapy, PL-53114 Wroclaw, Poland. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR USA. RP Offner, H (reprint author), Portland VA Med Ctr, R&D 31, 3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. FU NIAID NIH HHS [AI42376]; NINDS NIH HHS [NS23221, NS23444] NR 30 TC 9 Z9 9 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JAN 1 PY 2003 VL 71 IS 1 BP 89 EP 103 DI 10.1002/jnr.10450 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 628TW UT WOS:000180013500009 PM 12478617 ER PT J AU Berntson, A Taylor, WR Morgans, CW AF Berntson, A Taylor, WR Morgans, CW TI Molecular identity, synaptic localization, and physiology of calcium channels in retinal bipolar cells SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE mouse; electrophysiology; patch-clamp; alpha 1F; immunohistochemistry ID STATIONARY NIGHT BLINDNESS; RAT RETINA; CONE PHOTORECEPTORS; CURRENTS; GENE; EXPRESSION; SUBUNIT; ROD AB Bipolar cells convey information through the retina via graded changes in their membrane potential and modulate transmitter release through the influx of calcium via L-type calcium channels. However, the molecular identity of the a, subunit has not been confirmed. We report the presence of the newly cloned alpha(1F) subunit in mouse bipolar cell synaptic terminals. The alpha(1F) subunits are localized to hot spots, possibly corresponding to active zones. We also report the physiological properties of two calcium currents present in mouse bipolar cells, a low-voltage-activated L-type current and a low-voltage-activated T-type calcium cur-rent. The physiological properties of the T-type current suggest that it is completely inactivated under physiological conditions. The L-type current may be mediated by the alpha(1F) subunit, and influx of calcium through the alpha(1F) channel may control neurotransmitter release from the bipolar cell terminal. (C) 2002 willey-Liss, Inc. C1 Australian Natl Univ, John Curtin Sch Med Res, Ctr Visual Sci, Canberra, ACT 2601, Australia. RP Berntson, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 429 Wellman Bldg, Boston, MA 02114 USA. OI Taylor, William/0000-0002-6806-3249 NR 24 TC 51 Z9 51 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JAN 1 PY 2003 VL 71 IS 1 BP 146 EP 151 DI 10.1002/jnr.10459 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 628TW UT WOS:000180013500016 PM 12478624 ER PT J AU Counter, SA AF Counter, SA TI Neurophysiological anomalies in brainstem responses of Mercury-exposed children of Andean gold miners SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID AMAZONIAN POPULATIONS; ELEMENTAL MERCURY; EVOKED-POTENTIALS; NERVOUS-SYSTEM; FRENCH-GUIANA; MINING AREA; METHYLMERCURY; FISH; BRAZIL; VAPOR AB The health hazards of occupational exposure to Mercury (Hg) in adult gold miners are well known, but little attention has been given to the effects of Hg exposure in the children of gold miners. Children who assist their parents in gold mining operations or live in mining enclaves may be exposed to elemental Hg vapors or methylmercury-contaminated food, both of which may induce neurodevelopmental disabilities. Brainstem auditory-evoked responses (BAER) were measured as biomarkers of subtle mercury-induced neurological impairment in Andean children of gold miners living in the Ecuadorian gold mining settlement of Nambija, where Hg exposure is prevalent. Thirty-one children (19 boys and 12 girls, aged 4-14 years, mean age: 10 years) in the study group were found to have a mean blood mercury (HgB) Level of 23.0 mug/L (SD: 19, range. 2.0-89.0 mug/L; median: 20 mug/L), which was significantly higher than the mean HgB level of a reference group of 21 Ecuadorian children (4.5 mug/L, SD: 2.3; t = 4.39, P = 0.0001), and in excess of the health-based biological limits for the U.S. (10 mug/L). The BAER measures indicated statistically significant differences in interpeak III-V (P = 0.03) and I-V (P = 0.008) neural conduction times for children with HgB Levels above the median. BAERs at the conventional click stimulus rate of 10/second showed statistically sign icant positive correlations between HgB level and the absolute latency of wave V (P = 0. 03), and the neural conduction times of the eighth nerve to midbrain IT interval (P = 0. 02). BAER at 50/second revealed statistically significant relationships between HgB and the latency of wave VI (P = 0.03), and the I-VI interpeak interval (P = 0.02). Brainstem neural conduction times suggested that some of the Hg-intoxicated children in the study group have subtle neurophysiological anomalies that may be more manifest at higher BAER stimulus rates, and that the Hg-exposed children of gold miners are at risk for neurodevelopmental disabilities. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Biol Labs, Cambridge, MA 02138 USA. RP Counter, SA (reprint author), Harvard Univ, Biol Labs, Cambridge, MA 02138 USA. NR 37 TC 32 Z9 38 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JAN PY 2003 VL 45 IS 1 BP 87 EP 95 DI 10.1097/01.jom.0000048165.87707.fd PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 634WA UT WOS:000180363800016 PM 12553183 ER PT J AU Abukawa, H Terai, H Hannouche, D Vacanti, JP Kaban, LB Troulis, MJ AF Abukawa, H Terai, H Hannouche, D Vacanti, JP Kaban, LB Troulis, MJ TI Formation of a mandibular condyle in vitro by tissue engineering SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 83rd Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgeons CY SEP, 2001 CL ORLANDO, FLORIDA SP Amer Assoc Oral Maxillofac Surg ID BIODEGRADABLE POLYMER SCAFFOLDS; MESENCHYMAL STEM-CELLS; BONE-FORMATION; IN-VITRO; CULTURE; OSTEOTOMY; MODEL AB Purpose: Mandibular reconstructive procedures often produce significant donor site morbidity. Recently, the use of minimally invasive techniques has been reported for mandibular reconstruction with decreased morbidity at the primary operative site. To date, these techniques have not addressed the graft donor site. We hypothesize that tissue-engineering techniques may be used to fabricate bone and thereby eliminate donor site morbidity. Methods: Porcine mesenchymal stem cells (pMSCs) were isolated from the bone marrow of 3 Yucatan minipigs and grown in standard culture flasks. When they became near-confluent, cells were detached and replated with the addition of osteogenic supplements. A model of a porcine mandibular condyle was made and used to fabricate porous polymer scaffolds from biodegradable Poly (DL)-lactic-co-glycolic acid (PLGA). Differentiated osteoblasts were transferred to the PLGA scaffold and cultured for 6 weeks in a rotational oxygen-permeable bioreactor system. The cultured constructs, consisting of scaffold and cells, were evaluated by gross, radiologic, and histologic examinations. Results: The engineered constructs were white and hard and had a shape that closely resembled that of the model condyle. Plain radiographs demonstrated that the radiodensity of the construct was between that of the normal condyle and that of control scaffolds. Histologically, bone was observed on the entire surface of the PLGA scaffolds with an average thickness of 0.03 mm. Bone was not observed in the control scaffolds. Conclusion: in this pilot study, autologous tissue-engineered bone constructs were successfully made by combining biodegradable polymers and pMSCs. (C) 2003 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Troulis, MJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren Bldg 1201,55 Fruit St, Boston, MA 02114 USA. NR 22 TC 75 Z9 92 U1 0 U2 9 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JAN PY 2003 VL 61 IS 1 BP 94 EP 100 DI 10.1053/joms.2003.50015 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 630ZZ UT WOS:000180143100017 PM 12524615 ER PT J AU Schildhauer, TA Ledoux, WR Chapman, JR Henley, MB Tencer, AF Routt, MLC AF Schildhauer, TA Ledoux, WR Chapman, JR Henley, MB Tencer, AF Routt, MLC TI Triangular osteosynthesis and iliosacral screw fixation for unstable sacral fractures: A cadaveric and biomechanical evaluation under cyclic loads SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE pelvis; Sacrum; fracture fixation; internal; biomechanics; iliosacral screw; triangular osteosynthesis ID POSTERIOR INTERNAL-FIXATION; PELVIC RING DISRUPTIONS; OPEN REDUCTION; STABILITY; INJURIES AB Objective: To conduct a biomechanical comparison of a new triangular osteosynthesis and the standard iliosacral screw osteosynthesis for unstable transforaminal sacral fractures in the immediate postoperative situation as well as in the early postoperative weight-bearing period. Design: Twelve preserved human cadaveric lumbopelvic specimens were cyclicly tested in a single-limb-stance model. A transforaminal sacral fracture combined with ipsilateral superior and inferior pubic rami fractures were created and stabilized. Loads simulating muscle forces and body Weight were applied. Fracture site displacement in three dimensions was evaluated using an electromagnetic motion sensor system. Intervention: Specimens were randomly assigned to either an iliosacral and superior pubic ramus screw fixation or to a triangular osteosynthesis consisting of lumbopelvic stabilization (between L5 pedicle and posterior ilium) combined with iliosacral and superior pubic ramus screw fixation. Main Outcome Measures: Peak loaded displacement at the fracture site was measured for assessment of initial stability. Macroscopic fracture behavior through 10,000 cycles of loading, simulating the early postoperative weight-bearing period, was classified into type I with minimal motion at the fracture site, type 2 with complete displacement of the inferior pubic ramus, or type 3 with catastrophic failure. Results: The triangular osteosynthesis had a statistically significantly smaller displacement under initial peak loads (mean +/- standard deviation [SD], 0.163 +/- 0.073 cm) and therefore greater initial stability than specimens with (lie standard iliosacral screw fixation (mean +/- SD, 0.611 +/- 0.453 cm) (p = 0.0104), independent of specimen age or sex. All specimens With the triangular osteosynthesis demonstrated type I fracture behavior, whereas iliosacral screw fixation resulted in one type 1, two type 2, and three type 3 fracture behaviors before or at 10,000 cycles, of loading. Conclusion: Triangular osteosynthesis for unstable transforaminal sacral fractures provides significantly greater stability than iliosacral screw fixation under in vitro cyclic loading conditions. In vitro cyclic loading, as a limited simulation of early stages of patient mobilization in the postoperative period, allows for a time-dependent evaluation of any fracture fixation system. C1 Univ Washington, Harborview Med Ctr, Dept Orthopaed & Sports Med, Seattle, WA 98104 USA. Univ Washington, Harborview Med Ctr, Orthopaed Sci Lab, Seattle, WA 98104 USA. VA Puget Sound, RR&D Ctr Excellence, Seattle, WA USA. RP Schildhauer, TA (reprint author), Ruhr Univ Bochum, Chirurg Klin & Poliklin, BG Kliniken Bergmannsheil, Burkle Camp Pl 1, D-44789 Bochum, Germany. RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 NR 48 TC 75 Z9 96 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD JAN PY 2003 VL 17 IS 1 BP 22 EP 31 DI 10.1097/00005131-200301000-00004 PG 10 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 630PP UT WOS:000180117400004 PM 12499964 ER PT J AU Sang, CN Max, MB Gracely, RH AF Sang, CN Max, MB Gracely, RH TI Stability and reliability of detection thresholds for human A-beta and A-Delta sensory afferents determined by cutaneous electrical stimulation SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE electric stimulation; pain threshold; pain measurement; sensory thresholds; primary afferent; hyperesthesia ID PAIN; HYPERSENSITIVITY; INFLAMMATION; ANTAGONIST; ALLODYNIA; REFLEX AB Activity in primary afferent fibers that usually mediate fine touch can evoke sensations of pain in conditions in which there is sensitization of central neurons. Input from these large diameter Abeta afferents may also sustain and exacerbate these central mechanisms. The role of these fibers in clinical pain syndromes can be evaluated by applications of electrical stimuli that preferentially activate Abeta axons. This study assessed the stability and reliability of a method of electrical stimulation (ES) useful for clinical evaluation. Monopolar constant current rectangular pulses were delivered to 5 equi-spaced sites on the volar aspect of the left forearm along a transverse line 5 cm, distal to the antecubital crease. Current intensity was gradually increased to determine detection threshold and pain detection threshold. This study determined: 1) Effect of pulse duration (1, 2, and 5 msec); 2) the variation of detection threshold and pain threshold over repeated stimulation; 3) the effect of electrode position with respect to distance from the trunk of underlying ulnar or median nerves; and 4) the effect of repositioning the electrode on variability of detection threshold and pain threshold. There was no significant variability over time for either detection threshold (DT) or pain threshold (PT) at any of the 3 pulse durations tested. There was also no significant effect on variability of shifting the electrode between sites, nor was there a significant difference in variability between sites when placed either over or adjacent to peripheral nerves. Under simulated clinical conditions of electrode re-positioning, the mean detection threshold in 300 trials and ten subjects was 0.30 mA with an overall standard error of 0.007, standard errors of 0.014 over the 10 subjects, 0.003 over the 6 trials, and 0.012 over the 5 locations. Similarly, mean pain threshold in these 300 trials was 3.24 +/- 0.093, with standard errors of 0.12 over the 10 subjects, 0.023 over the 6 trials, and 0.13 over the 5 locations. Mean ratio of pain threshold divided by detection threshold ratio was 10.9 +/- 0.25 with a range of 2.0-28.3. Single pulse, constant current electrical stimulation of the skin at threshold levels is a quantifiable and reliable sensory method that is repeatable within and between testing sessions. Our results suggest that in skin unaffected by allodynia, a ratio of the two sensory thresholds (pain threshold and detection threshold) of less than 2.0 is uncommon. We propose that, in the presence of mechanical allodynia, a pain threshold/detection threshold of less than 2.0 suggests that altered central nervous system processing of Ap input may contribute to allodynia. (C) 2003 U.S. Cancer Pain Relief Committee. Published by Elsevier. All rights reserved. C1 Harvard Univ, Dept Anesthesia, Clin 3, Sch Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. US Dept Hlth & Human Serv, Natl Inst Dent Res, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD USA. RP Sang, CN (reprint author), Harvard Univ, Dept Anesthesia, Clin 3, Sch Med,Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. NR 34 TC 38 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JAN PY 2003 VL 25 IS 1 BP 64 EP 73 AR PII S0885-3924(02)00541-9 DI 10.1016/S0885-3924(02)00541-9 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 640XZ UT WOS:000180715400012 PM 12565190 ER PT J AU Yassir, WK Grottkau, BE Goldberg, MJ AF Yassir, WK Grottkau, BE Goldberg, MJ TI Costello syndrome: Orthopedic manifestations and functional health SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE Costello syndrome; orthopaedic manifestations; vertical talus; functional health ID EMBRYONAL RHABDOMYOSARCOMA; RETARDATION SYNDROME; NATURAL-HISTORY; CUTIS LAXA; INVOLVEMENT; PATIENT; BOY AB Sixteen individuals with Costello syndrome underwent a complete history, physical examination, and medical record review. Medical history and record review were performed for two additional children with Costello syndrome. The POSNA Functional Health Outcome Questionnaire Baseline Assessment was completed by the parents of all 18 children. All the children were below the fifth percentile for height and all had ligamentous laxity. All children demonstrated delayed walking and none was able to run. Orthopaedic problems included tight heel cords, congenital vertical talus, planovalgus feet, hip subluxation, kyphosis, scoliosis, radial head subluxation, elbow flexion deformity, reduced shoulder range of motion, and limitation of overhead activity. Foot problems were most frequently encountered. Two children had no orthopaedic symptoms. All children with Costello syndrome had poor scores on the POSNA Functional Health Outcome Questionnaire. Orthopaedic problems are a significant part of Costello syndrome, and affected individuals should be evaluated and followed-up regularly by an orthopaedic surgeon. C1 Tufts Univ, New England Med Ctr, Sch Med, Dept Orthopaed, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr, Boston Floating Hosp Children, Dept Orthopaed,Sch Med, Boston, MA 02111 USA. Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Yassir, WK (reprint author), Tufts Univ, New England Med Ctr, Sch Med, Dept Orthopaed, Box 016,750 Washington St, Boston, MA 02111 USA. NR 25 TC 15 Z9 17 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-6798 J9 J PEDIATR ORTHOPED JI J. Pediatr. Orthop. PD JAN-FEB PY 2003 VL 23 IS 1 BP 94 EP 98 DI 10.1097/00004694-200301000-00019 PG 5 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 632ZA UT WOS:000180253700019 PM 12499952 ER PT J AU del Monte, F Hajjar, RJ AF del Monte, F Hajjar, RJ TI Targeting calcium cycling proteins in heart failure through gene transfer SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article; Proceedings Paper CT Symposium on Normal and Pathological Excitation - Contraction Coupling in the Heart CY MAR 15, 2002 CL TUBINGEN, GERMANY ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; RECOMBINANT ADENOASSOCIATED VIRUS; HUMAN VENTRICULAR MYOCARDIUM; NONFAILING HUMAN MYOCARDIUM; FORCE-FREQUENCY-RELATIONSHIP; CHANNEL RYANODINE RECEPTOR; IN-VIVO; DILATED CARDIOMYOPATHY; ADENOVIRAL VECTORS; CARDIAC MYOCYTES AB Our understanding of cardiac excitation-contraction coupling has improved significantly over the last 10 years. Furthermore, defects in the various steps of excitation-contraction coupling that characterize cardiac dysfunction have been identified in human and experimental models of heart failure. The various abnormalities in ionic channels, transporters, kinases and various signalling pathways collectively contribute to the 'failing phenotype.' However, deciphering the causative changes continues to be a challenge. An important tool in dissecting the importance of the various changes in heart failure has been the use of cardiac gene transfer. To achieve effective cardiac gene transfer a number of obstacles remain, including appropriate vectors for gene delivery, appropriate delivery systems, and a better understanding of the biology of the disease. In this review, we will examine our current understanding of these various factors. Gene transfer provides not only a potential therapeutic modality but also an approach to identifying and validating molecular targets. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Cardiovasc Gene Therapy,Cardiovasc Res Ct, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Hajjar, RJ (reprint author), Massachusetts Gen Hosp E, Cardiovasc Res Ctr, 149 13th St,CNY-4,Room 4215, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL57623, HL50361] NR 107 TC 60 Z9 60 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JAN 1 PY 2003 VL 546 IS 1 BP 49 EP 61 DI 10.1113/jphysiol.2002.026732 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 690UT UT WOS:000183569400006 PM 12509478 ER PT J AU Sorensen, G Stoddard, AM LaMontagne, AD Emmons, K Hunt, MK Youngstrom, R McLellan, D Christiani, DC AF Sorensen, G Stoddard, AM LaMontagne, AD Emmons, K Hunt, MK Youngstrom, R McLellan, D Christiani, DC TI A comprehensive worksite cancer prevention intervention: Behavior change results from a randomized controlled trial (United States) SO JOURNAL OF PUBLIC HEALTH POLICY LA English DT Article ID SITE HEALTH PROMOTION; WHITE-COLLAR WORKERS; COLORECTAL-CANCER; INTEGRATIVE PERSPECTIVE; VEGETABLE INTAKE; PROGRAM; RISK; WORKPLACE; WELLNESS; SMOKING AB Objective: Workplace cancer prevention initiatives have been least successful with blue-collar workers. This study assesses whether an intervention integrating health promotion with occupational health and safety results in significant and meaningful increases in smoking cessation and consumption of fruits and vegetables, compared to a standard health promotion intervention, for workers overall and for blue-collar workers in particular. Methods: A randomized controlled design was used, with 15 manufacturing worksites assigned to a health promotion (HP) or a health promotion plus occupational health and safety intervention (HP/OHS), and compared from baseline (1997) to final (1999). The response rates to the survey were 80% at baseline (n = 9019) and 65% at final (n = 7327). Both groups targeted smoking and diet; the HP/OHS condition additionally incorporated reduction of occupational exposures. Results: Smoking quit rates among blue-collar workers in the HP/OHS condition more than doubled relative to those in the HP condition (OR=2.13, P=0.04), and were comparable to quit rates of white-collar workers. No statistically significant differences between groups were found for mean changes in fruits and vegetables. Conclusions: Integration of occupational health and safety and health promotion may be an essential means of enhancing the effectiveness of worksite tobacco control initiatives with blue-collar workers. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. Monash Univ Sch Med, Dept Epidemiol & Prevent Med, Prahran, Vic 3181, Australia. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [5 RO1 CA68087] NR 65 TC 26 Z9 26 U1 1 U2 6 PU JOURNAL PUBLIC HEALTH POLICY PI S BURLINGTON PA 208 MEADOWOOD DR, S BURLINGTON, VT 05403 USA SN 0197-5897 J9 J PUBLIC HEALTH POL JI J. Public Health Policy PY 2003 VL 24 IS 1 BP 5 EP 25 DI 10.2307/3343174 PG 21 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 674ZJ UT WOS:000182667800001 PM 12760241 ER PT J AU da Cunha, IT Henson, H Wankadia, S Protas, EJ AF da Cunha, IT Henson, H Wankadia, S Protas, EJ TI Reliability of measures of gait performance and oxygen consumption with stroke survivors SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE gait performance; oxygen consumption; reliability; stroke ID ENERGY-EXPENDITURE; WALKING; GENERALIZABILITY; CLASSIFICATION; REHABILITATION AB This study assessed the reliability of gait performance with concurrent measures of oxygen consumption (VO2) in stroke survivors (SS). Nine male SS (60.00 +/- 15.08 yr) had a recent history of stroke (44.56 +/- 51.35 days since the stroke) and were receiving rehabilitation. Four had a right cerebrovascular accident (CVA), and five had a left CVA. Subjects walked without assistance, although three used a single cane to complete the test. Within 30 minutes, subjects completed two trials of a 5 min walk while walking back and forth on a 5 m walkway wearing a portable gas analyzer to collect samples of gases. The intraclass correlation coefficient (ICC) was used to assess reliability. The ICC for gait energy expenditure, walk distance, gait speed, and gait energy cost were 0.64, 0.97, 0.95, and 0.97, respectively. Assessment of gait performance with concurrent measures of VO2 is a reliable procedure with SS. C1 Univ Texas, Med Branch, Dept Phys Therapy, Sch Allied Hlth Sci, Galveston, TX 77555 USA. Texas Womans Univ, Sch Phys Therapy, Houston, TX USA. Houston Vet Affiars Med Ctr, Dept Phys Med & Rehabil, Houston, TX USA. Houston Vet Affairs Med Ctr, Rehabil Res & Dev Ctr Excellence Hralthy Aging Di, Houston, TX USA. RP Protas, EJ (reprint author), Univ Texas, Med Branch, Dept Phys Therapy, Sch Allied Hlth Sci, 301 Univ Blvd, Galveston, TX 77555 USA. FU NIA NIH HHS [P30 AG024832] NR 25 TC 19 Z9 19 U1 0 U2 2 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JAN-FEB PY 2003 VL 40 IS 1 BP 19 EP 25 PG 7 WC Rehabilitation SC Rehabilitation GA 661WQ UT WOS:000181913200005 PM 15150717 ER PT J AU Oates, JC Levesque, MC Hobbs, MR Smith, EG Molano, ID Page, GP Hill, BS Weinberg, JB Cooper, GS Gilkeson, GS AF Oates, JC Levesque, MC Hobbs, MR Smith, EG Molano, ID Page, GP Hill, BS Weinberg, JB Cooper, GS Gilkeson, GS TI Nitric oxide synthase 2 promoter Polymorphisms and systemic lupus erythematosus in African-Americans SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE blacks; polymorphism (genetics); microsatellite repeats; promoter regions (genetics); genetic predisposition to disease ID FUNCTIONAL-ANALYSIS; TANZANIAN CHILDREN; DISEASE-ACTIVITY; GENE; MALARIA; SERUM; PEROXYNITRITE; REGION; 3-NITROTYROSINE; DISEQUILIBRIUM AB Objective. Systemic lupus erythematosus (SLE) is an autoimmune disease in which morbidity and-mortality are higher in African-Americans. The etiology of this racial disparity is unknown. A genetic predisposition to enhanced nitric oxide (NO) production may predispose African-Americans to develop SLE and may increase disease severity. We have demonstrated a correlation between NO production and disease activity in SLE. Two polymorphisms in the inducible NO synthasie (NOS2) promoter region (G-954C and CCTTT microsatellite repeat polymorphisms) are associated with improved outcome in some African patients with malaria. This study was designed to determine if these polymorphisms are. associated with SLE. Methods. We assessed the frequency of both the G-954C and CCTTT microsatellite repeat NOS2 promoter polymorphisms in a cohort of patients with SLE and age, sex, and race matched controls in North Carolina and South Carolina. Results. Both polymorphisms were more frequent among African-American female SLE patients when compared with controls (p=0.04 for the,G-954C polymorphism and p=0.03 for the CCTTT-8 repeat polymorphism). Further, the G-954C and CCTTT-8 repeat polymorphisms were in,linkage disequilibriurn (D'=0.89, p=0.0001) among African-American female SLE patients. Conclusion. Altered genetic control of NOS2 transcription may be a risk factor for SLE among African-American females. The extent of linkage disequilibrium between the G-954C and CCTTT-8 repeat NOS2 promoter polymorphisms suggests that they were co-inherited. C1 Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Med, Charleston, SC USA. Durham VAMC, Dept Med, Durham, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT USA. Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. Ctr Arthrit & Rheumat Dis, Concord, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Oates, JC (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol, 96 Jonathan Lucas St,Suite 912,POB 250623, Charleston, SC 29425 USA. FU NIAID NIH HHS [AI41764]; NIAMS NIH HHS [AR39162, R01 AR045476, AR45476] NR 48 TC 29 Z9 30 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2003 VL 30 IS 1 BP 60 EP 67 PG 8 WC Rheumatology SC Rheumatology GA 633LW UT WOS:000180285600011 PM 12508391 ER PT J AU Chase, KA O'Farrell, TJ Murphy, CM Fals-Stewart, W Murphy, M AF Chase, KA O'Farrell, TJ Murphy, CM Fals-Stewart, W Murphy, M TI Factors associated with partner violence among female alcoholic patients and their male partners SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article; Proceedings Paper CT Annual Conference of the Association-for-the-Advancement-of-Behavior-Therapy CY NOV, 2001 CL PHILADELPHIA, PENNSYLVANIA SP Assoc Advancement Behav Therapy ID FAMILY VIOLENCE; WOMEN; SCALES; ABUSE; VICTIMIZATION; RELIABILITY; INVENTORY; CONFLICT AB Objective: This study described the extent of partner violence victimization and perpetration among married or cohabiting female alcoholic patients and the factors associated with it. Method: Male-to-female and female-to-male physical partner violence were examined for 103 female alcoholic patients seeking couples-based outpatient alcoholism treatment. Partner violent (PV) and nonpartner violent (NPV) groups were compared on hypothesized risk factors. Results: In the year before treatment, about two thirds of the women were victimized by their male partners, and a similar proportion engaged in violence toward their male partners. Severe violence also was high, with 22% victimization and 50% perpetration prevalence. Women committed more violent acts overall and were more likely to commit severely violent acts than the men in these couples. Risk factors for PV in both the victimization and perpetration models were as predicted: less education, lower income, greater relationship problems, stronger beliefs in the link between relationship problems and the female patient's drinking, greater cocaine use by the perpetrator of violence and greater emotional distress of the men. Greater alcohol and drug use and more severe alcohol problems also distinguished male perpetrators from their nonviolent counterparts in the female victimization model. Predictions that female patients in the PV group would report greater substance use and problems, childhood violence exposure and emotional distress than their female counterparts in the NPV group were not supported for either victimization or perpetration models. Conclusions:. Partner violence is a serious problem for women in alcoholism treatment. More research is needed to increase understanding of risk factors and explanatory models for such violence. (J Stud. Alcohol 64: 137-149, 2003). C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat,Harvard Families & Addict Program, Brockton, MA 02301 USA. RP O'Farrell, TJ (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat,Harvard Families & Addict Program, 116B1,940 Belmont St, Brockton, MA 02301 USA. FU NIAAA NIH HHS [AA08637, AA10356, K02AA0234, R21AA12433]; NIMH NIH HHS [T32MH16259] NR 52 TC 58 Z9 58 U1 3 U2 9 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD JAN PY 2003 VL 64 IS 1 BP 137 EP 149 PG 13 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 643RC UT WOS:000180873400017 PM 12608494 ER PT J AU Geller, AC Zhang, Z Sober, AJ Halpern, AC Weinstock, MA Daniels, S Miller, DR Demierre, MF Brooks, DR Gilchrest, BA AF Geller, AC Zhang, Z Sober, AJ Halpern, AC Weinstock, MA Daniels, S Miller, DR Demierre, MF Brooks, DR Gilchrest, BA TI The first 15 years of the American Academy of Dermatology Skin Cancer Screening Programs: 1985-1999 SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; OF-DERMATOLOGY; MASSACHUSETTS; PREVALENCE AB Background: In response to the precipitous increase of melanoma, the American Academy of Dermatology (AAD) has coupled melanoma/skin cancer education with free skin cancer screening programs throughout the United States since 1985. The purpose of this analysis is to investigate the risk factors, access to dermatologic services, and screening results of participants in AAD-sponsored programs during the first 15 years that this service was available to the US public. Methods: Before screening, participants completed a standardized AAD screening form. Screening forms were counted in the AAD central office and recorded in annual summaries. Forms were sent for keypunching and returned to the AAD on a computer disk annually. In 1999, disks were sent to Boston University and a master file was created. Results: Computerized records were available for 819,019 screening forms and 639,835 individuals. in all, 65% of screenees had at least I risk factor and 33% had at least 2 risk factors. of screenees, 33% reported a changing mole and 37% had skin type I or II. Among all screenees, nearly 80% did not have a regular dermatologist, 78% reported no prior AAD skin cancer screening, 60% had never had their skin checked by any doctor, and 51% would not have seen a doctor for skin cancer without the free screening. Nearly 30% of screenees had a presumptive diagnosis of skin cancer or a precursor lesion. Melanomas confirmed by postscreening biopsy were more likely than those in population-based registries to be less than 1.50 mm in thickness. Conclusions: AAD national screening and educational programs have expanded to all 50 states, provided educational messages about sun protection and early detection to millions, and served many US citizens with an above average risk for skin cancer and suboptimal access to dermatologic care. Screenees had a disturbingly high point prevalence of malignant and premalignant skin lesions. Sustained commitment by the AAD leadership and membership to the screening program is critical to reducing the morbidity and mortality of skin cancer. C1 Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Brown Univ, Dept Dermatol, Providence, RI 02912 USA. Dept Vet Affairs Med Ctr, Dermatoepidemiol Unit, Providence, RI USA. Massachusetts Dept Publ Hlth, Boston, MA USA. RP Geller, AC (reprint author), Boston Univ, Sch Med, Dept Dermatol, 720 Harrison Ave,DOB 801A, Boston, MA 02118 USA. OI Brooks, Daniel/0000-0001-6220-6889 NR 24 TC 71 Z9 72 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2003 VL 48 IS 1 BP 34 EP 41 DI 10.1067/mjd.2003.9 PG 8 WC Dermatology SC Dermatology GA 634PC UT WOS:000180348600004 PM 12522368 ER PT J AU Streams, BN Liu, V Liegeois, N Moschella, SM AF Streams, BN Liu, V Liegeois, N Moschella, SM TI Clinical and pathologic features of nephrogenic fibrosing dermopathy: A report of two cases SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID SYSTEMIC-SCLEROSIS; SCLERODERMA; SCLEROMYXEDEMA; CLASSIFICATION AB Nephrogenic fibrosing dermopathy is a rare, recently described fibrotic skin condition that primarily affects patients with a history of renal disease. We describe 2 patients on hemodialysis with the characteristic clinical and pathologic features. Nephrogenic fibrosing dermopathy should be distinguished from other fibrotic disorders, such as scleromyxedema, systemic sclerosis, and eosinophilic fasciitis. C1 Massachusetts Gen Hosp, Dermatopathol Unit, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatopathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Lahey Clin, Burlington, MA USA. RP Liu, V (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, Dept Dermatol, Warren Bldg,8th Floor, Boston, MA 02114 USA. NR 12 TC 82 Z9 85 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2003 VL 48 IS 1 BP 42 EP 47 DI 10.1067/mjd.2003.77 PG 6 WC Dermatology SC Dermatology GA 634PC UT WOS:000180348600005 PM 12522369 ER PT J AU Schouten, R AF Schouten, R TI Commentary: Training for competence-form or substance? SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Editorial Material C1 Massachusetts Gen Hosp, Law & Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Schouten, R (reprint author), Massachusetts Gen Hosp, Law & Psychiat Serv, 60 Staniford St, Boston, MA 02114 USA. NR 6 TC 5 Z9 5 U1 0 U2 1 PU AMER ACAD PSYCHIATRY LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PY 2003 VL 31 IS 2 BP 202 EP 204 PG 3 WC Law; Psychiatry SC Government & Law; Psychiatry GA 829OC UT WOS:000222057500007 PM 12875498 ER PT J AU Sreenivasan, S Weinberger, LE Garrick, T AF Sreenivasan, S Weinberger, LE Garrick, T TI Expert testimony in sexually violent predator commitments: Conceptualizing legal standards of "mental disorder" and "likely to reoffend" SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Article ID OFFENDER RECIDIVISM RISK; SEX OFFENDERS; ACTUARIAL; ASSESSMENTS; METAANALYSIS; PREDICTION AB The most recent type of civil commitment for dangerous sex offenders is found under the sexually violent predator laws. Forensic psychiatrists or psychologists must render an opinion as to whether the sex offender has a diagnosed mental disorder and, as such, represents a risk to public safety if released from custody into the community. Thus, expert testimony provided by these professionals has taken a central role in the commitment determinations. There is considerable debate as to what disorders predispose individuals to sexual recidivism and what the term "likely" signifies. In this article, the authors explore the debate in terms of whether Antisocial Personality Disorder is a qualifying diagnosed mental disorder for classification as a sexually violent predator and how a likely threshold of risk of sexual recidivism can be conceptualized. C1 Greater Los Angeles VA Med Ctr, Gen Hosp Psychiat, Los Angeles, CA 90073 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Sreenivasan, S (reprint author), Greater Los Angeles VA Med Ctr, Gen Hosp Psychiat, 11301 Wilshire Blvd,691-B116, Los Angeles, CA 90073 USA. EM shoba.sreenivasan@med.va.gov NR 38 TC 20 Z9 20 U1 0 U2 0 PU AMER ACAD PSYCHIATRY LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PY 2003 VL 31 IS 4 BP 471 EP 485 PG 15 WC Law; Psychiatry SC Government & Law; Psychiatry GA 829OJ UT WOS:000222058300011 PM 14974803 ER PT J AU Thomas, SH Silen, W Cheema, F Reisner, A Aman, S Goldstein, JN Kumar, AM Stair, T AF Thomas, SH Silen, W Cheema, F Reisner, A Aman, S Goldstein, JN Kumar, AM Stair, T TI Effects of morphine analgesia on diagnostic accuracy in emergency department patients with abdominal pain: A prospective, randomized trial SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID ACUTE ABDOMEN; RELIEF AB BACKGROUND: Because of concerns about masking important physical findings, there is controversy surrounding whether it is safe to provide analgesia to patients with undifferentiated abdominal pain. The purpose of this study was to address the effects of analgesia on the physical examination and diagnostic accuracy for patients with abdominal pain. STUDY DESIGN: The study was a prospective, double-blind clinical trial in which adult Emergency Department (ED) patients with undifferentiated abdominal pain were randomized to receive placebo (control group, n = 36) or morphine sulphate (MS group, n = 38). Diagnostic and physical examination assessments were recorded before and after a 60-minute period during which study medication was titrated. Diagnostic accuracy and physical examination changes were compared between groups using univariate statistical analyses. RESULTS: There were no differences between control and MS groups with respect to changes in physical or diagnostic accuracy. The overall likelihood of change in severity of tenderness was similar in MS (37.7%) as compared with control (35.3%) patients (risk ratio [RR] 1.07, 95% confidence interval [CI] 0.64-1.78). MS patients were no more likely than controls to have a change in pain location (34.0% versus 41.2%, RR 0.82, 95% CI 0.50-1.36). Diagnostic accuracy did not differ between MS and control groups (64.2% versus 66.7%, RR 0.96, 95% CI 0.73-1.27). There were no differences between groups with respect to likelihood of any change occurring in the diagnostic list (37.7% versus 31.4%, RR 1.20, 95% CI 0.71-2.05). Correlation with clinical course and final diagnosis revealed no instance of masking of physical examination findings. CONCLUSIONS: Results of this study support a practice of early provision of analgesia to patients with undifferentiated abdominal pain. (C) 2003 by the American College of Surgeons. C1 Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Emergency Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Thomas, SH (reprint author), Massachusetts Gen Hosp, Dept Emergency Serv, Clin Bldg Room 115, Boston, MA 02114 USA. RI Goldstein, Joshua/H-8953-2016 NR 28 TC 73 Z9 77 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JAN PY 2003 VL 196 IS 1 BP 18 EP 31 AR PII S1072-7515(02)01480-1 DI 10.1016/S1072-7515(02)01480-1 PG 14 WC Surgery SC Surgery GA 634PN UT WOS:000180349600002 PM 12517545 ER PT J AU Pierie, JPEN Choudry, U Muzikansky, A Finkelstein, DM Ott, MJ AF Pierie, JPEN Choudry, U Muzikansky, A Finkelstein, DM Ott, MJ TI Prognosis and management of extramammary Paget's disease and the association with secondary malignancies SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the Society-of-Surgical-Oncology CY MAR 15-18, 2001 CL WASHINGTON, D.C. SP Soc Surg Oncol ID RADIOTHERAPY; VULVA AB BACKGROUND: Extramammary Paget's disease (EMPD) is a rare clinical entity and can be associated with other malignancies. We analyzed our experience for prognosis and impact of therapy on outcomes. STUDY DESIGN: We conducted a retrospective review of all patients (n = 33) with EMPD treated at a tertiary care center from 1971 to 1998. Pathologic features of EMPD, concurrent secondary malignancies, and the effect of operations on recurrence were analyzed. Overall survival was compared with that of the general population. RESULTS: Male-to-female ratio was 4:29, and median age was 70 years. Median followup was 68 months, and no patient died from EMPD. The lesion was predominantly found on the vulva (76%). Patch-like, nonconfluent growth was present in 45% of patients, and no patient had pathologic lymph nodes. The most common signs and symptoms were irritation or pruritus (73%) and rash (61%). The presence of patches, invasive tumor growth, or a second malignancy were significantly associated with a higher recurrence rate. The type of operation, either local excision or hemivulvectomy, was not related to the time to recurrence. Complete gross resection was achieved in 94% of cases. Fifty-six percent of patients had microscopically positive margin and this correlated with a significantly higher recurrence rate (p = 0.002). The tumor recurred clinically in 14 of 33 patients (42%) after a median of 152 months (range 5 to 209 months). In those patients, between one and six reexcisions were performed. In 14 of 33 patients with EMPD (42%), 16 concurrent secondary malignancies were found. Overall survival rates for EMPD patients were similar to those of the general population. CONCLUSIONS: EMPD is an infrequently diagnosed disease that is preferably managed with complete local excision and reexcisions if needed. A thorough search for frequently occurring secondary malignancies might be beneficial to provide the best outcomes for these patients. (C) 2003 by the American College of Surgeons. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg Oncol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Stat Ctr, Boston, MA USA. Med Ctr Leeuwarden, Dept Surg, Leeuwarden, Netherlands. RP Ott, MJ (reprint author), LDS Hosp, 324 10th Ave,Suite 184, Salt Lake City, UT 84103 USA. NR 19 TC 69 Z9 72 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JAN PY 2003 VL 196 IS 1 BP 45 EP 50 AR PII S1072-7515(02)0619-8 DI 10.1016/S1072-7515(02)01619-8 PG 6 WC Surgery SC Surgery GA 634PN UT WOS:000180349600005 PM 12517548 ER PT J AU Lui, LY Stone, K Cauley, JA Hillier, T Yaffe, K AF Lui, LY Stone, K Cauley, JA Hillier, T Yaffe, K TI Bone loss predicts subsequent cognitive decline in older women: The study of osteoporotic fractures SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE bone loss; cognitive decline; older women ID APOLIPOPROTEIN-E POLYMORPHISM; ESTROGEN REPLACEMENT THERAPY; MINERAL DENSITY; ALZHEIMERS-DISEASE; HIP FRACTURE; RISK-FACTORS; COMMUNITY WOMEN; ELDERLY WOMEN; WEIGHT CHANGE; E PHENOTYPE AB OBJECTIVES: To determine whether the rate of bone loss predicts subsequent cognitive decline independently of baseline bone mass and whether apolipoprotein E (ApoE) genotype explains the association. DESIGN: A prospective cohort study. SETTING: Clinical centers in Baltimore, Maryland; Minneapolis, Minnesota; Pittsburgh, Pennsylvania; and Portland, Oregon. PARTICIPANTS: Four thousand four hundred sixty-two women aged 70 and older (mean = 75.8) participating in the Study of Osteoporotic Fractures. MEASUREMENTS: Total hipbone mineral density (BMD) was measured 2 and 6 years after enrollment (mean follow-up = 3.5 years), and expressed as annualized percentage rate of bone change. A modified Mini-Mental State Examination (mMMSE) was administered at 6 and 10 years (mean follow-up = 4.5 years) and defined cognitive decline as a decline of three or more points on repeat mMMSE score. ApoE genotype information was available on 883 women. RESULTS: Cognitive decline occurred in 12% of the women with the least bone loss (by quartile), 14% in the second, 16% in the third, and 20% in those with the greatest bone loss. After adjustment for age, education, stroke, functional status, estrogen use, body mass index, and smoking, the results were similar. Those who lost the most BMD were almost 40% more likely than women in the lowest quartile to develop cognitive decline in the multivariate model (odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.1-1.8). A similar association between hipbone loss and cognitive decline was observed in the multivariate model further adjusting for ApoE e4 (OR = 1.5, 95% CI = 0.8-2.7). CONCLUSIONS: Women with more rapid hipbone loss were more likely to develop cognitive decline than those who had lower rate of loss (or who gained bone mass). Differences in functional status, estrogen use, and ApoE did not explain this association. Further investigation is needed to determine the mechanisms that link osteoporosis and cognitive decline. C1 Univ Calif San Francisco, Dept Med, San Francisco, CA 94105 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94105 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94105 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94105 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94105 USA. Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Lui, LY (reprint author), Univ Calif San Francisco, Dept Med, 74 New Montgomery St,Suite 600, San Francisco, CA 94105 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [AG05394, AG05407, K23-AG00888]; NIAMS NIH HHS [AR35582, AR35583, AR35584] NR 28 TC 26 Z9 26 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2003 VL 51 IS 1 BP 38 EP 43 DI 10.1034/j.1601-5215.2002.51007.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 635ML UT WOS:000180403200006 PM 12534843 ER PT J AU Walter, LC Lui, LY Eng, C Covinsky, KE AF Walter, LC Lui, LY Eng, C Covinsky, KE TI Risk of hip fracture in disabled community-living older adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hip fracture; frail; older ID NURSING-HOME RESIDENTS; BONE-MINERAL DENSITY; OSTEOPOROTIC FRACTURES; COGNITIVE IMPAIRMENT; PHYSICAL-ACTIVITY; ELDERLY MEN; FALLS; CARE AB OBJECTIVES: To determine the rate of hip fracture and risk factors associated with hip fractures in disabled older persons who enroll in the Program of All-Inclusive Care for the Elderly (PACE), a program providing comprehensive care to community-living nursing-home-eligible persons. DESIGN: Prospective cohort study between January 1990 and December 1997. SETTING: The twelve PACE demonstration sites: San Francisco, California; Columbia, South Carolina; Detroit, Michigan; Denver, Colorado; East Boston, Massachusetts; El Paso, Texas; Milwaukee, Wisconsin; Oakland, California; Portland, Oregon; Rochester, New York; Sacramento, California; and the Bronx, New York. PARTICIPANTS: Five thousand one hundred eighty-seven individuals in PACE; mean age 79, 71% female, 49% white, 47% with dementia. MEASUREMENTS: Functional status, cognitive status, demographics, and comorbid conditions were recorded on all the participants, who were tracked for occurrence of a hip fracture. The goals were to determine the rate of hip fracture and identify risk factors. RESULTS: Two hundred thirty-eight hip fractures (4.6%) occurred during follow-up. The rate of hip fracture was 2.2% per person-year. Four independent predictors of hip fracture were identified using Cox proportional hazard analysis: age of 75 and older (adjusted hazard ratio (HR) = 2.0, 95% confidence interval (CI) = 1.4-2.8); white ethnicity (HR = 2.1, 95% CI = 1.6-2.8); ability to transfer independently to and from bed, chair, and toilet (HR = 3.0, 95% Cl = 1.2-7.2); and five or more Short Portable Mental Status Questionnaire errors (HR = 1.6, 95% CI = 1.3-2.1). The incidence of hip fracture ranged from 0.5% per person-year in persons with zero to one independent risk factors to 4.7% per person-year in those with all four independent risk factors. CONCLUSIONS: The rate of hip fracture in this cohort of disabled community-living older adults was similar to that reported in nursing home cohorts. Older age, white race, ability to transfer independently, and cognitive impairment were independent predictors of hip fracture. Persons with these risk factors should be targeted for preventive interventions, which should include strategies for making transferring safer. C1 San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. On Lok Senior Hlth Serv, San Francisco, CA USA. RP Walter, LC (reprint author), San Francisco VA Med Ctr, Div Geriatr, 181G,4150 Clement St, San Francisco, CA 94121 USA. FU NIA NIH HHS [5 T32 AG00212-09]; PHS HHS [K02H500006-01] NR 23 TC 25 Z9 27 U1 8 U2 16 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2003 VL 51 IS 1 BP 50 EP 55 DI 10.1034/j.1601-5215.2002.51009.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 635ML UT WOS:000180403200008 PM 12534845 ER PT J AU Simmons, SF Lam, HY Rao, G Schnelle, JF AF Simmons, SF Lam, HY Rao, G Schnelle, JF TI Family members' preferences for nutrition interventions to improve nursing home residents' oral food and fluid intake SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE nutrition interventions; preferences; nursing homes ID LONG-TERM-CARE; DECISION-MAKING; WEIGHT-LOSS; DEMENTIA; QUALITY AB OBJECTIVES: To measure family members' preferences for nutrition interventions to improve the oral food and fluid intake of their relatives in a nursing home. DESIGN: Cross-sectional descriptive. SETTING: Three skilled nursing facilities in Southern California. PARTICIPANTS: One hundred five residents from the three skilled nursing facilities and their respective family members. MEASUREMENTS: A mailed questionnaire to family members that consisted of 15 forced-choice comparisons between six nutrition interventions. An assessment of oral food and fluid intake during mealtime for 3 days (nine meals) for each participant using direct observations and estimations of percentage consumed (0% to 100%) by trained research staff. RESULTS: In order of most to least desirable, the family members preferred the following interventions to improve their relative's oral food and fluid intake: (1) improve quality of food; (2) improve quality and quantity of feeding assistance; (3) provide multiple small meals and snacks throughout the day; (4) place resident in preferred dining location; (5) provide an oral liquid nutritional supplement between meals; and (6) provide a medication to stimulate appetite. The average +/- standard deviation total percentage intake for residents whose family members reported that they thought their relative had a problem with their intake was 50% +/- 16%. CONCLUSIONS: Family members prefer that other nutrition interventions be attempted before the use of oral supplements or pharmacological approaches. Family members perceive a need for interventions when residents consume, on average, only half of the food and fluid items provided during mealtime. C1 Univ Calif Los Angeles, Borun Ctr Gerontol Res, Los Angeles Jewish Home Aging, Sch Med,Dept Geriatr, Reseda, CA 91335 USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA USA. Vet Adm Greater Los Angeles Healthcare Syst, Sepulveda Geriatr Res Educ & Clin Ctr, Sepulveda, CA USA. RP Simmons, SF (reprint author), Univ Calif Los Angeles, Borun Ctr Gerontol Res, Los Angeles Jewish Home Aging, Sch Med,Dept Geriatr, 7150 Tampa Ave, Reseda, CA 91335 USA. FU NIA NIH HHS [AG10415] NR 29 TC 16 Z9 17 U1 1 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2003 VL 51 IS 1 BP 69 EP 74 DI 10.1034/j.1601-5215.2002.51012.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 635ML UT WOS:000180403200011 PM 12534848 ER PT J AU Gruenewald, DA Matsumoto, AM AF Gruenewald, DA Matsumoto, AM TI Testosterone supplementation therapy for older men: Potential benefits and risks SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE testosterone; aging; hormone replacement therapy; androgens; hypogonadism ID CORONARY-ARTERY DISEASE; BONE-MINERAL DENSITY; NURSING-HOME MEN; MIDDLE-AGED MEN; HYPOGONADAL MEN; TRANSDERMAL TESTOSTERONE; ANDROGEN DEFICIENCY; REPLACEMENT THERAPY; ELDERLY MEN; BIOAVAILABLE TESTOSTERONE AB Serum testosterone levels decline gradually and progressively with aging in men. Many manifestations associated with aging in men, including muscle atrophy and weakness, osteoporosis, reduced sexual functioning, and increased fat mass, are similar to changes associated with testosterone deficiency in young men. These similarities suggest that testosterone supplementation may prevent or reverse the effects of aging. A MEDLINE search was performed to identify studies of testosterone supplementation therapy in older men. A structured, qualitative review was performed of placebo-controlled trials that included men aged 60 and older and evaluated one or more physical, cognitive, affective, functional, or quality-of-life outcomes. Studies focusing on patients with severe systemic diseases and hormone deficiencies related to specific diseases were excluded. In healthy older men with low-normal to mildly decreased testosterone levels, testosterone supplementation increased lean body mass and decreased fat mass. Upper and lower body strength, functional performance, sexual functioning, and mood were improved or unchanged with testosterone replacement. Variable effects on cognitive function were reported, with improvements in some cognitive domains (e.g., spatial, working, and verbal memory). Testosterone supplementation improved exercise-induced coronary ischemia in men with coronary heart disease, whereas angina pectoris was improved or unchanged. In a few studies, men with low testosterone levels were more likely to experience improvements in lumbar bone mineral density, self-perceived functional status, libido, erectile function, and exercise-induced coronary ischemia with testosterone replacement than men with less marked testosterone deficiency. No major unfavorable effects on lipids were reported, but hematocrit and prostate specific antigen levels often increased. Based on these results, testosterone supplementation cannot be recommended at this time for older men with normal or low-normal testosterone levels and no clinical manifestations of hypogonadism. However, testosterone replacement may be warranted in older men with markedly decreased testosterone levels, regardless of symptoms, and in men with mildly decreased testosterone levels and symptoms or signs suggesting hypogonadism. The long-term safety and efficacy of testosterone supplementation remain uncertain. Establishment of evidence-based indications will depend on further demonstrations of favorable clinical outcomes and symptomatic, functional, and quality-of-life benefits in carefully performed, long-term, randomized, placebo-controlled clinical trials. C1 Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Populat Ctr Res Reprod, Seattle, WA 98195 USA. RP Gruenewald, DA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, S-182-GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. NR 98 TC 145 Z9 155 U1 1 U2 12 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2003 VL 51 IS 1 BP 101 EP 115 DI 10.1034/j.1601-5215.2002.51018.x PG 15 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 635ML UT WOS:000180403200017 PM 12534854 ER PT J AU Yoo, SD Gao, ZF Cantini, C Loescher, WH van Nocker, S AF Yoo, SD Gao, ZF Cantini, C Loescher, WH van Nocker, S TI Fruit ripening in sour cherry: Changes in expression of genes encoding expansins and other cell-wall-modifying enzymes SO JOURNAL OF THE AMERICAN SOCIETY FOR HORTICULTURAL SCIENCE LA English DT Article DE Prunus cerasus; expansin; PME; PEL; XET; fruit ripening; fruit softening ID TOMATO FRUIT; MOLECULAR CHARACTERIZATION; PECTATE LYASE; XYLOGLUCAN ENDOTRANSGLYCOSYLASE; ANTISENSE SUPPRESSION; STRAWBERRY FRUIT; REGULATED GENES; SEQUENCE; PLANTS; AUXIN AB A preliminary understanding of developmental processes among divergent species is essential to evaluate the applicability of information from model species to plants of agricultural importance. In tomato (Lycopersicon esculentum Mill.), where the molecular biology associated with fruit ripening has been studied most extensively, tissue softening is due at least in part to the activity of proteins called expansins, in concert with enzymatic activities that modify the pectin and xyloglucan components of the cell wall. We evaluated the potential for the concerted action of expansins and other cell wall-modifying enzymes during ripening in a highly divergent fruit species, sour cherry (Prunus cerasus L.). We identified a family of four expansin genes that was strongly upregulated at the advent of ripening. Activation of these genes was accompanied by strong upregulation of gene(s) encoding potential pectin methylesterases, pectate lyase(s), and xyloglucan endotransglycosylase(s). Initiation of ripening and gene induction were also associated with a rapid decrease in cell wall weight. These results suggest that expansin and several other distinct activities could be involved in ripening-associated cell wall modification in cherries. C1 Michigan State Univ, Dept Hort, E Lansing, MI 48824 USA. RP van Nocker, S (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. EM vannocke@msu.edu NR 38 TC 14 Z9 20 U1 1 U2 8 PU AMER SOC HORTICULTURAL SCIENCE PI ALEXANDRIA PA 113 S WEST ST, STE 200, ALEXANDRIA, VA 22314-2851 USA SN 0003-1062 J9 J AM SOC HORTIC SCI JI J. Am. Soc. Hortic. Sci. PD JAN PY 2003 VL 128 IS 1 BP 16 EP 22 PG 7 WC Horticulture SC Agriculture GA 629VM UT WOS:000180072400003 ER PT J AU Allen, DN Goldstein, G Warnick, E AF Allen, DN Goldstein, G Warnick, E TI A consideration of neuropsychologically normal schizophrenia SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE schizophrenia; abstract reasoning; cluster analysis; premorbid ability ID COGNITIVE HETEROGENEITY AB Neuropsychological deficits are considered by many to be core features of schizophrenia. However, about 20% of patients with schizophrenia appear to have normal neuropsychological function. This study investigates this subgroup by comparing a "neuropsychologically normal" schizophrenia group to a non-schizophrenic, non-brain damaged patient comparison (PC) sample, and to patients with definitive brain damage who performed normally on neuropsychological testing. All patients completed the Halstead-Reitan Neuropsychological Test Battery and were classified as neuropsychologically normal or impaired using the Average Impairment Rating (AIR). In a sample of 113 patients with schizophrenia, 19.5% were classified as neuropsychologically normal. The brain damaged neuropsychologically normal group (BD-NN) consisted of 14.3% of 124 subjects. These groups were compared with a patient non-schizophrenic. non-brain damaged group who were selected on the basis of having an Average Impairment Rating in the neuropsychologically normal range. The neuropsychologically normal schizophrenic group performed less well than the non-brain damaged, non-schizophrenic patient comparison group on a number of tests, indicating that patients in this group may not be completely neuropsychologically normal, and would be better characterized as "high-functioning," or near normal. The results are discussed in regard to possible neurobiological differences between neuropsychologically impaired and intact schizophrenic patients, and implications for course and outcome. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Nevada, Dept Psychol, Las Vegas, NV 89154 USA. Univ Pittsburgh, Pittsburgh, PA 15213 USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr 151R, Pittsburgh, PA 15206 USA. NR 31 TC 46 Z9 46 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD JAN PY 2003 VL 9 IS 1 BP 56 EP 63 DI 10.1017/S135561770391006X PG 8 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 661HL UT WOS:000181885100006 PM 12570358 ER PT J AU Kremen, WS Seidman, LJ Faraone, SV Tsuang, MT AF Kremen, WS Seidman, LJ Faraone, SV Tsuang, MT TI Is there disproportionate impairment in semantic or phonemic fluency in schizophrenia? SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE verbal fluency; semantic memory; frontal cortex; temporoparietal cortex; schizophrenia ID VERBAL FLUENCY; FRONTAL-LOBE; NEUROPSYCHOLOGICAL FUNCTION; AFFECTIVE-DISORDERS; MEMORY IMPAIRMENT; THOUGHT-DISORDER; MATCHING FALLACY; BRAIN; DYSFUNCTION; RELATIVES AB Phonemic and semantic fluency involve the capacity to generate words beginning with particular letters or belonging to particular categories, respectively. The former has been associated with frontal lobe function and the latter with temporoparietal function, but neuroimaging studies indicate overlap of underlying neural networks. Schizophrenia patients may experience disproportionate semantic fluency impairment owing to abnormal semantic organization; however, executive dysfunction in schizophrenia suggests possible disproportionate phonemic fluency impairment. Moreover, little is known about the diagnostic specificity of either verbal fluency deficit to schizophrenia or their stability over time. We examined 83 schizophrenia patients, 15 bipolar disorder patients, and 83 normal controls. Both fluency types were impaired in schizophrenia patients. Schizophrenia patients as a whole manifested disproportionate semantic fluency impairment relative to bipolar disorder patients, but only a subset of schizophrenia patients manifested disproportionate semantic fluency impairment relative to controls. Few characteristics, except to some extent paranoid-nonparanoid subtype, meaningfully differentiated schizophrenia patients with and without this disproportionate impairment. Verbal fluency measures were moderately stable over a 4-year period in schizophrenia patients and controls (.48 < rs <.79). These results mirror a literature that overall suggests a small degree of disproportionate semantic fluency impairment in schizophrenia, but also some heterogeneity in fluency deficits. C1 Univ Calif Davis, Sch Med, Dept Psychiat, Sacramento, CA 95817 USA. Univ Calif Davis, Napa Psychiat Res Ctr, Napa State Hosp, Napa, CA USA. Harvard Univ, Sch Med, Dept Psychiat,Massachusetts Mental Hlth Ctr, Brockton W Roxbury VA Med Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. RP Kremen, WS (reprint author), Univ Calif Davis, Sch Med, Dept Psychiat, 2230 Stockton Blvd, Sacramento, CA 95817 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH46318, MH43518-01] NR 62 TC 37 Z9 37 U1 3 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD JAN PY 2003 VL 9 IS 1 BP 79 EP 88 DI 10.1017/S1355617703910095 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 661HL UT WOS:000181885100009 PM 12570361 ER PT J AU Saha, S Saint, S Christakis, DA AF Saha, S Saint, S Christakis, DA TI Impact factor: a valid measure of journal quality? SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB Objectives: Impact factor, an index based on the frequency with which a journal's articles are cited in scientific publications, is a putative marker of journal quality. However, empiric studies on impact factor's validity as an indicator of quality are lacking. The authors assessed the validity of impact factor as a measure of quality for general medical journals by testing its association with journal quality as rated by clinical practitioners and researchers. Methods: We surveyed physicians specializing in internal medicine in the United States, randomly sampled from the American Medical Associations Physician Masterfile (practitioner group, n = 113) and from a list of graduates from a national postdoctoral training program in clinical and health services research (research group, n = 151). Respondents rated the quality of nine general medical journals, and we assessed the correlation between these ratings and the journals' impact factors. Results: The correlation between impact factor and physicians' ratings of journal quality was strong (r(2) = 0.82, P = 0.001). The correlation was higher for the research group (r(2) = 0.83, P = 0.001) than for the practitioner group (r(2) = 0.62, P = 0.01). Conclusions: Impact factor may be a reasonable indicator of quality for general medical journals. C1 Portland VA Med Ctr, Div Gen Internal Med & Geriatr, Portland, OR 97207 USA. Portland VA Med Ctr, Dept Med Informat & Outcomes Res, Portland, OR 97207 USA. Portland VA Med Ctr P3MED, Portland, OR 97207 USA. Univ Michigan, Div Gen Med, Taubman Ctr 3116, Ann Arbor, MI 48109 USA. Univ Washington, Dept Pediat, Seattle, WA 98103 USA. Univ Washington, Inst Child Hlth, Seattle, WA 98103 USA. RP Saha, S (reprint author), Portland VA Med Ctr, Div Gen Internal Med & Geriatr, 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. NR 11 TC 227 Z9 237 U1 5 U2 31 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JAN PY 2003 VL 91 IS 1 BP 42 EP 46 PG 5 WC Information Science & Library Science SC Information Science & Library Science GA 642BN UT WOS:000180784300008 PM 12572533 ER PT J AU Quarterman, RL McMillan, A Ratcliffe, MB Block, MI AF Quarterman, RL McMillan, A Ratcliffe, MB Block, MI TI Effect of preoperative delay on prognosis for patients with early stage non-small cell lung cancer SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Western-Thoracic-Surgical-Association CY JUN 20-23, 2001 CL SAN DIEGO, CALIFORNIA SP Western Thorac Surg Assoc ID MICROMETASTASES; CARCINOMA; SURVIVAL; PROJECT; IMPACT AB Objective: Screening for lung cancer will discover many nodules of indeterminate pathology. Observation has the theoretic risk of permitting dissemination of a localized cancer and worsening prognosis, whereas immediate evaluation of benign conditions generates morbidity and cost. This study was conducted to assess the effect of delay in surgical intervention on survival for patients with early stage non-small cell lung cancer. Methods: Records for patients with resected pathologic stage I and II non-small cell lung cancer (1989-1999) were abstracted for patient age, race, sex, medical history, date of presentation, date and type of surgical treatment, pathologic stage, and date of death or last follow-up. Kaplan-Meier survival analysis was performed to test for the effect of delay (time from presentation to surgical intervention) on survival. Results: Eighty-four patients were identified. Median age was 66 years, median preoperative interval was 82 days (range, 1-641 days), and median follow-up was 3.3 years (range, 5 days-11.9 years). Median survival was 3.7 years. Overall 5-year survival was 40%; disease-specific 5-year survival was 63%. Log-rank analysis of the effect of delay on overall survival generated a P value of .54, with an estimated hazard ratio for a 90-day delay of 1.06 (95% confidence interval, 0.87-1.30). Conclusions: For this population, we were unable to detect a significant effect of delay on prognosis. Although these results suggest that the risk of judicious observation of indeterminate pulmonary nodules might be low, the 95% confidence interval is broad. Larger sample sizes are needed to reach definitive conclusions. C1 Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. San Francisco Vet Affairs Med Ctr, Dept Surg, Div Cardiothorac Surg, San Francisco, CA USA. Univ Calif San Francisco, Div Biostat, Ctr Canc, San Francisco, CA 94143 USA. RP Block, MI (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, 96 Jonathan Lucas St,409 CSB, Charleston, SC 29425 USA. NR 20 TC 47 Z9 48 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 2003 VL 125 IS 1 BP 108 EP 114 DI 10.1067/mtc.2003.93 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 638PK UT WOS:000180579300021 PM 12538992 ER PT J AU Kumanohoso, T Otsuji, Y Yoshifuku, S Matsukida, K Koriyama, C Kisanuki, A Minagoe, S Levine, RA Tei, CW AF Kumanohoso, T Otsuji, Y Yoshifuku, S Matsukida, K Koriyama, C Kisanuki, A Minagoe, S Levine, RA Tei, CW TI Mechanism of higher incidence of ischemic mitral, regurgitation in patients with inferior myocardial infarction: Quantitative analysis of left ventricular and, mitral valve geometry in 103 patients with prior myocardial infarction SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID END-STAGE CARDIOMYOPATHY; HEART-FAILURE; PAPILLARY-MUSCLE; 3-DIMENSIONAL ECHOCARDIOGRAPHY; PROGNOSTIC IMPLICATIONS; DILATED CARDIOMYOPATHY; DOPPLER ASSESSMENT; DYSFUNCTION; SHAPE; SECONDARY AB Objective: The mechanism of higher incidence of ischemic mitral regurgitation in patients with inferior compared, with anterior myocardial infarction despite less global left ventricular remodeling and dysfunction is controversial. We hypothesized that inferior myocardial infarction causes left ventricular remodeling, which displaces posterior papillary muscle away from its normal position, leading to ischemic mitral regurgitation: Methods: In 103 patients with prior myocardial infarction (61 anterior and 42 inferior) and 20 normal control subjects, we evaluated the grade of ischemic mitral regurgitation on the basis of the percentage of Doppler jet area, left ventricular end-diastolic and end-systolic volumes, midsystolic mitral annular area, and midsystolic leaflet-tethering distance between papillary muscle tips and the contralateral anterior mitral annulus, which were determined by means of quantitative echocardiography. Results: Global left ventricular dilatation and dysfunction were significantly less pronounced in patients with inferior myocardial infarction (left ventricular endsystolic volume: 52 +/- 18 vs 60 +/- 24 mL, inferior vs anterior infarction, P< .05; left ventricular ejection fraction: 51% +/- 9% vs 42% +/- 7%, P <.0001). However, the percentage of mitral regurgitation jet area and the incidence of significant regurgitation (percentage of jet area of 10% or greater) was greater in inferior infarction (percentage of jet area: 10.1% +/- 7.5% vs 4.4% +/- 7.0%, P =.0002; incidence: 16/42 (38%) vs 6/61 (10%), P <.0001). The mitral annulus (area = 8.2 +/- 1.2 cm(2) in control subjects) was similarly dilated in both inferior and anterior myocardial infarction (9.7 +/- 1.7 vs. 9.5 +/- 2.3 cm(2), no significant difference), and the anterior papillary muscle-tethering distance (33.8 +/- 2.6 mm in control subjects) was also similarly and mildly increased in both groups (35.2 +/- 2.4 vs 35.2 +/- 2.8 mm, no significant difference). However, the posterior papillary muscle-tethering distance (33.3 +/- 2.3 mm in control subjects) was significantly greater in inferior compared with anterior myocardial infarction (38.3 +/- 4.1 vs 34.7 +/- 2.9 mm, P =.0001). Multiple stepwise regression analysis identified the increase in posterior papillary muscle-tethering distance divided by body surface area as an independent contributing factor to the percentage of mural regurgitation jet area (r(2) = 0.70, P <.0001). Conclusions: It is suggested that the higher incidence and greater severity of ischemic mitral regurgitation in patients with inferior compared with anterior myocardial infarction can be related to more severe geometric changes in the mitral valve apparatus with greater displacement of posterior papillary muscle caused by localized inferior basal left ventricular remodeling, which results in therapeutic implications for potential benefit of procedures, such as infarct plication and leaflet or chordal elongation, to reduce leaflet tethering. C1 Kagoshima Univ, Sch Med, Dept Internal Med 1, Kagoshima 8908520, Japan. Kagoshima Univ, Sch Med, Dept Publ Hlth, Kagoshima 8908520, Japan. Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA USA. RP Otsuji, Y (reprint author), Kagoshima Univ, Sch Med, Dept Internal Med 1, 8-35-1 Sakuragaoka, Kagoshima 8908520, Japan. NR 44 TC 140 Z9 152 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 2003 VL 125 IS 1 BP 135 EP 143 DI 10.1067/mtc.2003.78 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 638PK UT WOS:000180579300026 PM 12538997 ER PT J AU Hobbins, JC Lezotte, DC Persutte, WH DeVore, GR Benacerraf, BR Nyberg, DA Vintzileos, AM Platt, LD Carlson, DE Bahado-Singh, RO Abuhamad, AZ AF Hobbins, JC Lezotte, DC Persutte, WH DeVore, GR Benacerraf, BR Nyberg, DA Vintzileos, AM Platt, LD Carlson, DE Bahado-Singh, RO Abuhamad, AZ TI An 8-center study to evaluate the utility of midterm genetic sonograms among high-risk pregnancies SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE Down syndrome; prenatal diagnosis; second trimester; ultrasonography ID 2ND-TRIMESTER ULTRASOUND; DOWN-SYNDROME; TRISOMY-21; POPULATION AB Objective. A multicenter study was undertaken to evaluate the diagnostic efficacy of a genetic sonogram. Methods. Eight centers provided data on 176 pregnancies complicated by fetal Down syndrome. One hundred thirty-four pregnancies were considered high risk because of advanced maternal age (>35 years), and 42 were considered high risk for having "abnormal" triple-screen results (risk >1:250). Each center provided fetal biometric data, information regarding the presence or absence of major structural abnormalities, and between 3 and 6 additional ultrasonographic markers for trisomy 21. The heterogeneity of our 8 independent "sensitivity estimates" was evaluated by Poisson regression, and a single combined estimate of the sensitivity was calculated. Results. Of the total 176 cases of trisomy 21, 125 fetuses (71.0%) had either an abnormal long bone length (femur length, humerus length, or both), a major structural abnormality, or a Down syndrome marker. The combined diagnostic sensitivity was 71.6%, with a range of 63.6% (7 of 11) to 80% (8 of 10). Five centers had sensitivity estimates falling between 64% and 76%. The sensitivity of individual markers varied between 3% (sandal gap) and 46.5% (nuchal skin fold thickness). A condensed regimen of nuchal skin fold thickness, femur length, and a standard anatomic survey would screen in 56.8% of fetuses with Down syndrome. Conclusions. This 8-center study that included many fetuses with Down syndrome validates the concept that the genetic sonogram can be used to better adjust the Down syndrome risk for high-risk patients. C1 Univ Colorado, Hlth Sci Ctr, Dept Obstet & Gynecol, Sch Med, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Prevent Med & Biostat, Denver, CO 80262 USA. Fetal Diagnost Ctr Pasadena & Alfigen, Inst Genet, Pasadena, CA USA. Harvard Univ, Sch Med, Dept Obstet & Gynecol, Massachusetts Gen Hosp, Boston, MA USA. Pacific NW Diagnost Ultrasound, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA USA. Univ Med & Dent New Jersey, Dept Maternal Fetal Med & Obstet, New Brunswick, NJ USA. Univ Calif Los Angeles, Sch Med, Dept Obstet & Gynecol, Cedars Sinai Med Ctr, Los Angeles, CA USA. Yale Univ, Sch Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, New Haven, CT USA. Eastern Virginia Med Sch, Div Maternal Fetal Med, Norfolk, VA 23501 USA. RP Hobbins, JC (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Obstet & Gynecol, Sch Med, 4200 E 9th Ave,Mail Stop B198, Denver, CO 80262 USA. NR 9 TC 41 Z9 41 U1 0 U2 2 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD JAN PY 2003 VL 22 IS 1 BP 33 EP 38 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 632ZT UT WOS:000180255300006 PM 12523608 ER PT J AU Tabatabaei, S McDougal, WS AF Tabatabaei, S McDougal, WS TI Primary skin closure of large groin defects after inguinal lymphadenectomy for penile cancer using an abdominal cutaneous advancement flap SO JOURNAL OF UROLOGY LA English DT Article DE penis; penile neoplasms; surgical flaps; groin; lymph node excision ID DISSECTION; COVER AB Purpose: Large groin defects may be created after inguinal lymphadenectomy for bulky metastatic penile cancer. We describe a new method of primary closure of a large groin skin defect. Materials and Methods: In 3 patients with large volume inguinal lymph node metastases with skin breakdown and secondary infection extensive inguinal lymphadenectomy was done with wide surgical excision of skin and subcutaneous tissue. The procedures resulted in a large groin defect. Sartorius muscle was transferred to cover the femoral vessels. An abdominal advancement cutaneous flap was placed for soft tissue and skin coverage of the wound. Results: Primary closure of a large skin defect was possible using an abdominal advancement flap. In all patients the wound healed primarily with good cosmesis. A single patient underwent postoperative external beam radiation therapy to the flap site with no untoward effect on graft survival. Conclusions: Large groin skin defects can be closed primarily using an abdominal advancement flap. This technique may also be used for bilateral groin defects. Compared with other types of flaps advocated for this purpose the main advantages of the procedure are simplicity, lower morbidity and superior cosmetic results. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Tabatabaei, S (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 11 TC 9 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2003 VL 169 IS 1 BP 118 EP 120 DI 10.1097/01.ju.0000035363.77382.b2 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 627EX UT WOS:000179921200032 PM 12478117 ER PT J AU Visser, K Kuntz, KM Donaldson, MC Gazelle, GS Hunink, MGM AF Visser, K Kuntz, KM Donaldson, MC Gazelle, GS Hunink, MGM TI Pretreatment imaging workup for patients with intermittent claudication: A cost-effectiveness analysis SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE cost-effectiveness; extremities, blood supply; peripheral vascular disease ID ARTERIAL OCCLUSIVE DISEASE; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; MAGNETIC-RESONANCE ANGIOGRAPHY; MR-ANGIOGRAPHY; STENT PLACEMENT; LOWER-EXTREMITY; RUNOFF VESSELS; LOWER-LIMB; HEALTH; REVASCULARIZATION AB PURPOSE: To determine the optimal imaging strategy in pretreatment workup of patients with intermittent claudication with use of noninvasive imaging modalities and intraarterial digital subtraction angiography (DSA). MATERIALS AND METHODS: A decision-analytic model that considered test characteristics such as sensitivity, complications induced by the test, implications of missing lesions, and the consequences of overtreating patients, was developed to evaluate the societal cost-effectiveness (CE) of magnetic resonance (MR) angiography, duplex ultrasonography (US), and DSA. Our main outcome measures were quality-adjusted life years (QALYs), lifetime costs (in dollars), and incremental CE ratios. The base-case analysis considered a cohort of 60-year old male patients without a history of coronary artery disease who presented with severe claudication to undergo pretreatment imaging workup. RESULTS: The range in effectiveness and lifetime costs among different diagnostic workup strategies was small (largest difference in effectiveness: 0.025 QALYs; largest difference in lifetime costs: $1,800). If treatment was limited to angioplasty in patients with suitable lesions, MR angiography had an incremental CE ratio of $35,000 per QALY compared with no diagnostic workup, and DSA had an incremental CE ratio of $471,000 per QALY compared with MR angiography. If treatment options included both angioplasty and bypass surgery, DSA had an incremental CE ratio of $179,000 per QALY compared with no diagnostic workup, and MR angiography and duplex US were less effective and more costly. CONCLUSIONS: The differences in costs and effectiveness among diagnostic imaging strategies for patients with intermittent claudication are slight and MR angiography or duplex US can replace DSA without substantial loss in effectiveness and with a slight cost reduction. C1 Univ Med Ctr Rotterdam, ART Program, Dept Epidemiol & Biostat, Erasmus MC, NL-3015 GE Rotterdam, Netherlands. Univ Med Ctr Rotterdam, Erasmus MC, Dept Radiol, NL-3015 GE Rotterdam, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Decis Anal & Technol Assessment Grp, Boston, MA USA. Brigham & Womens Hosp, Div Vasc Surg, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Cambridge, MA 02138 USA. RP Visser, K (reprint author), Univ Med Ctr Rotterdam, ART Program, Dept Epidemiol & Biostat, Erasmus MC, Room EE21-18,Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands. NR 38 TC 14 Z9 14 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JAN PY 2003 VL 14 IS 1 BP 53 EP 62 DI 10.1097/01.RVI.0000052291.26939.82 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 645EA UT WOS:000180962200007 PM 12525586 ER PT J AU Musicant, SE Giswold, ME Olson, CJ Landry, GJ Taylor, LM Yeager, RA Edwards, JM Moneta, GL AF Musicant, SE Giswold, ME Olson, CJ Landry, GJ Taylor, LM Yeager, RA Edwards, JM Moneta, GL TI Postoperative duplex scan surveillance of axillofemoral bypass grafts SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the American-Association-for-Vascular-Surgery CY JUN 09-12, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Vascular Surg ID SUPPORTED POLYTETRAFLUOROETHYLENE; FEMOROPOPLITEAL BYPASS; AXILLOBIFEMORAL BYPASS; INFRAINGUINAL BYPASS; PATENCY; VEIN; ULTRASONOGRAPHY; PROGRAM AB Objective: Duplex scan surveillance (DS) for axillofemoral bypass grafts (AxFBGs) has not been extensively studied. The intent of this study was twofold: 1, to characterize the flow velocities within AxFBGs; and 2, to determine whether postoperative DS is useful in assessment of future patency of AxFBGs. Methods. We identified all patients who underwent AxFBG procedures between January 1996 and January 2001 at our combined university and Veterans Affairs hospital vascular surgical service. All grafts were performed with ringed 8-mm polytetrafluoroethylene with the distal limb of the axillofemoral component anastomosed to the hood of the femoral-femoral graft. DS was every 3 months for 1 year and every 6 months thereafter. Duplex scan results were compared in primarily patent grafts with grafts that thrombosed. Graft failures from infection were excluded. Influences of ankle-brachial index, blood pressure, outflow patency, operative indication, and comorbidities on graft patency were analyzed. Results. One hundred twenty patients underwent AxFBG procedures. Twenty-eight were excluded because of infection or death before surveillance examination. Fourteen were lost to follow-up, 23 had failed grafts from occlusion, and 55 had grafts that remained patent. In the 78 patients evaluated during long-term follow-up period, the mean peak systolic velocities (PSVs) at the proximal (axillary) anastomosis during the first postoperative year ranged from 153 to 194 cm/s. Mean PSVs at the mid portion of the axillofemoral graft during the first postoperative year ranged from 100 to 125 cm/s, whereas those for the distal axillofemoral anastomosis ranged from 93 to 129 cm/s. Mean midgraft and distal anastomotic velocities obtained before thrombosis were significantly lower in the thrombosed grafts compared with the last recorded velocities at the same sites in the patent grafts (mean PSV, 84 versus 112 cm/s; P = .015; mean PSV, 89 versus 127 cm/s; P = .024, respectively). Forty-eight percent of occluded grafts had a mean midgraft PSV at last observation of less than 80 cm/s. Blood pressure correlated with midgraft velocity (r = 0.415; P < .05). With multivariate logistic regression analysis, a mean midgraft velocity less than 80 cm/s was the sole independent factor associated with graft failure (P < .01). No patients with midgraft velocities greater than 155 cm/s had occlusion. Conclusion: Flow velocity varies widely within and among AxFBGs. Patency of AxFBGs is associated with higher midgraft PSV, and thrombosis with midgraft velocities less than 80 cm/s. C1 Oregon Hlth Sci Univ, Div Vasc Surg, Dept Surg, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Moneta, GL (reprint author), Oregon Hlth Sci Univ, Div Vasc Surg, Dept Surg, OP-11,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. NR 27 TC 12 Z9 12 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JAN PY 2003 VL 37 IS 1 BP 54 EP 60 DI 10.1067/mva.2003.43 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 636PN UT WOS:000180465200014 PM 12514578 ER PT J AU Merfeld, DM AF Merfeld, DM TI Rotation otolith tilt-translation reinterpretation (ROTTR) hypothesis: A new hypothesis to explain neurovestibular spaceflight adaptation SO JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION LA English DT Article; Proceedings Paper CT 6th Symposium on the Role of the Vestibular Organs in the Exploration of Space CY SEP 30-OCT 03, 2002 CL Portland, OR DE spaceflight; adaptation; vestibular; otolith organs; neurovestibular ID CANADIAN VESTIBULAR EXPERIMENTS; GRAVITO-INERTIAL CUES; EYE-MOVEMENT RESPONSES; HORIZONTAL ANGULAR VOR; LINEAR ACCELERATION; SQUIRREL-MONKEY; VESTIBULOOCULAR REFLEX; SPATIAL ORIENTATION; ECCENTRIC ROTATION; SPACELAB-1 MISSION AB Normally, the nervous system must process ambiguous graviceptor (e.g., otolith) cues to estimate tilt and translation. The neural processes that help perform these estimation processes must adapt upon exposure to weightlessness and readapt upon return to Earth. In this paper we present a review of evidence supporting a new hypothesis that explains some aspects of these adaptive processes. This hypothesis, which we label the rotation otolith tilt-translation reinterpretation (ROTTR) hypothesis, suggests that the neural processes resulting in spaceflight adaptation include deterioration in the ability of the nervous system to use rotational cues to help accurately estimate the relative orientation of gravity ("tilt"). Changes in the ability to estimate gravity then also influence the ability of the nervous system to estimate linear acceleration ("translation"). We explicitly hypothesize that such changes in the ability to estimate "tilt" and "translation" will be measurable upon return to Earth and will, at least partially, explain the disorientation experienced when astronauts return to Earth. In this paper, we present the details and implications of ROTTR, review data related to ROTTR, and discuss the relationship of ROTTR to the influential otolith tilt-translation reinterpretation (OTTR) hypothesis as well as discuss the distinct differences between ROTTR and OTTR. C1 Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Merfeld, DM (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. EM dan_merfeld@meei.harvard.edu FU NIDCD NIH HHS [R01 DC04158] NR 64 TC 14 Z9 14 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0957-4271 J9 J VESTIBUL RES-EQUIL JI J. Vestib. Res.-Equilib. Orientat. PY 2003 VL 13 IS 4-6 BP 309 EP 320 PG 12 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 824UD UT WOS:000221711500015 PM 15096674 ER PT J AU Spear, MA Schuback, D Miyata, K Grandi, P Sun, F Yoo, L Nguyen, A Brandt, CR Breakefield, XO AF Spear, MA Schuback, D Miyata, K Grandi, P Sun, F Yoo, L Nguyen, A Brandt, CR Breakefield, XO TI HSV-1 amplicon peptide display vector SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article; Proceedings Paper CT 91st Annual Meeting of the American-Association-for-Cancer-Research CY APR 01-05, 2000 CL SAN FRANCISCO, CALIFORNIA SP Amer Assoc Canc Res DE gene therapy; herpes simplex virus type-1; amplicon; phage display; peptide expression vector; vector targeting; glioblastoma multiforme ID SIMPLEX VIRUS TYPE-1; MALIGNANT GLIOMA; PACKAGING SYSTEM; RECEPTOR; CELLS; DNA; LOCALIZATION; REPLICATION; PROTEINS; BINDING AB There are significant uses for expressing foreign peptide epitopes in viral surface attachment proteins in terms of investigating viral targeting, biology, and immunology. HSV-1 attachment, followed by fusion and entry, is mediated in large part by the binding of viral surface glycoproteins to cell surface receptors, primarily through heparan sulfate (HS) glycosaminoglycan residues. We constructed a HSV-1 amplicon plasmid (pCONGA) carrying the gC primary attachment protein gene with unique restriction sites flanking the HS binding domain (HSBD) (residues 33-176) to allow rapid, high efficiency substitution with foreign peptide domains. To test this system, a His tag with an additional unique restriction site (for selection and assay digests) was recombined into the pCONGA HSBD site to create pCONGAH. Infection of pCONGAH transfected Vero cells with HSV-1 helper virus (gCDelta2-3 or hrR3) produced His-modified gC as demonstrated by western blot analysis with co-localization of anti-gC and anti-His tag antibodies to a protein of appropriate molecular weight (50 kd). As CONGA and CONGAH amplicons carry a GFP transgene and the gCDelta2-3 and hrR3 viruses carry a lacZ transgene, vector stocks produced from 1 x 10(5) Vero cells could be titered for competent vector on cell monolayers and were demonstrated to contain 2 x 10(5) amplicon vector transducing units (t.u.)/ml and 1 x 10(7) virus t.u./ml. As the amplicon plasmids also contain the neomycin resistance gene (neo(r)), long term vector producer cell lines were created using 6418 selection. This amplicon system provides means to rapidly and efficiently generate HSV-1 amplicon and viral vector expressing surface attachment proteins modified with different peptide epitopes for investigational and therapeutic uses, with the advantages of an amplicon plasmid that can be used with interchangeable helper virus vectors, is designed specifically for easy manipulation, and carries GFP and neo(r) transgenes for marker and selection functions. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Calif San Diego, UCSD Med Ctr, UCSD Canc Ctr, Gene Therapy Program, La Jolla, CA 92093 USA. Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Wisconsin, Dept Opthalmol, Madison, WI USA. RP Spear, MA (reprint author), Univ Calif San Diego, UCSD Med Ctr, UCSD Canc Ctr, Gene Therapy Program, MC 8757,200 W Arbor Dr, La Jolla, CA 92093 USA. FU NCI NIH HHS [CA 69246] NR 26 TC 11 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD JAN PY 2003 VL 107 IS 1 BP 71 EP 79 AR PII S0166-0934(02)00193-3 DI 10.1016/S0166-0934(02)00193-3 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 633BA UT WOS:000180258300010 PM 12445940 ER PT J AU Raja, A Venturi, M Kwong, P Sodroski, J AF Raja, A Venturi, M Kwong, P Sodroski, J TI CD4 binding site antibodies inhibit human immunodeficiency virus gp120 envelope glycoprotein interaction with CCR5 SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; INFLUENZA-VIRUS; TYPE-1; NEUTRALIZATION; EPITOPES; RECEPTOR; HEMAGGLUTININ; ATTACHMENT; INFECTION; MECHANISM AB The human immunodeficiency virus type 1 (HIV-1) gp120 exterior glycoprotein is conformationally flexible. Upon binding the host cell receptor, CD4, gp120 assumes a conformation that is able to bind the chemokine receptors CCR5 or CXCR4, which act as coreceptors for the virus. CD4-binding-site (CD4BS) antibodies are neutralizing antibodies elicited during natural infection that are directed against gp120 epitopes that overlap the binding site for CD4. Recent studies (S. H. Xiang et al., J. Virol. 76:9888-9899, 2002) suggest that CD4BS antibodies recognize conformations of gp120 distinct from the CD4-bound conformation. This predicts that the binding of CD4BS antibodies will inhibit chemokine receptor binding. Here, we show that Fab fragments and complete immunoglobulin molecules of CD4BS antibodies inhibit CD4-independent gp120 binding to CCR5 and cell-cell fusion mediated by CD4-independent HIV-1 envelope glycoproteins. These results are consistent with a model in which the binding of CD4BS antibodies limits the ability of gp120 to assume a conformation required for coreceptor binding. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Jimmy Fund Bldg,Room 824,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI031783, AI31783, AI41851, R01 AI041851, AI42848, R37 AI024755, R01 AI024030, AI24030, P30 AI042848, AI24755] NR 33 TC 17 Z9 17 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 1 BP 713 EP 718 DI 10.1128/JVI.77.1.713-718.2003 PG 6 WC Virology SC Virology GA 626CU UT WOS:000179855400071 PM 12477875 ER PT J AU Owens, CA Yang, PC Gottlinger, H Sodroski, J AF Owens, CA Yang, PC Gottlinger, H Sodroski, J TI Human and simian immunodeficiency virus capsid proteins are major viral determinants of early, postentry replication blocks in simian cells SO JOURNAL OF VIROLOGY LA English DT Article ID REVERSE-TRANSCRIPTASE INHIBITORS; LOCUS AFFECTING RESISTANCE; MURINE LEUKEMIA VIRUSES; CYCLOPHILIN-A; HIV-1 VIRIONS; ENVELOPE GLYCOPROTEINS; FUSION COFACTORS; LIFE-CYCLE; TYPE-1; GAG AB The cells of most Old World monkey species exhibit early, postentry restrictions on infection by human immunodeficiency virus type 1 (HIV-1) but not by simian immunodeficiency virus of macaques (SIVmac). Conversely, SIVmac but not HIV-1, infection is blocked in most New World monkey cells. By using chimeric HIV-I/SIVmac viruses capable of a single round of infection, we demonstrated that a major viral determinant of this restriction is the capsid (CA) protein. The efficiency of early events following HIV-1 and SIVmac entry is apparently determined by the interaction of the incoming viral CA and species-specific host factors. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NHLBI NIH HHS [P50 HL054785, HL54785]; NIAID NIH HHS [AI28691, P30 AI028691] NR 56 TC 115 Z9 118 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 1 BP 726 EP 731 DI 10.1128/JVI.77.1.726-731.2003 PG 6 WC Virology SC Virology GA 626CU UT WOS:000179855400073 PM 12477877 ER PT J AU Ibrahim, SA Burant, CJ Kwoh, CK AF Ibrahim, SA Burant, CJ Kwoh, CK TI Elderly hospitalized patients with diastolic heart failure: Lack of gender and ethnic differences in 18-month mortality rates SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID VENTRICULAR EJECTION FRACTION; CONVERTING ENZYME-INHIBITORS; PRIOR MYOCARDIAL-INFARCTION; CLINICAL-FEATURES; SYSTOLIC FUNCTION; COMMUNITY; DYSFUNCTION; PROGNOSIS; DIURETICS; OUTCOMES AB Background. Racial and gender differences in mortality rates have been reported for patients with systolic heart failure. Relatively little is known regarding diastolic heart failure prognosis. Methods. Our sample consisted of 1058 patients 65 years of age or older who were admitted to 30 hospitals in Northeastern Ohio with a principal diagnosis of heart failure and a left ventricular ejection fraction of greater than or equal to 50% by echocardiogram. Results. Of the 1058 patients with diastolic heart failure (13% African American and 87% white), African Americans and whites were comparable with respect to history of angina, stroke, being on dialysis, and alcohol use; the proportion of male patients was also comparable. The African American to white adjusted odds ratio for 18-month mortality (all cause) was 1.03 (0.66-1.59). For men versus women (30% vs 70%), the above-mentioned comorbidities were comparable, except women were More likely to have a do not resuscitate status (16% vs 7.3%; p = .000) and to be older (79.5 +/- 8 vs 77 +/- 7; p = .000). Men were more likely to have a history of tobacco use (30% vs 14%: p = .000) and alcohol use (36% vs 15%; p = .000), and a higher serum creatinine level (1.7 +/- 1.2 vs 1.4 +/- 1.1: p = .001). The men to women adjusted odds ratio for 18-month mortality (all cause) was 1.06 (0.76-1.46). Conclusion. In this cohort of elderly patients admitted with diastolic heart failure. there were no ethnic or gender differences in 18-month mortality rates. C1 VA Pittsburgh HealthCare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Case Western Reserve Univ, Sch Med, Dept Bioeth, Cleveland, OH 44106 USA. RP Ibrahim, SA (reprint author), VA Pittsburgh HealthCare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,11 East,130 A-U, Pittsburgh, PA 15240 USA. NR 20 TC 14 Z9 14 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2003 VL 58 IS 1 BP 56 EP 59 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 636GB UT WOS:000180445300008 PM 12560412 ER PT J AU Goodman, WG Juppner, H Salusky, IB Sherrard, DJ AF Goodman, WG Juppner, H Salusky, IB Sherrard, DJ TI Parathyroid hormone (PTH), PTH-derived peptides, and new PTH assays in renal osteodystrophy SO KIDNEY INTERNATIONAL LA English DT Article DE immunometric PTH assay; clinical management; end-stage renal disease; peptides and bone cells; chronic renal failure; skeletal lesions; PTH(1-84); renal bone disease ID CARBOXYL-TERMINAL REGION; INTERMITTENT CALCITRIOL THERAPY; PHOTOAFFINITY CROSS-LINKING; OSTEOBLAST-LIKE CELLS; BONE-DISEASE; SECONDARY HYPERPARATHYROIDISM; IMMUNORADIOMETRIC ASSAY; TUBEROINFUNDIBULAR PEPTIDE; CALCIUM-CONCENTRATION; ALKALINE-PHOSPHATASE AB Reliable measurements of parathyroid hormone (PTH) concentrations in serum or plasma are critical for the appropriate diagnosis and management of patients with renal osteodystrophy. With the introduction of second generation immunometric assays for PTH, it is now possible to measure exclusively full-length, biologically active PTH(1-84). In contrast, first generation immunometric assays that have been used widely for many years detect not only PTH(1-84), but also other large amino-terminally-truncated, PTH-derived peptides. This development will require a careful re-evaluation of PTH measurements, as determined by either first or second generation immunometric assays, and their relationship to bone histology and bone remodeling rates in patients with end-stage renal disease (ESRD). Such information is essential for proper clinical management, but only limited bone biopsy data are available to guide the interpretation of PTH results using second generation PTH assays. The different performance characteristics of first and second generation immunometic PTH assays also makes it possible to quantify the plasma levels of amino-terminally-truncated, PTH-derived peptides, which may accumulate disproportionately in patients with ESRD. Recent experimental evidence indicates that one or more of these peptides can modify bone cell activity and skeletal remodeling, possibly by interacting with a PTH receptor distinct from the type I PTH receptor that binds to the amino-terminal portion of PTH and mediates the classical biological actions of the hormone. The putative C-PTH receptor interacts with mid- and/or carboxyterminal regions of PTH and other amino-terminally-truncated PTH-derived peptides; signaling through it may contribute to the skeletal resistance to PTH that characterizes ESRD. The current review discusses certain aspects of the molecular structure of PTH and its interaction with various receptors, briefly comments about selected components of PTH secretion, highlights recent technical advances in PTH assays, and summarizes the effects of various PTH-derived peptides on bone cells and on skeletal metabolism. C1 Univ Calif Los Angeles, Med Ctr, Div Nephrol, Sch Med,Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Div Pediat Nephrol, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Vet Adm Puget Sound Hlth Care Syst, Seattle, WA USA. RP Goodman, WG (reprint author), Univ Calif Los Angeles, Med Ctr, Div Nephrol, Sch Med,Dept Med, 7-155 Factor Bldg,10833 Le Conte Ave, Los Angeles, CA 90095 USA. FU NCRR NIH HHS [RR-00865]; NIDDK NIH HHS [DK-35423, DK-50708, DK-07721, DK-52905, DK-60107, DK-46718] NR 80 TC 33 Z9 38 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2003 VL 63 IS 1 BP 1 EP 11 DI 10.1046/j.1523-1755.2003.00700.x PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 624NU UT WOS:000179766600001 PM 12472763 ER PT J AU Kiley, SC Thornhill, BA Tang, SS Ingelfinger, JR Chevalier, RL AF Kiley, SC Thornhill, BA Tang, SS Ingelfinger, JR Chevalier, RL TI Growth factor-mediated phosphorylation of proapoptotic BAD reduces tubule cell death in vitro and in vivo SO KIDNEY INTERNATIONAL LA English DT Article DE apoptosis; mechanical stress; ureteral obstruction; epidermal growth factor; p42 MAP kinase ID PROTEIN-KINASE-C; POLYCYSTIC KIDNEY-DISEASE; ACUTE-RENAL-FAILURE; URETERAL OBSTRUCTION; NEONATAL RAT; AKT PHOSPHORYLATION; ACTIVATION; APOPTOSIS; INHIBITION; CASPASE-9 AB Background. Exogenous growth factors administered during unilateral ureteral obstruction (UUO) in neonatal rats significantly reduce apoptosis and tubular atrophy. Because the mechanism underlying these salutary effects is largely unknown, we investigated signaling pathways potentially activated by growth factors to determine their roles in therapeutic action. Methods. Mechanical strain was applied to confluent cultures of immortalized rat proximal tubule cells to simulate obstruction-induced stretch injury in vivo. Growth factors, inhibitory antibodies or pharmacological inhibitors were added to cultures that were subsequently processed for TUNEL analysis or immunoblots to identify signaling pathways that could be modulating cell survival. For in vivo studies, kidneys harvested from rats +/- UUO +/- epidermal growth factor (EGF) were fixed or frozen for immunohistochemistry or immunoblot analysis. Results. Treatment with EGF or insulin-like growth factor-1 (IGF-1) during stretch decreased apoptosis by 50% (P < 0.001). Neutralizing antibodies (Abs) directed against either growth factor or its receptor blocked the reduction in apoptosis. Stretch decreased BAD phosphorylation by similar to50% (P < 0.001) relative to unstretched cells and each growth factor restored phosphorylation to basal levels. Kinase-specific inhibitors that blocked growth factor-mediated BAD phosphorylation promoted apoptosis in vitro. BAD phosphorylation decreased by similar to50% (P < 0.001) in the tubules of obstructed hydronephrotic rat kidneys and administration of EGF restored BAD phosphorylation to basal levels. Conclusions. Signaling pathways converging at BAD phosphorylation are key to growth factor-mediated attenuation of stretch-induced apoptosis in vitro and in vivo. C1 Univ Virginia, Sch Med, Dept Pediat, Charlottesville, VA 22908 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA USA. RP Kiley, SC (reprint author), Univ Virginia, Sch Med, Dept Pediat, Box 801334,Bldg MR-4,Room 2034,300 Lane Rd, Charlottesville, VA 22908 USA. FU NHLBI NIH HHS [HL48455]; NICHD NIH HHS [HD28810]; NIDDK NIH HHS [DK50836, DK52612, DK44756] NR 40 TC 28 Z9 29 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2003 VL 63 IS 1 BP 33 EP 42 DI 10.1046/j.1523-1755.2003.00706.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 624NU UT WOS:000179766600004 PM 12472766 ER PT J AU Ullian, ME Gantt, BJ Ford, AK Tholanikunnel, BG Spicer, EK Fitzgibbon, WR AF Ullian, ME Gantt, BJ Ford, AK Tholanikunnel, BG Spicer, EK Fitzgibbon, WR TI Potential importance of glomerular citrate synthase activity in remnant nephropathy SO KIDNEY INTERNATIONAL LA English DT Article DE Wistar-Furth rats; mineralocorticoid receptors; aldosterone; radioligand binding; citrate synthase; remnant nephropathy; glomeruli; progressive renal injury ID RATS RESISTANT; ALDOSTERONE; HYPERTENSION; RECEPTOR; PSEUDOHYPOALDOSTERONISM; DISEASE; KIDNEY AB Background. Aldosterone fosters progressive renal injury, but the mechanism is unknown. Both Wistar-Furth rats, which are resistant to aldosterone actions, and adrenalectomized Sprague-Dawley rats, which lack aldosterone, are characterized by resistance to remnant nephropathy and by reduced whole kidney citrate synthase activity. Increase in citrate synthase activity is a well-characterized, specific renal response to aldosterone. Therefore, we performed experiments to test the hypothesis that enhanced citrate synthase activity contributes to remnant nephropathy. Methods. Rat models included Wistar (control for Wistar-Furth), Wistar-Furth (resistant to aldosterone), Sprague-Dawley (normal), adrenalectomy (lacking aldosterone), and 5/6 nephrectomy (renal injury). Glomeruli were obtained by differential sieving. Citrate synthase activity was determined spectrophotometrically. Binding characteristics of cytosolic mineralocorticoid receptors were determined by equilibrium competition binding between tritiated and unlabeled aldosterone. Gene sequencing was performed with reverse transcription-polymerase chain reaction (RT-PCR) and fluorescent dye terminators. Results. In glomeruli isolated from adrenalectomized Wistar rats with intact renal mass, aldosterone stimulated a threefold increase in citrate synthase activity; this stimulation was not observed in glomeruli from Wistar-Furth rats. Similarly, citrate synthase activity in glomeruli isolated from adrenally intact Sprague-Dawley rats was 65% greater than that from adrenalectomized Sprague-Dawley rats. Compared to sham surgery, subtotal nephrectomy resulted in 100% greater glomerular citrate synthase activity in Sprague-Dawley rats. In Wistar-Furth rats, mineralocorticoid receptor binding was not reduced, and mutations in the mineralocorticoid receptor DNA binding segment were not found. Conclusion. Citrate synthase activity is elevated in remnant glomeruli, and experimental models characterized by reduced glomerular citrate synthase activity (Wistar-Furth rats, adrenalectomized Sprague-Dawley rats) are protected from remnant nephropathy. C1 Med Univ S Carolina, Div Nephrol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Ullian, ME (reprint author), Med Univ S Carolina, Div Nephrol, Clin Sci bldg 829,171 Ashley Ave, Charleston, SC 29425 USA. NR 22 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2003 VL 63 IS 1 BP 156 EP 164 DI 10.1046/j.1523-1755.2003.00731.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 624NU UT WOS:000179766600016 PM 12472778 ER PT J AU Johansen, KL Shubert, T Doyle, J Soher, B Sakkas, GK Kent-Braun, JA AF Johansen, KL Shubert, T Doyle, J Soher, B Sakkas, GK Kent-Braun, JA TI Muscle atrophy in patients receiving hemodialysis: Effects on muscle strength, muscle quality, and physical function SO KIDNEY INTERNATIONAL LA English DT Article DE end-stage renal disease; hemodialysis; magnetic resonance imaging; muscle; strength; physical performance ID CHRONIC-RENAL-FAILURE; SKELETAL-MUSCLE; BODY-COMPOSITION; PARATHYROID-HORMONE; EXERCISE CAPACITY; MAINTENANCE DIALYSIS; SUBMAXIMAL EXERCISE; DISEASE; ACTIVATION; IMPEDANCE AB Background. Dialysis patients are less active and have reduced functional capacity compared to individuals with normal renal function. Muscle atrophy and weakness may contribute to these problems. This investigation was undertaken to quantify the extent of atrophy in the lower extremity muscles, to determine whether defects in muscle specific strength (force per unit mass) or central nervous system (CNS) activation are present, and to assess the relationship between muscle size and physical performance in a group of patients on hemodialysis. Methods. Thirty-eight dialysis subjects (aged 55 +/- 15 years) and nineteen healthy sedentary controls (aged 55 +/- 13 years) were enrolled. Magnetic resonance imaging of the lower leg was used to determine the total cross-sectional area (CSA) and the area of contractile and non-contractile tissue of the ankle dorsiflexor muscles. Isometric dorsiflexor strength was measured during a maximal voluntary contraction with and without superimposed tetanic stimulation (N = 22 for dialysis subjects, N = 12 for controls). Physical activity was measured by accelerometry, and gait speed was recorded as a measure of physical performance. Results. Dialysis subjects were weaker, less active, and walked more slowly than controls. Total muscle compartment CSA was not significantly different between dialysis subjects and controls, but the contractile CSA was smaller in the dialysis patients even after adjustment for age, gender, and physical activity. Central activation and specific strength were normal. Gait speed was correlated with contractile CSA. Conclusions. Significant atrophy and increased non-contractile tissue are present in the muscle of patients on hemodialysis. The relationship between contractile area and strength is intact in this population. Muscle atrophy is associated with poor physical performance. Thus, interventions to increase physical activity or otherwise address atrophy may improve performance and quality of life. C1 Univ Calif San Francisco, Nephrol Sect, Dept Med, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, No Calif Inst Res & Educ, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, Dept Radiol, San Francisco, CA 94121 USA. Univ Massachusetts, Dept Exercise Sci, Amherst, MA 01003 USA. RP Johansen, KL (reprint author), Univ Calif San Francisco, Nephrol Sect, Dept Med, San Francisco VA Med Ctr, 111J San Francisco,4150 Clement St, San Francisco, CA 94121 USA. FU NCRR NIH HHS [RR-00083]; NIDDK NIH HHS [1R01-DK56182] NR 46 TC 137 Z9 150 U1 1 U2 10 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2003 VL 63 IS 1 BP 291 EP 297 DI 10.1046/j.1523-1755.2003.00704.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 624NU UT WOS:000179766600033 PM 12472795 ER PT J AU Bornstien-Quevedo, L Lehmann, L Vargas, SO Kozakewich, HPW Perez-Atayde, AR AF Bornstien-Quevedo, L Lehmann, L Vargas, SO Kozakewich, HPW Perez-Atayde, AR TI Alk plus anaplastic large cell lymphoma (ALCL) in children. A clinicopathologic analysis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Childrens Hosp, 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 LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 BP 1P EP 1P PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501531 ER PT J AU Amell, PM Rosenberg, AE Nielsen, GP AF Amell, PM Rosenberg, AE Nielsen, GP TI beta-catenin expression in reactive and neoplastic fibroblastic proliferations SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 22 BP 8A EP 9A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500037 ER PT J AU Hoch, BL Inwards, C Rosenberg, AE AF Hoch, BL Inwards, C Rosenberg, AE TI Multicentric giant cell tumor of bone: A clinicopathologic analysis of thirty cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 46 BP 13A EP 14A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500061 ER PT J AU Hoch, BL Nielsen, GP Liebsch, NJ Rosenberg, AE AF Hoch, BL Nielsen, GP Liebsch, NJ Rosenberg, AE TI Base of skull chordomas in children and adolescents: A clinicopathologic analysis of 72 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 45 BP 13A EP 13A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500060 ER PT J AU Gundogan, F George, S Erban, J Sharifi, S AF Gundogan, F George, S Erban, J Sharifi, S TI Can nm23 and stromelysin-3 expression predict the invasive potential of extensive ductal carcinoma in-situ? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Tufts New England Med Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 128 BP 31A EP 31A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500143 ER PT J AU Nasser, SM Fan, MJ AF Nasser, SM Fan, MJ TI Does atypical columnar cell hyperplasia on breast core biopsy warrant follow-up excision? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 176 BP 42A EP 42A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500191 ER PT J AU Chen, AA Tambouret, RH Wilbur, DC AF Chen, AA Tambouret, RH Wilbur, DC TI Benign shed endometrial cells in the SurePath liquid-based method: A potential pitfall for overinterpretation as "a typical endometrial cells" SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 267 BP 61A EP 61A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500282 ER PT J AU Dong, Q McKee, GT Pitman, MB Geisinger, KR Tambouret, R AF Dong, Q McKee, GT Pitman, MB Geisinger, KR Tambouret, R TI The epithelioid variant of gastrointestinal stromal tumor: Diagnosis by fine-needle aspiration biopsy SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 274 BP 63A EP 63A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500289 ER PT J AU Eichhom, JH Gelfand, JA Brauns, TA Wilbur, DC AF Eichhom, JH Gelfand, JA Brauns, TA Wilbur, DC TI A novel automated screening and interpretation process for cervical cytology using Internet transmission of low resolution images: A pilot study SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 278 BP 64A EP 64A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500293 ER PT J AU Faquin, WC Cibas, ES Renshaw, AA AF Faquin, WC Cibas, ES Renshaw, AA TI Atypical thyroid cyst lining cells: A pitfall for the FNA diagnosis of cystic thyroid lesions SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Baptist Hosp Miami, Miami, FL 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 282 BP 64A EP 65A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500297 ER PT J AU Rahemtullah, A Misdraji, J Pitman, MB AF Rahemtullah, A Misdraji, J Pitman, MB TI Adenosquamous carcinoma of the pancreas: Cytological and clinical features in a series of 15 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol C1 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 347 BP 78A EP 79A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500361 ER PT J AU Ahmad, NM Crowson, AN Mihm, MC Vlassov, D Werling, RW Phillips, RS Magro, C AF Ahmad, NM Crowson, AN Mihm, MC Vlassov, D Werling, RW Phillips, RS Magro, C TI Cutaneous immunocytoma: A clinical histologic and phenotypic study of 8 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Ohio State Univ, Columbus, OH 43210 USA. Univ Oklahoma, Reg Med Lab, Tulsa, OK USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 386 BP 87A EP 87A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500400 ER PT J AU King, R Gorge, PB Page, RN Mihm, MC AF King, R Gorge, PB Page, RN Mihm, MC TI Microphthalmia transcription factor (Mitf),Mart-1,HMB-45, and S100 expression in radial growth phase melanoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Univ Tennessee, Grad Sch Med, Knoxville, TN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 415 BP 93A EP 93A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500428 ER PT J AU Lu, D Hoch, B Dehner, LP Lind, AC AF Lu, D Hoch, B Dehner, LP Lind, AC TI Proliferative activity in melanocytic nevi from patients grouped by age SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Washington Univ, St Louis, MO USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 420 BP 94A EP 94A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500433 ER PT J AU Srinivasan, M Werling, RW Phillips, RS Ahmad, N Vlassov, D Crowson, AN Mihm, MC Magro, CM AF Srinivasan, M Werling, RW Phillips, RS Ahmad, N Vlassov, D Crowson, AN Mihm, MC Magro, CM TI Assessment of T cell clonality via a single stranded DNA polymorphism conformational assay SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Ohio State Univ, Columbus, OH 43210 USA. Univ Oklahoma, Reg Med Lab, Tulsa, OK USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 449 BP 100A EP 100A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500462 ER PT J AU Werling, RW Crowson, AN Mihm, MC Phillips, RS Ahmad, NM Vlassov, D Porcu, P Cynthia, M AF Werling, RW Crowson, AN Mihm, MC Phillips, RS Ahmad, NM Vlassov, D Porcu, P Cynthia, M TI Primary cutaneous T-cell rich CD30+large cell B-cell lymphoma: A series of cases describing a distinct clinicopathologic disease entity SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Ohio State Univ, Columbus, OH 43210 USA. Univ Oklahoma, Reg Med Lab, Tulsa, OK USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 455 BP 101A EP 101A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500468 ER PT J AU Nakatani, Y Masudo, K Nozawa, A Inayama, Y Ito, T Kitamura, H Notohara, K Kashima, K Yokoyama, S Tsujimoto, M Tamai, S Abe, Y Matsubara, O Resl, M Mark, EJ AF Nakatani, Y Masudo, K Nozawa, A Inayama, Y Ito, T Kitamura, H Notohara, K Kashima, K Yokoyama, S Tsujimoto, M Tamai, S Abe, Y Matsubara, O Resl, M Mark, EJ TI Biotin-rich optically clear nuclei (BROCN) express estrogen receptor beta (ER beta) but not ER alpha SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Yokohama City Univ, Ctr Med, Yokohama, Kanagawa 232, Japan. Ito Hosp, Tokyo, Japan. Hosp Yokohama City Univ, Yokohama, Kanagawa, Japan. Yokohama City Univ, Sch Med, Yokohama, Kanagawa 232, Japan. Okayama Univ, Grad Sch Med & Dent, Okayama 7008530, Japan. Med Coll Oita, Oita 87956, Japan. Osaka Police Hosp, Osaka, Japan. Natl Def Med Coll, Tokorozawa, Saitama, Japan. Natl Kanagawa Hosp, Hadano, Japan. Charles Univ, Hradec Kralove, Czech Republic. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 481 BP 107A EP 107A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500494 ER PT J AU Kaimaktchiev, V Dimhofer, S Sauter, G Korcheva, V Mirlacher, M Loda, M Corless, CL AF Kaimaktchiev, V Dimhofer, S Sauter, G Korcheva, V Mirlacher, M Loda, M Corless, CL TI Selective staining of gastrointestinal adenocarcinomas by the homeobox intestinal differentiation factor CDX2 SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Inst Pathol, Basel, Switzerland. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 556 BP 123A EP 123A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500569 ER PT J AU Lauwers, GY Mino, M Ban, S Sevestre, H AF Lauwers, GY Mino, M Ban, S Sevestre, H TI CK-7, CK-20 and mucin gene expression in gastric inlet patch SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Saitama Med Sch, Moroyama, Saitama, Japan. CHU Amiens, Amiens, France. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 568 BP 125A EP 126A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500581 ER PT J AU Lauwers, GY Ban, S Mino, M Ota, S Matsumoto, T Arai, S Brugge, WR Shimizu, M AF Lauwers, GY Ban, S Mino, M Ota, S Matsumoto, T Arai, S Brugge, WR Shimizu, M TI Endoscopic mucosal resection for gastric epithelial neoplasm. A study of 39 cases with analysis of pathologic features SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Saitama Med Sch, Moroyama, Saitama, Japan. Kyushu Univ, Fukuoka 812, Japan. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 567 BP 125A EP 125A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500580 ER PT J AU Lechpammer, M Xu, X Bhattacharya, N Ellis, HF Loda, M AF Lechpammer, M Xu, X Bhattacharya, N Ellis, HF Loda, M TI Experimentaly induced carcinogenesis of esophageal mucosa and its inhibition by flavopiridol in p27 konckout mice SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 569 BP 126A EP 126A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500582 ER PT J AU Tang, Z Jing, W Deshpande, V Lauwers, G Ferry, J Harris, N Zukerberg, L AF Tang, Z Jing, W Deshpande, V Lauwers, G Ferry, J Harris, N Zukerberg, L TI Lymphoid lesions of the colon: Analysis of histologic features SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 610 BP 135A EP 135A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500623 ER PT J AU Yantiss, RK Rosenberg, AR Antonescu, CR AF Yantiss, RK Rosenberg, AR Antonescu, CR TI KIT mutation analysis in NF-1 patients with multiple gastrointestinal stromal tumors (GIST) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 UMass Mem Hlth Care, Worcester, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 622 BP 137A EP 137A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500635 ER PT J AU Cubilla, AL Velazquez, EF Arbo, M Young, RH AF Cubilla, AL Velazquez, EF Arbo, M Young, RH TI The inter relationship among subtypes of precancerous lesions and invasive neoplasms of the penis indicates heterogeneous pathways of cancer progression SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Inst Patol & Invest, Asuncion, Paraguay. NYU, Med Ctr, New York, NY 10016 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 662 BP 146A EP 146A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500675 ER PT J AU Henley, JD Michael, H Young, RH Ulbright, TM AF Henley, JD Michael, H Young, RH Ulbright, TM TI Solid pattern of yolk sac tumor of the testis: A histologic and immunohistochemical study of 9 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Indiana Univ, Sch Med, Indianapolis, IN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 696 BP 153A EP 153A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500709 ER PT J AU Oliva, E Moch, H Cabrera, R Young, RH Reuter, V Amin, MB AF Oliva, E Moch, H Cabrera, R Young, RH Reuter, V Amin, MB TI Nephrogenic adenoma (NA): An immunohistochemical (ICH) study of 40 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Basel, Basel, Switzerland. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Emory Hosp, Atlanta, GA 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 748 BP 164A EP 164A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500761 ER PT J AU Vanguri, VK Woda, BA Yang, XJ Wu, CL Savas, L Jiang, Z AF Vanguri, VK Woda, BA Yang, XJ Wu, CL Savas, L Jiang, Z TI Detection of high-grade prostatic intraepithelial neoplasia (PIN) by alpha-methylacyl-CoA racemase/P504S immunohistochemistry in previously negative biopsies SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Univ Massachusetts, Sch Med, Worcester, MA USA. Univ Chicago, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 796 BP 175A EP 175A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500809 ER PT J AU Brachtel, EF Littell, RD Lynch, MP Rueda, B Oliva, E AF Brachtel, EF Littell, RD Lynch, MP Rueda, B Oliva, E TI Is there any in vivo or in vitro correlation between beta-catenin and hormonal receptors (HRs) in endometrioid endometrial carcinoma (EEC)? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 832 BP 183A EP 183A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500845 ER PT J AU Dong, Q Rueda, B Oliva, E Zukerberg, L AF Dong, Q Rueda, B Oliva, E Zukerberg, L TI Loss of cables, a novel gene on chromosome 18q, is associated with malignant transformation of the endometrium SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 857 BP 188A EP 188A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500870 ER PT J AU Gupta, A Bhan, AK Bell, DA AF Gupta, A Bhan, AK Bell, DA TI Can the implants of serous borderline tumors of the ovary be distinguished from mesothelial proliferations by use of immunohistochemistry? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 867 BP 190A EP 190A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500880 ER PT J AU Nucci, MR Young, RH AF Nucci, MR Young, RH TI Arias-stella reaction of the endocervix: A study of 14 cases with emphasis on its varied morphology SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. 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 LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 924 BP 203A EP 203A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500937 ER PT J AU Tambouret, R Clement, PB Young, RH AF Tambouret, R Clement, PB Young, RH TI Endometrial endometrioid adenocarcinoma with a deceptive pattern of spread to the uterine cervix SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Vancouver Gen Hosp, Vancouver, BC, Canada. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 965 BP 212A EP 212A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500978 ER PT J AU Hirsch, MS Faquin, WC Krane, JF AF Hirsch, MS Faquin, WC Krane, JF TI TTF-1, but not p53, is helpful in distinguishing moderately differentiated neuroendocrine carcinoma of the larynx from medullary carcinoma of the thyroid SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. 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 LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1002 BP 219A EP 220A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501015 ER PT J AU Wang, L Zukerberg, L Ferry, JA Tang, Z Amrein, PC Harris, NL AF Wang, L Zukerberg, L Ferry, JA Tang, Z Amrein, PC Harris, NL TI Chronic myelogenous leukemia with Gleevec/ST1571 treatment leads to a rapid hematological but slower cytogenetic response SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1175 BP 257A EP 258A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501188 ER PT J AU Deshpande, V Muzikansky, A Fernandez-del Castillo, C Lauwers, GY AF Deshpande, V Muzikansky, A Fernandez-del Castillo, C Lauwers, GY TI Cytokeratin 19 is a powerful predictor or survival in pancreatic endocrine tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1242 BP 272A EP 272A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501255 ER PT J AU Graeme-Cook, FM Lauwers, GY Eatherton, DE Mino, M AF Graeme-Cook, FM Lauwers, GY Eatherton, DE Mino, M TI Immunophenotyping in sinusoidal elements in hepatocellular carcinogenesis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1252 BP 274A EP 274A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501265 ER PT J AU Mino, M Varnholt, H Muzikansky, A Terris, B Batts, KP Yamabe, H Flejou, JF Cleary, K Vauthey, JN Lauwers, GY AF Mino, M Varnholt, H Muzikansky, A Terris, B Batts, KP Yamabe, H Flejou, JF Cleary, K Vauthey, JN Lauwers, GY TI Influence of age on hepatocellular carcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Hop Beaujon, Paris, France. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Kyoto Univ Hosp, Kyoto 606, Japan. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1282 BP 281A EP 281A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501295 ER PT J AU Misdraji, J Thiim, M Graeme-Cook, FM AF Misdraji, J Thiim, M Graeme-Cook, FM TI Autoimmune hepatitis with centrilobular necrosis: A clinicopathologic study of 6 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1283 BP 281A EP 281A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501296 ER PT J AU Richards, CJ McGrath, D Bayliss, U Fernandez-del Castillo, C Lauwers, GY AF Richards, CJ McGrath, D Bayliss, U Fernandez-del Castillo, C Lauwers, GY TI Association and correlation of grade of pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mutinous tumors (IPMT) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 UHL NHS Trust, Leicester, Leics, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1297 BP 284A EP 285A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501310 ER PT J AU Soupir, CP Myers, MD Sielaff, TD Coad, JE AF Soupir, CP Myers, MD Sielaff, TD Coad, JE TI Hepatic changes following vertical banded gastroplasty (VBG) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 W Virginia Univ, Morgantown, WV 26506 USA. Univ Minnesota, Minneapolis, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1302 BP 285A EP 286A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501315 ER PT J AU Houser, SL Dor, FJMF Gollackner, B Cooper, DK AF Houser, SL Dor, FJMF Gollackner, B Cooper, DK TI Histology of splenic allograft rejection in MHC-matched and MHC-disparate miniature swine SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1351 BP 296A EP 296A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501364 ER PT J AU Matsubara, O Imazeki, N Okochi, Y Tanimoto, T Shinto, E Nakatani, Y Mark, EJ AF Matsubara, O Imazeki, N Okochi, Y Tanimoto, T Shinto, E Nakatani, Y Mark, EJ TI TGF-beta 1 and CTGF expression in diffuse alveolar damage and advanced pulmonary fibrosis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Natl Def Med Coll, Tokorozawa, Saitama 359, Japan. Yokohama City Univ, Med Ctr, Yokohama, Kanagawa 232, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1420 BP 311A EP 311A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501433 ER PT J AU Arnell, PM Selig, MK Nielsen, GP Balis, UJ AF Arnell, PM Selig, MK Nielsen, GP Balis, UJ TI Computer assisted three-dimensional reconstruction and visualization of the Birbeck granule SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1506 BP 329A EP 329A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501519 ER PT J AU Rollins, SE Nielsen, GP Hedley-Whyte, E AF Rollins, SE Nielsen, GP Hedley-Whyte, E TI Light microscopy, electron microscopy and mitochondrial enzyme function in muscle biopsies for suspected mitochondrial cytopathies SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1514 BP 331A EP 331A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501527 ER PT J AU Cohen, T Sommers, B Murray, M AF Cohen, T Sommers, B Murray, M TI The effect of drug resistance on the fitness of Mycobacterium tuberculosis SO LANCET INFECTIOUS DISEASES LA English DT Review ID ISONIAZID RESISTANCE; MOLECULAR EPIDEMIOLOGY; ESCHERICHIA-COLI; ANTIBIOTIC-RESISTANCE; SALMONELLA-TYPHIMURIUM; COMPENSATORY EVOLUTION; RIFAMPIN RESISTANCE; KATG GENE; MUTATIONS; VIRULENCE AB Mycobacterium tuberculosis remains a leading infectious cause of morbidity and mortality. While antibiotic resistance is cited as a potential threat to efforts aimed at controlling the spread of this pathogen, it is not clear how drug resistance affects disease dynamics. The effect of mutational events that lead to anti biotic-resistant phenotypes may or may not have a predictable effect on the fitness of drug-resistant tuberculosis strains. Here, we review the literature on laboratory studies of the fitness of drug-resistant tuberculosis, we examine the evidence from cluster studies, and we consider the effect of drug resistance on disease dynamics in mathematical models. On the basis of these diverse lines of evidence, we conclude that the fitness estimates of drug-resistant M tuberculosis are quite heterogeneous and that this variation may preclude our ability to predict future trends of this pathogen. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Murray, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Massachusetts Gen Hosp, 677 Huntington Ave, Boston, MA 02115 USA. RI Sommers, Benjamin/D-2871-2011; Cohen, Ted/G-8101-2011 FU NIAID NIH HHS [K08 AI055985-01A1, T32 AI07433]; PHS HHS [K08 A1 01930-01, R01 A10 46669-02] NR 57 TC 104 Z9 111 U1 1 U2 7 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD JAN PY 2003 VL 3 IS 1 BP 13 EP 21 DI 10.1016/S1473-3099(03)00483-3 PG 9 WC Infectious Diseases SC Infectious Diseases GA 632AU UT WOS:000180201400020 PM 12505028 ER PT J AU Kamil, SH Kojima, K Vacanti, MP Bonassar, LJ Vacanti, CA Eavey, RD AF Kamil, SH Kojima, K Vacanti, MP Bonassar, LJ Vacanti, CA Eavey, RD TI In vitro tissue engineering to generate a human-sized auricle and nasal tip SO LARYNGOSCOPE LA English DT Article DE tissue engineering; chondrocytes; scaffolds; internal support ID BIOREACTOR CULTIVATION; CARTILAGE; RECONSTRUCTION; CHONDROCYTES; MICROTIA; SUPPORT; CALCIUM; GROWTH; SHAPE AB Objectives/Hypothesis: Tissue engineering has successfully generated cartilage in a xenograft and an autograft model. However, challenges remain with both of these in vivo techniques before clinical application can be realized. We hypothesized that a human-sized cartilaginous structure could be generated completely in vitro as a complementary or an alternative technique. Methods: Scaffolds were created in the shape of five fall-sized human auricles and five nasal tip cartilaginous skeletons. Bovine shoulder chondrocytes at a concentration of 50 million cells/mL were seeded onto the scaffolds and were grown for 12 weeks in vitro. Two of the auricular scaffolds had internal support provided by soft acrylic sheets and were later implanted into nude rats. Results: All of the scaffolds maintained shape and size through 12 weeks of in vitro culture. On gross examination the scaffolds were progressively replaced by cartilage, which was confirmed by histological and biochemical analysis. The auricular scaffolds with the acrylic internal support had the most natural rigidity, which was observed by gentle palpation. The nasal scaffolds maintained excellent definition even without internal support. Conclusion: An adult human-sized auricle and nasal tip cartilaginous structure can be grown entirely in vitro using principles of tissue engineering. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Lab Tissue Engn, Dept Anesthesiol, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. RP Eavey, RD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. RI Bonassar, Lawrence/C-2103-2016 OI Bonassar, Lawrence/0000-0003-1094-6433 NR 15 TC 44 Z9 51 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2003 VL 113 IS 1 BP 90 EP 94 DI 10.1097/00005537-200301000-00017 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 637EX UT WOS:000180499500017 PM 12514389 ER PT S AU Castano, AP Gad, F Zahra, T Hamblin, MR AF Castano, AP Gad, F Zahra, T Hamblin, MR BE Jacques, SL Duncan, DD Kirkpatrick, SJ Kriete, A TI Specific anti-tumor immune response with photodynamic therapy mediated by benzoporphyrin derivative and chlorin(6) SO LASER-TISSUE INTERACTION XIV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Laser-Tissue Interaction XIV CY JAN 25-29, 2003 CL SAN JOSE, CA SP SPIE DE tumor immunity; photodynamic therapy; benzoporphyrin derivative; chlorin(e6); EMT6 ID HEAT-SHOCK PROTEINS; DENDRITIC CELLS; MOUSE-TUMORS; MECHANISMS; VACCINES; CANCERS; SYSTEM; UPDATE; DEATH AB The purpose of this study was to investigate the induction of anti-tumor immunity by photodynamic therapy (PDT). We used EMT-6 mammary sarcoma, a moderately immunogenic tumor, with 10(6) cells injected s.c. in thighs of immunocompetent Balb/c mice. Mice were treated 10 days later when tumors were 6-mm diameter. Two PDT regimens were equally effective in curing tumors: 1-mg/kg of liposomal benzoporphyrin derivative (BPD) followed after 15 min by 150 J/cm(2) 690 nm light or 10-mg/kg chlorin(e6) (ce6) followed-after 6 hours by 150 J/cm(2) 665 nm light. BPD-PDT produced a black eschar 24-48 hours after treatment with no visible tumor, followed by healing of the lesion. By contrast ce6-PDT showed no black eschar, but a slow disappearance of tumor over 5-7 days. When cured mice were rechallenged with 10(6) EMT-6 cells in the opposite thigh.. all ce6-PDT cured mice rejected the challenge, but BPD-PDT cured mice grew tumors in a proportion of cases. When mice. were cured by amputation of the tumor bearing leg, all mice subsequently grew tumors upon rechallenge. Mice were given two EMT6 tumors (I in each leg) and the mouse was injected with ce6 or BPD but only one tumor was treated with light. Both tumors (PDT-treated and contralateral) regressed at an equal rate until they became undetectable. but in some mice the untreated tumor recurred. Those mice cured of both tumors rejected a subsequent EMT6 rechallenge. Amputation of the tumor bearing leg did. not lead to regression of the contralateral tumor. Mice that rejected an EMT6 rechallenge failed to reject a subsequent cross-challenge with J774 reticulum cell sarcoma (an alternative Balb/c murine tumor). These data show that PDT generates a tumor-specific memory immune response, and in addition an active tumoricidal immune response capable of destroying distant established tumors. We hypothesize that ce6-PDT is more effective than BPD-PDT due to more necrotic rather than apoptotic cell death and/or generation of heat-shock proteins that are known for efficient presentation of tumor antigens via dendritic cells to cytotoxic T-cells. PDT could be used to treat a locally advanced tumor while at the same time destroying distant metastases via an induced immune response. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Castano, AP (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 55 Fruit St, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 23 TC 5 Z9 5 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4761-7 J9 P SOC PHOTO-OPT INS PY 2003 VL 4961 BP 1 EP 9 DI 10.1117/12.477654 PG 9 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BX32Z UT WOS:000184961100001 ER PT S AU Hamblin, MR Tawakol, A Castano, AP Gad, F Zahra, T Ahmadi, A Stern, J Ortel, B Chirico, S Shirazi, A Syed, S Muller, JE AF Hamblin, MR Tawakol, A Castano, AP Gad, F Zahra, T Ahmadi, A Stern, J Ortel, B Chirico, S Shirazi, A Syed, S Muller, JE BE Bass, LS Kollias, N Malek, RS Katzir, A Shah, UK Wong, BJF Trowers, EA Woodward, TA DeRiese, WTW Robinson, DS Reidenbach, HD Paulsen, KD Gregory, KW TI Macrophage-targeted photodynamic detection of vulnerable atherosclerotic plaque SO LASERS IN SURGERY: ADVANCED CHARACTERIZATION, THERAPEUTICS, AND SYSTEMS XIII SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Lasers in Surgery - Advanced Characterization, Therapeutics and Systems XIII CY JAN 25-26, 2003 CL SAN JOSE, CA SP SPIE DE atherosclerosis; photodynamic therapy; fluorescence; biodistribution; macrophage; scavenger receptor; chlorin(e6) ID OPTICAL COHERENCE TOMOGRAPHY; SCAVENGER-RECEPTOR; INTRAVASCULAR ULTRASOUND; MYOCARDIAL-INFARCTION; CORONARY-ARTERIES; FIBROUS CAP; IN-VITRO; THERAPY; RUPTURE; VISUALIZATION AB Rupture of a vulnerable atherosclerotic plaque (VP) leading to coronary thrombosis is the chief cause of sudden cardiac death. VPs are angiographically insignificant lesions, which are excessively inflamed and characterized by dense macrophage infiltration, large necrotic lipid cores, thin fibrous caps, and paucity of smooth muscle cells. We have recently shown that chlorin(e6) conjugated with maleylated albumin can target macrophages with high selectivity via the scavenger receptor. We report the potential of this macrophage-targeted fluorescent probe to localize in VPs in a rabbit model of atherosclerosis, and allow detection and/or diagnosis by fluorescence spectroscopy or imaging. Atherosclerotic lesions were induced in New Zealand White rabbit aortas by balloon injury followed by administration of a high-fat diet. 24-hours after IV injection of the conjugate into atherosclerotic or normal rabbits, the animals were sacrificed, and aortas were removed, dissected and examined for fluorescence localization in plaques by fiber-based spectrofluorimetry and confocal microscopy. Dye uptake within the aortas was also quantified by fluorescence extraction of samples from aorta segments. Biodistribution of the dye was studied in many organs of the rabbits. Surface spectrofluorimetry after conjugate injection was able to distinguish between plaque and adjacent aorta, between atherosclerotic and normal aorta, and balloon-injured and normal iliac arteries with high significance. Discrete areas of high fluorescence (up to 20 times control were detected in the balloon-injured segments, presumably corresponding to macrophage-rich plaques. Confocal microscopy showed red ce6 fluorescence localized in plaques that showed abundant foam cells and macrophages by histology. Extraction data on aortic tissue corroborated the selectivity of the conjugate for plaques. These data support the strategy of employing macrophage-targeted fluorescent dyes to detect VP by intravascular spectrofluorimetry. It may also be possible to use macrophage-targeted PDT to therapeutically modify inflammatory cell-laden VPs leading to plaque stabilization and reduction of sudden cardiovascular death. C1 Harvard Univ, Sch Med, Wellman Labs Photomed, Massachusetts Gen Hosp, Boston, MA USA. RP Hamblin, MR (reprint author), Harvard Univ, Sch Med, Wellman Labs Photomed, Massachusetts Gen Hosp, Boston, MA USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 34 TC 2 Z9 2 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4749-8 J9 P SOC PHOTO-OPT INS PY 2003 VL 4949 BP 466 EP 476 DI 10.1117/12.476218 PG 11 WC Engineering, Biomedical; Optics; Surgery SC Engineering; Optics; Surgery GA BX17B UT WOS:000184498100060 ER PT J AU Soukos, NS Mulholland, SE Socransky, SS Doukas, AG AF Soukos, NS Mulholland, SE Socransky, SS Doukas, AG TI Photodestruction of human dental plaque bacteria: Enhancement of the photodynamic effect by photomechanical waves in an oral biofilm model SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE photodynamic therapy; photosensitizer; microbial biofilms; confocal scanning laser microscopy ID PSEUDOMONAS-AERUGINOSA BIOFILMS; GRAM-POSITIVE BACTERIA; LIPID-SOLUBLE PHTHALOCYANINES; ELECTRICAL ENHANCEMENT; ESCHERICHIA-COLI; IN-VITRO; EFFICIENT PHOTOSENSITIZERS; SUBGINGIVAL PLAQUE; MOLECULAR DELIVERY; STRESS GRADIENT AB Background and Objectives: Periodontal disease results from the accumulation of subgingival bacterial biofilms on tooth surfaces. There is reduced susceptibility of these biofilms to antimicrobials for reasons that are not known. The goals of this study were to investigate the photodynamic effects of a conjugate between the photosensitizer (PS) chlorin(e6) (c(e6)) and a poly-L-lysine (pL) with five lysine residues on human dental plaque bacteria as well as on biofilms of the oral species Actinomyces naeslundii after their exposure to photomechanical waves (PW) generated by a laser in the presence of the conjugate. Study Design/Materials and Methods: Subgingival plaque samples from 12 patients with chronic destructive periodontitis were divided in 3 groups that were incubated for 5 minutes with 5 muM c(e6) equivalent from the pL-c(e6) conjugate in the presence of fresh medium (group 1), PBS (group II), and 80% PBS/20% ethylenediaminetetra-acetic acid (EDTA) (group 111) and were exposed to red light. Also, biofilms of A. naeslundii (formed on bovine enamel surfaces) were exposed to PW in the presence of 5 muM c(e6) equivalent from the pL-c(e6) conjugate and were then irradiated with red light. The penetration depth of the conjugate was measured by confocal scanning laser microscopy (CSLM). In both cases, after illumination serial dilutions were prepared and aliquots were spread over the surfaces of blood agar plates. Survival fractions were calculated by counting bacterial colonies. Results: The PS/light combination achieved almost 90% killing of human dental plaque species. In biofilms of A. naeslundii, CSLM revealed that PW were sufficient to induce a 50% increase in the penetration depth of the pL-c(e6) conjugate into the biofilm. This enabled its destruction (99% killing) after photodynamic therapy (PDT). Conclusions: PW-assisted photodestruction of dental plaque may be a potentially powerful tool for treatment of chronic destructive periodontal disease. (C) 2003 Wiley-Liss, Inc. C1 Forsyth Inst, Appl Mol Photomed Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA USA. Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Soukos, NS (reprint author), Forsyth Inst, Appl Mol Photomed Lab, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-11814] NR 57 TC 57 Z9 61 U1 1 U2 11 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2003 VL 33 IS 3 BP 161 EP 168 DI 10.1002/lsm.10208 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 727ZM UT WOS:000185690800003 PM 12949945 ER PT J AU Pfefer, TJ Paithankar, DY Poneros, JM Schomacker, KT Nishioka, NS AF Pfefer, TJ Paithankar, DY Poneros, JM Schomacker, KT Nishioka, NS TI Temporally and spectrally resolved fluorescence spectroscopy for the detection of high grade dysplasia in Barrett's esophagus SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE laser-induced fluorescence; fluorophore lifetime; precancer detection; esophagus ID LASER-INDUCED FLUORESCENCE; GASTROINTESTINAL-DISEASES; EXCITATION WAVELENGTHS; COLONIC DYSPLASIA; CANCER-DIAGNOSIS; VIVO; AUTOFLUORESCENCE; ENDOSCOPY; TISSUE; SYSTEM AB Background and Objectives: Temporal and spectral fluorescence spectroscopy can identify adenomatous colonic polyps accurately. In this study, these techniques were examined as a potential means of improving the surveillance of high grade dysplasia (HGD) in Barrett's esophagus (BE). Study Design/Materials and Methods: Using excitation wavelengths of 337 and 400 nm, 148 fluorescence spectra, and 108 transient decay profiles (at 550 20 nm) were obtained endoscopically in 37 patients. Corresponding biopsies were collected and classified as carcinoma, HGD, or low risk tissue (LRT) [non-dysplastic BE, indefinite for dysplasia (IFD), and low grade dysplasia (LGD)]. Diagnostic algorithms were developed retrospectively using linear discriminant analysis (LDA) to separate LRT from HGD. Results: LDA produced diagnostic algorithms based solely on spectral data. Moderate levels of sensitivity (Se) and specificity (Sp) were obtained for both 337 nm (Se = 74%, Sp = 67%) and 400 nm (Se = 74%, Sp = 85%) excitation. Conclusions: In the diagnosis of HGD in BE, steady-state fluorescence was more effective than time-resolved data, and excitation at 400 nm excitation was more effective than 337 nm. While fluorescence-targeted biopsy is approaching clinical usefulness, increased sensitivity to dysplastic changes-possibly through modification of system parameters-is needed to improve accuracy levels. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Pfefer, TJ (reprint author), US FDA, CDRH, HFZ-134,12725 Twinbrook Pkwy,201, Rockville, MD 20857 USA. RI Pfefer, Josh/I-9055-2012 NR 39 TC 60 Z9 62 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2003 VL 32 IS 1 BP 10 EP 16 DI 10.1002/lsm.10136 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 639QF UT WOS:000180640200003 PM 12516065 ER PT J AU Brinkmann, R Koop, N Ozdemir, M Alt, C Schule, G Lin, CP Birngruber, R AF Brinkmann, R Koop, N Ozdemir, M Alt, C Schule, G Lin, CP Birngruber, R TI Targeting of the retinal pigment epithelium (RPE) by means of a rapidly scanned continuous wave (CW) laser beam SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE fluorescence microscopy; melanosome; laser scanner; RPE damage; selective treatment; photocoagulation; viability assay ID PHOTOCOAGULATION; DAMAGE; IRRADIATION; CELLS AB Background and Objectives: Selective treatment of the retinal pigment epithelium (RPE) by repetitively applying green is-laser pulses is a new method for retinal diseases associated with a degradation of the RPE, which spares the neural retina. We investigated an alternative approach to realize repetitive mus-laser exposure by rapidly scanning a continuous wave (CW)-laser-beam across the RPE. Study Design/Materials and Methods: An Ar+ laser beam (514 nm) with a diameter of 18.75 mum was repetitively scanned across porcine RPE samples in vitro providing an irradiation time of 1.6 mus per point on the central scan axis. RPE cell damage was investigated by means of the fluorescence viability assay Calcein-AM. Results: The ED50 cell damage is 305 mJ/cm(2) when applying 10 scans with a repetition rate of 500 Hz. The threshold decreases with the number of scans, a saturation was found at 135 mJ/cm(2) with more than 500 exposures applied. The depth of focus in beam direction is 350 mum, defined by an increase of the threshold radiant exposure by 20%. Conclusions: Targeting of pigmented cells with high local resolution has been proved with a laser-scanning device. Looking ahead selective RPE-treatment, the adaptation of a laser-scanning device on a slit-lamp or into a modified retina angiograph seems to be an attractive alternative to the pulsed mus laser device. (C) 2003 Wiley-Liss, Inc. C1 Med Laser Ctr Lubeck GmbH, D-23562 Lubeck, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Brinkmann, R (reprint author), Med Laser Ctr Lubeck GmbH, Peter Monnik Weg 4, D-23562 Lubeck, Germany. RI Brinkmann, Ralf/E-6701-2012; Birngruber, Reginald/Q-2342-2016 FU NEI NIH HHS [EY12970] NR 22 TC 13 Z9 13 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2003 VL 32 IS 4 BP 252 EP 264 DI 10.1002/lsm.10150 PG 13 WC Dermatology; Surgery SC Dermatology; Surgery GA 674MW UT WOS:000182641400002 PM 12696092 ER PT J AU Kuwahara, K Gladstone, HB Gupta, V Kireev, V Neel, V Moy, RL AF Kuwahara, K Gladstone, HB Gupta, V Kireev, V Neel, V Moy, RL TI Rupture of fat cells using laser-generated ultra short stress waves SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE cavitation; liposuction; ultrasound ID TUMESCENT LIPOSUCTION; SPALLATION TECHNIQUE; POWERED LIPOSUCTION; INTERFACE STRENGTH; ENERGY AB Background and Objectives: Ultrasound-assisted liposuction has been investigated as an aid to breakup fat for its less traumatic removal, and minimizing the post-operative recovery period. This research focused on understanding the mechanism of fat interaction with laser-generated ultra short stress waves with high amplitudes. Study Design/Materials and Methods: Freshly extracted human fat was secured in an Aluminum (Al) cavity. Sixteen nanoseconds duration stress waves were generated by exfoliating the bottom surface of the Al cavity by focusing 3 nanoseconds-long YAG laser pulses over a 2 mm. diameter area at 10 Hz with a maximum pulse energy of 0.95 J. The lipids released due to cell rupture were extracted and measured Results: Four minutes of pulsing released about 0.005 g, which was over 1% of the initial weight of the tissue. In situ temperature rise of only 5degreesC was measured at the maximum stress wave loading duration of 5 minutes. This was evidenced by histological sections, which showed no burn artifacts. Conclusions: This research shows that ultra short stress waves can mechanically cavitate fat in vitro without significant damage to adjacent structures, and forms the basis for future clinical work. (C) 2003 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, Dept Mech & Aerosp Engn, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Div Dermatol, Los Angeles, CA 90024 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. Stanford Univ, Sch Med, Dept Dermatol, Stanford, CA 94305 USA. RP Gupta, V (reprint author), Univ Calif Los Angeles, Dept Mech & Aerosp Engn, 38-137E Eng 4 Bldg, Los Angeles, CA 90095 USA. NR 14 TC 9 Z9 10 U1 1 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2003 VL 32 IS 4 BP 279 EP 285 DI 10.1002/lsm.10154 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 674MW UT WOS:000182641400005 PM 12696095 ER PT J AU Strasswimmer, J Pierce, MC Park, BH deBoer, JF AF Strasswimmer, J Pierce, MC Park, BH deBoer, JF TI Characterization of basal cell carcinoma by multimode optical coherence tomography SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 09-13, 2003 CL ANAHEIM, CALIFORNIA SP American Soc Laser Med Surg C1 Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2003 SU 15 MA 13 BP 5 EP 5 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 661FK UT WOS:000181880400014 ER PT J AU Khatri, K Manstein, D Erofeev, A Altshuler, G AF Khatri, K Manstein, D Erofeev, A Altshuler, G TI Treatment of rhytids with subsurface-focused Er : YLF laser SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 09-13, 2003 CL ANAHEIM, CALIFORNIA SP American Soc Laser Med Surg C1 Skin & Laser Surg Ctr, Cambridge, MA USA. Palomar Med Technol Inc, Burlington, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2003 SU 15 MA 68 BP 21 EP 21 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 661FK UT WOS:000181880400068 ER PT J AU Lewis, KG Schmidt, A Nahm, WK Moy, RL AF Lewis, KG Schmidt, A Nahm, WK Moy, RL TI Lack of difference between rates of leukoderma after skin resurfacing with 90 mu s pulsed and 900 mu s dwell time carbon dioxide lasers SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 09-13, 2003 CL ANAHEIM, CALIFORNIA SP American Soc Laser Med Surg C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2003 SU 15 MA 70 BP 22 EP 22 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 661FK UT WOS:000181880400070 ER PT J AU Yang, MU Yaroslavsky, AN Farinelli, WA Tsao, SS Anderson, RR AF Yang, MU Yaroslavsky, AN Farinelli, WA Tsao, SS Anderson, RR TI Long-pulsed Nd : YAG laser treatment for portwine stains SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 09-13, 2003 CL ANAHEIM, CALIFORNIA SP American Soc Laser Med Surg C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Laser Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2003 SU 15 MA 90 BP 28 EP 28 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 661FK UT WOS:000181880400090 ER PT J AU Yaroslavsky, AN Yang, MU Farinelli, WA Anderson, RR AF Yaroslavsky, AN Yang, MU Farinelli, WA Anderson, RR TI Quantitative digital photography for objective evaluation of vascular lesions SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 09-13, 2003 CL ANAHEIM, CALIFORNIA SP American Soc Laser Med Surg C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2003 SU 15 MA 91 BP 28 EP 28 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 661FK UT WOS:000181880400091 ER PT J AU Manstein, D Bowes, LE Poureshagh, M Altshuler, GB Anderson, RR AF Manstein, D Bowes, LE Poureshagh, M Altshuler, GB Anderson, RR TI Hair growth management with a low-dose, continuous-wave diode laser used in scanning mode SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 09-13, 2003 CL ANAHEIM, CALIFORNIA SP American Soc Laser Med Surg C1 Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. Palomar Med Technol, Burlington, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2003 SU 15 MA 106 BP 32 EP 32 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 661FK UT WOS:000181880400106 ER PT J AU Yaroslavsky, I Altshuler, G Yaroslavsky, A Pankratov, M Stoll, M Manstein, D Anderson, RR AF Yaroslavsky, I Altshuler, G Yaroslavsky, A Pankratov, M Stoll, M Manstein, D Anderson, RR TI Photon recycling as a means of increasing efficacy and safety of flashlamp systems SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 09-13, 2003 CL ANAHEIM, CALIFORNIA SP American Soc Laser Med Surg C1 Palomar Med Technol Inc, Burlington, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2003 SU 15 MA 121 BP 36 EP 36 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 661FK UT WOS:000181880400121 ER PT J AU Hirsch, RJ Farinelli, WA Laughlin, SA Campos, V Dover, JS Pon, K Van Laborde, S Arndt, KA Dierickx, C Anderson, RR AF Hirsch, RJ Farinelli, WA Laughlin, SA Campos, V Dover, JS Pon, K Van Laborde, S Arndt, KA Dierickx, C Anderson, RR TI Hair growth induced by laser hair removal SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 09-13, 2003 CL ANAHEIM, CALIFORNIA SP American Soc Laser Med Surg C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. Laserderm, Ottawa, ON, Canada. Clin Valeria Campos, Junduau, Brazil. Skin Phys Chestnut Hill, Chestnut Hill, MA USA. Yale Univ, Sch Med, New Haven, CT USA. State Univ Ghent, B-9000 Ghent, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2003 SU 15 MA 229 BP 63 EP 63 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 661FK UT WOS:000181880400216 ER PT J AU Manstein, D Smirnov, MZ Zenzie, HH AF Manstein, D Smirnov, MZ Zenzie, HH TI New technique for hair growth evaluation SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 09-13, 2003 CL ANAHEIM, CALIFORNIA SP American Soc Laser Med Surg C1 Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. Inst Fine Mech, St Petersburg, Russia. Opt Laser Ctr, St Petersburg, Russia. Palomar Med Technol, Burlington, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2003 SU 15 MA 256 BP 70 EP 70 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 661FK UT WOS:000181880400240 ER PT J AU Yang, MU Tsao, SS AF Yang, MU Tsao, SS TI Lupus pernio: Treatment with the 595 nm pulsed dye laser SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 09-13, 2003 CL ANAHEIM, CALIFORNIA SP American Soc Laser Med Surg C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatol Laser Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2003 SU 15 MA 280 BP 76 EP 76 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 661FK UT WOS:000181880400264 ER PT J AU Zenzie, HH Khatri, K Stoll, M Manstein, D Altshuler, G Anderson, R AF Zenzie, HH Khatri, K Stoll, M Manstein, D Altshuler, G Anderson, R TI Long-term hair reduction from multiple treatments with continuous-wave diode laser SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 09-13, 2003 CL ANAHEIM, CALIFORNIA SP American Soc Laser Med Surg C1 Palomar Med Technol, Burlington, MA USA. Skin & Laser Surg Ctr, Cambridge, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2003 SU 15 MA 281 BP 76 EP 76 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 661FK UT WOS:000181880400265 ER PT J AU Lentzsch, S LeBlanc, R Podar, K Davies, F Lin, B Hideshima, T Catley, L Stirling, DI Anderson, KC AF Lentzsch, S LeBlanc, R Podar, K Davies, F Lin, B Hideshima, T Catley, L Stirling, DI Anderson, KC TI Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo SO LEUKEMIA LA English DT Article DE thalidomide; multiple myeloma; Hs Sultan ID HUMAN MULTIPLE-MYELOMA; BONE-MARROW ANGIOGENESIS; POTENT INHIBITORS; TNF-ALPHA; PROGRESSION; THERAPY AB We have previously shown that thalidomide and its potent immunomodulatory derivatives (IMiDs) inhibit the in vitro growth of multiple myeloma (MM) cell lines and patient MM cells that are resistant to conventional therapy. In this study, we further characterize the effect of these drugs on growth of B cell malignancies and angiogenesis. We established a beige-nude-xid (BNX) mouse model to allow for simultaneous in vivo measurement of both anti-tumor and anti-angiogenic effects of thalidomide and its analogs. Daily treatment (50 mg/kg/d) with thalidomide or IMiDs was nontoxic. The IMiDs were significantly more potent than thalidomide in vivo in suppressing tumor growth, evidenced by decreased tumor volume and prolonged survival, as well as mediating anti-angiogenic effects, as determined by decreased microvessel density. Our results therefore show that the IMiDs have more potent direct antitumor and anti-angiogenic effects than thalidomide in vivo, providing the framework for clinical protocols evaluating these agents in MM and other B cell neoplasms. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Adult Onc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Celgene Corp, Warren, NJ USA. Humboldt Univ, Med Ctr, Charite, Robert Roessle Klin, Berlin, Germany. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Adult Onc, 44 Binney St, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 FU PHS HHS [P0-1 78378, R0-1 50947] NR 17 TC 129 Z9 131 U1 0 U2 5 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 2003 VL 17 IS 1 BP 41 EP 44 DI 10.1038/sj.leu.2402745 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 638ZG UT WOS:000180602700006 PM 12529658 ER PT J AU Higuchi, Y Zeng, H Ogawa, M AF Higuchi, Y Zeng, H Ogawa, M TI CD38 expression by hematopoietic stem cells of newborn and juvenile mice SO LEUKEMIA LA English DT Article DE CD38; hematopoietic stem cells; transplantation; developmental changes ID MURINE CD38; TRANSPLANTATION AB While investigators in a number of laboratories have documented that the hematopoietic stem cells (HSCs) of fetal and adult mice are CD38(+), no information is available about CD38 expression by HSCs of newborn and juvenile mice. We used a murine, transplantation model to examine HSC CD38 expression. First, we observed that all HSCs from newborn bone marrow are CD38(-). Next, it was determined that the majority of HSCs in the bone marrow of 5-week-old mice are CD38(-), with a minority being CD38(+). These observations indicated that the CD38(+) subpopulation of HSC appears before the age of 5 weeks and expands during adolescence. However, the majority of HSCs of 5-week-old mice became CD38(+) following injection of 5-fluorouracil, indicating that activation of juvenile stem cells enhances CD38 expression. These observations may have implications for CD38 expression by HSCs from human umbilical cord blood and bone marrow of young children in steady state and under pathological conditions. C1 Med Univ S Carolina, Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Ogawa, M (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. FU NCI NIH HHS [P01-CA78582]; NIDDK NIH HHS [R01-DK54197] NR 16 TC 9 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JAN PY 2003 VL 17 IS 1 BP 171 EP 174 DI 10.1038/sj.leu.2402785 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 638ZG UT WOS:000180602700023 PM 12529675 ER PT J AU Iyer, R Ding, LM Batchu, RB Naugler, S Shammas, MA Munshi, NC AF Iyer, R Ding, LM Batchu, RB Naugler, S Shammas, MA Munshi, NC TI Antisense p53 transduction leads to overexpression of bcl-2 and dexamethasone resistance in multiple myeloma SO LEUKEMIA RESEARCH LA English DT Article DE multiple myeloma; p53; bcl-2; dexamethasone resistance; apoptosis ID WILD-TYPE P53; CHEMOTHERAPY-INDUCED APOPTOSIS; BREAST-CANCER CELLS; GENE-MUTATIONS; PLASMA-CELLS; GROWTH; INVOLVEMENT; EXPRESSION; SUPPRESSION; MALIGNANCY AB Multiple myeloma is a malignant proliferation of plasma cells which fail to undergo apoptosis. To understand events associated with lack of apoptosis in these cells, we studied effect of antisense p53 gene transduction in a multiple myeloma cell line, ARH77. Adeno-associated virus was used as a vector to introduce p53 cDNA in an antisense orientation driven by a herpes virus thymidine kinase promoter. We observed, that an antisense p53 (p53as) transduced cell line showed marked reduction in p53 mRNA and protein expression and increased growth when compared to the control cell lines transduced with neomycin-resistance gene or untransduced cells. There was a concomitant up-regulation of bcl-2 expression by over five-fold in p53as-transduced cells compared with controls; while there was no significant change in expression of c-myc and IL-6, genes implicated in myeloma growth. We measured apoptosis in the transduced cells by DNA end-labeling reaction which revealed decrease in apoptosis from 15.6% in control cells to 1.6% in p53as-transduced cells. Additionally, the p53as cells over expressing bcl-2 also showed resistance to killing by dexamethasone. In summary, our data demonstrates that loss of p53 function leads to myeloma cell progression and resistant phenotype through bcl-2-related mechanisms. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Arkansas Med Sci, Myeloma & Transplantat Res Ctr, Little Rock, AR 72205 USA. Cent Arkansas VA Med Ctr, Little Rock, AR 72205 USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, 44 Binney St,M557, Boston, MA 02115 USA. NR 31 TC 16 Z9 18 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD JAN PY 2003 VL 27 IS 1 BP 73 EP 78 AR PII S0145-2126(02)00064-4 DI 10.1016/S0145-2126(02)00064-4 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 638JW UT WOS:000180568700011 PM 12479855 ER PT J AU Arbuckle, MR James, JA Dennis, GJ Rubertone, MV McClain, MT Kim, XR Harley, JB AF Arbuckle, MR James, JA Dennis, GJ Rubertone, MV McClain, MT Kim, XR Harley, JB TI Rapid clinical progression to diagnosis among African-American men with systemic lupus erythematosus SO LUPUS LA English DT Article DE African-American; autoantibodies; ethnicity; gender; lupus; SLE ID 3 ETHNIC-GROUPS; DESCRIPTIVE ANALYSIS; GENDER DIFFERENCES; REVISED CRITERIA; GENOME SCAN; DISEASE; FEATURES; AUTOANTIBODIES; MANIFESTATIONS; CLASSIFICATION AB The initial clinical course of systemic lupus erythematosus (SLE) is variable, ranging from relatively minor manifestations progressing over years to rapid onset of fulminate disease. We sought to identify factors associated with the rapid manifestation of SLE. Chart review of military medical records was used to identify 130 patients who met the American College of Rheumatology classification criteria for SLE. Demographics, clinical criteria date of occurrence, and the date of SLE classification (at least four clinical criteria) met were documented. Prospectively stored serum samples prior to the diagnosis were evaluated for SLE autoantibodies. Median time from the first recorded criteria to diagnosis was significantly shorter in African-American (AA) males compared with AA females and European American (EA) females and males combined. AA males were more likely to have nephritis as their first clinical symptom. Also, less time transpired between the first clinical criterion and SLE diagnosis in AA males with nephritis than in other groups presenting with nephritis. Even when cases presenting with nephritis were excluded, a diagnosis of SLE was made more rapidly in AA males. African-American men progress from initial clinical manifestations to SLE diagnosis more rapidly than other ethnic or gender groups. C1 Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. Walter Reed Army Med Ctr, Dept Rheumatol, Washington, DC 20307 USA. USA, Ctr Hlth Promot & Prevent Med, Army Med Surveillance Act, Washington, DC 20310 USA. Oklahoma Med Res Fdn, Genet Epidemiol Unit, Oklahoma City, OK 73104 USA. US Dept Vet Affairs, Oklahoma City, OK USA. RP James, JA (reprint author), Oklahoma Med Res Fdn, Arthrit & Immunol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. FU NIAID NIH HHS [AI24717, AI31584]; NIAMS NIH HHS [AR01981, AR42460, AR45084, AR45231] NR 29 TC 42 Z9 46 U1 0 U2 1 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2003 VL 12 IS 2 BP 99 EP 106 DI 10.1191/0961203303lu334oa PG 8 WC Rheumatology SC Rheumatology GA 651EU UT WOS:000181308200004 PM 12630753 ER PT J AU Fisher, DE AF Fisher, DE TI The Henry Kunkel legacy: from the eyes of his last graduate student SO LUPUS LA English DT Biographical-Item C1 Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2003 VL 12 IS 3 BP 172 EP 174 DI 10.1191/0961203303lu351xx PG 3 WC Rheumatology SC Rheumatology GA 666GG UT WOS:000182168400006 PM 12708776 ER PT J AU Holliday, SL Navarrete, MG Hermosillo-Romo, D Valdez, CR Saklad, AR Escalante, A Brey, RL AF Holliday, SL Navarrete, MG Hermosillo-Romo, D Valdez, CR Saklad, AR Escalante, A Brey, RL TI Validating a computerized neuropsychological test battery for mixed ethnic lupus patients SO LUPUS LA English DT Article DE neuropsychiatric; neuropsychological testing; systemic lupus erythematosus ID COGNITIVE IMPAIRMENT; NEUROPSYCHIATRIC SYNDROMES; RATING-SCALE; ERYTHEMATOSUS; PREVALENCE; DYSFUNCTION; DEFINITIONS; DEPRESSION; INDEX AB Patients with systemic lupus erythematosus (SLE) often show cognitive impairment on traditional neuropsychological tests; however, many of these tests are unsuitable for use with mixed ethnic populations. Computer-administered cognitive tests are promising, but have not been validated against traditional tests or with predominantly Hispanic samples. We gave 67 lupus patients a computer-administered test battery (Automated Neuropsychological Assessment Metrics - ANAM) and a battery of traditional neuropsychological tests. The two batteries were compared using correlation and multiple regression analyses. All patients were fluent in English, 54% were Hispanic and 13% were bilingual. Non-Hispanic patients were predominantly European American (37%). About 80% of patients were rated as impaired on traditional tests. Hispanics were younger, had less education and more current SLE disease activity than non-Hispanics; but did not differ in lifetime SLE-related organ damage or current steroid use. Hispanics and younger patients were more impaired on many of the traditional tests, while ANAM was not affected by Hispanic ethnicity or education. ANAM tests were moderately correlated with analogous traditional tests. Age and selected ANAM scores accounted for about 60% of the variance in the traditional battery. These results replicate the high prevalence of cognitive deficits in SLE found by others and suggest that computer-administered tests like ANAM may be useful for assessment of cognitive impairment in mixed-ethnic samples. Confounding variables such as age, education, English language fluency and prior experience with tests were identified and need to be controlled statistically or with comparison groups in future studies. C1 S Texas Vet Hlth Care Syst, Psychol Serv 116B, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Neurol, San Antonio, TX 78229 USA. RP Holliday, SL (reprint author), S Texas Vet Hlth Care Syst, Psychol Serv 116B, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. RI Valdez, Carmen/K-6313-2012 FU NCRR NIH HHS [M01 RR01346-19]; NINDS NIH HHS [NS35477] NR 32 TC 30 Z9 31 U1 1 U2 1 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2003 VL 12 IS 9 BP 697 EP 703 DI 10.1191/0961203303lu442oa PG 7 WC Rheumatology SC Rheumatology GA 721MJ UT WOS:000185319900008 PM 14514133 ER PT J AU Reese, TG Heid, O Weisskoff, RM Wedeen, VJ AF Reese, TG Heid, O Weisskoff, RM Wedeen, VJ TI Reduction of eddy-current-induced distortion in diffusion MRI using a twice-refocused spin echo SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE diffusion MRI; eddy currents; image distortion; pulse sequence; artifact ID CURRENT-INDUCED ARTIFACTS; MAGNETIC-RESONANCE; WATER DIFFUSION; PLANAR IMAGES; FIBER ARCHITECTURE; SPECTROSCOPY; ANISOTROPY; FIELDS AB Image distortion due to field gradient eddy currents can create image artifacts in diffusion-weighted MR images. These images, acquired by measuring the attenuation of NMR signal due to directionally dependent diffusion, have recently been shown to be useful in the diagnosis and assessment of acute stroke and in mapping of tissue structure. This work presents an improvement on the spin-echo (SE) diffusion sequence that displays less distortion and consequently improves image quality. Adding a second refocusing pulse provides better image quality with less distortion at no cost in scanning efficiency or effectiveness, and allows more flexible diffusion gradient timing. By adjusting the timing of the diffusion gradients, eddy currents with a single exponential decay constant can be nulled, and eddy currents with similar decay constants can be greatly reduced. This new sequence is demonstrated in phantom measurements and in diffusion anisotropy images of normal human brain. (C) 2003 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Siemens AG, Med Engn Div, D-8520 Erlangen, Germany. Epix Med Inc, Cambridge, MA USA. RP Reese, TG (reprint author), MGH NMR Ctr, Bldg 149,13th St 2301,Charlestown Navy Yard, Charlestown, MA 02129 USA. FU NIMH NIH HHS [R01 MH64044] NR 29 TC 790 Z9 793 U1 2 U2 29 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JAN PY 2003 VL 49 IS 1 BP 177 EP 182 DI 10.1002/mrm.10308 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 631BW UT WOS:000180148100023 PM 12509835 ER PT B AU Lauwers, GY AF Lauwers, GY BE Berr, F Bruix, J Hauss, J Wands, J Wittekind, C TI Hepatocellular carcinoma: Pathological indicators of prognosis SO MALIGNANT LIVER TUMOURS: BASIC CONCEPTS AND CLINICAL MANAGEMENT SE FALK SYMPOSIUM LA English DT Proceedings Paper CT Falk Workshop on Malignant Liver Tumours - Basic Concepts and Clinical Management CY JAN 24-25, 2002 CL LEIPZIG, GERMANY SP Falk Fdn ID LYMPH-NODE METASTASIS; HEPATIC RESECTION; INTRAHEPATIC RECURRENCE; POSTOPERATIVE RECURRENCE; CLINICAL-SIGNIFICANCE; VENOUS INVASION; HEPATECTOMY; LIVER; SURVIVAL; CLASSIFICATION C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lauwers, GY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,Warren 256, Boston, MA 02114 USA. NR 54 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8779-1 J9 FALK SYMP PY 2003 VL 127 BP 75 EP 86 PG 12 WC Oncology; Cell Biology; Gastroenterology & Hepatology; Genetics & Heredity; Pathology SC Oncology; Cell Biology; Gastroenterology & Hepatology; Genetics & Heredity; Pathology GA BV81P UT WOS:000180115400010 ER PT J AU Anderson, KC AF Anderson, KC TI Multiple myeloma: How far have we come? SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID CHEMOTHERAPY; THALIDOMIDE; SURVIVAL C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St,Rm M557, Boston, MA 02115 USA. NR 22 TC 25 Z9 28 U1 0 U2 1 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 2003 VL 78 IS 1 BP 15 EP 17 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 632VQ UT WOS:000180244500002 PM 12528872 ER PT J AU Chang, JS Van Remmen, H Cornell, J Richardson, A Ward, WF AF Chang, JS Van Remmen, H Cornell, J Richardson, A Ward, WF TI Comparative proteomics: characterization of a two-dimensional gel electrophoresis system to study the effect of aging on mitochondrial proteins SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article; Proceedings Paper CT International Conference on Functional Genomics of Ageing CY APR 24-27, 2002 CL SEVILLE, SPAIN DE 2-D PAGE; mitochondria proteins; aging; skeletal muscle ID IMMOBILIZED PH GRADIENTS; 2-DIMENSIONAL ELECTROPHORESIS; OXIDATIVE STRESS; IDENTIFICATION; COMPLEX; LIVER AB To study the effect of aging and anti-aging strategies on mitochondria, we have characterized a two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) system to analyze the profile of mitochondrial proteins. We have optimized the separation of proteins by 2-D PAGE and established the linearity and reproducibility of the system with mitochondria isolated from skeletal muscle of mice. Using total mitochondria protein ranging from 10 to 200 mug, we found that 74% of the proteins resolved by 2-D PAGE had coefficient of determination (R-2) values greater than 0.8, showing a linear increase in fluorescence with increasing protein concentration. The coefficient of variation (CV) was less than 50% for at least 93% of the 424 spots analyzed for both gel-to-gel variance and animal-to-animal variance. Using mitochondrial protein fractions prepared from skeletal muscle of 18-month-old mice, we show that 10 animals will be sufficient to detect a 100% difference in the 97% (i.e. 505) of the proteins resolved by 2-D PAGE. Thus, 2-D PAGE provides a sensitive and reliable technique for analysis of protein expression in mitochondria. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Div Geriatr & Gerontol, San Antonio, TX 78229 USA. RP Ward, WF (reprint author), Univ Texas, Hlth Sci Ctr, Dept Physiol, 7703 Floyd Curl Dr,MSC 7756, San Antonio, TX 78229 USA. FU NIA NIH HHS [P01 AG20591, P01 AG13319, P01 AG19316, P01AG14674] NR 32 TC 32 Z9 36 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JAN PY 2003 VL 124 IS 1 BP 33 EP 41 AR PII S0047-6374(02)00167-7 DI 10.1016/S0047-6374(02)00167-7 PG 9 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 665BJ UT WOS:000182099500006 PM 12618004 ER PT J AU Smetana, GW Macpherson, DS AF Smetana, GW Macpherson, DS TI The case against routine preoperative laboratory testing SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID CHEST X-RAYS; CARDIAC SURGICAL-PROCEDURES; CATARACT-SURGERY; ADMISSION URINALYSIS; NONCARDIAC SURGERY; UNPROVEN UTILITY; ELDERLY PATIENTS; BLEEDING-TIME; RISK-FACTORS; RADIOGRAPHY AB Clinicians often obtain routine laboratory tests with the intent of identifying patients at risk for postoperative complications. Such tests should be performed selectively based on patient characteristics and the type of planned surgery. Most laboratory abnormalities can be predicted based on clinical evaluation and add little to the preoperative risk assessment or management. The incidence of unanticipated abnormalities that influences management for many preoperative tests is less than 1 %. In this article, we provide the evidence base to support a strategy of selective preoperative testing and to make a case against routine preoperative laboratory testing. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Univ Pittsburgh, Dept Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. RP Smetana, GW (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 330 Brookline Ave, Boston, MA 02215 USA. NR 84 TC 63 Z9 70 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JAN PY 2003 VL 87 IS 1 BP 7 EP + AR PII S0025-7125(02)00147-5 DI 10.1016/S0025-7125(02)00147-5 PG 35 WC Medicine, General & Internal SC General & Internal Medicine GA 640ZT UT WOS:000180719600003 PM 12575882 ER PT J AU Arozullah, AM Conde, MV Lawrence, VA AF Arozullah, AM Conde, MV Lawrence, VA TI Preoperative evaluation for postoperative pulmonary complications SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID POSITIVE AIRWAY PRESSURE; UPPER ABDOMINAL-SURGERY; DEEP BREATHING EXERCISES; OBSTRUCTIVE LUNG-DISEASE; INCENTIVE SPIROMETRY; RISK-FACTORS; RESPIRATORY-FAILURE; CONSERVATIVE THERAPY; CHEST PHYSIOTHERAPY; THORACIC-SURGERY AB This article reviews the morbidity and mortality associated with postoperative pulmonary complications and the risk factors associated with the development of postoperative pulmonary complications. The authors discuss indications for specific preoperative tests, including preoperative pulmonary function testing. Risk indices for predicting postoperative pulmonary complications are also presented. Finally, the authors review the evidence for various risk reduction strategies. C1 Univ Illinois, Coll Med, Gen Internal Med Sect, Chicago, IL 60612 USA. Vet Affairs Chicago Healthcare Syst, Westside Div, Chicago, IL USA. Univ Texas, Hlth Sci Ctr, Audie Murphy Div, S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Audie Murphy Div, Gen Internal Med Sect, San Antonio, TX USA. RP Arozullah, AM (reprint author), Univ Illinois, Coll Med, Gen Internal Med Sect, M-C 718,840 S Wood St,Suite 440-M, Chicago, IL 60612 USA. NR 86 TC 33 Z9 36 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JAN PY 2003 VL 87 IS 1 BP 153 EP + AR PII S0025-7125(02)00151-7 DI 10.1016/S0025-7125(02)00151-7 PG 22 WC Medicine, General & Internal SC General & Internal Medicine GA 640ZT UT WOS:000180719600009 PM 12575888 ER PT J AU Rizvon, MK Chou, CL AF Rizvon, MK Chou, CL TI Surgery in the patient with liver disease SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID ACUTE ACALCULOUS CHOLECYSTITIS; POSTOPERATIVE RENAL-FUNCTION; CIRRHOTIC-PATIENTS; HEPATOCELLULAR-CARCINOMA; LAPAROSCOPIC CHOLECYSTECTOMY; OBSTRUCTIVE-JAUNDICE; HEPATIC RESECTION; RISK-FACTORS; ABDOMINAL OPERATIONS; SURGICAL RISK AB Patients with liver disease scheduled for surgery need to be evaluated in a stepwise manner with careful emphasis on history and physical examination. Appropriate laboratory testing should be done in patients with clinical evidence of liver disease. Elective surgery should be postponed in patients with active hepatitis. Child's classification still remains an important prognostic factor in evaluating surgical patients with cirrhosis. Newer techniques, such as laparoscopic procedures, seem to be associated with a better postoperative course. C1 Nassau Univ, Med Ctr, Med Consultat Serv, E Meadow, NY 11554 USA. SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. San Francisco Vet Affairs Med Ctr, Med Consultat Serv, San Francisco, CA USA. RP Rizvon, MK (reprint author), Nassau Univ, Med Ctr, Med Consultat Serv, 2201 Hempstead Turnpike, E Meadow, NY 11554 USA. NR 100 TC 18 Z9 19 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JAN PY 2003 VL 87 IS 1 BP 211 EP + AR PII S0025-7125(02)00153-0 DI 10.1016/S0025-7125(02)00153-0 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 640ZT UT WOS:000180719600012 PM 12575891 ER PT J AU King, JT Justice, AC Roberts, MS Chang, CCH AF King, JT Justice, AC Roberts, MS Chang, CCH TI Long-term HIV/AIDS survival estimation in the highly active antiretroviral therapy era SO MEDICAL DECISION MAKING LA English DT Article DE AIDS; anti-infective agents/therapeutic use; CD4 lymphocyte count; life expectancy; Markov chains; models, theoretical ID IMMUNODEFICIENCY-VIRUS INFECTION; COST-EFFECTIVENESS; HIV-INFECTION; ZIDOVUDINE TREATMENT; AIDS; MORTALITY; DISEASE; REGIMEN; COHORT; COUNT AB Background. Highly active antiretroviral therapy (HAART) prolongs short-term survival in patients with HIV/AIDS. HAART has only been available since 1996; thus, no long-term survival data are available. Computer simulation models extrapolating short-term survival data can provide estimates of long-term survival. These survival estimates may assist patients and clinicians in HAART treatment planning. The authors construct a computer simulation model based on observational data to estimate long-term survival in a cohort of HIV/AIDS patients undergoing treatment with HAART Methods. The authors use data from the Collaboration in HIV Outcomes Research-US (CHORUS) observational cohort (N = 4791), the published literature, and US Life Tables to specify a computer simulation model of expected survival accounting for baseline CD4 cell count, progressive HAART treatment failure, progressive risk of HAART on-treatment mortality, and age-associated mortality. Time to treatment failure for each of three rounds of HAART and risk of mortality on-treatment were estimated using parametric survival models with censoring of follow-up fit to CHORUS data. Off-treatment survival after HAART failure was estimated from the pre-HAART literature. Age-associated mortality was taken from US Life Tables. Results. Median projected survivals stratified by baseline CD4 cell count subgroups were CD4 > 200 cells/mm(3), 15.4 years; CD4 less than or equal to 200 cells/mm(3), 8.5 years; and CD4 less than or equal to 50 cells/mm(3), 5.5 years. These values are 4 to 6 years longer than pre-HAART cohorts. The sensitivity analyses showed that the model survival predictions were most sensitive to the treatment failure rate, the on-treatment mortality rate, and the number of treatment rounds. Conclusions. Computer simulation modeling of long-term survival of patients with HIV/AIDS on HAART-accounting for differential treatment failure and death rates stratified by CD4 cell count and age-associated mortality-suggests a relatively consistent 4- to 6-year survival benefit over pre-HAAART therapies. C1 VA Pittsburgh Healthcare Syst, Surg Serv Line, Neurosurg Sect, Pittsburgh, PA USA. Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Dept Med, Div Gen Internal Med, Sect Decis Sci & Clin Syst Modeling, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Hlth Care, Pittsburgh, PA USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA USA. GlaxoSmithKline Inc, N Amer Med Affairs, Res Triangle Pk, NC USA. RP Justice, AC (reprint author), Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Univ Dr C,11E-124 130-U, Pittsburgh, PA 15240 USA. NR 28 TC 43 Z9 45 U1 0 U2 3 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 2003 VL 23 IS 1 BP 9 EP 20 DI 10.1177/0272989X02239652 PG 12 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 640BC UT WOS:000180665300001 PM 12583451 ER PT S AU Kim, HK Rattner, DW Srinivasan, MA AF Kim, HK Rattner, DW Srinivasan, MA BE Ellis, RE Peters, TM TI The role of simulation fidelity in laparoscopic surgical training SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2003, PT 1 SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 6th International Conference on Medical Imaging Computing and Computer-Assisted Intervention CY NOV 15-18, 2003 CL MONTREAL, CANADA SP Robarts Res Inst, No Digital Inc ID VIRTUAL ENVIRONMENTS AB Although there have been significant advances in the development of virtual reality based surgical simulations, there still remain fundamental questions concerning the fidelity required for effective surgical training. A dual station experimental platform was built for the purpose of investigating these fidelity requirements. Analogous laparoscopic surgical tasks were implemented in a virtual and a real station, with the virtual station modeling the real environment to various degrees of fidelity. After measuring subjects' initial performance in the real station, different groups of subjects were trained on the virtual station under a variety of conditions and tested finally at the real station. Experiments involved bimanual pushing and cutting tasks on a nonlinear elastic object. The results showed that force feedback results in a significantly improved training transfer compared to training without force feedback. The training effectiveness of a linear approximation model was comparable to the effectiveness of a more accurate nonlinear model. C1 MIT, Dept Engn Mech, Cambridge, MA 02139 USA. MIT, Res Lab Electron, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. RP Kim, HK (reprint author), MIT, Dept Engn Mech, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM hyunkim@mit.edu NR 12 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-20462-8 J9 LECT NOTES COMPUT SC PY 2003 VL 2878 BP 1 EP 8 PG 8 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Medicine, Research & Experimental; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Research & Experimental Medicine; Radiology, Nuclear Medicine & Medical Imaging GA BY26L UT WOS:000188592600001 ER PT S AU Kim, J Tay, BK Stylopoulos, N Rattner, DW Srinivasan, MA AF Kim, J Tay, BK Stylopoulos, N Rattner, DW Srinivasan, MA BE Ellis, RE Peters, TM TI Characterization of intra-abdominal tissues from in vivo animal experiments for surgical simulation SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2003, PT 1 SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 6th International Conference on Medical Imaging Computing and Computer-Assisted Intervention CY NOV 15-18, 2003 CL MONTREAL, CANADA SP Robarts Res Inst, No Digital Inc ID VIRTUAL ENVIRONMENTS; SURGERY AB The lack of data on in vivo material properties of soft tissues is one of the impediments in the development of realistic surgical simulators. The measurement of these properties is not a trivial task, due to the difficulty of the testing itself and the complexity of tissue mechanical behavior. We have developed a system for measuring the mechanical properties of soft tissues in vivo using a robotic device fitted with a force transducer. We measured the response of soft tissues in intra-abdominal organs including the liver and lower esophagus of pigs by using both static and dynamic indentations. We characterize these properties using nonlinear models as well as a linear model. These material models can be effectively integrated into a simulator to provide the user with realistic visual and haptic feedback. C1 MIT, Dept Engn Mech, Touch Lab, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. RP Kim, J (reprint author), MIT, Dept Engn Mech, Touch Lab, Cambridge, MA 02139 USA. EM jungkim@mit.edu RI Kim, Jung/C-1636-2011 NR 13 TC 6 Z9 7 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-20462-8 J9 LECT NOTES COMPUT SC PY 2003 VL 2878 BP 206 EP 213 PG 8 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Medicine, Research & Experimental; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Research & Experimental Medicine; Radiology, Nuclear Medicine & Medical Imaging GA BY26L UT WOS:000188592600026 ER PT J AU Leaf, AN Propert, K Corcoran, C Catalano, PJ Trump, DL Harris, JE Davis, TE AF Leaf, AN Propert, K Corcoran, C Catalano, PJ Trump, DL Harris, JE Davis, TE TI Phase III study of combined chemohormonal therapy in metastatic prostate cancer (ECOG 3882) - An eastern cooperative oncology group study SO MEDICAL ONCOLOGY LA English DT Article DE metastatic prostate cancer; doxorubicin; intravenous diethylstilbestrol diphosphate ID TRIAL; DIETHYLSTILBESTROL; CARCINOMA AB This study, a phase III multicenter randomized trial opened by ECOG in April 1983 and closed in June 1986 was designed to evaluate whether a combination of doxorubicin and an intravenous formulation of diethylstilbestrol diphosphate (DES) was superior to doxorubicin alone in men with hormone refractory prostate cancer. All patients received doxorubicin at a dose of 50 mg/m(2) iv every 3 wk either alone or with I g DES iv daily for 5 d followed by 1 g iv twice weekly for four cycles (12 wk). The 51 evaluable patients with visceral metastases displayed a significantly increased response rate (27% vs 63%) on the combined therapy arm (p = 0.04). However, the 111 evaluable patients with osseous disease exhibited no difference in response rate between either arm with a p-value of >0.99. Similarly, clinical response rates revealed no difference between the two arms. Cases of cardiac toxicity graded as severe, life threatening, or lethal in the combined therapy arm were 10 times more frequent in the combined-therapy arm than in the doxorubicin-alone group (6.75% compared to 0.7%). This difference was statistically significant (p = 0.0041). All of the cases of superficial and deep venous thrombosis occurred on the combined-therapy arm. There were no other significant differences in the numbers of grade 3 or 4 toxic events. The most common toxicity was hematologic. Failure-free survival duration did reach statistical significance in the combined-therapy group (p = 0.012), although the actual durations were short (2.6-3.2 mo). There was no difference in overall survival between the two groups. C1 Univ Penn, Philadelphia, PA 19104 USA. Utah State Univ, Logan, UT 84322 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Dept Vet Affairs Med Ctr, Brooklyn, NY USA. RP Leaf, AN (reprint author), Vet Affairs Med Ctr, Dept Hematol Oncol, 111D,800 Poly Pl, Brooklyn, NY 11209 USA. RI Corcoran, Chris/F-2155-2010 FU NCI NIH HHS [CA 23318, CA 21076, CA 66636, CA 17145, CA 21115] NR 20 TC 8 Z9 8 U1 1 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. PY 2003 VL 20 IS 2 BP 137 EP 145 DI 10.1385/MO:20:2:137 PG 9 WC Oncology SC Oncology GA 702WF UT WOS:000184247200004 PM 12835516 ER PT S AU Stylopoulos, N Cotin, S Dawson, S Ottensmeyer, M Neumann, P Bardsley, R Russell, M Jackson, P Rattner, D AF Stylopoulos, N Cotin, S Dawson, S Ottensmeyer, M Neumann, P Bardsley, R Russell, M Jackson, P Rattner, D BE Westwood, JD Hoffman, HM Mogel, GT Phillips, R Robb, RA Stredney, D TI CELTS: a clinically-based computer enhanced laparoscopic training system SO MEDICINE MEETS VIRTUAL REALITY 11: NEXTMED: HEALTH HORIZON SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th Annual Medicine Meets Virtual Reality Conference CY JAN 22-25, 2003 CL Newport Beach, CA SP Univ Calif, Irvine Coll Med, Aligned Management Associates Inc, Telemed & Adv Technol Res Ctr, USA Med Res & Mat Command C1 Massachusetts Gen Hosp, Simulat Grp, CIMIT, Cambridge, MA 02139 USA. RP Stylopoulos, N (reprint author), Massachusetts Gen Hosp, Simulat Grp, CIMIT, 65 Landsdowne St, Cambridge, MA 02139 USA. NR 5 TC 13 Z9 13 U1 0 U2 1 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-320-4 J9 ST HEAL T PY 2003 VL 94 BP 336 EP 342 PG 7 WC Computer Science, Interdisciplinary Applications; Medicine, Research & Experimental SC Computer Science; Research & Experimental Medicine GA BY87U UT WOS:000189484800067 PM 15455919 ER PT J AU Pinkerton, JV Shifren, JL La Valleur, J Rosen, A Roesinger, M Siddhanti, S AF Pinkerton, JV Shifren, JL La Valleur, J Rosen, A Roesinger, M Siddhanti, S TI Influence of raloxifene on the efficacy of an estradiol-releasing ring for treating vaginal atrophy in postmenopausal women SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE raloxifene; estradiol-releasing vaginal ring; vaginal atrophy; menopause ID ESTROGEN-RECEPTOR MODULATORS; HORMONE REPLACEMENT THERAPY; TRIAL; OSTEOPOROSIS; ENDOMETRIUM; PLACEBO; RISK AB Objective: To determine the potential interaction of oral raloxifene 60 mg/day on the efficacy of a low-dose, estradiol-releasing vaginal ring used to treat signs and symptoms of vaginal atrophy in postmenopausal women. Design: Randomized, double-blind, placebo-controlled, parallel treatment trial of raloxifene and placebo with open-label 17beta-estradiol ring. At 10 sites in the United States, 91 postmenopausal women with at least two signs of vaginal atrophy were treated with a 17beta-estradiol ring and randomized to receive concomitant raloxifene 60 mg/day or placebo for 6 months. Efficacy of treatments was evaluated by comparing investigator assessments of genitourinary atrophic signs, vaginal maturation value, and participant assessments of vaginal symptoms at 6 months. Other measures included rate and severity of hot flashes and assessment of sexual function. Uterine safety was assessed by endometrial biopsy and transvaginal ultrasound. Results: In women treated with a 17beta-estradiol ring, both the raloxifene and placebo treatment groups showed improvements in signs and symptoms of vaginal atrophy at 6 months, with no significant differences in degree of improvement between groups. There were no signs of endometrial proliferation in either group. Conclusions: Concomitant administration of raloxifene does not alter the effects of the 17beta-estradiol ring on alleviating signs and symptoms of genitourinary atrophy in postmenopausal women. C1 Univ Virginia, Hlth Syst, Womens Pl Midlife Hlth Ctr, Charlottesville, VA 22908 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Minnesota, Minneapolis, MN USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Pinkerton, JV (reprint author), Univ Virginia, Hlth Syst, Womens Pl Midlife Hlth Ctr, 2955 Ivy Rd,Suite 104,POB 801104, Charlottesville, VA 22908 USA. NR 23 TC 33 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN-FEB PY 2003 VL 10 IS 1 BP 45 EP 52 DI 10.1097/01.GME.0000030261.27673.65 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 635FQ UT WOS:000180388600008 PM 12544676 ER PT J AU Kennedy, DN Haselgrove, C McInerney, S AF Kennedy, DN Haselgrove, C McInerney, S TI MRI-based morphometric analysis of typical and atypical brain development SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE magnetic resonance imaging; volume; quantitative brain anatomy; database; image analysis; morphometry ID VOXEL-BASED MORPHOMETRY; SURFACE-BASED ANALYSIS; CORTICAL SURFACE; IN-VIVO; COORDINATE SYSTEM; SEGMENTATION; NEUROSCIENCE; NEURONAMES; SCIENCE; CORTEX AB The neuroinformatics landscape in which human brain morphometry occurs has advanced dramatically over the past few years. Rapid advancement in image acquisition methods, image analysis tools and interpretation of morphometric results make the study of in vivo anatomic analysis both challenging and rewarding. This has revolutionized our expectations for current and future diagnostic and investigative work with the developing brain. This paper will briefly cover the methods of morphometric analysis that available for neuroanatomic analysis, and tour some sample results from a prototype retrospective database of neuroanatomic volumetric information. From these observations, issues regarding the anatomic variability of developmental maturation of neuroanatomic structures in both typically and atypically developing populations can be discussed. (C) 2003 Wiley-Liss, Inc. C1 MGH, CMA, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Dept Neurol, Boston, MA 02114 USA. MGH MIT HMS, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. RP Kennedy, DN (reprint author), MGH, CMA, 149 13th St, Charlestown, MA 02129 USA. RI Kennedy, David/H-3627-2012 FU NINDS NIH HHS [NS20489, NS02126, NS34189] NR 49 TC 21 Z9 21 U1 2 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 2003 VL 9 IS 3 BP 155 EP 160 DI 10.1002/mrdd.10075 PG 6 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 719HB UT WOS:000185196600004 PM 12953294 ER PT J AU Chan, C Berthiaume, F Lee, K Yarmush, ML AF Chan, C Berthiaume, F Lee, K Yarmush, ML TI Metabolic flux analysis of hepatocyte function in hormone- and amino acid-supplemented plasma SO METABOLIC ENGINEERING LA English DT Article ID ADULT-RAT HEPATOCYTES; CULTURED-HEPATOCYTES; FATTY-ACIDS; CARBOHYDRATE-METABOLISM; BIOARTIFICIAL LIVER; GENE-EXPRESSION; CELLS; DEHYDROGENASE; GLUCAGON; GLUCOSE AB Understanding the metabolic and regulatory pathways of hepatocytes is important for biotechnological applications involving liver cells. Previous attempts to culture hepatocytes in plasma yielded poor functional results. Recently we reported that hormone (insulin and hydrocortisone) and amino acid supplementation reduces intracellular lipid accumulation and restores liver-specific function in hepatocytes exposed to heparinized human plasma. In the current study, we performed metabolic flux analysis (MFA) using a simplified metabolic network model of cultured hepatocytes to quantitively estimate the changes in lipid metabolism and relevant intracellular pathways in response to hormone and amino acid supplementation. The model accounts for the majority of central carbon and nitrogen metabolism, and assumes pseudo-steady-state with no metabolic futile cycles. We found that beta-oxidation and tricarboxylic acid (TCA) cycle fluxes were upregulated by both hormone and amino acid supplementation, thus enhancing the rate of lipid oxidation. Concomitantly, hormone and amino acid supplementation increased gluconeogenic fluxes. This, together with an increased rate of glucose clearance, caused an increase in predicted glycogen synthesis. Urea synthesis was primarily derived from ammonia and aspartate generated through transamination reactions, while exogenous ammonia removal accounted for only 3-6% of the urea nitrogen. Amino acid supplementation increased the endogenous synthesis of oxaloacetate, and in turn that of aspartate, a necessary substrate for the urea cycle. These findings from MFA provide cues as to which genes/pathways relevant to fatty acid oxidation, urea production, and gluconeogenesis may be upregulated by plasma supplementation, and are consistent with current knowledge of hepatic amino acid metabolism, which provides further credence to this approach for evaluating the metabolic state of hepatocytes under various environmental conditions. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med,Surg Serv, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med,Surg Serv, 55 Fruit St,Bigelow 1401, Boston, MA 02114 USA. RI Lee, Kyongbum/D-9230-2013 FU NIDDK NIH HHS [R01 DK 41709]; NIGMS NIH HHS [R01GM 07035] NR 47 TC 71 Z9 73 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7176 J9 METAB ENG JI Metab. Eng. PD JAN PY 2003 VL 5 IS 1 BP 1 EP 15 DI 10.1016/S1096-7176(02)00011-3 PG 15 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 681UU UT WOS:000183054600001 PM 12749840 ER PT S AU Doria, A AF Doria, A BE Crepaldi, G Tiengo, A Avogaro, A TI Adipokine genes and the insulin-resistance syndrome SO METABOLIC SYNDROME: DIABETES, OBESITY, HYPERLIPIDEMIA AND HYPERTENSION SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 8th European Symposium on Metabolism CY OCT 02-05, 2002 CL PADUA, ITALY DE adipokine; insulin; resistin ID OBESITY; ADIPONECTIN; PROTEIN; SENSITIVITY; ASSOCIATION; CAUCASIANS; RISK; POLYMORPHISM; EXPRESSION; POPULATION AB Adipocytes secrete several molecules that are involved in the regulation of whole-body metabolism and other vital functions related to inflammation and immune responses. Genetic variability in the expression or activity of these cytokines, or adipokines, may be involved in the development of the insulin-resistance syndrome and type 2 diabetes. Two of these molecules-resistin and adiponectin-have been intensively studied during the past year. We and others have identified a single nucleotide polymorphism in the resistin gene that interacts with obesity in determining the risk of insulin-resistance and type 2 diabetes. A haplotype associated with several features of the insulin-resistance syndrome has also been identified at the adiponectin locus. Whether these polymorphisms are themselves responsible for the association with insulin-resistance or are markers in linkage disequilibrium with as yet unidentified causal variants is unknown at this time. Further studies extending the polymorphism analysis to flanking regions and investigating variants for regulatory effects on gene expression are necessary to address this issue. Identification of diabetes-predisposing variants in adipokine genes will provide novel insights in the cellular mechanisms through which increased adiposity leads to insulin-resistance and type 2 diabetes, with possible implications on the development of new drugs to prevent these disorders. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. RP Doria, A (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. NR 27 TC 1 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-51242-X J9 INT CONGR SER PY 2003 VL 1253 BP 63 EP 71 DI 10.1016/S0531-5131(03)00136-5 PG 9 WC Endocrinology & Metabolism; Medicine, General & Internal; Medicine, Research & Experimental SC Endocrinology & Metabolism; General & Internal Medicine; Research & Experimental Medicine GA BX86F UT WOS:000186667300008 ER PT J AU Song, MK Hwang, IK Rosenthal, MJ Harris, DM Yamaguchi, DT Yip, I Go, VLW AF Song, MK Hwang, IK Rosenthal, MJ Harris, DM Yamaguchi, DT Yip, I Go, VLW TI Antidiabetic actions of arachidonic acid and zinc in genetically diabetic Goto-Kakizaki rats SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID INSULIN-RECEPTOR KINASE; SKELETAL-MUSCLE; IN-VITRO; HIS-PRO; MELLITUS; GLUCOSE; TRANSPORT; PROSTAGLANDIN-E2; ADIPOCYTES; DEFICIENCY AB In previous studies, we showed that feeding arachidonic acid (AA) supplemented with a fixed amount of zinc lowered blood glucose concentrations in the fed state and water intake in rats with streptozotocin-induced diabetes. The present study was designed to determine dose-dependent effects of AA supplemented with a fixed amount of zinc on fed blood glucose levels, water intake, and glucose tolerance in genetically type 2 diabetic Goto-Kakizaki (G-K) Wistar rats. In an acute study, 20 mg/kg AA plus 10 mg/kg zinc administered via gastric gavage significantly improved oral glucose tolerance in G-K rats when compared to rats given distilled water (DW) only. When rats were treated chronically (2 weeks) with increasing doses of AA in drinking water, fed blood glucose concentrations and water intake were maximally decreased with diets containing 20 or 30 mg/L AA plus 10 mg/L zinc. Three-hour average area-above-fasting glucose concentrations (TAFGC; index of oral glucose tolerance) in diabetic G-K rats treated with 10, 20, or 30 mg/L AA plus 10 mg/L zinc for 2 weeks were significantly decreased relative to DW-treated rats. The effect on TAFGC values was maintained for an additional 2 weeks after cessation of treatment. Plasma insulin levels significantly increased in rats treated with 20 mg/L AA only or 10 mg/L AA plus 10 mg/L zinc, but not in rats treated with 20 or 30 mg/L AA plus 10 mg/L zinc, which are the most effective doses for the improvement of clinical signs of diabetes in G-K rats. In in vitro assays, 0.2 mg/mL AA in the incubation media was optimal for glucose uptake in isolated soleus muscle slices. These results suggest that treatment of genetically diabetic G-K rats with AA plus zinc lowers blood glucose levels via improvement of insulin sensitivity. Copyright 2003, Elsevier Science (USA). All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Ctr Human Nutr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Hlthcare Syst, Los Angeles, CA USA. RP Harris, DM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Human Nutr, 900 Veteran Ave,13-145 Warren Hall, Los Angeles, CA 90095 USA. FU NIDDK NIH HHS [1 R43 DK 56546-01] NR 34 TC 23 Z9 26 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JAN PY 2003 VL 52 IS 1 BP 7 EP 12 DI 10.1053/meta.2003.50031 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 632VU UT WOS:000180244800002 PM 12524655 ER PT J AU Mollica, F Jain, RK Netti, PA AF Mollica, F Jain, RK Netti, PA TI A model for temporal heterogeneities of tumor blood flow SO MICROVASCULAR RESEARCH LA English DT Article DE tumor blood flow; temporal heterogeneities; mathematical modeling; tumor vascular permeability ID SOLID TUMORS; ADENOCARCINOMA; MECHANISM AB Tumor blood flow (TBF) plays a fundamental role in tumor growth and treatment, and is characterized by spatial and temporal heterogeneities. Here we show that the interstitial fluid pressure (IFP), which is higher in tumoral tissue than in normal tissue, coupled with the tumor microvascular pressure (MVP) and the higher permeability of tumoral vessels, can explain the sustained oscillatory behavior of TBF, observed in vivo. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Univ Naples Federico II, Dept Mat & Prod Engn, I-80125 Naples, Italy. CNR, Inst Composite Mat Technol, Naples, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Netti, PA (reprint author), Univ Naples Federico II, Dept Mat & Prod Engn, Ple Tecchio 80, I-80125 Naples, Italy. RI Mollica, Francesco/I-8826-2012; OI NETTI, PAOLO/0000-0002-2435-7181 NR 14 TC 44 Z9 45 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD JAN PY 2003 VL 65 IS 1 BP 56 EP 60 AR PII S0026-2862(02)00012-2 DI 10.1016/S0026-2862(02)00012-2 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 642KW UT WOS:000180804400010 PM 12535873 ER PT J AU Bornstein-Quevedo, L Lehmann, L Vargas, SO Kozakewich, HPW Perez-Atayde, AR AF Bornstein-Quevedo, L Lehmann, L Vargas, SO Kozakewich, HPW Perez-Atayde, AR TI ALK plus anaplastic large cell lymphoma (ALCL) in children. A clinicopathologic analysis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 BP 1P EP 1P PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101528 ER PT J AU Amell, PM Rosenberg, AE Nielsen, GP AF Amell, PM Rosenberg, AE Nielsen, GP TI beta-catenin expression in reactive and neoplastic fibroblastic proliferations SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol C1 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA A22 BP 8A EP 9A PG 2 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100036 ER PT J AU Hoch, BL Inwards, C Rosenberg, AE AF Hoch, BL Inwards, C Rosenberg, AE TI Multicentric giant cell tumor of bone: A clinicopathologic analysis of thirty cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA A46 BP 13A EP 14A PG 2 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100060 ER PT J AU Hoch, BL Nielsen, GP Liebsch, NJ Rosenberg, AE AF Hoch, BL Nielsen, GP Liebsch, NJ Rosenberg, AE TI Base of skull chordomas in children and adolescents: A clinicopathologic analysis of 72 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol C1 Harvard Univ, Massachusetts Gen Hosp, 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA A45 BP 13A EP 13A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100059 ER PT J AU Gundogan, F George, S Erban, J Sharifi, S AF Gundogan, F George, S Erban, J Sharifi, S TI Can nm23 and stromelysin-3 expression predict the invasive potential of extensive ductal carcinoma in-situ? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 128 BP 31A EP 31A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100142 ER PT J AU Nasser, SM Fan, MJ AF Nasser, SM Fan, MJ TI Does atypical columnar cell hyperplasia on breast core biopsy warrant follow-up excision? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 176 BP 42A EP 42A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100190 ER PT J AU Chen, AA Tambouret, RH Wilbur, DC AF Chen, AA Tambouret, RH Wilbur, DC TI Benign shed endometrial cells in the SurePath liquid-based method: A potential pitfall for overinterpretation as "atypical endometrial cells" SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 267 BP 61A EP 61A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100281 ER PT J AU Dong, Q McKee, GT Pitman, MB Geisinger, KR Tambouret, R AF Dong, Q McKee, GT Pitman, MB Geisinger, KR Tambouret, R TI The epithelioid variant of gastrointestinal stromal tumor: Diagnosis by fine-needle aspiration biopsy SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 274 BP 63A EP 63A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100288 ER PT J AU Eichhorn, JH Gelfand, JA Brauns, TA Wilbur, DC AF Eichhorn, JH Gelfand, JA Brauns, TA Wilbur, DC TI A novel automated screening and interpretation process for cervical cytology using Internet transmission of low resolution images: A pilot study SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 278 BP 64A EP 64A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100292 ER PT J AU Faquin, WC Cibas, ES Renshaw, AA AF Faquin, WC Cibas, ES Renshaw, AA TI Atypical thyroid cyst lining cells: A pitfall for the FNA diagnosis of cystic thyroid lesions SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 282 BP 64A EP 65A PG 2 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100296 ER PT J AU Rahemtullah, A Misdraji, J Pitman, MB AF Rahemtullah, A Misdraji, J Pitman, MB TI Adenosquamous carcinoma of the pancreas: Cytological and clinical features in a series of 15 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol C1 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 347 BP 78A EP 79A PG 2 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100360 ER PT J AU Ahmad, NM Crowson, AN Mihm, MC Vlassov, D Werling, RW Phillips, RS Magro, C AF Ahmad, NM Crowson, AN Mihm, MC Vlassov, D Werling, RW Phillips, RS Magro, C TI Cutaneous immunocytoma: A clinical histologic and phenotypic study of 8 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Ohio State Univ, Columbus, OH 43210 USA. Univ Oklahoma, Reg Med Lab, Tulsa, OK USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 386 BP 87A EP 87A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100399 ER PT J AU King, R Googe, PB Page, RN Mihm, MC AF King, R Googe, PB Page, RN Mihm, MC TI Microphthalmia transcription factor (Mitf), Mart-1, HMB-45, and S100 expression in radial growth phase melanoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Univ Tennessee, Grad Sch Med, Knoxville, TN 37996 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 415 BP 93A EP 93A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100427 ER PT J AU Lu, D Hoch, B Dehner, LP Lind, AC AF Lu, D Hoch, B Dehner, LP Lind, AC TI Proliferative activity in melanocytic nevi from patients grouped by age SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Washington Univ, St Louis, MO 63130 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 420 BP 94A EP 94A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100432 ER PT J AU Srinivasan, M Werling, RW Phillips, RS Ahmad, N Vlassov, D Crowson, AN Mihm, MC Magro, CM AF Srinivasan, M Werling, RW Phillips, RS Ahmad, N Vlassov, D Crowson, AN Mihm, MC Magro, CM TI Assessment of T cell clonality via a single stranded DNA polymorphism conformational assay SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Ohio State Univ, Columbus, OH 43210 USA. Univ Oklahoma, Reg Med Lab, Tulsa, OK 74136 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 449 BP 100A EP 100A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100460 ER PT J AU Werling, RW Crowson, AN Mihm, MC Phillips, RS Ahmad, NM Vlassov, D Porcu, P Cynthia, M AF Werling, RW Crowson, AN Mihm, MC Phillips, RS Ahmad, NM Vlassov, D Porcu, P Cynthia, M TI Primary cutaneous T-cell rich CD30+large cell B-cell lymphoma: A series of cases describing a distinct clinicopathologic disease entity SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Ohio State Univ, Columbus, OH 43210 USA. Univ Oklahoma, Reg Med Lab, Tulsa, OK 74136 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 455 BP 101A EP 101A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100466 ER PT J AU Nakatani, Y Masudo, K Nozawa, A Inayama, Y Ito, T Kitamura, H Notohara, K Kashima, K Yokoyama, S Tsujimoto, M Tamai, S Abe, Y Matsubara, O Resl, M Mark, EJ AF Nakatani, Y Masudo, K Nozawa, A Inayama, Y Ito, T Kitamura, H Notohara, K Kashima, K Yokoyama, S Tsujimoto, M Tamai, S Abe, Y Matsubara, O Resl, M Mark, EJ TI Biotin-rich optically clear nuclei (BROCN) express estrogen receptor beta (ER beta) but not ER alpha SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Yokohama City Univ, Med Ctr, Yokohama, Kanagawa 232, Japan. Ito Hosp, Tokyo, Japan. Hosp Yokohama City Univ, Yokohama, Kanagawa, Japan. Yokohama City Univ, Sch Med, Yokohama, Kanagawa 232, Japan. Okayama Univ, Grad Sch Med & Dent, Okayama 7008530, Japan. Med Coll Oita, Oita 87956, Japan. Osaka Police Hosp, Osaka, Japan. Natl Def Med Coll, Tokorozawa, Saitama 359, Japan. Natl Kanagawa Hosp, Hadano, Japan. Charles Univ, CS-50165 Hradec Kralove, Czech Republic. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 481 BP 107A EP 107A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100492 ER PT J AU Kaimaktchiev, V Dimhofer, S Sauter, G Korcheva, V Mirlacher, M Loda, M Corless, CL AF Kaimaktchiev, V Dimhofer, S Sauter, G Korcheva, V Mirlacher, M Loda, M Corless, CL TI Selective staining of gastrointestinal adenocarcinomas by the homeobox intestinal differentiation factor CDX2 SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Basel, Inst Pathol, Basel, Switzerland. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 556 BP 123A EP 123A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100566 ER PT J AU Lauwers, GY Mino, M Ban, S Sevestre, H AF Lauwers, GY Mino, M Ban, S Sevestre, H TI CK-7, CK-20 and mucin gene expression in gastric inlet patch SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Saitama Med Sch, Moroyama, Saitama 35004, Japan. CHU Amiens, Amiens, 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 568 BP 125A EP 126A PG 2 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100578 ER PT J AU Lauwers, GY Ban, S Mino, M Ota, S Matsumoto, T Arai, S Brugge, WR Shimizu, M AF Lauwers, GY Ban, S Mino, M Ota, S Matsumoto, T Arai, S Brugge, WR Shimizu, M TI Endoscopic mucosal resection for gastric epithelial neoplasm. A study of 39 cases with analysis of pathologic features SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Saitama Med Sch, Moroyama, Saitama 35004, Japan. Kyushu Univ, Fukuoka 812, 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 567 BP 125A EP 125A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100577 ER PT J AU Lechpammer, M Xu, X Bhattacharya, N Ellis, HF Loda, M AF Lechpammer, M Xu, X Bhattacharya, N Ellis, HF Loda, M TI Experimentaly induced carcinogenesis of esophageal mucosa and its inhibition by flavopiridol in p27 knockout mice SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 569 BP 126A EP 126A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100579 ER PT J AU Tang, Z Jing, W Deshpande, V Lauwers, G Ferry, J Harris, N Zukerberg, L AF Tang, Z Jing, W Deshpande, V Lauwers, G Ferry, J Harris, N Zukerberg, L TI Lymphoid lesions of the colon: Analysis of histologic features SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 610 BP 135A EP 135A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100620 ER PT J AU Yantiss, RK Rosenberg, AE Antonescu, CR AF Yantiss, RK Rosenberg, AE Antonescu, CR TI Mutation analysis in NF-1 patients with multiple gastrointestinal stromal tumors (GIST) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Univ Massachusetts, Worcester, MA 01605 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 622 BP 137A EP 137A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100632 ER PT J AU Cubilla, AL Velazquez, EF Arbo, M Young, RH AF Cubilla, AL Velazquez, EF Arbo, M Young, RH TI The inter relationship among subtypes of precancerous lesions and invasive neoplasms of the penis indicates heterogeneous pathways of cancer progression SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol C1 Inst Patol & Invest, Asuncion, Paraguay. NYU Med Ctr, New York, NY 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 662 BP 146A EP 146A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100672 ER PT J AU Henley, JD Michael, H Young, RH Ulbright, TM AF Henley, JD Michael, H Young, RH Ulbright, TM TI Solid pattern of yolk Sac tumor of the testis: A histologic and immunohistochemical study of 9 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol C1 Indiana Univ, Sch Med, Indianapolis, IN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 696 BP 153A EP 153A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100706 ER PT J AU Oliva, E Moch, H Cabrera, R Young, RH Reuter, V Amin, MB AF Oliva, E Moch, H Cabrera, R Young, RH Reuter, V Amin, MB TI Nephrogenic adenoma (NA): An immunohistochemical (ICH) study of 40 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Basel, Basel, Switzerland. Mem Sloan Kettering Canc Ctr, New York, NY USA. Emory Hosp, Atlanta, GA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 748 BP 164A EP 164A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100758 ER PT J AU Yang, XJ Vanguri, VK Woda, BA Wu, CL Savas, L Jiang, Z AF Yang, XJ Vanguri, VK Woda, BA Wu, CL Savas, L Jiang, Z TI Detection of high-grade prostatic intraepithelial neoplasia (PIN) by alpha-methylacyl-CoA racemase P504S immunohistochemistry in previously negative biopsies SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Univ Chicago, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 796 BP 175A EP 175A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100806 ER PT J AU Brachtel, EF Littell, RD Lynch, MP Rueda, B Oliva, E AF Brachtel, EF Littell, RD Lynch, MP Rueda, B Oliva, E TI Is there any in vivo or in vitro correlation between beta-catenin and hormonal receptors (HRs) in endometrioid endometrial carcinoma (EEC)? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 832 BP 183A EP 183A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100842 ER PT J AU Dong, Q Rueda, B Oliva, E Zukerberg, L AF Dong, Q Rueda, B Oliva, E Zukerberg, L TI Loss of cables, a novel gene on chromosome 18q is associated with staining. malignant transformation of the endometrium SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 857 BP 188A EP 188A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100867 ER PT J AU Gupta, A Bhan, AK Bell, DA AF Gupta, A Bhan, AK Bell, DA TI Can the implants of serous borderline tumors of the ovary be distinguished from mesothelial proliferations by use of immunohistochemistry? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 867 BP 190A EP 190A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100877 ER PT J AU Nucci, MR Young, RH AF Nucci, MR Young, RH TI Arias-Stella reaction of the endocervix: A study of 14 cases with emphasis on its varied morphology SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC 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 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 924 BP 203A EP 203A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100934 ER PT J AU Tambouret, R Clement, PB Young, RH AF Tambouret, R Clement, PB Young, RH TI Endometrial endometrioid adenocarcinoma with a deceptive pattern of spread to the uterine cervix SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Vancouver Gen Hosp, Vancouver, BC, Canada. 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 965 BP 212A EP 212A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100975 ER PT J AU Hirsch, MS Faquin, WC Krane, JF AF Hirsch, MS Faquin, WC Krane, JF TI TTF-1, but not p53, is helpful in distinguishing moderately differentiated neuroendocrine carcinoma of the larynx from medullary carcinoma of the thyroid SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. 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 LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1002 BP 219A EP 220A PG 2 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101012 ER PT J AU Wang, L Zukerberg, L Ferry, JA Tang, Z Amrein, PC Harris, NL AF Wang, L Zukerberg, L Ferry, JA Tang, Z Amrein, PC Harris, NL TI Chronic myelogenous leukemia with Gleevec/ST1571 treatment leads to a rapid hematological but slower cytogenetic response SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1175 BP 257A EP 258A PG 2 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101185 ER PT J AU Deshpande, V Muzikansky, A Fernandez-del Castillo, C Lauwers, GY AF Deshpande, V Muzikansky, A Fernandez-del Castillo, C Lauwers, GY TI Cytokeratin 19 is a powerful predictor of survival in pancreatic endocrine tumors SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1242 BP 272A EP 272A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101252 ER PT J AU Graeme-Cook, FM Lauwers, GY Eatherton, DE Mino, M AF Graeme-Cook, FM Lauwers, GY Eatherton, DE Mino, M TI Immunophenotyping in sinusoidal elements in hepatocellular carcinogenesis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1252 BP 274A EP 274A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101262 ER PT J AU Mino, M Varnholt, H Muzikansky, A Terris, B Batts, KP Yamabe, H Flejou, JF Cleary, K Vauthey, JN Lauwers, GY AF Mino, M Varnholt, H Muzikansky, A Terris, B Batts, KP Yamabe, H Flejou, JF Cleary, K Vauthey, JN Lauwers, GY TI Influence of age on hepatocellular carcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Hop Beaujon, Paris, France. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Kyoto Univ, Kyoto 6110011, Japan. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1282 BP 281A EP 281A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101292 ER PT J AU Misdraji, J Thiim, M Graeme-Cook, FM AF Misdraji, J Thiim, M Graeme-Cook, FM TI Autoimmune hepatitis with centrilobular necrosis: A clinicopathologic study of 6 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1283 BP 281A EP 281A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101293 ER PT J AU Richards, CJ McGrath, D Bayliss, U Fernandez-del Castillo, C Lauwers, GY AF Richards, CJ McGrath, D Bayliss, U Fernandez-del Castillo, C Lauwers, GY TI Association and correlation of grade of pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous tumors (IPMT) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 UHL NHS Trust, Leicester, Leics, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1297 BP 284A EP 285A PG 2 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101307 ER PT J AU Soupir, CP Myers, MD Sielaff, TD Coad, JE AF Soupir, CP Myers, MD Sielaff, TD Coad, JE TI Hepatic changes following vertical banded gastroplasty (VBG) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 W Virginia Univ, Morgantown, WV 26506 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Minnesota, Minneapolis, MN 55455 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1302 BP 285A EP 286A PG 2 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101312 ER PT J AU Houser, SL Dor, FJMF Gollackner, B Cooper, DK AF Houser, SL Dor, FJMF Gollackner, B Cooper, DK TI Histology of splenic allograft rejection in MHC-matched and MHC-disparate miniature swine SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol C1 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 2003 VL 16 IS 1 MA 1351 BP 296A EP 296A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101361 ER PT J AU Green, LK AF Green, LK TI Basaloid squamous cell carcinoma of the lung: A review of 292 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Houston Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1404 BP 307A EP 307A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101414 ER PT J AU Matsubara, O Imazeki, N Okochi, Y Tanimoto, T Shinto, E Nakatani, Y Mark, EJ AF Matsubara, O Imazeki, N Okochi, Y Tanimoto, T Shinto, E Nakatani, Y Mark, EJ TI TGF-beta 1 and CTGF expression in diffuse alveolar damage and advanced pulmonary fibrosis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Natl Def Med Coll, Tokorozawa, Saitama 359, Japan. Yokohama City Univ, Med Ctr, Yokohama, Kanagawa 232, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1420 BP 311A EP 311A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101430 ER PT J AU Arnell, PM Selig, MK Nielsen, GP Balis, UJ AF Arnell, PM Selig, MK Nielsen, GP Balis, UJ TI Computer assisted three-dimensional reconstruction and visualization of the Birbeck granule SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1506 BP 329A EP 329A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101516 ER PT J AU Rollins, SE Nielsen, GP Hedley-Whyte, ET AF Rollins, SE Nielsen, GP Hedley-Whyte, ET TI Light microscopy, electron microscopy and mitrichondrial enzyme function in muscle biopsies for suspected mitochondrial cytopathies SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1514 BP 331A EP 331A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101524 ER PT J AU Liu, ZJ Shirakawa, T Li, Y Soma, A Oka, M Dotto, GP Fairman, RM Velazquez, OC Herlyn, M AF Liu, ZJ Shirakawa, T Li, Y Soma, A Oka, M Dotto, GP Fairman, RM Velazquez, OC Herlyn, M TI Regulation of Notch1 and Dll4 by vascular endothelial growth factor in arterial endothelial cells: Implications for modulating arteriogenesis and angiogenesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-KINASE-B; PHOSPHATIDYLINOSITOL 3-KINASE; DROSOPHILA EYE; ACTIVATION; EXPRESSION; MICE; GENE; RECEPTOR; DIFFERENTIATION; LIGAND AB Notch and its ligands play critical roles in cell fate determination. Expression of Notch and ligand in vascular endothelium and defects in vascular phenotypes of targeted mutants in the Notch pathway have suggested a critical role for Notch signaling in vasculogenesis and angiogenesis. However, the angiogenic signaling that controls Notch and ligand gene expression is unknown. We show here that vascular endothelial growth factor (VEGF) but not basic fibroblast growth factor can induce gene expression of Notch1 and its ligand, Delta-like 4 (DII4), in human arterial endothelial cells. The VEGF-induced specific signaling is mediated through VEGF receptors I and 2 and is transmitted via the phosphatidylinositol 3-kinase/Akt pathway but is independent of mitogen-activated protein kinase and Src tyrosine kinase. Constitutive activation of Notch signaling stabilizes network formation of endothelial cells on Matrigel and enhances formation of vessel-like structures in a three-dimensional angiogenesis model, whereas blocking Notch signaling can partially inhibit network formation. This study provides the first evidence for regulation of Notch/Delta gene expression by an angiogenic growth factor and insight into the critical role of Notch signaling in arteriogenesis and angiogenesis. C1 Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. RP Herlyn, M (reprint author), Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA. FU NCI NIH HHS [P01 CA025874, CA10815, CA25874, CA47159, P30 CA010815, R01 CA047159] NR 53 TC 293 Z9 308 U1 1 U2 24 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2003 VL 23 IS 1 BP 14 EP 25 DI 10.1128/MCB.23.1.14-25.2003 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 628AR UT WOS:000179970000002 PM 12482957 ER PT J AU Hsieh, JJD Ernst, P Erdjument-Bromage, H Tempst, P Korsmeyer, SJ AF Hsieh, JJD Ernst, P Erdjument-Bromage, H Tempst, P Korsmeyer, SJ TI Proteolytic cleavage of MLL generates a complex of N- and C-terminal fragments that confers protein stability and subnuclear localization SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID 11Q23 CHROMOSOMAL TRANSLOCATIONS; DROSOPHILA-TRITHORAX; ACUTE-LEUKEMIA; SET DOMAIN; MAMMALIAN TRITHORAX; EXPRESSION PATTERN; BITHORAX COMPLEX; POLYCOMB-GROUP; GENE ENCODES; FUSION AB The mixed-lineage leukemia gene (MLL, ALL1, HRX) encodes a 3,969-amino-acid nuclear protein homologous to Drosophila trithorax and is required to maintain proper Hox gene expression. Chromosome translocations in human leukemia disrupt MLL (11q23), generating chimeric proteins between the N terminus of MLL and multiple translocation partners. Here we report that MLL is normally cleaved at two conserved sites (D/GADD and D/GVDD) and that mutation of these sites abolishes the proteolysis. MLL cleavage generates N-terminal p320 (N320) and C-terminal p180 (C180) fragments, which form a stable complex that localizes to a subnuclear compartment. The FYRN domain of N320 directly interacts with the FYRC and SET domains of C180. Disrupting the interaction between N320 and C180 leads to a marked decrease in the level of N320 and a redistribution of C180 to a diffuse nuclear pattern. These data suggest a model in which a dynamic post-cleavage association confers stability to N320 and correct nuclear sublocalization of the complex, to control the availability of N320 for target genes. This predicts that MLL fusion proteins of leukemia which would lose the ability to complex with C180 have their stability conferred instead by the fusion partners, thus providing one mechanism for altered target gene expression. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst,Howard Hughes Med Inst, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst,Howard Hughes Med Inst, Dept Med, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Howard Hughes Med Inst, Dept Pathol, 1 Jimmy Fund Way, Boston, MA 02115 USA. OI Tempst, Paul/0000-0002-6680-3987 FU NCI NIH HHS [P01 CA68484, P01 CA068484] NR 36 TC 135 Z9 137 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2003 VL 23 IS 1 BP 186 EP 194 DI 10.1128/MCB.23.1.186-194.2003 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 628AR UT WOS:000179970000017 PM 12482972 ER PT J AU Barthel, R Tsytsykova, AV Barczak, AK Tsai, EY Dascher, CC Brenner, MB Goldfeld, AE AF Barthel, R Tsytsykova, AV Barczak, AK Tsai, EY Dascher, CC Brenner, MB Goldfeld, AE TI Regulation of tumor necrosis factor alpha gene expression by mycobacteria involves the assembly of a unique enhanceosome dependent on the coactivator proteins CBP/p300 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CREB-BINDING-PROTEIN; TRANSCRIPTION FACTORS; INTERFERON-BETA; B-CELLS; IN-VIVO; T-CELLS; TUBERCULOSIS; INFECTION; P300; INDUCTION AB Tumor necrosis factor alpha (TNF-alpha) plays an important role in host containment of infection by Mycobacterium tuberculosis, one of the leading causes of death by an infectious agent globally. Using the pathogenic M. tuberculosis strain H37Rv, we present evidence that upon stimulation of monocytic cells by M. tuberculosis a unique TNF-a enhanceosome is formed, and it is distinct from the TNF-alpha enhanceosome that forms in T cells stimulated by antigen engagement or virus infection. A distinct set of activators including ATF-2, c-jun, Ets, Sp1, Egr-1 and the coactivator proteins CBP/p300 are recruited to the TNF-alpha promoter after stimulation with M. tuberculosis. Furthermore, the formation of this enhanceosome is dependent on inducer-specific helical phasing relationships between transcription factor binding sites. We also show that the transcriptional activity of CBP/p300 is potentiated by mycobacterial stimulation of monocytes. The identification of TNF-alpha regulatory elements and coactivators involved in M. tuberculosis-stimulated gene expression thus provides potential selective molecular targets in the modulation of TNF-alpha gene expression in the setting of mycobacterial infection. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Goldfeld, AE (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL59838, R01 HL059838]; NIGMS NIH HHS [R01 GM056492, GM56492] NR 30 TC 64 Z9 64 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2003 VL 23 IS 2 BP 526 EP 533 DI 10.1128/MCB.23.2.526-533.2003 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 632VE UT WOS:000180243500009 PM 12509451 ER PT J AU Weng, AP Nam, Y Wolfe, MS Pear, WNS Griffin, JD Blacklow, SC Aster, JC AF Weng, AP Nam, Y Wolfe, MS Pear, WNS Griffin, JD Blacklow, SC Aster, JC TI Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of notch signaling SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GAMMA-SECRETASE INHIBITORS; BARR-VIRUS EBNA2; CAENORHABDITIS-ELEGANS; HUMAN HOMOLOG; RBP-J; NEOPLASTIC TRANSFORMATION; ACTIVATE TRANSCRIPTION; NUCLEAR-LOCALIZATION; INTRACELLULAR DOMAIN; FUNCTIONAL-ANALYSIS AB Constitutive NOTCH signaling in lymphoid progenitors promotes the development of immature T-cell lymphoblastic neoplasms (T-ALLs). Although it is clear that Notch signaling can initiate leukemogenesis, it has not previously been established whether continued NOTCH signaling is required to maintain T-ALL growth. We demonstrate here that the blockade of Notch signaling at two independent steps suppresses the growth and survival of NOTCH1-transformed T-ALL cells. First, inhibitors of presenilin specifically induce growth suppression and apoptosis of a murine T-ALL cell line that requires presenilin-dependent proteolysis of the Notch receptor in order for its intracellular domain to translocate to the nucleus. Second, a 62-amino-acid peptide derived from a NOTCH coactivator, Mastermind-like-1 (MAML1), forms a transcriptionally inert nuclear complex with NOTCH1 and CSL and specifically inhibits the growth of both murine and human NOTCH1-transformed T-ALLs. These studies show that continued growth and survival of NOTCH1-transformed lymphoid cell lines require nuclear access and transcriptional coactivator recruitment by NOTCH1 and identify at least two steps in the Notch signaling pathway as potential targets for chemotherapeutic intervention. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Univ Penn, Sch Med, Abramson Family Canc Res Inst, Inst Med & Engn,Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Aster, JC (reprint author), Brigham & Womens Hosp, Dept Pathol, 20 Shattuck St,Thorn 503, Boston, MA 02115 USA. RI Weng, Andrew/I-5015-2014 NR 61 TC 259 Z9 266 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2003 VL 23 IS 2 BP 655 EP 664 DI 10.1128/MCB.23.2.655-664.2003 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 632VE UT WOS:000180243500021 PM 12509463 ER PT J AU Carter, AR Berry, EM Segal, RA AF Carter, AR Berry, EM Segal, RA TI Regional expression of p75NTR contributes to neurotrophin regulation of cerebellar patterning SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID NERVE GROWTH-FACTOR; AFFINITY NGF RECEPTOR; GRANULE NEURONS; DIFFERENTIAL EXPRESSION; SIGNAL-TRANSDUCTION; RAT CEREBELLUM; PURKINJE-CELLS; BRAIN; BDNF; DEATH AB Neurotrophins were initially identified as critical regulators of neuronal survival. However, these factors have many additional functions. In the developing cerebellum the roles of the neurotrophins BDNF and NT3 include a surprising effect on patterning, as revealed by changes in foliation in neurotrophin-deficient mice. Here we examine the potential role of p75NTR in cerebellar development and patterning. We show that p75NTR is expressed at highest levels in the region of the cerebellum where foliation is altered in BDNF and NT3 mutants. Although the cerebellar phenotype of p75NTR mutant animals is indistinguishable from wild type, mutation of p75NTR in BDNF heterozygotes results in defects in foliation and in Purkinje cell morphologic development. Taken together, these data suggest that p75NTR activity is critical for cerebellar development under pathologic circumstances where neurotrophin levels are reduced. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Segal, RA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NINDS NIH HHS [NS 37757] NR 55 TC 29 Z9 31 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD JAN PY 2003 VL 22 IS 1 BP 1 EP 13 DI 10.1016/S1044-7431(02)00015-5 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 651ZG UT WOS:000181353400001 PM 12595234 ER PT J AU Rivera, OJ Song, CS Centonze, VE Lechleiter, JD Chatterjee, B Roy, AK AF Rivera, OJ Song, CS Centonze, VE Lechleiter, JD Chatterjee, B Roy, AK TI Role of the promyelocytic leukemia body in the dynamic interaction between the androgen receptor and steroid receptor coactivator-1 in living cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID NUCLEAR-BODIES; ESTROGEN-RECEPTOR; PREMATURE SENESCENCE; BINDING-PROTEIN; ONCOGENIC RAS; CANCER CELLS; PML; SUMO-1; TRANSCRIPTION; PROTEASOME AB The dynamic interaction between the androgen receptor (AR) and steroid receptor coactivator-1 (SRC-1) was explored in living cells expressing chimeric forms of the receptor and the coactivator containing two spectral variants of jellyfish fluorescent protein. Laser scanning confocal imaging of transfected cells expressing fluorescently labeled SRC-1 revealed that in an unsynchronized cell population, the coactivator is distributed in approximately 40% cells as nuclear bodies of 0.2-1.0 gm in diameter. Immunostaining of cyan fluorescent protein-labeled SRC-1 (CFP-SRC1)-expressing cells with antibody to promyelocytic leukemia (PML) protein showed significant overlap of the CFP fluorescence with the antibody stain. Cotransfection of cells with a plasmid expressing the CFP conjugate of Sp100 (another marker protein for the PML nuclear body) also showed colocalization of the yellow fluorescent protein (YFP)-SRC1 containing nuclear foci with the PML bodies in living cells. Analysis of the three-dimensional structure revealed that the PML bodies are round to elliptical in shape with multiple satellite bodies on their surface. Some of these satellite bodies contain the SRC-1. Activation and nuclear import of CFP-AR by the agonistic ligand 5alpha-dihydrotestosterone, but not by the antagonist casodex, transferred YFP-SRC1 from the PML bodies to an interlacing filamentous structure. In a single living cell, agonist-activated AR caused a time-dependent movement of YFP-SRC1 from the PML bodies to this filamentous structure. Additionally, coexpression of a constitutively active mutant of AR (AR-Deltaligand binding domain) also displaced YFP-SRC1 from the PML bodies to this intranuclear filamentous structure. The fluorescence recovery after photobleaching approach was used to examine changes in the kinetics of movement of YFP-SRC1 during its mobilization from the PML bodies to the intranuclear filamentous structure by the agonist-activated AR. Results of the relative half-times (t1/2) of replacement of YFP-SRC1 within the photobleached region of a single PML body from its surrounding nuclear space supported the conclusion that SRC-1 is actively transported from the PML bodies to the intranuclear filamentous structure by the ligand-activated AR. This observation also suggests an interaction between AR and SRC-1 before its binding to the target gene. The PML bodies have been implicated as a cross-road for multiple regulatory pathways that control cell proliferation, cellular senescence, and apoptosis. Our present results along with other recent reports expand the role of this subnuclear structure to include the regulation of steroid hormone action. C1 Univ Texas, Ctr Hlth Sci, Inst Biotechnol, Dept Mol Med, San Antonio, TX 78245 USA. Univ Texas, Ctr Hlth Sci, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Roy, AK (reprint author), Univ Texas, Ctr Hlth Sci, Inst Biotechnol, Dept Mol Med, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM roy@uthscsa.edu FU NIA NIH HHS [R37AG-10486, T32-AG-00165]; NIDDK NIH HHS [R01-DK-14744] NR 46 TC 26 Z9 26 U1 1 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JAN PY 2003 VL 17 IS 1 BP 128 EP 140 DI 10.1210/me.2002-0165 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 632VL UT WOS:000180244100011 PM 12511612 ER PT J AU Manis, JP Michaelson, JS Birshtein, BK Alt, FW AF Manis, JP Michaelson, JS Birshtein, BK Alt, FW TI Elucidation of a downstream boundary of the 3 ' IgH regulatory region SO MOLECULAR IMMUNOLOGY LA English DT Article DE class switch recombination; 3 ' immunoglobulin heavy chain regulatory region ID HEAVY-CHAIN LOCUS; CLASS-SWITCH RECOMBINATION; VIRTUALLY IDENTICAL ENHANCERS; B-CELL DIFFERENTIATION; CONSTANT-REGION; IMMUNOGLOBULIN; GENE; IDENTIFICATION; TRANSCRIPTION; ELEMENTS AB Class switch recombination (CSR) changes the immunoglobulin heavy chain (IgH) constant region gene (C-H) in B cells from IgM to IgG, IgA, or IgE, without modifying the variable region gene segment. This process requires transcription through switch (S) regions located upstream of the CH genes targeted for CSR, a process that relies on the activity of an uncharacterized regulatory region at the 3' end of the C-H locus (3' IgH RR) that has been implicated via the effects of pgk-neo cassettes inserted into the locus. The 30 kb region just downstream of the most 3' C-H gene (Ca) contains four known enhancer elements including HS3a, HS1,2, HS3b, and HS4. Replacement of either of the proximal two enhancer elements (HS3a or HS1,2) with a pgk-neo gene cassette disrupted germline transcription of and CSR to most C-H genes. However, replacement of either of the enhancers with a loxP sequence had no effect on CSR indicating that these elements are not critical for CSR. Insertion of a pgk-neo cassette at various sites within the C-H locus inhibited CSR to upstream, but not downstream C-H genes, supporting the notion that the pgk-neo cassette insertion into the locus short-circuits the ability of the 3' RR to facilitate CSR of dependent C-H genes upstream of the insertion. These analyses also indicated that the key elements of the 3' IgH RR were downstream from HS1,2. In this study, we have sought to localize the 3' IgH RR by defining its 3' boundary. For this purpose, a pgk-neo gene cassette was targeted 2 kb downstream of the HS4 element in ES cells that had normal ability to undergo CSR. We then employed Rag-2 deficient blastocyst complementation to generate chimeric mice that harbored B cells homozygous for this mutation. Such chimeras exhibited normal reconstitution of the splenic compartment and had normal serum immunoglobulin levels. Upon in vitro activation, transcription from the pgk-neo cassette was induced in B cells, however, CSR to all measured IgH isotypes occurred at normal levels. These findings, coupled with previous pgk-neo insertion studies, suggest that key elements of the 3' IgH RR lie within a 17 kb region between HS 1,2 and 2 kb downstream of HS4. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. RP Alt, FW (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Enders Bldg,Room 861,320 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [AI 31541, AI 13509] NR 32 TC 13 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2003 VL 39 IS 12 BP 753 EP 760 AR PII S0161-5890(02)00256-0 DI 10.1016/S0161-5890(02)00256-0 PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 643EV UT WOS:000180849700007 PM 12531286 ER PT S AU Moskowitz, MA Le, DA Whalen, MJ AF Moskowitz, MA Le, DA Whalen, MJ BE Abe, K TI Caspases and upstream mechanisms in central nervous system ischemic injury SO MOLECULAR MECHANISMS AND EPOCHAL THERAPEUTICS OF ISCHEMIC STROKE AND DEMENTIA SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT International Symposium on Molecular Mechanism and Epochal Therapeutics of Ischemic Stroke and Dementia CY OCT 18-20, 2002 CL OKAYAMA, JAPAN SP Int Soc Cerebral Blood Flow & Metabolism, Minist Educ, Sci Sport & Culture Japan, Okayama Univ, Okayama Med Fdn DE caspases; upstream mechanisms; ischemic injury ID TRAUMATIC BRAIN-INJURY; FOCAL CEREBRAL-ISCHEMIA; NECROSIS-FACTOR-ALPHA; NEURONAL CELL-DEATH; INTERLEUKIN-1-BETA CONVERTING-ENZYME; CYTOCHROME-C RELEASE; CLOSED-HEAD INJURY; INDUCED APOPTOSIS; MICE LACKING; FAS RECEPTOR AB Programmed or apoptotic-like cell death plays an important role in cell demise following ischemic or traumatic brain injury. Caspases -1, -3, -8, and -11, the pro-death bcl-2 family member BID, and the Fas death receptor have been implicated. We recently showed that caspases-8 and -3 are activated, BID is cleaved in mouse brain after cerebral ischemia, neuronal BID is a substrate of caspase-8, and that Bid null mice are resistant to ischemia. These novel findings suggest that BID promotes caspase activation and contributes importantly to ischemic neuronal cell death. Consistent with its role in programmed cell death, caspase-3 null mice are resistant to mild ischemia, and in vitro neuronal death was inhibited in cultured caspase-3 - / - neurons subjected to OGD. Interestingly, we observed that caspase-3 substrates such as poly(ADP-ribose) polymerase (PARP) are still cleaved in the absence of caspase-3, albeit in reduced amounts. Upstream, the Fas death receptor is an important initiating mechanism of cell death after ischemia and TBI. Fas expression and Fas-Fas ligand interaction is markedly increased in injured brain early after experimental traumatic brain injury (TBI), and Fas activation is followed by robust assembly of Fas-Fas-associated protein with a death domain (FADD)-procaspase-8 death inducing signaling complex (DISC) assembly within hours. DISC assembly is temporally associated with cleavage of caspases-8 and -3 and neuronal cell death, and robust assembly of Fas DISC occurs in contused human brain after TBI. All of the components needed to assemble a DISC are intrinsic to neurons based on in vitro studies. Fas ligand overexpression induces DISC assembly in cultured neurons, and resultant cell death is attenuated by adding a broad spectrum caspase inhibitor. Together, these data suggest that death receptors play an important role in initiating caspase-mediated cell death after TBI, and that death receptors or their downstream DISC components may be attractive therapeutic targets to reduce cell death after CNS injury. (C) 2003 Published by Elsevier Science B.V. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Ctr,Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Ctr,Dept Neurol, Boston, MA 02114 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Ctr,Dept Radiol, Boston, MA 02114 USA. NR 39 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-51222-5 J9 INT CONGR SER PY 2003 VL 1252 BP 155 EP 161 DI 10.1016/S0531-5131(03)00047-5 PG 7 WC Medicine, Research & Experimental; Neurosciences; Peripheral Vascular Disease SC Research & Experimental Medicine; Neurosciences & Neurology; Cardiovascular System & Cardiology GA BX30T UT WOS:000184904200019 ER PT B AU Tonomura, N Goldsby, RA Granowitz, EV Osborne, B AF Tonomura, N Goldsby, RA Granowitz, EV Osborne, B BE Shi, Y Cidlowski, JA Scott, D Wu, JR Shi, YB TI Oxidative stress and thymocyte apoptosis SO MOLECULAR MECHANISMS OF PROGRAMMED CELL DEATH LA English DT Proceedings Paper CT 2nd International Symposium on Programmed Cell Death CY SEP 01-03, 2002 CL Shanghai, PEOPLES R CHINA SP NICHHD, NIEHS, Amer Red Cross, Univ Med & Dent NJ Robert Wood Johnson Med Sch, Chinese Acad Sci, Shanghai Inst Biol Sci ID BCL-2 FAMILY-MEMBERS; CYTOCHROME-C; HYDROGEN-PEROXIDE; ELECTRON-TRANSPORT; OXYGEN-TENSION; CELL-DEATH; MITOCHONDRIA; GENERATION; PATHWAY; RELEASE AB Mitochondria play a major role in making decisions in programmed cell death. During thymocyte apoptosis, the function of mitochondrial electron transport chain becomes pro-apoptotic and produces increased levels of reactive oxygen species (ROS). The resulting oxidative stress can further aggravate apoptotic events, leading thymocytes to death. The site of ROS production during thymocyte apoptosis is most likely at complex III of the electron transport chain, and the pro-apoptotic function of electron transport chain is regulated by the proteasome. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Tonomura, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. NR 40 TC 0 Z9 0 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-47778-5 PY 2003 BP 79 EP 93 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BAR63 UT WOS:000223268200007 ER PT J AU Li, JH Kokkola, R Tabibzadeh, S Yang, RK Ochani, M Qiang, XL Harris, HE Czura, CJ Wang, HC Ulloa, L Wang, H Warren, HS Moldawer, LL Fink, MP Andersson, U Tracey, KJ Yang, H AF Li, JH Kokkola, R Tabibzadeh, S Yang, RK Ochani, M Qiang, XL Harris, HE Czura, CJ Wang, HC Ulloa, L Wang, H Warren, HS Moldawer, LL Fink, MP Andersson, U Tracey, KJ Yang, H TI Structural basis for the proinflammatory cytokine activity of high mobility group box 1 SO MOLECULAR MEDICINE LA English DT Article ID HMG CHROMOSOMAL-PROTEINS; MOBILITY-GROUP PROTEIN-1; NF-KAPPA-B; TRANSCRIPTION FACTOR; HEMORRHAGIC-SHOCK; MICE; DNA; BOX; INFLAMMATION; MONOCYTES AB High mobility group box 1 (HMGB1), a ubiquitous DNA-binding protein, has been implicated as a proinflammatory cytokine and late mediator of lethal endotoxemia. HMGB1 is released by activated macrophages. It amplifies and extends the inflammatory response by inducing cytokine release and mediating acute lung injury, anorexia, and the inflammatory response to tissue necrosis. The kinetics of HMGB1 release provide a wide therapeutic window for endotoxemia because extracellular levels of HMGB1 begin to increase 12 to 24 h after exposure to inflammatory stimuli. Here, we demonstrate that a DNA-binding domain of HMGB1, the B box, recapitulates the cytokine activity of full length HMGB1 and efficiently activates macrophages to release tumor necrosis factor (TNF) and other proinflammatory cytokines. Truncation of the B box revealed that the TNF-stimulating activity localizes to 20 amino acids (HMGB1 amino acids 89 to 108). Passive immunization of mice with antibodies raised against B box conferred significant protection against lethal endotoxemia or sepsis, induced by cecal perforation. These results indicate that a proinflammatory domain of HMGB1 maps to the highly conserved DNA-binding B box, making this primary sequence a suitable target in the design of therapeutics. C1 N Shore Long Isl Jewish Res Inst, Lab Biomed Sci, Manhasset, NY 11030 USA. Karolinska Inst, Ctr Mol Med, S-17176 Stockholm, Sweden. SUNY Stony Brook, Dept Obstet & Gynecol, Stony Brook, NY 11794 USA. Univ Pittsburgh, Med Ctr, Dept Crit Care Med, Pittsburgh, PA 15261 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Univ Florida, Coll Med, Dept Surg, Shands Hosp, Gainesville, FL 32610 USA. RP Yang, H (reprint author), N Shore Long Isl Jewish Res Inst, Lab Biomed Sci, 350 Community Dr, Manhasset, NY 11030 USA. RI Wang, Haichao/K-6310-2012; OI Wang, Haichao/0000-0002-0211-9000; Tracey, Kevin J/0000-0003-1884-6314 NR 40 TC 172 Z9 215 U1 0 U2 8 PU NORTH SHORE-LONG ISLAND JEWISH RESEARCH INSTITUTE PI MANHASSET PA 350 COMMUNITY DRIVE, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD JAN-FEB PY 2003 VL 9 IS 1-2 BP 37 EP 45 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 740WC UT WOS:000186424100006 PM 12765338 ER PT J AU Bush, G Shin, LM Holmes, J Rosen, BR Vogt, BA AF Bush, G Shin, LM Holmes, J Rosen, BR Vogt, BA TI The Multi-Source Interference Task: validation study with fMRI in individual subjects SO MOLECULAR PSYCHIATRY LA English DT Article DE cingulate; Stroop; Eriksen; Simon; cognition; interference; oddball; attention; clinical; diagnostic ID ANTERIOR CINGULATE CORTEX; EVENT-RELATED FMRI; MEDIAL PREFRONTAL CORTEX; CEREBRAL BLOOD-FLOW; OBSESSIVE-COMPULSIVE DISORDER; POSITRON EMISSION TOMOGRAPHY; EMOTION-INDUCED CHANGES; HUMAN FRONTAL-LOBE; HUMAN BRAIN; RESPONSE CONFLICT AB Dorsal anterior cingulate cortex (dACC) plays critical roles in cognitive processing, but group-averaging techniques have generally been required to obtain significant dACC activation in functional neuroimaging studies. Development of a task that reliably and robustly activates dACC within individuals is needed to improve imaging studies of neuropsychiatric disorders and localization of dACC in normal volunteers. By combining sources of cognitive interference (Stroop, Eriksen and Simon) with factors known to increase dACC activity, the Multi-Source Interference Task (MSIT) maximally taxes dACC, making it possible to reliably activate dACC within individuals using functional magnetic resonance imaging (fMRI). In this study, eight normal adult volunteers performed the MSIT during fMRI. We compared fMRI responses and performance data between interference and control trials. Significant dACC activation (P<1.7 x 10(-4)) was observed in all eight individuals and in the group-averaged fMRI data. In addition to dACC activation, group data also showed activation of presumably networked regions including dorsolateral prefrontal, premotor, and parietal cortices. The MSIT's reaction time interference effect (overall mean 312+/-61 ms) was up to 10 times greater than that of its component predecessors and temporally stable over hundreds of trials. The robustness, reliability and stability of the neuroimaging and performance data should make the MSIT a useful task with which to study normal human cognition and psychiatric pathophysiology. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, MGH MIT HMS Athinoula A Martinos Ctr Funct & Stru, Boston, MA 02115 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. MIT, Cambridge, MA 02139 USA. Cingulum Neurosci Inst, Syracuse, NY USA. RP Bush, G (reprint author), Massachusetts Gen Hosp E, Psychiat Neuroimaging Program, CNY-9117,Bldg 149,13th St, Charlestown, MA 02129 USA. RI Vogt, Brent/C-4038-2015 OI Vogt, Brent/0000-0003-1228-4410 NR 99 TC 116 Z9 117 U1 10 U2 21 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. PY 2003 VL 8 IS 1 BP 60 EP 70 DI 10.1038/sj.mp.4001217 PG 11 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 640ZF UT WOS:000180718400010 PM 12556909 ER PT J AU Leonard, S Freedman, R AF Leonard, S Freedman, R TI Recombination in a schizophrenic proband fails to exclude CHRNA7 at chromosome 15q14 SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID RECEPTOR GENE CHRNA7; SUBUNIT GENE; DUPLICATION; LOCUS C1 Denver VA Med Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. RP Freedman, R (reprint author), Denver VA Med Ctr, Dept Psychiat, 4200 E 9th Ave C-268-71, Denver, CO 80262 USA. NR 5 TC 5 Z9 5 U1 0 U2 0 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. PY 2003 VL 8 IS 2 BP 145 EP 146 DI 10.1038/sj.mp.4001209 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 649FG UT WOS:000181195900006 PM 12610645 ER PT J AU Chen, H Wang, N Huo, Y Sklar, P MacKinnon, DF Potash, JB McMahon, F Antonarakis, SE DePaulo, JR Ross, CA McInnis, MG AF Chen, H Wang, N Huo, Y Sklar, P MacKinnon, DF Potash, JB McMahon, F Antonarakis, SE DePaulo, JR Ross, CA McInnis, MG TI Trapping and sequence analysis of 1138 putative exons from human chromosome 18 SO MOLECULAR PSYCHIATRY LA English DT Article DE exon trapping; gene identification; genome; BLAST; bipolar disorder ID BIPOLAR AFFECTIVE-DISORDER; CHROMOSOME 18Q21; GENE-CLUSTER; HUMAN GENOME; REGION; LINKAGE; LOCUS; MAP; IDENTIFICATION; PREDICTION AB In a search for novel genes on chromosome 18 (HC18), on which several regions have been linked to bipolar disorder, we applied exon trapping to HC18-specific cosmids. Among the 1138 exons trapped, 1052 of them have been mapped to HC18, and the remaining 86 have not been localized. No exons were localized to genomic regions other than HC18. BLAST database search revealed that 190 exons were identical to 98 Unigenes on HC18; 98 identical to additional 82 clusters of ESTs not present in the HC18 Unigene set; 39 homologous to genes from human and other species (e < 10(-3)); and the remaining 811 exons had no significant homology to transcripts in public databases. The mapped exons were compared to the 867 annotated genes on HC18 in the Celera databases; 216 exons were identical to 104 Celera 'genes' and the remaining 836 exons were not found in the Celera databases. On average, there were two exons for a matched transcript ( known genes and ESTs). Therefore, the 850 novel exons may represent hundreds of novel genes on chromosome 18. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21278 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21278 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NIMH, NIH, Bethesda, MD 20892 USA. Univ Geneva, Sch Med, Div Med Genet, CH-1211 Geneva, Switzerland. RP Chen, H (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 4-141,600 N Wolfe St, Baltimore, MD 21278 USA. EM hc@jhmi.edu; mmcinnis@jhmi.edu RI McMahon, Francis/A-7290-2009; McInnis, Melvin/F-6963-2012; Antonarakis, Stylianos/N-8866-2014; OI McInnis, Melvin/0000-0002-0375-6247; Antonarakis, Stylianos/0000-0001-8907-5823; McMahon, Francis/0000-0002-9469-305X NR 33 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2003 VL 8 IS 6 BP 619 EP 623 DI 10.1038/sj.mp.4001288 PG 5 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 699RD UT WOS:000184069000005 PM 12851638 ER PT J AU Glatt, SJ Faraone, SV Tsuang, MT AF Glatt, SJ Faraone, SV Tsuang, MT TI Meta-analysis identifies an association between the dopamine D2 receptor gene and schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Article DE meta-analysis; association; dopamine; D2 receptor; gene; schizophrenia ID MOLECULAR VARIANT; NO ASSOCIATION; DRD2 SER311CYS; CYS311 VARIANT; POLYMORPHISM; SER311/CYS311; MUTATION AB The D2 subtype of dopamine receptor has been widely implicated in the pathogenesis of schizophrenia. Early evidence supporting an association between the Cys311Ser polymorphism of the D2 receptor gene (DRD2) and schizophrenia was subsequently refuted and, eventually, dismissed. From all 24 published case-control studies, we calculated a pooled estimate of this association. The pooled odds ratio was 1.3 for the Cys allele, which was highly significant (P=0.007). The odds ratio derived from each study was unrelated to the ethnicity or gender composition of the sample, or the age of the control group. There was no evidence of publication bias or excessive influence attributable to any given study. Although more family-based studies are needed to confirm this relation, our results provide strong evidence that DRD2 influences susceptibility to schizophrenia. C1 Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Brockton W Roxbury Vet Affairs Med Ctr, Psychiat Serv, Brockton, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. RP Tsuang, MT (reprint author), Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, 74 Fenwood Rd, Boston, MA 02115 USA. OI Glatt, Stephen/0000-0002-0360-7567; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01MH43518, R01MH59624, R01MH60485, R25MH60485] NR 32 TC 84 Z9 88 U1 1 U2 1 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. PY 2003 VL 8 IS 11 BP 911 EP 915 DI 10.1038/sj.mp.4001321 PG 5 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 741JA UT WOS:000186453900005 PM 14593428 ER PT J AU Troen, BR AF Troen, BR TI The biology of aging SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT Geriatric Medicine Update and Board Review Meeting CY OCT 05-08, 2001 CL MT SINAI SCH MED, NEW YORK, NEW YORK HO MT SINAI SCH MED DE aging; senescence; cellular; lifespan; mortality; antagonistic pleiotropy; cancer ID DELETED MITOCHONDRIAL-DNA; REPLICATIVE LIFE-SPAN; PROGRAMMED CELL-DEATH; IMMORTALIZED HUMAN FIBROBLASTS; AGE-ASSOCIATED ACCUMULATION; SENESCENT HUMAN FIBROBLASTS; GENE-EXPRESSION PROFILE; COMPLEX-I DEFICIENCY; CALORIC RESTRICTION; PARKINSONS-DISEASE AB In humans, aging is inexorable. The progressive decrease in physiological capacity and the reduced ability to respond to environmental stresses lead to increased susceptibility and vulnerability to disease. Consequently, mortality due to all causes increases exponentially with aging. Attempts at understanding the causes of aging are limited by the complexity of the problem. Aging changes are manifest from the molecular to the organismic level; environmental factors affect experimental observations; secondary effects complicate elucidation of primary mechanisms; and precisely defined, easily measurable "biomarkers" are lacking. No one unifying theory may exist, since the mechanisms of aging could be quite distinct in different organisms, tissues, and cells. Evolutionary pressures have selected for successful reproduction, making it likely that the post-reproductive physiology of an organism (i.e., aging) is an epigenetic and pleiotropic manifestation of the optimization for early fitness. Indeed, antagonistic pleiotropy, wherein genes that enhance early survival and function but are disadvantageous later in life, may play an overriding role in aging. Theories of aging can be divided into two general categories: stochastic and developmental-genetic. These are not mutually exclusive, particularly when considering the free radical/mitochondrial DNA theory of aging. Increasing evidence suggests that cellular senescence and organismic aging are antagonistically pleiotropic manifestations of evolutionary pressures to prevent malignant transformation. In other words, aging may be the price we pay to avoid cancer. The beneficial paradox may be that the maximum lifespan potential of humans may have been achieved, in part, due to our ability to grow old. C1 Bronx Vet Adm Med Ctr, Brookdale Dept Geriatr & Adult Dev, Bronx, NY USA. RP Troen, BR (reprint author), Miami Vet Adm Med Ctr, 11GRC,1201 NW 16th St, Miami, FL 33125 USA. NR 219 TC 170 Z9 185 U1 1 U2 16 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD JAN PY 2003 VL 70 IS 1 BP 3 EP 22 PG 20 WC Medicine, General & Internal SC General & Internal Medicine GA 629MT UT WOS:000180054000003 PM 12516005 ER PT S AU Donnet, C Sweadner, KJ AF Donnet, C Sweadner, KJ BE Jorgensen, PL Karlish, SJD Maunsbach, AB TI The mechanism of Na-K interaction on Na,K-ATPase SO NA,K-ATPASE AND RELATED CATION PUMPS: STRUCTURE, FUNCTION, AND REGULATORY MECHANISMS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 10th International Conference on Na,K-ATPase and Related Cation Pumps CY AUG 08-14, 2002 CL ELSINORE, DENMARK DE kinetics; competition; K-Na; Na-K interaction; mechanism ID GAMMA-SUBUNIT C1 Massachusetts Gen Hosp, Lab Membrane Biol, Charlestown, MA 02129 USA. RP Donnet, C (reprint author), Massachusetts Gen Hosp, Lab Membrane Biol, 149 13th St,6118, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL36271] NR 3 TC 3 Z9 3 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-401-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 986 BP 249 EP 251 PG 3 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BW85L UT WOS:000183407000045 PM 12763810 ER PT S AU Sweadner, KJ Arystarkhova, E Donnet, C Wetzel, RK AF Sweadner, KJ Arystarkhova, E Donnet, C Wetzel, RK BE Jorgensen, PL Karlish, SJD Maunsbach, AB TI FXYD proteins as regulators of the Na,K-ATPase in the kidney SO NA,K-ATPASE AND RELATED CATION PUMPS: STRUCTURE, FUNCTION, AND REGULATORY MECHANISMS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 10th International Conference on Na,K-ATPase and Related Cation Pumps CY AUG 08-14, 2002 CL ELSINORE, DENMARK DE FXYD; gamma; phospholemman; genomic DNA; gene family ID NA+-K+-ATPASE; GAMMA-SUBUNIT; IMMUNOCYTOCHEMICAL LOCALIZATION; RENAL NA,K-ATPASE; FUNCTIONAL-ROLE; KINASE-C; EXPRESSION; CHIF; PHOSPHOLEMMAN; AFFINITY AB The FXYD gene family has seven members in mammals and others in fish. Five of these (FXYD1, FXYD2, FXYD4, FXYD7, and PLMS from shark) have been shown to alter the activity of the Na,K-ATPase, as described by other papers in this volume. The gene structure of FXYD family members suggests assembly from protein domain modules and gene duplication. They subunit is unique in the family for having alternative splice variants in the coding region and can be posttranslationally modified with different final consequences for enzyme properties. The nonoverlapping distribution of gamma and CHIF (FXYD4) in kidney helps to explain physiological differences in Na(+) affinity among nephron segments. We also detected phospholemman (FXYD1) in kidney. By immunofluorescence, it was found in extraglomerular mesangial cells (EM cells) of the juxtaglomerular apparatus and in the afferent arteriole. Contrary to many reports that only alpha1 and beta1 are expressed in the kidney, we found that alpha2 and beta2 are present, although not in any nephron segment. Both were detected in arterioles, and beta2 was found in the EM cells. In contrast, alpha1, beta1, and gamma were found in adjacent macula densa. Phospholemman, alpha2, and beta2 are proposed to have distinct roles in regulating the sodium pump in structures involved in tubuloglomerular feedback. C1 Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA 02129 USA. RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA 02129 USA. EM sweadner@helix.mgh.harvard.edu NR 33 TC 25 Z9 26 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-401-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 986 BP 382 EP 387 PG 6 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BW85L UT WOS:000183407000089 PM 12763854 ER PT S AU Arystarkhova, E Wetzel, RK AF Arystarkhova, E Wetzel, RK BE Jorgensen, PL Karlish, SJD Maunsbach, AB TI Gamma structural variants differentially regulate Na,K-ATPase properties SO NA,K-ATPASE AND RELATED CATION PUMPS: STRUCTURE, FUNCTION, AND REGULATORY MECHANISMS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 10th International Conference on Na,K-ATPase and Related Cation Pumps CY AUG 08-14, 2002 CL ELSINORE, DENMARK DE FXYD2; gamma subunit; Na+ affinity; K+ affinity; splice variants; oligomers ID RENAL NA,K-ATPASE; RAT-KIDNEY; SUBUNIT; NA+ AB Renal Na,K-ATPase is tightly bound to a small regulatory protein, the gamma subunit (FXYD2). In rat, it occurs in two splice variants with different N-termini. Immunolocalization on kidney sections revealed distinct distribution of the gamma splice variants along the rat nephron. Where coexpressed, they coimmunoprecipitated with each other along with the alpha subunit, suggesting assembly in oligomeric complexes. Functional consequences of association with gamma were monitored in stably transfected NRK-52E cells. The outcome was that splice variants can differentially modulate the major intrinsic properties of the Na,K-ATPase under normal and stress-related conditions. The data imply an adaptive physiological mechanism of regulation of renal Na,K-ATPase through modulation of pump properties, gene expression, or both. C1 Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Arystarkhova, E (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA 02129 USA. NR 6 TC 5 Z9 5 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-401-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 986 BP 416 EP 419 PG 4 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BW85L UT WOS:000183407000094 PM 12763859 ER PT S AU Ellis, DZ Sweadner, KJ AF Ellis, DZ Sweadner, KJ BE Jorgensen, PL Karlish, SJD Maunsbach, AB TI NO regulation of Na,K-ATPase - Nitric oxide regulation of the Na,K-ATPase in physiological and pathological states SO NA,K-ATPASE AND RELATED CATION PUMPS: STRUCTURE, FUNCTION, AND REGULATORY MECHANISMS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 10th International Conference on Na,K-ATPase and Related Cation Pumps CY AUG 08-14, 2002 CL ELSINORE, DENMARK DE Na,K-ATPase; nitric oxide (NO); amyotrophic lateral sclerosis ID CARBACHOL C1 Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02129 USA. RP Ellis, DZ (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, CNY 149-6118, Boston, MA 02129 USA. NR 3 TC 3 Z9 3 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-401-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 986 BP 534 EP 535 PG 2 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BW85L UT WOS:000183407000115 PM 12763880 ER PT J AU Lee, SS Lee, RYN Fraser, AG Kamath, RS Ahringer, J Ruvkun, G AF Lee, SS Lee, RYN Fraser, AG Kamath, RS Ahringer, J Ruvkun, G TI A systematic RNAi screen identifies a critical role for mitochondria in C-elegans longevity SO NATURE GENETICS LA English DT Article ID CAENORHABDITIS-ELEGANS; LIFE-SPAN; OXIDATIVE STRESS; TELOMERE LENGTH; FAMILY MEMBER; GENE; INSULIN; YEAST; DAF-2; RESISTANCE AB We report a systematic RNA interference (RNAi) screen of 5,690 Caenorhabditis elegans genes for gene inactivations that increase lifespan. We found that genes important for mitochondrial function stand out as a principal group of genes affecting C. elegans lifespan. A classical genetic screen identified a mutation in the mitochondrial leucyl-tRNA synthetase gene (lrs-2) that impaired mitochondrial function and was associated with longer-lifespan. The long-lived worms with impaired mitochondria had lower ATP content and oxygen consumption, but differential responses to free-radical and other stresses. These data suggest that the longer lifespan of C. elegans with compromised mitochrondria cannot simply be assigned to lower free radical production and suggest a more complex coupling of metabolism and longevity. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Dept Genet, Sch Med, Boston, MA 02114 USA. Univ Cambridge, Wellcome Trust Canc Res UK Inst, Cambridge, England. RP Ruvkun, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. OI Lee, Raymond/0000-0002-8151-7479; Fraser, Andrew/0000-0001-9939-6014 FU Wellcome Trust [054523] NR 46 TC 538 Z9 572 U1 4 U2 30 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2003 VL 33 IS 1 BP 40 EP 48 DI 10.1038/ng1056 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 630XH UT WOS:000180136100015 PM 12447374 ER PT J AU Ramaswamy, S Ross, KN Lander, ES Golub, TR AF Ramaswamy, S Ross, KN Lander, ES Golub, TR TI A molecular signature of metastasis in primary solid tumors SO NATURE GENETICS LA English DT Article ID EXPRESSION; CANCER; BREAST; CELLS; GENE; CLASSIFICATION; CARCINOMA; REVEALS AB Metastasis is the principal event leading to death in individuals with cancer, yet its molecular basis is poorly understood(1). To explore the molecular differences between human primary tumors and metastases, we compared the gene-expression profiles of adenocarcinoma metastases of multiple tumor types to unmatched primary adenocarcinomas. We found a gene-expression signature that distinguished primary from metastatic adenocarcinomas. More notably, we found that a subset of primary tumors resembled metastatic tumors with respect to this gene-expression signature. We confirmed this finding by applying the expression signature to data on 279 primary solid tumors of diverse types. We found that solid tumors carrying the gene-expression signature were most likely to be associated with metastasis and poor clinical outcome (P < 0.03). These results suggest that the metastatic potential of human tumors is encoded in the bulk of a primary tumor, thus challenging the notion that metastases arise from rare cells within a primary tumor that have the ability to metastasize(2). C1 MIT, Ctr Genome Res, Whitehead Inst, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Ramaswamy, S (reprint author), MIT, Ctr Genome Res, Whitehead Inst, 1 Kendall Sq,Bldg 300, Cambridge, MA 02139 USA. NR 29 TC 1501 Z9 1563 U1 13 U2 63 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2003 VL 33 IS 1 BP 49 EP 54 DI 10.1038/ng1060 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 630XH UT WOS:000180136100016 PM 12469122 ER PT J AU Bhardwaj, N Walker, BD AF Bhardwaj, N Walker, BD TI Immunotherapy for AIDS virus infections: Cautious optimism for cell-based vaccine SO NATURE MEDICINE LA English DT Editorial Material ID DENDRITIC CELLS; RESPONSES; VIREMIA; HIV-1; IMMUNITY C1 NYU, New York, NY 10003 USA. Rockefeller Univ, New York, NY 10021 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. Harvard Univ, Div Aids, Sch Med, Boston, MA USA. RP Bhardwaj, N (reprint author), NYU, New York, NY 10003 USA. NR 16 TC 11 Z9 13 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2003 VL 9 IS 1 BP 13 EP 14 DI 10.1038/nm0103-13 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 632EC UT WOS:000180209900010 PM 12514710 ER PT J AU Weissleder, R Ntziachristos, V AF Weissleder, Ralph Ntziachristos, Vasilis TI Shedding light onto live molecular targets SO NATURE MEDICINE LA English DT Review AB Optical sensing of specific molecular targets and pathways deep inside living mice has become possible as a result of a number of advances. These include design of biocompatible near-infrared fluorochromes, development of targeted and activatable 'smart' imaging probes, engineered photoproteins and advances in photon migration theory and reconstruction. Together, these advances will provide new tools making it possible to understand more fully the functioning of protein networks, diagnose disease earlier and speed along drug discovery. C1 [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. EM weissleder@helix.mgh.harvard.edu NR 85 TC 1143 Z9 1171 U1 22 U2 173 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2003 VL 9 IS 1 BP 123 EP 128 DI 10.1038/nm0103-123 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA V27VJ UT WOS:000208640400007 PM 12514725 ER PT J AU D'Andrea, AD Grompe, M AF D'Andrea, AD Grompe, M TI The Fanconi anaemia BRCA pathway SO NATURE REVIEWS CANCER LA English DT Review ID ANEMIA GROUP-C; NUCLEOTIDE EXCISION-REPAIR; DOUBLE-STRAND BREAKS; ATM-DEPENDENT PHOSPHORYLATION; INDUCED APOPTOTIC RESPONSES; HEMATOPOIETIC STEM-CELLS; HOMOLOGY-DIRECTED REPAIR; INTERSTRAND CROSS-LINKS; UMBILICAL-CORD BLOOD; IN-VIVO SELECTION AB Fanconi anaemia (FA) is a rare genetic cancer-susceptibility syndrome that is characterized by congenital abnormalities, bone-marrow failure and cellular sensitivity to DNA crosslinking agents. Seven FA-associated genes have recently been cloned, and their products were found to interact with well-known DNA-damage-response proteins, including BRCA1, ATM and NBS1. The FA proteins could therefore be involved in the cell-cycle checkpoint and DNA-repair pathways. Recent studies implicate the FA proteins in the process of repairing chromosome defects that occur during homologous recombination, and disruption of the FA genes results in chromosome instability - a common feature of many human cancers. C1 Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 120 TC 515 Z9 519 U1 5 U2 38 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD JAN PY 2003 VL 3 IS 1 BP 23 EP 34 DI 10.1038/nrc970 PG 12 WC Oncology SC Oncology GA 636HK UT WOS:000180448400012 PM 12509764 ER PT B AU Masland, RH AF Masland, RH BE Kaneko, A TI Some functions of amacrine cells SO NEURAL BASIS OF EARLY VISION SE KEIO UNIVERSITY INTERNATIONAL SYMPOSIA FOR LIFE SCIENCES AND MEDICINE LA English DT Proceedings Paper CT 12th Keio-University International Symposium for Life Sciences and Medicine CY SEP 02-04, 2002 CL KEIO UNIV, TOKYO, JAPAN SP Keio Univ Med Sci Fund HO KEIO UNIV C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Masland, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 37-3, HONGO 3-CHOME BONKYO-KU, TOKYO, 113, JAPAN BN 4-431-00459-9 J9 KEIO U INT SYMP LIFE JI Keio Univ. Int. Symp. Life Sci. Med PY 2003 VL 11 BP 48 EP 49 PG 2 WC Biophysics; Neurosciences; Ophthalmology SC Biophysics; Neurosciences & Neurology; Ophthalmology GA BX14A UT WOS:000184414300013 ER PT J AU Giovanello, KS Alexander, M Verfaellie, M AF Giovanello, KS Alexander, M Verfaellie, M TI Differential impairment of person-specific knowledge in a patient with semantic dementia SO NEUROCASE LA English DT Article DE semantic dementia; proper names; person-specific knowledge ID SLOWLY PROGRESSIVE APHASIA; TEMPORAL-LOBE ATROPHY; PROPER NAME ANEMIA; RETROGRADE-AMNESIA; MEMORY; IDENTIFICATION; ORGANIZATION; GRADIENT; REVERSAL; PEOPLE AB We report the case of ST, a 61-year-old gentleman of superior intelligence, who presented with a five-year history of slowly progressive word finding difficulty for proper names. MRI (magnetic resonance imaging) showed marked atrophy in the left anterior temporal lobe and SPECT (single photon emission computed tomography) demonstrated hypoperfusion in the left anterior and inferior temporal region. A detailed behavioral analysis of the integrity of his semantic system revealed naming deficits for both proper and common names. ST also showed severe impairments in person-specific semantic knowledge, but preservation of knowledge for famous places and common objects. ST's semantic knowledge deficit for people emerged whether he was tested with the faces or the names of famous individuals. Variables that affect name retrieval, such as familiarity, age of acquisition, and frequency of concept encounter, do not account for the selective impairment of person-specific knowledge evidenced by ST. Qualitative differences between the nature of knowledge representations for people and for common objects may underlie this effect. Disruptions in left temporal regions associated with semantic processing may be sufficient to produce a selective deficit in person-specific knowledge. C1 Boston VA Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Cambridge, MA 02138 USA. RP Giovanello, KS (reprint author), Boston VA Healthcare Syst, Memory Disorders Res Ctr, 151-A,150 S Huntington Ave, Boston, MA 02130 USA. FU NIMH NIH HHS [MH57681]; NINDS NIH HHS [NS26985] NR 53 TC 13 Z9 13 U1 1 U2 2 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1355-4794 J9 NEUROCASE JI Neurocase PY 2003 VL 9 IS 1 BP 15 EP 26 DI 10.1076/neur.9.1.15.14369 PG 12 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 698CL UT WOS:000183980000002 PM 16210222 ER PT J AU Mendez, MF Perryman, KM AF Mendez, MF Perryman, KM TI Disrupted facial empathy in drawings from artists with frontotemporal dementia SO NEUROCASE LA English DT Article DE frontotemporal dementia; empathy; right temporal lobe; art; faces ID FUSIFORM FACE AREA; SPECT CHARACTERISTICS; HUMAN AMYGDALA; TEMPORAL-LOBE; DEGENERATION; EXPRESSIONS; PERCEPTION; EMOTIONS; DAMAGE; PROSOPAGNOSIA AB The sense of empathy may be altered by brain disease. We report the drawing performance of four artists who developed frontotemporal dementia (FTD). The first three, but not the fourth, had a prominent decrease in empathy for others as well as alterations in their caricatures of people. Their drawings of faces became distorted, menacing, skeleton-like, or 'alien'. None of the four had facial recognition difficulties, problems in interpreting facial emotions, or a decreased appreciation of the distinction between animate and inanimate objects. Functional brain imaging in the patients revealed bilateral frontal hypometabolism or hypoperfusion, and the three with altered drawings had additional prominent involvement of the right temporal lobe. These FTD patients and the literature suggest that FTD, possibly with greater right temporal involvement, disrupts the sense of empathy from human faces. C1 VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 37 TC 15 Z9 16 U1 0 U2 4 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1355-4794 J9 NEUROCASE JI Neurocase PY 2003 VL 9 IS 1 BP 44 EP 50 DI 10.1076/neur.9.1.44.14375 PG 7 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 698CL UT WOS:000183980000004 PM 16210224 ER PT J AU MacDonald, ME Gines, S Gusella, JF Wheeler, VC AF MacDonald, ME Gines, S Gusella, JF Wheeler, VC TI Huntington's disease SO NEUROMOLECULAR MEDICINE LA English DT Article DE Huntington's disease; huntingtin; knock-in mice; polyglutamine disorder; HD ID KNOCK-IN MICE; TRANSGENIC MOUSE MODEL; AGE-OF-ONSET; CAG REPEAT; MUTANT HUNTINGTIN; STRIATAL NEURONS; NEURODEGENERATIVE DISEASE; SACCHAROMYCES-CEREVISIAE; INTRANUCLEAR INCLUSIONS; INCREASED APOPTOSIS AB Huntington's disease (HD) research is aimed at understanding the root cause of the disorder, for the thrill of uncovering new biology, and for the serious purpose of finding effective therapeutic agents. Molecular genetics has revealed the disease trigger, an inherited unstable CAG expansion in a novel 4p16.3 gene (HD), that lengthens a polyglutamine segment in huntingtin. Now studies with HD patients and model systems that are genetic HD replicas are homing in on the trigger mechanism and the first formative steps that cast HD as a distinct clinical entity. At the same time, assays at the biochemical, cellular, and whole organism levels are starting to yield potential disease modifying genes and candidate drugs. These can be prioritized by testing in a panel of genetic and phenotypic HD mouse models to yield analytical tools for dissecting the early and late stages of the disease process and to maximize the chance of success in trials with HD patients. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP MacDonald, ME (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Charlestown, MA 02129 USA. OI Gines Padros, Silvia/0000-0002-9479-8185 FU NINDS NIH HHS [NS16367, NS32765] NR 81 TC 49 Z9 49 U1 1 U2 12 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2003 VL 4 IS 1-2 BP 7 EP 20 DI 10.1385/NMM:4:1-2:7 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 736KU UT WOS:000186170600002 PM 14528049 ER PT J AU Guenette, SY AF Guenette, SY TI Mechanisms of A beta clearance and catabolism SO NEUROMOLECULAR MEDICINE LA English DT Review DE beta-amyloid; degradation; clearance; Alzheimer's disease ID INSULIN-DEGRADING ENZYME; ENDOTHELIN-CONVERTING ENZYME; ONSET ALZHEIMERS-DISEASE; AMYLOID PLAQUE-FORMATION; TRANSGENIC MICE; MOUSE-BRAIN; IN-VIVO; NEUTRAL ENDOPEPTIDASE; ENDOSOMAL PROTEOLYSIS; CELLULAR-LOCALIZATION AB Mutations that result in an increased generation of amyloid beta peptide (Abeta) account for less than 5% of Alzheimer's disease (AD). Data suggesting that late onset AD risk factors play a role in Abeta turnover in the brain have shifted some of the research focus to the study of Abeta clearance and degradation and the impact of these processes on the etiology of Alzheimer's disease (AD). This review will examine the data obtained from studies performed in knockout and transgenic mice on the proteases; the cells and the physiological mechanisms that play a part in the removal of Abeta from the brain. C1 Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Guenette, SY (reprint author), Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM guenette@helix.mgh.harvard.edu NR 100 TC 19 Z9 22 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2003 VL 4 IS 3 BP 147 EP 160 DI 10.1385/NMM:4:3:147 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 760MM UT WOS:000187837700001 PM 14716023 ER PT J AU Papakostas, GI Petersen, T Sonawalla, SB Merens, W Iosifescu, DV Alpert, JE Fava, M Nierenberg, AA AF Papakostas, GI Petersen, T Sonawalla, SB Merens, W Iosifescu, DV Alpert, JE Fava, M Nierenberg, AA TI Serum cholesterol in treatment-resistant depression SO NEUROPSYCHOBIOLOGY LA English DT Article DE cholesterol; nortriptyline; treatment-resistant depression ID CORONARY-ARTERY DISEASE; MAJOR DEPRESSION; ANGER ATTACKS; VASCULAR DEPRESSION; FENFLURAMINE CHALLENGE; FLUOXETINE TREATMENT; UNIPOLAR DEPRESSION; RISK-FACTORS; MEN; SUICIDE AB Objective: Patients with major depressive disorder (MDD) may have significant differences in cholesterol levels compared with healthy controls. A previous study by our group reported that depressed patients with elevated cholesterol levels (greater than or equal to200 mg/dl) were significantly more likely to be nonresponders to fluoxetine treatment than depressed patients with nonelevated cholesterol levels. However, very little is known regarding cholesterol in patients with treatment-resistant depression (TRID). The purpose of this study was to compare cholesterol levels at baseline between depressed patients with and without TRD and to test whether cholesterol levels at baseline can predict clinical response in patients with TRD treated with open-label nortriptyline (NT). Methods: Ninety-two patients with TRD entered a 6-week open trial of NT. Baseline cholesterol levels were randomly collected for 59 of these patients. Controlling for age and gender, we compared baseline cholesterol and triglyceride levels for 35 patients with TRD who did not respond to NT with 205 non-TRD patients who responded to an 8-week open trial of fluoxetine. Furthermore, with the use of logistic regression, we tested whether baseline cholesterol levels predicted clinical response to NT in the patients with TRD. Results: Patients with TRID had higher triglyceride levels at baseline compared with depressed patients without TRID. Cholesterol defined as a dichotomous variable being elevated if equal to or greater than 200 mg/dl, predicted poor response to a 6-week open trial of NT in patients with TRID. Conclusions: The results of this study confirm the relationship between hypercho-lesterolemia and poor outcome in the treatment of MDD for patients with TRID. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R01 MH484305, R29 MH46952] NR 53 TC 24 Z9 24 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-282X J9 NEUROPSYCHOBIOLOGY JI Neuropsychobiology PY 2003 VL 47 IS 3 BP 146 EP 151 DI 10.1159/000070584 PG 6 WC Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 686LB UT WOS:000183322300007 PM 12759558 ER PT J AU Mendez, MF Cherrier, MM AF Mendez, MF Cherrier, MM TI Agnosia for scenes in topographagnosia SO NEUROPSYCHOLOGIA LA English DT Article DE topographic disorientation; environmental disorientation; spatial agnosia; visual agnosia; prosopagnosia; route(s) ID TOPOGRAPHICAL DISORIENTATION; ALZHEIMERS-DISEASE; SPATIAL MEMORY; PARAHIPPOCAMPAL CORTEX; FACE RECOGNITION; LESIONS; IMPAIRMENT; DEFICITS; LOCALIZATION; PERCEPTION AB Topographagnosia is most commonly attributed to an agnosia for landmarks. In order to define the nature of this agnosia, we studied a patient with isolated topographic disorientation (TD) after a stroke in the right medial occipitotemporal region. The patient got lost in familiar environments but could readily read and draw maps, describe familiar routes, and provide correct directions. He had normal perceptual test performance and met criteria for topographagnosia rather than for other forms of topographic disorientation. Two ecologically valid route tests assessed the nature of his agnosia. On a familiar route, he could recognize major landmarks. He could not, however, recognize route configurations made up of combinations of visual features each lacking individual distinctiveness. On a test of route learning, he learned landmarks that differed in minor details and could use them to orient himself along a route. He had difficulty, however, recognizing and learning scenes lacking salient landmarks. This agnosia for scenes was worse for semantically-related environments, but improved with semantic knowledge such as street names. In addition, the patient lacked overt prosopagnosia but tended toward semantic errors in the recognition of famous faces. Together these findings suggest that this patient's inability to recognize a route resulted from an inability of intact perceptual units for scenes, composed of specific visual configurations of individually indefinite features, from accessing stored representations. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. RP Mendez, MF (reprint author), W Los Angeles Vet Affairs Med Ctr, Neurobehav Unit, 116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 60 TC 55 Z9 56 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2003 VL 41 IS 10 BP 1387 EP 1395 DI 10.1016/S0028-3932(03)00041-1 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 687GN UT WOS:000183368300010 PM 12757910 ER PT J AU Casey, DE Daniel, DG Wassef, AA Tracy, KA Wozniak, P Sommerville, KW AF Casey, DE Daniel, DG Wassef, AA Tracy, KA Wozniak, P Sommerville, KW TI Effect of divalproex combined with olanzapine or risperidone in patients with an acute exacerbation of schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE divalproex; olanzapine; risperidone; psychosis; schizophrenia ID VALPROIC ACID; PLASMA-CONCENTRATIONS; ANTIEPILEPTIC DRUGS; SERUM-LIPIDS; CARBAMAZEPINE; HALOPERIDOL; CHILDREN; LIPOPROTEINS; AUGMENTATION; DISORDERS AB This double-blind, randomized, multicenter study investigated the use of divalproex with an antipsychotic agent in patients hospitalized for acute exacerbation of schizophrenia. Patients (n = 249) who met DSM-IV criteria for schizophrenia were randomly assigned to receive olanzapine monotherapy, risperidone monotherapy, divalproex plus olanzapine, or divalproex plus risperidone for 28 days. Dvalproex was initiated at 15 mg/kg/day and titrated over 12 days to a maximum dosage of 30 mg/kg/day. Olanzapine and risperidone, were, respectively, initiated at 5 and 2 mg/day and were titrated over the first 6 days to respective target fixed daily dosages of 15 and 6 mg/day. Improvements from baseline were observed at all evaluation points throughout the 28-day treatment period in the two combination therapy and the two antipsychotic monotherapy groups, with statistically significant treatment differences favoring combination therapy as soon as day 3 for Positive and Negative Syndrome Scale (PANSS) total score, derived Brief Psychiatric Rating Scale (BPRSd) total score, as well as PANSS and BPRSd subscales. These findings were confirmed in post hoc repeated-measures analyses of variance in which treatment differences favoring combination therapy were observed for PANSS total (p = 0.020) and PANSS positive scale scores (p=0.002). Both combination therapy and antipsychotic monotherapy were well tolerated. Treatment with divalproex in combination with an atypical antipsychotic agent resulted in earlier improvements in a range of psychotic symptoms among acutely hospitalized patients with schizophrenia. Further evaluation is warranted to confirm these findings. C1 George Washington Univ, Washington, DC USA. Bioniche Dev, Falls Church, VA USA. Univ Texas, HCPC, Houston, TX USA. Abbott Labs, Abbott Pk, IL 60064 USA. Univ Illinois, Chicago, IL USA. Portland VA Med Ctr, Mental Ilness Res Educ & Clin Ctr, Portland, OR 97201 USA. RP Casey, DE (reprint author), Portland VA Med Ctr, Mental Ilness Res Educ & Clin Ctr, P3MIRECC,VISN 20,3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. NR 39 TC 145 Z9 148 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2003 VL 28 IS 1 BP 182 EP 192 DI 10.1038/sj.npp.1300023 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 642GT UT WOS:000180796400021 PM 12496955 ER PT J AU Tzika, AA Astrakas, LG Zarifi, MK Petridou, N Young-Poussaint, T Goumnerova, L Zurakowski, D Anthony, DC Black, PM AF Tzika, AA Astrakas, LG Zarifi, MK Petridou, N Young-Poussaint, T Goumnerova, L Zurakowski, D Anthony, DC Black, PM TI Multiparametric MR assessment of pediatric brain tumors SO NEURORADIOLOGY LA English DT Article DE brain; tumors; MRI; MRSI; children; physiology ID MAGNETIC-RESONANCE SPECTROSCOPY; HIGH-SPATIAL-RESOLUTION; CEREBRAL BLOOD-VOLUME; IN-VIVO; GLIOBLASTOMA-MULTIFORME; PROTON SPECTROSCOPY; STEREOTAXIC BIOPSY; GENE-THERAPY; RAT GLIOMA; DIFFUSION AB MR assessment of pediatric brain tumors has expanded to include physiologic information related to cellular metabolites, hemodynamic and diffusion parameters. The purpose of this study was to investigate the relationship between MR and proton MR spectroscopic imaging in children with primary brain tumors. Twenty-one patients (mean age 9 years) with histologically verified brain tumors underwent conventional MR imaging, hemodynamic MR imaging (HMRI) and proton MR spectroscopic imaging (MRSI). Fourteen patients also had diffusion-weighted MR imaging (DWMRI). Metabolic indices including choline-containing compounds (Cho), total creatine (tCr) and lipids/lactate (L) were derived by proton MRSI, relative cerebral blood volume (rCBV) by HMRI, and apparent tissue water diffusion coefficients (ADC) by DWMRI. Variables were examined by linear regression and correlation as well as by ANOVA. Cho (suggestive of tumor cellularity and proliferative activity) correlated positively with rCBV, while the relationship between Cho and ADC (suggestive of cellular density) was inverse (P < 0.001). The relationship between rCBV and ADC was also inverse (P = 0.004). Cho and lipids (suggestive of necrosis and/or apoptosis) were not significantly correlated (P = 0.51). A positive relationship was found between lipids and ADC (P = 0.002). The relationships between Cho, rCBV, ADC and lipids signify that tumor physiology is influenced by the tumor's physical and chemical environment. Normalized Cho and lipids distinguished high-grade from low-grade tumors (P < 0.05). Multiparametric MR imaging using MRSI, HMRI and DWMRI enhances assessment of brain tumors in children and improves our understanding of tumor physiology while promising to distinguish higher- from lower-malignancy tumors, a distinction that is particularly clinically important among inoperable tumors. C1 Harvard Univ, Sch Med, Childrens Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, NMR Surg Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Shriners Burns Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pathol, Boston, MA 02114 USA. RP Tzika, AA (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dept Radiol, Boston, MA 02114 USA. RI Astrakas, Loukas/F-5918-2011; Anthony, Daniel/F-7765-2010; OI Anthony, Daniel/0000-0003-1380-6655; Anthony, Douglas/0000-0002-3815-2240 NR 54 TC 41 Z9 41 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-3940 J9 NEURORADIOLOGY JI Neuroradiology PD JAN PY 2003 VL 45 IS 1 BP 1 EP 10 DI 10.1007/s00234-002-0865-0 PG 10 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 644CU UT WOS:000180901000001 PM 12525947 ER PT J AU Qiu, Z Crutcher, KA Hyman, BT Rebeck, GW AF Qiu, Z Crutcher, KA Hyman, BT Rebeck, GW TI apoE isoforms affect neuronal N-methyl-D-aspartate calcium responses and toxicity via receptor-mediated processes SO NEUROSCIENCE LA English DT Article DE Alzheimer's disease; hippocampus; fluo-3; alpha 2-macroglobulin; calcium; lipoprotein ID DENSITY-LIPOPROTEIN RECEPTOR; APOLIPOPROTEIN-E RECEPTOR; CENTRAL-NERVOUS-SYSTEM; CULTURED HIPPOCAMPAL-NEURONS; THROMBIN-CLEAVAGE FRAGMENT; DEVELOPING CNS NEURONS; E EPSILON-4 ALLELE; ALZHEIMERS-DISEASE; GENE FAMILY; CELL-DEATH AB Apolipoprotein E (apoE) alters the pathophysiology of Alzheimer's disease, but its mechanism is not fully understood. We examined the effects of recombinant human apoE3 and apoE4 on the neuronal calcium response to N-methyl-D-aspartate (NMDA), and compared them to their toxicity. ApoE4 (100 nM) significantly increased the resting calcium (by 70%) and the calcium response to NMDA (by 185%), whereas similar changes were not obtained in apoE3-treated neurons. ApoE4, but not apoE3, also significantly increased neurotoxicity, as evidenced by enhanced lactate dehydrogenase release (by 53%) and reduced 3-(4,5-dimethylthiazol-2-yl)-2,5,diphenyltetrazolium bromide levels (by 32%). ApoE4-induced changes in the calcium response to NMDA and associated neurotoxicity were blocked by coincubation with MK-801. Both the receptor-associated protein, which inhibits interaction of apoE with members of the LDL receptor family, including the low-density lipoprotein receptor-related protein (LRP), and activated alpha2-macroglobulin, another LRP ligand, prevented apoE4-induced enhancement of the calcium response to NMDA, resting calcium levels, and neurotoxicity. A tandem apoE peptide (100 nM) containing only the receptor binding region residues also eliminated the enhanced calcium signaling and neurotoxicity by apoE4. Taken together, our data demonstrate that differential effects of apoE3 and apoE4 on the calcium signaling in neurons correlate with their effect on neurotoxicity, which are secondary to receptor binding. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Georgetown Univ, Dept Neurosci, Washington, DC 20057 USA. Univ Cincinnati, Coll Med, Dept Neurosurg, Cincinnati, OH 45267 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. RP Rebeck, GW (reprint author), Georgetown Univ, Dept Neurosci, 3970 Reservoir Rd NW, Washington, DC 20057 USA. RI Crutcher, Keith/A-4037-2008; OI Crutcher, Keith/0000-0002-9176-5759 FU NIA NIH HHS [AG12406, AG14473] NR 66 TC 54 Z9 57 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 122 IS 2 BP 291 EP 303 DI 10.1016/j.neuroscience.2003.08.017 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 748LD UT WOS:000186862600002 PM 14614897 ER PT J AU Lao, LJ Song, B Marvizon, JCG AF Lao, LJ Song, B Marvizon, JCG TI Neurokinin release produced by capsaicin acting on the central terminals and axons of primary afferents: Relationship with N-methyl-D-aspartate and GABA(B) receptors SO NEUROSCIENCE LA English DT Article DE C fiber; dorsal horn; internalization; neurokinin 1 receptor; substance P; vanilloid 1 receptor ID RAT SPINAL-CORD; GENE-RELATED PEPTIDE; SUBSTANCE-P RELEASE; POTASSIUM-STIMULATED RELEASE; GAMMA-AMINOBUTYRIC-ACID; LONG-TERM DEPRESSION; DORSAL-HORN NEURONS; GELATINOSA NEURONS; EVOKED RELEASE; IMMUNOREACTIVITY RELEASE AB Capsaicin stimulates neurokinin release in the spinal cord when applied both centrally and peripherally. To determine whether these two actions have different mechanisms, we measured neurokinin 1 receptor (NK1R) internalization in rat spinal cord slices elicited by incubating the whole slice or just the dorsal root with capsaicin. NK1R internalization produced by incubating the slices with capsaicin was abolished by the NK1R antagonist RP-67580, by the vanilloid receptor 1 (VR1) antagonist capsazepine, and by eliminating Ca2+ from the medium, but was not affected by the Na+ channel blocker lidocaine. Therefore, the internalization was due to neurokinin release mediated by Ca2+ entry through VR1 receptors, but did not require the firing of action potentials. Incubating the root with capsaicin produced NK1R internalization in the ipsilateral dorsal horn that was abolished when capsazepine or lidocaine was included in, or when Ca2+ was omitted from, the medium surrounding the root. Therefore, the internalization was mediated by Ca2+ entry in the axons through VR1, and required firing of action potentials. The efficacy of capsaicin when applied to the root (36 +/- 3%) was lower than when applied to the slice (91 +/- 3%), but its potency was the same (0.49 muM and 0.37 muM, respectively). We also investigated whether presynaptic N-methyl-D-aspartate (NMDA) and GABA(B) receptors modulate these two actions of capsaicin. Neither the NMDA receptor blocker MK-801 nor the GABA(B) agonist baclofen decreased NK1R internalization produced by 1 muM capsaicin applied to the slices, but they inhibited the internalization produced by 0.3 muM capsaicin applied to the slices or 1 muM capsaicin applied to the root. Therefore, capsaicin can produce neurokinin release from primary afferents 1) by a direct action on their central terminals and 2) by increasing the firing of action potentials on their axons. The first effect largely bypasses other modulatory mechanism, but the second does not. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Digest Dis Res Ctr,Div Digest Dis,Dept Med, CURE,Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90095 USA. RP Marvizon, JCG (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 115,Room 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDA NIH HHS [R01-DA12609] NR 73 TC 30 Z9 30 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 121 IS 3 BP 667 EP 680 DI 10.1016/S0306-4522(03)00501-3 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 743QC UT WOS:000186584200014 PM 14568027 ER PT J AU Lu, X Huang, X Ma, HF Gooley, JJ Aparacio, J Roof, DJ Chen, C Chen, DF Li, T AF Lu, X Huang, X Ma, HF Gooley, JJ Aparacio, J Roof, DJ Chen, C Chen, DF Li, T TI Normal retinal development and retinofugal projections in mice lacking the retina-specific variant of actin-binding LIM domain protein SO NEUROSCIENCE LA English DT Article DE retina; axon guidance; retinal ganglion cell; LIM domain ID NITRIC-OXIDE; AXON GUIDANCE; VISUAL-SYSTEM; C-ELEGANS; RETINOGENICULATE; GENE; HOMEODOMAIN; MEMBER; BRAIN; ORDER AB The actin-binding LIM domain protein (abLIM) is the mammalian homologue of UNC-115, a protein mediating axon guidance in C. elegans. AbLIM is widely expressed with three isoforms differing from one another by the length of their amino termini. Experiments utilizing dominant-negative mutants in the chick retina suggested a role for abLIM in axon path finding in retinal ganglion cells (RGCs). To investigate which variant is involved in the regulation of mammalian RGC axon guidance, we analyzed their expression profile in mice. The longest variant, abLIM-L, is highly enriched in the ganglion cell layer. AbLIM-L is up-regulated postnatally which temporally overlaps with the period of RGC axon remodeling. In contrast, the abLIM-M and abLIM-S variants are widespread and remain relatively constant through development. By selective gene targeting, we ablated abLIM-L to explore its functional significance in vivo. AbLIM-L mutant mice exhibit no apparent morphological or functional defects in photoreceptors and inner retinal neurons. Retinofugal projections and synaptic maturation also appear normal. These data suggest that abLIM-M is likely the isoform performing the essential function related to axon guidance. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmoimmunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Neurosci, Boston, MA 02115 USA. RP Li, T (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. NR 22 TC 2 Z9 2 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 120 IS 1 BP 121 EP 131 DI 10.1016/S0306-4522(03)00263-X PG 11 WC Neurosciences SC Neurosciences & Neurology GA 703AH UT WOS:000184257500012 ER PT J AU Snider, BJ Moss, JL Revilla, FJ Lee, CS Wheeler, VC Macdonald, ME Choi, DW AF Snider, BJ Moss, JL Revilla, FJ Lee, CS Wheeler, VC Macdonald, ME Choi, DW TI Neocortical neurons cultured from mice with expanded CAG repeats in the huntingtin gene: Unaltered vulnerability to excitotoxins and other insults SO NEUROSCIENCE LA English DT Article DE polyglutamine; Huntington's disease; apoptosis; proteasome; oxidative stress ID D-ASPARTATE RECEPTOR; KNOCK-IN MICE; TRANSGENIC MOUSE MODEL; CELL-DEATH; MUTANT HUNTINGTIN; STRIATAL NEURONS; OXIDATIVE STRESS; NEURODEGENERATIVE DISEASE; 3-NITROPROPIONIC ACID; POLYGLUTAMINE DISEASE AB Glutamate-mediated excitotoxicity might contribute to the pathogenesis of Huntington's disease and other polyglutamine repeat disorders. We used murine neocortical cultures derived from transgenic and knock-in mice to test the effect of expression of expanded polyglutamine-containing huntingtin on neuronal vulnerability to excitotoxins or other insults. Neurons cultured from mice expressing either a normal length (Hdh Q20) or expanded (Hdh(Q111)) CAG repeat as a knock-in genetic alteration in exon one of the mouse Hdh gene [Hum Mol Genet 8 (1999) 115] had similar vulnerability to N-methyl-D-aspartate (NMDA) and kainate-mediated excitotoxicity. These neurons also exhibited similar vulnerability to oxidative stress (24 h exposure to 10-100 muM paraquat or 1-10 muM menadione), apoptosis (48 h exposure to 30-100 nM staurosporine or 1 muM dizocilpine maleate (MK-801) and proteasome inhibition (48 h exposure to 0.3-3 muM MG-132). Neocortical neurons cultured from mice transgenic for an expanded CAG repeat-containing exon 1 of the human HD gene (Mangiarini et al., 1996, R6/2 line) and non-transgenic littermate controls also had similar vulnerability to NMDA and kainate-mediated excitotoxicity. These observations suggest that expression of expanded polyglutamine-containing huntingtin does not acutely alter the vulnerability of cortical neurons to excitotoxic, oxidative or apoptotic insults. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Washington Univ, Sch Med, Ctr Study Nervous Syst Injury, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Massachusetts Gen Hosp East, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Snider, BJ (reprint author), Washington Univ, Sch Med, Ctr Study Nervous Syst Injury, Campus Box 8111,660 S Euclid, St Louis, MO 63110 USA. FU NINDS NIH HHS [NS30337, NS16367, NS32765] NR 77 TC 23 Z9 25 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 120 IS 3 BP 617 EP 625 DI 10.1016/S0306-4522(03)00382-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 711XR UT WOS:000184766800003 PM 12895502 ER PT J AU Minnis, JG Patierno, S Kohlmeier, SE Brecha, NC Tonini, M Sternini, C AF Minnis, JG Patierno, S Kohlmeier, SE Brecha, NC Tonini, M Sternini, C TI Ligand-induced mu opioid receptor endocytosis and recycling in enteric neurons SO NEUROSCIENCE LA English DT Article DE guinea-pig ileum; gastrointestinal motility; G protein-coupled receptors; receptor trafficking ID GUINEA-PIG ILEUM; GASTROINTESTINAL MOTILITY; MEDIATED ENDOCYTOSIS; MOLECULAR-BIOLOGY; MYENTERIC PLEXUS; OPIATE RECEPTOR; RAT-BRAIN; INTERNALIZATION; MORPHINE; AGONIST AB Immunohistochemistry and confocal microscopy were used to investigate endocytosis and recycling of the native mu opioid receptor (muOR) in enteric neurons. Isolated segments of the guinea-pig ileum were exposed to increasing concentrations of muOR agonists at 4 degreesC to allow ligand binding and warming to 37 degreesC for 0 min (baseline) to 6 h in ligand-free medium to allow receptor internalization and recycling. The endogenous ligand, [Met]enkephalin, and [D-Ala(2),MePhe(4),Gly-ol(5)] enkephalin (DAMGO), an opioid analog, and the alkaloids, etorphine and fentanyl, induced rapid internalization of muOR immunoreactivity in enteric neurons, whereas morphine did not. muOR internalization was prevented by muOR antagonists. Basal levels of muOR immunoreactivity in the cytoplasm were 10.52+/-2.05%. DAMGO (1 nM-100 muM) induced a concentration-dependent increase of muOR immunofluorescence density in the cytoplasm to a maximum of 84.37+/-2.26%. Translocation of muOR immunoreactivity in the cytoplasm was detected at 2 min, reached the maximum at 15-30 min, remained at similar levels for 2 h, began decreasing at 4 h, and was at baseline values at 6 h. A second exposure to DAMGO (100 nM) following recovery of internalized muOR immunoreactivity at the cell surface induced a translocation of muOR immunoreactivity in the cytoplasm comparable to the one observed following the first exposure (46.89+/-3.11% versus 43.31+/-0.80%). muOR internalization was prevented by hyperosmolar sucrose, phenylarsine oxide or potassium depletion, which inhibit clathrin-mediated endocytosis. muOR recycling was prevented by pre-treatment with bafilomycin A1, an acidotropic agent that inhibits endosomal acidification, but not by the protein synthesis inhibitor, cycloheximide. This study shows that native muOR in enteric neurons undergoes ligand-selective endocytosis, which is primarily clathrin-mediated, and recycles following endosomal acidification. Following recycling, muOR is activated and internalized by DAMGO indicating that recycled receptors are functional. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Vet Adm Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Pavia, Dept Physiol & Pharmacol Sci, I-27100 Pavia, Italy. Univ Calif Los Angeles, Opioid Res Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. RP Sternini, C (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Div Digest Dis, Bldg 115,Room 224,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDA NIH HHS [DA 05010, P50 DA005010]; NIDDK NIH HHS [DK 41301, DK54155] NR 55 TC 48 Z9 49 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 119 IS 1 BP 33 EP 42 DI 10.1016/S0306-4522(03)00135-0 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 688DN UT WOS:000183418000005 PM 12763066 ER PT J AU Zheng, F Johnson, SW AF Zheng, F Johnson, SW TI Dual modulation of gabaergic transmission by metabotropic glutamate receptors in rat ventral tegmental area SO NEUROSCIENCE LA English DT Article DE non-dopamine neurons; t-ACPD; neuronal excitation; synaptic inhibition; midbrain ID GABA-CONTAINING NEURONS; DOPAMINE NEURONS; NUCLEUS-ACCUMBENS; PREFRONTAL CORTEX; SYNAPTIC INPUTS; INWARD CURRENT; ACTIVATION; REWARD; NMDA; STIMULATION AB The effects of metabotropic glutamate receptor (mGluR) activation on non-dopamine (putative GABAergic) neurons and inhibitory synaptic transmission in the ventral tegmental area were examined using intracellular recordings from rat midbrain slices. Perfusion of (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD; agonist for group I and II mGluRs), but not L-amino-4-phosphonobutyric acid (L-AP4; agonist for group III mGluRs), produced membrane depolarization (current clamp) and inward current (voltage clamp) in non-dopamine neurons. The t-ACPD-induced depolarization was concentration-dependent (concentration producing 50% maximal depolarization [EC50]=6.1+/-2.5 muM), and was blocked by the antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine, but not by tetrodotoxin and ionotropic glutamate-receptor antagonists. The t-ACPD-evoked responses were mimicked comparably by selective group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG). Furthermore, the DHPG-induced depolarization in non-dopamine neurons was greatly reduced by mGluR1-specific antagonist 7(hydroxyimino)cyclopropachromen-1a-carboxylate ethyl ester. When recorded in dopamine neurons, the frequency of spontaneous GABA(A) receptor-mediated inhibitory postsynaptic potentials was increased by t-ACPD but not L-AP4. However, the amplitude of evoked inhibitory postsynaptic currents in dopamine neurons was reduced by all three group mGluR agonists. These results reveal a dual modulation of mGluR activation on inhibitory transmission in midbrain ventral tegmental area: enhancing putative GABAergic neuronal excitability and thus potentiating tonic inhibitory synaptic transmission while reducing evoked synaptic transmission at inhibitory terminals. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Portland VA Med Ctr, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97239 USA. RP Johnson, SW (reprint author), Portland VA Med Ctr, RD-61,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. FU NIMH NIH HHS [MH40416] NR 41 TC 15 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 119 IS 2 BP 453 EP 460 DI 10.1016/S0306-4522(03)00190-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 688DP UT WOS:000183418100012 PM 12770559 ER PT J AU Balcioglu, A Zhang, K Tarazi, FI AF Balcioglu, A Zhang, K Tarazi, FI TI Dopamine depletion abolishes apomorphine- and amphetamine-induced increases in extracellular serotonin levels in the striatum of conscious rats: A microdialysis study SO NEUROSCIENCE LA English DT Article DE 6-OHDA; Parkinson's disease; autoradiography; HPLC ID IN-VIVO MICRODIALYSIS; FREELY MOVING RATS; ADULT-RAT; NEONATAL 6-HYDROXYDOPAMINE; NUCLEUS-ACCUMBENS; SUBSTANTIA-NIGRA; INTRACEREBRAL DIALYSIS; ACETYLCHOLINE-RELEASE; RECEPTOR-BINDING; MONOAMINE LEVELS AB We investigated how serotonergic neurotransmission was affected by 6-hydroxydopamine (6-OHDA) lesioning of the adult rat brain dopamine (DA) system. In this animal model for Parkinson's disease (PD), the effect of destroying ascending DA pathways on extracellular levels of serotonin (5-HT) and 5-HT innervation in rat striatum were examined. Profound unilateral lesions of the nigrostriatal DA pathways were made by infusing 6-OHDA unilaterally into either the right medial forebrain bundle or the right substantia nigra. At 5 weeks after lesioning extracellular levels of DA and 5-HT were determined with microdialysis and high-pressure liquid chromatography under basal conditions and after systemic injections of apomorphine or amphetamine. DA nerve-terminal destruction and 5-HT innervation were determined with quantitative autoradiography. 6-OHDA lesioning reduced extracellular levels of DA below detection limits and led to statistically significant increases in extracellular 5-HT. Apomorphine, and amphetamine, respectively increased extracellular 5-HT to 8.2- and 2.2-fold above baseline levels in intact animals; these effects were absent in 6-OHDA-lesioned animals. Basal levels of [H-3]paroxetine binding to 5-HT transporters in caudate-putamen increased by 41% in 6-OHDA lesioned animals. These results suggest that 6-OHDA lesioning led to hyperinnervation of 5-HT nerve terminals and increases in basal extracellular 5-HT levels, but also to an unexplained loss of apomorphine and amphetamine-induced release of 5-HT. Addressing whether this impairment has significance in the onset of PD might lead to development of new strategies to manage parkinsonian symptoms. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, McLean Hosp, Neuroregenerat Labs, Belmont, MA 02478 USA. Harvard Univ, Sch Med, McLean Hosp, Neuropharmacol Lab, Belmont, MA 02478 USA. RP Balcioglu, A (reprint author), Massachusetts Gen Hosp, 16th St Blvd,114 CGN Room 2925F, Boston, MA 02129 USA. FU NINDS NIH HHS [P50 NS39793] NR 65 TC 33 Z9 39 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 119 IS 4 BP 1045 EP 1053 DI 10.1016/S0306-4522(03)00219-7 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 700HT UT WOS:000184107100013 PM 12831863 ER PT J AU Hohmann, JG Jureus, A Teklemichael, DN Matsumoto, AM Clifton, DK Steiner, RA AF Hohmann, JG Jureus, A Teklemichael, DN Matsumoto, AM Clifton, DK Steiner, RA TI Distribution and regulation of galanin receptor 1 messenger RNA in the forebrain of wild type and galanin-transgenic mice SO NEUROSCIENCE LA English DT Article DE galanin; receptor; transgenic; knockout; hypothalamus; mouse ID LOCUS-COERULEUS NEURONS; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; NEUROPEPTIDE-Y; SPINAL-CORD; MAGNOCELLULAR NEURONS; HORMONE SECRETION; FEMALE RAT; EXPRESSION; HYPOTHALAMUS AB To learn more about molecular alterations in the brain that occur as a consequence of either the chronic excess or absence of peptide neurotransmitters, we examined the impact of genetically manipulating the neuropeptide galanin on the expression of one of its cognate receptors, galanin receptor 1. First, we examined the distribution of galanin receptor 1 messenger RNA in the mouse forebrain, and found it to be abundantly expressed in many brain regions, including in numerous hypothalamic and other forebrain regions associated with neuroendocrine function. The distribution of galanin receptor 1 messenger RNA in the mouse was similar to previous reports in the rat, with additional expression noted in the caudate putamen and in several midbrain regions. Next, using quantitative in situ hybridization, we measured cellular levels of galanin receptor 1 messenger RNA in the brains of mice that either overexpress galanin (galanin transgenic) or lack a functional galanin gene (galanin knockout). We report that relative to wild-type controls, the expression of galanin receptor 1 messenger RNA was increased in discrete areas of the brain in galanin-transgenic mice, but that depletion of galanin/noradrenergic innervation to the hypothalamus with the neurotoxin 6-hydroxy-dopamine did not alter levels of galanin receptor 1 messenger RNA. We also report that levels of galanin receptor 1 messenger RNA were not different between galanin-knockout and wild-type mice. These results suggest that compensatory adjustments in the expression of cognate receptors represent one mechanism by which the developing nervous system attempts to maintain homeostasis in response to overexpression of a peptidergic transmitter. However, the lack of significant changes in galanin receptor 1 messenger RNA in galanin-knockout mice suggests that developmentally programmed levels of receptor expression are maintained even in the complete absence of ligand. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. Univ Washington, Neurobiol & Behav Program, Seattle, WA 98195 USA. Univ Washington, Dept Zool, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. RP Steiner, RA (reprint author), Univ Washington, Dept Physiol & Biophys, Box 357290, Seattle, WA 98195 USA. FU NIA NIH HHS [AG05136]; NICHD NIH HHS [R01 HD27142]; PHS HHS [U5412629] NR 58 TC 40 Z9 40 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 117 IS 1 BP 105 EP 117 DI 10.1016/S0306-4522(02)00798-4 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 653AA UT WOS:000181412000012 PM 12605897 ER PT J AU Agdeppa, ED Kepe, V Petric, A Satyamurthy, N Liu, J Huang, SC Small, GW Cole, GM Barrio, JR AF Agdeppa, ED Kepe, V Petric, A Satyamurthy, N Liu, J Huang, SC Small, GW Cole, GM Barrio, JR TI In vitro detection of (S)-naproxen and ibuprofen binding to plaques in the Alzheimer's brain using the positron emission tomography molecular imaging probe 2-(1-{6-[(2[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene) malononitrile SO NEUROSCIENCE LA English DT Article DE anti-aggregation; beta-amyloid fibrils; competitive binding; digital autoradiography; fluorescence microscopy; non-steroidal anti-inflammatory drugs ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; AMYLOID-BETA-PROTEIN; CONTROLLED TRIAL; CACHE COUNTY; DOUBLE-BLIND; DISEASE; DISPOSITION; AGGREGATION; ANTAGONISTS; METABOLISM AB Epidemiological studies have suggested that the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the relative risk of Alzheimer's disease (AD). The possible neuroprotection by NSAIDs in AD is generally attributed to anti-inflammatory activity. An additional mode of drug action may involve anti-aggregation of P-amyloid (Abeta) peptides by commonly used NSAIDs. We utilized in vitro competition assays, autoradiography, and fluorescence microscopy with AD brain specimens to demonstrate concentration-dependent decreases in the binding of the in vivo molecular imaging probe, 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl) amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP), against (S)-naproxen and (R)- and (S)-ibuprofen (but not diclofenac) to Abeta fibrils and ex vivo Abeta senile plaques. Conversely, in vitro amyloid dyes Congo Red and Thioflavine T were demonstrated in the same experiments not to bind to the FDDNP binding site. FDDNP and the NSAIDs that share the same binding site also exhibit anti-aggregation effects on Abeta peptides, suggesting that the shared binding site on Abeta fibrils and plaques may be a site of anti-aggregation drug action. Our results indicate for the first time the binding of select NSAIDs to plaques, specifically to the binding site of the molecular imaging probe [F-18]FDDNP. Our understanding of the molecular requirements of FDDNP binding may help in the optimization of the Abeta anti-aggregation potency of experimental drugs. [F-18]FDDNP has been used to image plaques in vivo with positron emission tomography (PET), and investigations into the influence of Abeta anti-aggregation on the risk-reduction effects of NSAIDs on AD could utilize [F-18]FDDNP and PET in determining the occupancy rate of NSAIDs and experimental drugs in plaques in the living brain of AD patients. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Nucl Med, Dept Mol & Med Pharmacol,Lab Struct Biol & Mol Me, Los Angeles, CA 90095 USA. Univ Ljubljana, Fac Chem & Chem Technol, Ljubljana, Slovenia. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Inst Neuropsychiat, Los Angeles, CA 90095 USA. Greater Los Angles Vet Affairs Healthcare Syst, Sepulveda Geritr Res Educ & Clin Ctr, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. RP Barrio, JR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Nucl Med, Dept Mol & Med Pharmacol,Lab Struct Biol & Mol Me, Box 956948, Los Angeles, CA 90095 USA. NR 46 TC 136 Z9 144 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 117 IS 3 BP 723 EP 730 DI 10.1016/S0306-4522(02)00907-7 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 656TJ UT WOS:000181624300020 PM 12617976 ER PT J AU Ogilvy, CS Carter, BS AF Ogilvy, CS Carter, BS TI Stratification of outcome for surgically treated unruptured intracranial aneurysms SO NEUROSURGERY LA English DT Article DE risk stratification; unruptured aneurysm ID CEREBRAL ANEURYSMS; METAANALYSIS; MANAGEMENT; MORBIDITY; MORTALITY; SURGERY AB OBJECT: The combination of low anticipated rupture rates for many unruptured aneurysms, better delineation of treatment risks, and the availability of alternative modalities of treatment have led to heightened scrutiny of the surgical management of unruptured intracranial aneurysms. Most reports to date have provided aggregate data concerning surgical treatment risks. This study was performed to better delineate risk estimates for the surgical treatment of patients with unruptured intracranial aneurysms according to a patient's risk profile with regard to age, aneurysm location, and aneurysm size. METHODS: We studied 493 patients who were treated with surgical clipping of 604 unruptured saccular aneurysms. Information regarding aneurysm size, location, patient age, and 6-month or greater outcome were gathered prospectively from 1992 to 1999. Multivariate analysis was performed to identify independent risk factors for outcome. On the basis of the model, risk stratification curves were generated. RESULTS: In our series, the mean patient age was 53 years, and the mean lesion size was 8.8 mm. Lesion locations included the internal carotid artery (n = 259, 43%), the middle cerebral artery (n = 174, 28%), the anterior cerebral artery (n = 99, 17%), and the vertebrobasilar artery (n = 67, 11%). Multivariate analysis revealed that aneurysm size (beta = 0.122, P < 0.001.), patient age (beta = 0.0308, P < 0.05), and vertebrobasilar location (beta = 1.37, P = 0.0080) were independently associated with high risk of poor outcome or death. CONCLUSION: Small aneurysms in the anterior circulation in young patients carry a very low treatment risk (approximately 1%), and treatment in elderly individuals (ages 70 years and older) with large lesions (greater than 10 mm), carries a significant risk of poor outcome (5% in the anterior circulation, 15% in the posterior circulation). The nomograms generated by this study should be particularly useful in discussing with patients the risks and benefits of surgical treatment of unruptured aneurysms. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA 01114 USA. RP Ogilvy, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, 55 Fruit St,VBK710, Boston, MA 01114 USA. NR 9 TC 47 Z9 50 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 2003 VL 52 IS 1 BP 82 EP 87 DI 10.1227/01.NEU.0000038944.88607.16 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 631YL UT WOS:000180195800017 PM 12493104 ER PT S AU Sattler, M Scheijen, B Weisberg, E Griffin, JD AF Sattler, M Scheijen, B Weisberg, E Griffin, JD BE LlombartBosch, A Felipo, V TI Mutated tyrosine kinases as therapeutic targets in myeloid leukemias SO NEW TRENDS IN CANCER FOR THE 21ST CENTURY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Cancer Symposium on New Trends in Cancer for the 21st Century CY NOV 10-13, 2002 CL VALENCIA, SPAIN ID CHRONIC MYELOGENOUS LEUKEMIA; INTERNAL TANDEM DUPLICATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; DNA-BINDING ACTIVITY; BCR-ABL ONCOGENE; HEMATOPOIETIC-CELL LINES; PHOSPHATIDYLINOSITOL 3-KINASE/AKT PATHWAY; SIGNAL-TRANSDUCTION PATHWAYS; GROWTH-FACTOR INDEPENDENCE; C-KIT RECEPTOR AB Tyrosine kinases are commonly mutated and activated in both acute and chronic myeloid leukemias. Here, we review the functions, signaling activities, mechanism of transformation, and therapeutic targeting of two prototypic tyrosine kinase oncogenes, BCR-ABL and FLT3, associated with chronic myeloid leukemia (CML) and acute myeloid leukemia (AML), respectively. BCR-ABL is generated by the Philadelphia chromosome translocation between chromosomes 9 and 22, creating a chimeric oncogene in which the BCR and c-ABL genes are fused. The product of this oncogene, BCR-ABL, has elevated ABL tyrosine kin se activity and transforms hematopoietic cells by exerting a wide variety of biological effects, including reduction in growth factor dependence, enhanced viability, and altered adhesion of chronic myelocytic leukemia (CML) cells. Elevated tyrosine kinase activity of BCR-ABL is critical for activating downstream signalling cascades and for all aspects of transformation, explaining the remarkable clinical efficacy of the tyrosine kinase inhibitor, imatinib mesylate (ST1571). By comparison, FLT3 is mutated in about one third of all cases of AML, most often through a mechanism that involves an internal tandem duplication (ITD) of a small number of amino acid residues in the juxtamembra ne domain of the receptor. As is the case for BCR-ABL, these mutations activate the kinase activity constitutively, activate multiple signaling pathways, and result in an augmentation of proliferation and viability. Transformation by FLT3-ITD can readily be observed in murine models, and FLT3 cooperates with-other types of oncogenes to create a fully transformed acute leukemia. FLT3 tyrosine kinase inhibitors are currently being evaluated in clinical trials and may be very useful. therapeutic agents in AML. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. RI Scheijen, Blanca/E-3523-2016 OI Scheijen, Blanca/0000-0001-8029-9230 NR 166 TC 21 Z9 21 U1 0 U2 4 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47762-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 532 BP 121 EP 140 PG 20 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BX19E UT WOS:000184568400011 PM 12908554 ER PT S AU George, D AF George, D BE LlombartBosch, A Felipo, V TI Targeting PDGF receptors in cancer - Rationales and proof of concept clinical trials SO NEW TRENDS IN CANCER FOR THE 21ST CENTURY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Cancer Symposium on New Trends in Cancer for the 21st Century CY NOV 10-13, 2002 CL VALENCIA, SPAIN ID GROWTH-FACTOR RECEPTORS; GASTROINTESTINAL STROMAL TUMORS; CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; FACTOR-B CHAINS; PROSTATE-CANCER; BETA-RECEPTOR; FACTOR-A; ALPHA-RECEPTOR; PHASE-II AB The platelet-derived growth factors (PDGF) are a pleotrophic family of peptide growth factors that signal through cell surface, tyrosine kinase receptors (PDGFR) and stimulate various cellular functions including growth, proliferation, and differentiation. To date, PDGF expression has been demonstrated in a number of different solid tumors, from glioblastomas to prostate carcinomas. In these various tumor types, the biologic role of PDGF signaling can vary from autocrine stimulation of cancer cell growth to subtler paracrine interactions involving adjacent stroma. and vasculature. The tyrosine kinase inhibitor imatinib mesylate (formerly ST1571, Gleevec(TM), Novartis Pharmaceuticals Corp, East Hanover, NJ) blocks activity of the Bcr-Abl oncoprotein and the cell surface tyrosine kinase receptor c-Kit, and as such was recently approved for several indications in the treatment on chronic myeloid leukemia and gastrointestinal stromal tumors. In both of these examples the target protein was identified by an oncogenic, activating mutation. Imatinib mesylate is also a potent inhibitor of PDGFR kinase and is currently being evaluated for the treatment of chronic myelomonocytic leukemia and glioblastoma multiforme, based upon evidence in these diseases of activating mutations in PDGFR. However, the PDGF pathway may represent a therapeutic target in other solid tumors in which it is not part of the oncogenic transformation. In order to investigate the potential biologic implications of inhibiting PDGFR in these tumor types, clinical trials that investigate both established clinical endpoints of response and benefit, as well as surrogate endponits that describe the biologic significance of PDGF inhibition in vivo are needed. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP George, D (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 33 TC 52 Z9 54 U1 1 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47762-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 532 BP 141 EP 151 PG 11 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BX19E UT WOS:000184568400012 PM 12908555 ER PT J AU Vaglio, P Lamesch, P Reboul, J Rual, JF Martinez, M Hill, D Vidal, M AF Vaglio, P Lamesch, P Reboul, J Rual, JF Martinez, M Hill, D Vidal, M TI WorfDB: the Caenorhabditis elegans ORFeome database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID FUNCTIONAL GENOMIC ANALYSIS; C-ELEGANS; GENES; RNAI AB WorfDB (Worm ORFeome DataBase; http://worfdb.dfci.harvard.edu) was created to integrate and disseminate the data from the cloning of complete set of similar to19000 predicted protein-encoding Open Reading Frames (ORFs) of Caenorhabditis elegans ( also referred to as the 'worm ORFeome'). WorfDB serves as a central data repository enabling the scientific community to search for availability and quality of cloned ORFs. So far, ORF sequence tags (OSTs) obtained for all individual clones have allowed exon structure corrections for similar to3400 ORFs originally predicted by the C. elegans sequencing consortium. In addition, we now have OSTs for similar to4300 predicted genes for which no ESTs were available. The database contains this OST information along with data pertinent to the cloning process. WorfDB could serve as a model database for other metazoan ORFeome cloning projects. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Smith 858,1 Jimmy Fund Way, Boston, MA 02115 USA. EM philippe_vaglio@dfci.harvard.edu; marc_vidal@dfci.harvard.edu RI Hill, David/B-6617-2011; Reboul, Jerome/P-9103-2016; OI Reboul, Jerome/0000-0002-5513-4546; Vaglio, Philippe/0000-0003-2900-5596; Rual, Jean-Francois/0000-0003-4465-8819 FU NCI NIH HHS [7 R33 CA81658-02]; NHGRI NIH HHS [5R01HG01715-02, R01 HG001715]; PHS HHS [232] NR 18 TC 28 Z9 28 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2003 VL 31 IS 1 BP 237 EP 240 DI 10.1093/nar/gkg092 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 647EP UT WOS:000181079700054 PM 12519990 ER PT J AU Benedict, S AF Benedict, S TI The nadir of nursing: Nurse-perpetrators of the Ravensbruck concentration camp SO NURSING HISTORY REVIEW LA English DT Article C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Benedict, S (reprint author), Med Univ S Carolina, 99 Jonathan Lucas St, Charleston, SC 29425 USA. NR 3 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER PUBLISHING CO PI NEW YORK PA 536 BROADWAY, NEW YORK, NY 10012 USA SN 1062-8061 J9 NURS HIST REV JI Nurs. Hist. Rev. PY 2003 VL 11 BP 129 EP 146 PG 18 WC History & Philosophy Of Science; History Of Social Sciences; Nursing SC History & Philosophy of Science; Social Sciences - Other Topics; Nursing GA 607DC UT WOS:000178775200008 PM 12418154 ER PT J AU Bandera, EV Kushi, LH Olson, SH Chen, WY Muti, P AF Bandera, EV Kushi, LH Olson, SH Chen, WY Muti, P TI Alcohol consumption and endometrial cancer: Some unresolved issues SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID UNITED-STATES ADULTS; BREAST-CANCER; POSTMENOPAUSAL WOMEN; CIGARETTE-SMOKING; ESTROGEN-LEVELS; NUTRIENT INTAKE; BODY-WEIGHT; LIFE-STYLE; RISK; DIET AB The role of hormonal factors, in particular unopposed estrogens, on endometrial cancer occurrence is well established. Progesterone deficiency has also been suggested as a possible risk factor Alcohol use has been shown to be associated with elevated estrogen levels and reduced progesterone. Epidemiologic studies, however have not offered much support for a positive association between alcohol intake and endometrial cancer, with results generally indicating no association or suggesting an inverse relationship with endometrial cancer However, certain methodologic limitations, such as small sample size, limited range of alcohol intake, and confounding may have explained those findings. Moreover, there are some unexplored aspects of the possible effect of alcohol, such as the possible interaction with use of exogenous estrogens, and other factors, that need clarification. C1 SUNY Buffalo, Sch Med & Biomed Sci, Dept Social & Prevent Med, Buffalo, NY 14214 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Kaiser Permanente, Div Res, Oakland, CA 94611 USA. Rutgers State Univ, Dept Nutrit Sci, New Brunswick, NJ 08901 USA. RP Bandera, EV (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Surg Oncol,Dept Surg, Canc Inst New Jersey, 195 Little Albany St, New Brunswick, NJ 08901 USA. RI Bandera, Elisa/M-4169-2014; OI Bandera, Elisa/0000-0002-8789-2755; Kushi, Lawrence/0000-0001-9136-1175 NR 37 TC 12 Z9 12 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2003 VL 45 IS 1 BP 24 EP 29 DI 10.1207/S15327914NC4501_3 PG 6 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 691CL UT WOS:000183587200003 PM 12791501 ER PT J AU Learman, LA Gerrity, MS Field, DR van Blaricom, A Romm, J Choe, J AF Learman, LA Gerrity, MS Field, DR van Blaricom, A Romm, J Choe, J TI Effects of a depression education program on residents' knowledge, attitudes, and clinical skills SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PRIMARY-CARE PHYSICIANS; RECOGNITION; INSTRUMENTS; MANAGEMENT; DISORDERS; PATIENT AB OBJECTIVE: To determine whether an interactive educational program would improve obstetrics and gynecology residents' knowledge, attitudes, confidence, and skills in caring for depressed patients. METHODS: We recruited 74 residents from eight residency programs to attend the Depression Education Program, which consists of a 1-hour lecture and two 2-hour workshops combining discussion, diagnosis and treatment tools, critique of a videotape, practice with feedback, and audio-tape self-assessment. Before and after the program, participants 1) completed a questionnaire measuring knowledge, attitudes, and reported actions taken with a recent depressed patient; 2) received a standardized patient visit; and 3) kept lists of patients they suspected were depressed. Clinic patients completed a depression screening questionnaire. To assess improvement, we used paired t tests, Mc-Nemar chi(2) tests, and multivariate models adjusting for training site. RESULTS: The education program led to 3-month improvements in participants' reported use of formal diagnostic criteria (38% before, 66% after; P = .004), clinical actions documented for suspected depression (P = .035), and perceived self-efficacy in depression care (P < .001). Perceived preparedness to diagnose depression, treat with medications, and comanage with a mental health practitioner improved (P < .05 for each). Small improvements in clinical behaviors with standardized patients and clinic-based depression detection rates were not statistically significant. CONCLUSION: The Depression Education Program improved residents' knowledge, confidence, and reported clinical actions with depressed patients, but did not improve most objectively assessed outcomes. (C) 2003 by The American College of Obstetricians and Gynecologists. C1 Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. Portland Vet Affairs Med Ctr, Div Hosp & Specialty Med, Portland, OR USA. Kaiser Permanente Med Ctr, Dept Obstet & Gynecol, San Francisco, CA USA. Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR USA. RP Learman, LA (reprint author), San Francisco Gen Hosp, Dept Obstet & Gynecol, 1001 Potrero St,Room 6D-9, San Francisco, CA 94110 USA. NR 23 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2003 VL 101 IS 1 BP 167 EP 174 AR PII S0029-7844(02)02510-3 DI 10.1016/S0029-7844(02)02510-3 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 632UN UT WOS:000180241800029 PM 12517663 ER PT J AU Campos, S AF Campos, S TI Liposomal anthracyclines: Adjuvant and neoadjuvant therapy for breast cancer SO ONCOLOGIST LA English DT Article DE anthracyclines; liposome; adjuvant chemotherapy; neoadjuvant therapy; breast neoplasms ID PHASE-II TRIAL; DOXORUBICIN-CONTAINING THERAPY; ENCAPSULATED DOXORUBICIN; RANDOMIZED-TRIAL; COMBINATION CHEMOTHERAPY; CONVENTIONAL DOXORUBICIN; MULTICENTER TRIAL; CYCLOPHOSPHAMIDE; FLUOROURACIL; CARDIOPROTECTION AB Conventional anthracyclines, particularly doxorubicin, have played an important role in the treatment of patients with breast cancer for many decades. Conventional doxorubicin has shown excellent antitumor activity in the metastatic, neoadjuvant, and adjuvant settings. However, its clinical utility is limited due to acute and chronic toxicities, particularly cardiotoxicity, myelosuppression, nausea and vomiting, and alopecia. Liposomal doxorubicin formulations (liposomal doxorubicin [D-99] and pegylated liposomal doxorubicin) currently under investigation for the treatment of breast cancer have demonstrated similar efficacies and favorable toxicity profiles compared with conventional doxorubicin in patients with metastatic breast cancer. These agents have also shown efficacy and tolerability in several small studies as neoadjuvant therapy in patients with locally advanced breast cancer. While there are currently no studies with liposomal doxorubicin or pegylated liposomal doxorubicin as adjuvant therapy, their demonstrated activities and tolerabilities in the metastatic and neoadjuvant settings provide the rationale for the future study of these agents in adjuvant therapy for patients with early-stage breast cancer. C1 Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Campos, S (reprint author), Brigham & Womens Canc Ctr, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 37 TC 19 Z9 19 U1 0 U2 1 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2003 VL 8 SU 2 BP 10 EP 16 PG 7 WC Oncology SC Oncology GA 724YF UT WOS:000185515300003 PM 13679591 ER PT J AU Haddad, R Tishler, RB Norris, CM Mahadevan, A Busse, P Wirth, L Goguen, LA Sullivan, CA Costello, R Case, MA Posner, MR AF Haddad, R Tishler, RB Norris, CM Mahadevan, A Busse, P Wirth, L Goguen, LA Sullivan, CA Costello, R Case, MA Posner, MR TI Docetaxel, cisplatin, 5-fluorouracil (TPF)-based induction chemotherapy for head and neck cancer and the case for sequential, combined-modality treatment SO ONCOLOGIST LA English DT Article DE head and neck cancer; chemoradiotherapy; sequential chemoradiotherapy ID SQUAMOUS-CELL CARCINOMA; LOCALLY ADVANCED HEAD; PROSPECTIVE RANDOMIZED TRIAL; PHASE-III TRIAL; RADIATION-THERAPY; CONCOMITANT CHEMORADIOTHERAPY; ONCOLOGY-GROUP; STAGE-III; I-II; RADIOTHERAPY AB Since the publication of the Veterans Affairs study in the early 1990s, much has been learned regarding the role of chemotherapy, radiation therapy, and more importantly, the role of combined-modality treatment with chemoradiation in the therapy of locally advanced head and neck cancer. There continues to be widespread variation and controversy in the timing, schedule, and intensity of chemotherapy and chemoradiation. Herein, we present the various approaches currently used in the year 2003 with a specific emphasis on the role of sequential combined-modality therapy combining chemotherapy, chemoradiotherapy, and surgery in the treatment of these malignancies. C1 Dana Farber Canc Inst, Head & Neck Oncol Program, Dept Adult Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Boston, MA 02115 USA. RP Posner, MR (reprint author), Dana Farber Canc Inst, Head & Neck Oncol Program, Dept Adult Oncol, 44Binney St, Boston, MA 02115 USA. NR 53 TC 39 Z9 42 U1 0 U2 1 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2003 VL 8 IS 1 BP 35 EP 44 DI 10.1634/theoncologist.8-1-35 PG 10 WC Oncology SC Oncology GA 646UZ UT WOS:000181055100005 PM 12604730 ER PT J AU Ebert, BL Niemierko, E Shaffer, K Salgia, R AF Ebert, BL Niemierko, E Shaffer, K Salgia, R TI Use of temozolomide with other cytotoxic chemotherapy in the treatment of patients with recurrent brain metastases from lung cancer SO ONCOLOGIST LA English DT Article DE temozolomide; lung cancer; brain metastases ID PHASE-II TRIAL; SYSTEMIC CHEMOTHERAPY; CEREBRAL METASTASES; MALIGNANT-MELANOMA; CARCINOMA; ETOPOSIDE; RADIOTHERAPY; IRRADIATION; TENIPOSIDE; CISPLATIN AB The use of chemotherapy for the treatment of brain metastases arising from lung cancer has been limited by poor efficacy and high toxicity. Temozolomide, an orally bioavailable alkylating agent that crosses the blood-brain barrier, has activity against brain metastases from both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) when used as a single agent, but response rates are low. Preclinical experiments and early clinical studies in other malignancies indicate that temozolomide may have additive or synergistic effects when used with other chemotherapeutic agents. We report a case of a patient with SCLC with recurrent brain metastases after treatment with multiple chemotherapeutic regimens and whole-brain radiation therapy (WBRT) who was treated with temozolomide (150 Mg/m(2) for 5 days in a 28-day cycle) and oral etoposide (50 mg/m(2) for 10 days in a 28-day cycle). A second patient with NSCLC and brain metastases who progressed after treatment with chemotherapy and WBRT was treated with temozolomide (150 mg/m(2) for 5 days in a 28-day cycle) and gemcitabine (1,000 mg/m(2) weekly for 2 weeks in a 3-week cycle). In both patients, the temozolomide regimens were extremely well tolerated and resulted in dramatic and durable responses. The combination of temozolomide with other chemotherapeutic agents represents a promising strategy for treating patients with lung cancer and recurrent brain metastases and merits further study. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Commonwealth Hematol Oncol, Concord, MA USA. RP Salgia, R (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Adult Oncol, D1234B,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [T32 CA009172] NR 34 TC 26 Z9 34 U1 1 U2 2 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2003 VL 8 IS 1 BP 69 EP 75 DI 10.1634/theoncologist.8-1-69 PG 7 WC Oncology SC Oncology GA 646UZ UT WOS:000181055100008 PM 12604733 ER PT J AU Knuti, KA Wharton, RH Wharton, KL Chabner, BA Lynch, TJ Penson, RT AF Knuti, KA Wharton, RH Wharton, KL Chabner, BA Lynch, TJ Penson, RT TI Living as a cancer surpriser: A doctor tells his story SO ONCOLOGIST LA English DT Article DE prognosis; palliative care; hospice; death; living AB Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to the caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers and gain insight and support from fellow staff members. We tell the story of one physician with incurable non-small cell lung cancer (NSCLC) who had an unexpectedly favorable response to an experimental treatment while receiving it as a part of his palliative care. His unique insight provides an opportunity to elucidate some of the issues that arise from living both as a patient-caregiver and as a cancer "surpriser." When caregivers face their own cancer, their reflections as patient-caregivers offer an internal perspective on the illness experience and help us as fellow caregivers to better understand and support all patients who face serious illnesses, both those who are colleagues and those who are not. Just like any patient with cancer, patient-caregivers experience the dramatic changes in health, daily life, and perspective that come with serious illness. Within the context of a life-threatening illness, caregiver-patients and their families search for new meaning as they face an uncertain future and address the issues of life and death. In addition to such processes, patient-caregivers with cancer also find that their own medical knowledge and their colleagues' reactions shape their experiences and to an extent separate them from those of other patients. C1 Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Cox 548,100 Blossom St, Boston, MA 02114 USA. NR 19 TC 9 Z9 9 U1 2 U2 7 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2003 VL 8 IS 1 BP 108 EP 122 DI 10.1634/theoncologist.8-1-108 PG 15 WC Oncology SC Oncology GA 646UZ UT WOS:000181055100012 PM 12604737 ER PT J AU Penson, RT Nunn, C Younger, J Schaeffer, NJ Chabner, BA Fricchione, GL Quinn, TE Lynch, TJ AF Penson, RT Nunn, C Younger, J Schaeffer, NJ Chabner, BA Fricchione, GL Quinn, TE Lynch, TJ TI Trust violated: Analgesics for addicts SO ONCOLOGIST LA English DT Article DE oncology; support; psychosocial; opioids; morphine ID CANCER PAIN MANAGEMENT; DRUG-USERS; KNOWLEDGE; ATTITUDES; DIVERSION; OPIOIDS; CARE AB Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (NIGH), founded The Kenneth B. Schwartz Center at MGH. The. Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Addiction among cancer patients on strong analgesics is a rare but difficult management challenge. The case is presented of a 28-year-old woman with breast cancer and painful bone metastases, suffering with dysfunctional social chaos and addicted to Percocet(R) (oxyrodone and acetaminophen). Having broken the trust of her health care team, trust was rebuilt by incorporating the substance abuse clinic and enforcing a contractual agreement. With open and honest support, the team was able to both care for and empower the patient. Issues of trust, liability, opioid tolerance, and barriers to optimal analgesia for cancer pain are discussed. C1 Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Cox 548,100 Blossom St, Boston, MA 02114 USA. NR 23 TC 2 Z9 2 U1 2 U2 4 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2003 VL 8 IS 2 BP 199 EP 209 DI 10.1634/theoncologist.8-2-199 PG 11 WC Oncology SC Oncology GA 666VR UT WOS:000182197600008 PM 12697944 ER PT J AU Frei, E AF Frei, E TI BJ Kennedy, MD - In memoriam SO ONCOLOGIST LA English DT Biographical-Item C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Frei, E (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2003 VL 8 IS 4 BP 302 EP 302 DI 10.1634/theoncologist.8-4-302 PG 1 WC Oncology SC Oncology GA 707GG UT WOS:000184502000001 ER PT J AU Penson, RT Fergus, LA Haston, RJ Clark, JR Demotses, A O'Connell, JJ Chabner, BA Lynch, TJ AF Penson, RT Fergus, LA Haston, RJ Clark, JR Demotses, A O'Connell, JJ Chabner, BA Lynch, TJ TI The Kenneth B. Schwartz Center at Massachusetts General Hospital Hematology-Oncology Department: Hope for the homeless SO ONCOLOGIST LA English DT Article DE oncology; support; psychosocial; communication ID NEW-YORK-CITY; PHARYNGEAL CANCER; HEALTH-INSURANCE; SOCIAL SUPPORT; UNITED-STATES; NECK-CANCER; ADULTS; HEAD; PHILADELPHIA; MORTALITY AB Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (NIGH), founded the Kenneth B. Schwartz Center at NIGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient and support to caregivers and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum during which caregivers discuss a specific cancer patient, reflect on the important psychological issues faced by patients, their families, and their caregivers, and gain insight and support from their fellow staff members. A homeless man with head and neck cancer presents to the emergency room: a sad and familiar story. But this story is redeemed by his 35-year friendship with a priest, a man whose unconditional love and support became critical to the patient's care and treatment. The patient had lived for 30 years in homeless shelters, had problems with alcohol abuse, and was notoriously noncompliant with medical caregivers. He could not speak due to his disease, was illiterate with limited intellectual capacity, and had neither a job nor a family. Despite huge and apparently insurmountable problems for the patient, the oncology team was able to carve out a package of care, successfully communicate, and mobilize a support network to allow successful completion of chemoradiation therapy. The team developed a strong commitment to his care and an affectionate bond, which very positively affected all of Hope for the Homeless those involved. We discuss issues of access to cancer care, and the special problems presented by homeless patients. C1 Massachusetts Gen Hosp, Div Hematol & Oncol, Dept Med, Boston, MA 02114 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Cox 548,100 Blossom St, Boston, MA 02114 USA. NR 31 TC 3 Z9 3 U1 2 U2 5 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2003 VL 8 IS 5 BP 488 EP 495 DI 10.1634/theoncologist.8-5-488 PG 8 WC Oncology SC Oncology GA 729YR UT WOS:000185802900010 PM 14530502 ER PT J AU Ballantyne, JC AF Ballantyne, JC TI Chronic pain following treatment for cancer: The role of opioids SO ONCOLOGIST LA English DT Article DE narcotics; pain; neoplasms; opioid-related disorders ID CHRONIC NONMALIGNANT PAIN; PLACEBO-CONTROLLED TRIAL; NEUROPATHIC PAIN; MORPHINE-TOLERANCE; POSTHERPETIC NEURALGIA; DRIVING ABILITY; THERAPY; METHADONE; ANALGESICS; MANAGEMENT AB Opioids are the most effective analgesics for severe pain and the mainstay of acute and terminal cancer pain treatments. In those settings, opioids are used over a limited time period so that opioid tolerance, if it develops, is relatively easy to overcome, and other problems of opioid use, including substance abuse, are unlikely to be problematic. As cancer treatments improve and increasing numbers of cancer patients experience long remissions, chronic pain due to cancer, or to cancer treatment, becomes a clinical problem that oncologists will encounter. Chronic pain differs from acute and terminal pain in several fundamental respects. In the case of chronic pain, functional restoration is a predominant goal of treatment. Because it is often due to neuronal damage, the pain may be particularly sensitive to nonopioid medications, and opioids can be reserved for refractory pain. If opioids are chosen, tolerance, dependence, and addiction can interfere, and safeguards designed to minimize these must be built into the treatment plan. This article reviews the principles of chronic opioid therapy for non-cancer pain and how these principles may be adapted for patients with chronic pain due to cancer. C1 Massachusetts Gen Hosp, Pain Ctr, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ballantyne, JC (reprint author), Massachusetts Gen Hosp, Pain Ctr, Dept Anesthesia & Crit Care, 15 Parkman St,WACC 333, Boston, MA 02114 USA. NR 54 TC 23 Z9 24 U1 0 U2 1 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2003 VL 8 IS 6 BP 567 EP 575 DI 10.1634/theoncologist.8-6-567 PG 9 WC Oncology SC Oncology GA 748LG UT WOS:000186862900011 PM 14657535 ER PT J AU Dias, L Chabner, BA Lynch, TJ Penson, RT AF Dias, L Chabner, BA Lynch, TJ Penson, RT TI Breaking bad news: A patient's perspective SO ONCOLOGIST LA English DT Article DE oncology; support; psychosocial; communication care ID CANCER-PATIENTS; COMMUNICATION-SKILLS AB Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Clinicians in the field of oncology are unavoidably forced to break bad news. The Schwartz Center Rounds focuses on issues of communication between patients and their caregivers, one of the most difficult aspects of which is breaking bad news. The invited patient, a woman who had been living with a low-grade cancer for many years, spoke about her experiences both as a person living with cancer and as the daughter of a patient diagnosed with cancer. Her father's suicide, precipitated by being told his diagnosis, puts the horror of receiving bad news into stark relief. She provides a fascinating account of how she proactively adjusted to her diagnosis, and fought for optimal quality of life. This article discusses issues of support, abandonment, and how hope is conveyed, and reviews the literature that informs good clinical practice in breaking bad news. C1 Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Cox 548,100 Blossom St, Boston, MA 02114 USA. NR 30 TC 35 Z9 38 U1 5 U2 12 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2003 VL 8 IS 6 BP 587 EP 596 DI 10.1634/theoncologist.8-6-587 PG 10 WC Oncology SC Oncology GA 748LG UT WOS:000186862900013 PM 14657537 ER PT J AU Campos, SM Winer, EP AF Campos, SM Winer, EP TI Hormonal therapy in postmenopausal women with breast cancer SO ONCOLOGY LA English DT Review DE antiaromatase agents; breast cancer; hormonal therapy ID SURGICAL-ADJUVANT-BREAST; FIRST-LINE THERAPY; MULTICENTER RANDOMIZED TRIAL; PHASE-II TRIAL; AROMATASE INHIBITORS; MEGESTROL-ACETATE; ENDOCRINE THERAPY; DOUBLE-BLIND; MEDROXYPROGESTERONE ACETATE; PREMENOPAUSAL WOMEN AB The treatment of postmenopausal women with breast cancer presents a number of challenges. Tamoxifen has had a substantial impact on mortality in women with early-stage, estrogen-receptor-positive tumors. Despite the improvement in the treatment of breast cancer, many patients will ultimately experience a recurrence. Present treatment approaches can provide effective palliation in the advanced disease setting, but, at best, there has been a modest impact on survival. Numerous options are now available to provide effective palliation for patients with advanced disease. These options include antiestrogens, pure antiestrogens, aromatase inhibitors and progestins and LHRH agonists. Recently, several studies have reviewed the efficacy of aromatase inhibitors as first-line agents in postmenopausal women. Anastrozole and letrozole have recently been approved as first-line agents in women with metastatic breast cancer. In addition to their role in metastatic breast, trials investigating the potential of aromatase inhibitors in the early breast cancer, both in the adjuvant and neoadjuvant setting are underway. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Campos, SM (reprint author), Dana Farber Canc Inst, 44 Binney St,Rm D1242, Boston, MA 02115 USA. NR 104 TC 20 Z9 20 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2003 VL 64 IS 4 BP 289 EP 299 DI 10.1159/000070284 PG 11 WC Oncology SC Oncology GA 681TA UT WOS:000183050400001 PM 12759523 ER PT J AU Fujishita, T Loda, M Turner, RE Gentler, M Kashii, T Breathnach, OS Johnson, BE AF Fujishita, T Loda, M Turner, RE Gentler, M Kashii, T Breathnach, OS Johnson, BE TI Sensitivity of non-small-cell lung cancer cell lines established from patients treated with prolonged infusions of paclitaxel SO ONCOLOGY LA English DT Article DE carcinoma; non-small-cell lung neoplasm; docetaxel; paclitaxel; multidrug resistance; HER2/neu ID PHASE-II TRIAL; 96-HOUR CONTINUOUS-INFUSION; HER-2/NEU GENE-EXPRESSION; PROSTATE-CANCER; OVARIAN-CANCER; PROTEIN MRP; CISPLATIN; CYTOTOXICITY; TAXOTERE; TAXOL AB Objective: Regimens with prolonged infusions of taxanes have been developed for patients with cancer to overcome drug resistance. Our objective of the present study was to examine the impact of prolonged exposure on the cytotoxicity of taxanes against non-small-cell lung carcinoma (NSCLC) cell lines and the clinical response and outcome of the patients. Methods: Five cell lines (NCl-H2882, -H2887, -H2973, -H3122, -H3255) were derived from previously untreated patients with NSCLC who participated in clinical trials of continuous 96-hour infusions of paclitaxel followed by bolus cisplatin. Two additional cell lines (NCl-H838, -H1299) with previously published data were used as controls. Drug sensitivities were assessed by the MTS (Promega) assay. Multidrug resistance (MDR) phenotypes were assessed by quantitative real-time PCR and HER-2/neu by both immunohistochemistry and ELISA. Results: The median of mean IC50 values of docetaxel at the exposure durations of 3, 24, 72 and 120 h were 0.52, 0.06, 0.03 and 0.06 muM, respectively. The median of mean IC50 values of paclitaxel at the exposure duration of 3, 24, 72 and 120 h were 0.48, 0.13, 0.03 and 0.02 muM, respectively. In all cell lines studied, there was a less than 4-fold difference in the IC50 values between docetaxel and paclitaxel at 3-, 72-, and 120-hour exposure times. The single cell line with moderate MDR1 expression (NCl-H2887) was the only cell line established from a patient with progressive disease when treated with paclitaxel. Conclusions: This study demonstrates prolonged exposure to both docetaxel and paclitaxel inhibits the growth of NSCLC cell lines in similar fashion. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Natl Canc Inst, Bethesda, MD USA. Toyama Med & Pharmaceut Univ, Dept Internal Med 1, Toyama, Japan. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Adult Oncol, Dana 1234,44 Binney St, Boston, MA 02115 USA. NR 30 TC 13 Z9 15 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2003 VL 64 IS 4 BP 399 EP 406 DI 10.1159/000070299 PG 8 WC Oncology SC Oncology GA 681TA UT WOS:000183050400016 PM 12759538 ER PT J AU Ficorella, C Cannita, K Ricevuto, E Toniato, E Fusco, C Sinopoli, NT De Galitiis, F Di Rocco, ZC Porzio, G Frati, L Gulino, A Martinotti, S Marchetti, P AF Ficorella, C Cannita, K Ricevuto, E Toniato, E Fusco, C Sinopoli, NT De Galitiis, F Di Rocco, ZC Porzio, G Frati, L Gulino, A Martinotti, S Marchetti, P TI P16 hypermethylation contributes to the characterization of gene inactivation profiles in primary gastric cancer SO ONCOLOGY REPORTS LA English DT Article DE gastric cancer; p16 methylation; CpG islands; p53 ID SQUAMOUS-CELL CARCINOMA; ISLAND METHYLATOR PHENOTYPE; KINASE-4 INHIBITOR GENE; MICROSATELLITE INSTABILITY; FAMILIAL MELANOMA; HOMOZYGOUS DELETION; P53 MUTATIONS; SUPPRESSOR; P16(INK4A); CDKN2 AB The objective of this study was to investigate the contribution of p16 inactivation in gastric cancer and to compare it with p53. A cohort of 34 primary GCs were analyzed for p16 mutations and transcriptional silencing of the gene due to hypermethylation of the promoter. SSCP analysis and direct sequencing of exons 1 and 2 of the p16 gene were performed to detect any structural alterations. The methylation specific PCR (MSP) assay was applied to reveal hypermethylation of the 'CpG' island in the regulatory region using specific primer pairs for methylated and unmethylated nucleotides after a chemical reaction converting cytosines into uracile when unmethylated. SSCP and direct sequencing analysis did not detect any p16 mutations. The MSP assay showed 4 MSP+ variants (11.8%). Three MSP+ were stage III-IV disease and 1 MSP+ was detected in an early stage disease (1B). All MSP+ were diffuse type adenocarcinomas. The MSP+ samples were different from previously reported samples harboring p53 mutations in the same cohort. These data increase the number of gastric cancers showing alterations of either p53 or p16 to 29.4% (10/34). Functional inactivation by hypermethylation of the p16 locus and p53 mutations could play a significant, complementary role in the pathogenesis of sporadic gastric cancer. C1 Univ Aquila, Dipartimento Med Sperimentale, I-67100 Laquila, Italy. Harvard Univ, Massachusetts Gen Hosp, CBRC, Dept Dermatol, Boston, MA 02129 USA. Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy. Neuromed Inst, Pozzilli, Isernia, Italy. RP Ficorella, C (reprint author), Univ Aquila, Dipartimento Med Sperimentale, Via Vetoio,Coppito II, I-67100 Laquila, Italy. RI Marchetti, Paolo/K-1469-2016; OI RICEVUTO, Enrico/0000-0001-5641-3187 NR 33 TC 6 Z9 10 U1 1 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD JAN-FEB PY 2003 VL 10 IS 1 BP 169 EP 173 PG 5 WC Oncology SC Oncology GA 625NP UT WOS:000179822800031 PM 12469165 ER PT J AU Huang, CM Meyer, DR Patrinely, JR Soparkar, CNS Dailey, RA Maus, M Rubin, PAD Yeatts, RP Bersani, TA Karesh, JW Harrison, AR Shovlin, JP AF Huang, CM Meyer, DR Patrinely, JR Soparkar, CNS Dailey, RA Maus, M Rubin, PAD Yeatts, RP Bersani, TA Karesh, JW Harrison, AR Shovlin, JP TI Medial rectus muscle injuries associated with functional endoscopic sinus surgery - Characterization and management SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the American-Society-of-Ophthalmic-Plastic-and-Reconstructive-Surgery CY NOV, 2001 CL NEW ORLEANS, LOUISIANA SP Amer Soc Ophthalm Plast & Reconstruct Surg ID ANTERIOR CILIARY VESSELS; ORBITAL COMPLICATIONS; MAJOR COMPLICATIONS; OPHTHALMIC COMPLICATIONS; STRABISMUS SURGERY; SECONDARY; PRESERVATION AB Objective: To characterize and evaluate treatment options for medial rectus muscle (MR) injury associated with functional endoscopic sinus surgery (FESS). Design: Retrospective interventional case series Participants: A total of 30 cases were gathered from 10 centers. Methods: Cases of orbital MR injury associated with FESS surgery, were solicited from members of the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) through an e-mail discussion group. Main Outcome Measures: Variables assessed included patient demographics. computerized tomography and operative findings. extent of MR injury and entrapment, secondary orbital/ocular injuries. initial and final ocular alignment and ductions, and interventions. Results: A spectrum of MR injury ranging from simple contusion to complete MR transection. with and without entrapment. was observed. Four general patterns of presentation and corresponding injury were categorized, Conclusions: Medial rectus muscle injury as a complication of FESS can vary markedly. Proper characterization and treatment are important. particularly with reference to the degree of direct MR injury, (muscle tissue loss) and entrapment. Patients with severe MR disruption can benefit from intervention but continue to show persistent limitation of ocular motility and functional impairment. Prevention and early recognition and treatment of these injuries are emphasized. C1 Albany Med Coll, Dept Ophthalmol, Albany, NY 12208 USA. Plast Eye Surg Associates PLLC, Houston, TX USA. Casey Eye Inst, Portland, OR USA. Wills Eye Hosp & Res Inst, Philadelphia, PA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Wake Forest Univ, Ctr Eye, Winston Salem, NC 27109 USA. Eye Plast & Reconstruct Surg CNY, Syracuse, NY USA. Sinai Hosp, Krieger Eye Inst, Baltimore, MD 21215 USA. Univ Minnesota, Minneapolis, MN USA. Geisinger Med Clin, Ophthalmol Clin, Danville, PA USA. RP Meyer, DR (reprint author), Albany Med Ctr, Lions Eye Inst, 35 Hackett Blvd, Albany, NY 12208 USA. NR 37 TC 32 Z9 37 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHALMIC PLAST REC JI Ophthalmic Plast. Reconstr. Surg. PD JAN PY 2003 VL 19 IS 1 BP 25 EP 37 DI 10.1097/01.IOP.0000031378.02394.45 PG 13 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 636XE UT WOS:000180481900004 PM 12544790 ER PT S AU Alt, C Pitsillides, CM Roegener, J Lin, CP AF Alt, C Pitsillides, CM Roegener, J Lin, CP BE Manns, F Soderberg, PG Ho, A TI Monitoring intracellular cavitation during selective targeting of the retina pigment epithelium SO OPHTHALMIC TECHNOLOGIES XIII SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 13th Conference on Ophthalmic Technologies CY JAN 25-26, 2003 CL SAN JOSE, CA SP SPIE DE selective retinal photocoagulation; retinal pigment epithelium; melanosomes; cavitation; bubble formation; laser scanner; slit lamp; online detection of cell death; back scatter ID PHOTOCOAGULATION; DAMAGE AB PURPOSE Selective targeting of the Retinal Pigment Epithelium (RPE), by either applying trains of microsecond laser pulses or, in our approach, by repetitively scanning a tightly focused spot across the retina, achieves destruction of RPE cells while avoiding damage to the overlying photoreceptors. Both techniques have been demonstrated as attractive methods for the treatment of retinal diseases that are caused by a dysfunction of the RPE. Because the lesions are ophthalmoscopically invisible, an online control system that monitors cell death during irradiation is essential to ensure efficient and selective treatment in a clinical application. MATERIALS AND METHODS Bubble formation inside the RPE cells has been shown to be the cell damage mechanism for nano- and picosecond pulses. We built an optical system to investigate whether the same mechanism extends into the microsecond regime. The system detects changes in backscattered light of the irradiating beam during exposure. Samples of young bovine eyes were exposed in vitro using single pulses ranging from 3 mus to 50 mus. Using the viability assay calcein-AM the ED50 threshold for cell death was determined and compared to the threshold for bubble formation. We also set up a detection system on our slit lamp adapted scanning system in order to determine the feasibility of monitoring threshold RPE damage during selective laser treatment in vivo. RESULTS AND DISCUSSION Intracellular cavitation was detected as a transient increase in backscattering signal, either of an external probe beam or of the irradiation beam itself. Monitoring with the irradiation beam is both simpler and more sensitive. We found the threshold for bubble formation to coincide with the threshold for cell damage for pulse durations up to 20 mus, suggesting that cavitation is the main mechanism of cell damage. For pulse widths longer than 20 mus, the cell damage mechanism appears to be increasingly thermal as the two thresholds diverge. We conclude that bubble detection can be, used to monitor therapeutic endpoint for pulse durations up to 20 mus (or equivalent dwell time in a scanning approach). We have integrated a detection module into our slit lamp adapted laser scanner in order to determine threshold RPE damage during selective laser treatment in vivo. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Alt, C (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 17 TC 6 Z9 6 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4751-X J9 P SOC PHOTO-OPT INS PY 2003 VL 4951 BP 48 EP 55 DI 10.1117/12.477956 PG 8 WC Engineering, Biomedical; Ophthalmology; Optics SC Engineering; Ophthalmology; Optics GA BX31W UT WOS:000184938700007 ER PT J AU Dunn, AK Devor, A Bolay, H Andermann, ML Moskowitz, MA Dale, AM Boas, DA AF Dunn, AK Devor, A Bolay, H Andermann, ML Moskowitz, MA Dale, AM Boas, DA TI Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation SO OPTICS LETTERS LA English DT Article ID CORTICAL SPREADING DEPRESSION; LASER-DOPPLER; SPECKLE; CORTEX; SPECTROSCOPY; STIMULATION; SIGNALS; VOLUME; MODEL; BRAIN AB A simple instrument is demonstrated for high-resolution simultaneous imaging of total hemoglobin concentration and oxygenation and blood flow in the brain by combining rapid multiwavelength imaging with laser speckle contrast imaging. The instrument was used to image changes in oxyhemoglobin and deoxyhemoglobin and blood flow during cortical spreading depression and single whisker stimulation in rats through a thinned skull. The ability to image blood flow and hemoglobin concentration changes simultaneously with high resolution will permit detailed quantitative analysis of the spatiotemporal hemodynamics of functional brain activation, including imaging of oxygen metabolism. This is of significance to the neuroscience community and will lead to a better understanding of the interrelationship of neural, metabolic, and hemodynamic processes in normal and diseased brains. (C) 2003 Optical Society of America. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. RP Dunn, AK (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Stroke & Neurovasc Regulat Lab, 149 13th St, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Dale, Anders/A-5180-2010; Dunn, Andrew/I-9527-2014 FU NCRR NIH HHS [P41-RR14075]; NIBIB NIH HHS [R01 EB000790, R01EB00790-01A2]; NINDS NIH HHS [5K25NS041291] NR 17 TC 204 Z9 205 U1 4 U2 25 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD JAN 1 PY 2003 VL 28 IS 1 BP 28 EP 30 DI 10.1364/OL.28.000028 PG 3 WC Optics SC Optics GA 627JM UT WOS:000179930100009 PM 12656525 ER PT J AU Sowers, MR Finkelstein, JS Ettinger, B Bondarenko, I Neer, RM Cauley, JA Sherman, S Greendale, GA AF Sowers, MR Finkelstein, JS Ettinger, B Bondarenko, I Neer, RM Cauley, JA Sherman, S Greendale, GA TI The association of endogenous hormone concentrations and bone mineral density measures in pre- and perimenopausal women of four ethnic groups: SWAN SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE BMD; estradiol; FSH; menopause; menopause transition ID FOLLICLE-STIMULATING-HORMONE; PREMENOPAUSAL WOMEN; INHIBIN-B; PHYSICAL-ACTIVITY; DIMERIC INHIBIN; RISK-FACTORS; MASS; OVARIAN; MENOPAUSE; ENDOCRINOLOGY AB We evaluated bone mineral density (BMD), hormone concentrations and menstrual cycle status to test the hypothesis that greater variations in reproductive hormones and menstrual bleeding patterns in mid-aged women might engender an environment permissive for less bone. We studied 2336 women, aged 4252 years, from the Study of Women's Health Across the Nation (SWAN) who self-identified as African-American (28.2%), Caucasian (49.9%), Japanese (10.5%) or Chinese (11.4%). Outcome measures were lumbar spine, femoral neck and total hip BMD by dual-energy X-ray densitometry (DXA). Explanatory variables were estradiol, testosterone, sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) from serum collected in the early follicular phase of the menstrual cycle or menstrual status [premenopausal (menses in the 3 months prior to study entry without change in regularity) or early perimenopause (menstrual bleeding in the 3 months prior to study entry but some change in the regularity of cycles)]. Total testosterone and estradiol concentrations were indexed to SHBG for the Free Androgen Index (FAI) and the Free Estradiol Index (FEI). Serum logFSH concentrations were inversely correlated with BMD (r = -0.10 for lumbar spine [95% confidence interval (0): -0.13, -0.06] and r = -0.08 for femoral neck (95% Cl: -0.11, -0.05). Lumbar spine BMD values were approximately 0.5% lower for each successive FSH quartile. There were no significant associations of BMD with serum estradiol, total testosterone, FEI or FAI, respectively, after adjusting for covariates. BMD tended to be lower (p values = 0.009 to 0.06, depending upon the skeletal site) in women classified as perimenopausal versus premenopausal, after adjusting for covariates. Serum FSH but not serum estradiol, testosterone or SHBG were significantly associated with BMD in a multi-ethnic population of women classified as pre- versus perimenopausal, supporting the hypothesis that alterations in hormone environment are associated with BMD differences prior to the final menstrual period. C1 Univ Michigan, Dept Epidemiol, Sch Publ Hlth, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Div Geriatr, Sch Med, Los Angeles, CA USA. RP Sowers, MR (reprint author), Univ Michigan, Dept Epidemiol, Sch Publ Hlth, Rm 3073,SPH-1,109 Observ St, Ann Arbor, MI 48109 USA. RI Perez , Claudio Alejandro/F-8310-2010; Cauley, Jane/N-4836-2015 OI Perez , Claudio Alejandro/0000-0001-9688-184X; Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [U01 AG12531, U01 AG12495, U01 AG12546, U01 AG12553, U01 AG12554, U01 AG2539]; NINR NIH HHS [U01 NR04061] NR 40 TC 62 Z9 63 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD JAN PY 2003 VL 14 IS 1 BP 44 EP 52 DI 10.1007/s00198-002-1307-x PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 650FA UT WOS:000181251200007 PM 12577184 ER PT J AU Silverman, SL Crans, GG Wong, M Stock, JL Genant, HK AF Silverman, SL Crans, GG Wong, M Stock, JL Genant, HK TI Relationships between age, number and maximal severity of prevalent vertebral fractures with health-related quality of life SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT 4th European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ECCEO 4) CY NOV 14-17, 2003 CL NICE, FRANCE SP WHO Collaborat Ctr Public Hlth Aspects Osteoart Disorders, Int Osteoporosis Fdn C1 Univ Calif Los Angeles, Greater Los Angeles VA Hlth Syst, Cedars Sinai Med Ctr, Los Angeles, CA USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Univ Calif San Francisco, Osteoporosis & Arthrit Res Grp, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PY 2003 VL 14 SU 7 BP S49 EP S50 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 756ZJ UT WOS:000187515400143 ER PT J AU Metson, R AF Metson, R TI Image-guided sinus surgery: Lessons learned from the first 1000 cases SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID GUIDANCE SYSTEMS AB OBJECTIVE: To study physician utilization and experience with image-guidance technology for sinus surgery. STUDY DESIGN AND SETTING: Retrospective review of the first 1000 image-guided sinus operations performed by 42 surgeons at an academic medical center. RESULTS: Utilization of image-guidance systems showed a dramatic increase in both number of cases performed and surgeons who used this equipment (70.6% and 92.8%, respectively) during the first 2 years of its availability. Surgical volume subsequently decreased by a mean of 9.3% per year, whereas the number of surgeons using this technology plateaued. The majority of surgeons continued to perform image-guided surgery throughout the study period for selected cases. The knowledge base gained from this experience can best be summarized as a series of lessons learned. CONCLUSION: It is likely that the availability and utilization of image-guidance systems for sinus surgery will continue to increase in the future. Physicians who learn to use this new technology must do so with an appreciation for both its potential benefits and pitfalls. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm,Dept Otolaryngol, Cambridge, MA 02138 USA. RP Metson, R (reprint author), Zero Emerson Pl, Boston, MA 02114 USA. NR 7 TC 42 Z9 46 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JAN PY 2003 VL 128 IS 1 BP 8 EP 13 DI 10.1067/mhn.2003.40 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 643HU UT WOS:000180856500003 PM 12574752 ER PT J AU Kentala, E Rauch, SD AF Kentala, E Rauch, SD TI A practical assessment algorithm for diagnosis of dizziness SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 09-14, 2001 CL DENVER, COLORADO SP Amer Acad Otolaryngol Head & Neck Surg ID DIZZY PATIENT; EXPERT-SYSTEM AB OBJECTIVE: We sought to test a 3-parameter model for diagnosis of dizziness based on the type and temporal characteristics of the dizziness and on hearing status. STUDY DESIGN AND SETTING: We conducted a prospective blinded study at a tertiary referral neurotology practice. Before examination, patients completed a questionnaire reporting type and timing of dizziness symptoms and hearing status. Clinical diagnoses were compared with questionnaire results. RESULTS: Fifty-seven patients completed the questionnaire. We were able to correctly classify 21 (60%) of the 35 subjects who had a common otogenic cause of vertigo by the diagnostic algorithm. CONCLUSION: A simple classification of dizziness by type, timing, and hearing status can be self-reported by patients using a brief questionnaire. This classification scheme is as good as others of much greater complexity. SIGNIFICANCE: The simple classification scheme reported here is based on history alone and facilitates triage of dizzy patients into diagnostic groups for work-up and management. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. Helsinki Univ Hosp, Dept Otol & Laryngol, Helsinki, Finland. RP Rauch, SD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 11 TC 17 Z9 17 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JAN PY 2003 VL 128 IS 1 BP 54 EP 59 DI 10.1067/mhn.2003.47 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 643HU UT WOS:000180856500011 PM 12574760 ER PT S AU Biaglow, JE Lee, I Donahue, J Held, K Mieyal, J Dewhirst, M Tuttle, S AF Biaglow, JE Lee, I Donahue, J Held, K Mieyal, J Dewhirst, M Tuttle, S BE Dunn, JF Swartz, HM TI Glutathione depletion or radiation treatment alters respiration and induces apoptosis in R3230AC mammary carcinoma SO OXYGEN TRANSPORT TO TISSUE XXIV SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the International-Society-on-Oxygen-Transport-to-Tissue CY AUG 28-SEP 02, 1999 CL DARTMOUTH MED SCH, HANOVER, NEW HAMPSHIRE SP Int Soc Oxygen Transport Tissue HO DARTMOUTH MED SCH DE apoptosis; bioreduction; carcinoma cells; glutathione; oxygen uptake; radiation ID BUTHIONINE SULFOXIMINE; OXIDATIVE STRESS; CELLS; SENSITIVITY; INHIBITION; PROTEIN; GROWTH; THIOLS AB Glutathione depletion by L-buthionine sulfoximine inhibits the growth of Ehrlich mouse mammary carcinoma, R3230Ac rat mammary carcinoma and the PC3 human prostrate carcinoma cells, in vitro. Inhibition of growth occurs within the first 24 hours after exposure to the drug. The cell density does not increase over the initial cell density over 7 days. A549 human lung carcinoma and the DU145 human prostrate carcinoma cells show no inhibition of growth under the same treatment conditions. A comparative study of the R3230Ac and A549 cells demonstrated a marked increase in apoptosis following L-BSO treatment in R3230Ac, which was dependent on L-BSO concentration and incubation time. L-BSO did not induce apoptosis in A549 cells at any of the concentrations tested. The incidence of apoptosis for R3230Ac cells following exposure to 0.1 mM L-BSO was similar to the incidence of radiation-induced apoptosis observed after exposure to 10 Gy. Treatment with L-BSO or radiation alone inhibited O-2 utilization in of R3230ac, while no effect on O-2 utilization was observed in A549 cells. LBSO altered the bioreductive capacity of both the R3230Ac and A549 cells. These results suggest that the ability of L-BSO to block mitochondrial O-2 utilization may be involved in the apoptotic response in R3230Ac cells. C1 Univ Penn, Sch Med, Dept Biochem, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA. Duke Univ, Dept Radiat Oncol, Durham, NC USA. RP Biaglow, JE (reprint author), Univ Penn, Sch Med, Dept Biochem, Philadelphia, PA 19104 USA. FU NCI NIH HHS [CA 44982]; NIA NIH HHS [AG15885] NR 36 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47774-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 530 BP 153 EP 164 PG 12 WC Medicine, Research & Experimental; Physiology SC Research & Experimental Medicine; Physiology GA BX70X UT WOS:000186182800015 PM 14562713 ER PT J AU Ellinor, PT Guy, ML Ruskin, JN McGovern, BA AF Ellinor, PT Guy, ML Ruskin, JN McGovern, BA TI Variability in implantable cardioverter defibrillator pulse generator longevity between manufacturers SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE implantable cardioverter defibrillator; pulse generator; elective replacement; malfunction; longevity ID FAILURE; PACEMAKER; DISEASE AB ICDs are used frequently to treat malignant ventricular arrhythmias. Despite the expanding role of these devices, little is known about the manufacturer variability in the performance of ICD generators. The purpose of this study is to explore the indications for ICD pulse generator replacement and to examine performance differences between the three major manufacturers of ICDs in the United States. The authors performed a retrospective review of ICD pulse generators that were implanted and replaced at Massachusetts General Hospital between February 1998 and March 2002. During the study period, 50 (7%) of the 707 devices in the study cohort were replaced. The most common indication for pulse generator replacement was related to battery performance followed by device recall, upgrade to a dual chamber device, and pulse generator malfunction. After exclusion of the recalled devices, a significantly higher number of pulse generators manufactured by St. Jude Medical (14/229) required replacement for battery depletion or prolonged charge times during the study period compared with devices from Guidant (2/220) or Medtronic (0/273), P = 0.003 and P < 0.0001, respectively. This difference was attributable to reduced longevity in the Angstrom series of defibrillators. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Div Cardiol, Boston, MA 02114 USA. RP McGovern, BA (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Div Cardiol, 55 Fruit St,GRB 109, Boston, MA 02114 USA. NR 14 TC 13 Z9 13 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JAN PY 2003 VL 26 IS 1 BP 71 EP 75 DI 10.1046/j.1460-9592.2003.00153.x PN 1 PG 5 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 661TR UT WOS:000181906300012 PM 12685143 ER PT J AU Goudsouzian, N AF Goudsouzian, N TI Do we need a new muscle relaxant in paediatrics? SO PAEDIATRIC ANAESTHESIA LA English DT Editorial Material ID RAPID-SEQUENCE INDUCTION; INTUBATING CONDITIONS; LARYNGEAL MASK; ADULT PATIENTS; CHILDREN; RAPACURONIUM; VECURONIUM; SUCCINYLCHOLINE; ANESTHESIA; INFANTS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Goudsouzian, N (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 14 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1155-5645 J9 PAEDIATR ANAESTH JI Paediatr. Anaesth. PD JAN PY 2003 VL 13 IS 1 BP 1 EP 2 DI 10.1046/j.1460-9592.2003.00870.x PG 2 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 636AX UT WOS:000180433300001 PM 12535031 ER PT J AU Raut, CP Fernandez-del Castillo, C AF Raut, CP Fernandez-del Castillo, C TI Giant lipoma of the pancreas: Case report and review of lipomatous lesions of the pancreas SO PANCREAS LA English DT Article ID INTRAPANCREATIC LIPOMA; CT; TUMORS C1 Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Raut, CP (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. NR 12 TC 13 Z9 14 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 2003 VL 26 IS 1 BP 97 EP 99 DI 10.1097/00006676-200301000-00018 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 630EL UT WOS:000180094500018 PM 12499926 ER PT S AU Arlotta, P Magavi, SS Macklis, JD AF Arlotta, P Magavi, SS Macklis, JD BE Federoff, HJ Burke, RE Fahn, S Fiskum, G TI Induction of adult neurogenesis - Molecular manipulation of neural precursors in situ SO PARKINSON'S DISEASE: THE LIFE CYCLE OF THE DOPAMINE NEURON SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Parkinsons Disease - The Life Cycle of the Dopamine Neuron CY SEP 18-20, 2002 CL PRINCETON, NEW JERSEY SP New York Acad Sci DE neurogenesis; neocortex; neural precursors; neural stem cells; targeted apoptosis; neuronal recruitment ID CENTRAL-NERVOUS-SYSTEM; MAMMALIAN SPINAL-CORD; STEM-CELLS; PROJECTION NEURONS; EMBRYONIC NEURONS; PYRAMIDAL NEURONS; MOUSE NEOCORTEX; RADIAL GLIA; BRAIN; DEGENERATION AB Over most of the past century, it was thought that the adult brain was completely incapable of generating new neurons. However, in the last decade, the development of new techniques has resulted in an explosion of new research showing that (i) neurogenesis, the birth of new neurons, is not restricted to embryonic development, but normally also occurs in two limited regions of the adult mammalian brain (the olfactory bulb and the dentate gyrus of the hippocampus); (ii) that there are significant numbers of multipotent neural precursors in many parts of the adult mammalian brain; and (iii) that it is possible to induce neurogenesis even in regions of the adult mammalian brain, like the neocortex, where it does not normally occur, via manipulation of endogenous multipotent precursors in situ. In the neocortex, recruitment of small numbers of new neurons can be induced in a region-specific, layer-specific, and neuronal type-specific manner, and newly recruited neurons can form long-distance connections to appropriate targets. This suggests that elucidation of the relevant molecular controls over adult neurogenesis from endogenous neural precursors/stem cells may allow the development of neuronal replacement therapies for neurodegenerative disease and other central nervous system injuries that may not require transplantation of exogenous cells. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Program, Boston, MA 02114 USA. RP Macklis, JD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Nervous Syst Repair,Dept Neurosurg, Edwards 4,55 Fruit St, Boston, MA 02114 USA. FU NICHD NIH HHS [HD18655, HD28478]; NINDS NIH HHS [NS41590, NS45523] NR 36 TC 32 Z9 35 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-448-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 991 BP 229 EP 236 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences; Neurosciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics; Neurosciences & Neurology GA BX10S UT WOS:000184302100022 PM 12846990 ER PT S AU Heidenreich, KA AF Heidenreich, KA BE Federoff, HJ Burke, RE Fahn, S Fiskum, G TI Molecular mechanisms of neuronal cell death SO PARKINSON'S DISEASE: THE LIFE CYCLE OF THE DOPAMINE NEURON SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Parkinsons Disease - The Life Cycle of the Dopamine Neuron CY SEP 18-20, 2002 CL PRINCETON, NEW JERSEY SP New York Acad Sci DE neuron; cell death; apoptosis ID AMYOTROPHIC-LATERAL-SCLEROSIS; CEREBELLAR GRANULE NEURONS; CYTOCHROME-C RELEASE; GROWTH-FACTOR-I; MITOCHONDRIAL PERMEABILITY TRANSITION; NECROSIS-FACTOR-ALPHA; BCL-2 FAMILY MEMBERS; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE AB Chronic neurodegenerative diseases, including Parkinson's disease, are characterized by a selective loss of specific subsets of neuronal populations over a period of years or even decades. While the underlying causes of the various neurodegenerative diseases are not clear, the death of neurons and the loss of neuronal contacts are key pathological features. Pinpointing molecular events that control neuronal cell death is critical for the development of new strategies to prevent and treat neurodegenerative disorders. C1 Denver VAMC, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Program Neurosci, Denver, CO 80262 USA. RP Heidenreich, KA (reprint author), Denver VAMC, 111H,1055 Clermont St, Denver, CO 80220 USA. FU NINDS NIH HHS [NS38619-01A1] NR 64 TC 18 Z9 19 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-448-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 991 BP 237 EP 250 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences; Neurosciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics; Neurosciences & Neurology GA BX10S UT WOS:000184302100023 PM 12846991 ER PT S AU Brownell, AL Chen, IY Wang, XK Yu, MX Jenkins, BG AF Brownell, AL Chen, IY Wang, XK Yu, MX Jenkins, BG BE Federoff, HJ Burke, RE Fahn, S Fiskum, G TI Neurotoxicity-induced changes in striatal dopamine receptor function SO PARKINSON'S DISEASE: THE LIFE CYCLE OF THE DOPAMINE NEURON SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Parkinsons Disease - The Life Cycle of the Dopamine Neuron CY SEP 18-20, 2002 CL PRINCETON, NEW JERSEY SP New York Acad Sci DE dopamine receptor; dopamine transporter; striatum ID HUNTINGTONS-DISEASE; PET; MARKERS C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Brownell, AL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 7 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-448-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 991 BP 281 EP 283 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences; Neurosciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics; Neurosciences & Neurology GA BX10S UT WOS:000184302100027 ER PT S AU Duda, JE Giasson, BI Lee, VMY Trojanowski, JQ AF Duda, JE Giasson, BI Lee, VMY Trojanowski, JQ BE Federoff, HJ Burke, RE Fahn, S Fiskum, G TI Is the initial insult in Parkinson's disease and dementia with Lewy bodies a neuritic dystrophy? SO PARKINSON'S DISEASE: THE LIFE CYCLE OF THE DOPAMINE NEURON SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Parkinsons Disease - The Life Cycle of the Dopamine Neuron CY SEP 18-20, 2002 CL PRINCETON, NEW JERSEY SP New York Acad Sci DE Parkinson's disease; dementia with Lewy bodies; neuritic dystrophy; alpha-synuclein ID ALPHA-SYNUCLEIN; PATHOLOGY C1 Univ Penn, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. RP Trojanowski, JQ (reprint author), Univ Penn, Ctr Neurodegenerat Dis Res, 3600 Spruce St,3 Maloney, Philadelphia, PA 19104 USA. NR 7 TC 8 Z9 8 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-448-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 991 BP 295 EP 297 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences; Neurosciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics; Neurosciences & Neurology GA BX10S UT WOS:000184302100031 ER PT J AU Richardson, P AF Richardson, P TI Hemostatic complications of hematopoietic stem cell transplantation: From hemorrhage to microangiopathies and VOD SO PATHOPHYSIOLOGY OF HAEMOSTASIS AND THROMBOSIS LA English DT Article; Proceedings Paper CT 2nd International Conference on Thrombosis and Hemostasis Issues in Cancer CY SEP 19-21, 2003 CL BERGAMO, ITALY ID BONE-MARROW-TRANSPLANTATION; HEPATIC VENOOCCLUSIVE DISEASE; THROMBOTIC THROMBOCYTOPENIC PURPURA; HIGH-RISK POPULATION; PLATELET TRANSFUSIONS; PLASMINOGEN-ACTIVATOR; VENOCCLUSIVE DISEASE; SIGNIFICANT TOXICITY; COMPASSIONATE-USE; RANDOMIZED-TRIAL C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. RP Richardson, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. NR 30 TC 0 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8832 J9 PATHOPHYSIOL HAEMO T JI Pathophysiol. Haemost. Thromb. PY 2003 VL 33 SU 1 BP 50 EP 53 DI 10.1159/000073293 PG 4 WC Hematology SC Hematology GA 724ZJ UT WOS:000185517900019 PM 12955004 ER PT J AU Ohtsuka, Y Sanderson, IR AF Ohtsuka, Y Sanderson, IR TI Dextran sulfate sodium-induced inflammation is enhanced by intestinal epithelial cell chemokine expression in mice SO PEDIATRIC RESEARCH LA English DT Article ID BINDING-PROTEIN GENE; DIETARY-REGULATION; TRANSGENIC MICE; MESSENGER-RNA; NEUTROPHIL; LYMPHOCYTES; SECRETION; ANTIGEN; CHEMOATTRACTANT; INTERLEUKIN-8 AB Dextran sulfate sodium (DSS) induces an inflammatory bowel disease-like colitis in animals. To determine the contribution of epithelium to inflammation in the intestine, we examined the effects of DSS in transgenic mice that specifically secrete macrophage inflammatory protein-2 (MIP-2) from the intestinal epithelium. We first confirmed the production of MIP-2 from intestinal epithelial cells by Western blots in transgenic mice. MIP-2 transgenic mice were therefore an appropriate model to examine the role of epithelial cell chemokines in an inflammatory state induced by DSS. We then examined the neutrophil migration into the intestine and the effect of DSS on this migration by myeloperoxidase staining. There was an increase of myeloperoxidase-positive neutrophils in the intestine from wild-type and transgenic mice after the DSS treatment. Furthermore, the increase of neutrophils under stimulation with DSS was confirmed quantitatively by measuring specific tissue myeloperoxidase activities. It was significantly greater in DSS-treated MIP-2 transgenic mice than in wild-type mice in both the small intestine and colon. These results suggest that the inflammatory effects of DSS on both small intestine and colon are enhanced by MIP-2 secreted by epithelial cells in the transgenic mice. In conclusion, intestinal epithelial cells can act in concert with other inflammatory stimuli in maintaining inflammation. C1 St Bartholomews & Royal London Sch Med & Dent, Dept Adult & Paediat Gastroenterol, London, England. Massachusetts Gen Hosp, Dev Gastroenterol Lab, Harvard Clin Nutr Res Ctr, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02129 USA. Juntendo Univ, Sch Med, Dept Pediat, Tokyo 113, Japan. RP Sanderson, IR (reprint author), Royal London Hosp, Dept Adult & Paediat Gastroenterol, Digest Dis Res Ctr, Turner St, London E1 2AD, England. FU NIAID NIH HHS [AI43472]; NIDDK NIH HHS [DK47753] NR 29 TC 38 Z9 39 U1 0 U2 5 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD JAN PY 2003 VL 53 IS 1 BP 143 EP 147 DI 10.1203/01.PDR.0000041519.16507.06 PG 5 WC Pediatrics SC Pediatrics GA 630ZW UT WOS:000180142800023 PM 12508094 ER PT J AU Spitzer, TR AF Spitzer, TR TI The expanding applications of non-myeloablative stem cell transplantation SO PEDIATRIC TRANSPLANTATION LA English DT Article; Proceedings Paper CT Meeting on Marrow Transplantation in Children: Current Results and Controversies CY NOV 08-10, 2001 CL ST AUGUSTINE, FLORIDA DE applications; non-myeloblative; stem cell transplantation ID BONE-MARROW TRANSPLANTATION; MIXED ALLOGENEIC CHIMERISM; HEMATOLOGIC MALIGNANCIES; BREAST-CANCER; TOLERANCE; THERAPY; ALLOGRAFT; DISEASE; RECONSTITUTION; ENGRAFTMENT AB Non-myeloablative preparative strategies for allogeneic stem cell transplantation (SCT) have been increasingly utilized for a variety of hematological malignancies, solid tumours, and for tolerance induction. These regimens are associated with less transplant-related morbidity and mortality than conventional transplant conditioning regimens. It is not yet clear whether graft-vs.-host disease (GVHD) protection is afforded. Potent antitumour responses have been described in a variety of advanced malignancies. We have utilized a cyclophosphamide/anti-T-cell antibody therapy approach, which has resulted in the uniform induction of mixed chimerism. In many cases, this has served as an immunological platform for adoptive cellular immunotherapy (via donor leukocyte infusions). The results of this experience, as well as the outcomes of non-myeloablative stem cell transplantation (NST) for other malignant and nonmalignant conditions are described. C1 Massachusetts Gen Hosp, Bone Marrow Transplant Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Spitzer, TR (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplant Program, 100 Blossom St,COX 640, Boston, MA 02114 USA. NR 27 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1397-3142 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PY 2003 VL 7 SU 3 BP 95 EP 100 DI 10.1034/j.1399-3046.7.s3.15.x PG 6 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA 647DT UT WOS:000181077700016 PM 12603701 ER PT J AU Winickoff, JP Hillis, VJ Palfrey, JS Perrin, JM Rigotti, NA AF Winickoff, JP Hillis, VJ Palfrey, JS Perrin, JM Rigotti, NA TI A smoking cessation intervention for parents of children who are hospitalized for respiratory illness: The Stop Tobacco Outreach Program SO PEDIATRICS LA English DT Article DE parent; smoking; tobacco; smoking cessation; respiratory illness; hospitalization ID RANDOMIZED CONTROLLED TRIAL; PASSIVE SMOKING; ASTHMATIC-CHILDREN; MATERNAL SMOKING; ADOLESCENT SMOKING; EXPOSURE; SMOKERS; OPPORTUNITY; WORKPLACE; REDUCTION AB Objective. Parental smoking is associated with increased rates and severity of childhood respiratory illness. No previous studies have examined child hospitalization as an opportunity for parental smoking cessation. We evaluated the feasibility of implementing a smoking cessation intervention for parents at the time of child hospitalization for respiratory illness. Methods. We performed a prospective cohort study of smoking parents who had a child who was admitted to an academic children's hospital for a respiratory illness between January and April 2000. All enrollees were offered the Stop Tobacco Outreach Program, which includes an initial motivational interview, written materials, nicotine replacement therapy (NRT), telephone counseling, and fax referral to parents' primary clinician. The primary outcome was completion of all 3 counseling sessions. Two-month follow-up outcomes were quit attempts, cessation, NRT use, primary care visits, household smoking prohibition, and satisfaction. Results. A total of 126 smoking parents met eligibility criteria, and 71 (56%) enrolled in the study. Of the 71, 80% completed all counseling sessions and 56% accepted free NRT at the time of enrollment. At the 2-month follow-up, of the 71 initial enrollees, 49% reported having made a quit attempt that lasted at least 24 hours, 21% reported not smoking a cigarette in the last 7 days, 27% reported having used NRT, and 38% had had a visit with their own primary clinician. The proportion of parents who reported rules prohibiting smoking in the house increased (29% vs 71%). Parental rating of the overall usefulness of the program was 4.3 +/- 0.9 (1 standard deviation) on the 5-point scale 1 = not at all and 5 = a great extent. Conclusions. This study demonstrates the feasibility of engaging parents in smoking cessation interventions at the time of child hospitalization for respiratory illness. Previous work done in a similar sample of parental smokers has shown extremely low ever-use rates of cessation programs. High rates of acceptance of in-hospital and telephone counseling in this study support the notion of child hospitalization as a teachable moment to address parental smoking. C1 MassGen Hosp Children, MGH Ctr Child & Adolescent Hlth Policy, Div Gen Pediat, Boston, MA USA. Massachusetts Gen Hosp, Div Gen Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. RP Winickoff, JP (reprint author), MGH Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Ste 901, Boston, MA 02144 USA. FU AHRQ HHS [T32-HS00063]; NHLBI NIH HHS [K24-HL04440] NR 41 TC 74 Z9 75 U1 1 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 2003 VL 111 IS 1 BP 140 EP 145 DI 10.1542/peds.111.1.140 PG 6 WC Pediatrics SC Pediatrics GA 630XC UT WOS:000180135200038 PM 12509567 ER PT J AU Wilens, TE Faraone, SV Biederman, J Gunawardene, S AF Wilens, TE Faraone, SV Biederman, J Gunawardene, S TI Does stimulant therapy of attention-deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature SO PEDIATRICS LA English DT Review DE attention-deficit/hyperactivity disorder; substance use; pharmacotherapy ID DEFICIT HYPERACTIVITY DISORDER; 15-YEAR FOLLOW-UP; PSYCHIATRIC STATUS; DRUG-USE; CONDUCT DISORDER; YOUNG ADULTHOOD; ADHD; METHYLPHENIDATE; COMORBIDITY; CHILDREN AB Objective. Concerns exist that stimulant therapy of youths with attention-deficit/hyperactivity disorder (ADHD) may result in an increased risk for subsequent substance use disorders (SUD). We investigated all long-term studies in which pharmacologically treated and untreated youths with ADHD were examined for later SUD outcomes. Methods. A search of all available prospective and retrospective studies of children, adolescents, and adults with ADHD that had information relating childhood exposure to stimulant therapy and later SUD outcome in adolescence or adulthood was conducted through PubMed supplemented with data from scientific presentations. Meta-analysis was used to evaluate the relationship between stimulant therapy and subsequent SUD in youths with ADHD in general while addressing specifically differential effects on alcohol use disorders or drug use disorders and the potential effects of covariates. Results. Six studies-2 with follow-up in adolescence and 4 in young adulthood-were included and comprised 674 medicated subjects and 360 unmedicated subjects who were followed at least 4 years. The pooled estimate of the odds ratio indicated a 1.9-fold reduction in risk for SUD in youths who were treated with stimulants compared with youths who did not receive pharmacotherapy for ADHD (z = 2.1; 95% confidence interval for odds ratio [OR]: 1.1-3.6). We found similar reductions in risk for later drug and alcohol use disorders (z = 1.1). Studies that reported follow-up into adolescence showed a greater protective effect on the development of SUD (OR: 5.8) than studies that followed subjects into adulthood (OR: 1.4). Additional analyses showed that the results could not be accounted for by any single study or by publication bias. Conclusion. Our results suggest that stimulant therapy in childhood is associated with a reduction in the risk for subsequent drug and alcohol use disorders. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Clin, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Glaxo Smith Kline, Res Triangle Pk, NC 27709 USA. Pfizer Inc, Pharmaceut, New York, NY 10017 USA. Wyeth Ayerst Res, Princeton, NJ 08543 USA. Shire Labs Inc, Rockville, MD 20850 USA. Alza Pharmaceut, Menlo Pk, CA USA. Cephalon Pharmaceut, W Chester, PA 19380 USA. Noven Pharmaceut Inc, Miami, FL 33186 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Clin, Clin Res Program Pediat Psychopharmacol, ACC 725, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 56 TC 364 Z9 376 U1 9 U2 50 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 2003 VL 111 IS 1 BP 179 EP 185 DI 10.1542/peds.111.1.179 PG 7 WC Pediatrics SC Pediatrics GA 630XC UT WOS:000180135200045 PM 12509574 ER PT J AU Seitz, A Nanez, JE Sasaki, Y Engles, MP Holloway, R Wantanabe, T AF Seitz, A Nanez, JE Sasaki, Y Engles, MP Holloway, R Wantanabe, T TI Learning spillover to invisible dots SO PERCEPTION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Arizona State Univ W, Coll Arts & Sci, Phoenix, AZ 85069 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Tamagawa Univ, Res Inst, Brain Sci Res Ctr, Tokyo 1948610, Japan. Boston Univ, Dept Psychol, Boston, MA 02215 USA. RI Holloway, Steven/B-8780-2008; Holloway, Steven/O-3032-2013 OI Holloway, Steven/0000-0001-8900-5315 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2003 VL 32 SU S BP 89 EP 90 PG 2 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 720KH UT WOS:000185259600240 ER PT J AU Goodson, JM AF Goodson, JM TI Gingival crevice fluid flow SO PERIODONTOLOGY 2000 LA English DT Article ID ALKALINE-PHOSPHATASE; SAMPLING TIME; TETRACYCLINE; PLAQUE; INFLAMMATION; DELIVERY; THERAPY; SALIVA; FIBERS C1 Forsyth Inst, Boston, MA USA. RP Goodson, JM (reprint author), Forsyth Inst, Boston, MA USA. NR 36 TC 64 Z9 66 U1 0 U2 4 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0906-6713 J9 PERIODONTOL 2000 JI Periodontol. 2000 PY 2003 VL 31 BP 43 EP 54 DI 10.1034/j.1600-0757.2003.03104.x PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 641VX UT WOS:000180768700004 PM 12656995 ER PT J AU Ellis, CN Drake, LA Prendergast, MM Abramovits, W Boguniewicz, M Daniel, CR Lebwohl, M Stevens, SR Whitaker-Worth, DL Tong, KB AF Ellis, CN Drake, LA Prendergast, MM Abramovits, W Boguniewicz, M Daniel, CR Lebwohl, M Stevens, SR Whitaker-Worth, DL Tong, KB TI Validation of expert opinion in identifying comorbidities associated with atopic dermatitis/eczema SO PHARMACOECONOMICS LA English DT Article ID CONSENSUS METHODS; UNITED-STATES; COST; EPILEPSY; EXPENDITURES; QUALITY; ASTHMA AB Background: The use of expert opinion is widespread in economic studies of healthcare utilisation; however, few studies have attempted to assess the validity of assumptions derived from such sources. Objective: To examine the use of such expert opinion in determining comorbidities associated with atopic dermatitis/eczema (AD/E), which were assessed as part of a recent third-party payer cost-of-illness study. Design: To identify the disease-related comorbidities that would represent costs associated with AD/E, physicians on an expert panel were asked individually and then collectively to group all International Classification of Diseases, 9th Edition-Clinical Modification (ICD-9-CM) diagnosis codes as 'most likely', 'possibly' or 'definitely not' related to the costs of identifying and treating patients with AD/E. Claims representing $US464 million in payer reimbursements from nearly 125 000 patients with AD/E were identified within two separate claims databases (1997 values). Over 850 ICD-9-CM diagnosis codes were identified in the first-listed position from these claims. For each group of 'most likely', 'possibly' and 'definitely not' related diagnosis codes, prevalence rates were compared within AD/E and non-AD/E populations from the two historical payer claims databases. Adjusted and non-adjusted odds ratios were calculated by comparing prevalence rates between AD/E and non-AD/E patients in the same payer population. Results: The mean prevalence rate of any diagnosis code in the AD/E population was 0.65 +/- 1.82% (SD) with a mean odds ratio of 1.81 +/- 0.96. Comorbidities considered by the expert panel 'most likely' to be associated with AD/E had higher prevalence rates (3.28 +/- 3.63%) and odds ratios (2.14 +/- 1.14). Comorbidities considered to be 'possibly' related to AD/E had prevalence rates and odds ratios of 3.01 +/- 5.06% and 1.84 +/- 0.82, respectively. Comorbidities considered to be 'definitely not' related to AD/E had the lowest prevalence rates (0.45 +/- 1.09%) and odds ratios (1.80 +/- 0.97). Conclusions: Comparing the result of consensus panels with actual claims histories validated the use of expert opinion in determining comorbidities associated with AD/E. Expert opinion yielded valid results in terms of identifying comorbidities that manifested frequently and disproportionately in the AD/E population. Limited statistical measurements of comorbidities would have been less specific than expert opinion. Future cost-of-illness studies should consider alternative data sources and methodologies to enhance the validity and importance of expert opinion and to corroborate their findings. C1 Quorum Consulting Inc, San Francisco, CA 94102 USA. Univ Michigan, Dept Dermatol, Sch Med, Ann Arbor, MI 48109 USA. Vet Adm Med Ctr, Ann Arbor, MI 48105 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Fujisawa Healthcare Inc, Deerfield, IL USA. Baylor Univ, Med Ctr, Dallas, TX USA. Univ Texas, SW Sch Med, Dallas, TX 75230 USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Univ Mississippi, Jackson, MS 39216 USA. NYU, Mt Sinai Sch Med, New York, NY USA. Case Western Reserve Univ, Univ Hosp Cleveland, Cleveland, OH 44106 USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. RP Tong, KB (reprint author), Quorum Consulting Inc, 442 Post St,9th Floor, San Francisco, CA 94102 USA. NR 22 TC 3 Z9 3 U1 0 U2 3 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2003 VL 21 IS 12 BP 875 EP 883 DI 10.2165/00019053-200321120-00004 PG 9 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 714PN UT WOS:000184922800004 PM 12908843 ER PT J AU Metlay, JP Hardy, C Strom, BL AF Metlay, JP Hardy, C Strom, BL TI Agreement between-patient self-report and a Veterans Affairs national pharmacy database for identifying recent exposures to antibiotics SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE epidemiologic methods; recall; antibiotics; data collection ID RISK-FACTORS; BETA-LACTAM; RESISTANCE; ERYTHROMYCIN; CONSUMPTION; PENICILLIN; MACROLIDE; VALIDATION; CARE AB Purpose The dramatic rise in antibiotic drug resistance among community pathogens has stimulated interest in the epidemiological relationship between antibiotic exposure and drug resistance. In assessing the strength of this relationship, studies are hampered by the lack of data on the accuracy of subject self-report of antibiotic exposure. The authors compared self-report with pharmacy dispensing data to determine the accuracy of self-reported antibiotic exposure. Methods The study design Was a cross-sectional survey of veterans seen at the Philadelphia Veterans Affairs (VA) Medical Center in 1999 and 2000. Subjects reported exposures to antibiotics, antihypertensive drugs and nonsteroidal anti-inflammatory drugs through a structured telephone interview. The instrument included open-ended questions, condition-specific prompts and drug-specific prompts. Subject responses were linked to a national-VA pharmacy database that served as the reference standard for evaluating self-reported exposures. Results The authors found that the sensitivity of self-report of antibiotic exposure increased with increasing use of prompts. A comprehensive assessment of antibiotic exposure identified 73% of antibiotic exposures, compared to 73% of antihypertensive drug exposures and 92% of nonsteroidal anti-inflammatory drug exposures. Conclusions Assessment of antibiotic exposure appears to be comparable to assessment of other chronic and episodic drugs. Multistep assessment of exposure improves the sensitivity of assessment. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. RP Metlay, JP (reprint author), Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, 712 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 20 TC 16 Z9 17 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JAN-FEB PY 2003 VL 12 IS 1 BP 9 EP 15 DI 10.1002/pds.772 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 642TE UT WOS:000180819900002 PM 12622056 ER PT J AU Ferrari, S Vairo, D Ausubel, FM Cervone, F De Lorenzo, G AF Ferrari, S Vairo, D Ausubel, FM Cervone, F De Lorenzo, G TI Tandemly duplicated arabidopsis genes that encode polygalacturonase-inhibiting proteins are regulated coordinately by different signal transduction pathways in response to fungal infection SO PLANT CELL LA English DT Article ID PATHOGENESIS-RELATED PROTEINS; PHASEOLUS-VULGARIS L; DISEASE SUSCEPTIBILITY MUTANTS; SYSTEMIC ACQUIRED-RESISTANCE; LEUCINE-RICH REPEATS; PLANT DEFENSIN GENE; RECEPTOR KINASE; BOTRYTIS-CINEREA; SALICYLIC-ACID; HYPERSENSITIVE RESPONSE AB Polygalacturonase-inhibiting proteins (PGIPs) are plant proteins that counteract fungal polygalacturonases, which are important virulence factors. Like many other plant defense proteins, PGIPs are encoded by gene families, but the roles of individual genes in these families are poorly understood. Here, we show that in Arabidopsis, two tandemly duplicated PGIP genes are upregulated coordinately in response to Botrytis cinerea infection, but through separate signal transduction pathways. AtPGIP2 expression is mediated by jasmonate and requires COI1 and JAR1, whereas AtPGIP1 expression is upregulated strongly by oligogalacturonides but is unaffected by salicylic acid, jasmonate, or ethylene. Both AtPGIP1 and AtPGIP2 encode functional inhibitors of polygalacturonase from Botrytis, and their overexpression in Arabidopsis significantly reduces Botrytis disease symptoms. Therefore, gene duplication followed by the divergence of promoter regions may result in different modes of regulation of similar defensive proteins, thereby enhancing the likelihood of defense gene activation during pathogen infection. C1 Univ Roma La Sapienza, Dipartimento Biol Vegetale, I-00185 Rome, Italy. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP De Lorenzo, G (reprint author), Univ Roma La Sapienza, Dipartimento Biol Vegetale, Piazzale Aldo Moro 5, I-00185 Rome, Italy. EM delorenzo@uniroma1.it RI De Lorenzo, Giulia/F-5475-2013; Cervone, Felice/G-9905-2013 OI De Lorenzo, Giulia/0000-0002-1707-5418; FU NIGMS NIH HHS [GM48707, R01 GM048707, R37 GM048707] NR 74 TC 172 Z9 189 U1 0 U2 14 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 J9 PLANT CELL JI Plant Cell PD JAN PY 2003 VL 15 IS 1 BP 93 EP 106 DI 10.1105/tpc.005165 PG 14 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA 637KQ UT WOS:000180510600008 PM 12509524 ER PT J AU Yaremchuk, MJ AF Yaremchuk, MJ TI Restoring palpebral fissure shape after previous lower blepharoplasty SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID LOWER EYELID RETRACTION; LOWER LID BLEPHAROPLASTY; ECTROPION FOLLOWING BLEPHAROPLASTY; COSMETIC SURGERY; TARSAL STRIP; DRY-EYE; MANAGEMENT; PREVENTION; SUSPENSION; CANTHOPEXY AB The youthful palpebral fissure can be described as long and narrow. Both the aging process and transcutaneous lower blepharoplasty can cause descent of the lower lid margin and medial migration of the lateral canthus, resulting in a rounding of the palpebral fissure. This article presents a technique to correct significant postsurgical lower lid malposition and palpebral fissure distortion without the use of outer or inner lamellar grafts. In overview, subperiosteal dissection frees scarred lid structures and cheek soft tissues, creating a continuous composite flap. Elevation of the cheek soft tissues recruits deficient outer lamellae and allows the sub-orbicularis oculi fat to be positioned between the orbital rim and scarred lid structures, filling this space and helping to support the repositioned lid margin. Titanium screws placed in the lateral orbit provide a point for secure fixation of elevated cheek tissues. Transosseous wire fixation securely repositions the lateral canthus. This procedure not only restores lower lid position and the vertical height of the palpebral fissure, but it also restores the palpebral fissure's horizontal length and the lateral canthal angle. It has been effective in correcting palpebral fissure distortion after lower blepharoplasty in 15 patients during a 6-year period. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Plast Surg, Boston, MA 02114 USA. RP Yaremchuk, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Plast Surg, 55 Fruit St,WACC 453, Boston, MA 02114 USA. NR 43 TC 16 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JAN PY 2003 VL 111 IS 1 BP 441 EP 450 DI 10.1097/01.PRS.0000036036.82797.4C PG 10 WC Surgery SC Surgery GA 631WY UT WOS:000180191700080 PM 12496617 ER PT B AU Ji, RR AF Ji, RR BE Dostrovsky, JO Carr, DB Koltzenburg, M TI Activation of MAP kinases in primary sensory neurons SO PROCEEDINGS OF THE 10TH WORLD CONGRESS ON PAIN SE PROGRESS IN PAIN RESEARCH AND MANAGEMENT LA English DT Proceedings Paper CT 10th World Congress on Pain CY AUG 17-22, 2002 CL SAN DIEGO, CA SP Allergan Inc, AstraZeneca, Eli Lilly & Co, Endo Pharmaceut Inc, Grunenthal GmbH, Janssen Pharmaceut, Pfizer Inc, Pharmacia Corp, Purdue-Mundipharma-Napp Associated Co ID SIGNAL-REGULATED KINASE; PAIN HYPERSENSITIVITY; NOCICEPTIVE NEURONS; INFLAMMATORY PAIN; PLASTICITY; SENSITIZATION; HYPERALGESIA; CONTRIBUTES; RECEPTOR; MICE C1 Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia, Charlestown, MA 02129 USA. RP Ji, RR (reprint author), Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia, 149 13th St,Room 4309, Charlestown, MA 02129 USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU INT ASSOC STUDY PAIN (IASP) PRESS PI SEATTLE PA 909 NE 43RD ST, SUITE 304, SEATTLE, WA 98105 USA BN 0-931092-46-9 J9 PROG PAIN RES MANAG PY 2003 VL 24 BP 81 EP 87 PG 7 WC Anesthesiology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA BW84M UT WOS:000183367100008 ER PT B AU Scholz, J Broom, DC Kohno, T Lekan, HA Coggeshall, RE Woolf, CJ AF Scholz, J Broom, DC Kohno, T Lekan, HA Coggeshall, RE Woolf, CJ BE Dostrovsky, JO Carr, DB Koltzenburg, M TI Animal models of neuropathic pain induce apoptosis and a loss of GABAergic inhibition in the spinal dorsal horn SO PROCEEDINGS OF THE 10TH WORLD CONGRESS ON PAIN SE PROGRESS IN PAIN RESEARCH AND MANAGEMENT LA English DT Proceedings Paper CT 10th World Congress on Pain CY AUG 17-22, 2002 CL SAN DIEGO, CA SP Allergan Inc, AstraZeneca, Eli Lilly & Co, Endo Pharmaceut Inc, Grunenthal GmbH, Janssen Pharmaceut, Pfizer Inc, Pharmacia Corp, Purdue-Mundipharma-Napp Associated Co ID SUBSTANTIA-GELATINOSA NEURONS; PERIPHERAL-NERVE INJURY; CELL-DEATH; RAT; CORD C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02139 USA. Univ Texas, Med Branch, Dept Anat & Neurosci, Galveston, TX 77550 USA. RP Scholz, J (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St,Room 4309, Charlestown, MA 02139 USA. NR 17 TC 2 Z9 2 U1 0 U2 0 PU INT ASSOC STUDY PAIN (IASP) PRESS PI SEATTLE PA 909 NE 43RD ST, SUITE 304, SEATTLE, WA 98105 USA BN 0-931092-46-9 J9 PROG PAIN RES MANAG PY 2003 VL 24 BP 387 EP 395 PG 9 WC Anesthesiology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA BW84M UT WOS:000183367100033 ER PT B AU Gukovskaya, AS Vaquero, EC Edderkaoui, M Pandol, SJ AF Gukovskaya, AS Vaquero, EC Edderkaoui, M Pandol, SJ BE Sikiric, P Seiwerth, S Mozsik, G Arakawa, T Takeuchi, K TI Survival signals in pancreatic cancer SO PROCEEDINGS OF THE 11TH INTERNATIONAL CONFERENCE ON ULCER RESEARCH LA English DT Proceedings Paper CT 11th International Conference on Ulcer Research CY SEP 15-20, 2003 CL Dubrovnik, CROATIA ID CELL-DEATH; APOPTOSIS; NECROSIS; GROWTH AB Pancreatic adenocarcinoma is one of the most malignant tumors with a very poor prognosis. This cancer is unresponsive to treatment with all forms of therapy including chemotherapy, radiotherapy and immunotherapy. One of the reasons for the poor response of this cancer to therapy is that it is resistant to apoptosis-the common form of cell death that occurs with successful treatments of cancers. We have been investigating signaling systems responsible for preventing apoptosis in this cancer so that strategies can be developed to overcome these "survival" signals for treatment. To date, we have identified both extracellular matrix and reactive oxygen species (ROS) as survival factors in this cancer. Furthermore, we have found that this cancer undergoes apoptosis when exposed to several plant-derived polyphenolic compounds. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. RP Gukovskaya, AS (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-021-7 PY 2003 BP 345 EP 348 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BY68F UT WOS:000189437800060 ER PT B AU Pandol, SJ Gukovsky, I Satoh, A Fischer, L Lugea, A Gukovskaya, AS AF Pandol, SJ Gukovsky, I Satoh, A Fischer, L Lugea, A Gukovskaya, AS BE Sikiric, P Seiwerth, S Mozsik, G Arakawa, T Takeuchi, K TI Molecular mechanisms of pancreatitis SO PROCEEDINGS OF THE 11TH INTERNATIONAL CONFERENCE ON ULCER RESEARCH LA English DT Proceedings Paper CT 11th International Conference on Ulcer Research CY SEP 15-20, 2003 CL Dubrovnik, CROATIA ID KAPPA-B ACTIVATION; ACINAR-CELLS; NEUTROPHILS; CYTOKINES; ETHANOL; RATS C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. RP Pandol, SJ (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-021-7 PY 2003 BP 349 EP 352 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BY68F UT WOS:000189437800061 ER PT S AU Barbieri, R Matten, EC Brown, EN AF Barbieri, R Matten, EC Brown, EN GP IEEE TI Instantaneous monitoring of heart rate variability SO PROCEEDINGS OF THE 25TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-4: A NEW BEGINNING FOR HUMAN HEALTH SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 25th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 17-21, 2003 CL Cancun, MEXICO SP IEEE Engn Med & Biol Soc, Coral, Univ Autonome Metropolitana, Sandia Natl Lab DE heart rate; heart rate variability; stochastic processes; inverse Gaussian ID TIME-SERIES ANALYSIS; MYOCARDIAL-INFARCTION; SPECTRAL-ANALYSIS; NEUROPATHY AB Most of the currently accepted approaches to compute heart rate and assess heart rate variability operate on interpolated, continuous-valued heart rate signals, thereby ignoring the underlying discrete structure of human heart beats. To overcome this limitation, we model the stochastic structure of heart beat intervals as a history-dependent, inverse Gaussian process and derive from it an explicit probability density describing heart rate and heart rate variability. We estimate the parameters of the inverse Gaussian model by local maximum likelihood and assess model goodness-of-fit using Q-Q plot analyses. We apply our model in an analysis of human heart beat intervals from a tilt-table experiment. Our results suggest that the new definitions of heart rate and heart rate variability convey different information than other conventional indices, both in time and frequency domains, and may have important implications for research studies of cardiovascular and autonomic regulation. C1 Harvard Univ, MIT,Sch Med, Massachusetts Gen Hosp,Div Hlth Sci & Technol, Dept Anesthesia & Crit Care,Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Barbieri, R (reprint author), Harvard Univ, MIT,Sch Med, Massachusetts Gen Hosp,Div Hlth Sci & Technol, Dept Anesthesia & Crit Care,Neurosci Stat Res Lab, Boston, MA 02114 USA. OI Barbieri, Riccardo/0000-0001-9381-3833 NR 19 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7789-3 J9 P ANN INT IEEE EMBS PY 2003 VL 25 BP 204 EP 207 DI 10.1109/IEMBS.2003.1279570 PN 1-4 PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Medicine, Research & Experimental; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Computer Science; Engineering; Research & Experimental Medicine; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BY50W UT WOS:000189395300056 ER PT B AU Monga, U Garber, SL Thornby, J Vallbona, C Monga, TN AF Monga, U Garber, SL Thornby, J Vallbona, C Monga, TN TI Exercise prevents fatigue and improves quality of life in prostate cancer patients undergoing radiation therapy SO PROCEEDINGS OF THE 2ND WORLD CONGRESS OF THE INTERNATIONAL SOCIETY OF PHYSICAL AND REHABILITATION MEDICINE - ISPRM LA English DT Proceedings Paper CT 2nd World Congress of the International-Society-of-Physical-and-Rehabilitation-Medicine (ISPRM) CY MAY 18-23, 2003 CL Prague, CZECH REPUBLIC SP Int Soc Phys & Rehabilitat Med ID AEROBIC EXERCISE; DEPRESSION; ADULTS C1 Houston VA Med Ctr, Houston, TX 77211 USA. RP Monga, U (reprint author), Houston VA Med Ctr, Houston, TX 77211 USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-3124-1 PY 2003 BP 499 EP 504 PG 6 WC Rehabilitation SC Rehabilitation GA BX04U UT WOS:000184053400103 ER PT B AU Kohane, DS AF Kohane, DS BE Reisman, S Foulds, R Mantilla, B TI Microparticulate focal drug delivery to the peripheral and central nervous systems SO PROCEEDINGS OF THE IEEE 29TH ANNUAL NORTHEAST BIOENGINEERING CONFERENCE LA English DT Proceedings Paper CT IEEE 29th Annual Northeast Bioengineering Conference CY MAR 22-23, 2003 CL NJ INST TECHNOL, NEWARK, NJ SP Schering Plough, Becton Dickinson, Boston Sci, Reva Med, Vyteris, Whitaker Fdn, NJIT Pre Coll Programs, NJIT Student Senate, NJIT Grad Student Assoc HO NJ INST TECHNOL DE analgesia; anticonvulsant; microsphere ID PROTEIN-SUGAR PARTICLES; BIOCOMPATIBILITY; TETRODOTOXIN; BUPIVACAINE AB Focal drug delivery using microparticles holds great promise in treating specific disorders in the peripheral and central nervous systems. In the peripheral nervous system, controlled release technology is readily applicable to providing prolonged nerve blockade, while in the central nervous system there is increasing interest in its uses for epilepsy and movement disorders. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Intens Care Unit, Boston, MA 02115 USA. RP Kohane, DS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Intens Care Unit, Boston, MA 02115 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-7767-2 PY 2003 BP 313 EP 314 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BX14C UT WOS:000184414900155 ER PT S AU Cariani, P AF Cariani, P GP IEEE IEEE TI Recurrent timing nets for auditory scene analysis SO PROCEEDINGS OF THE INTERNATIONAL JOINT CONFERENCE ON NEURAL NETWORKS 2003, VOLS 1-4 SE IEEE International Joint Conference on Neural Networks (IJCNN) LA English DT Proceedings Paper CT International Joint Conference on Neural Networks CY JUL 20-24, 2003 CL PORTLAND, OR SP Int Neural Network Soc, IEEE Neural Networks Soc ID DIFFERENT FUNDAMENTAL FREQUENCIES; CONCURRENT VOWELS; PITCH; PERCEPTION; IDENTIFICATION; SYSTEM; MODEL; TIME AB We have recently proposed neural timing networks that operate on temporal fine structure of inputs to build up and separate periodic signals with different fundamental periods (Neural Networks, 14: 737-753, 2001). Simple recurrent nets consist of arrays of coincidence detectors fed by common input lines and conduction delay loops of different recurrence times. Short-term facilitation amplifies correlations between input and loop signals to amplify periodic patterns and segregate those with different periods, thereby allowing constituent waveforms to be recovered. Timing nets constitute a new, general strategy for scene analysis that builds up correlational invariances rather than feature-based labeling, segregation and binding of channels. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab & Auditory Physiol, Boston, MA 02114 USA. RP Cariani, P (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab & Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. NR 39 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1098-7576 BN 0-7803-7898-9 J9 IEEE IJCNN PY 2003 BP 1575 EP 1580 PG 6 WC Computer Science, Artificial Intelligence SC Computer Science GA BX30P UT WOS:000184903300288 ER PT B AU El-Zaatari, FAK Hulten, K Collins, MT Huchzermeier, R Graham, DY AF El-Zaatari, FAK Hulten, K Collins, MT Huchzermeier, R Graham, DY BE Juste, RA Geijo, MV Garrido, JM TI p35-based ELISA assay for the detection of Mycobacterium avium subsp paratuberculosis infection in cattle with Johne's disease SO PROCEEDINGS OF THE SEVENTH INTERNATIONAL COLLOQUIUM ON PARATUBERCULOSIS LA English DT Proceedings Paper CT 7th International Colloquium on Paratuberculosis CY JUN 12-14, 2002 CL Bilbao, SPAIN SP Int Assoc Paratuberculos Inc DE p35; ELISA; subclinical; Johne's disease ID BOVINE PARATUBERCULOSIS; CROHNS-DISEASE; DIAGNOSIS; ETIOLOGY; COWS AB Early diagnosis of paratuberculosis (Johne's disease) in cattle is essential for controlling the spread of the disease. Available tests lack sensitivity. A purified p35-based ELISA assay was developed and optimized and its efficacy as compared to that of commercial ELISA assays was evaluated on 44 reference sera. Sera from 10 Mycobacterium avium subsp. paratuberculosis (Map)-free cattle and 3 cows artificially inoculated with multiple doses of viable Map were negative by most assays. Sera from 12 cattle with clinically advanced Johne's disease were positive by all assays. For sera from cows with subclinical infection, p35-ELISA was positive in 13/19 (68%) as compared to 42%, 47% and 53% for the most commonly used commercial ELISAs. An additional subclinical case (14/19; 73%) was positive by only p35 immunoblotting. The specificity and the positive predictive values of p35-based ELISA and the three most commonly used commercial ELISAs were 100% and the negative predictive values were 63% for p35-ELISA and 48%, 50% and 53% for the commercial ELISAs, respectively. Based on this limited initial evaluation, the p35-ELISA shows promise as a potentially more sensitive and specific test for paratuberculosis. The addition of p35-based immunoblot test further improved detection of subclinical cases. Evaluation of p35-ELISA on a larger set of well-characterized sera is warranted. C1 VA Med Ctr, Houston, TX 77030 USA. RP El-Zaatari, FAK (reprint author), VA Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU INT ASSOC PARATUBERCULOSIS INC PI PROVIDENCE PA SWP 526, RI HOSPITAL 593 EDDY STREET, PROVIDENCE, RI 02903 USA BN 0-9633043-5-6 PY 2003 BP 136 EP 139 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases; Microbiology; Veterinary Sciences SC Public, Environmental & Occupational Health; Infectious Diseases; Microbiology; Veterinary Sciences GA BAD78 UT WOS:000221711100031 ER PT J AU Freedland, SJ Amling, CL Terris, MK Presti, JC Elashoff, D Kane, CJ AF Freedland, SJ Amling, CL Terris, MK Presti, JC Elashoff, D Kane, CJ CA SEARCH Database Study Grp TI Is there a difference in outcome after radical prostatectomy between patients with biopsy Gleason sums 4, 5, and 6? results from the SEARCH database SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article DE radical prostatectomy; PSA recurrence; Gleason sum; needle biopsy ID BIOCHEMICAL RECURRENCE; SEXTANT BIOPSIES; RADIATION-THERAPY; NEEDLE-BIOPSY; CANCER; ADENOCARCINOMA; DIAGNOSIS; PREDICTOR; TRENDS; GRADE AB Purpose: Fewer patients newly diagnosed with prostate cancer today have biopsy Gleason sums <6 compared to several years ago. Several tables and nomograms for predicting disease recurrence after definitive therapy provide little or no discrimination between biopsy Gleason sums 4, 5, and 6. We sought to examine the significance of biopsy Gleason sum for predicting biochemical failure following radical prostatectomy ( RP) for men with biopsy Gleason sums of 4, 5, and 6. Materials and methods: We examined data from 988 men treated with RP between 1988 and 2002 who had biopsy Gleason sums of 4 - 6. Clinical and pathological variables as well as outcome information were compared between men with biopsy Gleason sums of 4 - 6. The log-rank and Cox proportional hazards analysis were used to determine whether biopsy Gleason sum provided unique prognostic information for men with low biopsy Gleason sums undergoing RP. Results: There was statistically significant, but overall weak correlation between biopsy Gleason sum and Gleason sum of the RP specimen ( Spearman's r = 0.277, P<0.001). As biopsy Gleason sum increased from 4 to 5 to 6, there was a steady rise (HR = 1.31 for each one point increase in Gleason sum, Cox's model) in the risk of PSA failure ( P = 0.025, log-rank). On multivariate analysis comparing biopsy Gleason sum, preoperative PSA, clinical stage, year of surgery, percent of biopsy cores positive, and age for their ability to predict time to biochemical recurrence, only PSA ( HR 2.09, CI 1.56 - 2.80, P<0.001) and biopsy Gleason sum ( HR 1.33, CI 1.05 - 1.70, P = 0.019) were significant independent predictors of PSA failure. Conclusions: Despite weak correlation between biopsy and pathologic Gleason sum among men with biopsy Gleason sum 4 - 6 tumors, grade was a significant independent predictor of PSA failure following RP. In the range of 4 - 6, biopsy Gleason sum acted as a continuous variable for predicting PSA failure. The routine use of Gleason sums 4 and 5 to grade prostate needle biopsy specimens should not be abandoned. C1 Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90095 USA. San Diego Naval Hosp, Dept Urol, San Diego, CA USA. Med Coll Georgia, Div Urol, Augusta, GA 30912 USA. Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. Vet Adm Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Biostat, Los Angeles, CA USA. Vet Adm Med Ctr, Dept Surg, Urol Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. RP Freedland, SJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Urol, Box 951738, Los Angeles, CA 90095 USA. OI Terris, Martha/0000-0002-3843-7270 NR 24 TC 5 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PY 2003 VL 6 IS 3 BP 261 EP 265 DI 10.1038/sj.pcan.4500673 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 724UY UT WOS:000185506100016 PM 12970733 ER PT S AU Rauch, SL AF Rauch, SL BE Ng, V Barker, GJ Hendler, T TI Neuroimaging: A contemporary approach to improved understanding of mental illness SO PSYCHIATRIC NEUROIMAGING SE NATO SCIENCE SERIES, SUB-SERIES I: LIFE AND BEHAVIOURAL SCIENCES LA English DT Proceedings Paper CT NATO Advanced Research Workshop on Psychiatric Neuroimaging CY SEP 29-OCT 01, 2002 CL Chiavari, ITALY ID OBSESSIVE-COMPULSIVE DISORDER; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; BASAL GANGLIA VOLUMES; SYMPTOM PROVOCATION; CAUDATE-NUCLEUS; PREDICTORS; IMPLICIT; THERAPY; PET AB Neuroimaging methods can be used to advance understanding of mental illnesses in a variety of ways. Generally, neuroimaging research can contribute to the development of pathophysiologic models of psychiatric diseases which, in turn, can influence the diagnostic scheme in psychiatry. Clinically, neuroimaging tests can be developed to aid in differential diagnosis, facilitate early diagnosis, and provide information to guide treatment (such as predictors of treatment response). Neuroimaging can also be used synergistically, in conjunction with other modes of inquiry; for instance, neuroimaging profiles can be used to provide extended phenotypes for genetic research. There now exist a panoply of imaging tools and imaging strategies which can be applied in an integrated fashion to achieve these ends. This paper will review various approaches and provide examples, as background for the subsequent sections of this volume which will address many of these issues in greater detail. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Rauch, SL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 29 TC 0 Z9 0 U1 2 U2 3 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1566-7693 BN 1-58603-344-1 J9 NATO SCI SER I LIFE PY 2003 VL 348 BP 3 EP 8 PG 6 WC Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BBP50 UT WOS:000226885400001 ER PT S AU Chen, YI Brownell, A Choi, JK Nguyen, TV Rosen, BR Jenkins, BG AF Chen, YI Brownell, A Choi, JK Nguyen, TV Rosen, BR Jenkins, BG BE Ng, V Barker, GJ Hendler, T TI Pharmacologic imaging of the dopamine system SO PSYCHIATRIC NEUROIMAGING SE NATO SCIENCE SERIES, SUB-SERIES I: LIFE AND BEHAVIOURAL SCIENCES LA English DT Proceedings Paper CT NATO Advanced Research Workshop on Psychiatric Neuroimaging CY SEP 29-OCT 01, 2002 CL Chiavari, ITALY ID MRI; PET; TRANSPLANTATION; STIMULATION AB Pharmacologically-mediated MRI (phMRI) is a new concept to probe the neurotransmitter circuitry. A neurotransmitter specific pharmacological ligand is administrated and the cerebral hemodynamic changes (either BOLD, cerebral blood flow CBF or cerebral blood volume CBV) are continuously monitored by MRI. We have particularly focused on the dopaminergic system. Our prior studies have shown that the response to dopaminergic ligands is not correlated with changes in systemic physiological variables such as CO2 and is dependent on dopaminergic innervation. This technique allows us to probe the dopaminergic function in diseases, such as neurodegeneration, drug abuse, and mental illness. In the following, we used Parkinson's disease (PD) as an example here 1. Probing neurodegeneration:We mimicked PD in rats by using unilateral lesioning with 6-hydroxydopamine (6-OHDA) in the medial forebrain bundle. This destroys the dopamine input from substantia nigra to the striatum unilaterally. phMRI with D-amphetamine showed ablation of the hemodynamic response in the ipsilateral striatum. We also tested phMRI with amphetamine in MPTP treated monkeys --- a PD model typically used in primates. phMRI with amphetamine showed nearly complete loss of hemodynamic response in caudate, putamen and substantia nigra compared to the normal control monkeys. However, the activation in nucleus accumbens was spared in the MPTP monkeys. 2. Receptor supersensitivity:When animals were lesioned with 6-OHDA, upregulation of postsynaptic dopamine receptors developed due to the insufficient dopamine innervation. phMRI with apormorphine showed greater rCBV increase in the striatum ipsilateral to the 6-OHDA lesion. The opposite effect was observed with amphetamine. These results were correlated with PET imaging of post-synaptic D2 receptors. 3. Probing the survivability of neurotransplantation:When either fetal dopaminergic cells or embryonic stem cells were transplanted into the dopamine depleted striatum, phMRI with amphetamine challenge showed a restoration of the hemodynamic response in the graft site.There was also a restoration of hemodynamic activity in cortical areas indicating the establishment of the neuronal interaction between the grafted cells and cortical neurons. 4. Validation of the phMRI results with PET.-We used positron emission tomography (PET) to validate the phMRI results. All the PET results with dopaminergic ligands (11C-CFT, 11Craclopride, 11C-SCH23390) correlated with our phMRI findings in 6-OHDA rats and MPTP treated monkeys, as well as in those animals with neurotransplantations. 5. Questions and discussion: 1. What factors contribute to the hemodynamic changes we measure in phMRI? 2. Can we probe any kind of neurotransmitter in the brain by using phMRI technique? Are we just lucky to pick dopamine at the first place? 3. What can we learn from the phMRI hemodynamic change? Can we model the time course to quantify the receptor dynamics?. C1 Massachusetts Gen Hosp, Athionaoula A Martinos, Boston, MA 02129 USA. RP Chen, YI (reprint author), Massachusetts Gen Hosp, Athionaoula A Martinos, Boston, MA 02129 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1566-7693 BN 1-58603-344-1 J9 NATO SCI SER I LIFE JI Nato Sci. Ser. Sub-Ser. I-Life Behav. Sci. PY 2003 VL 348 BP 207 EP 214 PG 8 WC Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BBP50 UT WOS:000226885400029 ER PT J AU Tapp, A Wood, AE Secrest, L Erdmann, J Cubberley, L Kilzieh, N AF Tapp, A Wood, AE Secrest, L Erdmann, J Cubberley, L Kilzieh, N TI Combination antipsychotic therapy in clinical practice SO PSYCHIATRIC SERVICES LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 09-14, 2000 CL SAN JUAN, PUERTO RICO SP Amer Coll Neuropsychopharmacol ID REFRACTORY SCHIZOPHRENIA; CLOZAPINE; RISPERIDONE; AUGMENTATION; POLYPHARMACY AB Objective: Surveys have shown that antipsychotic drug combinations are frequently prescribed, vet few clinical studies have examined this practice. Experts have generally recommended antipsychotic combinations, especially those combining an atypical and a conventional antipsychotic, as a measure of last resort. A survey of prescribers was conducted to examine why combination antipsychotic therapy is being used in outpatient clinical practice. Methods: Antipsychotic prescribing practices in the Department of Veterans Affairs Puget Sound Health System were reviewed for a six-month period during 1998-1999. Data on the use of atypical and conventional antipsychotics in combination were collected. Results: A total of 1,794 patients received prescriptions for at least one antipsychotic medication during the study period, of which 715 (40 percent) received an atypical agent. Ninety-three patients (13 percent) who were treated with an atypical antipsychotic received a prescription for combination antipsychotic therapy for at least 30 days. In cases in which both a conventional and an atypical agent were prescribed, the primary reason given for adding a conventional antipsychotic medication was to treat persistent positive symptoms. The primary, reason an atypical agent was added to a conventional agent was to switch medications to the atypical agent; however, a significant number of patients became "stuck" on the combination. Conclusions: The results of this study support previous reports of the frequent use of combination antipsychotic therapy in clinical practice. Prospective controlled trials are needed to substantiate perceptions that combination antipsychotic therapy is clinically beneficial and to provide guidelines on when and for whom antipsychotic polypharmacy should be considered. C1 VA Puget Sound Hlth Care Syst, Amer Lake Div, Tacoma, WA 98493 USA. Univ Washington, Dept Psychiat, Seattle, WA USA. Dept Vet Affairs Puget Sound Hlth Care Syst, Tacoma, WA USA. RP Tapp, A (reprint author), VA Puget Sound Hlth Care Syst, Amer Lake Div, Tacoma, WA 98493 USA. NR 23 TC 111 Z9 112 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD JAN PY 2003 VL 54 IS 1 BP 55 EP 59 DI 10.1176/appi.ps.54.1.55 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 631XL UT WOS:000180193300010 PM 12509667 ER PT J AU Frueh, BC Elhai, JD Gold, PB Monnier, J Magruder, KM Keane, TM Arana, GW AF Frueh, BC Elhai, JD Gold, PB Monnier, J Magruder, KM Keane, TM Arana, GW TI Disability compensation seeking among veterans evaluated for posttraumatic stress disorder SO PSYCHIATRIC SERVICES LA English DT Article ID COMBAT VETERANS; VIETNAM VETERANS; SUPPORTED EMPLOYMENT; MENTAL-ILLNESS; LEAST WELL; PTSD; OUTCOMES; PSYCHOPATHOLOGY; EXAGGERATION; THERAPY AB Objective: This study sought to further examine the relationship between compensation-seeking status and reporting of symptoms among combat veterans who were evaluated for posttraumatic stress disorder (PTSD). Methods: Archival data were drawn for 320 adult male combat veterans who were consecutively evaluated at a Department of Veterans Affairs (VA) PTSD outpatient clinic from 1995 to 1999. The veterans were compared on variables from their clinical evaluation, including diagnostic status and self-report measures such as the Minnesota Multiphasic Personality Inventory-2, which includes scales designed to detect feigned or exaggerated psychopathology. Results: Compensation-seeking veterans reported significantly more distress across domains of psychopathology, even after the effects of income had been controlled for and despite an absence of differences in PTSD diagnoses between groups. However, compensation-seeking veterans also were much more likely to overreport or exaggerate their symptoms than were non-compensation-seeking veterans. Conclusions: This study provided further evidence that VA disability compensation incentives influence the way some veterans report their symptoms when they are being evaluated for PTSD. These data suggest that current VA disability policies have problematic implications for the delivery of clinical care, evaluation of treatment outcome, and rehabilitation efforts within the VA. C1 Vet Affairs Med Ctr, Mental Hlth Serv 116, Charleston, SC 29401 USA. Univ S Carolina, Vet Affairs Med Ctr, Charleston, SC USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. Vet Affairs Med Ctr, Natl Ctr PTSD, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Frueh, BC (reprint author), Vet Affairs Med Ctr, Mental Hlth Serv 116, 109 Bec St, Charleston, SC 29401 USA. FU NIMH NIH HHS [MH-01660, MH-61983] NR 46 TC 69 Z9 69 U1 1 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD JAN PY 2003 VL 54 IS 1 BP 84 EP 91 DI 10.1176/appi.ps.54.1.84 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 631XL UT WOS:000180193300015 PM 12509672 ER PT J AU Aisen, PS Berg, JD Craft, S Peskind, ER Sano, M Teri, L Mulnard, RA Thomas, RG Thal, LJ AF Aisen, PS Berg, JD Craft, S Peskind, ER Sano, M Teri, L Mulnard, RA Thomas, RG Thal, LJ TI Steroid-induced elevation of glucose in Alzheimer's disease: relationship to gender, apolipoprotein E genotype and cognition SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Alzheimer's disease; prednisone; hyperglycemia; apolipoprotein E; gender; cognition ID RANDOMIZED CONTROLLED-TRIAL; INSULIN-RESISTANCE; MEMORY; ENHANCEMENT; METABOLISM; DEMENTIA AB Glucose and insulin may play an important role in the pathophysiology and symptomatology of Alzheimer s disease (AD), and prior studies suggest interactions among glucose, insulin, gender and apolipoprotein E genotype. We analyzed the relationship between steroid-induced glucose elevation and gender, presence of the apolipoprotein E epsilon4 (APOE-4) allele and cognition using data from a multicenter trial of prednisone therapy in AD. The low-dose prednisone regimen (initial dose: 20 mg/day. maintenance dose: 10 mg/day) caused a moderate increase in random blood. glucose (mean post-baseline glucose 115 mg/dl). There was a significant interaction between rise in glucose, gender and presence of the APOE-4 allele. There was no important relationship between glucose and cognitive function at baseline or with prednisone treatment. Meta-analysis including data from three other AD trial,, showed a small influence of random blood glucose oil cognitive scores. These results support a relationship between gender, apolipoprotein F. genotype and glucose metabolism, but do not indicate that mild changes in glucose have an important impact on cognitive function. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA. Univ Calif San Diego, Alzheimers Dis Cooperat Study, San Diego, CA 92103 USA. Univ Washington, Sch Med, Geriatr Res Educ & Clin Ctr, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Med, Mental Illness Res Educ & Clin Ctr, Vet Affairs Puget Sound Hlth Care, Seattle, WA USA. Columbia Univ Coll Phys & Surg, Dept Neurol, Gertrude H Sergievsky Ctr, New York, NY 10032 USA. Univ Washington, Sch Med, Dept Psychosocial & Community Hlth, Seattle, WA USA. Univ Calif Irvine, Inst Brain Aging & Dementia, Irvine, CA USA. Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. RP Aisen, PS (reprint author), Georgetown Univ, Med Ctr, Dept Neurol, 1 Bles Bldg,3800 Reservoir Rd NW, Washington, DC 20007 USA. EM psa@georgetown.edu FU NIA NIH HHS [U19 AG010483, U01-AG10483] NR 18 TC 7 Z9 9 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN PY 2003 VL 28 IS 1 BP 113 EP 120 AR PII S0306-4530(02)00015-X DI 10.1016/S0306-4530(02)00015-X PG 8 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 634RK UT WOS:000180354300008 PM 12445840 ER PT J AU Kisley, MA Olincy, A Robbins, E Polk, SD Adler, LE Waldo, MC Freedman, R AF Kisley, MA Olincy, A Robbins, E Polk, SD Adler, LE Waldo, MC Freedman, R TI Sensory gating impairment associated with schizophrenia persists into REM sleep SO PSYCHOPHYSIOLOGY LA English DT Article DE sensory gating; REM sleep; schizophrenia; auditory event-related potentials; P50; N100 ID AUDITORY-EVOKED-RESPONSES; P50 SUPPRESSION; MISMATCH NEGATIVITY; PARADOXICAL SLEEP; NATURAL SLEEP; POTENTIALS; DEFICITS; STRESS; INTENSITY; DISORDER AB Physiological measures of sensory gating are increasingly used to study biological factors associated with attentional dysfunction in psychiatric and neurologic patient populations, The present study as designed to assess sensory gating during rapid eye movement (REM) sleep in patients with schizophrenia, a population bearing a genetic load for gating impairment. Auditory event-related potentials (ERPs) were recorded in response to paired clicks during separate waking and overnight sleep recording sessions in controls and schizophrenia patients. Suppression of ERP component P50 was significantly impaired in the patient group during both waking and REM sleep. whereas the difference between groups for N100 gating was dependent on state. These results suggest that REM sleep is an appropriate state during,which to assess P50 gating in order to disentangle the effects of state and trait on sensors gating impairment in other clinical populations. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Boulder, CO 80309 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Kisley, MA (reprint author), Univ Colorado, Dept Psychol, 1420 Austin Bluffs Pkwy, Colorado Springs, CO 80933 USA. FU NIMH NIH HHS [MH64466, MH38321] NR 70 TC 33 Z9 34 U1 4 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JAN PY 2003 VL 40 IS 1 BP 29 EP 38 DI 10.1111/1469-8986.00004 PG 10 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 636KT UT WOS:000180455300004 PM 12751801 ER PT J AU Sitnikova, T Kuperberg, G Holcomb, PJ AF Sitnikova, T Kuperberg, G Holcomb, PJ TI Semantic integration in videos of real-world events: An electrophysiological investigation SO PSYCHOPHYSIOLOGY LA English DT Article DE comprehension of real-world events; viewing video film clips; semantic anomalies; event-retated potentials (ERPs) ID BRAIN POTENTIALS; PICTURES; LANGUAGE; WORDS; N400 AB Event-related potentials (ERPs) discriminated between contextually appropriate and inappropriate objects appearing in video film clips of common activities. Incongruent objects elicited a larger negative-going deflection which was similar to the N400 component described previously in association with words and static pictures and which has been argued to reflect the integration of semantic information into a mental representation of the preceding context. The onset of this potential occurred shortly after object presentation, indicating that semantic integration is a rapid online component of real-world perception. In addition, the anomalies in movies evoked a large late positive potential at posterior regions, suggesting that in event perception, semantic incongruity may trigger cognitive processes other than those mediating pure semantic integration. C1 Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Sitnikova, T (reprint author), Tufts Univ, Dept Psychol, Medford, MA 02155 USA. FU NICHD NIH HHS [HD25889] NR 20 TC 103 Z9 103 U1 3 U2 10 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JAN PY 2003 VL 40 IS 1 BP 160 EP 164 DI 10.1111/1469-8986.00016 PG 5 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 636KT UT WOS:000180455300016 PM 12751813 ER PT J AU McCarley, R Salisbury, D Wible, C Kubicki, M AF McCarley, R Salisbury, D Wible, C Kubicki, M TI ERP and MRI investigations of echoic memory in schizophrenia via the mismatch paradigm SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 29-NOV 02, 2003 CL CHICAGO, ILLINOIS SP Soc Psychophysiol Res C1 VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2003 VL 40 SU 1 BP S9 EP S9 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 715BV UT WOS:000184951400028 ER PT J AU McCarley, RW AF McCarley, RW TI Gamma frequency abnormalities and schizophrenia SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 29-NOV 02, 2003 CL CHICAGO, ILLINOIS SP Soc Psychophysiol Res C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2003 VL 40 SU 1 BP S17 EP S17 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 715BV UT WOS:000184951400065 ER PT J AU Miller, MW Dillon, AL Kanter, FS AF Miller, MW Dillon, AL Kanter, FS TI Effects of exogenous cortisol on amplitude of the startle reflex SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 29-NOV 02, 2003 CL CHICAGO, ILLINOIS SP Soc Psychophysiol Res DE startle; cortisol C1 Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2003 VL 40 SU 1 BP S60 EP S60 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 715BV UT WOS:000184951400238 ER EF