FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Zorn, E Floyd, B Kim, H Lee, S Alyea, E Soiffer, R Antin, J Ritz, J AF Zorn, E Floyd, B Kim, H Lee, S Alyea, E Soiffer, R Antin, J Ritz, J TI Chronic Graft-Versus-Host-Disease correlates with a quantitative defect in CD4+CD25+ T cell populations after allogeneic stem cell transplantation SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting of the International-Society-for-Experimental-Hematology CY JUL 05-08, 2003 CL PARIS, FRANCE SP Int Soc Exptl Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2003 VL 31 IS 7 SU 1 MA 73 BP 83 EP 84 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 701HR UT WOS:000184162600069 ER PT J AU Iwasaki, H Mizuno, S Shigematsu, H Takatsu, K Akashi, K AF Iwasaki, H Mizuno, S Shigematsu, H Takatsu, K Akashi, K TI Eosinophil-committed progenitors are generated from granulocyte/monocyte progenitors by instructive action of GATA-2 SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting of the International-Society-for-Experimental-Hematology CY JUL 05-08, 2003 CL PARIS, FRANCE SP Int Soc Exptl Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Med Sci, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2003 VL 31 IS 7 SU 1 MA 131 BP 102 EP 103 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 701HR UT WOS:000184162600122 ER PT J AU Elfenbein, G Oblon, D Falvey, M Morgan, D Sackstein, R AF Elfenbein, G Oblon, D Falvey, M Morgan, D Sackstein, R TI Post-grafting G-CSF accelerates granulocyte engraftment after G-CSF pretreated allogeneic stem cell transplantation SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting of the International-Society-for-Experimental-Hematology CY JUL 05-08, 2003 CL PARIS, FRANCE SP Int Soc Exptl Hematol C1 Roger Williams Med Ctr, Providence, RI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2003 VL 31 IS 7 SU 1 MA 165 BP 115 EP 115 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 701HR UT WOS:000184162600156 ER PT J AU Maia, S Ghia, P Haining, W Sallan, S Nadler, L Cardoso, A AF Maia, S Ghia, P Haining, W Sallan, S Nadler, L Cardoso, A TI The BAX isoform BAX-DELTA is expressed by leukemia cells and is a novel tumor-associated antigen SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting of the International-Society-for-Experimental-Hematology CY JUL 05-08, 2003 CL PARIS, FRANCE SP Int Soc Exptl Hematol C1 Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Turin, IRCC, Turin, Italy. NR 0 TC 0 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2003 VL 31 IS 7 SU 1 MA 241 BP 140 EP 141 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 701HR UT WOS:000184162600231 ER PT J AU Shigematsu, H Iwasaki, H Mizuno, S Akashi, K AF Shigematsu, H Iwasaki, H Mizuno, S Akashi, K TI The majority of plasmacytoid dendritic cells originate from myeloid progenitors in murine hematopoiesis SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting of the International-Society-for-Experimental-Hematology CY JUL 05-08, 2003 CL PARIS, FRANCE SP Int Soc Exptl Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2003 VL 31 IS 7 SU 1 MA 401 BP 195 EP 195 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 701HR UT WOS:000184162600390 ER PT J AU Kraus, AB Shaffer, J Toh, HC Preffer, F Dombkowski, D Saidman, S Colby, C George, R McAfee, S Sackstein, R Dey, B Spitzer, TR Sykes, M AF Kraus, AB Shaffer, J Toh, HC Preffer, F Dombkowski, D Saidman, S Colby, C George, R McAfee, S Sackstein, R Dey, B Spitzer, TR Sykes, M TI Early host CD8 T-cell recovery and sensitized anti-donor interleukin-2-producing and cytotoxic T-cell responses associated with marrow graft rejection following nonmyeloablative allogeneic bone marrow transplantation SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID MINOR HISTOCOMPATIBILITY ANTIGENS; CYTOLYTIC LYMPHOCYTES-T; INTENSIVE CHEMOTHERAPY; MIXED CHIMERISM; CLASS-I; LEUKEMIA; FAILURE; DEPLETION; DISEASE; THERAPY AB Objective. We developed a nonmyeloablative conditioning regimen for allogeneic bone marrow transplantation (BMT) followed by donor lymphocyte infusions (DLI) for treatment of chemotherapy refractory malignancies. Although the majority of patients who receive this regimen achieve lasting mixed or full allogeneic chimerism, approximately 30% show initial mixed chimerism followed by loss of the donor graft. These patients recover host hematopoiesis without significant cytopenias. To assess the role of immunologic rejection in graft loss, we compared T-cell recovery and in vitro alloresponses in six patients who lost their marrow graft to that in 16 concurrent patients with sustained donor chimerism. Patients and Methods. Conditioning included pretransplant cyclophosphamide (150-200 mg/ kg), thymic irradiation (700 cGy), and pre- and post-transplant equine antithymocyte globulin (ATG; ATGANI). HLA-identical related donor BMT was followed by DLI at approximately day 35 in patients without graft-vs-host disease. Results. The group with transient chimerism showed significantly increased circulating host T-cell (median 416 cells/mm(3) vs 10 cells/mm(3), p < 0.05) and CD8 T-cell numbers (354 cells/mm(3) vs 71 cells/mm(3), p < 0.05) compared to the group with stable mixed or full donor chimerism within the first 100 days post-BMT. All DLI recipients who lost chimerism following DLI had greater than 80% recipient T cells at the time of DLI, whereas those with persistent chimerism had <60% host T cells. Graft rejection was associated with the development of a sensitized anti-donor bulk cytotoxic T-lymphocyte (CTL) response in 4 of 6 evaluated patients, compared to only 1 of 10 evaluated patients with sustained chimerism (P < 0.05). Additionally, 3 of 5 evaluated transient chimeras showed high anti-donor CTL precursor frequencies in limiting dilution assays, and 3 of 4 evaluated transient chimeras showed high anti-donor interleukin-2 (IL-2)-producing T-helper (T-H) cell frequencies. High anti-donor T-H or cytotoxic T-lymphocyte precursors were not detected in sustained chimeras. Conclusion. These data indicate that loss of chimerism in patients receiving this nonmyeloablative regimen is due to immune-mediated rejection. This rejection appears to be mediated by recovering recipient cytolytic CD8(+) cells as well as IL-2-producing recipient T-H cells. These data are the first to demonstrate sensitization of recipient anti-donor IL-2-producing cells in association with human marrow allograft rejection. (C) 2003 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr,Dept Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Sykes, M (reprint author), Massachusetts Gen Hosp E, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [R01 CA79986]; NHLBI NIH HHS [R01 HL63474] NR 51 TC 39 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2003 VL 31 IS 7 BP 609 EP 621 DI 10.1016/S0301-472X(03)00082-1 PG 13 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 699JB UT WOS:000184052300006 PM 12842706 ER PT J AU Mizoguchi, E Xavier, RJ Reinecker, HC Uchino, H Bhan, AK Podolsky, DK Mizoguchi, A AF Mizoguchi, E Xavier, RJ Reinecker, HC Uchino, H Bhan, AK Podolsky, DK Mizoguchi, A TI Colonic epithelial functional phenotype varies with type and phase of experimental colitis SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; ALPHA-MUTANT MICE; T-CELLS; INTESTINAL INFLAMMATION; CALPROTECTIN EXPRESSION; INTERFERON-GAMMA; GENE-EXPRESSION; RECEPTOR; INHIBITION; HYPERPLASIA AB Background & Aims: Colonic crypt elongation occurs during both chronic colitis and in the recovery phase of acute colitis. The impact of these alterations on epithelial cell functions is not fully defined. Methods: DNA microarray analysis of freshly isolated colonic epithelial cells (CECs) from acute and chronic colitis was performed, and the results were confirmed by reverse transcription polymerase chain reaction. Localization of the selected molecules was examined by immunohistochemistry using newly generated antibodies. The function of selected molecules detected in this study was examined by administering the specific inhibitors in dextran sodium sulfate (DSS) colitis. Results: Several detoxification-associated molecules, which contribute to prevent inflammation by regulating physiological balance under normal conditions, were markedly down-regulated, and anti-inflammatory molecules, which are not normally expressed, were up-regulated in the CECs under the chronic colitis. Among the detoxification-associated molecules, carbonic anhydrase IV was specifically down-regulated in CEC of Th2- but not Th1-mediated colitis. Functionally, inhibition of carbonic anhydrase activity led to the enhancement of recovery from DSS-induced acute colitis by directly stimulating CEC proliferation. Increased expression of regeneration-associated molecules such as regenerating gene-IIIgamma was detectable in the CECs of acute and chronic colitis but not in the recovery phase of colitis. The expression of this molecule was restricted in surface epithelium and upper crypts but not lower crypts. Conclusions: These studies suggest that functional alterations, which result in either the exacerbation or the suppression of colitis, coexist in the CECs during chronic colitis. CEC functions are likely to be differentially regulated in the context of the stage and mechanism of colitis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA. RP Mizoguchi, E (reprint author), Massachusetts Gen Hosp, Immunopathol Unit, Warren 501C,55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK33506, DK43351, DK47677, DK54427] NR 62 TC 62 Z9 62 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2003 VL 125 IS 1 BP 148 EP 161 DI 10.1016/S0016-5085(03)00665-6 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 699GH UT WOS:000184048000020 PM 12851880 ER PT J AU Ahmad, NA Kochman, ML Brensinger, C Brugge, WR Faigel, DO Gress, FG Kimmey, MB Nickl, NJ Savides, TJ Wallace, MB Wiersema, MJ Ginsberg, GG AF Ahmad, NA Kochman, ML Brensinger, C Brugge, WR Faigel, DO Gress, FG Kimmey, MB Nickl, NJ Savides, TJ Wallace, MB Wiersema, MJ Ginsberg, GG TI Interobserver agreement among endosonographers for the diagnosis of neoplastic versus non-neoplastic pancreatic cystic lesions SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID TUMORS; CT; EUS AB Background: The aim of this study was to evaluate the degree of agreement among endosonographers for EUS diagnosis of neoplastic versus non-neoplastic pancreatic cystic lesions and the specific type of cystic lesion. Methods: Videotapes of EUS procedures from 31 consecutive cases of a range of histopathologically proven lesions, including mucinous cystic neoplasm, serous cystadenoma, neuroendocrine tumor, intraductal papillary mucinous tumor, and pseudocyst, were used to make a study video-tape, which was reviewed by 8 experienced endosonographers. The reviewers, blinded to clinical and surgical histopathology results, reviewed each case for the presence or absence of the following features: abnormality of pancreatic duct and parenchyma, margins, solid component, debris, and septations. They were asked to identify each lesion as neoplastic or non-neoplastic and to give a specific diagnosis for each lesion. Results: There was fair agreement between endosonographers for diagnosis of neoplastic versus non-neoplastic lesions (K = 0.24). Agreement for individual types of lesions was moderately good for serous cystadenomas (K = 0.46) but fair for the remainder. Agreement was moderately good for presence or absence of solid component (K = 0.43); fair for presence or absence of abnormal pancreatic duct (K = 0.29), debris (K = 0.21), and septations (K = 0.30); and slight for presence or absence of margins (K = 0.01) and abnormal pancreatic parenchyma (K = 0.01). Accuracy rates of EUS for the diagnosis of neoplastic versus non-neoplastic lesions ranged from 40% to 93%. Conclusions: There is little more than chance interobserver agreement among experienced endosonographers for diagnosis of neoplastic versus non-neoplastic, specific type, and EUS features of pancreatic cystic lesions. C1 Hosp Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Philadelphia VAMC, Philadelphia, PA USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Portland VAMC, Portland, OR USA. Winthrop Univ Hosp, Long Isl City, NY USA. Univ Washington, Seattle, WA 98195 USA. Univ Hosp, Chandler Med Ctr, Lexington, KY USA. UCSD, Med Ctr, San Diego, CA USA. MUSC, Charleston, SC USA. Mayo Clin, Rochester, MN USA. RP Ahmad, NA (reprint author), Hosp Univ Penn, Dept Med, Div Gastroenterol, 3rd Floor,Ravdin Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. NR 19 TC 136 Z9 140 U1 1 U2 2 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 JUL PY 2003 VL 58 IS 1 BP 59 EP 64 DI 10.1067/mge.2003.298 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 697YU UT WOS:000183971500010 PM 12838222 ER PT J AU Dobscha, SK Gerrity, MS Corson, K Bahr, A Cuilwik, NM AF Dobscha, SK Gerrity, MS Corson, K Bahr, A Cuilwik, NM TI Measuring adherence to depression treatment guidelines in a VA primary care clinic SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE depression; primary health care; guideline adherence ID QUALITY IMPROVEMENT PROGRAMS; HEALTH-CARE; COLLABORATIVE CARE; RANDOMIZED TRIAL; DISORDERS; INTERVENTION; MANAGEMENT; VALIDATION; DISABILITY; SYMPTOMS AB The primary objectives of this pilot study were to develop a measure of adherence for depression practice guidelines and to assess the degree to which providers and patients adhere to guidelines in a VA primary care setting. The Depression Guideline Measure (DGM) is based on three national guidelines. The DGM was used to review medical records of 111 patients with Patient Health Questionnaire (PHQ) scores greater than or equal to10. Interrater reliability for 15 of 19 DGM checklist items was excellent (kappa > 0.75). There was a broad range of adherence to guideline criteria: only 13.5% of patients were contacted for follow-up within 2 weeks, while 100% of providers documented follow-up plans. Forty percent of patients saw mental health providers, and 63% were prescribed antidepressants. A secondary objective of the study was to explore the relationship between guideline adherence and changes in PHQ scores. Among 51 patients who completed follow-up PHQs, no associations were detected. The results suggest that the DGM shows promise as a reliable measure of guideline adherence and that guideline criteria are frequently not met in busy primary care clinics. More research is needed to determine the validity of the DGM and the impact of guideline adherence on depression outcomes. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Portland VA Med, Behav Hlth & Clin Neurosci Div, Portland, OR 97207 USA. Portland VA Med Ctr, Div Hosp & Specialty Med, Portland, OR USA. Oregon Hlth Sci Univ, Sch Med, Portland, OR 97201 USA. RP Dobscha, SK (reprint author), Portland VA Med, Behav Hlth & Clin Neurosci Div, Portland, OR 97207 USA. NR 35 TC 19 Z9 19 U1 1 U2 4 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 JUL-AUG PY 2003 VL 25 IS 4 BP 230 EP 237 DI 10.1016/S0163-8343(03)00020-3 PG 8 WC Psychiatry SC Psychiatry GA 702AH UT WOS:000184201800003 PM 12850654 ER PT J AU Jhala, US Canettieri, G Screaton, RA Kulkarni, RN Krajewski, S Reed, J Walker, J Lin, XY White, M Montminy, M AF Jhala, US Canettieri, G Screaton, RA Kulkarni, RN Krajewski, S Reed, J Walker, J Lin, XY White, M Montminy, M TI CAMP promotes pancreatic beta-cell survival via CREB-mediated induction of IRS2 SO GENES & DEVELOPMENT LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; PROTEIN-KINASE; INSULIN-RESISTANCE; C-FOS; GROWTH; TRANSCRIPTION; DISRUPTION; APOPTOSIS; MICE; PHOSPHORYLATION AB The incretin hormone GLP1 promotes islet-cell survival via the second messenger cAMP. Here we show that mice deficient in the activity of CREB, caused by expression of a dominant-negative A-CREB transgene in pancreatic beta-cells, develop diabetes secondary to beta-cell apoptosis. Remarkably, A-CREB severely disrupted expression of IRS2, an insulin signaling pathway component that is shown here to be a direct target for CREB action in vivo. As induction of IRS2 by cAMP enhanced activation of the survival kinase Akt in response to insulin and IGF-1, our results demonstrate a novel mechanism by which opposing pathways cooperate in promoting cell survival. C1 Salk Inst Biol Studies, La Jolla, CA 92037 USA. Burnham Inst, La Jolla, CA 92037 USA. Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. RP Montminy, M (reprint author), Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. FU NIDDK NIH HHS [DK43828, DK49777, R01 DK049777]; NIGMS NIH HHS [GM37828, R37 GM037828] NR 24 TC 354 Z9 367 U1 3 U2 16 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUL 1 PY 2003 VL 17 IS 13 BP 1575 EP 1580 DI 10.1101/gad.1097103 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 698KL UT WOS:000183998600003 PM 12842910 ER PT J AU Lee, BC Cheng, T Adams, GB Attar, EC Miura, N Lee, SB Saito, Y Olszak, I Dombkowski, D Olson, DP Hancock, J Choi, PS Haber, DA Luster, AD Scadden, DT AF Lee, BC Cheng, T Adams, GB Attar, EC Miura, N Lee, SB Saito, Y Olszak, I Dombkowski, D Olson, DP Hancock, J Choi, PS Haber, DA Luster, AD Scadden, DT TI P2Y-like receptor, GPR105 (P2Y(14)), identifies and mediates chemotaxis of bone-marrow hematopoietic stem cells SO GENES & DEVELOPMENT LA English DT Article DE stem cells; hematopoiesis; chemotaxis; G-protein-coupled receptors; P2Y receptors ID PROTEIN-COUPLED RECEPTOR; UMBILICAL-CORD BLOOD; EX-VIVO EXPANSION; PROGENITOR CELLS; FUNCTIONAL-CHARACTERIZATION; CHEMOKINE RECEPTOR; NOD/SCID MICE; MOLECULAR-CLONING; LIMITING DILUTION; HUMAN EOSINOPHILS AB Hematopoiesis in mammals undergoes a developmental shift in location from fetal liver to bone marrow accompanied by a gradual transition from highly proliferative to deeply quiescent stem cell populations. P2Y receptors are G-protein-coupled nucleotide receptors participating in vascular and immune responses to injury. We identified a P2Y-like receptor for UDP-conjugated sugars, GPR105 (P2Y(14)), with restricted expression on primitive cells in the hematopoietic lineage. Anti-GPR105 antibody selectively isolated a subset of hematopoietic cells within the fetal bone marrow, but not in the fetal liver, that was enriched for GO cell cycle status and for in vitro stem-cell-like multipotential long-term culture capability. Conditioned media from bone marrow stroma induced receptor activation and chemotaxis that was sensitive to Galphai and anti-receptor antibody inhibition. GPR105 is a G-protein-coupled receptor identifying a quiescent, primitive population of hematopoietic cells restricted to bone marrow. It mediates primitive cell responses to specific hematopoietic microenvironments and extends the known immune system functions of P2Y receptors to the stem cell level. These data suggest a new class of receptors participating in the regulation of the stem cell compartment. C1 Harvard Univ, Sch Med, Ctr Regenerat Med & Technol, Massachusetts Gen Hosp, Boston, MA 02129 USA. Harvard Univ, Sch Med, MGH Canc Ctr, Massachusetts Gen Hosp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp, Boston, MA 02129 USA. RP Scadden, DT (reprint author), Harvard Univ, Sch Med, Ctr Regenerat Med & Technol, Massachusetts Gen Hosp, Boston, MA 02129 USA. NR 55 TC 54 Z9 57 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUL 1 PY 2003 VL 17 IS 13 BP 1592 EP 1604 DI 10.1101/gad.1071503 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 698KL UT WOS:000183998600005 PM 12842911 ER PT J AU Poulaki, V AF Poulaki, V TI Microdissection, microarrays and proteomics: a new approach to the study of eye diseases SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Editorial Material ID CANCER; PATTERNS; SERUM C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Res Lab, Boston, MA 02115 USA. RP Poulaki, V (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Res Lab, 325 Cambridge St, Boston, MA 02115 USA. NR 7 TC 2 Z9 3 U1 0 U2 2 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 JUL PY 2003 VL 241 IS 7 BP 527 EP 528 DI 10.1007/s00417-003-0713-x PG 2 WC Ophthalmology SC Ophthalmology GA 711ZN UT WOS:000184771100001 PM 12836036 ER PT J AU Agrawal, HR Hauser, ST Miller, M Penn, H AF Agrawal, HR Hauser, ST Miller, M Penn, H TI "My father did this to me!" - The psychodynamic treatment of an angry, sad, and violent young man SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE case report; Fairbairn; psychodynamic; resilience; Winnicott C1 Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Judge Baker Childrens Ctr, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Agrawal, HR (reprint author), Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat, 115 Mill St, Belmont, MA 02478 USA. NR 13 TC 4 Z9 4 U1 0 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 JUL-AUG PY 2003 VL 11 IS 4 BP 194 EP 209 DI 10.1080/10673220390235340 PG 16 WC Psychiatry SC Psychiatry GA 716XJ UT WOS:000185054700003 PM 12944127 ER PT J AU Yarnitsky, D Goor-Aryeh, I Bajwa, ZH Ransil, BI Cutrer, FM Sottile, A Burstein, R AF Yarnitsky, D Goor-Aryeh, I Bajwa, ZH Ransil, BI Cutrer, FM Sottile, A Burstein, R TI 2003 Wolff Award: Possible parasympathetic contributions to peripheral and central sensitization during migraine SO HEADACHE LA English DT Article DE migraine; allodynia; pain; headache; sphenopalatine ganglion; nociceptors; trigeminal ID NITRIC-OXIDE; SPHENOPALATINE GANGLION; CEREBRAL-ARTERIES; NERVE-FIBERS; MUSCLE TENDERNESS; COMMON MIGRAINE; SUBSTANCE-P; RAT SKIN; MECHANICAL HYPERALGESIA; PERICRANIAL TENDERNESS AB Background.-Neurologic signs of increased parasympathetic outflow to the head often accompany migraine attacks. Because increased parasympathetic outflow to the cranial cavity induces vasodilation of cerebral and meningeal blood vessels, it can enhance plasma protein extravasation and the release of proinflammatory mediators that activate perivascular nociceptors. We recently showed that activation of intracranial perivascular nociceptors induces peripheral and central sensitization along the trigeminovascular pathway and proposed that these sensitizations mediate the intracranial hypersensitivity and the cutaneous allodynia of migraine. Methods.-The present study investigates possible parasympathetic contributions to the generation of peripheral and central sensitization during migraine by applying intranasal lidocaine to reduce cranial parasympathetic outflow through the sphenopalatine ganglion. Results.-In the absence of migraine, patients were pain-free, and their skin sensitivity was normal. Their mean baseline pain thresholds were less than 15degreesC for cold, more than 45degreesC for heat, and more than 100 g for mechanical pressure. Their mean pain score was 7.5 of 10 (standard deviation, 1.4) during untreated migraine and 3.5 of 10 (standard deviation, 2.4) after the nasal lidocaine-induced sphenopalatine ganglion block (P<.0001). Most patients developed cutaneous allodynia during migraine, and their mean pain thresholds changed to more than 25degreesC for cold, less than 40degreesC for heat, and less than 10 g for mechanical pressure. Following the nasal lidocaine administration (sphenopalatine ganglion block), this allodynia remained unchanged in spite of the pain relief. Conclusion.-These findings suggest that cranial parasympathetic outflow contributes to migraine pain by activating or sensitizing (or both) intracranial nociceptors, and that these events induce parasympathetically independent allodynia by sensitizing the central nociceptive neurons in the spinal trigeminal nucleus. C1 Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Rambam Med Ctr, Dept Neurol, Haifa, Israel. Technion Fac Med, Haifa, Israel. RP Burstein, R (reprint author), Harvard Univ, Inst Med, Dept Anesthesia & Crit Care, Room 830,77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE 10904]; NINDS NIH HHS [NS 35611-01] NR 64 TC 67 Z9 68 U1 0 U2 11 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0017-8748 J9 HEADACHE JI Headache PD JUL PY 2003 VL 43 IS 7 BP 704 EP 714 DI 10.1046/j.1526-4610.2003.03127.x PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 705HP UT WOS:000184389900001 PM 12890124 ER PT J AU Blumenthal, D AF Blumenthal, D TI Toil and trouble? Growing the physician supply SO HEALTH AFFAIRS LA English DT Article ID NONPHYSICIAN CLINICIAN AB Richard Cooper outlines several obstacles to increasing the supply of U.S.-trained physicians. His analysis paints a bleak picture, but he may be underselling the possible benefits of technological advances that could increase medical school capacity and of increasing the volume of qualified applicants by broadening eligibility criteria. Another issue that would confront medical educators is that imbalances between supply and demand would not be uniform across states. This development could signal increased involvement from state policymakers, but public and private policymakers; should take steps to assure that resources are funneled to where doctors are needed most and to exploit opportunities for innovative curriculum development. C1 Massachusetts Gen Hosp, Partners HealthCare Syst, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Partners HealthCare Syst, Inst Hlth Policy, Boston, MA 02114 USA. NR 10 TC 6 Z9 6 U1 1 U2 1 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUL-AUG PY 2003 VL 22 IS 4 BP 85 EP 87 DI 10.1377/hlthaff.22.4.85 PG 3 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 699JY UT WOS:000184054800010 PM 12889753 ER PT J AU Imboden, M Shi, FS Pugh, TD Freud, AG Thom, NJ Hank, JA Hao, ZL Staelin, ST Sondel, PM Mahvi, DM AF Imboden, M Shi, FS Pugh, TD Freud, AG Thom, NJ Hank, JA Hao, ZL Staelin, ST Sondel, PM Mahvi, DM TI Safety of interleukin-12 gene therapy against cancer: A murine biodistribution and toxicity study SO HUMAN GENE THERAPY LA English DT Article ID MECHANISM AB As a prerequisite for a human clinical trial using interleukin (IL)-12 gene therapy, the biodistribution and safety of IL-12, administered as an intradermal naked DNA injection, was evaluated in mice. The pNGVL3-mIL12 plasmid used in this study is a nonviral vector designed to induce a high level of IL-12 protein expression during a transient transfection of the host cell. The biodistribution was evaluated by a polymerase chain reaction (PCR) assay that is capable of detecting less than 100 copies of the plasmid in the context of host DNA. Twenty-four hours after three intradermal injections of 0.5 mug or 5 mug of pNGVL3-mIL12 plasmid, the plasmid was detectable in various internal organs, the blood, and the injection site. The plasmid was detectable in the gonads of only one animal at the high-dose treatment 24 hr after the injections. In the majority of the organs the plasmid was undetectable throughout the study. Possible side effects were monitored by histology and clinical chemistry, and the level of IL-12 protein expression was assessed by enzyme-linked immunosorbent assay (ELISA). No treatment-related histologic abnormalities were detected and the blood chemistry parameters showed no toxicity. The IL-12 protein was undetectable at all times at the injection site and interferon (IFN)-gamma levels at the injection site and in the serum were at background levels. The results of this murine safety study indicate that based on the distribution pattern of the plasmid in the body and the undetectable toxicities in the tissues, the use of the pNGVL3-hIL12 plasmid in cancer gene therapy clinical trials can be considered as safe. C1 Univ Wisconsin, Dept Human Oncol, Madison, WI 53792 USA. Univ Wisconsin, Dept Surg, Madison, WI 53792 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53792 USA. Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. RP Mahvi, DM (reprint author), H4 724 Univ Wisconsin Hosp & Clin, 600 Highland Ave, Madison, WI 53792 USA. FU NCI NIH HHS [P30-CA 14520]; NIA NIH HHS [AG00650] NR 10 TC 22 Z9 22 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL PY 2003 VL 14 IS 11 BP 1037 EP 1048 DI 10.1089/104303403322124765 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 702BW UT WOS:000184205600001 PM 12885344 ER PT J AU Yunis, EJ AF Yunis, EJ TI D. Bernard Amos, 1923-2003 SO HUMAN IMMUNOLOGY LA English DT Biographical-Item C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Yunis, EJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD JUL PY 2003 VL 64 IS 7 BP 659 EP 661 DI 10.1016/S0198-8859(03)00129-0 PG 3 WC Immunology SC Immunology GA 697XV UT WOS:000183969300001 ER PT J AU Wang, DJ Oparil, S Feng, JA Li, P Perry, G Chen, LB Dai, MR John, SWM Chen, YF AF Wang, DJ Oparil, S Feng, JA Li, P Perry, G Chen, LB Dai, MR John, SWM Chen, YF TI Effects of pressure overload on extracellular matrix expression in the heart of the atrial natriuretic peptide-null mouse SO HYPERTENSION LA English DT Article DE atrial natriuretic factor; constriction; aorta; pressure overload; hypertrophy, cardiac; extracellular matrix; growth substances ID GROWTH-FACTOR PLEIOTROPHIN; RECEPTOR GENE-EXPRESSION; CARDIAC-HYPERTROPHY; OSTEOPONTIN EXPRESSION; MYOCARDIAL-INFARCTION; TISSUE INHIBITORS; DNA-SYNTHESIS; RAT-HEART; MICE; ANP AB This study tested the hypothesis that atrial natriuretic peptide has direct antihypertrophic actions on the heart by modulating expression of genes involved in cardiac hypertrophy and extracellular matrix production. Hearts of male, atrial natriuretic peptide-null and control wild-type mice that had been subjected to pressure overload after transverse aortic constriction and control unoperated hearts were weighed and subjected to microarray, Northern blot, and immunohistochemical analyses. Microarray and Northern blot analyses were used to identify genes that are regulated differentially in response to stress in the presence and absence of atrial natriuretic peptide. Immunohistochemical analysis was used to identify and localize expression of the protein products of these genes. Atrial natriuretic peptide-null mice demonstrated cardiac hypertrophy at baseline and an exaggerated hypertrophic response to transverse aortic constriction associated with increased expression of the extracellular matrix molecules periostin, osteopontin, collagen I and III, and thrombospondin, as well as the extracellular matrix regulatory proteins, matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-3, and the novel growth factor pleiotrophin compared with wild-type controls. These results support the hypothesis that atrial natriuretic peptide protects against pressure overload-induced cardiac hypertrophy and remodeling by negative modulation of genes involved in extracellular matrix deposition. C1 Univ Alabama, Vasc Biol & Hypertens Program, Div Cardiovasc Dis, Dept Med, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Cardiol Sect, Birmingham, AL USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Howard Hughes Med Inst, Bar Harbor, ME USA. RP Chen, YF (reprint author), Univ Alabama, Vasc Biol & Hypertens Program, Div Cardiovasc Dis, Dept Med, 1008 ZRB, Birmingham, AL 35294 USA. FU NHLBI NIH HHS [HL-44195, HL-07457, HL-50147, HL-56046, HL-64614]; NIGMS NIH HHS [GM20069] NR 40 TC 105 Z9 113 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2003 VL 42 IS 1 BP 88 EP 95 DI 10.1161/01.HYP.0000074905.22908.A6 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 697NP UT WOS:000183949900015 PM 12756220 ER PT J AU Li, W Rosenzweig, A Huber, BT AF Li, W Rosenzweig, A Huber, BT TI Differential T-cell activation by B7-1 expression SO IMMUNOLOGY LA English DT Article ID AGE-ASSOCIATED INCREASE; IMMUNE-RESPONSE; GENE-THERAPY; COSTIMULATION; MACROPHAGES; TOLERANCE; INDUCTION; PEPTIDES; PROTEINS; PATHWAYS AB T-cell receptor-mediated T-cell activation requires cosimulation signal, which can be provided by B7-1 molecule. Our previous study demonstrated that the coexpression of a covalent peptide/major histocompatibility complex class II molecule complex and costimulatory molecule B7-1 by recombinant adenovirus leads to synergy in peptide-specific T-cell activation. However, the viral antigen-specific T-cell activation is not enhanced by B7-1 expressed by the adenovirus. To verify the differential T cell activation by B7-1 and investigate its underlying mechanisms, we constructed an adenovirus coexpressing a covalent complex of hen egg lysozyme peptide/I-A(k) (HEL46-61/I-A(k)) and B7-1 in the present study. In vivo studies revealed that HEL46-61-specific T-cell response, but not viral antigen-specific T-cell response, was enhanced by B7-1 expression mediated by the adenovirus, suggesting that exogenous B7-1 expression may regulate T-cell response to these two different antigens through distinct mechanisms. Furthermore, our results revealed that antigen-presenting cells were unsusceptible to adenovirus infection in vivo. Based on these findings, the possible mechanism of differential B7-1 costimulation on peptide-specific and viral antigen-specific T-cell activation is discussed. C1 Univ Miami, Sch Med, Dept Ophthalmol, Coral Gables, FL 33124 USA. Univ Miami, Sch Med, Dept Microbiol & Immunol, Coral Gables, FL 33124 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. RP Li, W (reprint author), McKnight Res Ctr, Dept Ophthalmol, 1638 NW 10th Ave, Miami, FL 33136 USA. FU NEI NIH HHS [R03 EY013698, R03 EY-013698]; NIDDK NIH HHS [T32-DK-07471, T32 DK007471] NR 24 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JUL PY 2003 VL 109 IS 3 BP 336 EP 342 DI 10.1046/j.1365-2567.2003.01658.x PG 7 WC Immunology SC Immunology GA 691BG UT WOS:000183584500005 PM 12807478 ER PT J AU Midorikawa, K Ouhara, K Komatsuzawa, H Kawai, T Yamada, S Fujiwara, T Yamazaki, K Sayama, K Taubman, MA Kurihara, H Hashimoto, K Sugai, M AF Midorikawa, K Ouhara, K Komatsuzawa, H Kawai, T Yamada, S Fujiwara, T Yamazaki, K Sayama, K Taubman, MA Kurihara, H Hashimoto, K Sugai, M TI Staphylococcus aureus susceptibility to innate antimicrobial peptides, beta-defensins and CAP18, expressed by human keratinocytes SO INFECTION AND IMMUNITY LA English DT Article ID METHICILLIN RESISTANCE; VANCOMYCIN RESISTANCE; HUMAN BETA-DEFENSIN-1; EPITHELIAL-CELLS; HOST-DEFENSE; LIPOTEICHOIC ACID; CANDIDA-ALBICANS; GENE-EXPRESSION; BINDING-PROTEIN; IMMUNITY AB The antimicrobial peptides human beta-defensin-1 (hBD1), hBD2, hBD3, and CAP18 expressed by keratinocytes have been implicated in mediation of the innate defense against bacterial infection. To gain insight into Staphylococcus aureus infection, the susceptibility of S. aureus, including methicillin-resistant S. aureus (MRSA), to these antimicrobial peptides was examined. Based on quantitative PCR, expression of hBD2 mRNA by human keratinocytes was significantly induced by contact with S. aureus, and expression of hBD3 and CAP18 mRNA was slightly induced, while hBD1 mRNA was constitutively expressed irrespective of the presence of S. aureus. Ten clinical S. aureus isolates, including five MRSA isolates, induced various levels of expression of hBD2, hBD3, and CAP18 mRNA by human kertinocytes. The activities of hBD3 and CAP18 against S. aureus were found to be greater than those of hBD1 and bBD2. A total of 44 S. aureus clinical isolates, including 22 MRSA strains, were tested for susceptibility to hBD3 and CAP18. Twelve (55%) and 13 (59%) of the MRSA strains exhibited more than 20% survival in the presence of hBD3 (1 mug/ml) and CAP18 (0.5 mug/ml), respectively. However, only three (13%) and two (9%) of the methicillin-sensitive S. aureus isolates exhibited more than 20% survival with hBD3 and CAP18, respectively, suggesting that MRSA is more resistant to these peptides. A synergistic antimicrobial effect between suboptimal doses of methicillin and either hBD3 or CAP18 was observed with 10 MRSA strains. Furthermore, of several genes associated with methicillin resistance, inactivation of the fmtC gene in MRSA strain COL increased susceptibility to the antimicrobial effect mediated by hBD3 or CAP18. C1 Ehime Univ, Sch Med, Dept Dermatol, Onsen, Ehime 7910295, Japan. Hiroshima Univ, Grad Sch Biomed Sci, Dept Bacteriol, Hiroshima 7348553, Japan. Hiroshima Univ, Grad Sch Biomed Sci, Dept Periodontol & Endodontol, Hiroshima 7348553, Japan. Kawasaki Med Univ, Dept Microbiol, Okayama 7010192, Japan. Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. RP Komatsuzawa, H (reprint author), Hiroshima Univ, Fac Dent, Dept Microbiol, Minami Ku, Kasumi 1-2-3, Hiroshima 7348553, Japan. FU NIDCR NIH HHS [DE14551-01, DE03420, K22 DE014551, R01 DE003420, R37 DE003420] NR 51 TC 127 Z9 136 U1 2 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2003 VL 71 IS 7 BP 3730 EP 3739 DI 10.1128/IAI.71.7.3730-3739.2003 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 694WB UT WOS:000183797200008 PM 12819054 ER PT J AU Lau, GW Goumnerov, BC Walendziewicz, CL Hewitson, J Xiao, WZ Mahajan-Miklos, S Tompkins, RG Perkins, LA Rahme, LG AF Lau, GW Goumnerov, BC Walendziewicz, CL Hewitson, J Xiao, WZ Mahajan-Miklos, S Tompkins, RG Perkins, LA Rahme, LG TI The Drosophila melanogaster toll pathway participates in resistance to infection by the gram-negative human pathogen Pseudomonas aeruginosa SO INFECTION AND IMMUNITY LA English DT Article ID ANTIMICROBIAL PEPTIDE GENES; IMMUNE-RESPONSE; BACTERIAL VIRULENCE; HOST-DEFENSE; MOLECULAR-MECHANISMS; NUCLEAR IMPORT; REL PROTEINS; DORSAL; DIF; EXPRESSION AB Pseudomonas aeruginosa is a gram-negative pathogen that infects immunocompromised and cystic fibrosis patients. The molecular basis of the host-P. aeruginosa interaction and the effect of specific P. aeruginosa virulence factors on various components of the innate immunity pathways are largely unknown. We examine interactions between P. aeruginosa virulence factors and components of innate immunity response in the Drosophila melanogaster model system to reveal the importance of the Toll signaling pathway in resistance to infection by the P. aeruginosa human isolate PA14. Using the two PA14-isogenic mutants plcS and dsbA, we show that Drosophila loss-of-function mutants of Spatzle, the extracellular ligand of Toll, and Dorsal and Dif, two NF-kappaB-like transcription factors, allow increased P. aeruginosa infectivity within fly tissues. In contrast, a constitutively active Toll mutant and a loss-of-function mutant of Cactus, an IkappaB-like factor that inhibits the Toll signaling, reduce infectivity. Our finding that Dorsal activity is required to restrict P. aeruginosa infectivity in Drosophila provides direct in vivo evidence for Dorsal function in adult fly immunity. Additionally, our results provide the basis for future studies into interactions between P. aeruginosa virulence factors and components of the Toll signaling pathway, which is functionally conserved between flies and humans. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. Shriners Burns Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. RP Rahme, LG (reprint author), Massachusetts Gen Hosp, Dept Surg, Wellman 3,50 Blossom St, Boston, MA 02114 USA. OI xiao, wenzhong/0000-0003-4944-6380 NR 44 TC 102 Z9 108 U1 0 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2003 VL 71 IS 7 BP 4059 EP 4066 DI 10.1128/IAI.71.7.4059-4066.2003 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 694WB UT WOS:000183797200050 PM 12819096 ER PT J AU Wei, J Goldberg, MB Burland, V Venkatesan, MM Deng, W Fournier, G Mayhew, GF Plunkett, G Rose, DJ Darling, A Mau, B Perna, NT Payne, SM Runyen-Janecky, LJ Zhou, S Schwartz, DC Blattner, FR AF Wei, J Goldberg, MB Burland, V Venkatesan, MM Deng, W Fournier, G Mayhew, GF Plunkett, G Rose, DJ Darling, A Mau, B Perna, NT Payne, SM Runyen-Janecky, LJ Zhou, S Schwartz, DC Blattner, FR TI Complete genome sequence and comparative genomics of Shigella flexneri serotype 2a strain 2457T (vol 71, pg 2775, 2003) SO INFECTION AND IMMUNITY LA English DT Correction C1 Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. Univ Wisconsin, Genome Ctr Anim Hlth & Biol Sci, Madison, WI 53706 USA. Univ Wisconsin, Genome Ctr, Madison, WI 53706 USA. Univ Wisconsin, Dept Chem, Madison, WI 53706 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Walter Reed Army Inst Res, Dept Enter Infect, Div Communicable Dis & Immunol, Silver Spring, MD 20910 USA. Univ Texas, Inst Mol & Cellular Biol, Austin, TX 78712 USA. RP Wei, J (reprint author), Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. NR 1 TC 6 Z9 6 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2003 VL 71 IS 7 BP 4223 EP 4223 DI 10.1128/IAI.71.7.4223.2003 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 694WB UT WOS:000183797200078 ER PT J AU Mizoguchi, A Mizoguchi, E Bhan, AK AF Mizoguchi, A Mizoguchi, E Bhan, AK TI Immune networks in animal models of inflammatory bowel disease SO INFLAMMATORY BOWEL DISEASES LA English DT Editorial Material DE animal models; IBD; colitis; regulatory cells; pathogenic cells ID CD4(+) T-CELLS; ALPHA-MUTANT MICE; DEXTRAN SULFATE SODIUM; TUMOR-NECROSIS-FACTOR; CHRONIC INTESTINAL INFLAMMATION; CHAIN-DEFICIENT MICE; COLONIC LAMINA PROPRIA; TNBS-INDUCED COLITIS; GAMMA-DELTA-CELLS; NF-KAPPA-B AB The animal models of inflammatory bowel disease provide a framework to define the immunopathogenesis of intestinal inflammation. Studies in these models support the hypothesis that exaggerated immune responses to normal enteric microflora are involved in the initiation and perpetuation of chronic intestinal inflammation. A major pathway involves development of acquired immune responses by the interactions of CD4(+) T-cell receptor alphabeta T cells with antigen-presenting cells (dendritic cells). Immunoregulatory cells, including Trl cells, Th3 cells, and CD4(+) CD25(+) T cells and B cells, directly or indirectly affect the T-cell receptor alphabeta T cell-induced immune responses and bridge innate and acquired immunity. The study of these complicated immune networks provides the rationale for the development of new therapeutic interventions in inflammatory bowel disease. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis,Dept Pathol,Immu, Boston, MA 02114 USA. RP Bhan, AK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis,Dept Pathol,Immu, Warren 501,55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK43351, DK47677] NR 268 TC 54 Z9 54 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JUL PY 2003 VL 9 IS 4 BP 246 EP 259 DI 10.1097/00054725-200307000-00005 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 699RH UT WOS:000184069400005 PM 12902848 ER PT J AU Muthukumar, N Smith, RM McCaskie, AW Batchelor, AGG Joyce, AD AF Muthukumar, N Smith, RM McCaskie, AW Batchelor, AGG Joyce, AD TI A rare presentation of pelvic fracture as haematuria SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article ID BLADDER TRAUMA; MANAGEMENT; DIAGNOSIS; INJURY; RUPTURE C1 Hull Royal Infirm, Dept Trauma & Orthopaed Surg, Kingston Upon Hull HU3 2JZ, N Humberside, England. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Univ Newcastle, Sch Med, Dept Trauma & Orthopaed Surg, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. St James Univ Hosp, Dept Plast Surg, Leeds LS9 7TF, W Yorkshire, England. St James Univ Hosp, Dept Urol, Leeds LS9 7TF, W Yorkshire, England. RP Muthukumar, N (reprint author), Hull Royal Infirm, Dept Trauma & Orthopaed Surg, Anlaby Rd, Kingston Upon Hull HU3 2JZ, N Humberside, England. NR 12 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD JUL PY 2003 VL 34 IS 7 BP 540 EP 542 AR PII S0020-1383(02)00263-2 DI 10.1016/S0020-1383(02)00263-2 PG 3 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 703DK UT WOS:000184264600016 PM 12832185 ER PT J AU Hess, DR Dillman, C Kacmarek, RM AF Hess, DR Dillman, C Kacmarek, RM TI Vitro evaluation of aerosol bronchodilator delivery during mechanical ventilation: pressure-control vs. volume control ventilation SO INTENSIVE CARE MEDICINE LA English DT Article DE mechanical ventilation; aerosol therapy; nebulizer; pressurized metered dose inhaler ID METERED-DOSE INHALER; COPD PATIENTS; IN-VITRO; NEBULIZER; EFFICIENCY; MODEL; FLOW; THERAPY AB Objective. To determine the effect of inspiratory time and inspiratory flow pattern on albuterol delivery by aerosol during mechanical ventilation. Design. A ventilator was connected to a lung model and set to deliver a tidal volume of 0.6 l, PEEP 5 cmH(2)O, and respiratory rate of 15/min. We evaluated inspiratory times of 1 and 2 s, lung mechanics of 0.05 l/cmH(2)O compliance and 50 cmH(2)O/l/s resistance, or 0.02 l/cmH(2)O compliance and 5 cmH(2)O/l/s resistance, and three inspiratory flow patterns (constant flow volume-controlled ventilation, descending ramp flow volume-controlled ventilation, and pressure-controlled ventilation). Albuterol was delivered into the ventilator circuit by a nebulizer containing 5 mg (4 ml) albuterol or a pMDI and spacer (four actuations; 360 mug). A filter between the Y-piece and the lung model collected the aerosol, which was analyzed for albuterol by spectrophotometry. Results. For the nebulizer there were significant differences in albuterol delivered for inspiratory time, flow pattern, and lung mechanics. For the pMDI there were no significant differences for the amount of albuterol delivered for inspiratory time, flow pattern, or lung mechanics. Conclusions. Albuterol delivery by nebulizer is affected by inspiratory time and inspiratory flow pattern. When a pMDI is used, the amount of albuterol delivered is not affected by inspiratory flow pattern or inspiratory time. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. NR 27 TC 31 Z9 31 U1 1 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD JUL PY 2003 VL 29 IS 7 BP 1145 EP 1150 DI 10.1007/s00134-003-1792-1 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 698ZD UT WOS:000184030000019 PM 12750882 ER PT J AU Xu, GL Meyer, JS Huang, YG Du, F Chowdhury, M Quach, M AF Xu, GL Meyer, JS Huang, YG Du, F Chowdhury, M Quach, M TI Adapting Mini-Mental State Examination for dementia screening among illiterate or minimally educated elderly Chinese SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE elderly; Chinese; cognitive disorders; cultural influences; dementing disorders; cognitive screening ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; CLINICAL-DIAGNOSIS; VASCULAR DEMENTIA; TESTS; AGE; INSTRUMENT; HEALTH; MCI AB Background Illiteracy is prevalent among current elderly Chinese. There are few brief cognitive tests in Chinese designed to screen those possibly demented for more detailed evaluation in a clinical setting. Objectives The present study adapted the Mini-Mental State Examination (MMSE) for screening dementia among illiterate or less educated elderly Chinese. Methods Literacy-dependent items of the MMSE were modified or substituted by equivalent items that are not literacy-dependment. Some items were modified to provide socio-cultural compatibility. After developing it, the Chinese adapted MMSE (CAMSE) was administered to 370 elderly outpatients from Xijing hospitals located in Xi'an, China, 93 of whom were found to be demented and 277 non-demented. Sensitivities and specificities for detecting dementia were evaluated by adjusting for different CAMSE cut-off points. The optimal cut-off points of 22 for literates and 20 for illiterates yielded a sensitivity of 83.87% and a specificity of 84.48%. Corresponding positive predictive value (PPV) was 0.65, and negative predictive value (NPV) was 0.94. The impact of literacy on CAMSE and individual test items was also evaluated. Illiterate subjects got a higher CAMSE total score than literate subjects (p < 0.05). Only one out of 12 test items, serial sevens, was negatively influenced by illiteracy (p < 0.01). After an interval of 4-6 weeks, 32 randomly selected subjects were retested with CAMSE. The test-retest reliability for total scores was 0.75 (p 0.01). Conclusions Results suggest that in the socio-cultural context for Chinese, irrespective of their literacy skills, CAMSE proved feasible for use in clinical settings for dementia screening. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Baylor Coll Med, Cerebrovasc Res Lab, VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Hosp PLA, Dept Neurol, Yantai, Peoples R China. Fourth Mil Med Univ, Xijing Hosp, Dept Neurol, Xian 710032, Peoples R China. RP Meyer, JS (reprint author), Baylor Coll Med, Cerebrovasc Res Lab, VA Med Ctr, Bldg 110,Room 225,2002 Holcombe Blvd, Houston, TX 77030 USA. OI Xu, Gelin/0000-0002-6194-0341 NR 34 TC 43 Z9 46 U1 2 U2 16 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD JUL PY 2003 VL 18 IS 7 BP 609 EP 616 DI 10.1002/gps.890 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 701YM UT WOS:000184196600006 PM 12833305 ER PT J AU Rutan, JS AF Rutan, JS TI Sandor Ferenczi's contributions to psychodynamic group therapy SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article C1 Massachusetts Gen Hosp, Ctr Grp Psychotherapy, Boston, MA 02114 USA. Boston Inst Psychotherapies Inc, Boston, MA USA. RP Rutan, JS (reprint author), 71 Waban Hill Rd, Chestnut Hill, MA 02467 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD JUL PY 2003 VL 53 IS 3 BP 375 EP 384 DI 10.1521/ijgp.53.3.375.42825 PG 10 WC Psychology, Clinical SC Psychology GA 692PL UT WOS:000183669400006 PM 12841100 ER PT J AU Young, RH AF Young, RH TI Andrew G. Ostor, MD, 1943-2003 SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Biographical-Item ID MEDICAL EPONYMS; IMMORTAL WOMEN; ESSAYS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02115 USA. RP Young, RH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02115 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 2003 VL 22 IS 3 BP 217 EP 219 DI 10.1097/01.PGP.0000071047.12278.98 PG 3 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 693PB UT WOS:000183725000001 ER PT J AU Godinho, RN Kamil, S Keogh, I Sih, T Eavey, R AF Godinho, RN Kamil, S Keogh, I Sih, T Eavey, R TI The Internet - current trends and future expectations among Brazilian pediatricians and otolaryngologists with a special interest in pediatric otolaryngology SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE technology; Internet; Web site; Brazilian physicians ID WEB AB Objective: To assess Internet use among a group of Brazilian pediatricians and otolaryngologists and to inquire about possible Web based medical resources. Methods: Questionnaires were distributed among attendees of a 2001 Pediatric Otolaryngology meeting in Brazil. Multiple choice or yes/no questions related to the use of the Internet among physicians were presented. Results: All of the 99 respondents of an estimated 900 attendees, had Internet access (high-speed 18%, conventional 77%); 52% at home, 42% in the office and 6% at both sites. Eighty-one percent of those responding regularly used the Internet for medical updating. Sharing a pediatric otolayngology medical association Web site with patients was desired by 73%; an interest in personal Web based medical information and updates was demonstrated by 97%. Five percent of respondents already had established personal practice Web sites and 54% agreed with potential benefits for improving medical practice. Conclusion: The potential role of electronic communication and a desire to establish a pediatric otolaryngology Web site that would maximize inclusiveness is appreciated by this group of Brazilian otolaryngologists and pediatricians. (C) 2003 Published by Elsevier Science Ireland Ltd. C1 Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Pontificia Univ Catolica, Inst Ciencias Biol & Saude, Belo Horizonte, MG, Brazil. Univ Sao Paulo, Lab Med Invest, Sch Med, Sao Paulo, Brazil. RP Godinho, RN (reprint author), Rua Joaquim Coura 347 Cemig, BR-35700149 Sete Lagoas, MG, Brazil. RI KEOGH, IVAN/M-2704-2016 OI KEOGH, IVAN/0000-0001-6358-6377 NR 10 TC 3 Z9 5 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD JUL PY 2003 VL 67 IS 7 BP 729 EP 732 DI 10.1016/S0165-5876(03)00068-5 PG 4 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 692TK UT WOS:000183676200002 PM 12791446 ER PT J AU Lawenda, BD Taghian, AG Kachnic, LA Hamdi, H Smith, BL Gadd, MA Mauceri, T Powell, SN AF Lawenda, BD Taghian, AG Kachnic, LA Hamdi, H Smith, BL Gadd, MA Mauceri, T Powell, SN TI Dose-volume analysis of radiotherapy for T1N0 invasive breast cancer treated by local excision and partial breast irradiation by low-dose-rate interstitial implant SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE radiation; breast cancer; brachytherapy; dose-volume ID RANDOMIZED CLINICAL-TRIAL; PRIMARY RADIATION-THERAPY; CONSERVATIVE SURGERY; STAGE-I; CONSERVING SURGERY; DEFINITIVE RADIATION; AXILLARY DISSECTION; COSMETIC EVALUATION; PRESERVING SURGERY; PROGNOSTIC FACTORS AB Purpose: To evaluate the toxicity of partial breast irradiation (RT) using escalating doses of low-dose-rate interstitial implant as the sole adjuvant local therapy for selected T1N0 breast cancer patients treated by wide local excision. The results of a European Organization for Research and Treatment of Cancer study have demonstrated a significant local control benefit using external beam RT to 65 Gy compared with 50 Gy. Thus, the tolerance of escalating doses of partial breast RT should be determined, because this approach may become a standard treatment for patients with early-stage breast cancer. Methods and Materials: Between 1997 and 2001, 48 patients with T1N0M0 breast cancer were enrolled into an institutional review board-approved Phase I/II protocol using low-dose-rate brachytherapy implants after wide local excision and lymph node staging surgery. Brachytherapy was started 3-4 days after surgery at a dose rate of 50 cGy/h, using Ir-192 sources evenly spaced to cover 3 cm around the resection margins. Typically, 2-3 planes were used, with a median of 14 catheters (range 10-16). The total dose was escalated in three groups: 50 Gy (n = 19), 55 Gy (n = 16), and 60 Gy (n = 13). The implant volume was calculated and used to classify patients into quartiles: 76-127 cm(3) (n = 12), 128-164 cm(3) (n = 12), 165-204 cm(3) (n = 12), and >204 cm(3) (n = 12). Cosmesis, patient satisfaction, treatment-related complications, mammographic abnormalities, rebiopsies, and disease status were recorded at each scheduled patient visit. Results: The median follow-up for all patients was 23.1 months (range 2-43). Very good to excellent cosmetic results were observed in 91.8% of patients. Ninety-two percent of patients were satisfied with their cosmetic outcome and said they would choose brachytherapy again over the standard course of external beam RT. Six perioperative complications occurred: two developed bleeding at the time of catheter removal, two had abscesses, one developed a hematoma, and one had a nonhealing sinus tract requiring surgical intervention. Significant fibrosis (moderate-to-severe scarring and thickening of the skin and breast) was noted in only 4 patients; I had received 55 Gy and 3 had received 60 Gy. Abnormal posttreatment mammograms were seen in 19 patients. Eight patients underwent rebiopsy for abnormalities found either by mammography or on physical examination; all proved to be fat necrosis or post-RT changes. The rebiopsy rates appeared to correlate with doses greater than or equal to55 Gy (6 [75%] of 8 compared with 29 [60%]of 48 overall) and implant volumes greater than or equal to128 cm(3) (7 [87.5%] of 8 compared with 36 [75%] of 48 overall). To date, no local, regional, or distant recurrences have been observed. Conclusion: Low-dose-rate implants up to 60 Gy were well-tolerated overall. With an implant dose of 60 Gy, the incidence of posttreatment fibrosis (25%) appeared to be increased. Only the long-term follow-up of this and other implant studies will allow an understanding of the total radiation dose necessary for tumor control and the volume of breast that requires treatment. (C) 2003 Elsevier Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Powell, SN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Cox 3,100 Blossom St, Boston, MA 02114 USA. NR 67 TC 79 Z9 81 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 JUL 1 PY 2003 VL 56 IS 3 BP 671 EP 680 DI 10.1016/S0360-3016(03)00071-3 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 687DY UT WOS:000183361800010 PM 12788172 ER PT J AU Zhang, H Sekiguchi, Y Hanada, S Hugenholtz, P Kim, H Kamagata, Y Nakamura, K AF Zhang, H Sekiguchi, Y Hanada, S Hugenholtz, P Kim, H Kamagata, Y Nakamura, K TI Gemmatimonas aurantiaca gen. nov., sp nov., a gram-negative, aerobic, polyphosphate-accumulating micro-organism, the first cultured representative of the new bacterial phylum Gemmatimonadetes phyl. nov. SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID ACTIVATED-SLUDGE; RIBOSOMAL-RNA; 16S RDNA; MICROBIAL-POPULATIONS; DIVERSITY; SOILS; IDENTIFICATION; COMMUNITY; REMOVAL; SEQUENCES AB A phylogenetically novel aerobic bacterium was isolated from an anaerobic-aerobic sequential batch reactor operated under enhanced biological phosphorus removal conditions for wastewater treatment. The isolation strategy used targeted slowly growing polyphosphate-accumulating bacteria by combining low-speed centrifugations and prolonged incubation on a low-nutrient medium. The isolate, designated strain T-27(T), was a Gram-negative, rod-shaped aerobe. Cells often appeared to divide by budding replication. Strain T-27(T) grew at 25-35degreesC with an optimum growth temperature of 30 C, whilst no growth was observed below 20 C or above 37 C within 20 days incubation. The pH range for growth was 6.5-9.5, with an optimum at pH 7.0. Strain T-27(T) was able to utilize a limited range of substrates, such as yeast extract, polypepton, succinate, acetate, gelatin and benzoate. Neisser staining was positive and 4,6-diamidino-2-phenylindole-stained cells displayed a yellow fluorescence, indicative of polyphosphate inclusions. Menaquinone 9 was the major respiratory quinone. The cellular fatty acids of the strain were mainly composed of iso-C15:0, C16:1 and C14:0. The G+C content of the genomic DNA was 66 mol%. Comparative analyses of 16S rRNA gene sequences indicated that strain T-27(T) belongs to candidate division BD (also called KS-B), a phylum-level lineage in the bacterial domain, to date comprised exclusively of environmental 16S rDNA clone sequences. Here, a new genus and species are proposed, Gemmatimonas aurantiaca (type strain T-27(T) = JCM 11422(T) = DSM 14586(T)) gen. nov., sp. nov., the first cultivated representative of the Gemmatimonadetes phyl. nov. Environmental sequence data indicate that this phylum is widespread in nature and has a phylogenetic breadth (19 % 16S rDNA sequence divergence) that is greater than well-known phyla such as the Actinobacteria (18 % divergence). C1 Natl Inst Adv Ind Sci & Technol, Inst Biol Resources & Funct, Tsukuba, Ibaraki 3058556, Japan. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Calif Berkeley, Dept Environm Sci Policy & Management, Berkeley, CA 94720 USA. RP Hanada, S (reprint author), Natl Inst Adv Ind Sci & Technol, Inst Biol Resources & Funct, Tsukuba, Ibaraki 3058556, Japan. RI Hugenholtz, Philip/G-9608-2011; OI hugenholtz, philip/0000-0001-5386-7925 NR 53 TC 162 Z9 170 U1 5 U2 43 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD JUL PY 2003 VL 53 BP 1155 EP 1163 DI 10.1099/ijs.0.02520-0 PN 4 PG 9 WC Microbiology SC Microbiology GA 702RR UT WOS:000184237700035 PM 12892144 ER PT J AU Giese, MJ Rayner, SA Fardin, B Sumner, HL Rozengurt, N Mondino, BJ Gordon, LK AF Giese, MJ Rayner, SA Fardin, B Sumner, HL Rozengurt, N Mondino, BJ Gordon, LK TI Mitigation of neutrophil infiltration in a rat model of early Staphylococcus aureus endophthalmitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 29-MAY 04, 2001 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID POLYMORPHONUCLEAR LEUKOCYTE; LUNG INJURY; EXPRESSION; VIRULENCE; SEPSIS AB PURPOSE. Infectious endophthalmitis is characterized by neutrophil migration into the eye. The purpose of this study was to determine whether systemic neutrophil depletion mitigates the ocular influx of neutrophils during the early phases of experimental endophthalmitis. METHODS. Endophthalmitis was induced in rats by intravitreal injection of Staphylococcus aureus. Animals received a single systemic dose of an anti-neutrophil-depleting antibody (dAb) or normal rabbit serum (NRS) 6 or 12 hours after intravitreal injection. Inflammation was graded both in vivo and by histopathology. Myeloperoxidase (MPO) was used as a biomarker of neutrophil infiltration. Bacterial clearance was evaluated by determining the amount of viable bacteria recovered from ocular specimens. RESULTS. Rats that received dAb 6 hours after bacterial injection exhibited significantly lower clinical scores, MPO activity, fewer vitreous exudates, and higher vitreous bacterial counts at 24 hours (P < 0.05). As the neutrophil population returned in this group, measured by the number in the peripheral blood, increasing intraocular inflammation was observed. Rats receiving dAb 12 hours after vitreous injection also demonstrated significantly lower clinical scores, MPO activity and less vitreous exudates at the 24-hour time point (P < 0.05). No significant differences from the control were detected at any of the subsequent time points, except in bacterial counts and MPO activity. CONCLUSIONS. Depletion of neutrophils early in the inflammatory response delayed the onset of severe ocular inflammation but also prevented adequate bacterial clearance. These results confirm the important role of neutrophils in ocular host defense during the early stages of experimental endophthalmitis. C1 Univ Calif Los Angeles, Sch Med, Ocular Inflammatory Dis Ctr, Jules Stein Eye Inst,Dept Ophthalmol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Ocular Inflammatory Dis Ctr, Jules Stein Eye Inst,Dept Pathol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Ocular Inflammatory Dis Ctr, Jules Stein Eye Inst,Dept Lab Med, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP Giese, MJ (reprint author), Ohio State Univ, Coll Ophthalmol, 320 W 10th Ave,A144, Columbus, OH 43210 USA. NR 25 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 JUL PY 2003 VL 44 IS 7 BP 3077 EP 3082 DI 10.1167/iovs.02-1250 PG 6 WC Ophthalmology SC Ophthalmology GA 694VL UT WOS:000183795800038 PM 12824254 ER PT J AU Hinton, DP Wald, LL Pitts, J Schmitt, F AF Hinton, DP Wald, LL Pitts, J Schmitt, F TI Comparison of cardiac MRI on 1.5 and 3.0 Tesla clinical whole body systems SO INVESTIGATIVE RADIOLOGY LA English DT Article DE 3.0 Tesla; cardiac MRI; phased array coils ID STEADY-STATE PRECESSION; PHASED-ARRAY; HEART AB Rationale and Objectives: A cardiac imaging pilot study was performed on 1.5 and 3.0 Tesla (T) whole body magnetic resonance units equipped with identical gradient sets and geometrically equivalent body coils. The goals were to compare the signal-to-noise (SNR) and contrast-to-noise (CNR) ratios on matched studies conducted at both field strengths and demonstrate the potential for functional and morphologic cardiac evaluation at 3.0 T. Methods: Short axis cine true fast imaging with steady precession (True FISP) was compared at 1.5 and 3.0 T using the body coil in transmit-receive mode and transmit-only with single loop and phased array receiver coils. SNR of the myocardium and CNR of the ventricular blood and myocardium were calculated from a quantitative region of interest analysis of these data. Additionally at 3.0 T, long axis and 4-chamber cine as well as "dark blood" imaging are demonstrated with sequence and parameter settings comparable to current state of the art for cardiac evaluation at 1.5 T. Results: The 3.0 T data consistently demonstrates increases in SNR when all imaging conditions are closely matched but the increase has a large variability ranging from 20 to 85% depending on the radiofrequency coil configuration. Ventricular blood-myocardium CNR greater than 30 is obtained at 3.0 T, which is comparable to an optimized 1.5 T acquisition despite the specific absorption rate limitation of flip angle to nearly one half the value. The increased SNR at 3.0 T improves detection of fine anatomic detail, such as the chordae tendineae and mitral valve structure. Conclusions: Increased specific absorption rate can be a limiting fact; however, we have demonstrated that 3.0 T cardiac imaging shows gains in SNR while maintaining the CNR. The SNR gain is advantageous, and phased array coil technology is key for improving cardiac magnetic resonance imaging at 3.0 T. C1 Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, NMR Ctr, Siemens Med Solut Inc, Charlestown, MA 02129 USA. Siemens Med Solut Inc, Malvern, PA USA. RP Hinton, DP (reprint author), Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, 149 13th St,Room 2301, Charlestown, MA 02129 USA. RI Wald, Lawrence/D-4151-2009 NR 18 TC 66 Z9 69 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUL PY 2003 VL 38 IS 7 BP 436 EP 442 DI 10.1097/01.RLI.0000067489.31556.70 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 696ZM UT WOS:000183917800009 PM 12821858 ER PT J AU Bacskai, BJ Skoch, J Hickey, GA Allen, R Hyman, BT AF Bacskai, BJ Skoch, J Hickey, GA Allen, R Hyman, BT TI Fluorescence resonance energy transfer determinations using multiphoton fluorescence lifetime imaging microscopy to characterize amyloid-beta plaques SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE amyloid-beta; multiphoton; microscopy; fluorescence lifetime imaging microscopy; fluorescence lifetime; Alzheimer's disease ID ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; IN-VIVO; CLOSE ASSOCIATION; LIVING CELLS; PROTEIN; KINASE; DIAGNOSIS; CONFORMATION; ACTIVATION AB We describe the implementation of a commercial fluorescence lifetime imaging microscopy (FLIM) instrument used in conjunction with a commercial laser scanning multiphoton microscope. The femtosecond-pulsed near-infrared laser is an ideal excitation source for time-domain fluorescence lifetime measurements. With synchronization from the x-y scanners, fluorescence lifetimes can be acquired on a pixel-by-pixel basis, with high spatial resolution. Mulfiexponential curve fits for each pixel result in two-dimensional fluorescence resonance energy transfer (FRET) measurements that allow the determination of both proximity of fluorescent FRET pairs, as well as the fraction of FRET pairs close enough for FRET to occur. Experiments are described that characterize this system, as well as commonly used reagents valuable for FRET determinations in biological systems. Constructs of CFP and YFP were generated to demonstrate FRET between this pair of green fluorescent protein (GFP) color variants. The lifetime characteristics of the FRET pair fluorescein and rhodamine, commonly used for immunohistochemistry, were also examined. Finally, these fluorophores were used to demonstrate spatially resolved FRET with senile plaques obtained from transgenic mouse brain. Together these results demonstrate that FLIM allows sensitive measurements of protein-protein interactions on a spatial scale less than 10 nm using commercially available components. (C) 2003 Society of Photo-Optical Instrumentation Engineers. C1 Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Ctr, Charlestown, MA 02129 USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Ctr, 114 16th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG08487]; NIBIB NIH HHS [EB00768] NR 35 TC 95 Z9 97 U1 0 U2 15 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUL PY 2003 VL 8 IS 3 BP 368 EP 375 DI 10.1117/1.1584442 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 709CD UT WOS:000184606400007 PM 12880341 ER PT J AU Quinn, DA Moufarrej, R Volokhov, A Syrkina, O Hales, CA AF Quinn, DA Moufarrej, R Volokhov, A Syrkina, O Hales, CA TI Combined smoke inhalation and scald burn in the rat SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article ID ACUTE LUNG INJURY; THERMAL-INJURY; PULMONARY COMPLICATIONS; NEUTROPHIL DEPLETION; LIPID-PEROXIDATION; SYNTHETIC SMOKE; L-SELECTIN; SHEEP; EDEMA; ACROLEIN AB The combination of burn injury with smoke inhalation from fires significantly increases mortality. The mechanism of increased mortality is poorly understood but has been associated with multiple organ dysfunction syndrome, including cardiac dysfunction. Impaired cardiac function correlates with decreased survival in burn patients. We investigated smoke inhalation from burning cotton combined with a 40% body surface area, third-degree burn during the first 4 hours after injury in rats. In the early phase after injury, burn caused a significant rise in lung neutrophil infiltration but no increase in lung water. Smoke led to a rise in lung water but only a mild increase in neutrophil infiltration. Combined smoke and burn did not increase neutrophil accumulation or lung water above that which occurred with either injury alone. Only in combined smoke and burn was there a drop in cardiac output and stroke volume with pulmonary edema and lung neutrophil influx. C1 Harvard Univ, Sch Med, Boston, MA USA. RP Quinn, DA (reprint author), Massachusetts Gen Hosp, Pulm Crit Care Unit, Dept Med, Boston, MA 02114 USA. NR 65 TC 11 Z9 12 U1 0 U2 0 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 JUL-AUG PY 2003 VL 24 IS 4 BP 208 EP 216 DI 10.1097/01.BCR.0000079276.15969.B7 PG 9 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 702GF UT WOS:000184215600005 PM 14501414 ER PT J AU Mansour, M Marrouche, N Ruskin, J Natale, A Keane, D AF Mansour, M Marrouche, N Ruskin, J Natale, A Keane, D TI Incessant nonreentrant tachycardia due to simultaneous conduction over dual atrioventricular nodal pathways mimicking atrial fibrillation in patients referred for pulmonary vein isolation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE nonreentrant tachycardia; atrioventricular nodal pathway ablation ID SUPRAVENTRICULAR TACHYCARDIA; RADIOFREQUENCY ABLATION; DETERMINANTS AB Incessant Nonreentrant AV Nodal Tachycardia. It has been reported that conduction over the fast and slow pathways of the AV node can occur simultaneously, leading to a double ventricular response from each atrial beat. We report the cases of two patients referred to us for evaluation of symptomatic, incessant, and irregular narrow-complex tachycardia, misdiagnosed as atrial fibrillation, for consideration of pulmonary vein isolation. At presentation, careful evaluation of the electrograms revealed the presence of two ventricular activations for each atrial beat. At electrophysiologic study, both patients were found to have nonreentrant tachycardias arising from simultaneous conduction over the fast and slow pathways of the AV node. In one patient, the tachycardia had resulted in cardiomyopathy. Slow AV nodal pathway ablation performed in both patients resulted in cure of their tachycardias and recovery of ventricular function in the patient with cardiomyopathy. C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Gray 109,55 Fruit St, Boston, MA 02114 USA. NR 14 TC 19 Z9 19 U1 0 U2 0 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JUL PY 2003 VL 14 IS 7 BP 752 EP 755 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 699YQ UT WOS:000184085200015 PM 12930257 ER PT J AU Pagon, Z Volker, J Cooper, GM Hansen, U AF Pagon, Z Volker, J Cooper, GM Hansen, U TI Mammalian transcription factor LSF is a target of ERK signaling SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE ERK; LSF; T cells; fibroblasts; DNA-binding; phosphorylation ID IMMUNODEFICIENCY-VIRUS TYPE-1; THYMIDYLATE SYNTHASE EXPRESSION; LONG TERMINAL REPEAT; HUMAN-FACTORS YY1; FACTOR CP2; KINASE CASCADES; PROTEIN-KINASES; GENE-EXPRESSION; IN-VITRO; TRANSDUCTION AB LSF is a mammalian transcription factor that is rapidly and quantitatively phosphorylated upon growth induction of resting, peripheral human T cells, as assayed by a reduction in its electrophoretic mobility. The DNA-binding activity of LSF in primary T cells is greatly increased after this phosphorylation event (Volker et al. [19971: Genes Dev 11:1435-1446). We demonstrate here that LSF is also rapidly and quantitatively phosphorylated upon growth induction in NIH 3T3 cells, although its DNA-binding activity is not significantly altered. Three lines of experimentation established that ERK is responsible for phosphorylating LSF upon growth induction in both cell types. First, phosphorylation of LSF by ERK is sufficient to cause the reduced electrophoretic mobility of LSF. Second, the amount of ERK activity correlates with the extent of LSF phosphorylation in both primary human T cells and NIH 3T3 cells. Finally, specific inhibitors of the Ras/Raf/MEK/ERK pathway inhibit LSF modification in vivo. This phosphorylation by ERK is not sufficient for activation of LSF DNA-binding activity, as evidenced both in vitro and in mouse fibroblasts. Nonetheless, activation of ERK is a prerequisite for the substantial increase in LSF DNA-binding activity upon activation of resting T cells, indicating that ERK phosphorylation is necessary but not sufficient for activation of LSF in this cell type. (C) 2003 Wiley-Liss, Inc. C1 Boston Univ, Dept Biol, Boston, MA 02215 USA. Dana Farber Canc Inst, Div Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hansen, U (reprint author), Boston Univ, Dept Biol, 5 Cummington St, Boston, MA 02215 USA. FU NCI NIH HHS [R01 CA081157, R01 CA18689, R01 CA081157-05, R01 CA018689, R01 CA81157] NR 41 TC 19 Z9 19 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUL 1 PY 2003 VL 89 IS 4 BP 733 EP 746 DI 10.1002/jcb.10549 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 695FB UT WOS:000183819500009 PM 12858339 ER PT J AU Cummings, DE Shannon, MH AF Cummings, DE Shannon, MH TI Ghrelin and gastric bypass: Is there a hormonal contribution to surgical weight loss? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CIRCULATING GHRELIN; ACYLATED PEPTIDE; HUMAN OBESITY; FOOD-INTAKE; SECRETION; SURGERY; RATS; STOMACH; HUMANS; APPETITE C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. RP Cummings, DE (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 1660 S Columbian Way,S-111 Endo, Seattle, WA 98108 USA. EM davidec@u.washington.edu NR 40 TC 118 Z9 119 U1 1 U2 8 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 JUL PY 2003 VL 88 IS 7 BP 2999 EP 3002 DI 10.1210/jc.2003-030705 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 697DE UT WOS:000183926300005 PM 12843132 ER PT J AU Azad, N Pitale, S Barnes, WE Friedman, N AF Azad, N Pitale, S Barnes, WE Friedman, N TI Testosterone treatment enhances regional brain perfusion in hypogonadal men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; HUMAN TEMPORAL-LOBE; ANDROGEN RECEPTOR; RAT-BRAIN; SEX-DIFFERENCES; OLDER MEN; MOOD; EXPRESSION; HORMONES; STEROIDS AB The positive effect of testosterone replacement therapy on psychosocial well-being in hypogonadal men has been demonstrated by various psychometric tests. However, there is no report available that objectively demonstrates the effect of testosterone on the function of the central nervous system in men. In this report we studied cerebral perfusion in seven hypogonadal men on testosterone replacement therapy. The blood perfusion to the central nervous system was assessed using single-photon emission-computed tomography. (99m)Tc-hexamethylpropylene-amine oxime crosses the blood brain barrier and localizes in brain tissue, depending on the intensity of the local blood flow. Psychosocial well-being was assessed with an Androgen Deficiency in Aging Men questionnaire. The study demonstrated that testosterone replacement enhanced cerebral perfusion in midbrain and superior frontal gyrus (Brodman area 8) at 3-5 wk of treatment. At 12 - 14 wk the study continued to show increased perfusion in midbrain in addition to the appearance of a new activated region in the midcingulate gyrus ( Brodman area 24). The results of this study provide objective evidence that testosterone and / or its metabolites increased cerebral perfusion in addition to the improvement in cognitive function. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Med Serv, Endocrinol Sect, Hines, IL 60141 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Nucl Med Serv, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Dept Med, Maywood, IL 60153 USA. Loyola Univ, Stritch Sch Med, Dept Nucl Med, Maywood, IL 60153 USA. RP Azad, N (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Med Serv, Endocrinol Sect, 111A,Bldg 200,Suite 1422, Hines, IL 60141 USA. EM nasrin.azad@med.va.gov NR 37 TC 54 Z9 58 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2003 VL 88 IS 7 BP 3064 EP 3068 DI 10.1210/jc.2002-020632 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 697DE UT WOS:000183926300017 PM 12843144 ER PT J AU Bassuk, SS Murphy, JM AF Bassuk, SS Murphy, JM TI Characteristics of the Modified Mini-Mental State Exam among elderly persons SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE aged; cognition; mental status tests; psychometrics ID COGNITIVE IMPAIRMENT; PREVALENCE; DEMENTIA; 3MS; RELIABILITY; POPULATION; DEPRESSION; DECLINE; COUNTY; AGE AB This study assesses psychometric properties of the Modified Mini-Mental State Exam (3MS) and present population norms and demographic risk factors for low 3MS scores. The subjects were 885 persons aged 65 and older who took the 3MS as part of the Stirling County Study, a population-based longitudinal study of adult residents of a county in Atlantic Canada. 3MS scores were not dependent on the specific rater who scored the test; thus, the 3MS is free of rater bias. Interrater reliability was high (intraclass correlation coefficient = 0.98), as was internal consistency (coefficient alpha = 0.91). Test-retest reliability over 3 years was 0.78. One third of subjects tested as cognitively impaired. Risk factors for low scores include older age, less education, male gender, and examination in French. The correlation between 3MS and Mini Mental State Exam scores was 0.95. The 3MS can be used as an epidemiologic measure of global cognitive performance among elderly persons. (C) 2003 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Bassuk, SS (reprint author), Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. FU NIA NIH HHS [T32-AG00251]; NIMH NIH HHS [R01-MH39576] NR 30 TC 29 Z9 29 U1 0 U2 5 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 JUL PY 2003 VL 56 IS 7 BP 622 EP 628 DI 10.1016/S0895-4356(03)00111-2 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 715KX UT WOS:000184972000004 PM 12921930 ER PT J AU Alper, CA Xu, JH Cosmopoulos, K Dolinski, B Stein, R Uko, G Larsen, CE Dubey, DP Densen, P Truedsson, L Sturfelt, G Sjoholm, AG AF Alper, CA Xu, JH Cosmopoulos, K Dolinski, B Stein, R Uko, G Larsen, CE Dubey, DP Densen, P Truedsson, L Sturfelt, G Sjoholm, AG TI Immunoglobulin deficiencies and susceptibility to infection among homozygotes and heterozygotes for C2 deficiency SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE C2 deficiency; immunodeficiency diseases; infection; MHC ID MAJOR HISTOCOMPATIBILITY COMPLEX; CONSERVED EXTENDED HAPLOTYPE; CLASS-III REGION; SECOND COMPONENT; IMMUNE-RESPONSE; IGA DEFICIENCY; FACTOR-B; ASSOCIATION; ANTIBODIES; ANTIGEN AB About 25% of C2-deficient homozygotes have increased susceptibility to severe bacterial infections. C2-deficient homozygotes had significantly lower serum levels of IgG2, IgG4, IgD, and Factor B, significantly higher levels of IgA and IgG3 and levels of IgG1 and IgM similar to controls. Type I ( 28 bp deletion in C2 exon 6 on the [HLA-B18, S042, DR2] haplotype or its fragments) and type II ( non-type I) C2-deficient patients with increased susceptibility to bacterial infection had significantly lower mean levels of IgG4 ( p < 0.04) and IgA ( p < 0.01) than those without infections ( who had a higher than normal mean IgA level) but similar mean levels of other immunoglobulins and Factor B. Of 13 C2-deficient homozygotes with infections, 85% had IgG4 deficiency, compared with 64% of 25 without infections. IgD deficiency was equally extraordinarily common among infection-prone (50%) and noninfection-prone (70%) homozygous type I C2-deficient patients. IgD deficiency was also common (35%) among 31 type I C2-deficient heterozygotes ( with normal or type II haplotypes), but was not found in 5 type II C2-deficient heterozygotes or 1 homozygote. Thus, C2 deficiency itself is associated with many abnormalities in serum immunoglobulin levels, some of which, such as in IgG4 and IgA, may contribute to increased susceptibility to infection. In contrast, IgD deficiency appears not to contribute to increased infections and appears to be a dominant trait determined by a gene or genes on the extended major histocompatibility complex (MHC) haplotype [HLA-B18, S042, DR2] ( but probably not on type II C2-deficient haplotypes) similar to those previously identified on [HLA-B8, SC01, DR3] and [HLA-B18, F1C30, DR3]. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. VAMC, Iowa City, IA USA. Lund Univ, Inst Lab Med, Sect Microbiol Immunol & Glycobiol, Lund, Sweden. Lund Univ, Dept Rheumatol, Lund, Sweden. RP Alper, CA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-29583]; NIAID NIH HHS [AI-14157] NR 48 TC 25 Z9 25 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD JUL PY 2003 VL 23 IS 4 BP 297 EP 305 DI 10.1023/A:1024540917593 PG 9 WC Immunology SC Immunology GA 695YB UT WOS:000183857000007 PM 12959222 ER PT J AU Manis, JP Alt, FW AF Manis, JP Alt, FW TI Novel antibody switching defects in human patients SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID SINGLE-STRANDED-DNA; CYTIDINE DEAMINASE AID; SOMATIC HYPERMUTATION; RECOMBINATION; DIVERSIFICATION; MECHANISM; ENZYME AB Hyper-IgM syndrome (HIGM) is a primary immunodeficiency characterized by normal to elevated serum levels of IgM and low levels or the absence of IgG, IgA, and IgE. A new study (see related article on pages 136-142) characterizes HIGM type 4, a previously undocumented defect in antibody gene diversification caused by a selective block in class-switch recombination, providing significant insight towards understanding HIGM immunodeficiencies. C1 Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [AI31541, P01 AI031541, U19 AI031541] NR 21 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2003 VL 112 IS 1 BP 19 EP 22 DI 10.1172/JCI200319091 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 697DJ UT WOS:000183926700004 PM 12840053 ER PT J AU Harada, H Salama, AD Sho, M Izawa, A Sandner, SE Ito, T Akiba, H Yagita, H Sharpe, AH Freeman, GJ Sayegh, MH AF Harada, H Salama, AD Sho, M Izawa, A Sandner, SE Ito, T Akiba, H Yagita, H Sharpe, AH Freeman, GJ Sayegh, MH TI The role of the ICOS-B7h T cell costimulatory pathway in transplantation immunity SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; RESPONSES IN-VIVO; INDUCIBLE COSTIMULATOR; CUTTING EDGE; ALLOGRAFT-REJECTION; MOLECULE ICOS; CD40 LIGAND; ALLOIMMUNE RESPONSES; CARDIAC ALLOGRAFTS; DENDRITIC CELLS AB Inducible costimulatory molecule (ICOS) plays a pivotal role in T cell activation and Th1/Th2 differentiation. ICOS blockade has disparate effects on immune responses depending on the timing of blockade. Its role in transplantation immunity, however, remains incompletely defined. We used a vascularized mouse cardiac allograft model to explore the role of ICOS signaling at different time points after transplantation, targeting immune initiation (early blockade) or the immune effector phase (delayed blockade). In major histocompatibility-mismatched recipients, ICOS blockade prolonged allograft survival using both protocols but did so more effectively in the delayed-treatment group. By contrast, in minor histocompatibility-mismatched recipients, early blockade accelerated rejection and delayed blockade prolonged graft survival. Alloreactive CD4(+)T cell expansion and alloantibody production were suppressed in both treatment groups, whereas only delayed blockade resulted in suppression of effector CD8(+)T cell generation. After delayed ICOS blockade, there was a diminished frequency of allospecific IL-10-producing cells and an increased frequency of both IFN-gamma- and IL-4-producing cells. The beneficial effects of ICOS blockade in regulating allograft rejection were seen in the absence of CD28 costimulation but required CD8(+) cells, cytotoxic T lymphocyte antigen-4, and an intact signal transducer and activator of transcription-6 pathway. These data define the complex functions of the ICOS-B7h pathway in regulating alloimmune responses in vivo. C1 Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Nephrol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Juntendo Univ, Sch Med, Dept Immunol, Tokyo, Japan. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Sayegh, MH (reprint author), Brigham & Womens Hosp, Lab Immunogenet & Transplantat, 75 Francis St, Boston, MA 02115 USA. RI Salama, Alan/B-5183-2010 FU NCI NIH HHS [CA84500, R01 CA084500]; NIAID NIH HHS [1R01 AI51559, 5 P01 AI41521, P01 AI039671, P01 AI041521, P01 AI39671, R01 AI051559] NR 64 TC 105 Z9 114 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2003 VL 112 IS 2 BP 234 EP 243 DI 10.1172/JCI200317008 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 701YT UT WOS:000184197100012 PM 12865411 ER PT J AU Ebert, B Shaffer, K Rennke, H AF Ebert, B Shaffer, K Rennke, H TI Some unusual paraneoplastic syndromes - Case 4. Paraneoplastic nephrotic syndrome in a patient with lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ebert, B (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. OI Shaffer, Kitt/0000-0001-6488-6988 FU NCI NIH HHS [T32 CA009172] NR 6 TC 4 Z9 4 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 JUL 1 PY 2003 VL 21 IS 13 BP 2624 EP 2625 DI 10.1200/JCO.2003.11.021 PG 2 WC Oncology SC Oncology GA 695EU UT WOS:000183818800030 PM 12829687 ER PT J AU Mager, DL Ximenez-Fyvie, LA Haffajee, AD Socransky, SS AF Mager, DL Ximenez-Fyvie, LA Haffajee, AD Socransky, SS TI Distribution of selected bacterial species on intraoral surfaces SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE soft tissue microbiota; saliva; periodontal disease; supra- and subgingival plaque; systemically healthy ID ORAL MUCOSAL SURFACES; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; HUMAN MOUTH; PORPHYROMONAS-GINGIVALIS; PREVOTELLA-INTERMEDIA; EPITHELIAL-CELLS; TONGUE; PERIODONTITIS; STREPTOCOCCI; SALIVARY AB Background/aim: To examine the proportions of 40 bacterial species in samples from 8 oral soft tissue surfaces and saliva in systemically healthy adult subjects and to compare these microbiotas with those of supra- and subgingival plaque. Methods: Microbial samples were taken from 8 oral soft tissue surfaces of 225 systemically healthy subjects using a "buccal brush". Saliva was taken by expectoration. Forty-four of these subjects provided additional supra- and subgingival plaque samples. Samples were individually evaluated for their content of 40 bacterial species using checkerboard DNA-DNA hybridization. The percentage of total DNA probe count was determined for each species, at each sample location and averaged across subjects. The significance of differences among the proportions of the 40 test species at different sample locations was sought in the 225 and 44 subjects separately using the Quade test and adjusted for multiple comparisons. Cluster analysis was performed using the proportions of the 40 species at the different sample locations using the minimum similarity coefficient and an average unweighted linkage sort. The proportions of each species were averaged across subjects in the resulting cluster groups and the significance of differences was tested using the t -test and ANOVA. Results: Microbial profiles differed markedly among sample locations in the 225 subjects, with 34 of 40 species differing significantly. Proportions of Veillonella parvula and Prevotella melaninogenica were higher in saliva and on the lateral and dorsal surfaces of the tongue, while Streptococcus mitis and S. oralis were in significantly lower proportions in saliva and on the tongue dorsum. Cluster analysis resulted in the formation of 2 clusters with >85% similarity. Cluster 1 comprised saliva, lateral and dorsal tongue surfaces, while Cluster 2 comprised the remaining soft tissue locations. V. parvula, P. melaninogenica, Eikenella corrodens, Neisseria mucosa, Actinomyces odontolyticus, Fusobacterium periodonticum, F. nucleatum ss vincentii and Porphyromonas gingivalis were in significantly higher proportions in Cluster 1 and S. mitis, S. oralis and S. noxia were significantly higher in Cluster 2. These findings were confirmed using data from the 44 subjects providing plaque samples. The microbial profiles of supra- and subgingival plaque differed from the other sample locations, particularly in the increased proportions of the Actinomyces species. Species of different genera exhibited different proportions on the various intraoral surfaces, but even within the genus Streptococcus , there were differences in colonization patterns. S. oralis, S. mitis and S. constellatus colonized the soft tissues and saliva in higher proportions than the samples from the teeth, while the other 4 streptococcal species examined colonized the dental surfaces in proportions comparable to the soft tissue locations and saliva. Conclusions: Proportions of bacterial species differed markedly on different intraoral surfaces. The microbiota of saliva was most similar to that of the dorsal and lateral surfaces of the tongue. The microbiotas of the soft tissues resembled each other more than the microbiotas that colonized the teeth both above and below the gingival margin. C1 Forsyth Inst, Dept Periodontol & Mol Genet, Boston, MA 02115 USA. RP Forsyth Inst, Dept Periodontol & Mol Genet, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-10977, DE-12108, DE-12861, K23 DE-00453] NR 39 TC 178 Z9 184 U1 2 U2 20 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6979 EI 1600-051X J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD JUL PY 2003 VL 30 IS 7 BP 644 EP 654 DI 10.1034/j.1600-051X.2003.00376.x PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 696RC UT WOS:000183900000010 PM 12834503 ER PT J AU Yildiz, A Sachs, GS AF Yildiz, A Sachs, GS TI Do antidepressants induce rapid cycling? A gender-specific association SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID AFFECTIVE-DISORDER; LITHIUM-CARBONATE; CIRCADIAN-RHYTHMS; ANTI-DEPRESSANTS; BIPOLAR ILLNESS; COURSE MODIFIER; DSM-IV; IMIPRAMINE; CYCLERS; HAMSTER AB Objective: To investigate the influence of antidepressant use and gender in the genesis of rapid-cycling bipolar illness. Method: The charts of bipolar patients treated at the Massachusetts General Hospital Bipolar Clinic (Boston, Mass.) were reviewed for gender, presence or absence of rapid cycling, and antidepressant use prior to first mania. Results: Data were obtained for 129 bipolar patients (55% women), 45% of whom had experienced a rapid-cycling course. Overall, there was no significant difference in the rates of rapid cycling between the subjects who were exposed to antidepressants prior to their first manic/ hypomanic episode and those who were not. Additional analysis carried out separately by gender found a significant association between rapid cycling and antidepressant use prior to first mania/hypomania for women but not for men. A logistic regression analysis with rapid cycling as dependent variable revealed a significant interaction between antidepressant use prior to first mania/hypomania and gender. Conclusion: We found a gender-specific relationship between antidepressant use prior to first manic/hypomanic episode and rapid-cycling bipolar illness. When antidepressants are prescribed to depressed women who have a risk of bipolar disorder, the risk of inducing rapid cycling should be considered. Differing proportions of women and men in previous studies may account for conflicting results reported in the literature for the relationship of antidepressants and rapid cycling. However, this naturalistic trial was uncontrolled, and controlled research is required to confirm our findings. C1 Dokuz Eylul Med Sch, Dept Psychiat, Izmir, Turkey. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Program, Boston, MA 02115 USA. RP Yildiz, A (reprint author), 9109 Sokak 12-6 Halil Nevzat Sen Apt PK, TR-35370 Izmir, Turkey. NR 22 TC 20 Z9 20 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 PD JUL PY 2003 VL 64 IS 7 BP 814 EP 818 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 702QB UT WOS:000184233600012 PM 12934983 ER PT J AU Aquino, SL Asmuth, JC Alpert, NM Halpern, EF Fischman, AJ AF Aquino, SL Asmuth, JC Alpert, NM Halpern, EF Fischman, AJ TI Improved radiologic staging of lung cancer with 2-[F-18]-fluoro-2-deoxy-D-glucose-positron emission tomography and computed tomography registration SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE lung cancer; carcinoma; non-small-cell lung; radiography; thoracic; tomography; emmission-computed; neoplasms ID CT; ACCURACY; SYSTEM; FUSION; SCAN AB Purpose: To determine if volumetric nonlinear registration or registration of thoracic computed tomography (CT) and 2-[F-18]-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) datasets changes the detection of mediastinal and hilar nodal disease in patients undergoing staging for lung cancer and if it has any impact on radiologic lung cancer staging. Method: Computer-based image registration was performed on 45 clinical thoracic helical CT and FDG-PET scans of patients with lung cancer who were staged by mediastinoscopy and/or thoracotomy. Thoracic CT, FDG-PET, and registration datasets were each interpreted by 2 readers for the presence of metastatic nodal disease and were staged independently of each other. Results were compared with surgical pathologic findings. Results: One hundred and thirty lymph node stations in the mediastinum and hila were evaluated each on CT, PET, and registration datasets. Sensitivity, specificity, positive predictive value, and negative predictive value, respectively, for detecting metastatic nodal disease for CT were 74%, 78%, 55%, 88%; for PET with CT side by side, 59% to 76%, 77% to 89%, 48% to 68%, and 84% to 91%; and for CT-PET registration, 71% to 76%, 89% to 96%, 70% to 86%, and 90% to 91%. Registration images were significantly more sensitive in detecting nodal disease over PET for I reader (P = 0.0156) and were more specific than PET (P = 0.0107 and 0.0017) in identifying the absence of mediastinal disease for both readers. Registration was significantly more accurate for staging when compared with PET for both readers (P 0.002 and 0.035). Conclusion: Registration of CT and FDG-PET datasets significantly improved the specificity of detecting metastatic disease. In addition, registration improved the radiologic staging of lung cancer patients when compared with CT or FDG-PET alone. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Sarnoff Corp, Princeton, NJ USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND 202,55 Fruit St, Boston, MA 02114 USA. NR 19 TC 46 Z9 54 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JUL-AUG PY 2003 VL 27 IS 4 BP 479 EP 484 DI 10.1097/00004728-200307000-00004 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 707UL UT WOS:000184528200004 PM 12886128 ER PT J AU Ptak, T Hunter, GH Avakian, R Novelline, RA AF Ptak, T Hunter, GH Avakian, R Novelline, RA TI Clinical significance of cavernous carotid calcifications encountered on head computed tomography scans performed on patients seen in the emergency department SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE arteriosclerosis; carotid disease; head computed tomography (CT); predictor; systemic disease ID LEUKOARAIOSIS AB Purpose: To determine whether the presence of calcification in the cavernous segment of the internal carotid artery seen on head computed tomography (CT) performed in the emergency department shows any relationship to the existence of systemic disease. Significant and consistent relationships could be used as predictors in suggesting the presence of systemic disease in those patients receiving head CTs for unrelated symptoms. Methods: A retrospective investigation was performed on 295 consecutive patients presenting to the Massachusetts General Hospital emergency department for head CT scan during the course of I month. Head CT images were analyzed for carotid siphon calcifications. Data regarding multiple predictors of disease including gender, age, hypertension, diabetes, smoking, hypercholesterolemia, cardiac disease, and alcohol and intravenous drug abuse were abstracted from the medical record for each patient. Results: Strong univariate correlation was noted in the comparison between the presence of carotid siphon calcification and gender, age, diabetes, hypertension, smoking, and cardiac disease while alcohol and intravenous drug abuse correlated poorly. Multivariate models including categorized age and gender demonstrated a consistently strong interaction with diabetes, cardiac disease, and smoking while hypertension and hypercholesterolemia showed a loss of significance. Interaction term analysis indicated a strong (ie, significant) interaction between gender and both hypertension and hypercholesterolemia. Conclusions: Carotid siphon calcifications are strong predictors of existing medical disease in simple cases. In patients with a combination of diseases, a strong interaction between covariates is noted, suggesting a more complex interaction contributing to the formation of carotid siphon disease. C1 Massachusetts Gen Hosp, Div Emergency Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Ptak, T (reprint author), Massachusetts Gen Hosp, Div Emergency Radiol, 32 Fruit St,FND 210,POB 9625, Boston, MA 02114 USA. NR 6 TC 14 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JUL-AUG PY 2003 VL 27 IS 4 BP 505 EP 509 DI 10.1097/00004728-200307000-00009 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 707UL UT WOS:000184528200009 PM 12886133 ER PT J AU Aquino, SL Hayman, LA Loomis, SL Taber, KH AF Aquino, SL Hayman, LA Loomis, SL Taber, KH TI The source and direction of thoracic lymphatics, Part II: The lower thorax SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE computed tomography (CT); lung cancer; lymphatics; metastases; surgery; thorax; tumor; node; metastases classification ID POSITRON-EMISSION-TOMOGRAPHY; LUNG-CANCER; SEGMENTS; DRAINAGE; VESSELS AB The purpose of this set of 2 articles is to illustrate the source and direction of lymphatic drainage in the thorax on axial computed tomographic (CT) schematics. The first article describes the upper thorax. This article describes the lower thorax. The nodal groups are given conventional anatomic names and the corresponding terminology of the American Thoracic Society. Arrows indicate the direction of the flow. The region or organ drained is color-coded, and nodes that receive lymph from each area are assigned appropriately colored and numbered boxes. Major drainage patterns are also described. This information can be used to assess a suspicious lymph node by tracing it to the region of drainage and looking for pathology. Alternately, one may extrapolate the potential drainage routes of a tumor and scrutinize specific sites for nodal metastases. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Texas, Hlth Sci Ctr, Sch Hlth Informat Sci, Houston, TX USA. Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. Baylor Coll Med, Herbert J Frensley Ctr Imaging, Houston, TX 77030 USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND 202,55 Fruit St, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JUL-AUG PY 2003 VL 27 IS 4 BP 657 EP 661 DI 10.1097/00004728-200307000-00039 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 707UL UT WOS:000184528200039 PM 12886163 ER PT J AU Caselli, A Hanane, T Jane, B Carter, S Khaodhiar, L Veves, A AF Caselli, A Hanane, T Jane, B Carter, S Khaodhiar, L Veves, A TI Topical methyl nicotinate-induced skin vasodilation in diabetic neuropathy SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE laser Doppler; neuropathy; smooth muscle cell; microcirculation; diabetic foot ID PERCUTANEOUS PENETRATION; IN-VIVO; MICROCIRCULATION; FOOT; ACID; INFLAMMATION; DYSFUNCTION; EPIDERMIS; RESPONSES AB Objective: To evaluate the vasodilation induced by topical application of methyl nicotinate (MN) and to compare it with the vasodilatory response to acetylcholine (ACh) and sodium nitroprusside (SNP) in healthy subjects and diabetic neuropathic patients. Research design and methods: Ten diabetic patients with peripheral neuropathy (DN) and 10 age- and sex-matched healthy control subjects (C) were enrolled. The vasodilatory response to topical application of 1% MN and a placebo emulsion at the forearm and dorsum of the foot skin at 5, 15, 30, 60 and 120 min was measured using Laser Doppler Perfusion Imaging. The vasodilatory response to iontophoresis of 1% ACh and 1% SNP solutions was also evaluated. Results: The maximal vasodilatory response to ACh, SNP and MN was similar at the forearm and foot level in the diabetic patients. In the control group, the responses to MN, ACh and SNP were similar on the forearm but in the foot, the MN vasodilatory response was higher when compared to the ACh and SNP responses. MN-related vasodilation was present 5 min after the application, reached its peak at 15-30 min and declined to pre-application levels 120 min afterward. Conclusions: Topical application of MN at the forearm and foot levels of diabetic neuropathic patients results in skin vasodilation that is comparable to the maximal vasodilation that can be induced by iontophoresis of ACh or SNP and lasts for less than 2 It. Further studies will be required to explore the potential of MN to increase blood flow and to prevent diabetic foot problems in clinical practice. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med,Joslin Beth Israel Deaconess Foot Ctr, Beth Israel Deaconess Med Ctr, Microcirculat Lab,Dept Surg, Boston, MA 02115 USA. Univ Roma Tor Vergata, Dept Internal Med, Rome, Italy. BioChemComp Inc, Danvers, MA USA. RP Caselli, A (reprint author), Harvard Univ, Sch Med,Joslin Beth Israel Deaconess Foot Ctr, Beth Israel Deaconess Med Ctr, Microcirculat Lab,Dept Surg, Palmer 317,West Campus,1 Deaconess Rd, Boston, MA 02115 USA. FU NCRR NIH HHS [RR01032] NR 27 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 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD JUL-AUG PY 2003 VL 17 IS 4 BP 205 EP 210 DI 10.1016/S1056-8727(02)00256-8 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 696DK UT WOS:000183870600006 PM 12810244 ER PT J AU Hamedani, AG Brown, DFM Nadel, ES AF Hamedani, AG Brown, DFM Nadel, ES TI Headache and visual change SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID GIANT-CELL ARTERITIS; SUBARACHNOID HEMORRHAGE; INTRACRANIAL ANEURYSMS; CT ANGIOGRAPHY; MANAGEMENT; DIAGNOSIS C1 Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JUL PY 2003 VL 25 IS 1 BP 83 EP 87 DI 10.1016/S0736-4679(03)00127-6 PG 5 WC Emergency Medicine SC Emergency Medicine GA 700XM UT WOS:000184136500015 PM 12865114 ER PT J AU Hoch, DB Daly, L AF Hoch, DB Daly, L TI Anticonvulsants SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article ID ANTIEPILEPTIC DRUGS; CARBAMAZEPINE; GABAPENTIN; VALPROATE; EPILEPSY; ADULTS; LEVETIRACETAM; LAMOTRIGINE; PHENYTOIN C1 Massachusetts Gen Hosp, Dept Neurol Epilepsy, Boston, MA 02114 USA. RP Hoch, DB (reprint author), Massachusetts Gen Hosp, Dept Neurol Epilepsy, Boston, MA 02114 USA. OI Hoch, Daniel/0000-0002-4294-024X NR 15 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-9701 J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JUL-AUG PY 2003 VL 18 IS 4 BP 383 EP 386 PG 4 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 705GN UT WOS:000184387500008 ER PT J AU Stryker, JE AF Stryker, JE TI Media and marijuana: A longitudinal analysis of news media effects on adolescents' marijuana use and related outcomes, 1977-1999 SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article; Proceedings Paper CT 51st Annual Conference of the International-Communication-Association CY MAY 24-28, 2001 CL WASHINGTON, DC SP Int Commun Assoc ID MASS-MEDIA; BREAST-CANCER; SUBSTANCE-ABUSE; BEHAVIOR-CHANGE; PUBLIC-OPINION; DRUG-ABUSE; COVERAGE; HEALTH; AGENDA; INFORMATION AB This study examined how aggregate levels of news coverage about marijuana have impacted adolescents' marijuana behavior generally, and through the intervening variables of personal disapproval and perceived harmfulness of marijuana, two variables that existing research has identified as significant predictors of adolescent marijuana use at the aggregate level. It was hypothesized that news coverage of reasons why people should not use marijuana would cause increase in aggregate marijuana abstinence, perceived harmfulness, and personal disapproval. Conversely, news coverage of positive aspects of marijuana use would cause decreases in marijuana abstinence, perceived harmfulness, and personal disapproval. Results of distributed lagged time-series regression and non-linear modeling offered support for two of the three proposed hypotheses. Aggregate media coverage explained a significant portion of the variation in adolescents' abstinence from marijuana use over time. It also explained a significant portion of the variation in personal disapproval of marijuana. Personal disapproval was found to partially mediate the relationship between media coverage and marijuana abstinence. Implications for the conceptualization of media effects on health behaviors are discussed. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Stryker, JE (reprint author), Dana Farber Canc Inst, 44 Binney St,Smith 262, Boston, MA 02115 USA. EM jo_stryker@dfci.harvard.edu NR 86 TC 53 Z9 53 U1 2 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PD JUL-AUG PY 2003 VL 8 IS 4 BP 305 EP 328 DI 10.1080/10810730390223353 PG 24 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 721MN UT WOS:000185320300002 PM 12907398 ER PT J AU Albertson, RC Streelman, JT Kocher, TD AF Albertson, RC Streelman, JT Kocher, TD TI Genetic basis of adaptive shape differences in the cichlid head SO JOURNAL OF HEREDITY LA English DT Article ID QUANTITATIVE TRAIT LOCI; BRANCHIAL ARCH MUTANTS; LAKE-MALAWI; MORPHOLOGICAL INTEGRATION; PSEUDOTROPHEUS-ZEBRA; SALVELINUS-ALPINUS; SYMPATRIC MORPHS; FISHES; AFRICA; EVOLUTION AB East African cichlids exhibit an extraordinary level of morphological diversity. Key to their success has been a dramatic radiation in trophic biology, which has occurred rapidly and repeatedly in different lakes. In this report we take the first step in understanding the genetic basis of differences in cichlid oral jaw design. We estimate the effective number of genetic factors that control differences in the cichlid head through a comprehensive morphological assessment of two Lake Malawi cichlid species and their F-1 and F-2 hybrid progeny. We estimate that between one and 11 factors underlie shape difference of individual bony elements. We show that many of the skeletal differences in the head and oral jaw apparatus are inherited together, suggesting a degree of pleiotropy in the genetic architecture of this character complex. Moreover, we find that cosegregation of shape differences in different elements corresponds to developmental, rather than functional, units. C1 Univ New Hampshire, Dept Zool, Durham, NH 03824 USA. Univ New Hampshire, Hubbard Ctr Genome Studies, Durham, NH 03824 USA. RP Albertson, RC (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. RI Kocher, Thomas/B-3089-2013; OI Kocher, Thomas/0000-0002-7547-0133 FU NIDCR NIH HHS [R03 DE014446] NR 69 TC 77 Z9 77 U1 2 U2 24 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PD JUL PY 2003 VL 94 IS 4 BP 291 EP 301 DI 10.1093/jhered/esg071 PG 11 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 714PM UT WOS:000184922700003 PM 12920100 ER PT J AU Yasuhara, S Zhu, Y Matsui, T Tipirneni, N Yasuhara, Y Kaneki, M Rosenzweig, A Martyn, JAJ AF Yasuhara, S Zhu, Y Matsui, T Tipirneni, N Yasuhara, Y Kaneki, M Rosenzweig, A Martyn, JAJ TI Comparison of comet assay, electron microscopy, and flow cytometry for detection of apoptosis SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE apoptosis; necrosis; skeletal muscle; Jurkat cells; comet assay; flow cytometry; electron microscopy; TUNEL assay ID SKELETAL-MUSCLE APOPTOSIS; DOUBLE-STRAND BREAKS; DNA-DAMAGE; CELL-DEATH; GEL-ELECTROPHORESIS; ACTIVATION; RADIATION; NECROSIS; INJURY; ISCHEMIA AB Differentiating apoptosi s from necrosis is a challenge in single cells and in parenchymal tissues. The techniques available, including in situ TUNEL (Terminal deoxyribonucleotide transferase-mediated dUTP-X Nick End-Labeling) staining, DNA ladder assay, and flow cytometry, suffer from low sensitivity or from a high false-positive rate. This study, using a Jurkat cell model, initially evaluated the specificity of the neutral comet assay and flow cytometry compared to the gold standard, electron microscopy, for detection of apoptosis and necrosis. Neutral comet assay distinguished apoptosis from necrosis in Jurkat cells, as evidenced by the increased comet score in apoptotic cells and the almost zero comet score in necrotic cells. These findings were consistent with those of electron microscopy and flow cytometry. Furthermore, using rats with burn or ischemia/reperfusion injury, well-established models of skeletal and cardiac muscle tissue apoptosis, respectively, we applied the comet assay to detect apoptosis in these muscles. Neutral comet assay was able to detect apoptotic changes in both models. In the muscle samples from rats with burn or ischemia-reperfusion injury, the comet score was higher than that of muscle samples from their respective controls. These studies confirm the consistency of the comet assay for detection of apoptosis in single cells and provide evidence for its applicability as an additional method to detect apoptosis in parenchymal cells. C1 Shriners Hosp Children, Boston, MA USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA. RP Martyn, JAJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol & Crit Care, 55 Fruit St, Boston, MA 02114 USA. NR 33 TC 88 Z9 94 U1 1 U2 18 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUL PY 2003 VL 51 IS 7 BP 873 EP 885 PG 13 WC Cell Biology SC Cell Biology GA 692EK UT WOS:000183647700003 PM 12810838 ER PT J AU Abboud, SL Bunegin, M Ghosh-Choudhury, N Woodruff, K AF Abboud, SL Bunegin, M Ghosh-Choudhury, N Woodruff, K TI Analysis of the mouse CSF-1 gene promoter in a transgenic mouse model SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE macrophage colony-stimulating factor; gene expression; transgenic mice ID COLONY-STIMULATING FACTOR; FACTOR-I; STROMAL CELLS; GROWTH-FACTOR; TRANSCRIPTIONAL REGULATION; EXPRESSION; MICE; MACROPHAGES; CLONING; BONE AB CSF-1 stimulates monocyte and osteoclast populations. However, the molecular mechanisms involved in regulating CSF-1 gene expression are unclear. To identify regulatory regions that control normal CSF-1 gene expression, a -774/+183-bp fragment of the murine CSF-1 promoter was analyzed in vitro and in vivo. Transcriptional activity was high in cultured osteoblasts that express CSF-1 mRNA compared to ARH-77 B cells that lack CSF-1 gene expression. Transient transfection of osteoblasts with promoter deletion constructs showed that the -774-bp fragment conferred the highest transcriptional activity and contained activator and repressor sequences. To assess the ability of the CSF-1 promoter to confer normal tissue expression of CSF-1, transgenic mice containing the -774/+183-bp region driving the E. coli p-galactosidase (lacZ) reporter gene were generated. P-Gal analysis of whole tissue extracts showed transgene expression in all tissues tested except liver and kidney. At the cellular level, the pattern of P-gal expression in the spleen, thymus, bone, lung, and testes of adult transgenic mice mimicked normal endogenous CSF-1 mRNA expression in non-transgenic littermates detected by in situ hybridization. This region also directed appropriate transgene expression to sites in other tissues known to synthesize CSF-1, with the exception of the liver and kidney. These findings indicate that the -774-bp fragment contains cis-acting elements sufficient to direct CSF-1 gene expression in many tissues. CSF-1 promoter/lacZ mice may be useful for studying the transcriptional mechanisms involved in regulating CSF-1 gene expression in tissues throughout development. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Univ Texas, Audie L Murphy Div, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Abboud, SL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIAMS NIH HHS [AR 42306, R01 AR042306] NR 42 TC 4 Z9 4 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUL PY 2003 VL 51 IS 7 BP 941 EP 949 PG 9 WC Cell Biology SC Cell Biology GA 692EK UT WOS:000183647700009 PM 12810844 ER PT J AU Menon, GK Kollias, N Doukas, AG AF Menon, GK Kollias, N Doukas, AG TI Ultrastructural evidence of stratum corneum permeabilization induced by photomechanical waves SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE drug delivery; shock waves; transdermal delivery ID TRANSDERMAL DRUG-DELIVERY; GENERATED STRESS WAVES; CELL-MEMBRANE; SHOCK-WAVES; IN-VITRO; SKIN; ELECTROPORATION; IONTOPHORESIS; SONOPHORESIS; CONFINEMENT AB Photomechanical waves (high amplitude pressure transients generated by lasers) have been shown to permeabilize the stratum corneum in vivo and facilitate the transport of macromolecules into the viable epidermis. The permeabilization of the stratum corneum is transient and its barrier function recovers. Sites on the volar forearm of humans were exposed to photomechanical waves and biopsies were obtained immediately after the exposure and processed for electron microscopy. Electron microscopy showed an expansion of the lacunar spaces within the stratum corneum lipid bilayers but no changes in the organization of the secreted lamellar bodies at the stratum corneum-stratum granulosum boundary. The combination of photomechanical waves and sodium lauryl sulfate enhances the efficiency of transdermal delivery and delays the recovery of the barrier function of the stratum corneum. Electron microscopy from sites exposed to photomechanical waves and sodium lauryl sulfate showed that the lacunar spaces expanded significantly more and the secreted lamellar bodies also appeared to be altered. In either case, there were no changes in the papillary dermis. These observations support the hypothesis that the photomechanical waves induce the expansion of the lacunar spaces within the stratum corneum leading to the formation of transient channels. C1 Avon Prod Inc, Global Res & Dev, Suffern, NY 10901 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Med Sch, Dept Dermatol, Boston, MA USA. RP Menon, GK (reprint author), Avon Prod Inc, Global Res & Dev, Avon Pl, Suffern, NY 10901 USA. NR 36 TC 32 Z9 33 U1 0 U2 3 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 JUL PY 2003 VL 121 IS 1 BP 104 EP 109 DI 10.1046/j.1523-1747.2003.12302.x PG 6 WC Dermatology SC Dermatology GA 697XP UT WOS:000183968800018 PM 12839570 ER PT J AU Fuller, AP Palmer-Toy, D Erlander, MG Sgroi, DC AF Fuller, AP Palmer-Toy, D Erlander, MG Sgroi, DC TI Laser capture microdissection and advanced molecular analysis of human breast cancer SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE laser capture microdissection; breast cancer; gene expression; genomics; proteomics ID GENE-EXPRESSION PROFILES; CARCINOMA IN-SITU; COMPARATIVE GENOMIC HYBRIDIZATION; INVASIVE DUCTAL CARCINOMA; POLYMERASE-CHAIN-REACTION; ASSISTED MICRODISSECTION; 3-DIMENSIONAL CULTURE; MICROARRAY ANALYSIS; EPITHELIAL-CELLS; STROMAL REACTION AB Advances in comprehensive genomic and proteomic technologies are providing researchers with an unprecedented opportunity for high-throughput molecular analysis of human breast cancer. Adaptation of these technologies to laser capture microdissection (LCM) is poised to exert dramatic change on the pace of breast cancer research. Although technical limitations have impeded the coupling of these high-throughput technologies to LCM, recent advances have allowed for the successful application of this cellular-based approach to breast cancer, and the results of such studies have provided researchers with unique insight into the disease. This approach holds great potential for rapid advancement in our understanding of breast cancer, and it is hoped that such advancements will lead to novel predictive and therapeutic strategies for women with the disease. This review outlines the current status of the adaptation of advanced molecular technologies to LCM and highlights recent studies in which this approach has been applied to human breast cancer. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Arcturus, Appl Genom Div, Carlsbad, CA USA. RP Sgroi, DC (reprint author), MGH E, Mol Pathol Unit, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA89393] NR 73 TC 37 Z9 42 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD JUL PY 2003 VL 8 IS 3 BP 335 EP 345 DI 10.1023/B:JOMG.0000010033.49464.0c PG 11 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 757EH UT WOS:000187535500007 PM 14973377 ER PT J AU Lahdenne, P Panelius, J Saxen, H Heikkila, T Sillanpaa, H Peltomaa, M Arnez, M Huppertz, HI Seppala, IJT AF Lahdenne, P Panelius, J Saxen, H Heikkila, T Sillanpaa, H Peltomaa, M Arnez, M Huppertz, HI Seppala, IJT TI Improved serodiagnosis of erythema migrans using novel recombinant borrelial BBK32 antigens SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID EARLY LYME-DISEASE; BURGDORFERI; ANTIBODIES; REGION; ASSAY AB The performances of recombinant borrelial BBK32 proteins as antigens in the serology of erythema migrans (EM) were evaluated in an ELISA. Serum samples were obtained from 75 patients from different geographic areas where three borrelial species, Borrelia burgdorferi sensu stricto, Borrelia afzelii or Borrelia garinii, cause Lyme borreliosis. Antibodies to variant BBK32 proteins were compared with anti-flagella or with anti-IR6 peptide antibodies. In IgGi ELISA at presentation of EM, 65/75 (87 %) patients had antibodies to one or more variants of BBK32, 29/75 (39 %) had antibodies to flagella and 29/75 (39 %) had antibodies to the VIsE IR6 peptide antigen. The immunoreactivity against variant BBK32 proteins differed in patients from different geographic regions. The present results suggest that the BBK32 proteins used in combination or in parallel may improve the laboratory diagnosis of EM. C1 Univ Helsinki, Hosp Children & Adolescents, FIN-00290 Helsinki, Finland. Haartman Inst, Dept Bacteriol & Immunol, Helsinki 00014, Finland. Univ Helsinki, Cent Hosp, Dept Otolaryngol, FIN-00290 Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Lab Diagnost, FIN-00290 Helsinki, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Univ Ljubljana, Med Ctr, Dept Infect Dis, Ljubljana 61000, Slovenia. Prof Hess Children Hosp Bremen, Wurzburg, Germany. Univ Wurzburg, Childrens Hosp, Wurzburg, Germany. RP Lahdenne, P (reprint author), Univ Helsinki, Hosp Children & Adolescents, Stenbackinkatu 11, FIN-00290 Helsinki, Finland. OI Sillanpaa, Heidi/0000-0001-6649-6828 NR 15 TC 21 Z9 22 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD JUL PY 2003 VL 52 IS 7 BP 563 EP 567 DI 10.1099/jmm.0.05095-0 PG 5 WC Microbiology SC Microbiology GA 702PZ UT WOS:000184233400006 PM 12808077 ER PT J AU Rosenzweig, A AF Rosenzweig, A TI Vectors for cardiovascular gene therapy SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Editorial Material ID RECOMBINANT ADENOASSOCIATED VIRUS; IN-VIVO; LENTIVIRAL VECTORS; ADENOVIRAL VECTOR; STABLE TRANSDUCTION; CAROTID ARTERIES; DIRECT-INJECTION; EXPRESSION; EFFICIENT; DELIVERY C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02129 USA. RP Rosenzweig, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Cardiovasc Gene Therapy,CVRC, 114 16th St,Rm 2600, Boston, MA 02129 USA. EM arosenzweig@partners.org FU NHLBI NIH HHS [HL-59521, HL-61557] NR 40 TC 5 Z9 8 U1 0 U2 0 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 JUL PY 2003 VL 35 IS 7 BP 731 EP 733 DI 10.1016/S0022-2828(03)00144-5 PG 3 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 696DN UT WOS:000183871000003 PM 12818562 ER PT J AU Papakostas, GI Petersen, T Pava, J Masson, E Worthington, JJ Alpert, JE Fava, M Nierenberg, AA AF Papakostas, GI Petersen, T Pava, J Masson, E Worthington, JJ Alpert, JE Fava, M Nierenberg, AA TI Hopelessness and suicidal ideation in outpatients with treatment-resistant depression: Prevalence and impact on treatment outcome SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID COMPARATIVE EFFICACY; MAJOR DEPRESSION; ELDERLY PATIENTS; LATE-LIFE; RISK; PREDICTORS; ANTIDEPRESSANTS; PHARMACOTHERAPY; NORTRIPTYLINE; INHIBITORS AB Depression and hopelessness are risk factors for suicide. The purpose of this study was to examine the extent of suicidal ideation and hopelessness in outpatients with treatment-resistant depression (TRD) and to study the impact of suicidal ideation and hopelessness on treatment with nortriptyline (NT). The degree of suicidal ideation and hopelessness was assessed during the screen visit with the use of items #3 and #30 of the Hamilton Depression Rating Scale (HAM-D) in 89 patients with TRD who entered a 6-week open trial of NT. Forty of these patients also completed the Beck Hopelessness Index (BHI) during the screen visit. In separate logistic regressions, the scores from the BHI and the two HAM-D items were then tested as predictors of clinical response to the 6-week trial with NT, controlling for the severity of depression. More than half of patients reported thoughts or wishes of death to self and significant hopelessness. A greater degree of hopelessness before treatment in completers, reflected by the score on the HAM-D item #30, predicted response to NT. More than half of patients with prominent hopelessness who completed the trial responded. Patients with TRD are more likely than not to report prominent suicidal ideation and hopelessness. Furthermore, a full 6-week trial of NT, a relatively noradrenergic tricyclic antidepressant, may be particularly useful in patients who have failed to respond to several antidepressants and also report significant hopelessness. 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, WACC 812,15 Parkman St, Boston, MA 02114 USA. RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X NR 39 TC 27 Z9 28 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 2003 VL 191 IS 7 BP 444 EP 449 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 708DV UT WOS:000184552600005 PM 12891091 ER PT J AU Carpentieri, SC Meyer, EA Delaney, BL Victoria, ML Gannon, BK Doyle, JM Kieran, MW AF Carpentieri, SC Meyer, EA Delaney, BL Victoria, ML Gannon, BK Doyle, JM Kieran, MW TI Psychosocial and behavioral functioning among pediatric brain tumor survivors SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE brain tumor; pediatric ID ASSESSMENT SYSTEM; TEMPORAL-LOBE; CHILDREN; CANCER; MEDULLOBLASTOMA; ADJUSTMENT; QUALITY; CHILDHOOD; TEACHER; LIFE AB Objective: To describe the psychosocial and behavioral functioning, as described by patient, parent and teacher, of a cohort of adolescents who have been previously treated for a brain tumor. Methods: A cohort of 32 patients, 12-18 years old, were evaluated between 1 and 5 years post-treatment for brain tumor during the patient's regularly scheduled follow-up clinic appointment at the Dana-Farber Cancer Institute. The Self-Report questionnaire and the Parent-Report of the Behavioral Assessment System for Children (BASC) were administered to the patient and to one of the patient's parents, respectively. In addition, the BASC Teacher-Report was completed by the patient's teacher. Descriptive statistics were generated; binomial distribution analyses were carried out to assess whether the proportion of individuals with impaired performance on each measure exceeded normative expectations. Results: Comparison of the proportion of patients with elevated scores to normative expectations indicated no excess of elevated scores on any of the BASC scales of the Self-Report. However, parents endorsed items in the areas of attention problems and leadership; teachers endorsed items concerning learning problems; and both parents and teachers endorsed items indicative of somatization behaviors. Conclusions: Parent and teacher feedback indicate some level of psychosocial and behavioral morbidity for adolescents treated for a brain tumor; this finding contrasts with adolescent Self-Report indicating no difficulties in behavioral and psychosocial functioning. The extent to which these vulnerabilities impact quality of life and the discrepancy between reporters should be assessed in follow-up studies with a larger cohort of patients. C1 Harvard Univ, Sch Med, Childrens Hosp, Dept Psychiat,Div Psychol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Carpentieri, SC (reprint author), POB 57580, Webster, TX 77598 USA. OI Kieran, Mark/0000-0003-2184-7692 NR 47 TC 50 Z9 50 U1 3 U2 9 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JUL PY 2003 VL 63 IS 3 BP 279 EP 287 DI 10.1023/A:1024203323830 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 690RX UT WOS:000183563700008 PM 12892234 ER PT J AU Topcuoglu, MA Buonanno, FS AF Topcuoglu, MA Buonanno, FS TI Importance of jugular valve incompetence in contrast Transcranial Doppler ultrasonooratft for the diagnosis of patent foramen ovale SO JOURNAL OF NEUROIMAGING LA English DT Article DE Transcranial Doppler ultrasound; patent foramen ovale; jugular valve incompetence ID TO-LEFT SHUNTS; ULTRASOUND AB Transcranial Doppler (TCD) ultrasound with the intravenous injection of agitated saline as contrast (cTCD) is an effective method for detecting right-to-left intracardiac and extracardiac shunt (FILS); however, the sensitivity of cTCD in the diagnosis of RLS remains slightly less than that of transesophageal echocardiography, even in patients with adequate transtemporal ultrasonic bone windows. The authors present a case with cTCD underestimating RLS because of jugular valve incompetence in a 42-year-old man presenting with an episode of transient aphasia. Three weeks after transcatheter closure of a patent foramen ovale associated with an atrial septal aneurysm, he experienced 2 episodes of amaurosis fugax. Following a negative 45-minute embolus detection study with power M-mode TCD, the patient underwent a cTCID study with monitoring of the left middle cerebral artery (MCA), the anterior cerebral artery, and the submandibular extracranial internal carotid artery. A single microbubble (MB) was detected in the left MCA in only 1 of 5 studies; the remaining runs all failed to detect an RLS. Significant MB reflux was noted in the left internal jugular vein because of jugular valve incompetence. The authors conclude that incompetence of the jugular vein valve can result in a false negative cTCD study for RLS detection. C1 Massachusetts Gen Hosp, Stroke Serv, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Buonanno, FS (reprint author), Massachusetts Gen Hosp, Stroke Serv, Dept Neurol, VBK-802,Fruit St, Boston, MA 02114 USA. EM fbuonanno@partners.org NR 11 TC 3 Z9 3 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD JUL PY 2003 VL 13 IS 3 BP 272 EP 275 DI 10.1177/1051228403013003013 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 876CV UT WOS:000225474400013 PM 12889177 ER PT J AU Laurans, MSH DiLuna, ML Shin, D Niazi, F Voorhees, JR Nelson-Williams, C Johnson, EW Siegel, AM Steinberg, GK Berg, MJ Scott, RM Tedeschi, G Enevoldson, TP Anson, J Rouleau, GA Ogilvy, C Awad, IA Lifton, RP Gunel, M AF Laurans, MSH DiLuna, ML Shin, D Niazi, F Voorhees, JR Nelson-Williams, C Johnson, EW Siegel, AM Steinberg, GK Berg, MJ Scott, RM Tedeschi, G Enevoldson, TP Anson, J Rouleau, GA Ogilvy, C Awad, IA Lifton, RP Gunel, M TI Mutational analysis of 206 families with cavernous malformations SO JOURNAL OF NEUROSURGERY LA English DT Article DE cavernous angioma; cerebral cavernous malformation; KRIT1 gene ID MESSENGER-RNA DECAY; ENCODING KRIT1; NATURAL-HISTORY; CHROMOSOME 7Q; CCM1 GENE; HETEROGENEITY; ANGIOMAS; PROTEIN; EXONS AB Object. A gene contributing to the autosomal-dominant cerebral cavernous malformation (CCM) phenotype, KRIT1 (an acronym for Krev Interaction Trapped 1), has been identified through linkage analysis and mutation screening. The authors collected blood samples from 68 patients with familial CCM and 138 patients with apparently sporadic CCM as well as from their families, in an effort to characterize the prevalence and spectrum of disease-causing sequence variants in the KRIT1 gene. Methods. The authors used single-strand conformational polymorphism analysis to identify genomic variants in KRIT1, which were sequenced to determine the specific mutation. Among 43 Hispanic-American kindreds who immigrated to the southwestern US from northern Mexico, 31 share an identical founder mutation. This Q455X mutation is found in 18 (86%) of 21 persons with a positive family history and in 13 (59%) of 22 persons with apparently sporadic CCM. This mutation was not found among 13 persons with CCM who were recruited from Mexico. These findings establish the key role of a recent founder mutation in Hispanic persons with CCM who live in the US. Although nearly all Hispanic families in the US in which there are multiple CCM cases linked to the CCM1 locus, only 13 of 25 non-Hispanic CCM-carrying families have displayed evidence of linkage to the CCM1 locus. Among these 13 families, the authors identified eight independent mutations in nine kindreds. They identified four additional mutations among 22 familial CCM kindreds with no linkage information, bringing the total number of independent mutations to 12. Inherited KRIT1 mutations were not detected among 103 non-Hispanic persons in whom a family history of CCM was rigorously excluded. Conclusions. All mutations were nonsense mutations, frame-shift mutations predicting premature termination, or splice-site mutations located throughout the KRIT1 gene, suggesting that these are genetic loss-of-function mutations. These genetic findings, in conjunction with the clinical phenotype, are consistent with a two-hit model for the occurrence of CCM. C1 Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. Barrow Neurol Inst, Phoenix, AZ 85013 USA. Univ Hosp, Dept Neurol, Zurich, Switzerland. Stanford Univ, Sch Med, Dept Neurosurg, Palo Alto, CA USA. Univ Rochester, Ctr Med, Dept Neurol, Rochester, NY USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Second Univ, Inst Neurol Sci, Dept Neurol, Naples, Italy. Walton Ctr Neurol & Neurosurg, Las Vegas, NV USA. Walton Ctr Neurol & Neurosurg, Liverpool, Merseyside, England. McGill Univ, Ctr Res Neurosci, Montreal, PQ H3A 2T5, Canada. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA. Univ Colorado, Sch Med, Dept Neurosci, Denver, CO USA. RP Gunel, M (reprint author), Yale Univ, Sch Med, Dept Neurosurg, 333 Cedar St,Tompkins 4, New Haven, CT 06510 USA. FU NINDS NIH HHS [R01-NS36194-05] NR 27 TC 42 Z9 42 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUL PY 2003 VL 99 IS 1 BP 38 EP 43 DI 10.3171/jns.2003.99.1.0038 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 696BN UT WOS:000183865500007 PM 12854741 ER PT J AU Coumans, JVCE Reinhardt, MK Lieberman, IH AF Coumans, JVCE Reinhardt, MK Lieberman, IH TI Kyphoplasty for vertebral compression fractures: 1-year clinical outcomes from a prospective study SO JOURNAL OF NEUROSURGERY LA English DT Article DE bone cement; kyphoplasty; osteoporosis; polymethylmethacrylate; vertebral compression fracture; vertebroplasty ID VIVO BIOMECHANICAL EVALUATION; PERCUTANEOUS VERTEBROPLASTY; OSTEOLYTIC METASTASES; ACRYLIC CEMENT; OLDER WOMEN; MORTALITY; POLYMETHYLMETHACRYLATE; METHACRYLATE; OSTEOPOROSIS; INJECTION AB Object. Over the past 15 years, vertebroplasty has emerged as a treatment for vertebral compression fractures. This technique, however, does not restore vertebral height and is associated with a high rate of cement leakage. Recently, kyphoplasty was developed in an effort to circumvent this problem. Although its immediate results have been reported, it is unclear whether the benefits endure. Methods. Seventy-eight consecutive patients underwent 188 kyphoplasty procedures. The patients responded to Short Form-36 (SF-36) questionnaires, a visual analog scale (VAS) for pain rating, and the Oswestry disability index (ODI) instrument; additionally they underwent detailed neurological and radiographic examinations pre- and postoperatively. The preoperative SF-36, VAS, and ODI scores, the neurological examination results, and the radiographic data were compared with the postoperative findings. Thirteen patients died of disease progression or unrelated illness. Of the surviving patients, complete data were available in 62% (minimum follow-up period 12 months, mean 18 months). Complications included one myocardial infarction and five cases of asymptomatic cement extravasation. No case of neurological deterioration occurred during the follow-up period. Significant improvements in seven measures of the SF-36 inventory as well as on the ODI and VAS were noted early postoperatively, and these persisted throughout the follow-up period, despite a statistically insignificant decline in the measure of general health at last follow-up examination. Conclusions. Kyphoplasty is an effective treatment for vertebral compression fractures. The benefits presented in the early postoperative period and persisted at I year posttreatment. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02118 USA. Cleveland Clin Fdn, Dept Orthopaed Surg, Cleveland, OH 44195 USA. RP Coumans, JVCE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, WACC 021,Fruit St, Boston, MA 02118 USA. NR 29 TC 121 Z9 139 U1 0 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUL PY 2003 VL 99 IS 1 SU S BP 44 EP 50 DI 10.3171/spi.2003.99.1.0044 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 699AP UT WOS:000184034000011 PM 12859058 ER PT J AU Boyce, PD Waxman, AB AF Boyce, PD Waxman, AB TI Pulmonary hypertension: Work in progress SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article ID INHALED NITRIC-OXIDE; CONTINUOUS INTRAVENOUS EPOPROSTENOL; IMMUNODEFICIENCY-VIRUS INFECTION; MAGNETIC-RESONANCE ANGIOGRAPHY; PROTEIN-RECEPTOR-II; ARTERIAL-HYPERTENSION; SYSTEMIC-SCLEROSIS; LUNG-TRANSPLANTATION; VASCULAR-DISEASE; CONTROLLED TRIAL AB Pulmonary arterial hypertension is a rare disorder defined by mean pulmonary artery pressures that exceed 25 nun Hg at rest or are greater than 30 mm Hg with exercise. The mortality rate is high for untreated patients, mainly as a result of progressive right heart dysfunction. Pulmonary arterial hypertension has been historically classified as primary pulmonary hypertension or pulmonary hypertension resulting from an underlying disease process. Ongoing research in the nuclear medicine field holds great promise for understanding the pathophysiologic pathways for this condition, as well as the monitoring of the continually evolving therapeutic options. C1 Massachusetts Gen Hosp, Pulm Crit Care Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Pulm, Boston, MA 02115 USA. RP Waxman, AB (reprint author), Massachusetts Gen Hosp, Pulm Crit Care Unit, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. NR 99 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD JUL-AUG PY 2003 VL 10 IS 4 BP 413 EP 423 DI 10.1016/S1071-3581(03)00549-X PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 709KM UT WOS:000184624400010 PM 12900746 ER PT J AU Sesso, HD Liu, SM Gaziano, JM Buring, JE AF Sesso, HD Liu, SM Gaziano, JM Buring, JE TI Dietary lycopene, tomato-based food products and cardiovascular disease in women SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT 44th Annual Conference of the Canadian-Federation-of-Biological-Societies CY JUN, 2001 CL OTTAWA, CANADA SP Canadian Federat Biol Soc DE lycopene; cardiovascular disease; prevention; prospective studies; women ID LOW-DENSITY-LIPOPROTEIN; MYOCARDIAL-INFARCTION; BETA-CAROTENE; FREQUENCY QUESTIONNAIRE; ANTIOXIDANT VITAMINS; PROSTATE-CANCER; ADIPOSE-TISSUE; HEART-DISEASE; RISK-FACTORS; SUPPLEMENTATION AB In addition to the inverse association of dietary lycopene with various cancers, studies suggest a role for lycopene in cardiovascular disease (CVD) prevention. We determined whether the intake of lycopene or tomato-based foods is associated with the risk of CVD in a prospective cohort of 39,876 middle-aged and older women initially free of CVD and cancer. Participants completed a food-frequency questionnaire and provided self-reports of coronary risk factors. Dietary lycopene levels were divided into quintiles, and primary lycopene food sources (total tomato-based products, including tomatoes, tomato juice, tomato sauce and pizza) were categorized. During 7.2 y of follow-up, 719 CVD cases (including myocardial infarction, stroke, revascularization and CVD death) occurred. Compared with women in the 1st quintile of lycopene, those in increasing quintiles had multivariate relative risks (RR) of CVD of 1.11, 1.14, 1.15 and 0.90 (P for trend = 0.34). For the consumption of tomato-based products, women consuming 1.5 to <4, 4 to <7, 7 to <10 and greater than or equal to10 servings/wk had RR (95% Cl) of CVD of 1.02 (0.82-1.26), 1.04 (0.82-1.31), 0.68 (0.49-0.96) and 0.71 (0.42-1.17) (P for trend = 0.029) compared with women consuming <1.5 servings/wk. Among lycopene food sources, those in the highest levels of tomato sauce (greater than or equal to2 servings/wk) and pizza intake (greater than or equal to2 servings/wk), with multivariate RR of 0.76 (0.55-1.05) and 0.66 (0.37-1.18), respectively, had potential reductions in CVD risk. Dietary lycopene was not strongly associated with the risk of CVD. However, the possible inverse associations noted for higher levels of tomato-based products, particularly tomato sauce and pizza, with CVD suggest that dietary lycopene or other phytochemicals consumed as oil-based tomato products confer cardiovascular benefits. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. RP Sesso, HD (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. RI Liu, Simin/I-3689-2014 OI Liu, Simin/0000-0003-2098-3844 FU NCI NIH HHS [CA-47988]; NHLBI NIH HHS [HL-65727, HL-43851]; NIA NIH HHS [AG-15933]; NINDS NIH HHS [NS34108] NR 33 TC 113 Z9 126 U1 2 U2 15 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JUL PY 2003 VL 133 IS 7 BP 2336 EP 2341 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 699BW UT WOS:000184036900042 PM 12840203 ER PT J AU Halpern, LR Carter, JB Chuang, SK Dodson, TB AF Halpern, LR Carter, JB Chuang, SK Dodson, TB TI A comparison of 2 consultation and treatment strategies to manage impacted third molars SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID MINOR ORAL-SURGERY; REMOVAL; PERCEPTION; DENTISTS AB Purpose: This study compares the postoperative complication rates of 2 strategies for the evaluation and operative management (E&M) of patients with impacted third molars MO. Materials and Methods: We used a retrospective cohort study design and a sample composed of patients who had M3s extracted between 1985 and 2000. The predictor variable was the E&M strategy defined as 1) same-day surgery (SDS) in which the consultation and procedure were performed on the same day and 2) consult prior to surgery (CPS) in which the consultation and procedure were separated in time by more than 24 hours. The outcome variable was postoperative complications. Descriptive and bivariate statistics were computed and a multivariate model was developed to measure the relationship between E&M strategies and postoperative complications. Results: The sample was composed of 5,993 patients (mean age, 23.7 years; 61% female), and 1,556 patients (26%) were classified as having SDS. Overall, 36% of patients reported one or more postoperative complications. Variables included in the multivariate model were E&M strategy (SDS or CPS), age, gender, number of M3s removed, tobacco exposure, and type of anesthesia. Based on the results of the multivariate model, SDS was not associated with an increased risk for postoperative complications (P = .08). Conclusions: Optimal operative management of M3s would minimize the number of visits, maximize operator efficiency, and minimize morbidity. In comparison with CPS, SDS minimizes the number of patient visits without an increased risk for complications. (C) 2003 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Oral Surg Inst, Nashville, TN USA. RP Halpern, LR (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren 1201,55 Fruit St, Boston, MA 02114 USA. FU NIDCR NIH HHS [K24 DE000448, K16 DE000275] NR 31 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 2003 VL 61 IS 7 BP 779 EP 784 DI 10.1016/S0278-2391(03)00154-X PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 695HP UT WOS:000183825300009 PM 12856250 ER PT J AU Hwang, SS Chang, VT Rue, M Kasimis, B AF Hwang, SS Chang, VT Rue, M Kasimis, B TI Multidimensional independent predictors of cancer-related fatigue SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article; Proceedings Paper CT Annual Scientific Meeting of the American-Society-of-Clinical-Oncology CY 1999 CL LOS ANGELES, CALIFORNIA SP Amer Soc Clin Oncol DE cancer fatigue; predictors; analgesics; anemia; pain; feeling drowsy; dyspnea; lack of appetite; depression; veterans; sad ID QUALITY-OF-LIFE; BREAST-CANCER; FUNCTIONAL ASSESSMENT; SYMPTOM ASSESSMENT; MEDICAL-CENTER; DOUBLE-BLIND; THERAPY; SCALE; RADIOTHERAPY; CHEMOTHERAPY AB The purpose of this stud was to identify independent predictors of clinically significant fatigue based upon a multidimensional model. A total of 180 cancer patients completed the Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Fatigue (FACT-F), Memorial Symptom Assessment Scale Short Form (MSAS-SF), and the Zung Self-Rating Depression Scale (SDS). Additional data included Karnofsky Performance Status (KPS) score, laboratory tests, and demographic information. The BFI usual fatigue severity greater than or equal to 3/10 was defined as clinically significant fatigue. Possible independent variables were identified from a biopsychosocial model of fatigue. Fisher's exact test was used to univariately assess the association of each variable with clinically, significant fatigue. Multiple logistic regression analyses were used to identify independent predictors of fatigue within each dimension, and then across dimensions. Fatigue was present in 113 (62%) patients, and 80 (44.4%) patients had usual fatigue greater than or equal to 3/10. The unidimensional independent predictors were use of analgesics (situation dimension); hemoglobin and serum sodium (biomedical dimension); feeling drowsy, dyspnea, pain and lack of appetite (physical symptom dimension); and feeling sad and feeling irritable (psychological symptom dimension). In a multidimensional model, dyspnea, pain, lack of appetite, feeling drowsy, feeling sad, and feelings irritable predicted fatigue independently with good calibration (Hosmer Lemeshow Chi Square = 5.73, P = 0.68) and discrimination (area under the receiver operating characteristic curve = 0.88). Physical and psychological symptoms predict fatigue independently in the multidimensional model, and superseded laboratory data. These findings support a symptom-oriented approach to assessment of cancer-related fatigue. (C) 2003 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 VA New Jersey Hlth Care Syst, Hematol Oncol Sect, E Orange, NJ 07018 USA. VA New Jersey Hlth Care Syst, Patient Care Serv, E Orange, NJ 07018 USA. UMDNJ, Sch Nursing, Newark, NJ USA. UMDNJ, Sch Med, Newark, NJ USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Hwang, SS (reprint author), VA New Jersey Hlth Care Syst, Hematol Oncol Sect, 111,385 Tremont Ave, E Orange, NJ 07018 USA. RI Rue, Montserrat/B-5663-2009 OI Rue, Montserrat/0000-0002-7862-9365 NR 41 TC 70 Z9 72 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUL PY 2003 VL 26 IS 1 BP 604 EP 614 DI 10.1016/S0885-3924(03)00218-5 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 702GJ UT WOS:000184215900006 PM 12850643 ER PT J AU Casarett, DJ Karlawish, JHT Hirschman, KB AF Casarett, DJ Karlawish, JHT Hirschman, KB TI Identifying ambulatory cancer patients at risk of impaired capacity to consent to research SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE competence; decision-making capacity; ethics; research ethics; informed consent ID RANDOMIZED CONTROLLED-TRIAL; PALLIATIVE CARE RESEARCH; QUALITY-OF-LIFE; INFORMED CONSENT; TREATMENT DECISIONS; SYMPTOM ASSESSMENT; METASTATIC CANCER; ONCOLOGY PATIENTS; PAIN MANAGEMENT; COMPETENCE AB Ethicists and others have expressed concerns that some patients with cancer might lack adequate decision-making capacity to give consent,for research. Although this concern is plausible, it is not known what patient characteristics might be used to identify those Patients who are at risk and who therefore should undergo a formal assessment of decision-making capacity. Forty-five patients with cancer were Presented with a description of a randomized controlled trial, accompanied by an Institutional Review Board-approved consent form. Two raters who were blind to all patient characteristics assessed decision-making capacity using the MacArthur Competency Assessment Tool for Clinical Research. These scores were summarized in overall capacity judgments using criteria established by a panel of experts. Subjects also completed a symptom rating scale and a battery of neuropsychiatric tests. No relationship was observed between symptom severity and any domain of decision-making capacity (understanding, appreciation, reasoning, ability to express a choice) or summary judgments. However, several other patient characteristics, including age, education, and selected neuropsychiatric test results, were found to be strongly associated with capacity scores. These data suggest that several patient characteristics, such as age, education, and tests of cognitive functions, may help investigators to identify patients with impaired capacity to give consent for research. (C) 2003 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Geriatr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Alzheimers Dis Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Sch Social Work, Philadelphia, PA 19104 USA. RP Casarett, DJ (reprint author), Inst Aging, 3615 Chestnut St, Philadelphia, PA 19104 USA. FU NIA NIH HHS [K01-AG00931] NR 48 TC 28 Z9 28 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 JUL PY 2003 VL 26 IS 1 BP 615 EP 624 DI 10.1016/S0885-3924(03)00221-5 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 702GJ UT WOS:000184215900007 PM 12850644 ER PT J AU Waters, PM Bae, DS Kadiyala, RK AF Waters, PM Bae, DS Kadiyala, RK TI Short-term outcomes after surgical treatment of traumatic posterior sternoclavicular fracture-dislocations in children and adolescents SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE posterior sternoclavicular fracture-dislocation ID RETROSTERNAL DISLOCATION; EPIPHYSEAL SEPARATION; CLAVICLE; JOINT; INJURY; DISPLACEMENT; DIAGNOSIS; MIGRATION; REDUCTION; SHOULDER AB Posterior sternoclavicular joint (SCJ) dislocations and posteriorly displaced physeal fractures of the medial clavicle require prompt diagnosis and treatment to prevent persistent symptoms, recurrent instability, and potential complications. The purpose of this investigation was to review one institution's experience with these injuries. A retrospective review of 13 patients with posterior SCJ fracture-dislocations was performed. Average patient age was 14.6 years, and 85% of injuries were sustained during sporting activities. Patients with posterior dislocations underwent ligament repair and those with posteriorly displaced medial clavicular physeal fractures had open reduction and suture stabilization. At an average of 22.2 months follow-up, all patients had excellent functional outcomes. There were no respiratory or neurovascular complications. Skeletally immature patients may expect excellent functional outcomes following surgery for posterior SCJ dislocations or posteriorly displaced physeal fractures of the medial clavicle. C1 Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Harvard Univ, Combined Orthopaed Residency Program, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Iowa Hosp & Clin, Dept Orthopaed Surg, Iowa City, IA 52242 USA. RP Waters, PM (reprint author), Childrens Hosp, Dept Orthopaed Surg, 300 Longwood Ave, Boston, MA 02115 USA. NR 32 TC 25 Z9 27 U1 2 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 JUL-AUG PY 2003 VL 23 IS 4 BP 464 EP 469 DI 10.1097/00004694-200307000-00010 PG 6 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 695EX UT WOS:000183819100010 PM 12826944 ER PT J AU Gow, DW AF Gow, DW TI How representations help define computational problems: commentary on Grossberg, Gaskell and Greenberg SO JOURNAL OF PHONETICS LA English DT Editorial Material ID SPOKEN WORD RECOGNITION; SPEECH-PERCEPTION C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. Salem State Coll, Salem, MA USA. RP Gow, DW (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, VBK 821 55 Fruit St, Boston, MA 02114 USA. NR 21 TC 4 Z9 4 U1 1 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0095-4470 J9 J PHONETICS JI J. Phon. PD JUL-OCT PY 2003 VL 31 IS 3-4 BP 487 EP 493 DI 10.1016/S0095-4470(03)00015-9 PG 7 WC Linguistics; Language & Linguistics SC Linguistics GA 751WZ UT WOS:000187114200016 ER PT J AU Chang, JC Hart, DA Estey, AW Chan, JT AF Chang, JC Hart, DA Estey, AW Chan, JT TI Tensile bond strengths of five luting agents to two CAD-CAM restorative materials and enamel SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article ID INLAYS AB Statement of problem. CAD-CAM restorative materials arc popular because they have high esthetic value and short fabrication time. Unfortunately these materials are brittle and tend to fracture under heavy occlusal load. Purpose. The purpose of this in vitro study was to investigate the tensile bond strengths of 5 luting agents to 2 CAD-CAM restorative materials and enamel. Material and methods. One hundred truncated cones, with a 3-mm diameter bonding surface and 5-mm diameter base, were fabricated with Dicor MGC (n=50) or Cerec Vitablocs Mark II (n=50) with the Cercc system. Enamel surfaces of the crowns of 100 freshly extracted noncarious, anterior teeth, stored in 0.9% saline solution with 0.25% sodium azide (NaN3) as disinfectant, were prepared with sandpaper disks (320-grit size) on the Buehler Variable Speed Grinder-Polisher. The bonding surfaces of the Dicor MGC or Cercc Vitablocs Mark II truncated cones from each of the 2 tests systems were airborne particle abraded, chemically etched, and cemented on the prepared enamel surface of the tooth specimens with 5 luting agents: Vita Cerec Duo Cement, EnForce, Panavia 21, C&B Metabond, and Fuji Duct. All specimens were thermocycled 1000 times, in 5degrees C and 55degreesC water with a dwell time of 30 seconds in each temperature. Tensile force (MPa) was applied perpendicular to the bonding surfaces of the specimens with a universal testing machine until fracture. Fracture patterns were examined with a microscope at original magnification x 10. The differences in the tensile bond strengths were analyzed with the Tukey-Kramer test (alpha=.05). Results. The mean tensile bond strengths of Dicor MGC bonding to enamel with luting agents in descending order in MPa were EnForce (10.12 +/- 2.25), Panavia 21 (7.28 +/- 1.77), Cerec Duo (5.32 +/- 1.65), Fuji Duet (3.73 +/- 1.78), and C&B Metabond (3.11 +/- 1.11). EnForce had a significantly higher bond strength than C&B Metabond, Fuji Duet, Cerec Duo, and Panavia 21 (P=.05). The mean tensile bond strengths of Cerec Vitablocs Mark I I bonding to enamel with luting agents in descending order in MPa were as follow: Fuji Duet (11.51 +/- 2.79), EnForce (9.44 +/- 2.03), C&B Metabond (8.98 +/- 3.29), Cerec Duo (8.66 +/- 4.71), and Panavia 21 (5.10 +/- 2.49). Within this group, there was no significant difference between Fuji Duet and EnForce, but the bond strength of Fuji Duet was significantly higher than that of C&B Metabond, Panavia 21, and Cerec Duo (P=.05). The mean tensile strength of all the luting agents bonded to Cerec Vitablocs Mark II and enamel (8.74 MPa) was higher than Dicor MGC and enamel (5.91 MPa). Conclusion. In this in vitro study; within the Dicor MGC group, the mean bond strength of Panavia 21 with enamel was significantly higher than C&B Metabond, Panavia 21, Cerec Duo, and Fuji Duet. Within the Cercc Vitablocs Mark II group, the mean bond strength of Fuji Duet was significantly higher than C&B Metabond, Panavia 21, and Cerec Duo but was not significantly higher than EnForce. C1 Univ Texas, Dept Dent Publ Hlth & Dent Hyg, Houston Dent Branch, Houston, TX 77030 USA. Univ Texas, Dept Basic Sci, Houston Dent Branch, Houston, TX 77030 USA. VA Med Ctr, Adv Prosthodont Program, Dent Serv, Houston, TX USA. RP Chang, JC (reprint author), Univ Texas, Dept Dent Publ Hlth & Dent Hyg, Houston Dent Branch, 6516 MD Anderson Ave, Houston, TX 77030 USA. NR 8 TC 14 Z9 17 U1 2 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD JUL PY 2003 VL 90 IS 1 BP 18 EP 23 DI 10.1016/S0022-3913(03)00217-8 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 703KV UT WOS:000184279300005 PM 12869970 ER PT J AU Brambilla, P Harenski, K Nicoletti, M Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC AF Brambilla, P Harenski, K Nicoletti, M Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC TI MRI investigation of temporal lobe structures in bipolar patients SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2001 CL NEW ORLEANS, LOUISIANA SP Soc Biol Psychiat DE amygdala; hippocampus; temporal lobes; superior temporal gyrus; bipolar disorder; magnetic resonance imaging ID POSTTRAUMATIC-STRESS-DISORDER; MAGNETIC-RESONANCE; HIPPOCAMPAL VOLUME; MAJOR DEPRESSION; HUMAN AMYGDALA; HEALTHY-INDIVIDUALS; ALZHEIMERS-DISEASE; FACIAL EXPRESSIONS; ANATOMICAL MRI; MOOD DISORDERS AB Previous anatomical MRI studies have suggested abnormalities in amygdala volumes in bipolar disorder, whereas hippocampus, temporal lobe (TL), and superior temporal gyri (STG) measures have been reported to be normal. This study further investigated the existence of anatomical abnormalities in these brain structures in bipolar subjects, to attempt to replicate previously reported findings. Twenty-four DSM-IV bipolar patients (mean age+/-S.D. = 35+/-10 years) and 36 healthy controls (mean age+/-S.D. = 37+/-10 years) were studied. 3D SPGR images were obtained with a 1.5T-GE Signa magnet (TR = 25 ms, TE = 5 ms, FOV = 24 cm, slice-thickness = 1.5 mm, matrix-size = 256x192). Volumetric measurements of TL, hippocampus, amygdala, and STG were performed blindly, with a semi-automated software. Bipolar patients had significantly larger left amygdala volumes compared with controls (mean volumes+/-S.D. = 2.57+/-0.69 vs. 2.17+/-0.58 ml, respectively; ANCOVA, age, gender, ICV as covariates; F = 4.42, df = 1155, P = 0.04). The volumes of the other temporal lobe structures did not differ significantly between the two groups (ANCOVA, age, gender, and ICV as covariates, P > 0.05). Our findings of enlarged left amygdala in bipolar patients are in agreement with prior MRI studies, suggesting that abnormalities in this brain structure may be implicated in pathophysiology of the illness. Longitudinal studies in high-risk offspring and first-episode patients will be needed to examine whether such:abnormalities precede the appearance of symptoms, or whether they may appear subsequently as a result of illness course. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78229 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Sch Med, Pittsburgh, PA 15213 USA. Univ Pavia, Sch Med, Dept Psychiat, IRCCS S Matteo, Pavia, Italy. Univ Genoa, Adv Biotechnol Ctr, Genoa, Italy. Univ Sao Paulo, Sch Med, Dept Psychiat, Inst Psychiat, Sao Paulo, Brazil. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 FU NIMH NIH HHS [MH 01736, MH 29618, MH 30915] NR 57 TC 157 Z9 162 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD JUL-AUG PY 2003 VL 37 IS 4 BP 287 EP 295 DI 10.1016/S0022-3956(03)00024-4 PG 9 WC Psychiatry SC Psychiatry GA 684PE UT WOS:000183215100003 PM 12765851 ER PT J AU Pauls, DL AF Pauls, DL TI An update on the genetics of Gilles de la Tourette syndrome SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article; Proceedings Paper CT International Conference of the Tourette-Syndrome-Foundation-of-Canada CY MAY 31-JUN 02, 2002 CL MISSISSAUGA, CANADA SP Tourette Syndrome Fdn Canada DE Gilles de la Tourette syndrome; family studies; candidate gene studies; genetic linkage studies ID AUTOSOMAL-DOMINANT TRANSMISSION; OBSESSIVE-COMPULSIVE DISORDER; ATTENTION-DEFICIT DISORDER; RECEPTOR GENE; LINKAGE DISEQUILIBRIUM; D2-DOPAMINE RECEPTOR; SEGREGATION ANALYSIS; TRANSPORTER GENE; TIC DISORDERS; NO EVIDENCE AB Objectives: To summarize the current data suggesting that Gilles de la Tourette syndrome (GTS) is inherited and genetic. Methods: The extant literature on family studies, segregation analyses, candidate genes studies and linkage studies of GTS was reviewed and summarized. Results and conclusions: There is considerable data that suggests that: (1) genetic factors play an important role in the manifestation of GTS; (2) several genes are important with some possibly having major effect; and (3) several regions of the genome have been identified as potential locations of these susceptibility genes. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Charlestown, MA 02129 USA. RP Pauls, DL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, 149 13th St,10th Floor, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS-16648, NS-40024] NR 62 TC 64 Z9 72 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD JUL PY 2003 VL 55 IS 1 BP 7 EP 12 DI 10.1016/S0022-3999(02)00586-X PG 6 WC Psychiatry SC Psychiatry GA 699WE UT WOS:000184078300003 PM 12842226 ER PT J AU Greene, RW Ablon, JS Goring, JC AF Greene, RW Ablon, JS Goring, JC TI A transactional model of oppositional behavior - Underpinnings of the Collaborative Problem Solving approach SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article; Proceedings Paper CT International Conference of the Tourette-Syndrome-Foundation-of-Canada CY MAY 31-JUN 02, 2002 CL MISSISSAUGA, CANADA SP Tourette Syndrome Fdn Canada ID ATTENTION-DEFICIT HYPERACTIVITY; CONDUCT-DISORDERED CHILDREN; DEFIANT DISORDER; ANTISOCIAL-BEHAVIOR; EXECUTIVE FUNCTIONS; TOURETTES-DISORDER; AGGRESSIVE BOYS; JUVENILE MANIA; FOLLOW-UP; COMORBIDITY AB Oppositional defiant disorder (ODD) refers to a recurrent pattern of developmentally inappropriate levels of negativistic, defiant, disobedient, and hostile behavior toward authority figures. ODD is one of the most common (and debilitating) comorbid disorders within Tourette's disorder (TD). Diverse psychosocial treatment approaches have been applied to children's ODD-related behaviors. In this paper, the authors articulate a transactional developmental conceptualization of oppositional behavior and describe a cognitive-behavioral model of intervention-called Collaborative Problem Solving (CPS)-emanating from this conceptualization. The specific goals of the CPS approach are to help adults (1) understand the specific adult and child characteristics contributing to the development of a child's oppositional behavior; (2) become cognizant of three basic strategies for handling unmet expectations, including (a) imposition of adult will, (b) CPS, and (c) removing the expectation; (3) recognize the impact of each of these three approaches on parent-child interactions; and (4) become proficient, along with their children, at CPS as a means of resolving disagreements and defusing potentially conflictual situations so as to reduce oppositional episodes and improve parent-child compatibility. Summary data from an initial study documenting the effectiveness of the CPS approach (in comparison to the standard of care) are also presented. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, CPS Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Virginia Polytech Inst & State Univ, Dept Psychol, Blacksburg, VA 24061 USA. RP Greene, RW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, CPS Inst, Boston, MA 02114 USA. EM greene@helik.mgh.harvard.edu NR 94 TC 33 Z9 35 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD JUL PY 2003 VL 55 IS 1 BP 67 EP 75 DI 10.1016/S0022-3999(02)00585-8 PG 9 WC Psychiatry SC Psychiatry GA 699WE UT WOS:000184078300010 PM 12842233 ER PT J AU Dancewicz, TM Krebs, DE McGibbon, CA AF Dancewicz, TM Krebs, DE McGibbon, CA TI Lower-limb extensor power and lifting characteristics in disabled elders SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE biomechanics; disabled elders; functionally limited elders; lifting; power; strength ID HAND-HELD DYNAMOMETRY; PHYSICAL-DISABILITY; FLEXION-RELAXATION; BODY-COMPOSITION; MUSCLE STRENGTH; JOINT MOMENTS; BACK MUSCLES; EXERCISE; COORDINATION; PERFORMANCE AB Few reports address lifting in disabled elders. Resistance training may facilitate function by improving coordination and muscular recruitment in common lifting tasks. Subjects were considered "functionally limited" if they reported a limitation in at least I of 9 possible functional areas listed on the Short-Form Health Survey physical function scale (SF-36), excluding the vigorous activity item. Eighty-nine functionally limited elders (60.3 to 89.8 years old) consented to participate in an intervention trial consisting of a 6-month in home video-facilitated resistance exercise program using elastic bands. Biomechanical variables (leg extensor power, work, squared jerk), temporal outcomes (lift time and time to peak leg powers), and leg extensor strength were analyzed with the use of analysis of variance (ANOVA) between the (1) experimental group versus control group and the (2) subgroup of the weakest third of subjects (pretest leg extensor strength as percent of body weight [BW]). The experimental group had significant improvements in strength in knee extension (16.7%) and hip extension (20.5%). Resistance-trained weak subjects significantly increased hip extension strength compared to controls. A trend toward improved performance in lifting-decreased total lift time-was noted in the resistance-trained subjects. Significant correlations were found between total leg extension power, total leg extension strength, total work, and lift time. Resistance-trained disabled elders demonstrated strength benefits and several trends consistent with improved coordination and more efficient lifting. Leg-muscle power was related to better functional performance in lifting. C1 Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02129 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Krebs, DE (reprint author), Massachusetts Gen Hosp, Biomot Lab, 36 1st Ave,CNY 36, Boston, MA 02129 USA. FU NIA NIH HHS [R01-AG12561, P50-AG11669] NR 48 TC 15 Z9 15 U1 0 U2 1 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 JUL-AUG PY 2003 VL 40 IS 4 BP 337 EP 347 PG 11 WC Rehabilitation SC Rehabilitation GA 712CU UT WOS:000184779800007 PM 15074445 ER PT J AU Oglesby, AK Minshall, ME Shen, W Xie, S Silverman, SL AF Oglesby, AK Minshall, ME Shen, W Xie, S Silverman, SL TI The impact of incident vertebral and non-vertebral fragility fractures on health-related quality of life in established postmenopausal osteoporosis: Results from the teriparatide randomized, placebo-controlled trial in postmenopausal women SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE health-related quality of life; incident fracture; osteoporosis; OPAQ ID PREVALENT AB Objective. To report the combined impact of both vertebral and non-vertebral fractures on decreased health-related quality of life (HRQOL) in postmenopausal women (mean age 70.7) with osteoporosis who participated in a clinical trial to examine the anti-fracture efficacy of teriparatide [rhPTH(1-34)] injection. Methods. Patients were randomly assigned to 1 of 3 study arms: placebo, 20 mug or 40 mug of teriparatide by daily self-injection. All patients received daily calcium (1000 mg) and vitamin D (4001200 U) supplements. Patients were followed for a median of 21 months. Incident vertebral fractures were assessed by lateral spinal radiograph. Incident non-vertebral fractures were ascertained by patient self-report and verified by a review of radiological reports. HRQOL was assessed at baseline and annually until study termination using the Osteoporosis Assessment Questionnaire (OPAQ), a validated disease-targeted instrument. Results. Of the 365 women in the HRQOL sub-study, 53 had an incident vertebral or non-vertebral fracture during the study period. Compared to women without incident fractures, women who fractured reported significant declines in physical functioning, emotional status, and symptoms (all p < 0.05). Similarly, when analysis was limited to patients with significant loss in HRQOL, patients with incident fracture accounted for a greater proportion of those patients with decreased physical function, emotional status, and increased symptoms (all p < 0.05). Conclusion. Our results confirm and extend previous findings to show that a composite endpoint of incident vertebral and non-vertebral fractures in women with postmenopausal osteoporosis was associated with significant decreases in HRQOL. C1 Eli Lilly & Co, Lilly Corp Ctr, Global Econ Affairs, Indianapolis, IN 46285 USA. Cedars Sinai Med Ctr, Greater Los Angeles Vet Adm Hlth Syst, OMC Clin Res Ctr, Los Angeles, CA USA. RP Oglesby, AK (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Global Econ Affairs, DC 1834, Indianapolis, IN 46285 USA. NR 16 TC 32 Z9 32 U1 2 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 2003 VL 30 IS 7 BP 1579 EP 1583 PG 5 WC Rheumatology SC Rheumatology GA 699MT UT WOS:000184061100032 PM 12858462 ER PT J AU Gerber, A Marti, R Jupiter, J AF Gerber, A Marti, R Jupiter, J TI Surgical management of diaphyseal humeral nonunion after intramedullary nailing: Wave-plate fixation and autologous bone grafting without nail removal SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID COMPLEX NONUNION; FRACTURES; OSTEOSYNTHESIS; SHAFT AB Six patients with a nonunion of the humeral diaphysis after intramedullary nailing were treated with a wave plate and autologous bone graft but without removal of the intramedullary implant. The mean duration of the nonunion was 19 months (range, 6-36 months). At a mean follow-up of 12 months (range, 6-18 months), all six nonunions hod healed, and patient satisfaction was high. Five patients had regained full shoulder function. One patient, who was treated for a rotator cuff tear before the humeral fracture, had a satisfactory functional outcome. Elbow motion was full in all but one patient. One patient had a postoperative radial nerve palsy, which recovered partially but did not require further surgery. This report suggests that healing of humeral nonunions can be achieved in the presence of intramedullary hardware. C1 Humboldt Univ, Clin Trauma & Reconstruct Surg, Klinikum Rudolf Virchow, D-13353 Berlin, Germany. Acad Med Ctr, Dept Orthopaed Surg, Amsterdam, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand Serv, Boston, MA 02115 USA. RP Gerber, A (reprint author), Humboldt Univ, Clin Trauma & Reconstruct Surg, Klinikum Rudolf Virchow, Augustenburger Pl 1, D-13353 Berlin, Germany. RI Gerber Popp, Ariane/O-2781-2014 OI Gerber Popp, Ariane/0000-0002-6798-3676 NR 14 TC 15 Z9 15 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD JUL-AUG PY 2003 VL 12 IS 4 BP 309 EP 313 DI 10.1016/S1058-2746(03)00044-2 PG 5 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 714XM UT WOS:000184939600001 PM 12934021 ER PT J AU Zhou, XH Castelluccio, P AF Zhou, XH Castelluccio, P TI Nonparametric analysis for the ROC areas of two diagnostic tests in the presence of nonignorable verification bias SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE diagnostic tests; the ROC curve; verification bias; missing data; likelihood; EM; nonignorability ID INCOMPLETE DATA; NONRESPONSE; REGRESSION; MECHANISM; MODELS AB A paired design is often used to evaluate the accuracies of competing diagnostic tests. One common problem in a paired design is verification bias which occurs when some patients do not receive disease verification and when the reason for verification depends on the test results and other factors. Most of the existing methods for verification bias correction assume the verification process is ignorable, which means that the probability of verifying a patient depends only on the observed covariates, but not on the unobserved disease status of the patient. In this paper, we develop a bias correction procedure without assuming ignorability of the verification mechanism. As far as we know, this proposed method is the first attempt to combine nonignorable verification with estimation of the ROC areas. At issue is the possible existence of multiple local maxima and boundary solutions for the maximum likelihood (ML) equations, which can complicate the computation of the ML estimates. To deal with this computational difficulty, we propose a profile method combined with the EM algorithm to find the global ML estimators for the parameters of interest under a proposed nonignorable verification model. Furthermore, we also find a simple solution to the boundary point problem. After obtaining the ML estimates, we propose likelihood-based inferences on the relative accuracy of two diagnostic tests. Another issue in the analysis is the goodness-of-fit of the proposed nonignorable model for the verification mechanism. We propose to use a bootstrap-based goodness-of-fit test for the proposed nonignorable model. Finally, we apply our method to data from a real study that has motivated this research. In this example, the aim of our analysis is to compare the relative accuracy of MRI and CT imaging in detecting advanced stage pancreatic cancer. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Indiana Univ, Sch Med, Dept Med, Div Biostat, Indianapolis, IN 46202 USA. VA Puget Sound Hlth Care Syst, NW Ctr Hlth Serv Res & Dev, Seattle, WA 98108 USA. Indiana Univ, Sch Med, Dept Med & Mol Genet, Bloomington, IN 47405 USA. NR 17 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JUL 1 PY 2003 VL 115 IS 1 BP 193 EP 213 AR PII S0378-3758(02)00146-5 DI 10.1016/S0378-3758(02)00146-5 PG 21 WC Statistics & Probability SC Mathematics GA 680UF UT WOS:000182996400011 ER PT J AU Liu, JH Etzioni, DA O'Connell, JB Maggard, MA Ko, CY AF Liu, JH Etzioni, DA O'Connell, JB Maggard, MA Ko, CY TI Using volume criteria: Do California hospitals measure up? SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Association-for-Academic-Surgery CY NOV 07-09, 2002 CL BOSTON, MASSACHUSETTS SP Assoc Acad Surg DE surgery; quality of care; volume; procedural volume; outcome; Leapfrog; California ID NEW-YORK-STATE; AFFAIRS SURGICAL RISK; MORTALITY-RATE; UNITED-STATES; SURGERY; QUALITY; CARE; OUTCOMES; CANCER; OPERATIONS AB Background. Many studies have demonstrated a significant relationship between high procedural volume and better outcomes. As the public becomes increasingly aware of this medical literature, consumer groups have collaborated with medical researchers to operationalize this body of evidence. One such organization, the Leapfrog Group, has proposed annual volume criteria for four operations: coronary bypass grafting (CABG), abdominal aortic aneurysm (AAA), carotid endarterectomy (CEA), and esophageal cancer resection (ECR). This study analyzes California hospitals within the context of these volume criteria. Materials and methods. Using the California inpatient database from 2000, we identified all CABG, AAA, CEA, and ECR operations performed at metropolitan hospitals. The volume of each of the four operations was tabulated by hospital and evaluated. Comparisons were made between academic and nonacademic hospitals. Results. Most hospitals in California did not meet Leapfrog's volume criteria. Only 2 hospitals of 287 (0.7%) met the volume criteria for the operations that it performed. Of the 71 (25%) hospitals that performed all four procedures, none met the volume criteria of all four procedures. In fact, only 10% of California hospitals performing these operations were high-volume hospitals based on Leapfrog's volume criteria. When comparing academic to nonacademic hospitals, academic hospitals performed more AAA operations than nonacademic hospitals (36 vs 12, P = 0.02). Although academic hospitals tended to have higher caseloads for CABG, CEA, and ECR, these did not reach statistical significance. Also, academic hospitals were more likely to be high volume for AAA (43.8% vs 7.0%, P < 0.01) and for ECR (23.1% vs 4.0%, P < 0.01). Conclusions. California's hospital system is far from being regionalized. Although academic hospitals appear better positioned than nonacademic hospitals, the vast majority of all hospitals do not meet Leapfrog's volume criteria. As efforts to use volume as a proxy measure of quality gain momentum, hospitals and physicians will be forced to measure and report quality. As such, surgeons need to decide between accepting volume as an adequate measure of quality and developing other possibly more direct and reliable methods. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90024 USA. W Los Angeles Vet Adm, Dept Surg, Los Angeles, CA USA. W Los Angeles Vet Adm, Dept Gen Internal Med, Los Angeles, CA USA. RP Liu, JH (reprint author), 11301 W Olymp Blvd,648, Los Angeles, CA 90064 USA. NR 23 TC 7 Z9 7 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUL PY 2003 VL 113 IS 1 BP 96 EP 101 DI 10.1016/S0022-4804(03)00145-8 PG 6 WC Surgery SC Surgery GA 717GZ UT WOS:000185080300014 PM 12943816 ER PT J AU Maggard, MA O'Connell, JB Lane, KE Liu, JH Etzioni, DA Ko, CY AF Maggard, MA O'Connell, JB Lane, KE Liu, JH Etzioni, DA Ko, CY TI Do young breast cancer patients have worse outcomes? SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Association-for-Academic-Surgery CY NOV 07-09, 2002 CL BOSTON, MASSACHUSETTS SP Assoc Acad Surg DE breast cancer; young; survival; treatment; outcomes ID WOMEN; AGE; PROGNOSIS; CARCINOMA AB Introduction. Previous studies have suggested that young breast cancer patients have poorer survival as compared with their older counterparts. Most of this research reflects single institution experiences that may not be representative of the population. This study was designed to determine whether young breast cancer patients have poorer survival as compared with an older cohort using a national population-based cancer registry and, more specifically, to determine whether differences in survival are caused by more advanced tumor stage, more aggressive disease, or patient-specific characteristics. Materials and methods. Using the Surveillance, Epidemiology, and End Results cancer database (19921998), data for all patients with a diagnosis of invasive breast cancer were extracted. Two age categories were analyzed: young group (less than or equal to35 years old, n = 4,616) and older group (50-55 years old, n = 20,319). Patient demographics, 5-year survival rates, tumor characteristics (stage, grade, and receptor status), surgical treatment, and use of radiation were compared between the groups. Results. Overall, young patients had worse 5-year survival when compared with the older group (74.3% VS. 85.1%). Stage for stage, the young patients also had poorer survival (except for stage IV). They present with more advanced stage disease and have more aggressive tumor characteristics, that is, higher grade tumors and more estrogen- and progesterone receptor-negative tumors. Even after controlling for patient characteristics, tumor factors, and receipt of treatment, a multivariate regression showed that young age was an independent risk factor for death (HR = 1.095). Conclusions. Young breast cancer patients have poorer outcomes, which are in part attributed to later stage disease, more aggressive tumors, and less favorable receptor status. There still appears to be other important factors, not included in our study, that are contributing to the worse outcomes for these young patients, such as socioeconomic status. Physicians need to have heightened awareness when evaluating this population, and increasingly efficacious adjuvant therapies need to be developed. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Robert Wood Johnson VA Clin Scholars Program, Los Angeles, CA 90095 USA. Univ Calif San Francisco, Sch Med, Dept Surg, San Francisco, CA 94143 USA. W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA 90073 USA. RP Maggard, MA (reprint author), Univ Calif Los Angeles, Sch Med, Dept Surg, 10833 Conte Ave,CHS,Room 72-215, Los Angeles, CA 90095 USA. NR 10 TC 79 Z9 87 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUL PY 2003 VL 113 IS 1 BP 109 EP 113 DI 10.1016/S0022-4804(03)00179-3 PG 5 WC Surgery SC Surgery GA 717GZ UT WOS:000185080300016 PM 12943818 ER PT J AU Shera, CA AF Shera, CA TI Mammalian spontaneous otoacoustic emissions are amplitude-stabilized cochlear standing waves SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Review ID MIDDLE-EAR TRANSMISSION; OTO-ACOUSTIC EMISSIONS; HAIR-CELLS; DISTORTION-PRODUCT; RELAXATION DYNAMICS; EXTERNAL TONES; FINE-STRUCTURE; ACTIVE PROCESS; MECHANICAL STIMULATION; ENERGY REFLECTANCE AB Mammalian spontaneous otoacoustic emissions (SOAEs) have been suggested to arise by three different mechanisms. The local-oscillator model, dating back to the work of Thomas Gold, supposes that SOAEs arise through the local, autonomous oscillation of some cellular constituent of the organ of Corti (e.g., the "active process" underlying the cochlear amplifier). Two other models, by contrast, both suppose that SOAEs are a global collective phenomenon-cochlear standing waves created by multiple internal reflection-but differ on the nature of the proposed power source: Whereas the "passive" standing-wave model supposes that SOAEs are biological noise, passively amplified by cochlear standing-wave resonances acting as narrow-band nonlinear filters, the "active" standing-wave model supposes that standing-wave amplitudes are actively maintained by coherent wave amplification within the cochlea. Quantitative tests of key predictions that distinguish the local-oscillator and global standing-wave models are presented and shown to support the global standing-wave model. In addition to predicting the existence of multiple emissions with a characteristic minimum frequency spacing, the global standing-wave model accurately predicts the mean value of this spacing, its standard deviation, and its power-law dependence on SOAE frequency. Furthermore, the global standing-wave model accounts for the magnitude, sign, and frequency dependence of changes in SOAE frequency that result from modulations in middle-ear stiffness. Although some of these SOAE characteristics may be replicable through artful ad hoc adjustment of local-oscillator models, they all arise quite naturally in the standing-wave framework. Finally, the statistics of SOAE time waveforms demonstrate that SOAEs are coherent, amplitude-stabilized signals, as predicted by the active standing-wave model. Taken together, the results imply that SOAEs are amplitude-stabilized standing waves produced by the cochlea acting as a biological, hydromechanical analog of a laser oscillator. Contrary to recent claims, spontaneous emission of sound from the ear does not require the autonomous mechanical oscillation of its cellular constituents. (C) 2003 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Shera, CA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC003687, R01 DC03687] NR 114 TC 107 Z9 116 U1 2 U2 9 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2003 VL 114 IS 1 BP 244 EP 262 DI 10.1121/1.1575750 PG 19 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 699ZF UT WOS:000184087100026 PM 12880039 ER PT J AU Solomon, DH Wenger, NS Saliba, D Young, RT Adelman, AM Besdine, RK Blazer, DG Cassell, CK Cummings, JL Katz, PR Kitzman, DW Lavizzo-Mourey, RJ Mondoux, LC Popovich, R Pories, WJ Wenger, N AF Solomon, DH Wenger, NS Saliba, D Young, RT Adelman, AM Besdine, RK Blazer, DG Cassell, CK Cummings, JL Katz, PR Kitzman, DW Lavizzo-Mourey, RJ Mondoux, LC Popovich, R Pories, WJ Wenger, N CA Clinical Comm TI Appropriateness of quality indicators for older patients with advanced dementia and poor prognosis SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE quality of care; vulnerable elders; geriatric syndromes ID END-STAGE DEMENTIA; VULNERABLE ELDERS; ASSESSING CARE; OF-LIFE; PROJECT; DISEASE AB OBJECTIVES: To evaluate the applicability of process-of-care quality indicators (QIs) to vulnerable elders and to measure the effect of excluding indicators based on patients' preferences and for advanced dementia and poor prognosis. DESIGN: The Assessing Care of Vulnerable Elders (ACOVE) project employed 203 QIs for care of 22 conditions (including six geriatric syndromes and 11 age-associated diseases) for community-based persons aged 65 and older at increased risk of functional decline or death. Relevant QIs were excluded for persons deciding against hospitalization or surgery. A 12-member clinical committee (CC) of geriatric experts rated whether each QI should be applied in scoring quality of care for persons with advanced dementia (AdvDem) or poor prognosis (PoorProg). Using content analysis, CC ratings were formulated into a model of QI exclusion. Quality scores with and without excluded QIs were compared. SETTING: Enrollees in two senior managed care plans, one in the northeast United States and the other in the southwest. PARTICIPANTS: CC members evaluated applicability of QIs. QIs were applied to 372 vulnerable elders in two senior managed care plans. MEASUREMENTS: Frequency and type of QIs excluded and the effect of excluding QIs on quality of care scores. RESULTS: Of the 203 QIs, a patient's preference against hospiitalization or surgery excluded 10 and eight QIs, respectively. The CC voted to exclude 81.5 QIs (40%) for patients with AdvDem and 70 QIs (34%) for patients with PoorProg. Content analysis of the CC votes revealed that QIs aimed at care coordination, safety or prevention of decline, or short-term clinical improvement or prevention with nonburdensome interventions were usually voted for inclusion (90% and 98% included for AdvDem and PoorProg, respectively), but QIs directed at long-term benefit or requiring interventions of moderate to heavy burden were usually excluded (16% and 19% included, respectively). About half of QIs aimed at age-associated diseases were voted for exclusion, whereas fewer than one-quarter of QIs for geriatric syndromes were excluded. Thirty-nine patients (10%) in our field trial held preferences or had clinical conditions that would have excluded 68 QIs. This accounted for 5% of all QIs triggered by these 39 patients and 0.6% of QIs overall. The quality score without exclusion was 0.57 and with exclusion was 0.58 (P = .89). CONCLUSION: Caution is required in applying QIs to vulnerable elders. QIs for geriatric syndromes are more likely to be applicable to these individuals than are QIs for age-associated diseases. The objectives of care, intervention burdens, and interval before anticipated benefit affect QI applicability. At least for patients with AdvDem and PoorProg, identification of applicable or inapplicable QIs is feasible. In a community-based sample of vulnerable elders, few QIs are excluded. C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90049 USA. RAND Corp, Santa Monica, CA USA. Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. Penn State Univ, University Pk, PA 16802 USA. Brown Univ, Providence, RI 02912 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Oregon, Hlth Sci Ctr, Eugene, OR 97403 USA. Univ Rochester, Sch Med & Dent, Rochester, NY USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Soc Social Work Leadership Hlth Care, Philadelphia, PA USA. E Carolina Univ, Sch Med, Greenville, NC USA. Emory Univ, Atlanta, GA 30322 USA. Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. RP Solomon, DH (reprint author), Univ Calif Los Angeles, Sch Med, 2103 Ridge Dr, Los Angeles, CA 90049 USA. NR 18 TC 24 Z9 24 U1 2 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 2003 VL 51 IS 7 BP 902 EP 907 DI 10.1046/j.1365-2389.2003.513331.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 701TQ UT WOS:000184185400001 PM 12834508 ER PT J AU Cydulka, RK Rowe, BH Clark, S Emerman, CL Camargo, CA AF Cydulka, RK Rowe, BH Clark, S Emerman, CL Camargo, CA CA MARC Investigators TI Emergency department management of acute exacerbations of chronic obstructive pulmonary disease in the elderly: The Multicenter Airway Research Collaboration SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE elderly; obstructive airway disease; COPD; emergency department ID CLINICAL-PRACTICE GUIDELINES; INHALED CORTICOSTEROIDS; ASTHMA MANAGEMENT; UNITED-STATES; HEALTH-CARE; COPD; IMPLEMENTATION; EXPERIENCE; COMMUNITY; SYMPTOMS AB OBJECTIVES: To determine adherence of emergency department (ED) management of acute exacerbation of chronic obstructive pulmonary disease (COPD) to current treatment guidelines. DESIGN: A prospective cohort study, as part of the Multicenter Airway Research Collaboration. SETTING: The study was performed at 29 EDs in 15 U.S. states and three Canadian provinces. PARTICIPANTS: ED patients, aged 55 and older, who presented with COPD exacerbation and underwent a structured interview in the ED and another by telephone 2 weeks later. MEASUREMENTS: Adherence of ED management of COPD exacerbation to that recommended in current treatment guidelines. RESULTS: The cohort consisted of 397 subjects, of whom 224 (56%) reported only COPD and 173 (44%) reported asthma and COPD. The average age was 70. Most (80%) patients had used rescue medications in the 6 hours before seeking emergency care. Only 31% were evaluated using spirometry and 48% using arterial blood gas measurement. ED treatment included inhaled short-acting beta-agonists for 91% of patients, inhaled anticholinergics for 77%, methylxanthines for 0.3%, systemic corticosteroids for 62%, and antibiotics for 28%. More than half the patients required hospitalization. At 2-week follow-up, 43% of patients reported a relapse event or ongoing exacerbation. Overall, adherence to national and international guidelines was low. CONCLUSION: Important differences exist between guideline recommendations and actual ED management of COPD exacerbations in older adults. Outcomes after ED treatment are poor and may be related to these shortcomings in quality of care. Better adherence to guideline recommendations when caring for elderly patients with COPD exacerbations may lead to improved clinical outcomes and better resource usage. C1 Case Western Reserve Univ, Metrohlth Med Ctr, Dept Emergency Med, Cleveland, OH 44109 USA. Univ Alberta, Div Emergency Med, Edmonton, AB, Canada. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. RP Cydulka, RK (reprint author), Case Western Reserve Univ, Metrohlth Med Ctr, Dept Emergency Med, 2500 Metrohlth Dr,Room S1-203, Cleveland, OH 44109 USA. FU NHLBI NIH HHS [HL63253, HL-63841] NR 45 TC 42 Z9 43 U1 0 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 JUL PY 2003 VL 51 IS 7 BP 908 EP 916 DI 10.1046/j.1365-2389.2003.51302.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 701TQ UT WOS:000184185400002 PM 12834509 ER PT J AU Foody, JM Wang, Y Kiefe, CI Ellerbeck, EF Gold, J Radford, MJ Krumholz, HM AF Foody, JM Wang, Y Kiefe, CI Ellerbeck, EF Gold, J Radford, MJ Krumholz, HM TI Long-term prognostic importance of total cholesterol in elderly survivors of an acute myocardial infarction: The Cooperative Cardiovascular pilot Project SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cholesterol; acute myocardial infarction; elderly; prognosis ID CORONARY-HEART-DISEASE; HIGH BLOOD CHOLESTEROL; ADULT TREATMENT PANEL; ALL-CAUSE MORTALITY; SERUM-CHOLESTEROL; OLDER-ADULTS; RISK-FACTORS; HEALTH; PROGRAM; PEOPLE AB OBJECTIVES: To determine the long-term prognostic importance of in-hospital total serum cholesterol in elderly survivors of acute myocardial infarction (AMI). DESIGN: Retrospective medical record review. SETTING: Acute care, nongovernmental hospitals in Alabama, Connecticut, Iowa, and Wisconsin. PARTICIPANTS: Four thousand nine hundred twenty-three Medicare beneficiaries from four states aged 65 and older discharged alive with a principal diagnosis of AMI between June 1, 1992, and February 28, 1993, who had a measurement of total serum cholesterol during hospitalization. MEASUREMENTS: Primary endpoint of all-cause mortality within 6 years of discharge. RESULTS: Of the 7,166 hospitalizations meeting study inclusion criteria, 4,923 (68.7%) had total cholesterol assessed, and 22% had a cholesterol level of 240 mg/dL or greater. Of AMI hospitalization survivors with cholesterol of 240 md/dL or greater, 17.2% died within 1 year and 47.9% died within 6 years, compared with 17.4% (P = .73) and 48.7% (P = .98) of those with a cholesterol level less than 240 mg/dL. The adjusted hazard ratio for elevated total serum cholesterol measured during hospitalization for all-cause mortality in the 6 years after discharge was 0.97 (95% confidence interval (CI) = 0.87-1.09). The unadjusted 1- and 6-year mortality rates for those with total cholesterol less than 160 mg/dL were 22.2% and 55.5%, respectively, not significantly different from mortality for patients with cholesterol of 460 mg/dL or greater, even after adjustment. CONCLUSION: Among elderly survivors of AMI, elevated total serum cholesterol measured postinfarction is not associated with an increased risk of all-cause mortality in the 6 years after discharge. Furthermore, this study found no evidence of an increased risk of all-cause mortality in patients with low total cholesterol. Further studies are needed to determine the relationship of postinfarction lipid subfractions and mortality in older patients with coronary artery disease (CAD). C1 Yale Univ, Sch Med, Dept Med, Sect Cardiovasc Med, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Sect Chron Dis Epidemiol, New Haven, CT 06520 USA. Qualidigm, Middletown, CT USA. Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. Univ Alabama, Ctr Outcome & Effectivness Res & Educ, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Kansas, Sch Med, Dept Prevent Med, Kansas City, KS USA. Metastar, Madison, WI USA. RP Krumholz, HM (reprint author), Yale Univ, Sch Med, Dept Med, Sect Cardiovasc Med, 333 Cedar St,Pob 208025, New Haven, CT 06520 USA. RI Ellerbeck, Edward/I-8438-2014 OI Ellerbeck, Edward/0000-0002-7774-2729 NR 31 TC 14 Z9 14 U1 2 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 2003 VL 51 IS 7 BP 930 EP 936 DI 10.1046/j.1365-2389.2003.51305.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 701TQ UT WOS:000184185400005 PM 12834512 ER PT J AU Holtzer, R Tang, MX Devanand, DP Albert, SM Wegesin, DJ Marder, K Bell, K Albert, M Brandt, J Stern, Y AF Holtzer, R Tang, MX Devanand, DP Albert, SM Wegesin, DJ Marder, K Bell, K Albert, M Brandt, J Stern, Y TI Psychopathological features in Alzheimer's disease: Course and relationship with cognitive status SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE psychopathological features; cognition; Alzheimer's disease ID PSYCHIATRIC-SYMPTOMS; AGGRESSIVE-BEHAVIOR; PSYCHOLOGICAL SYMPTOMS; PHYSICAL AGGRESSION; DOUBLE-BLIND; DEMENTIA; DELUSIONS; PREDICTORS; PSYCHOSIS; DECLINE AB OBJECTIVES: To examine the course, clinical correlates, and relationship between cognitive status and psychopathological features in patients with probable Alzheimer's disease (AD) followed over a 5-year period. DESIGN: Cohort study with follow-up of 5 years. SETTING: Patients were recruited at three sites: 91 patients at Columbia Medical Center, 84 at Johns Hopkins School of Medicine, and 61 at Massachusetts General Hospital. PARTICIPANTS: Patients diagnosed with probable AD (n = 236) enrolled in a longitudinal study (Predictors study). MEASUREMENTS: Wandering/agitation, physical aggression, hallucinations, and delusions were evaluated at 6-month intervals using the Columbia Scale for Psychopathology in Alzheimer's Disease. Descriptive analyses were used to provide estimates of prevalence and course of psychopathological features. General estimating equations determined the odds of having any of the four psychopathological behaviors as a function of cognitive status. Markov analyses provided 6-month transition probabilities for psychopathological behaviors given patients' cognitive status and the presence or absence of such behaviors in the previous evaluation. RESULTS: For wandering/agitation, prevalence (39-57%) and persistence increased as a function of time and decrement in cognitive status. Physical aggression was less prevalent (6-22%) and increased as a function of cognitive decline but tended to persist only in the more severely impaired patients. Delusions (34-49%) reached a peak at the second year and then declined. The odds of delusions were maximal with intermediate decline but remained persistent regardless of cognitive status. Hallucinations, despite some fluctuations, were relatively stable during the follow-up period (8-17%) and moderately persistent. CONCLUSION: Psychopathological features, particularly wandering/agitation and delusions, in AD were common throughout the disease course. The natural history and persistence of the four psychopathological features varied. These findings provide important information to clinicians and caregivers regarding the course, predictability, and possible treatment of psychopathological behaviors in patients with probable AD. C1 Columbia Univ, Gertrude H Sergievsky Ctr, Coll Phys & Surg, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Harvard Univ, Massachusetts Gen Hosp, Med Ctr, Dept Psychiat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Med Ctr, Dept Neurol, Boston, MA USA. Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. RP Stern, Y (reprint author), Columbia Univ, Gertrude H Sergievsky Ctr, Coll Phys & Surg, 19th Floor,630 W 168th St,P&S Box 16, New York, NY 10032 USA. OI Brandt, Jason/0000-0001-7381-6244; Albert, Steven/0000-0001-6786-9956 FU NCRR NIH HHS [RR00645]; NIA NIH HHS [AG07370]; NIMH NIH HHS [MH55735] NR 53 TC 64 Z9 64 U1 1 U2 7 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 JUL PY 2003 VL 51 IS 7 BP 953 EP 960 DI 10.1046/j.1365-2389.2003.51308.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 701TQ UT WOS:000184185400008 PM 12834515 ER PT J AU Reuben, DB Shekelle, PG Wenger, NS AF Reuben, DB Shekelle, PG Wenger, NS TI Quality of care for older persons at the dawn of the third millennium SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE quality of care; quality improvement; elderly; healthcare delivery ID CLINICAL-PRACTICE GUIDELINES; RANDOMIZED CONTROLLED TRIAL; VULNERABLE ELDERS; MEDICARE BENEFICIARIES; HEART-FAILURE; INTERVENTION; MANAGEMENT; COMMUNITY; PROJECT; PEOPLE AB During the past quarter century, researchers, providers, insurers, and governmental agencies have devoted considerable effort to improving and standardizing the quality of health care provided to older persons. Because older persons differ from younger persons as a result of their life expectancy, disease prevalence and comorbidity, social resources, goals of treatment, and preferences for care, defining and measuring quality of care has been more difficult for this age group. Nevertheless, several decades of research have led to reliable, although imperfect, methods of measuring quality, including those for geriatric conditions. Using these measurement approaches, a variety of studies using different patient populations and sampling strategies have consistently identified deficiencies in quality of care provided to older persons. Moreover, efforts to improve quality of care for older persons have been difficult to design, implement, and sustain. Some have been successful, including having effects on outcome measures, but have not made the transition from research to clinical settings. Others have used quality improvement methods to improve the care of diseases (e.g., diabetes mellitus, congestive heart failure) that commonly affect older persons. However, the lack of alignment of incentives between providers and insurers for most older persons is a major barrier to this approach. In addition, there is no concerted effort among providers, regulatory agencies, and insurers to move the quality-of-care agenda for most Medicare recipients. Despite substantial progress in defining and measuring high-quality care for older persons, the goal of ensuring that older persons receiving such care remains a distant hope. C1 Univ Calif Los Angeles, Multicampus Program Geriatr Med & Gerontol, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Div Gen Internal Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RAND Hlth, Santa Monica, CA USA. RP Reuben, DB (reprint author), Univ Calif Los Angeles, Multicampus Program Geriatr Med & Gerontol, David Geffen Sch Med, 10945 Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. NR 38 TC 22 Z9 22 U1 5 U2 6 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 JUL PY 2003 VL 51 IS 7 SU S BP S346 EP S350 DI 10.1046/j.1365-2389.2003.51346.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 694DR UT WOS:000183759000010 PM 12823666 ER PT J AU Payne, TH Hoey, PJ Nichol, P Lovis, C AF Payne, TH Hoey, PJ Nichol, P Lovis, C TI Preparation and use of preconstructed orders, order sets, and order menus in a computerized provider order entry system SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID USAGE AB Objective: To describe the configuration and use of the computerized provider order entry (CPOE) system used for inpatient and outpatient care at the authors' facility. Design: Description of order configuration entities, use patterns, and configuration changes in a production CPOE system. Measurements: The authors extracted and analyzed the content of order configuration entities (order dialogs, preconfigured [quick] orders, order sets, and order menus) and determined the number of orders entered in their production order entry system over the previous three years. The authors measured use of these order configuration entities over a six-month period. They repeated the extract two years later to measure changes in these entities. Results: CPOE system configuration, conducted before and after first production use, consisted of preparing 667 order dialogs, 5,982 preconfigured (quick) orders, and 513 order sets organized in 703 order menus for particular contexts, such as admission for a particular diagnosis. Fifty percent of the order dialogs, 57% of the quick orders, and 13% of the order sets were used within a six-month period. Over the subsequent two years, the volume of order configuration entities increased by 26%. Conclusions: These order configuration steps were time-consuming, but the authors believe they were important to increase the ordering speed and acceptability of the order entry software. Lessons learned in the process of configuring the CPOE ordering system are given. Better understanding of ordering patterns may make order configuration more efficient because many of the order configuration entities that were created were not used by clinicians. C1 Univ Washington, Acad Med Ctr Informat Syst, Seattle, WA 98115 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Hosp Geneva, Geneva, Switzerland. RP Payne, TH (reprint author), Univ Washington, Acad Med Ctr Informat Syst, 9725 3rd Ave NE,Room 400,Box 359104, Seattle, WA 98115 USA. EM tpayne@u.washington.edu RI Lovis, Christian/D-2634-2012 OI Lovis, Christian/0000-0002-2681-8076 NR 21 TC 42 Z9 42 U1 1 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 2003 VL 10 IS 4 BP 322 EP 329 DI 10.1197/jamia.M1090 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 702UC UT WOS:000184241800005 PM 12668686 ER PT J AU Belkin, GS AF Belkin, GS TI Brain death and the historical understanding of bioethics SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES LA English DT Article; Proceedings Paper CT Meeting of the International-Society-for-the-History-of-Neuroscience CY JUN 13, 2000 CL PROVIDENCE, RHODE ISLAND SP International Soc History Neurosci DE brain death; bioethics; brain history; history of bioethics ID ELECTROENCEPHALOGRAPHIC CHANGES; UNCONSCIOUS PATIENT; ETHICS; LEGAL; HEART; COMA; LAW; EEG AB In a 1968 Report, the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death promulgated influential criteria for the idea and practice known as "brain death Before and since the Committee met, brain death has been a focal point of visions and nightmares of medical progress, purpose, and moral authority. Critics of the Committee felt it was deaf to apparently central moral considerations and focused on the self-serving purpose of expanding transplantation. Historical characterizations of the uses and meanings of brain death and the work of the Committee have tended to echo these themes, which means also generally repeating a widely held bioethical self-understanding of how the field appeared-that is, as a necessary antidote of moral expertise. This paper looks at the Committee and finds that historical depictions of it have been skewed by such a bioethical agenda. Entertaining different possibilities as to the motives and historical circumstances behind the Report it famously produced may point to not only different histories of the Committee, but also different perspectives on the historical legacy and role of bioethics as a discourse for addressing anxieties about medicine. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Belkin, GS (reprint author), Erich Lindemann Mental Hlth Ctr, 25 Staniford St, Boston, MA 02114 USA. NR 101 TC 22 Z9 24 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-5045 J9 J HIST MED ALL SCI JI J. Hist. Med. Allied Sci. PD JUL PY 2003 VL 58 IS 3 BP 325 EP 361 DI 10.1093/jhmas/jrg003 PG 37 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 704VW UT WOS:000184362300003 PM 12938717 ER PT J AU Mehta, A McLoud, TC AF Mehta, A McLoud, TC TI Voice recognition SO JOURNAL OF THORACIC IMAGING LA English DT Article; Proceedings Paper CT Symposium on Digital Chest Radiography CY MAY, 2002 CL LEUVEN, BELGIUM DE voice recognition (VR); speech recognition; radiology information system (RIS) AB Voice recognition represents one of the new technologies that are changing the practice of radiology. Thirty percent of radiology practices are either currently or plan to have voice recognition (VR) systems. VR software encompasses 4 core processes: spoken recognition of human speech, synthesis of human readable characters into speech, speaker identification and verification, and comprehension. Many software packages are available offering VR. All these packages should contain an interface with the radiology information system. The benefits include decreased turnaround time and cost savings. Its advantages include the transfer of secretarial duties to the radiologist with a result in decreased productivity. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP McLoud, TC (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. NR 5 TC 14 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD JUL PY 2003 VL 18 IS 3 BP 178 EP 182 DI 10.1097/00005382-200307000-00007 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 703RN UT WOS:000184294900008 PM 12867815 ER PT J AU Bauer, KA AF Bauer, KA TI Management of thrombophilia SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article; Proceedings Paper CT 19th Congress of the International-Society-of-Thrombosis-and-Haemostasis CY JUL 12-18, 2003 CL BIRMINGHAM, ENGLAND SP Int Soc thrombosis & Haemostasis DE anticoagulation; factor V Leiden; pregnancy; thrombophilia; venous thromboembolism; warfarin ID FACTOR-V-LEIDEN; RECURRENT VENOUS THROMBOEMBOLISM; ACTIVATED PROTEIN-C; ORAL ANTICOAGULANT-THERAPY; INHERITED ANTITHROMBIN DEFICIENCY; DEEP-VEIN THROMBOSIS; BLEEDING COMPLICATIONS; DECISION-ANALYSIS; PROTHROMBIN GENE; FIRST EPISODE AB It is now possible to identify acquired and hereditary risk factors in a substantial percentage of patients presenting with a venous thrombotic event. Discovery of the factor V Leiden and prothrombin G20210A mutations has greatly increased the percentage of patients in whom venous thrombosis can be attributed to hereditary thrombophilia. There is, however. considerable uncertainty as to how this information should be used in patient management. Although prolonged anticoagulation at an international normalized ratio of 2-3 is highly effective in preventing thrombotic recurrences, this benefit is partially offset by major bleeding which occurs at an average rate of 2%-3% per year. A decision as to the overall benefit of extended anticoaaulation in the individual patient requires assessment of the risk of recurrence in the absence of treatment vs. the bleeding risk associated with prolonged anticoagulation. Low-intensity warfarin therapy or novel anticoagulants such as oral direct thrombin inhibitors may prove effective strategies for preventing recurrent venous thromboembolism in patients with thrombophilia. C1 VA Boston Healthcare Syst, West Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 USA. RP Bauer, KA (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. NR 57 TC 29 Z9 32 U1 0 U2 0 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2003 VL 1 IS 7 BP 1429 EP 1434 DI 10.1046/j.1538-7836.2003.00274.x PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 701MG UT WOS:000184170900013 PM 12871277 ER PT J AU Xiong, JP Stehle, T Goodman, SL Arnaout, MA AF Xiong, JP Stehle, T Goodman, SL Arnaout, MA TI Integrins, cations and ligands: making the connection SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article; Proceedings Paper CT 19th Congress of the International-Society-of-Thrombosis-and-Haemostasis CY JUL 12-18, 2003 CL BIRMINGHAM, ENGLAND SP Int Soc thrombosis & Haemostasis DE activation; cell adhesion; integrins; therapeutics ID CALCIUM-BINDING DOMAINS; INSIDE-OUT ACTIVATION; METAL-ION BINDING; GLY-ASP-BINDING; CD11B A-DOMAIN; I-DOMAIN; CRYSTAL-STRUCTURE; CELL-ADHESION; DIVALENT-CATION; CONFORMATIONAL-CHANGES AB Integrins are cell adhesion receptors that couple extracellular divalent cation-dependent recognition events with intracellular mechanical and biochemical responses and vice versa, thus affecting every function of nucleated cells. The structural basis of this bidirectional signaling and its dependency on cations has been the focus of intensive study over the past three decades. Significant progress made recently in elucidating the three-dimensional structure of the extracellular and cytoplasmic segments of integrins is giving valuable new insights into the tertiary and quaternary changes that underlie activation, ligand recognition and signaling by these receptors. C1 Massachusetts Gen Hosp, Struct Biol Program, Leukocyte Biol & Inflammat Program, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Merck KGaA, Dept Oncol Res, Darmstadt, Germany. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Struct Biol Program, Leukocyte Biol & Inflammat Program, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. NR 90 TC 47 Z9 50 U1 0 U2 3 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2003 VL 1 IS 7 BP 1642 EP 1654 DI 10.1046/j.1538-7836.2003.00277.x PG 13 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 701MG UT WOS:000184170900037 PM 12871301 ER PT J AU Townsend, TC Saloner, D Pan, XM Rapp, JH AF Townsend, TC Saloner, D Pan, XM Rapp, JH TI Contrast material-enhanced MRA overestimates severity of carotid stenosis, compared with 3D time-of-flight MRA SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the Western-Vascular-Society CY SEP 22-25, 2002 CL NEWPORT BEACH, CALIFORNIA SP Western Vasc Soc ID MAGNETIC-RESONANCE ANGIOGRAPHY; BASIC PRINCIPLES; ARTERY STENOSIS; ULTRASONOGRAPHY; BIFURCATION; ULTRASOUND AB Objective: Non-contrast-enhanced magnetic resonance angiography (MRA) carotid imaging with the time-of-flight (TOF) technique compares favorably with angiography, ultrasound, and excised plaques. However, gadolinium, contrast-enhanced MRA (CE-MRA) has almost universally replaced TOF-MRA, because it reduces imaging time (25 seconds vs 10 minutes) and improves signal-to-noise ratio. In our practice we found alarming discrepancies between CE-MRA and TOF-MRA, which was the impetus for this study. Study design: To compare the two techniques, we measured stenosis, demonstrated on three-dimensional images obtained at TOF and CE-MRA, in 107 carotid arteries in 58 male patients. The measurements were made on a Cemax workstation equipped with enlargement and measurement tools. Measurements to 0.1 mm were made at 90 degrees to the flow channel at the area of maximal stenosis and distal to the bulb where the borders of the internal carotid artery lumen were judged to be parallel (North American Symptomatic Carotid Endarterectomy Trial criteria). Experiments with carotid phantoms were done to test the comtribution of imaging software to image quality. Results: Twelve arteries were occluded. In the remaining 95 arteries, compared with TOF-MRA, CE-MRA demonstrated a greater degree of stenosis in 42 arteries, a lesser degree of stenosis in 14 arteries, and similar (+/-5%) stenosis in 39 arteries (P = .02, chi(2) analysis). The largest discrepancies were arteries with 0% to 70% stenosis. In those arteries in which CE-MRA identified a greater degree of stenosis than shown with TOF-MRA, mean increase was 21% for 0% to 29% stenosis, 36% for 30% to 49% stenosis, and 38% for of 50% to 69% stenosis. The carotid phantom experiments showed that the imaging parameters of CE-MRA, particularly the plane on which frequency encoding gradients were applied, reduced signal acquisition at the area of stenosis. Conclusions. Collectively these data demonstrate that CE-MRA parameters must be retooled if the method is to be considered reliable for determination of severity of carotid artery stenosis. CE-MRA is an excellent screening technique, but only TOF-MRA should be used to determine degree of carotid artery stenosis. C1 San Francisco VA Med Ctr, Vasc Serv, San Francisco, CA USA. San Francisco VA Med Ctr, Serv Radiol, San Francisco, CA USA. RP Rapp, JH (reprint author), San Francisco DVA Med Ctr, Surg Serv 112G, 4150 Clement St, San Francisco, CA 94121 USA. NR 11 TC 24 Z9 24 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 JUL PY 2003 VL 38 IS 1 BP 36 EP 40 DI 10.1016/S0741-5214(03)00332-X PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 698EZ UT WOS:000183985900006 PM 12844086 ER PT J AU Song, EW Lee, SK Dykxhoorn, DM Novina, C Zhang, D Crawford, K Cerny, J Sharp, PA Lieberman, J Manjunath, N Shankar, P AF Song, EW Lee, SK Dykxhoorn, DM Novina, C Zhang, D Crawford, K Cerny, J Sharp, PA Lieberman, J Manjunath, N Shankar, P TI Sustained small interfering RNA-mediated human immunodeficiency virus type 1 inhibition in primary macrophages SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 INFECTION; GENE-EXPRESSION; HUMAN-CELLS; REPLICATION; DELIVERY; MICE; PATHOGENESIS; SUPPRESSION; THERAPY; SIRNAS AB Small interfering RNAs (siRNAs) can induce potent gene silencing by degradation of cognate mRNA. However, in dividing cells, the silencing lasts only 3 to 7 days, presumably because of siRNA dilution with cell division. Here, we investigated if sustained siRNA-mediated silencing of human immunodeficiency virus type 1 (HIV-1) is possible in terminally differentiated macrophages, which constitute an important reservoir of HIV in vivo. CCR5, the major HIV-1 coreceptor in macrophages, and the viral structural gene for p24 were targeted either singly or in combination. When transfected 2 days prior to infection, both CCR5 and p24 siRNAs effectively reduced HIV-1 infection for the entire 15-day period of observation, and combined targeting of both genes abolished infection. To investigate whether exogenously introduced siRNA is maintained stably in macrophages, we tested the kinetics of siRNA-mediated viral inhibition by initiating infections at various times (2 to 15 days) after transfection with CCR5 and p24 siRNAs. HIV suppression mediated by viral p24 siRNA progressively decreased and was lost by day 7 posttransfection. In contrast, viral inhibition by cellular CCR5 knockdown was sustained even when transfection preceded infection by 15 days, suggesting that the continued presence of target RNA may be needed for persistence of siRNA. The longer sustenance of CCR5 relative to p24 siRNA in uninfected macrophages was also confirmed by detection of internalized siRNA by modified Northern blot analysis. We also tested the potential of p24 siRNA to stably silence HIV in the setting of an established infection where the viral target gene is actively transcribed. Under these circumstances, long-term suppression of HIV replication could be achieved with p24 siRNA. Thus, siRNAs can induce potent and long-lasting HIV inhibition in nondividing cells such as macrophages. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. RP Shankar, P (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Cerny, Jan/C-1887-2012; Lieberman, Judy/A-2717-2015; Dykxhoorn, Derek/D-1357-2015 FU NIAID NIH HHS [AI42519, AI45306, AI46566, AI49792, F32 AI010523, F32-AI10523, R01 AI042519, R01 AI046566, R21 AI046566]; NIGMS NIH HHS [R37 GM034277, R37-GM34277]; PHS HHS [P01-42063] NR 36 TC 180 Z9 197 U1 0 U2 8 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 JUL PY 2003 VL 77 IS 13 BP 7174 EP 7181 DI 10.1128/JVI.77.13.7174-7181.2003 PG 8 WC Virology SC Virology GA 691GX UT WOS:000183598600003 PM 12805416 ER PT J AU Altfeld, M Addo, MM Shankarappa, R Lee, PK Allen, TM Yu, XG Rathod, A Harlow, J O'Sullivan, K Johnston, MN Goulder, PJR Mullins, JI Rosenberg, ES Brander, C Korber, B Walker, BD AF Altfeld, M Addo, MM Shankarappa, R Lee, PK Allen, TM Yu, XG Rathod, A Harlow, J O'Sullivan, K Johnston, MN Goulder, PJR Mullins, JI Rosenberg, ES Brander, C Korber, B Walker, BD TI Enhanced detection of human immunodeficiency virus type 1-specific T-cell responses to highly variable regions by using peptides based on autologous virus sequences SO JOURNAL OF VIROLOGY LA English DT Article ID LYMPHOCYTE RESPONSES; IMMUNE-RESPONSES; HIV-1 INFECTION; VIRAL LOAD; SUBTYPE-C; CTL EPITOPE; AIDS; ESCAPE; VIREMIA; PROGRESSION AB The antigenic diversity of human immunodeficiency virus type 1 (HIV-1) represents a significant challenge for vaccine design as well as the comprehensive assessment of HIV-1-specific immune responses in infected persons. In this study we assessed the impact of antigen variability on the characterization of HIV-1-specific T-cell responses by using an HIV-1 database to determine the sequence variability at each position in all expressed HIV-1 proteins and a comprehensive data set of CD8 T-cell responses to a reference strain of HIV-1 in infected persons. Gamma interferon Elispot analysis of HIV-1 clade B-specific T-cell responses to 504 overlapping peptides spanning the entire expressed HIV-1 genome derived from 57 infected subjects demonstrated that the average amino acid variability within a peptide (entropy) was inversely correlated to the measured frequency at which the peptide was recognized (P = 6 x 10(-7)). Subsequent studies in six persons to assess T-cell responses against p24 Gag, Tat, and Vpr peptides based on autologous virus sequences demonstrated that 29% (12 of 42) of targeted peptides were only detected with. peptides representing the autologous virus strain compared to the HIV-1 clade B consensus sequence. The use of autologous peptides also allowed the detection of significantly stronger HIV-1-specific T-cell responses in the more variable regulatory and accessory HIV-1 proteins Tat and Vpr (P = 0.007). Taken together, these data indicate that accurate assessment of T-cell responses directed against the more variable regulatory and accessory HIV-1 proteins requires reagents based on autologous virus sequences. They also demonstrate that CD8 T-cell responses to the variable HIV-1 proteins are more common than previously reported. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA USA. Allegheny Singer Res Inst, Ctr Genom Sci, Pittsburgh, PA 15212 USA. Nuffield Dept Med, Dept Paediat, Oxford, England. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. Los Alamos Natl Lab, Los Alamos, NM USA. RP Altfeld, M (reprint author), MGH E,CNY 5212,149 13th St, Charlestown, MA 02129 USA. RI Allen, Todd/F-5473-2011; OI Brander, Christian/0000-0002-0548-5778; Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [R01 AI44656, R01 AI030914, R01 AI040873, R01 AI044656, R01 AI050429, R01 AI30914, R01 AI40873, R01 AI50429, R37 AI128568, U01 AI041531, U01 AI41531, U01 AI41535] NR 51 TC 117 Z9 120 U1 1 U2 4 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 JUL PY 2003 VL 77 IS 13 BP 7330 EP 7340 DI 10.1128/JVI.77.13.7330-7340.2003 PG 11 WC Virology SC Virology GA 691GX UT WOS:000183598600018 PM 12805431 ER PT J AU Feeney, ME Roosevelt, KA Tang, Y Pfafferott, KJ McIntosh, K Burchett, SK Mao, C Walker, BD Goulder, PJR AF Feeney, ME Roosevelt, KA Tang, Y Pfafferott, KJ McIntosh, K Burchett, SK Mao, C Walker, BD Goulder, PJR TI Comprehensive screening reveals strong and broadly directed human immunodeficiency virus type 1-specific CD8 responses in perinatally infected children SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; CELLULAR IMMUNE-RESPONSES; HIV-1 INFECTION; VIRAL LOAD; HIV-1-INFECTED CHILDREN; ANTIRETROVIRAL THERAPY; HIGH-FREQUENCY; VIREMIA; CELLS; PLASMA AB Advances in antiviral therapy have dramatically shifted the demographics of pediatric human immunodeficiency virus type 1 (HIV-1) infection in the developed world, and a growing proportion of perinatally HIV-1-infected children are now entering their second or even third decade of life. Although cellular immune responses to HIV are known to be weak in early infancy, the magnitude, breadth, and specificity of responses later in childhood have not been characterized in detail. We performed a comprehensive characterization of HIV4-specific CD8 responses in 18 perinatally infected children (age range, 6 to 17 years), most of whom were on antiviral therapy, using both, previously defined HIV-1 epitopes and overlapping peptides spanning all HIV-1 proteins. Multispecific responses were detected in all subjects and accounted for a median of 0.25 to 0.3% of all peripheral blood mononuclear cells that was similar to the magnitude seen in HIV-infected adults. CD8 responses were broadly directed at an average of 11 epitopes (range, 2 to 27 epitopes) and targeted nearly all HIV-1 proteins, with the, highest proportion in Gag. Responses were readily detected even in those children with suppressed viremia on highly active antiretroviral therapy, although the breadth (P = 0.037) and the magnitude (P = 6.021) were significantly lower in these subjects. Each child recognized only a small minority of the HIV-1 optimal epitopes defined for his or her class I HLA alleles. Together, these data indicate that perinatally infected children who survive infancy mount a robust HIV-1-specific CD8 response that is much stronger than previously thought and is comparable in magnitude and breadth to that of adults. Moreover, this response has the-potential to be broadened to target more epitopes, making these children attractive candidates for immunotherapeutic interventions. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. John Radcliffe Hosp, Nuffield Dept Med, Oxford OX3 9DU, England. RP Goulder, PJR (reprint author), MGH E, 5th Fl,149 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [K30 HL004095, K30 HL04095]; NIAID NIH HHS [AI46995, R37 AI028568, AI52078, R01 AI046995, AI28568, K23 AI052078, R01 AI028568] NR 44 TC 31 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2003 VL 77 IS 13 BP 7492 EP 7501 DI 10.1128/JVI.77.13.7492-7501.2003 PG 10 WC Virology SC Virology GA 691GX UT WOS:000183598600036 PM 12805449 ER PT J AU Lee, BS Connole, M Tang, ZQ Harris, NL Jung, JU AF Lee, BS Connole, M Tang, ZQ Harris, NL Jung, JU TI Structural analysis of the Kaposi's sarcoma-associated herpesvirus K1 protein SO JOURNAL OF VIROLOGY LA English DT Article ID MULTICENTRIC CASTLEMANS-DISEASE; PRIMARY EFFUSION LYMPHOMA; SPINDLE CELLS; VIRAL INTERLEUKIN-6; SIGNAL-TRANSDUCTION; ENDOTHELIAL-CELLS; ACTIVATION MOTIF; GENE-EXPRESSION; DNA-SEQUENCES; HUMAN-HERPESVIRUS-8 AB The K1 protein of Kaposi's sarcoma-associated herpesvirus (KSHV) efficiently transduces extracellular signals to elicit cellular activation events through its cytoplasmic immunoreceptor tyrosine-based activation motif (ITAM). In addition, the extracellular domain of K1 demonstrates regional homology with the immunoglobulin (Ig) family and contains conserved regions (C1 and C2) and variable regions (V1 and V2). To generate mouse monoclonal antibodies directed against the KSHV K1 protein, BALB/c mice were primed and given boosters with K1 protein purified from mammalian cells. Twenty-eight hybridomas were tested for reactivity with K1 protein by enzyme-linked immunosorbent assay, immunofluorescence, flow cytometry, immunohistochemistry, and immunoblotting. Deletion mutants of the K1 extracellular domain were used to map the epitope of each antibody. All antibodies were directed to the Ig, C1, and C2 regions of K1. Furthermore, antibody recognition of a short sequence (amino acids 92 to 125) of the C2 region overlapping with the Ig region of K1 efficiently induced intracellular free calcium mobilization; antibody recognition of the other regions of K1 did not. The efficient signal transduction of K1 induced by antibody stimulation required both the ITAM sequence of the cytoplasmic domain and the normal structure of the extracellular domain. Finally, immunological assays showed that K1 was expressed during the early lytic cycle of viral replication in primary effusion lymphoma cells. K1 was readily detected in multicentric Castleman's disease tissues, whereas it was not detected in Kaposi's sarcoma lesions, suggesting that K1 is preferentially expressed in lymphoid cells. Thus, these results indicate that the conserved regions, particularly the Ig and C2 regions, of the K1 extracellular domain are exposed on the outer surface and play an important role in K1 structure and signal transduction, whereas the variable regions of K1 appear to be away from the surface. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Tumor Virol, Southborough, MA 01772 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Immunol, Southborough, MA 01772 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Jung, JU (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Tumor Virol, POB 9102,1 Pine Hill Dr, Southborough, MA 01772 USA. FU NCI NIH HHS [R01 CA091819, R01 CA082057, CA 82057, CA 91819]; NCRR NIH HHS [K26 RR000168, P51 RR000168, RR 00168] NR 47 TC 32 Z9 36 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2003 VL 77 IS 14 BP 8072 EP 8086 DI 10.1128/JVI.77.14.8072-8086.2003 PG 15 WC Virology SC Virology GA 696QX UT WOS:000183899200038 PM 12829846 ER PT J AU Hansen, K Abrass, CK AF Hansen, K Abrass, CK TI Laminin-8/9 is synthesized by rat glomerular mesangial cells and is required for PDGF-induced mesangial cell migration SO KIDNEY INTERNATIONAL LA English DT Article DE laminin; mesangial cells; migration; disintegration ID GROWTH-FACTOR; ALPHA-4 CHAIN; EPITHELIAL-CELLS; DEVELOPMENTAL EXPRESSION; EXTRACELLULAR-MATRIX; G-DOMAIN; A-CHAIN; KIDNEY; MICE; CULTURE AB Background. Laminin (LM), the major glycoprotein component of basement membranes is expressed as multiple isoforms in a developmentally regulated and tissue-specific manner. LM alpha4 has a limited tissue distribution and is highly expressed in the developing glomerulus. In the present study, we investigate the in vivo and in vitro expression and function of LM alpha4 in the glomerulus. Methods. LM alpha4 expression was examined by Northern blot, reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunofluorescence microscopy. Mesangial cells (MC) were plated on purified LM-1, LM-2, and LM-8/9. Immunofluorescence microscopy was performed to examine the cellular phenotypes induced by LM-1 and LM-8/9. A modified Boyden chamber method was used to assess laminin participation in platelet-derived growth factor (PDGF)-stimulated migration. Results. mRNA for LM alpha4 is expressed in cultured rat MC, and isolated rat and mouse glomeruli, but not in cultured rat glomerular epithelial cells or glomerular endothelial cells. Using antibodies specific for LM alpha4, a 240 kD band was detected in MC extract and a slightly smaller band was identified in extracted rat glomeruli. Purified LM-8/9 had MC adhesive activity comparable to LM-1 and LM-2. MC attached to LM-8/9 exhibited a unique phenotype. In contrast to LM-1, attachment of MC to LM-8/9 produced a highly arborized cell morphology with significantly reduced formation of focal contacts or stress fibers. LM alpha4 is utilized by MC during PDGF-stimulated migration. Conclusion. LM alpha4 is synthesized by MC and persists in the mature glomerulus. LM-8/9 stimulates a unique cellular morphology, and they are utilized in PDGF-induced migration. These factors suggest that LM alpha4 plays an important role in MC differentiation and in the maintenance of MC phenotype. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Div Nephrol, Seattle, WA 98195 USA. RP Abrass, CK (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 111A,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [R01 DK49771] NR 50 TC 12 Z9 13 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 JUL PY 2003 VL 64 IS 1 BP 110 EP 118 DI 10.1046/j.1523-1755.2003.00039.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 690KH UT WOS:000183547500014 PM 12787401 ER PT J AU MacMillan, DH AF MacMillan, DH TI Elements of a typical laboratory budget SO LABORATORY MEDICINE LA English DT Article C1 Massachusetts Gen Hosp, Div Lab Med, Boston, MA 02114 USA. RP MacMillan, DH (reprint author), Massachusetts Gen Hosp, Div Lab Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LAB MED JI Lab. Med. PD JUL PY 2003 VL 34 IS 7 BP 515 EP 519 DI 10.1309/99F7NNJ09M3TGQHW PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 694RP UT WOS:000183788300018 ER PT J AU Henderson, Z Ecker, JL AF Henderson, Z Ecker, JL TI Fetal scalp blood sampling - Limited role in contemporary obstetric practice: Part I SO LABORATORY MEDICINE LA English DT Editorial Material ID APGAR SCORE; ACIDEMIA; TERM; COMPLICATIONS; OXYGENATION; NEWBORN; GASES; SHEEP; BIRTH; FLOW C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Henderson, Z (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LAB MED JI Lab. Med. PD JUL PY 2003 VL 34 IS 7 BP 548 EP 553 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 694RP UT WOS:000183788300025 ER PT J AU Isacson, O AF Isacson, O TI The production and use of cells as therapeutic agents in neurodegenerative diseases SO LANCET NEUROLOGY LA English DT Review ID EMBRYONIC STEM-CELLS; AMYOTROPHIC-LATERAL-SCLEROSIS; INTRASTRIATAL NIGRAL GRAFTS; HUNTINGTONS-DISEASE; PARKINSONS-DISEASE; QUINOLINIC ACID; NEURAL TRANSPLANTATION; GANGLIONIC EMINENCE; DOPAMINE NEURONS; MOTOR-NEURON AB Although progressive neurodegenerative diseases have very different and highly specific causes, the dysfunction or loss of a vulnerable group of neurons is common to all these disorders and may allow the development of similar therapeutic approaches to the treatment of diseases such as amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease. When a disease is diagnosed, the first step is to instigate protective measures to prevent further degeneration. However, most patients are symptom-free until almost all of the vulnerable cells have become dysfunctional or have died. There are known molecular mechanisms and processes in stem cells and progenitor cells that may be of use in the future design and selection of cell-based replacement therapies for neurological diseases. This review provides examples of conceptual and clinical problems that have been encountered in the development of cell-based treatments, and specific criteria for the effective use of cells in the future treatment of neurodegenerative diseases. C1 Harvard Univ, Sch Med, McLean Hosp, Ctr Neuroregenerat Res,Neuroregenerat Labs, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Ctr Neurodegenerat & Repair, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Isacson, O (reprint author), Harvard Univ, Sch Med, McLean Hosp, Ctr Neuroregenerat Res,Neuroregenerat Labs, 115 Mill St, Belmont, MA 02478 USA. NR 81 TC 67 Z9 67 U1 2 U2 6 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD JUL PY 2003 VL 2 IS 7 BP 417 EP 424 DI 10.1016/S1474-4422(03)00437-X PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 694GF UT WOS:000183765300016 PM 12849120 ER PT J AU Sindwani, R Cohen, JT Pilch, BZ Metson, RB AF Sindwani, R Cohen, JT Pilch, BZ Metson, RB TI Myospherulosis following sinus surgery: Pathological curiosity or important clinical entity? SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the Triological-Society CY JAN 25, 2003 CL BOSTON, MASSACHUSETTS SP Triol Soc, Eastern Sect DE myospherulosis; lipid-based ointments; postoperative adhesions; revision sinus surgery ID PARANASAL SINUSES; DISEASE; TISSUES AB Objectives/Hypothesis. Myospherulosis is a foreign body reaction to lipid material used on nasal. packing at the conclusion of sinus surgery. This reaction has been associated with postoperative adhesion formation. The purpose of the study was to determine whether the occurrence of myospherulosis has an adverse effect on clinical outcome following sinus surgery. Study Design: Case-control study at an academic medical center. Methods. Thirty-two cases of myospherulosis were identified in 28 patients (4 with bilateral disease) who underwent sinus surgery between 1989 and 1999. Cases were staged according to histological and radiological grading systems. Clinical outcome was compared with a control group of 28 patients who had similar surgery during the same time period. Results. Patients with myospherulosis were found to have a significantly higher likelihood of developing postoperative adhesions compared with control subjects (50% vs. 18%, respectively [P = .023]). Histological stage, based on the extent of lipid vacuoles and spherules (erythrocyte remnants) present in the surgical specimen, was found to correlate with disease severity based on preoperative sinus computed tomography staging (P = .009). Patients with myospherulosis tended to have a shorter interval between their last two surgeries than did control subjects (2.2 +/- 2.1 vs. 4.5 +/- 7.1 y, respectively [P = .086]). Patient age, sex, comorbid conditions, CT stage, and number of previous operations were not predictive for the occurrence of myospherulosis. Conclusions: Patients who develop myospherulosis from lipid-based packing material used during sinus surgery are more likely to form postoperative adhesions. These adhesions appear to be clinically relevant and may hasten the need for revision surgery. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Eye & Ear Infirm,Dept Otolaryngol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Metson, RB (reprint author), Zero Emerson Pl, Boston, MA 02114 USA. NR 17 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUL PY 2003 VL 113 IS 7 BP 1123 EP 1127 DI 10.1097/00005537-200307000-00005 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 700YV UT WOS:000184139500005 PM 12838008 ER PT J AU Cherukupally, SR Adams, AB Mankarious, LA AF Cherukupally, SR Adams, AB Mankarious, LA TI Age-related mechanisms of cricoid cartilage response to injury in the developing rabbit SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 09-12, 2001 CL SCOTTSDALE, ARIZONA SP Amer Soc Pediat Otolaryngol DE subglottic stenosis; cricoid; rabbit; chondrocyte proliferation; immunohistochemistry ID CONGENITAL SUBGLOTTIC STENOSIS; GROWTH; TRAUMA AB Objective. To evaluate age-related mechanisms of cricoid cartilage response to injury in an animal model. Study Design: A pilot study using monoclonal antibodies to chondrocyte proliferation markers collagen II, aggrecan, and proliferating cell nuclear antigen (PCNA) to evaluate age-related response of injured cricoid cartilage. Methods. Twenty-seven New Zealand white rabbits aged 4 weeks, 8 weeks, and 1.5 years were studied. Six animals in each age group underwent intracartilaginous injury through cricofissure and tracheofissure. Three animals of each group were used as control subjects. The animals were killed 4 weeks after injury, their cricoid cartilages harvested, and 7-mum sections of tissue obtained. The cricoid tissue sections were stained with immunofluorescent monoclonal antibody markers to collagen II, aggrecan, and PCNA. Results. In all age groups, no control animals had symptoms of airway compromise or immunohistochemical abnormality. For all three markers of chondrocyte proliferation, the 4-week-old animals showed markedly increased staining at the injured edges of cartilage. The 8-week-old animals showed mild increased extracellular staining, and the 1.5-year-old animals showed no increased staining compared with uninjured areas of the cricoid ring and with control animals. Conclusion: There was a progressive, age-related attenuation of staining for markers of chondrocyte proliferation in the 8-week and 1.5-year-old rabbits compared with the 4-week-old rabbit cricoids. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Mankarious, LA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUL PY 2003 VL 113 IS 7 BP 1145 EP 1148 DI 10.1097/00005537-200307000-00009 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 700YV UT WOS:000184139500009 PM 12838012 ER PT J AU Stone, ME AF Stone, ME TI Childhood disorders diagnostic desk reference. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp, Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD JUL PY 2003 VL 128 IS 12 BP 71 EP 72 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA 696VL UT WOS:000183908200036 ER PT J AU Saab, S Ly, D Nieto, J Kanwal, F Lu, D Raman, S Amado, R Nuesse, B Durazo, F Han, S Farmer, DG Ghobrial, RM Yersiz, H Chen, P Schwegel, K Goldstein, LI Tong, M Busuttil, RW AF Saab, S Ly, D Nieto, J Kanwal, F Lu, D Raman, S Amado, R Nuesse, B Durazo, F Han, S Farmer, DG Ghobrial, RM Yersiz, H Chen, P Schwegel, K Goldstein, LI Tong, M Busuttil, RW TI Hepatocellular carcinoma screening in patients waiting for liver transplantation: A decision analytic model SO LIVER TRANSPLANTATION LA English DT Article ID PERCUTANEOUS ETHANOL INJECTION; TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; RANDOMIZED CONTROLLED TRIAL; COST-EFFECTIVENESS ANALYSIS; CIRRHOTIC-PATIENTS; HEPATITIS-C; RADIOFREQUENCY ABLATION; SURVEILLANCE PROGRAM; TREATMENT STRATEGY; PROGNOSTIC FACTORS AB De novo hepatocellular carcinoma (HCC) may have a large impact on patients waiting for liver transplantation. The presence of HCC can lead to a status upgrade or removal from the waitlist. Our aim is to compare costs and outcomes of different liver cancer surveillance strategies. A Markov-based decision analytic model is created to simulate costs and health outcomes for a hypothetical cohort awaiting liver transplantation undergoing HCC screening. Three strategies of HCC screening are compared with the referent strategy of using alphafetaprotein (AFP) level alone: (1) ultrasound (U/S), (2) AFP plus U/S, and (3) computed tomography (CT). Screening is performed for all strategies at 6-month intervals. Selected tumors are treated locally. Costs and clinical outcomes are discounted. Using baseline assumptions, incremental cost-effectiveness ratios (ICERs) for U/S, U/S plus AFP, and CT are $60,300/life-year saved (LY), $74,000/LY, and $101,100/LY, respectively. The most cost-effective strategy was dependent on the relative costs of each screening modality. U/S screening becomes the dominant strategy when the cost of an AFP test is decreased. Our results show that screening with CT is associated the greatest gain in life expectancy and greatest costs. U/S screening strategy is the preferred screening strategy based on the lowest ICER. Ultimately, costs of the screening modalities determine the most cost-effective strategy. C1 Univ Calif Los Angeles, Med Ctr, Div Digest Dis, Dept Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA 90095 USA. Dumont UCLA Liver Transplant Ctr, Dept Med, Los Angeles, CA USA. W Los Angeles Vet Adm Med Ctr, Dept Med, Los Angeles, CA 90073 USA. RP Saab, S (reprint author), Univ Calif Los Angeles, Med Ctr, Div Digest Dis, Dept Surg, 44-138 CHS MC 168417,10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 64 TC 47 Z9 49 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUL PY 2003 VL 9 IS 7 BP 672 EP 681 DI 10.1053/jlts.2003.50120 PG 10 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 696GD UT WOS:000183878500003 PM 12827551 ER PT J AU Wu, YT Ackerman, JL Chesler, DA Graham, L Wang, Y Glimcher, MJ AF Wu, YT Ackerman, JL Chesler, DA Graham, L Wang, Y Glimcher, MJ TI Density of organic matrix of native mineralized bone measured by water- and fat-suppressed proton projection MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE solid state MRI; water and fat suppression; bone matrix; bone mineralization ID SOLID-STATE NMR; SYNTHETIC CALCIUM PHOSPHATES; NUCLEAR-MAGNETIC-RESONANCE; SPECTROSCOPY; GRADIENTS; THERAPY; PHASES AB Water- and fat-suppressed projection MR imaging (WASPI) utilizes the large difference between the proton T-2*s of the solid organic matrix and the fluid constituents of bone to suppress the fluid signals while preserving solid matrix signals. The solid constituents include collagen and some molecularly immobile water and exhibit very short T-2*. The fluid constituents include mobile water and fat, with long T2*. In WASPI, chemical shift selective low-power pi/2 pulses excite mobile water an at magnetization which is subsequently dephased by gradient pulses, while the magnetization of collagen and immobile water remains mostly in the z-direction. Additional selective, pi pulses in alternate scans further cancel the residual water and fat magnetization. Following water and fat suppression, the matrix signal is excited by a short hard pulse and the free induction decay acquired in the presence of a gradient in a 3D projection method. WASPI was implemented on a 4.7 T MR imaging system and tested on phantoms and bone specimens, enabling excellent visualization of bone matrix. The bone matrix signal per unit volume of bovine trabecular specimens was measured by this MR technique and compared with that determined by chemical analysis. This method could be used in combination with bone mineral density measurement by solid state projection MRI to determine the degree of bone mineralization. Magn Reson Med 50:59-68, 2003. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Childrens Hosp, Dept Orthopaed Surg, Lab Study Skeletal Disorders & Rehabil,Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,NMR Ctr,Biomat Lab, Charlestown, MA USA. RP Wu, YT (reprint author), Harvard Univ, Childrens Hosp, Dept Orthopaed Surg, Lab Study Skeletal Disorders & Rehabil,Sch Med, 300 Longwood Ave, Boston, MA 02115 USA. RI Ackerman, Jerome/E-2646-2015 OI Ackerman, Jerome/0000-0001-5176-7496 FU NIA NIH HHS [R01-AG14701]; NIAMS NIH HHS [R01-AR42258, T32-AR07112] NR 41 TC 65 Z9 69 U1 0 U2 6 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 JUL PY 2003 VL 50 IS 1 BP 59 EP 68 DI 10.1002/mrm.10512 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 697UN UT WOS:000183961800009 PM 12815679 ER PT J AU Dou, JG Tseng, WYI Reese, TG Wedeen, VJ AF Dou, JG Tseng, WYI Reese, TG Wedeen, VJ TI Combined diffusion and strain MRI reveals structure and function of human myocardial laminar sheets in vivo SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; myocardium; sheets; mechanics; diffusion; strain; function ID MAGNETIC-RESONANCE; TENSOR; ARCHITECTURE AB The mechanism of ventricular thickening in normal humans was investigated using in vivo MRI. The hypothesis that myocardial laminar sheets contribute to ventricular thickening predominantly via sheet shear and sheet extension, as previously found invasively in canine studies at particular ventricular sites, was tested. In normal human subjects, registered images of myocardial sheet architecture and strain at the mid-left ventricle (mid-LV) at midsystole were acquired with diffusion and strain MRI. Sheet function was analyzed by computing myocardial strain in the local fiber-sheet coordinates. In general, myocardial sheets contribute to ventricular thickening through all three cross-fiber strain components: sheet shear, sheet extension, and sheet-normal thickening (previously undocumented). Each of these components demonstrated substantial spatial heterogeneity, with sheet shear and sheet extension usually predominant in the anterior free wall, and sheet-normal thickening predominant near the right ventricular (RV) insertions. However, considerable intersubject variability was also found. In all cases, the contributions to thickening of fiber strains were small. Sheet function in normal humans was found to be heterogeneous and variable, contrasting with the uniform and symmetric ventricular patterns of fiber shortening and wall thickening. The study demonstrates that noninvasive NMR imaging is a promising tool for investigations of myocardial sheet architecture and function, and is particularly suited to the evident complexity of this field of study. Magn Reson Med 50:107-113, 2003. (C) 2003 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Dept Nucl Engn, Cambridge, MA 02139 USA. Natl Taiwan Univ, Coll Med, Ctr Optoelect Biomed, Taipei, Taiwan. Natl Taiwan Univ, Coll Med, Dept Radiol, Taipei, Taiwan. RP Wedeen, VJ (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,13th St,MS 2301, Charlestown, MA 02129 USA. OI Tseng, Wen-Yih Isaac/0000-0002-2314-6868 FU NHLBI NIH HHS [1R01-HL56737] NR 19 TC 55 Z9 56 U1 0 U2 0 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 JUL PY 2003 VL 50 IS 1 BP 107 EP 113 DI 10.1002/mrm.10482 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 697UN UT WOS:000183961800015 PM 12815685 ER PT J AU Wu, O Ostergaard, L Weisskoff, RM Benner, T Rosen, BR Sorensen, AG AF Wu, O Ostergaard, L Weisskoff, RM Benner, T Rosen, BR Sorensen, AG TI Tracer arrival timing-insensitive technique for estimating flow in MR perfusion-weighted imaging using singular value decomposition with a block-circulant deconvolution matrix SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE perfusion-weighted imaging; humans; dynamic susceptibility contrast-enhanced magnetic resonance imaging; cerebral blood flow; ischemia ID CEREBRAL-BLOOD-FLOW; SUSCEPTIBILITY CONTRAST MRI; HIGH-RESOLUTION MEASUREMENT; HYPERACUTE STROKE; BOLUS PASSAGES; TRACKING C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MIT,Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. Aarhus Univ Hosp, Ctr Functionally Integrat Neurosci, Dept Neuroradiol, DK-8000 Aarhus, Denmark. EPIX Med, Cambridge, MA USA. RP Wu, O (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MIT,Athinoula A Martinos Ctr Biomed Imaging, Mailcode CNY149-2301, Boston, MA 02129 USA. RI Bonefeld, Birgit/B-7936-2010; Ostergaard, Leif/A-9281-2008 OI Ostergaard, Leif/0000-0003-2930-6997 FU NCRR NIH HHS [5P41 RR14075]; NHLBI NIH HHS [5 R01 HL39810]; NINDS NIH HHS [5 R01 NS38477] NR 26 TC 321 Z9 323 U1 0 U2 11 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 JUL PY 2003 VL 50 IS 1 BP 164 EP 174 DI 10.1002/mrm.10522 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 697UN UT WOS:000183961800021 PM 12815691 ER PT J AU Paganetti, H Gottschalk, B AF Paganetti, H Gottschalk, B TI Test of GEANT3 and GEANT4 nuclear models for 160 MeV protons stopping in CH2 SO MEDICAL PHYSICS LA English DT Article ID MONTE-CARLO; THERAPY CENTER; DOSIMETRY; BEAMS; NEUTRON; ENERGY; POWER AB Monte Carlo simulations are used for many problems in proton radiation therapy, some of which are sensitive to the nuclear interaction model. The available models have been little tested in the regime of interest, namely in their ability to predict the secondary particle yield, including their angle and energy, when 70-250 MeV protons stop in various materials. The present study provides one such test in carbon, complementing a previous one in copper. Using a multilayer Faraday cup we have measured the projected range distribution of charged nuclear secondaries from 160 MeV protons stopping in polyethylene (CH2). To test the popular GEANT Monte Carlo we have simulated the experiment with GEANT3 using the "Gheisha" (default) and "Fluka" models' and with GEANT4.5 using the "low-energy" and "precompound" models. The GEANT3/Fluka and GEANT4/precompound simulations agree moderately well with the observed range distribution. The data are given in a convenient form for testing other Monte Carlo programs. (C) 2003 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, High Energy Phys Lab, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 16 TC 34 Z9 34 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUL PY 2003 VL 30 IS 7 BP 1926 EP 1931 DI 10.1118/1.1586454 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 702DC UT WOS:000184209200041 PM 12906211 ER PT J AU LeMaster, JW Reiber, GE Smith, DG Heagerty, PJ Wallace, C AF LeMaster, JW Reiber, GE Smith, DG Heagerty, PJ Wallace, C TI Daily weight-bearing activity does not increase the risk of diabetic foot ulcers SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE weight-bearing; physical activity; diabetes; insensate; neuropathy; risk; foot ulceration ID CARDIORESPIRATORY FITNESS; PREVENTION; ULCERATION; POPULATION; PREDICTORS; MEN; MORTALITY; PRESSURE; STRESS; TRIAL AB Daily Weight-Bearing Activity Does Not Increase the Risk of Diabetic Foot Ulcers. Med. Sci. Sports Exerc., Vol. 35, No. 7, pp. 1093-1099, 2003. Purpose: This study had two purposes: to identify characteristics associated with participants' usual weight-bearing activity, and to determine whether weight-bearing activity increased the risk of foot ulcer among persons with diabetes and prior foot ulcer. Methods: We conducted a prospective cohort study of 400 participants with diabetes and a prior history of foot ulcer. Participants were from the Veterans Affairs Puget Sound Health Care System and Group Health Cooperative in Seattle, WA, and were originally assembled for a randomized controlled trial of footwear. Feet were examined and demographic and health history information was collected at enrollment. Daily weight-bearing activity was reported at enrollment and every 17 wk thereafter for 2 yr. All incident foot lesions were recorded. Results: Weight-bearing activity was significantly higher among women. Activity was lower among participants who were older, unmarried, or who had a history of congestive heart failure, respiratory disease, stroke, or depression. Activity decreased significantly over the study period but remained similar in those with or without insensate feet. After adjustment for foot-related and health-status characteristics, moderately active participants (4.5-7.4 weight-bearing h(.)d(-1)) were at substantially but nonsignificantly reduced risk of foot ulcer compared with "least active" participants (<4.5 weight-bearing h(.)d(-1)) (OR 0.50, 95% CI 0.22-1.16). "Most active" participants (greater than or equal to7.5 weight-bearing h(.)d(-1)) were at significantly reduced risk (OR 0.20, 95% CI 0.04-0.87). Weight-bearing activity exerted similar effects on foot ulcer risk in participants with insensate versus sensate feet. Conclusion: Increased weight-bearing activity did not increase the risk of foot re-ulceration. Further studies are needed to explore weight-bearing activities that are safe for those with diabetes and insensate feet. C1 Univ Missouri, Dept Family & Community Med, Columbia, MO 65212 USA. Washington Univ, Dept Hlth Serv, Seattle, WA USA. Washington Univ, Dept Epidemiol, Seattle, WA USA. Washington Univ, Dept Orthopaed Surg, Seattle, WA USA. Washington Univ, Dept Biostat, Seattle, WA USA. Dept Vet Affairs, VA Puget Sound Hlth Care Syst, Hlth Serv & Rehabil Res & Dev, Seattle, WA USA. RP LeMaster, JW (reprint author), Univ Missouri, Dept Family & Community Med, 1 Hosp Dr, Columbia, MO 65212 USA. NR 27 TC 44 Z9 44 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JUL PY 2003 VL 35 IS 7 BP 1093 EP 1099 DI 10.1249/01.MSS.0000074459.41029.75 PG 7 WC Sport Sciences SC Sport Sciences GA 697TG UT WOS:000183958900005 PM 12840628 ER PT J AU Hughes, KS Roche, CA AF Hughes, KS Roche, CA TI Hormone therapy revisited: data from the population, treatment for the patient SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID ESTROGEN REPLACEMENT THERAPY; RANDOMIZED CONTROLLED TRIAL; BREAST-CANCER; POSTMENOPAUSAL WOMEN; HOT FLASHES; RALOXIFENE; TAMOXIFEN; PROGESTIN; HISTORY C1 Massachusetts Gen Hosp, Div Surg Oncol, Avon Fdn Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. RP Hughes, KS (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Avon Fdn Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. OI Hughes, Kevin/0000-0003-4084-6484 NR 14 TC 0 Z9 0 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 JUL-AUG PY 2003 VL 10 IS 4 BP 269 EP 270 DI 10.1097/01.GME.0000079503.41032.AE PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 702WG UT WOS:000184247300001 PM 12851507 ER PT J AU Daly, C Rollins, BJ AF Daly, C Rollins, BJ TI Monocyte chemoattractant protein-1 (CCL2) in inflammatory disease and adaptive immunity: Therapeutic opportunities and controversies SO MICROCIRCULATION LA English DT Article DE chemokine; inflammation; T helper cell ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NEUTROPHIL-ACTIVATING PROPERTIES; MULTIPLE-SCLEROSIS LESIONS; HISTAMINE-RELEASING FACTOR; CHEMOKINE RECEPTOR (CCR)2; CORONARY-ARTERY DISEASE; SMOOTH-MUSCLE CELLS; ENDOTHELIAL-CELLS; KNOCKOUT MICE; NEOINTIMAL HYPERPLASIA AB Monocyte chemoattractant protein (MCP)-1 (CCL2) specifically attracts monocytes and memory T cells. Its expression occurs in a variety of diseases characterized by mononuclear cell infiltration, and there is substantial biological and genetic evidence for its essential role in atherosclerosis and multiple sclerosis. Despite intensive screening, there are as yet no small-molecule antagonists of the receptor of MCP-1/CCL2, CCR2. However, biological agents, including antibodies and inhibitory peptides, have been developed and may be useful for these indications. Recent evidence from genetically modified mice indicates that MCP-1 and CCR2 have unanticipated effects on T helper (Th) cell development. However, unlike the identical phenotypes of MCP-1/CCL2(-/-) and CCR2(-/-) mice in inflammatory diseases, the phenotypes of these mice are disparate in adaptive immunity: MCP-1 stimulates Th2 polarization, whereas CCR2 activation stimulates Th1 polarization. This presents both a challenge and an opportunity for targeting the MCP-1/CCL2/CCR2 axis in disease. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Med Oncol, Boston, MA USA. RP Rollins, BJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA53091]; NIAID NIH HHS [AI50225] NR 73 TC 148 Z9 156 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1073-9688 J9 MICROCIRCULATION JI Microcirculation PD JUL PY 2003 VL 10 IS 3-4 BP 247 EP 257 DI 10.1038/sj.mn.7800190 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 699QW UT WOS:000184068300002 PM 12851642 ER PT J AU McKenney, JK Amin, MB Young, RH AF McKenney, JK Amin, MB Young, RH TI Urothelial (transitional cell) papilloma of the urinary bladder: A clinicopathologic study of 26 cases SO MODERN PATHOLOGY LA English DT Article DE benign; classification; grading; neoplasm; papillary carcinoma; papilloma; transitional cell; urinary bladder; urothelial papilloma ID HYPERPLASIA; EXPRESSION; PRECURSOR; NEOPLASMS; GRADE AB The existence of a papillary lesion of the urinary bladder with a benign clinical course and recognizable morphologic features that merit the benign categorization "papilloma" has been controversial. The clinical aspects and histologic features of these lesions remain to be fully elucidated. We have studied the clinicopathologic features of 26 patients with urothelial papillomas and correlated them with outcome. Papillomas occurred in two distinct clinical settings: (1) de novo neoplasms (23/26) or (2) those occurring in patients with a known clinical history of bladder cancer ("secondary" papillomas; 3/26). Follow-up information was available in 14/23 of the de novo cases (mean = 39 mo) and in 3/3 secondary cases (mean = 24 mo). Patients with de novo papillomas had a mean age of 46 years; 16 were male and 7 were female. Twelve of 14 had a benign clinical course with no recurrences; I developed a recurrent papilloma at 3 years, and I developed a pT3a high-grade papillary urothelial carcinoma at 4 years. Patients with secondary papillomas had a mean age of 66 years; two were male and one was a female. One of these patients developed two additional recurrences, and two patients had no new recurrences. Morphologically, the papillary architecture ranged from a common simple, nonhierarchical arrangement to, infrequently, more complex anastomosing papillae with budding. The individual papillae ranged from small (most common), with scant stroma and slender fibrovascular cores, to large, with marked stromal edema and/or cystitis cystica-like urothelial invaginations. Common to all was a lining of normal-appearing urothelium without hyperplasia, maintenance of normal polarity, and frequent prominence of the umbrella cell layer. Overall, no patient with a diagnosis of papilloma died of disease; only one patient with a de novo lesion (7.0%) had a recurrent papilloma, and 1/14 (7.0%) progressed to a higher grade and stage of disease, although this patient was on immunosuppressive therapy secondary to a renal transplant. De novo urothelial papillomas occur in younger patients and usually have a benign course. Urothelial papillomas are histologically and probably biologically distinctive tumors and merit distinction from other higher risk papillary neoplasms of the urinary bladder. C1 Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Lab Med, Atlanta, GA 30322 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Amin, MB (reprint author), Emory Univ Hosp, Dept Pathol & Lab Med, Room G-167,1364 Clifton Rd NE, Atlanta, GA 30322 USA. NR 10 TC 20 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JUL PY 2003 VL 16 IS 7 BP 623 EP 629 DI 10.1097/01.MP.0000073973.74228.1E PG 7 WC Pathology SC Pathology GA 703MT UT WOS:000184284000001 PM 12861056 ER PT J AU Choi, EK Miller, JS Zaidi, NF Salih, E Buxbaum, JD Wasco, W AF Choi, EK Miller, JS Zaidi, NF Salih, E Buxbaum, JD Wasco, W TI Phosphorylation of calsenilin at Ser63 regulates its cleavage by caspase-3 SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID CASEIN KINASE-I; CALCIUM-BINDING PROTEIN; NEURONAL CA2+ SENSOR-1; ALZHEIMERS-DISEASE; MOLECULAR-CLONING; ENDOPLASMIC-RETICULUM; GUANYLATE-CYCLASE; NERVOUS-SYSTEM; PC12 CELLS; PRESENILIN-2 AB Calsenilin is a member of the neuronal calcium sensor (NCS) family of proteins that interacts with the presenilins. Calsenilin has been found to act as a Kv4alpha channel interactor and as a transcriptional repressor. We have recently shown that calsenilin can be cleaved by caspase-3 and that its cleavage separates the conserved calcium-binding domain from the variable N-terminal domain. Here, we demonstrate that calsenilin can be phosphorylated by casein kinase I and that its phosphorylation can be regulated by intracellular calcium. In addition, phosphorylated calsenilin is a substrate for serine/threonine protein phosphatase (PP) 1 and/or 2A. Phosphorylation within the N-terminal domain at Ser63. the major phosphorylation site of calsenilin, inhibits cleavage of the molecule by caspase-3. Given that the N-terminal domain of calsenilin is not conserved in the larger NCS family including other KChIP/CALP proteins, phosphorylation of calsenilin may regulate a functional role that is unique to this member of the superfamily. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Neurol, Genet & Aging Res Unit,Ctr Aging Genet & Neurodeg, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Orthoped Surg, Lab Study Skeletal Disorders & Rehabil, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Neurobiol, New York, NY 10029 USA. RP Wasco, W (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Neurol, Genet & Aging Res Unit,Ctr Aging Genet & Neurodeg, 114 16th St, Charlestown, MA 02129 USA. OI Salih, Erdjan/0000-0003-3322-2323; Buxbaum, Joseph/0000-0001-8898-8313 FU NIA NIH HHS [AG16361] NR 56 TC 14 Z9 17 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 JUL PY 2003 VL 23 IS 3 BP 495 EP 506 DI 10.1016/S1044-7431(03)00072-1 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 698HX UT WOS:000183993900014 PM 12837631 ER PT J AU Smith, KM Yacobi, R Van Etten, RA AF Smith, KM Yacobi, R Van Etten, RA TI Autoinhibition of Bcr-Abl through its SH3 domain SO MOLECULAR CELL LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE-ACTIVITY; CHRONIC MYELOGENOUS LEUKEMIA; GROWTH-FACTOR INDEPENDENCE; REGULATES C-ABL; PHILADELPHIA-CHROMOSOME; OLIGOMERIZATION DOMAIN; FAMILY KINASES; TRANSFORMATION; INHIBITOR AB Bcr-Abl is a dysregulated tyrosine kinase whose mechanism of activation is unclear. Here, we demonstrate that, like c-Abl, Bcr-Abl is negatively regulated through its SH3 domain. Kinase activity, transformation, and leukemogenesis by Bcr-Abl are greatly impaired by mutations of the Bcr coiled-coil domain that disrupt oligomerization, but restored by an SH3 point mutation that blocks ligand binding or a complementary mutation at the intramolecular SH3 binding site defined in c-Abl. Phosphorylation of tyrosines in the activation loop of the catalytic domain and the linker between the SH2 and catalytic domains (SH2-CD linker) is dependent on oligomerization and required for leukemogenesis. These results suggest that Bcr-Abl has a monomeric, unphosphorylated state with the SH3 domain engaged intramolecularly to Prol 124 in the SH2-CD linker, the form that is sensitive to the inhibitor imatinib (STI-571). The sole function of the coiled-coil domain is to disrupt the autoinhibited conformation through oligomerization and intermolecular autophosphorylation. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Van Etten, RA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. FU NCI NIH HHS [CA90576]; NHLBI NIH HHS [HL07623] NR 39 TC 86 Z9 92 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUL PY 2003 VL 12 IS 1 BP 27 EP 37 DI 10.1016/S1097-2765(03)00274-0 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 707UK UT WOS:000184528100005 PM 12887890 ER PT J AU Song, HK Eck, MJ AF Song, HK Eck, MJ TI Structural basis of degradation signal recognition by SspB, a specificity-enhancing factor for the ClpXP proteolytic machine SO MOLECULAR CELL LA English DT Article ID ATP-DEPENDENT PROTEOLYSIS; ESCHERICHIA-COLI; CRYSTAL-STRUCTURES; UBIQUITIN SYSTEM; CLPAP PROTEASE; TAGGING SYSTEM; CHAPERONE; PROTEINS; BINDING; RNA AB In prokaryotes, incomplete or misfolded polypeptides emanating from a stalled ribosome are marked for degradation by the addition of an 11 residue peptide (AANDENYALAA) to their C terminus. Substrates containing this conserved degradation signal, the SsrA tag, are targeted to specific proteases including ClpXP and CIpAP. SspB was originally characterized as a stringent starvation protein and has been found to bind specifically to SsrA-tagged proteins and to enhance recognition of these proteins by the CIpXP degradation machine. Here, we report the crystal structures of SspB alone and in complex with an SsrA peptide. Unexpectedly, SspB exhibits a fold found in Sm-family RNA binding proteins. The dimeric SspB structures explain the key determinants for recognition of the SsrA tag and define a hydrophobic channel that may bind unfolded substrates. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Eck, MJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. RI Song, Hyun Kyu/D-6763-2016 OI Song, Hyun Kyu/0000-0001-5684-4059 NR 58 TC 46 Z9 47 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUL PY 2003 VL 12 IS 1 BP 75 EP 86 DI 10.1016/S1097-2765(03)00271-5 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 707UK UT WOS:000184528100009 PM 12887894 ER PT J AU Camicioli, R Moore, MM Kinney, A Corbridge, E Glassberg, K Kaye, JA AF Camicioli, R Moore, MM Kinney, A Corbridge, E Glassberg, K Kaye, JA TI Parkinson's disease is associated with hippocampal atrophy SO MOVEMENT DISORDERS LA English DT Review DE Parkinson's disease; dementia; Alzheimer's disease; MRI; hippocampus; atrophy ID LEWY BODY DISEASE; PROGRESSIVE SUPRANUCLEAR PALSY; REGIONAL BRAIN ATROPHY; TEMPORAL-LOBE ATROPHY; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; CLINICAL-DIAGNOSIS; BODIES; MRI; HALLUCINATIONS AB Patients with Parkinson's disease (PD) may have hippocampal atrophy compared with controls. We compared hippocampal, and extra-hippocampal volumes between PD, PDD (patients with PD who have mild cognitive impairment or dementia), Alzheimer's disease (AD) and controls using volumetric magnetic resonance imaging (MRI). Participants (10 patients with PD, 10 with PDD, I I with AD, and 12 control subjects) had an informant interview, neurological examination, and psychometric testing. Established, reliable methods were used to measure the hippocampus, parahippocampal gyrus, temporal, frontal, and parieto-occipital lobes. Correction for intracranial volume was carried out before comparison . There was no age difference between groups (mean age, 74 years). On the Clinical Dementia Rating scale (CDR) cognitive impairment was mild (CDR = 0.5) in the majority of PDD and AD patients. Hippocampal (P < 0.0004) volumes were smaller in the patient groups. Effect sizes compared with the control group were: PD, 0.66; PDD, 1.22; and AD, 1.81. The other volumes did not differ significantly. Among PD and PDD patients, recognition memory (r = 0.54, P = 0.015) and Mini-Mental State Examination scores (r = 0.56, P = 0.01) correlated with left, but not right hippocampal volume. In conclusion, hippocampal volume showed a pattern (Control > PD > PDD > AD) suggesting progressive hippocampal volume loss in PD. Volumetric MRI imaging might provide an early marker for dementia in PD. (C) 2003 Movement Disorder Society. C1 Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Univ Alberta, Dept Med Neurol, Edmonton, AB, Canada. RP Camicioli, R (reprint author), Univ Alberta, Dept Med, Glenrose Rehabil Hosp, Room E-223,10230-11 Ave, Edmonton, AB T5G 0B7, Canada. OI Kaye, Jeffrey/0000-0002-9971-3478; Camicioli, Richard/0000-0003-2977-8660 FU NCRR NIH HHS [5M01RR0034]; NIA NIH HHS [AG08017] NR 48 TC 157 Z9 166 U1 2 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL PY 2003 VL 18 IS 7 BP 784 EP 790 DI 10.1002/mds.10444 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 701CA UT WOS:000184148300007 PM 12815657 ER PT J AU Lechner, A Habener, JF AF Lechner, A Habener, JF TI Bone marrow stem cells find a path to the pancreas SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID FUSION C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Lechner, A (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, 55 Fruit St,WEL 320, Boston, MA 02114 USA. NR 10 TC 11 Z9 12 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2003 VL 21 IS 7 BP 755 EP 756 DI 10.1038/nbt0703-755 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 696KL UT WOS:000183886000023 PM 12833093 ER PT J AU Daley, GQ AF Daley, GQ TI ES cells prove egg-straordinary SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID EMBRYONIC STEM-CELLS; DIFFERENTIATION; NEURONS C1 Harvard Univ, Sch Med, Dept Biol Chem, Cambridge, MA 02142 USA. Childrens Hosp, Div Pediat Hematol Oncol, Cambridge, MA 02142 USA. Whitehead Inst, Dana Farber Canc Inst, Cambridge, MA 02142 USA. RP Daley, GQ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem, 9 Cambridge Ctr, Cambridge, MA 02142 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2003 VL 21 IS 7 BP 760 EP 761 DI 10.1038/nbt0703-760 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 696KL UT WOS:000183886000027 PM 12833097 ER PT J AU Mootha, VK Lindgren, CM Eriksson, KF Subramanian, A Sihag, S Lehar, J Puigserver, P Carlsson, E Ridderstrale, M Laurila, E Houstis, N Daly, MJ Patterson, N Mesirov, JP Golub, TR Tamayo, P Spiegelman, B Lander, ES Hirschhorn, JN Altshuler, D Groop, LC AF Mootha, VK Lindgren, CM Eriksson, KF Subramanian, A Sihag, S Lehar, J Puigserver, P Carlsson, E Ridderstrale, M Laurila, E Houstis, N Daly, MJ Patterson, N Mesirov, JP Golub, TR Tamayo, P Spiegelman, B Lander, ES Hirschhorn, JN Altshuler, D Groop, LC TI PGC-1 alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes SO NATURE GENETICS LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; GAMMA COACTIVATOR-1 PGC-1; SKELETAL-MUSCLE; MITOCHONDRIAL BIOGENESIS; EXPRESSION PROFILE; DETERMINANTS; RESPIRATION; MECHANISMS; DISCOVERY; MELLITUS AB DNA microarrays can be used to identify gene expression changes characteristic of human disease. This is challenging, however, when relevant differences are subtle at the level of individual genes. We introduce an analytical strategy, Gene Set Enrichment Analysis, designed to detect modest but coordinate changes in the expression of groups of functionally related genes. Using this approach, we identify a set of genes involved in oxidative phosphorylation whose expression is coordinately decreased in human diabetic muscle. Expression of these genes is high at sites of insulin-mediated glucose disposal, activated by PGC-1alpha and correlated with total-body aerobic capacity. Our results associate this gene set with clinically important variation in human metabolism and illustrate the value of pathway relationships in the analysis of genomic profiling experiments. C1 MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Harvard Med Sch, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Lund Univ, Dept Endocrinol, Wallenberg Lab, Univ Hosp MAS, S-20502 Malmo, Sweden. Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. MIT, Dept Biol, Cambridge, MA USA. Harvard Med Sch, Dept Genet, Boston, MA USA. Childrens Hosp, Dept Pediat, 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. RP Altshuler, D (reprint author), MIT, Whitehead Inst, Ctr Genome Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Altshuler, David/A-4476-2009; Ridderstrale, Martin/F-7678-2012 OI Altshuler, David/0000-0002-7250-4107; FU Wellcome Trust [090532] NR 33 TC 2776 Z9 2830 U1 15 U2 145 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2003 VL 34 IS 3 BP 267 EP 273 DI 10.1038/ng1180 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 695DF UT WOS:000183815300013 PM 12808457 ER PT J AU Mostoslavsky, R Alt, FW Bassing, CH AF Mostoslavsky, R Alt, FW Bassing, CH TI Chromatin dynamics and locus accessibility in the immune system SO NATURE IMMUNOLOGY LA English DT Review ID CLASS-SWITCH RECOMBINATION; TCR-ALPHA ENHANCER; V(D)J RECOMBINATION; MECHANISM; AID; REGION; CELLS; H2AX; BETA AB Development invertebrates follows distinctive pathways of cellular differentiation. Starting from the zygote, newly formed cells continually differentiate until they reach a final mature fate. Whether differentiating into a neuron, a hepatocyte or a myofibril, every normal cell, with the exception of developing lymphocytes, carries the same genetic information enclosed within its nucleus. To acquire distinct cellular identities, cells need to control gene expression in a very regulated way. Genes encoding factors required for identity at a particular developmental stage need to be appropriately activated, whereas genes required for identity during the previous developmental stage are often silenced. Moreover, once a cell becomes terminally differentiated, 'heritable' gene expression must be maintained in all daughter cells and, thus, faithfully recapitulated after each cellular division. C1 Harvard Univ, Sch Med, Ctr Blood Res, Childrens Hosp,Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Childrens Hosp,Howard Hughes Med Inst, Boston, MA 02115 USA. NR 30 TC 39 Z9 43 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUL PY 2003 VL 4 IS 7 BP 603 EP 606 DI 10.1038/ni0703-603 PG 4 WC Immunology SC Immunology GA 697PN UT WOS:000183952500002 PM 12830134 ER PT J AU Ansel, KM Lee, DU Rao, A AF Ansel, KM Lee, DU Rao, A TI An epigenetic view of helper T cell differentiation SO NATURE IMMUNOLOGY LA English DT Review ID CYTOKINE GENE-EXPRESSION; HISTONE H3; LINEAGE COMMITMENT; IFN-GAMMA; IN-VIVO; LYMPHOCYTE DEVELOPMENT; HYPERSENSITIVE SITES; IL-4 PRODUCTION; CUTTING EDGE; TH2 CELLS AB Antigen and cytokine receptor signals act in synergy to direct the differentiation of CD4(+) T cells. These signals initiate reciprocal activation and silencing of the interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) cytokine gene loci, changes that are heritably maintained in the resulting T helper type I (T(H)1) or T(H)2 cells and their progeny. Early, unpolarized transcription and chromatin remodeling of the poised cytokine genes of naive T cells is followed by consolidation and spreading of epigenetic changes and the establishment of self-reinforcing transcription factor networks. Recent studies have begun to elucidate the molecular mechanisms that establish and maintain polarized cytokine gene expression, and thus the cellular identity of differentiated helper T cells. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 99 TC 288 Z9 300 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUL PY 2003 VL 4 IS 7 BP 616 EP 623 DI 10.1038/ni0703-616 PG 8 WC Immunology SC Immunology GA 697PN UT WOS:000183952500004 PM 12830136 ER PT J AU Letvin, NL Walker, BD AF Letvin, NL Walker, BD TI Immunopathogenesis and immunotherapy in AIDS virus infections SO NATURE MEDICINE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; COMBINATION ANTIRETROVIRAL THERAPY; NEUTRALIZING ANTIBODY-RESPONSES; CELLULAR IMMUNE-RESPONSES; LONG-TERM NONPROGRESSORS; CHRONIC HIV-1 INFECTION; AMINO-ACID CHANGE; TYPE-1 INFECTION; RHESUS-MONKEYS AB The heterogeneity of HIV and the different human leukocyte antigen (HLA) backgrounds of infected individuals have posed challenges to understanding the pathogenesis of HIV infection. But continuing advances in our knowledge of the role of immune responses in controlling HIV viremia should help to define goals for immune-based therapies and vaccine strategies against AIDS. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02114 USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. NR 106 TC 165 Z9 170 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2003 VL 9 IS 7 BP 861 EP 866 DI 10.1038/nm0703-861 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 698CD UT WOS:000183979300025 PM 12835706 ER PT J AU Haq, S Kilter, H Michael, A Tao, J O'Leary, E Sun, XM Walters, B Bhattacharya, K Chen, X Cui, L Andreucci, M Rosenzweig, A Guerrero, JL Patten, R Liao, R Molkentin, J Picard, M Bonventre, JV Force, T AF Haq, S Kilter, H Michael, A Tao, J O'Leary, E Sun, XM Walters, B Bhattacharya, K Chen, X Cui, L Andreucci, M Rosenzweig, A Guerrero, JL Patten, R Liao, R Molkentin, J Picard, M Bonventre, JV Force, T TI Deletion of cytosolic phospholipase A(2) promotes striated muscle growth SO NATURE MEDICINE LA English DT Article ID KINASE-C-ZETA; INSULIN-RECEPTOR SUBSTRATE-1; SIGNALING PATHWAYS; POSTNATAL-GROWTH; TRANSGENIC MICE; FACTOR-I; CARDIOMYOCYTE HYPERTROPHY; PHOSPHOINOSITIDE 3-KINASE; VENTRICULAR HYPERTROPHY; DIFFERENTIAL ACTIVATION AB Generation of arachidonic acid by the ubiquitously expressed cytosolic phospholipase A(2) (PLA(2)) has a fundamental role in the regulation of cellular homeostasis, inflammation and tumorigenesis. Here we report that cytosolic PLA(2) is a negative regulator of growth, specifically of striated muscle. We find that normal growth of skeletal muscle, as well as normal and pathologic stress-induced hypertrophic growth of the heart, are exaggerated in Pla2g4a(-/-) mice, which lack the gene encoding cytosolic PLA(2). The mechanism underlying this phenotype is that cytosolic PLA(2) negatively regulates insulin-like growth factor (IGF)-1 signaling. Absence of cytosolic PLA(2) leads to sustained activation of the IGF-1 pathway, which results from the failure of 3-phosphoinositide-dependent protein kinase (PDK)-1 to recruit and phosphorylate protein kinase C (PKC)-zeta, a negative regulator of IGF-1 signaling. Arachidonic acid restores activation of PKC-zeta, correcting the exaggerated IGF-1 signaling. These results indicate that cytosolic PLA(2) and arachidonic acid regulate striated muscle growth by modulating multiple growth-regulatory pathways. C1 Tufts Univ, Sch Med, Tufts New England Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. Boston Univ, Med Ctr, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Univ Cincinnati, Dept Pediat, Cincinnati, OH 45229 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Haq, S (reprint author), Tufts Univ, Sch Med, Tufts New England Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. OI Force, Thomas/0000-0002-0450-8659 FU NHLBI NIH HHS [HL61688, HL67371]; NIDDK NIH HHS [DK50282] NR 45 TC 59 Z9 60 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2003 VL 9 IS 7 BP 944 EP 951 DI 10.1038/nm891 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 698CD UT WOS:000183979300037 PM 12808451 ER PT J AU Freedman, SJ Sun, ZYJ Kung, AL France, DS Wagner, G Eck, MJ AF Freedman, SJ Sun, ZYJ Kung, AL France, DS Wagner, G Eck, MJ TI Structural basis for negative regulation of hypoxia-inducible factor-1 alpha by CITED2 SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID MELANOCYTE-SPECIFIC GENE; DNA-BINDING; TRANSCRIPTION FACTOR; O-2 HOMEOSTASIS; FACTOR 1-ALPHA; PROTEIN; RECOGNITION; HYDROXYLASE; TRANSACTIVATION; HIF-1-ALPHA AB Expression of hypoxia-responsive genes is mediated by the heterodimeric transcription factor hypoxia-inducible factor-1 (HIF-1) in complex with the p300/CREB-binding protein (p300/CBP) transcriptional coactivator. The protein CITED2, which binds p300/CBP, is thought to be a negative regulator of HIF-1 transactivation. We show that the CITED2 transactivation domain (TAD) disrupts a complex of the HIF-1alpha C-terminal TAD (C-TAD) and the cysteine-histidine rich 1 (CH1) domain of p300/CBP by binding CH1 with high affinity. The high-resolution solution structure of the CITED2 TAD p300 CH1 complex shows that the CITED2 TAD, like the HIF-1alpha C-TAD, folds on a helical, Zn2+-containing CH1 scaffold. The CITED2 TAD binds a different, more extensive surface of CH1 than does the HIF-1alpha C-TAD. However, a conserved 'LPXL' sequence motif in CITED2 and HIF-1alpha interacts with an overlapping binding site on CH1. Mutation of the LPEL sequence in full-length CITED2 abolishes p300 binding in vivo. These findings reveal that CITED2 regulates HIF-1 by competing for a hot spot on the p300 CH1 domain. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hemostasis & Thrombosis, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. Novartis Pharmaceut Corp, Dept Oncol, E Hanover, NJ 07936 USA. RP Eck, MJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA. NR 48 TC 121 Z9 124 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD JUL PY 2003 VL 10 IS 7 BP 504 EP 512 DI 10.1038/nsb936 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 694GZ UT WOS:000183767400008 PM 12778114 ER PT J AU Packard, SD Mandeville, JB Ichikawa, T Ikeda, K Terada, K Niloff, S Chiocca, EA Rosen, BR Marota, JJA AF Packard, SD Mandeville, JB Ichikawa, T Ikeda, K Terada, K Niloff, S Chiocca, EA Rosen, BR Marota, JJA TI Functional response of tumor vasculature to PaCO2: Determination of total and microvascular blood volume by MRI SO NEOPLASIA LA English DT Article DE glioma; vasculature; CO2 reactivity; cerebral blood volume; MRI ID CEREBRAL PLASMA-VOLUME; CARBON-DIOXIDE; BRAIN-TUMORS; IN-VIVO; PROPOFOL ANESTHESIA; GRADIENT-ECHO; RAT GLIOMA; CONTRAST; HYPERCAPNIA; FLOW AB In order to identify differences in functional activity, we compared the reactivity of glioma vasculature and the native cerebral vasculature to both dilate and constrict in response to altered PaCO2. Gliomas were generated by unilateral implantation of U87MGdEGFR human glioma tumor cells into the striatum of adult female athymic rats. Relative changes in total and microvascular cerebral blood volume were determined by steady state contrast agent-enhanced magnetic resonance imaging for transitions from normocarbia to hypercarbia and hypocarbia. Although hypercarbia induced a significant increase in both total and microvascular blood volume in normal brain and glioma, reactivity of glioma vasculature was significantly blunted in comparison to normal striatum; glioma total CBV increased by 0.6 +/- 0.1%/mm Hg CO2 whereas normal striatum increased by 1.5 +/- 0.2%/mm Hg CO2, (P<.0001, group t-test). Reactivity of microvascular blood volume was also significantly blunted. In contrast, hypocarbia decreased both total and microvascular blood volumes more in glioma than in normal striatum. These results indicate that cerebral blood vessels derived by tumor-directed angiogenesis do retain reactivity to CO2. Furthermore, reduced reactivity of tumor vessels to a single physiological perturbation, such as hypercarbia, should not be construed as a generalized reduction of functional activity of the tumor vascular bed. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH, NMR Ctr, Boston, MA 02114 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosurg Serv & Mol Neurooncol Labs, Boston, MA 02114 USA. RP Marota, JJA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,CLN 3, Boston, MA 02114 USA. NR 44 TC 22 Z9 23 U1 0 U2 2 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD JUL-AUG PY 2003 VL 5 IS 4 BP 330 EP 338 PG 9 WC Oncology SC Oncology GA 725DX UT WOS:000185529200006 PM 14511404 ER PT J AU Lin, CP Wedeen, VJ Chen, JH Yao, C Tseng, WYI AF Lin, CP Wedeen, VJ Chen, JH Yao, C Tseng, WYI TI Validation of diffusion spectrum magnetic resonance imaging with manganese-enhanced rat optic tracts and ex vivo phantoms SO NEUROIMAGE LA English DT Article DE diffusion spectrum; validation; Mn2+; MRI ID NARROW-PULSE APPROXIMATION; RESTRICTED DIFFUSION; HUMAN BRAIN; FIELD-GRADIENT; WEIGHTED MRI; AXONAL PROJECTIONS; NMR DIFFRACTION; POROUS-MEDIA; SPIN ECHOES; TENSOR AB Diffusion spectrum imaging (DSI) has been demonstrated to resolve crossing axonal fibers by mapping the probability density function of water molecules diffusion at each voxel. However, the accuracy of DSI in defining individual fiber orientation and the validity of Fourier relation under finite gradient pulse widths are not assessed yet. We developed an ex vivo and an in vivo model to evaluate the error of DSI with gradient pulse widths being relatively short and long, respectively. The ex vivo model was a phantom comprising sheets of parallel capillaries filled with water. Sheets were stacked on each other with capillaries crossed at 45degrees or 90degrees. High-resolution T2-weighted images (T2W1) of the phantom served as a reference for the orientation of intersecting capillaries. In the in vivo model, manganese ions were infused into rats' optic tracts. The optic tracts were enhanced on T1-weighted images (T1WI) and served as a reference for the tract orientation. By comparing DSI with T2WI, the deviation angles between the primary orientation of diffusion spectrum and the 90degrees and 45degrees phantoms were 1.19degrees +/- 4.82degrees and -0.71degrees +/- 4.91degrees, respectively. By comparing DSI with the T1WI of rat optic tracts, the deviation angle between primary orientation of diffusion spectrum and optic tracts was -0.41degrees +/- 6.18degrees. In addition, two sequences of DSI using short and long gradient pulses were performed in a rat brain. The bias of the primary orientation between these two sequences was approximately 10degrees. In conclusion, DSI can resolve crossing fiber orientation accurately. The effect of finite gradient pulse widths on the primary orientation is not critical. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Natl Taiwan Univ, Coll Med, Ctr Optoelect Biomed, Taipei 10018, Taiwan. Natl Taiwan Univ Hosp, Coll Med, Dept Radiol, Taipei, Taiwan. Natl Taiwan Univ, Dept Elect Engn, Interdisciplinary MRI MRS Lab, Taipei 10764, Taiwan. Natl Taiwan Univ, Inst Biomed Engn, Taipei, Taiwan. Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Boston, MA 02114 USA. Natl Hlth Res Inst, Div Med Engn Res, Taipei, Taiwan. RP Chen, JH (reprint author), Natl Taiwan Univ, Coll Med, Ctr Optoelect Biomed, Taipei 10018, Taiwan. RI Yao, Ching /E-3978-2010; OI Tseng, Wen-Yih Isaac/0000-0002-2314-6868 FU NIMH NIH HHS [MH64044] NR 42 TC 116 Z9 120 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL PY 2003 VL 19 IS 3 BP 482 EP 495 DI 10.1016/S1053-8119(03)00154-X PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 706ZR UT WOS:000184485400002 PM 12880782 ER PT J AU Chen, NK Dickey, CC Yoo, SS Guttman, CRG Panych, LP AF Chen, NK Dickey, CC Yoo, SS Guttman, CRG Panych, LP TI Selection of voxel size and slice orientation for fMRI in the presence of susceptibility field gradients: application to imaging of the amygdala SO NEUROIMAGE LA English DT Article ID FUNCTIONAL MRI; FACIAL EXPRESSIONS; ARTIFACTS; ACTIVATION; COMPENSATION; INHOMOGENEITIES; ACQUISITION; REDUCTION; REMOVAL; PULSES AB The impact of voxel geometry on the blood oxygenation level-dependent (BOLD) signal detectability in the presence of field inhomogeneity is assessed and a quantitative approach to selecting appropriate voxel geometry is developed in this report. Application of the developed technique to BOLD sensitivity improvement of the human amygdala is presented. Field inhomogeneity was measured experimentally at 1.5 T and 3 T and the dominant susceptibility field gradient in the human amygdala was observed approximately along the superior-inferior direction. Based on the field mapping studies, an optimal selection for the slice orientation would be an oblique pseudo-coronal plane with its frequency-encoding direction parallel to the field gradient measured from each subject. Experimentally this was confirmed by comparing the normalized standard deviation of time-series echo-planar imaging signals acquired with different slice orientations. in the absence of a functional stimulus. A further confirmation with a carefully designed functional magnetic resonance imaging study is needed. Although the BOLD sensitivity may generally be improved by a voxel size commensurable with the activation volume, our quantitative analysis shows that the optimal voxel size also depends on the susceptibility field gradient and is usually smaller than the activation volume. The predicted phenomenon is confirmed with a hybrid simulation, in which the functional activation was mathematically added to the experimentally acquired rest-period echo-planar imaging data. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Imaging, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Brigham Behav Neurol Grp, Boston, MA 02115 USA. VA Boston Healthcare Syst, Brockton Div, Brockton, MA USA. RP Panych, LP (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. RI Chen, Nan-kuei/E-7791-2016 OI Chen, Nan-kuei/0000-0001-6564-4219 FU NINDS NIH HHS [R01-NS37922] NR 29 TC 53 Z9 55 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL PY 2003 VL 19 IS 3 BP 817 EP 825 DI 10.1016/S1053-8119(03)00091-0 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 706ZR UT WOS:000184485400030 PM 12880810 ER PT J AU Alpert, NM Badgaiyan, RD Livni, E Fischman, AJ AF Alpert, NM Badgaiyan, RD Livni, E Fischman, AJ TI A novel method for noninvasive detection of neuromodulatory changes in specific neurotransmitter systems SO NEUROIMAGE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; STRIATAL DOPAMINE RELEASE; RECEPTOR BINDING; C-11 RACLOPRIDE; PET; PERFORMANCE; ACTIVATION; ATTENTION; DISEASE; INFUSION AB Over the last decade. it has become possible to study theories of cognition using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). These methods yield statistical parametric maps of changes in cerebral blood flow (CBF) elicited by cognitive tasks. A limitation of these studies is that they provide no information about the underlying neurochemistry. However, it is possible to extend the concept of activation studies to include measurements targeting neurotransmitters and specific receptor populations. Cognitive activation increases neuronal firing rate, increasing the endogenous neurotransmitter level. The increased neurotransmitter level can be used to alter the kinetics of specifically bound radioligands. We describe a new approach to the design and analysis of neuromodulation experiments. This approach uses PET, a single-scan session design. and a linear extension of the simplified reference region model (LSSRM) that accounts for changes in ligand binding induced by cognitive tasks or drug challenge. In the LSSRM, an "activation" parameter is included that represents the presence or absence of change in apparent dissociation rate. Activation of the neurotransmitter is detected statistically when the activation parameter is shown to violate the null hypothesis. Simulation was used to explore the properties of the LSSRM with regard to model identifiability, effect of statistical noise, and confounding effects of CBF-related changes. Simulation predicted that it is possible to detect and map neuromodulatory changes in single-subject designs. A human study was conducted to confirm the predictions of simulation using C-11-raclopride and a motor planning task. Parametric images of transport, binding potential, areas of significant dopamine release, and statistical parameters were computed. Examination of the kinetics of activation demonstrated that maximum dopamine release occurred immediately following task initiation and then decreased with a half-time of about 3 min. This method can be extended to explore neurotransmitter involvement in other behavioral and cognitive domains. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. RP Alpert, NM (reprint author), Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. FU NCI NIH HHS [T32CA09362] NR 36 TC 68 Z9 68 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL PY 2003 VL 19 IS 3 BP 1049 EP 1060 DI 10.1016/S1053-8119(03)00186-1 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 706ZR UT WOS:000184485400051 PM 12880831 ER PT J AU Davalos, DB Kisley, MA Polk, SD Ross, RG AF Davalos, DB Kisley, MA Polk, SD Ross, RG TI Mismatch negativity in detection of interval duration deviation in schizophrenia SO NEUROREPORT LA English DT Article DE interval discrimination; MMN; schizophrenia; time perception ID EVENT-RELATED POTENTIALS; TIME-ESTIMATION; AUDITORY-STIMULI; ATTENTION; DEFICITS; ERPS AB Temporal processing deficits have been noted in behavioral studies assessing patients with schizophrenia. The current study sought to explore the physiology of temporal perception while controlling the effects of motivation, attention and other cognitive processes that may contribute to behavioral measures of temporal processing. Mismatch negativity (MMN) waveforms were measured in response to variations in the temporal parameters of an ongoing train of pure tones. A standard inter-stimulus interval of 400 ms was interrupted, on average, every 20th tone by an inter-stimulus interval of 340 ms. Amplitude of MMN waveform elicited by the temporal deviance was significantly reduced in the schizophrenia group compared with controls (p=0.016). Results suggest that behavioral difficulties on time processing tasks in schizophrenia may reflect a physiological deficit in temporal perception in this population rather than simply more general difficulties in attention or motivation. C1 Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO 80262 USA. Univ Colorado, Colorado Springs, CO 80907 USA. RP Davalos, DB (reprint author), Univ Colorado, Hlth Sci Ctr, 4200 E 9th Ave,Campus Box C268-71, Denver, CO 80262 USA. FU NIMH NIH HHS [MH56539, MH152442] NR 25 TC 29 Z9 30 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 1 PY 2003 VL 14 IS 9 BP 1283 EP 1286 DI 10.1097/01.wnr.0000081874.45938.98 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 707AC UT WOS:000184486400019 PM 12824776 ER PT J AU Tan, TC Black, PM AF Tan, TC Black, PM TI Image-guided craniotomy for cerebral metastases: Techniques and outcomes SO NEUROSURGERY LA English DT Article DE craniotomy; image-guided surgery; metastases; neurosurgical outcomes; recursive partitioning analysis classes ID PARTITIONING ANALYSIS RPA; BRAIN METASTASES; SURGICAL-TREATMENT; PROGNOSTIC FACTORS; NEUROSURGICAL PROCEDURES; TRACKING SYSTEM; SURGERY; RESECTION; TUMORS; RADIOSURGERY AB OBJECTIVE: The purpose of the present study was to analyze the outcomes after craniotomies for brain metastases in a modern series using image-guided technologies either in the regular operating room or in the intraoperative magnetic resonance imaging unit. METHODS: Neurosurgical outcomes were analyzed for 49 patients who underwent 55 image-guided craniotomies for excision of brain metastases during a 5-year period. Tumors were located in critical and noncritical function regions of the brain. A total of 23 craniotomies for tumors in critical brain were performed using intravenous sedation anesthesia; craniotomies for noncritical function brain regions were completed under general anesthesia. The patients were also divided into Radiation Therapy Oncology Group recursive partitioning analysis (RPA) classes on the basis of age, Karnofsky Performance Scale scores, state of primary disease, and presence or absence-of extracranial metastases. RESULTS: There was no perioperative mortality. Gross total resection, as verified by postoperative contrast-enhanced computed tomography or magnetic resonance imaging, was achieved in 96% of patients. The median anesthesia time was 4.25 hours, and the median length of hospital stay was 3 days. In 51 symptomatic cases, there was complete resolution of symptoms in 70% (n = 36), improvement in 14% (n = 7), and no change in 12% (n = 6) postoperatively. No patient who was neurologically intact preoperatively deteriorated after surgery, and 93% of patients maintained or improved their functional status. Only two patients (3.6%) with significant preoperative deficits had increased long-term deficits postoperatively. The mean follow-up was 1 year, and the local recurrence rate was 16%. The median survival of the entire group was 16.23 months (17.5 mo in RPA Class I, 22.9 mo in RPA Class II, and 9.8 mo in RPA Class III). CONCLUSION: Gross total resection of brain metastases, including those involving critical function areas, can be safely achieved with a low morbidity rate using contemporary image-guided systems. RPA Class I and II patients with controlled primary disease benefit from aggressive treatment by surgery and radiation. C1 Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Dept Surg, Sch Med, Cambridge, MA 02138 USA. Queen Elizabeth Hosp, Dept Neurosurg, Kowloon, Hong Kong, Peoples R China. Dana Farber Canc Inst, Neurosurg Serv, Boston, MA 02115 USA. RP Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA. EM peter_black@hms.harvard.edu NR 51 TC 30 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUL PY 2003 VL 53 IS 1 BP 82 EP 89 DI 10.1227/01.NEU.0000068729.37362.F9 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 698FX UT WOS:000183988600017 PM 12823876 ER PT J AU Zhong, S Li, C Wong, WH AF Zhong, S Li, C Wong, WH TI ChipInfo: software for extracting gene annotation and gene ontology information for microarray analysis SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EXPRESSION AB To date, assembling comprehensive annotation information for all probe sets of any Affymetrix microarrays remains a time-consuming, error-prone and challenging task. ChipInfo is designed for retrieving annotation information from online databases such as NetAffx and Gene Ontology and organizing such information into easily interpretable tabular format outputs. As companion software to dChip and GoSurfer, ChipInfo enables users to independently update the information resource files of these software packages. It also has functions for computing related summary statistics of probe sets and Gene Ontology terms. ChipInfo is available at http://biosun1.harvard.edu/complab/chipinfo/. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Ctr Sci, Dept Stat, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Li, C (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. EM cli@hsph.harvard.edu; wwong@stat.harvard.edu FU NCI NIH HHS [P20 CA096470, P20 CA96470]; NHGRI NIH HHS [1R01HG02341, R01 HG002341] NR 11 TC 76 Z9 78 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 JUL 1 PY 2003 VL 31 IS 13 BP 3483 EP 3486 DI 10.1093/nar/gkg598 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 695LT UT WOS:000183832900041 PM 12824349 ER PT J AU Mazer, NA Shifren, JL AF Mazer, NA Shifren, JL TI Transdermal testosterone for women: A new physiological approach for androgen therapy SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Article ID METABOLIC-CLEARANCE RATE; HYPOGONADAL MEN; DELIVERY SYSTEMS; PHARMACOKINETICS; ESTRADIOL; CONVERSION; EFFICACY; SAFETY; MATRIX; GEL AB Transdermal testosterone patches and topically applied gels have become well accepted for the treatment of testosterone deficiency in men and are currently being developed in appropriate dosage strengths for androgen therapy in women. The furthest developed among these products is an investigational testosterone matrix patch which is now in phase III clinical trials for the treatment of sexual dysfunction in oophorectomized and naturally menopausal women. This review article discusses the biopharmaceutical rationale for the transdermal delivery of testosterone to women, illustrates and quantitatively analyzes the pharmacokinetics and metabolism of the testosterone matrix patch and a recently investigated testosterone gel, and summarizes the efficacy and safety data that have been reported in phase II studies of the testosterone matrix patch in surgically menopausal women with sexual dysfunction and HIV-infected women with the AIDS wasting syndrome. The different effects of oral and transdermal estrogen therapy (ET) on the concentrations of total and free testosterone attained with the testosterone matrix patch are contrasted. Although still in development, transdermal testosterone therapy appears to be a promising new approach for providing physiologically based androgen therapy to women. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to list the biopharmaceutical rationale for developing the testosterone transdermal delivery system, to describe the pharmacokinetics and metabolism of testosterone transdermal delivery systems in women, and to illustrate the influence of concomitant estrogen therapy on testosterone concentrations attained with the transdermal delivery system. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Menopause Program, Boston, MA 02114 USA. Univ Utah, Dept Pharmaceut, Salt Lake City, UT USA. NR 40 TC 15 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD JUL PY 2003 VL 58 IS 7 BP 489 EP 500 DI 10.1097/01.OGX.0000078485.98636.16 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 697EC UT WOS:000183928400004 PM 12832941 ER PT J AU Kocher, MS Klingele, K Rassman, SO AF Kocher, MS Klingele, K Rassman, SO TI Meniscal disorders - Normal, discoid, and cysts SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article ID TERM FOLLOW-UP; LATERAL-MENISCUS; HUMAN KNEE; ARTHROSCOPIC EVALUATION; AVASCULAR ZONE; CHILDREN; MENISCECTOMY; REPAIR; ADOLESCENTS; EXCISION AB Understanding the functional importance of menisci has been evolutionary. In 1897, Bland-Sutton characterized the menisci as "functionless remnants of intra-articular leg muscles" [1]. This sentiment was highly regarded through the 1970s, and menisci routinely were completely excised despite data from Fairbanks who, in 1948, published the first long-term follow-up of patients after total menisectomy [2]. His article warned that radiographic evidence of degenerative changes followed menisectomy in a substantial proportion of patients. Several reports have since established the deleterious consequences of total and even partial menisectomy [3-13]. Nowhere are these sequelae more important than in children and adolescents in whom long-term effects of menisectomy are magnified by activity level and longevity. C1 Harvard Univ, Sch Med, Dept Orthopaed Surg, Div Sports Med,Childrens Hosp, Boston, MA 02115 USA. Columbus Childrens Hosp, Dept Orthoped Surg, Gahanna, OH 43230 USA. Massachusetts Gen Hosp, Harvard Combined Orthoped Residency Program, Boston, MA 02115 USA. RP Kocher, MS (reprint author), Harvard Univ, Sch Med, Dept Orthopaed Surg, Div Sports Med,Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. NR 62 TC 21 Z9 24 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0030-5898 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD JUL PY 2003 VL 34 IS 3 BP 329 EP + DI 10.1016/S0030-5898(03)00008-7 PG 13 WC Orthopedics SC Orthopedics GA 706ZQ UT WOS:000184485300002 PM 12974483 ER PT J AU McGibbon, CA Trahan, CA AF McGibbon, CA Trahan, CA TI Measurement accuracy of focal cartilage defects from MRI and correlation of MRI graded lesions with histology: a preliminary study SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE cartilage defects; arthritis; histology; MRI ID SPIN-ECHO MR; ARTICULAR-CARTILAGE; HYALINE CARTILAGE; KNEE; ARTHROSCOPY; THICKNESS; ABNORMALITIES; SEQUENCES; OSTEOARTHRITIS; SATURATION AB Objectives: Although accurate spatial measurement of cartilage thickness from MRI is possible, no studies have assessed the accuracy of measuring cartilage defect dimensions from MRI. In addition, current MR grading scales for assessing cartilage lesions have limited categories, and little is known about how well these scales correlate with histological assessment of the lesion. The objective of this preliminary study is to address both these issues. Methods: We performed two experiments on four cadaver knee joints from elderly donors: Experiment 1 assessed the accuracy of measuring controlled defects in cartilage, and Experiment 2 compared MRI grading (Noyes scale) of natural cartilage lesions to histological grading (Mankin scale) of the sectioned cartilage tissue. MRI was performed on 1.5 T clinical scanner (fat-suppressed 3D-SPGR at TRITE/alpha=55/13.5/45 and 256x256 matrix). Results: The mean difference between defect diameters measured and introduced was less than 0.1 mm, which was statistically insignificant (P=0.754). Defect depth was less accurate at >0.4 mm, significantly under predicting actual defect depth (P=0.004). Correlation between Noyes grading scores and Mankin grading scores of natural lesions was moderately high (r=0.7) and statistically significant (P=0.001). Conclusions: Three-dimensional mapping of cartilage thickness shows great promise for the accurate measurement of focal cartilage defects, though improvement is needed. The Noyes grading scale is consistent with histological Mankin grading of cartilage lesions, though enhancement of MR grading scales is needed, and warranted, based on the signal intensity information available from clinical MRI. Integration of these two analyses-focal defect measurement and signal intensity analysis-could potentially result in a valuable clinical tool for early osteoarthritis diagnosis and longitudinal tracking. (C) 2003 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Orthopaed, Biomot Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed, Orthopaed Res Lab, Boston, MA 02114 USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Biomot Lab, 55 Fruit St,Ruth Sleeper Hall,Room 010, Boston, MA 02114 USA. FU NIAMS NIH HHS [R01 AR45278] NR 37 TC 51 Z9 55 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD JUL PY 2003 VL 11 IS 7 BP 483 EP 493 DI 10.1016/S1063-4584(03)00078-5 PG 11 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 693JC UT WOS:000183713000003 PM 12814611 ER PT J AU Merchant, S Rosowski, JJ AF Merchant, S Rosowski, JJ TI Biomechanics of stapesplasty: A review - Comment SO OTOLOGY & NEUROTOLOGY LA English DT Editorial Material ID STAPEDECTOMY; STAPEDOTOMY; DIAMETER C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Merchant, S (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JUL PY 2003 VL 24 IS 4 BP 557 EP 559 PG 3 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 702YR UT WOS:000184253100005 ER PT J AU McGhan, LJ Merchant, SN AF McGhan, LJ Merchant, SN TI Temporal bone histopathology case of the month - Erythromycin ototoxicity SO OTOLOGY & NEUROTOLOGY LA English DT Article ID SENSORINEURAL HEARING-LOSS; LACTOBIONATE C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol,Otopathol Lab, Boston, MA 02114 USA. RP Merchant, SN (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol,Otopathol Lab, 243 Charles St, Boston, MA 02114 USA. NR 10 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JUL PY 2003 VL 24 IS 4 BP 701 EP 702 DI 10.1097/00129492-200307000-00029 PG 2 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 702YR UT WOS:000184253100035 PM 12851569 ER PT J AU Jung, BF Ahrendt, GM Oaklander, AL Dworkin, RH AF Jung, BF Ahrendt, GM Oaklander, AL Dworkin, RH TI Neuropathic pain following breast cancer surgery: proposed classification and research update SO PAIN LA English DT Review DE neuropathic pain; phantom breast pain; intercostobrachial neuralgia; post-mastectomy pain; neuroma pain; breast cancer; mastectomy; lumpectomy ID PHANTOM LIMB PAIN; POSTHERPETIC NEURALGIA; POSTMASTECTOMY PAIN; AXILLARY DISSECTION; TOPICAL CAPSAICIN; RANDOMIZED-TRIAL; MORBIDITY; MASTECTOMY; SYMPTOMS; WOMEN C1 Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Surg, Rochester, NY 14642 USA. Harvard Univ, Sch Med, Nerve Injury Unit, Dept Anesthesiol Neurol & Pathol,Mass Gen Hosp, Boston, MA USA. RP Dworkin, RH (reprint author), Univ Rochester, Sch Med & Dent, Dept Anesthesiol, 601 Elmwood Ave,Box 604, Rochester, NY 14642 USA. FU NINDS NIH HHS [NS 42866] NR 77 TC 149 Z9 153 U1 3 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL PY 2003 VL 104 IS 1-2 BP 1 EP 13 DI 10.1016/S0304-3959(03)00241-0 PG 13 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 703CP UT WOS:000184262700001 PM 12855309 ER PT J AU Kohane, DS Smith, SE Louis, DN Colombo, G Ghoroghchian, P Hunfeld, NGM Berde, CB Langer, R AF Kohane, DS Smith, SE Louis, DN Colombo, G Ghoroghchian, P Hunfeld, NGM Berde, CB Langer, R TI Prolonged duration local anesthesia from tetrodotoxin-enhanced local anesthetic microspheres SO PAIN LA English DT Article DE tetrodotoxin; local anesthesia; nerves ID SCIATIC-NERVE BLOCKADE; PROTEIN-SUGAR PARTICLES; IN-VIVO; BUPIVACAINE; MYOTOXICITY; SAXITOXIN AB There is interest in developing prolonged duration local anesthesics. Here we examine whether tetrodotoxin (TTX) can be used to prolong the block from bupivacaine microspheres with and without dexamethasone. Rats received sciatic nerve blocks with 75 mg of microspheres containing 0.05% (w/w) TTX, 50% (w/w) bupivacaine and/or 0.05% (w/w) dexamethasone. 0.1% (w/w) TTX microspheres were also tested. The carrier fluid contained 1:100,000 epinephrine. Nociceptive and motor blockade of the hindpaw were quantified. Nerves and adjacent muscles were harvested 2 weeks after injection for histological assessment by light microscopy. The median nociceptive block duration in hours from the microsphere groups were: bupivacaine = 6.2, 0.05% TTX = 0, bupivacaine + TTX = 35.3, bupivacaine + dexamethasone = 31.3, TTX + dexamethasone = 8.1, TTX + bupivacaine + dexamethasone = 221.7. Some animals receiving particles containing 0.05% TTX had deficits in the uninjected extremity; all animals receiving 0.1% (w/w) TTX particles died. Pockets of particles were associated with localized inflammation, and all samples showed some evidence of myotoxicity in the vicinity of the injection. The nerves themselves appeared intact. In summary, coencapsulation of TTX in controlled release devices containing bupivacaine and dexamethasone resulted in very prolonged nerve blocks. As formulated here, this preparation had a narrow margin of safety. While the myotoxicity appears consistent with the well-known reversible myotoxicity associated with local anesthetics, its long-term significance remains to be established. (C) 2003 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. MIT, Boston, MA USA. Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. Univ Parma, Dept Pharmaceut, I-43100 Parma, Italy. Univ Penn, Philadelphia, PA 19104 USA. Univ Utrecht, Dept Biopharm & Pharmaceut Technol, Utrecht, Netherlands. RP Langer, R (reprint author), MIT, Dept Chem Engn, Bldg E25-342,45 Carleton St, Cambridge, MA 02139 USA. RI Colombo, Gaia/G-6837-2012 OI Colombo, Gaia/0000-0001-9033-2305 FU NIGMS NIH HHS [GM26698, GM00684] NR 17 TC 64 Z9 65 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL PY 2003 VL 104 IS 1-2 BP 415 EP 421 DI 10.1016/S0304-3959(03)00049-6 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 703CP UT WOS:000184262700044 PM 12855352 ER PT J AU Sepucha, KR Mulley, AG AF Sepucha, KR Mulley, AG TI Extending decision support: preparation and implementation SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE shared decision-making; decision aid; decision quality ID CANCER-PATIENTS; COMMUNICATION; PHYSICIANS; MODEL; CARE; AIDS AB The shift towards patient-centered care requires innovative, flexible decision-making models. Current decision aids provide information and help patients clarify values. By focusing almost exclusively on these two components, the aids miss some necessary elements that can improve decision quality. We discuss two such elements in this paper. First is avoiding the tendency to move into providing information about options and outcomes before adequate preparation. The second is the tendency to neglect to provide adequate implementation support. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Hlth Decis Res Unit, Boston, MA 02114 USA. RP Sepucha, KR (reprint author), Massachusetts Gen Hosp, Hlth Decis Res Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA. NR 19 TC 13 Z9 13 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JUL PY 2003 VL 50 IS 3 BP 269 EP 271 DI 10.1016/S0738-3991(03)00048-X PG 3 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 717PF UT WOS:000185098000009 PM 12900098 ER PT J AU Drapkin, RI Genest, DR Holmes, LB Huang, TS Vargas, SO AF Drapkin, RI Genest, DR Holmes, LB Huang, TS Vargas, SO TI Unilateral transverse arm defect with subterminal digital nubbins SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY LA English DT Article DE acheiria; congenital anomaly; congenital limb deformity; limb deficiency; limb reduction defect; nubbins ID HOLT-ORAM-SYNDROME; VERTEBRATE LIMB DEVELOPMENT; REDUCTION DEFECTS; PATTERN-FORMATION; FIRST-TRIMESTER; MUTATIONS; CALCIFICATION; ABNORMALITIES; MISOPROSTOL; PREGNANCY AB We present a case of unilateral terminal transverse forearm deficiency with subterminal digit-like nubbins, identified in a fetus from a pregnancy terminated electively in the second trimester because the distal right arm and hand could not be seen by ultrasound and were presumed to be absent. Pathologic evaluation showed distal transverse shortening, tapering to a point in the mid-forearm. Five primitive digital nubbins were present, located just proximal to the tapered point. The arm vessels appeared normal histologically, and the amnion showed no evidence of intrauterine disruption. Histologic examination of the nubbins revealed osteocartilaginous tissue, never described previously within digital nubbins. This fetus has the rare phenotype of terminal transverse limb defects with residual nubbins, but differs in that the nubbins are not at the tip of the terminal transverse limb defect. C1 Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. Childrens Hosp, Div Genet & Metab, Boston, MA 02115 USA. RP Vargas, SO (reprint author), Childrens Hosp, Dept Pathol, 300 Longwood Ave, Boston, MA 02115 USA. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 41 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1093-5266 J9 PEDIATR DEVEL PATHOL JI Pediatr. Dev. Pathol. PD JUL-AUG PY 2003 VL 6 IS 4 BP 348 EP 354 DI 10.1007/s10024-002-0112-z PG 7 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 724KJ UT WOS:000185486500009 PM 14692649 ER PT J AU Ostrow, JD Pascolo, L Tiribelli, C AF Ostrow, JD Pascolo, L Tiribelli, C TI Reassessment of the unbound concentrations of unconjugated bilirubin in relation to neurotoxicity in vitro SO PEDIATRIC RESEARCH LA English DT Article ID DEVELOPING RAT-BRAIN; SERUM-ALBUMIN; OXIDATIVE STRESS; TOXICITY; NEURONS; ASTROCYTES; APOPTOSIS; BINDING; ENCEPHALOPATHY; INHIBITION AB Most studies of the cellular toxicity of unconjugated bilirubin (UCB) have been performed at concentrations of unbound UCB (B-F) that exceed those in the plasma of neonates with bilirubin encephalopathy. We assessed whether UCB could be toxic to neurons and astrocytes at clinically relevant B-F values (less than or equal to 1.0 muM), a range in which spontaneous precipitation of UCB would be unlikely to occur, even though B-F exceeded the aqueous saturation limit of 70 nM. A meta-analysis yielded twelve published studies that had determined the in vitro effects of UCB on the function of cultured neurons or astrocytes at calculable BF values less than or equal to 1.0 muM. B-F values were recalculated from the stated UCB, albumin, and chloride concentrations by applying affinity constants derived from ultrafiltration of comparable solutions containing C-14-UCB and delipidated human serum albumin. At B-F slightly above aqueous solubility, UCB impaired mitochondrial function and viability of astrocytes. Exposure of neuroblastoma and embryonic neuronal cell lines to B-F above 250 nM impaired cellular proliferation and mitochondrial function and increased apoptosis. Purified UCB inhibited the uptake of glutamate into astrocytes at B-F as low as 309 nM and induced apoptosis in brain neurons at B-F as low as 85 nM. UCB can impair various cellular functions of astrocytes and neurons exposed to BF near or modestly above its aqueous solubility limit, at which UCB exists as soluble oligomers and metastable micro-aggregates. The results render doubtful the long-held concept that precipitation of UCB in or on cells is required to produce neurotoxicity. C1 VA Puget Sound Hlth Care Syst, Seattle Div, Res Serv 151L, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, GI Hepatol Div, Seattle, WA 98195 USA. Univ Trieste, Liver Study Ctr, I-34012 Trieste, Italy. RP Ostrow, JD (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, Res Serv 151L, 1660 S Columbian Way, Seattle, WA USA. NR 46 TC 49 Z9 56 U1 0 U2 2 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 JUL PY 2003 VL 54 IS 1 BP 98 EP 104 DI 10.1203/01.PDR.0000067486.79854.D5 PG 7 WC Pediatrics SC Pediatrics GA 692YC UT WOS:000183687000017 PM 12646712 ER PT J AU Lipshultz, SE Somers, MJG Lipsitz, SR Colan, SD Jabs, K Rifai, N AF Lipshultz, SE Somers, MJG Lipsitz, SR Colan, SD Jabs, K Rifai, N TI Serum cardiac troponin and subclinical cardiac status in pediatric chronic renal failure SO PEDIATRICS LA English DT Article DE chronic renal failure; hemodialysis; pediatrics; troponin; cardiomyopathy; myocardial dysfunction; child; uremia; chronic renal insufficiency ID LEFT-VENTRICULAR CONTRACTILITY; UREMIC CARDIOMYOPATHY; DIASTOLIC FUNCTION; YOUNG-ADULTS; HEMODIALYSIS-PATIENTS; MYOCARDIAL-FUNCTION; SODIUM-BICARBONATE; DIALYSIS PATIENTS; SKELETAL-MUSCLE; IN-VITRO AB Background. Patients with uremia often have elevated serum cardiac troponin T (cTnT) even without clinical heart damage. Pediatric patients are ideal for studies of the relationship between uremia and heart disease because they are unlikely to have cardiac risk factors other than uremia. Objective. To determine the relationship between uremia and cTnT levels. Design. Echocardiograms and blood chemistry results were obtained from 50 pediatric patients with chronic renal failure and without clinical heart disease. Levels of cTnT were tested for correlation with cardiac dysfunction. In multivariate analysis, biochemical aspects of renal disease and its treatment were tested for correlation with cardiac dysfunction. Results. Forty-nine patients had cardiovascular abnormalities, including increased left ventricular function and mass, elevated heart rate and blood pressure, and reduced LV afterload. LV contractility was inversely correlated with cTnT level (r = -0.36). Higher cTnT also correlated with higher serum creatine kinase-MB mass, lower serum parathyroid hormone, higher blood urea nitrogen and bicarbonate levels, and the use of diuretics, but not with higher cardiac troponin I. Left ventricular contractility was inversely related to serum creatinine, phosphorus, and the use of beta-blockers. Conclusions. Elevated cTnT levels are not artifactual, but are genuine indicators of cardiomyocyte damage. Cardiac damage, indicated by either elevated cTnT or low LV contractility, is related to uremia, deranged calcium and phosphorus metabolism, and bicarbonate levels. Serum cTnT and LV contractility identify subclinical cardiac damage that could be treated to hopefully reduce cardiovascular morbidity and mortality in this high-risk population. C1 Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Nephrol, Boston, MA 02115 USA. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Golisano Childrens Hosp Strong, Div Pediat Cardiol, Rochester, NY USA. Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. Vanderbilt Childrens Hosp, Div Nephrol, Nashville, TN USA. Univ Rochester, Med Ctr, Div Pediat Cardiol, Rochester, NY 14642 USA. RP Lipshultz, SE (reprint author), Univ Rochester, Med Ctr, Div Pediat Cardiol, 601 Elmwood Ave,Box 631, Rochester, NY 14642 USA. FU NCI NIH HHS [CA68484, CA06516, CA34183]; NHLBI NIH HHS [HL69800, HL48012] NR 52 TC 26 Z9 29 U1 0 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 2003 VL 112 IS 1 BP 79 EP 86 DI 10.1542/peds.112.1.79 PG 8 WC Pediatrics SC Pediatrics GA 696WR UT WOS:000183911000028 PM 12837871 ER PT J AU McMillen, RC Winickoff, JP Klein, JD Weitzman, M AF McMillen, RC Winickoff, JP Klein, JD Weitzman, M TI US adult attitudes and practices regarding smoking restrictions and child exposure to environmental tobacco smoke: Changes in the social climate from 2000-2001 SO PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies CY APR 29-MAY 13, 2001 CL BALTIMORE, MARYLAND SP Pediatr Acad Soc DE tobacco smoke pollution/prevention and control; child; adult ID CIGARETTE-SMOKING; PARENTAL SMOKING; SUBSTANCE-ABUSE; UNITED-STATES; PEDIATRICIAN; RESTAURANTS; ADOLESCENTS; CALIFORNIA; POPULATION; PREVENTION AB Objective. A substantial proportion of homes and automobiles serve as settings for environmental tobacco smoke (ETS) exposure, and many public settings that children frequent are still not smoke-free. Tobacco control efforts are attempting to increase smoking bans. The objective of this study was to describe the knowledge, attitudes, and practices of smokers and nonsmokers regarding smoking bans and child ETS exposure in multiple public and private settings and to report changes from 2000-2001. Methods. Cross-sectional data from the annual Social Climate Survey of Tobacco Control were analyzed for changes in knowledge, attitudes, and practices regarding tobacco. These data were collected via automated, random-digit-dialing telephone surveys that were conducted in the summers of 2000 and 2001. The samples were weighted by race and gender to be representative of the US population. Results. Response rates for eligible adults actually contacted were 1501 (75%) of 1876 in 2000 and 3002 (84%) of 3566 in 2001. The majority of adults, both smokers and nonsmokers, support smoking bans in a wide variety of places. The percentage of all respondents reporting the presence of smoking bans in several public and private places increased from 2000-2001: the household (69%-74%), in the presence of children (84%-88%), convenience stores (68%-74%), fast-food restaurants (52%-58%), and non-fast-food restaurants (25%-28%). Support for smoking bans also increased in shopping malls (71%-75%), fast-food restaurants (77%-80%), and indoor sporting events (78%-80%). There were no significant changes in support for smoking bans in convenience stores, restaurants, or outdoor parks. Adults' knowledge of the harm caused by tobacco was unchanged, with the vast majority of adults recognizing the dangers of exposure to ETS from parental smoking (95%) and exposure to ETS in cars (77%). Conclusions. Small improvements in adult attitudes and practices regarding children's ETS exposure occurred from 2000-2001. However, a significant number of adults in the United States still report ignorance of the harmful effects of child ETS exposure, and there was no improvement in reported knowledge in this 1-year period. In contrast, a growing majority of smokers and nonsmokers favor restrictions on smoking in public settings, suggesting that states and communities have public support for broad public smoking restriction policies. There are significant roles that pediatricians can play in preventing children's ETS exposure, through both patient and family education and by moving smoking restriction policies forward on their community's agenda. C1 Mississippi State Univ, Social Sci Res Ctr, Mississippi State, MS 39762 USA. Amer Acad Pediat, Ctr Child Hlth Res, Tobacco Consortium, Rochester, NY USA. MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Univ Rochester, Strong Childrens Res Ctr, Rochester, NY USA. RP McMillen, RC (reprint author), Mississippi State Univ, Social Sci Res Ctr, 103 Res Pk, Mississippi State, MS 39762 USA. RI McMillen, Robert/A-9326-2009; David, Maribel/E-2812-2012 FU PHS HHS [4 D1A RH 00005-01-01] NR 32 TC 56 Z9 57 U1 3 U2 8 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 JUL PY 2003 VL 112 IS 1 BP E55 EP E60 DI 10.1542/peds.112.1.e55 PG 6 WC Pediatrics SC Pediatrics GA 696WR UT WOS:000183911000010 PM 12837906 ER PT J AU Centorrino, F Albert, MJ Drago-Ferrante, G Koukopoulos, AE Berry, JM Baldessarini, RJ AF Centorrino, F Albert, MJ Drago-Ferrante, G Koukopoulos, AE Berry, JM Baldessarini, RJ TI Delirium during clozapine treatment: Incidence and associated risk factors SO PHARMACOPSYCHIATRY LA English DT Article DE anticholinergic; clozapine; delirium ID DRUG-INDUCED DELIRIUM; TOXIC DELIRIUM; CHLORPROMAZINE; PHYSOSTIGMINE; RISPERIDONE; MANAGEMENT; LORAZEPAM; EFFICACY; EEG AB Background: Incidence and risk factors for delirium during clozapine treatment require further clarification. Methods: We used computerized pharmacy records to identify all adult psychiatric inpatients treated with clozapine (1995-96), reviewed their medical records to score incidence and severity of delirium, and tested associations with potential risk factors. Results: Subjects (n = 139) were 72 women and 67 men, aged 40.8 +/- 12.1 years, hospitalized for 24.9 +/- 23.3 days, and given clozapine, gradually increased to an average daily dose of 282 +/- 203 mg (3.45 +/- 2.45 mg/kg) for 18.9 +/- 16.4 days. Delirium was diagnosed in 14 (10.1 % incidence, or 1.48 cases/person-years of exposure); 71.4 % of cases were moderate or severe. Associated factors were co-treatment with other centrally antimuscarinic agents, poor clinical outcome, older age, and longer hospitalization (by 17.5 days, increasing cost); sex, diagnosis or medical co-morbidity, and daily clozapine dose, which fell with age, were unrelated. Conclusions: Delirium was found in 10% of clozapine-treated inpatients, particularly in older patients exposed to other central anticholinergics. Delirium Was inconsistently recognized clinically in milder cases and was associated with increased length-of-stay and higher costs, and inferior clinical outcome. C1 Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Neurosci Program, Belmont, MA 02178 USA. Massachusetts Gen Hosp, McLean Div, Bipolar & Psychot Disorders Program, Belmont, MA USA. Int Consortium Bipolar Disorder Res, Belmont, MA USA. RP Centorrino, F (reprint author), McLean Hosp, Bipolar & Psychot Disorders Clin, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-47370] NR 40 TC 10 Z9 11 U1 2 U2 3 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0176-3679 J9 PHARMACOPSYCHIATRY JI Pharmacopsychiatry PD JUL PY 2003 VL 36 IS 4 BP 156 EP 160 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 717BK UT WOS:000185065600005 PM 12905102 ER PT J AU Zhuang, SA Kochevar, IE AF Zhuang, SA Kochevar, IE TI Ultraviolet A radiation induces rapid apoptosis of human leukemia if cells by Fas ligand-independent activation of the Fas death pathway SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID HUMAN SKIN FIBROBLASTS; OXYGEN-INDUCED APOPTOSIS; GROWTH-FACTOR RECEPTORS; CYTOCHROME-C RELEASE; PROTEIN-KINASE-C; SINGLET-OXYGEN; UVA RADIATION; HYDROGEN-PEROXIDE; CASPASE-3 ACTIVATION; HAIRLESS MICE AB Endogenous cellular chromophores absorb ultraviolet A radiation (UVA, 290-320 nm), the major UV component of terrestrial solar radiation, leading to the formation of reactive oxidizing species that initiate apoptosis, gene expression and mutagenesis. UVA-induced apoptosis of T helper cells is believed to underlie the UVA phototherapy for atopic dermatitis and other T cell-mediated inflammatory skin diseases. We have evaluated the involvement of the Fas-Fas ligand (FasL) pathway in rapid UVA-induced apoptosis in human leukemia HL-60 cells. UVA-induced apoptosis was not inhibited by pretreatment with a neutralizing anti-Fas antibody, although the same UVA treatment initiated cleavage of caspase-8 and subsequent processing of Bid and caspase-3-like proteases. Inhibition of caspase-8 by Lle-Glu (OMe)-Thr-Asp(OMe)-fluoromethyl ketone completely blocked caspase-3 cleavage and apoptosis in UVA-treated cells, suggesting that apoptosis was initiated by the Fas pathway. This inference was supported by demonstrating that immunoprecipitates obtained from UVA-treated cells using anti-Fas antibody contained caspase-8 and Fas-associating protein with death domain (FADD). In addition, Fas clustering in response to UVA treatment was observed by immunofluorescence microscopy. These data support a mechanism for rapid, UVA-induced apoptosis in HL-60 cells involving initial formation of the Fas-FADD-caspase-8 death complex in an FasL-independent manner. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Kochevar, IE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, WEL-224,55 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM30755] NR 43 TC 32 Z9 33 U1 0 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUL PY 2003 VL 78 IS 1 BP 61 EP 67 DI 10.1562/0031-8655(2003)078<0061:UARIRA>2.0.CO;2 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 701KE UT WOS:000184166100010 PM 12929750 ER PT J AU Ferrari, S Plotnikova, JM De Lorenzo, G Ausubel, FM AF Ferrari, S Plotnikova, JM De Lorenzo, G Ausubel, FM TI Arabidopsis local resistance to Botrytis cinerea involves salicylic acid and camalexin and requires EDS4 and PAD2, but not SID2, EDS5 or PAD4 SO PLANT JOURNAL LA English DT Article DE defense response; plant-pathogen interaction; Arabidopsis; Botrytis cinerea; salicylic acid; camalexin ID SYSTEMIC ACQUIRED-RESISTANCE; ENHANCED DISEASE SUSCEPTIBILITY; PHYTOALEXIN-DEFICIENT MUTANTS; PLANT DEFENSIN GENE; METHYL JASMONATE; ESSENTIAL COMPONENT; FUNGAL PATHOGENS; RESPONSES; THALIANA; INDUCTION AB Salicylic acid (SA) is an important regulator of plant defense responses, and a variety of Arabidopsis mutants impaired in resistance against bacterial and fungal pathogens show defects in SA accumulation, perception, or signal transduction. Nevertheless, the role of SA-dependent defense responses against necrotrophic fungi is currently unclear. We determined the susceptibility of a set of previously identified Arabidopsis mutants impaired in defense responses to the necrotrophic fungal pathogen Botrytis cinerea . The rate of development of B. cinerea disease symptoms on primary infected leaves was affected by responses mediated by the genes EIN2, JAR1, EDS4, PAD2, and PAD3, but was largely independent of EDS5, SID2 /ICS1, and PAD4 . Furthermore, plants expressing a nahG transgene or treated with a phenylalanine ammonia lyase (PAL) inhibitor showed enhanced symptoms, suggesting that SA synthesized via PAL, and not via isochorismate synthase (ICS), mediates lesion development. In addition, the degree of lesion development did not correlate with defensin or PR1 expression, although it was partially dependent upon camalexin accumulation. Although npr1 mutant leaves were normally susceptible to B. cinerea infection, a double ein2 npr1 mutant was significantly more susceptible than ein2 plants, and exogenous application of SA decreased B. cinerea lesion size through an NPR1-dependent mechanism that could be mimicked by the cpr1 mutation. These data indicate that local resistance to B. cinerea requires ethylene-, jasmonate-, and SA-mediated signaling, that the SA affecting this resistance does not require ICS1 and is likely synthesized via PAL, and that camalexin limits lesion development. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ Roma La Sapienza, Dipartimento Biol Vegetale, I-00185 Rome, Italy. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RI allasia, valerie/B-4214-2009; De Lorenzo, Giulia/F-5475-2013 OI De Lorenzo, Giulia/0000-0002-1707-5418 FU NIGMS NIH HHS [GM 48707] NR 48 TC 258 Z9 269 U1 7 U2 49 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0960-7412 J9 PLANT J JI Plant J. PD JUL PY 2003 VL 35 IS 2 BP 193 EP 205 DI 10.1046/j.1365-313X.2003.01794.x PG 13 WC Plant Sciences SC Plant Sciences GA 699EE UT WOS:000184042300005 PM 12848825 ER PT J AU Bergeron, BP AF Bergeron, BP TI Telemedicine in the practice setting - Infrastructure, not technology, limits practical application SO POSTGRADUATE MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bergeron, BP (reprint author), 27 Stearns Rd,8, Brookline, MA 02146 USA. EM bergeronbryan@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD JUL PY 2003 VL 114 IS 1 BP 9 EP + PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 835UD UT WOS:000222510100001 PM 12875053 ER PT J AU Solberg, LI Hollis, JA Stevens, VJ Rigotti, NA Quinn, VP Aickin, M AF Solberg, LI Hollis, JA Stevens, VJ Rigotti, NA Quinn, VP Aickin, M TI Does methodology affect the ability to monitor tobacco control activities? Implications for HEDIS and other performance measures SO PREVENTIVE MEDICINE LA English DT Article DE smoking cessation; questionnaires; counseling; health surveys; research design ID SMOKING CESSATION INTERVENTIONS; POPULATION-BASED SURVEY; NONRESPONSE BIAS; HEALTH; DEPENDENCE; PHYSICIANS; PATTERNS; SMOKERS AB Background. It is unclear whether methodological differences in sample size, survey methods, and analysis approach significantly affect the ability to accurately monitor tobacco control activities and to make rate comparisons. Methods. Questionnaires were sent to 64,764 members of nine health plans in diverse settings soon after their visit to a primary care clinician. Of these 41,677 completed responses were received. We compared responses received by mail and by telephone follow-up for the percentage of smokers, characteristics of smokers, and their rates of reporting physician cessation counseling. Results. Overall, 10.2% were current cigarette smokers, but the proportion was 8.6% for mail responders and 17.2% for phone follow-up responders. Smokers identified by phone follow-up were different from mail responders in most demographic and smoking characteristics and their reports of clinical smoking cessation activities differed for six of nine clinician smoking cessation actions. Calculating advice rates as a proportion of visits produced lower rates with more dispersion among plan rates than doing so without accounting for visit variation. Conclusions. Smoking surveys using only mailed questionnaires dramatically undersample smokers, especially in some demographic groups. Comparisons of tobacco counseling among health plans can be improved by ensuring an adequate sample size and response rate and by analyzing by frequency of quit advice. (C) 2003 American Health Foundation and Elsevier Science (USA). All rights reserved. C1 HealthPartners Res Fdn, Minneapolis, MN 55440 USA. Kaiser Permanente Ctr Hlth Res NW, Portland, OR USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Kaiser Permanente So Calif, Pasadena, CA USA. RP Solberg, LI (reprint author), HealthPartners Res Fdn, POB 1524, Minneapolis, MN 55440 USA. FU NCI NIH HHS [U19 CA79689] NR 33 TC 12 Z9 12 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL PY 2003 VL 37 IS 1 BP 33 EP 40 DI 10.1016/S0091-7435(03)00054-9 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 691VA UT WOS:000183625500005 PM 12799127 ER PT J AU Corey, E Quinn, JE Vessella, RL AF Corey, E Quinn, JE Vessella, RL TI A novel method of generating prostate cancer metastases from orthotopic implants SO PROSTATE LA English DT Article DE prostate cancer; prostate specific antigen; xenografts; metastasis ID NUDE-MICE; CELL-LINES; MODEL; LNCAP; BONE; PROGRESSION AB BACKGROUND. Spontaneous metastasis following implantation at the orthotopic site is a highly desired feature in prostate cancer (CaP) models, since it would enable studies of mechanisms associated with tumor cell dissemination. METHODS. LuCaP 23.8 and LuCaP 35, hormone-sensitive CaP xenografts that express PSA and the wild-type androgen receptor, were grown orthotopically in SCID mice. When tumor volumes reached similar to250-500 mg, primary tumors were removed to allow micrometastases to grow. RESULTS. Using this procedure we generated macroscopic metastases (>20 mg) in 71% (LuCaP 23.8) and 100% (LuCaP 35) of animals, respectively. CONCLUSIONS. These models may be used to evaluate new treatment modalities and study mechanisms associated with development of metastases. (C) 2003 Wiley-Liss, Inc. C1 Univ Washington, Dept Urol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Corey, E (reprint author), Univ Washington, Dept Urol, Mail Stop 356510,1959 NE Pacific St, Seattle, WA 98195 USA. FU NIDDK NIH HHS [2 P0 DK47656-08] NR 14 TC 19 Z9 22 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 0270-4137 J9 PROSTATE JI Prostate PD JUL 1 PY 2003 VL 56 IS 2 BP 110 EP 114 DI 10.1002/pros.10235 PG 5 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 693TC UT WOS:000183733600004 PM 12746835 ER PT J AU Bluman, LG Rimer, BK Sterba, KR Lancaster, J Clark, S Borstelmann, N Iglehart, JD Winer, EP AF Bluman, LG Rimer, BK Sterba, KR Lancaster, J Clark, S Borstelmann, N Iglehart, JD Winer, EP TI Attitudes, knowledge, risk perceptions and decision-making among women with breast and/or ovarian cancer considering testing for BRCA1 and BRCA2 and their spouses SO PSYCHO-ONCOLOGY LA English DT Article ID HUNTINGTON-DISEASE; HEREDITARY BREAST; SUSCEPTIBILITY; IMPACT; FAMILY; PATIENT; TRIAL AB A limited number of studies have examined the involvement of spouses in the decision-making process for genetic testing as well as impact of the actual testing. This report presents data from 40 women with a personal history of breast and/or ovarian cancer who were considering genetic testing for BRCA1 and BRCA2 and their spouses. We examined knowledge and attitudes regarding genetic testing for breast cancer susceptibility, perceptions of the likelihood that their wives (the women) had a BRCA1 or BRCA2 mutation, pros and cons of genetic testing, spouses' satisfaction with their involvement in the decision-making process and additional resources they would find helpful. Knowledge about cancer genetics and genetic testing for BRCA1 and BCA2 was limited among both women and their spouses. Up to one-third of spouses indicated that they would like to avail themselves of additional sources of information about BRCA1 and BRCA2 testing. Most spouses indicated that they thought their wives had a mutation in BRCA1 or BRCA2 and that their wives' breast cancers would recur. Pros of genetic testing were emphasized more than cons among both parties. Overall, spouses were satisfied with their role in the decision-making process. Future interventions to improve the decision-making process regarding genetic testing for breast cancer susceptibility should be undertaken. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. NCI, NIH, Div Canc Control & Populat, Bethesda, MD USA. Univ N Carolina, Chapel Hill, NC USA. Duke Univ, Ctr Med, Durham, NC USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Breast Oncol Ctr, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA668438] NR 35 TC 18 Z9 19 U1 3 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JUL-AUG PY 2003 VL 12 IS 5 BP 410 EP 427 DI 10.1002/pon.653 PG 18 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 701VL UT WOS:000184189600002 PM 12833555 ER PT J AU Gagnon, EM Recklitis, CJ AF Gagnon, EM Recklitis, CJ TI Parents' decision-making preferences in pediatric oncology: The relationship to health care involvement and complementary therapy use SO PSYCHO-ONCOLOGY LA English DT Article ID ALTERNATIVE MEDICINE; CANCER; INFORMATION; PREVALENCE; BEHAVIORS; DESIRE AB This study investigated how parents' preferred level of control in treatment decision-making is related to their personal health care involvement and to their decision to use complementary therapies (CTs) for their child. One hundred-eighteen parents of pediatric oncology patients completed an anonymous CT survey. The Krantz Health Opinion Survey (KHOS) was used to determine parents' preferred involvement in personal health care, and the Control Preferences Scale for Pediatrics (CPS-P) measured preferred role in pediatric treatment decision-making. Unlike previous studies of adult cancer patients, most parents preferred active or collaborative decision-making. The KHOS and CPS-P were significantly correlated, indicating that parents' preferred role in children's treatment decisions was related to their own personal health care involvement. Forty-six percent of parents used CTs for their child, and 33% began using a new CT after diagnosis. The hypothesized relationship between CT use and parents' own health care involvement was partially supported. Preference for control in decision-making was not associated with CT use. These findings provide validation for the newly developed CPS-P and indicate that parents' decisions to use CT for their child are related in part to individual health care preferences. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Yeshiva Univ, Ferkauf Grad Sch Psychol, Bronx, NY USA. RP Recklitis, CJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU AHRQ HHS [T32 HS00063] NR 34 TC 35 Z9 35 U1 1 U2 9 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JUL-AUG PY 2003 VL 12 IS 5 BP 442 EP 452 DI 10.1002/pon.655 PG 11 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 701VL UT WOS:000184189600004 PM 12833557 ER PT J AU Green, MF Nuechterlein, KH Breitmeyer, B Tsuang, J Mintz, J AF Green, MF Nuechterlein, KH Breitmeyer, B Tsuang, J Mintz, J TI Forward and backward visual masking in schizophrenia: influence of age SO PSYCHOLOGICAL MEDICINE LA English DT Article ID INFORMATION-PROCESSING DEFICITS; NEGATIVE-SYMPTOM SCHIZOPHRENIA; MEDICATION STATUS; POSITIVE-SYMPTOM; VULNERABILITY; OSCILLATIONS; PERFORMANCE; TRANSIENT; DISORDER; CHANNELS AB Background. Visual masking tasks assess the earliest stages of visual processing. This study was conducted to address: (1) whether schizophrenia patients show masking deficits after controlling for sensory input factors; (2) whether patients have relatively intact forward masking (when the mask precedes the target) compared with backward masking (when the mask follows the target); and (3) whether the masking deficits in schizophrenia reflect an accelerated age-related decline in performance. Method. A staircase method was used to ensure that the unmasked target identification was equivalent across subjects to eliminate any confounding due to differences in discrimination of simple perceptual inputs. Three computerized visual masking tasks were administered to 120 schizophrenia patients (ages 18-56) and 55 normal comparison subjects (ages 19-54) under both forward and backward masking conditions. The tasks included: (1) locating a target; (2) identifying a target with a high-energy mask; and (3) identifying a target with a low-energy mask. Results. Patients showed deficits across all three masking tasks. Interactions of group by forward versus backward masking were not significant, suggesting that deficits in forward and backward masking were comparable. All three conditions showed an age-related decline in performance and rates of decline were comparable between patients and controls. Two of the masking conditions showed increased rates of decline in backward, compared to forward, masking. Conclusions. We found age-related decline in performance that was comparable for the two groups. In addition, we failed to find evidence of a relative sparing of forward masking in schizophrenia. These results suggest that: (1) early visual processing deficits in schizophrenia are not due to a simple perceptual input problem; (2) sustained channels are involved in the masking deficit (in addition to transient channels); and (3) for the age range in this study, these deficits in schizophrenia are not age-related. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Harbor Med Ctr, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Houston, Dept Psychol, Houston, TX USA. RP Green, MF (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, 76 Westwood Plaza,C9-420, Los Angeles, CA 90024 USA. FU NIMH NIH HHS [MH-30911, MH-37705, MH-43292] NR 41 TC 33 Z9 33 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JUL PY 2003 VL 33 IS 5 BP 887 EP 895 DI 10.1017/S003329170200716X PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 704VZ UT WOS:000184362600014 PM 12877403 ER PT J AU Franceschini, MA Fantini, S Thomspon, JH Culver, JP Boas, DA AF Franceschini, MA Fantini, S Thomspon, JH Culver, JP Boas, DA TI Hemodynamic evoked response of the sensorimotor cortex measured noninvasively with near-infrared optical imaging SO PSYCHOPHYSIOLOGY LA English DT Article DE diffuse optical imaging; hemodynamic evoked response; sensorimotor cortex ID FUNCTIONAL MAGNETIC-RESONANCE; HUMAN SOMATOSENSORY CORTEX; MEDIAN NERVE-STIMULATION; CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; HUMAN VISUAL-CORTEX; MOTOR-CORTEX; HUMAN BRAIN; OXYGENATION CHANGES; TACTILE STIMULATION AB We have performed a noninvasive bilateral optical imaging study of the hemodynamic evoked response to unilateral finger opposition task, finger tactile, and electrical median nerve stimulation in the human sensorimotor cortex. This optical study shows the hemoglobin-evoked response to voluntary and nonvoluntary stimuli. We performed measurements on 10 healthy volunteers using block paradigms for motor, sensory, and electrical stimulations of the right and left hands separately. We analyzed the spatial/temporal features and the amplitude of the optical signal induced by cerebral activation during these three paradigms. We consistently found an increase (decrease) in the cerebral concentration of oxy-hemoglobin (deoxy-hemoglobin) at the cortical side contralateral to the stimulated side. We observed an optical response to activation that was larger in size and amplitude during voluntary motor task compared to the other two stimulations. The ipsilateral response was consistently smaller than the contralateral response, and even reversed (i.e., a decrease in oxy-hemoglobin, and an increase in deoxy-hemoglobin) in the case of the electrical stimulation. We observed a systemic contribution to the optical signal from the increase in the heart rate increase during stimulation, and we made a first attempt to subtract it from the evoked hemoglobin signal. Our findings based on optical imaging are in agreement with results in the literature obtained with positron emission tomography and functional magnetic resonance imaging. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA. RP Franceschini, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, 13th St Bldg 149,Room 2301, Charlestown, MA 02129 USA. FU NCRR NIH HHS [5P41-RR14075, P41 RR014075]; NIBIB NIH HHS [R01 EB001954, R01 EB001954-04A2, R01 EB001954-05]; NICHD NIH HHS [R01 HD042908, R01-HD42908]; NIMH NIH HHS [R01-MH62854]; NINDS NIH HHS [K25 NS044339, K25 NS44339A01, R29-NS38842] NR 75 TC 158 Z9 160 U1 1 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 JUL PY 2003 VL 40 IS 4 BP 548 EP 560 DI 10.1111/1469-8986.00057 PG 13 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 693RY UT WOS:000183733200008 PM 14570163 ER PT J AU Hammerness, P Basch, E Ulbricht, C Barrette, EP Foppa, I Basch, S Bent, S Boon, H Ernst, E AF Hammerness, P Basch, E Ulbricht, C Barrette, EP Foppa, I Basch, S Bent, S Boon, H Ernst, E CA Natural Standard Res Collaboration TI St. John's wort: A systematic review of adverse effects and drug interactions for the consultation psychiatrist SO PSYCHOSOMATICS LA English DT Review ID HYPERICUM-PERFORATUM EXTRACT; RANDOMIZED CONTROLLED TRIAL; INDUCED SEXUAL DYSFUNCTION; MILD-MODERATE DEPRESSION; AFFECTIVE-DISORDER SAD; CLINICAL-TRIALS; PHARMACOKINETIC INTERACTION; ANTIDEPRESSANT ACTIVITY; HERBAL ANTIDEPRESSANT; ALTERNATIVE MEDICINE AB St. John's wort is an herb commonly used in Europe for decades and more recently the topic of scientific investigation in this country. St. John's wort has been found more effective than placebo and equally as effective as tricyclic antidepressants in the short-term management of mild-to-moderate depression. Comparisons to selective serotonin reuptake inhibitors have provided equivocal data. While it is generally well tolerated in clinical use, there is accumulating evidence of significant interactions with drugs. This evidence-based presentation of the literature includes a brief description of pharmacodynamics and clinical applications, followed by a systematic review of adverse effects, toxicity, and drug interactions. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Northwestern Univ, Chicago, IL 60611 USA. Nat Stand Res Collaborat, Cambridge, MA 02139 USA. Univ Rhode Isl, Kingston, RI 02881 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Mt Sinai Sch Med, New York, NY USA. Univ Toronto, Toronto, ON, Canada. Univ Exeter, Exeter, Devon, England. Univ Plymouth, Plymouth PL4 8AA, Devon, England. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Ulbricht, C (reprint author), Nat Stand Res Collaborat, POB 390709, Cambridge, MA 02139 USA. NR 130 TC 57 Z9 58 U1 1 U2 7 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 2003 VL 44 IS 4 BP 271 EP 282 DI 10.1176/appi.psy.44.4.271 PG 12 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 694CQ UT WOS:000183756600001 PM 12832592 ER PT J AU Betancourt, JR AF Betancourt, JR TI Unequal treatment. The Institute of Medicine Report and its Public Health Implications SO PUBLIC HEALTH REPORTS LA English DT Editorial Material ID RACIAL-DIFFERENCES; LATINO CHILDREN; CARE; ACCESS; RACE; MANAGEMENT; ETHNICITY; CANCER; PAIN C1 Inst Hlth Policy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Social Med, Boston, MA USA. Hlth Resources & Services Adm, Boston, MA USA. RP Betancourt, JR (reprint author), Inst Hlth Policy, 50 Stanifold St,Suite 942, Boston, MA 02114 USA. NR 31 TC 18 Z9 18 U1 3 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JUL-AUG PY 2003 VL 118 IS 4 BP 287 EP 292 DI 10.1016/S0033-3549(04)50252-2 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 754AN UT WOS:000187280700001 PM 12815075 ER PT J AU Betancourt, JR Green, AR Carrillo, JE Ananeh-Firempong, O AF Betancourt, JR Green, AR Carrillo, JE Ananeh-Firempong, O TI Defining cultural competence: A practical framework for addressing racial/ethnic disparities in health and health care SO PUBLIC HEALTH REPORTS LA English DT Article ID SPANISH-SPEAKING PATIENTS; MEDICAL-SCHOOLS; HYPERTENSIVE PATIENTS; PATIENT SATISFACTION; RACIAL-DIFFERENCES; LANGUAGE BARRIERS; MANAGED CARE; RACE; PHYSICIANS; ETHNICITY AB Objectives. Racial/ethnic disparities in health in the U.S. have been well described. The field of "cultural competence" has emerged as one strategy to address these disparities. Based on a review of the relevant literature, the authors develop a definition of cultural competence, identify key components for intervention, and describe a practical framework for implementation of measures to address racial/ethnic disparities in health and health care. Methods. The authors conducted a literature review of academic, foundation, and government publications focusing on sociocultural barriers to care, the level of the health care system at which a given barrier occurs, and cultural competence efforts that address these barriers. Results. Sociocultural barriers to care were identified at the organizational (leadership/workforce), structural (processes of care), and clinical (provider-patient encounter) levels. A framework of cultural competence interventions-including minority recruitment into the health professions, development of interpreter services and language-appropriate health educational materials, and provider education on cross-cultural issues-emerged to categorize strategies to address racial/ethnic disparities in health and health care. Conclusions. Demographic changes anticipated over the next decade magnify the importance of addressing racial/ethnic disparities in health and health care. A framework of organizational, structural, and clinical cultural competence interventions can facilitate the elimination of these disparities and improve care for all Americans. C1 Inst Hlth Policy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Cornell Univ, Weill Med Coll, Dept Med, New York, NY USA. New York Presbyterian Healthcare Network, New York, NY USA. New York Presbyterian Hosp Community Hlth plan, New York, NY USA. Cornell Univ, Weill Med Coll, Dept Publ Hlth, New York, NY USA. RP Betancourt, JR (reprint author), Inst Hlth Policy, 50 Staniford St,Suite 942, Boston, MA 02114 USA. NR 89 TC 470 Z9 478 U1 21 U2 80 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JUL-AUG PY 2003 VL 118 IS 4 BP 293 EP 302 DI 10.1016/S0033-3549(04)50253-4 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 754AN UT WOS:000187280700002 PM 12815076 ER PT J AU Beal, AC Kuhlthau, K Perrin, JM AF Beal, AC Kuhlthau, K Perrin, JM TI Breastfeeding advice given to African American and white women by physicians and WIC counselors SO PUBLIC HEALTH REPORTS LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the Association-for-Health-Services-Research CY JUN 25-27, 2000 CL LOS ANGELES, CALIFORNIA SP Assoc Hlth Serv Res ID OTITIS-MEDIA; UNITED-STATES; INFANT-MORTALITY; RISK-FACTORS; HUMAN-MILK; DECISION; HEALTH; PREVENTION; ATTITUDES; INFECTION AB Objective. This study determined rates of breastfeeding advice given to African American and white women by medical providers and WIC nutrition counselors, and sought to determine whether racial differences in advice contributed to racial differences in rates of breastfeeding. Methods. The study used data from the 1988 National Maternal and Infant Health Survey, a cross-sectional survey of a nationally representative sample of mothers with a live birth, infant death, or fetal death in 1988. The authors compared white women (n=3,966) and African American women (n=4,791) with a live birth in 1988 on self-reported rates of medical provider and WIC advice to breastfeed, WIC advice to bottlefeed, and breastfeeding. Results. Self-reported racial identification did not predict medical provider advice. However, being African American was associated with less likelihood of breastfeeding advice and greater likelihood of bottlefeeding advice from WIC nutrition counselors. In multivariate analyses controlling for differences in advice, being African American was independently associated with lower breastfeeding rates (odds ratio [OR] = 0.41, 95% Cl 0.32, 0.52). Conclusions. African American women were less likely than white women to report having received breastfeeding advice from WIC counselors and more likely to report having received bottlefeeding advice from WIC counselors. However, African American and white women were equally likely to report having received breastfeeding advice from medical providers. Lower rates of breastfeeding advice from medical or nutritional professionals do not account for lower rates of breastfeeding among African American women. C1 Commonwealth Fund, New York, NY 10021 USA. Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Beal, AC (reprint author), Commonwealth Fund, 1 E 75th St, New York, NY 10021 USA. FU AHRQ HHS [R01 HSO9782] NR 50 TC 27 Z9 27 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JUL-AUG PY 2003 VL 118 IS 4 BP 368 EP 376 DI 10.1016/S0033-3549(04)50264-9 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 754AN UT WOS:000187280700013 PM 12815087 ER PT J AU O'Neill, MJ AF O'Neill, MJ TI Sonohysterography SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID BREAST-CANCER PATIENTS; SALINE CONTRAST SONOHYSTEROGRAPHY; TRANSVAGINAL SONOGRAPHY; ENDOMETRIAL CANCER; POSTMENOPAUSAL WOMEN; UTERINE CAVITY; PREOPERATIVE ASSESSMENT; DIAGNOSTIC-ACCURACY; TAMOXIFEN; ULTRASONOGRAPHY AB Sonohysterography (SHG) is a valuable, minimally invasive, sonographic examination that plays a crucial role in the triaging of abnormal uterine bleeding. SHG augments the traditional transvaginal ultrasound (TVUS) examination by distending the endometrial canal with saline, which allows each individual layer of the endometrial lining to be evaluated separately. The single-layer evaluation made possible with SHG significantly improves detection and characterization of focal and diffuse endometrial processes over that of TVUS alone [1-3]. Focal lesions involve less than 25% of the endometrial surface area and are unlikely to be diagnosed without hysteroscopically guided biopsy. Although the ability to accurately detect focal endometrial lesions noninvasively with SHG has had the largest impact on the management of abnormal bleeding in postmenopausal patients, the diagnosis and management of dysfunctional bleeding and infertility in premenopausal patients also have improved significantly. The improvement is largely because of the detailed evaluation that the study provided regarding the location and extent of subendometrial processes that affect the endometrium and endometrial cavity. This article reviews the technique, indications, and diagnostic findings during SHG. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Addominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP O'Neill, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Addominal Imaging & Intervent Radiol, White Bldg,Room 270,55 Fruit St, Boston, MA 02114 USA. NR 33 TC 9 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JUL PY 2003 VL 41 IS 4 BP 781 EP + DI 10.1016/S0033-8389(03)00038-1 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 707AG UT WOS:000184486800010 PM 12899492 ER PT J AU Delille, JP Slaneta, PJ Yeh, ED Halpern, EF Kopans, DB Garrido, L AF Delille, JP Slaneta, PJ Yeh, ED Halpern, EF Kopans, DB Garrido, L TI Invasive ductal breast carcinoma response to neoadjuvant chemotherapy: Noninvasive monitoring with functional MR imaging - Pilot study SO RADIOLOGY LA English DT Article; Proceedings Paper CT 86th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America (RSNA) CY NOV 26-DEC 01, 2000 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE breast neoplasms; breast neoplasms; chemotherapy magnetic resonance (MR), diffusion; magnetic resonance (MR), tissue characterization ID LOCALLY ADVANCED-CARCINOMA; INDUCTION CHEMOTHERAPY; PREOPERATIVE CHEMOTHERAPY; SOLID TUMORS; ENHANCED MRI; CANCER; THERAPY; ANGIOGENESIS; SURGERY; DIFFERENTIATION AB PURPOSE: To investigate if the extraction flow product (EFP), as determined on dynamic contrast material-enhanced magnetic resonance (MR) images, could be a potential marker of tumor response to neoadjuvant chemotherapy in patients with locally advanced breast cancer: MATERIALS AND METHODS: Fourteen women with proven breast cancer underwent MR imaging prior to and following neoadjuvant chemotherapy. Dynamic gradient-echo and echo-planar MR images were acquired before and after injection of gadopentetate dimeglumine: Precontrast T1s were measured before EFP maps were calculated by using a multicompartmental model. Mean EFP (EFPmean) and distribution analysis of EFP (EFPcount) were measured in tumors before and after neoadjuvant chemotherapy and were compared with tumor response at MR imaging. The significance of the difference in EFP values between the responders and nonresponders was calculated with a two-tailed Student t test. RESULTS: EFPmean after neoadjuvant chemotherapy in partial responders and non-responders was 33 mL . 100 g(-1) . min(-1) +/- 9.8 and 54.2 mL . 100 g(-1) . min(-1) +/- 10.3 +/- respectively (P <.005). EFPmean decreased after neoadjuvant chemotherapy in the responders and nonresponders by 37% +/- 30 and -5% +/- 35, respectively (P >.05). An increase in EFPmean values was observed only in nonresponders who received taxanes. For regimens without taxanes, EFPmean decreased regardless of the morphologic response. EFPcount decreased for all the responders by 77% +/- 33 and increased for all the nonresponders by 45% +/- 68 (P <.02). CONCLUSION: EFPcount appears to provide functional information regarding changes in tumor angiogenesis due to neoadjuvant chemotherapy. Functional MR, imaging of the breast may be useful in monitoring tumor response to neoadjuvant Chemotherapy. (C) RSNA, 2003. C1 St Elizabeths Med Ctr, Dept Radiol, Div Breast Imaging, Brighton, MA 02135 USA. Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Div Breast Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Slaneta, PJ (reprint author), St Elizabeths Med Ctr, Dept Radiol, Div Breast Imaging, 736 Cambridge St, Brighton, MA 02135 USA. RI Garrido, Leoncio/K-3092-2014; OI Garrido, Leoncio/0000-0002-7587-1260; Slanetz, Priscilla/0000-0003-1248-5116 NR 42 TC 60 Z9 66 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2003 VL 228 IS 1 BP 63 EP 69 DI 10.1148/radiol.2281011303 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692ZG UT WOS:000183689700011 PM 12775851 ER PT J AU D'Ippolito, G Ahmed, M Girnun, GD Stuart, KE Kruskal, JB Halpern, EF Goldberg, SN AF D'Ippolito, G Ahmed, M Girnun, GD Stuart, KE Kruskal, JB Halpern, EF Goldberg, SN TI Percutaneous tumor ablation: Reduced tumor growth with combined radio-frequency ablation and liposomal doxorubicin in a rat breast tumor model SO RADIOLOGY LA English DT Article DE adenocarcinoma; animals; breast neoplasms, experimental studies; chemotherapy; experimental study; radiofrequency (RF) ablation ID THERMAL ABLATION; HEPATIC-TUMORS; HEPATOCELLULAR-CARCINOMA; INCREASED NECROSIS; COLORECTAL-CANCER; OSTEOID OSTEOMA; METASTASES; LIVER; THERAPY; HYPERTHERMIA AB PURPOSE: To determine whether combined intravenous liposomal doxorubicin and radio-frequency (RF) ablation decreases tumor growth and increases endpoint survival over those with RF or liposomal doxorubicin alone in an animal tumor model. MATERIALS AND METHODS: Subcutaneous R3230 mammary adenocarcinoma (1.1-1.4 cm) was implanted in female Fischer rats. Initially, 35 tumors were randomized into four experimental groups: (a) conventional monopolar RF (70 degreesC for 5. minutes) alone, (b) liposomal doxorubicin (1 mg) alone, (c) RF ablation followed by liposomal doxorubicin, and (d) no treatment. Ten additional tumors were randomized into two groups that received a 90 degreesC RF dose either with or without liposomal doxorubicin. Tumor growth rates and the defined survival endpoint, the time at which the tumor reached 3.0 cm in diameter, were recorded. The effect of treatmeats on endpoint survival and tumor doubling time were analyzed by means of the Kaplan-Meier method, and analysis of variance statistics. RESULTS: Differences in endpoint survival and tumor doubling time in the six groups were highly significant (P <.001). Endpoint survivals were 9.1 days +/- 2.5 for the control group, 16 days +/- 3.7 for tumors treated with 70 &DEG;C RF alone, 16.5 days +/- 3.2 for tumors treated with liposomal doxorubicin alone; and 26.6 +/- 5.3 days with combined treatment. For 90 C RF ablation, endpoint survivals were 16:6 days +/- 1.2 and 31.5 days +/-3.0 without and with liposomal doxorubicin (P <.01). Mean endpoint survival and tumor doubling times for the three RF levels (070 degreesC, and 90 degreesC) were all significantly different (P =.01). Additionally, animals that received combined liposomal doxorubicin and 90 degreesC RF ablation survived longer than did I animals that received combined liposomal doxorubicin and 70 degreesC RF ablation (P <.01). CONCLUSION: Combined RF ablation and liposomal doxorubicin retards tumor growth and may increase animal survival compared with that with either therapy alone or no therapy. (C) RSNA; 2003. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol,Minimally Invas Tumor Therapy Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,DATA Grp, Boston, MA USA. RP Goldberg, SN (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol,Minimally Invas Tumor Therapy Lab, 330 Brookline Ave, Boston, MA 02215 USA. FU NCI NIH HHS [R01-CA87992-01A1] NR 42 TC 25 Z9 25 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2003 VL 228 IS 1 BP 112 EP 118 DI 10.1148/radiol.2281020358 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692ZG UT WOS:000183689700018 PM 12808127 ER PT J AU Kalra, MK Maher, MM Sahani, DV Blake, MA Hahn, PF Avinash, GB Toth, TL Halpern, E Saini, S AF Kalra, MK Maher, MM Sahani, DV Blake, MA Hahn, PF Avinash, GB Toth, TL Halpern, E Saini, S TI Low-dose CT of the abdomen: Evaluation of image improvement with use of noise reduction filters - Pilot study SO RADIOLOGY LA English DT Article DE abdomen, CT; computed tomography (CT), image processing; computed tomography (CT), image quality; computed tomography (CT), radiation exposure; radiations, exposure to patients and personnel ID TUBE CURRENT MODULATION; COMPUTED-TOMOGRAPHY; HELICAL CT; MULTISLICE AB A prospective assessment of improvement in image quality at low-radiation-close computed tomography (CT) of the abdomen by using noise reduction filters was performed. CT images acquired at standard and 50% reduced tube current were processed with six noise reduction filters and evaluated by three radiologists for image noise, sharpness, contrast, and overall image quality in terms of abdominal organ depiction. Quantitative image noise and contrast-to-noise ratio were measured. Baseline low-dose CT images were significantly worse than standard-dose CT images (P<.05). A statistically significant reduction of noise in low-dose images processed with three filters was noted. In conclusion, use of noise reduction filters decreased image noise at low-dose CT. (C) RSNA, 2003. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. GE Co, Med Syst, Milwaukee, WI 53201 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, White 270-E,55 Fruit St, Boston, MA 02114 USA. EM ssaini@partners.org NR 20 TC 94 Z9 100 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2003 VL 228 IS 1 BP 251 EP 256 DI 10.1148/radiol.2281020693 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692ZG UT WOS:000183689700039 PM 12832586 ER PT J AU Kalra, MK Wittram, C Maher, MM Sharma, A Avinash, GB Karau, K Toth, TL Halpern, E Saini, S Shepard, JA AF Kalra, MK Wittram, C Maher, MM Sharma, A Avinash, GB Karau, K Toth, TL Halpern, E Saini, S Shepard, JA TI Can noise reduction filters improve low-radiation-dose chest CT images? Pilot study SO RADIOLOGY LA English DT Article DE computed tomography (CT), radiation exposure; filters, radiographic; thorax, CT ID SPIRAL COMPUTED-TOMOGRAPHY; PULMONARY NODULES; MULTISLICE; QUALITY; EXPOSURE; SYSTEM; RADIOGRAPHY; PERFORMANCE; ALGORITHM; CANCER AB Effect of noise reduction filters on chest computed tomographic (CT) images acquired with 50% radiation dose reduction was evaluated. Two sets of images were acquired with multi-detector row CT at standard (220-280 mA) and 50% reduced (110-140 mA) tube current at the level of the carina. After postprocessing with six noise reduction filters, images were compared with baseline standard-dose images for noise, sharpness, and contrast in lungs, mediastinum, and chest wall. Quantitative image noise was measured in descending thoracic aorta. Modulation transfer functions were calculated from CT images of 50-mum wire. Noise reduction filters reduced image noise on low-radiation-dose chest CT images, with some compromise in image sharpness and contrast assessed qualitatively, and slightly altered modulation transfer function at higher spatial frequencies. (C) RSNA, 2003. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. GE Co, Med Syst, Waukesha, WI USA. RP Massachusetts Gen Hosp, Dept Radiol, Founders 202, Boston, MA 02114 USA. EM jshepard@partners.org NR 32 TC 65 Z9 68 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2003 VL 228 IS 1 BP 257 EP 264 DI 10.1148/radiol.2281020606 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692ZG UT WOS:000183689700040 PM 12750460 ER PT J AU Chiou, YY Rosenthal, DI Rosenberg, AE AF Chiou, YY Rosenthal, DI Rosenberg, AE TI "Beaded" osteoid osteoma: a possible transition between solitary and multicentric tumor SO SKELETAL RADIOLOGY LA English DT Article DE bone neoplasms; osteoid osteoma; osteoblastoma; therapy; radiofrequency (RF) ablation ID PERCUTANEOUS RADIOFREQUENCY ABLATION; NIDUS; OSTEOBLASTOMA; DIAGNOSIS; BONE AB An extremely rare example of an elongated (3 cm) osteoid osteoma is presented. The tumor demonstrated three focal enlargements connected by narrow areas, suggesting a 'string of beads' in appearance. The elongated shape suggested the possibility that lesional tissue was stretched in a longitudinal fashion as a result of the rapid skeletal growth. The tumor closest to the growth plate was densely ossified, while the furthest lesion was almost completely lytic, suggesting that the tumor enlarged in a centripetal direction. This case is believed to illustrate a continuum from solitary to multicentric osteoid osteoma. The tumor was treated successfully with three separate percutaneous radiofrequency ablations during a single session. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Taipei Vet Gen Hosp, Dept Radiol, Taipei 11217, Taiwan. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rosenthal, DI (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 26 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD JUL PY 2003 VL 32 IS 7 BP 412 EP 415 DI 10.1007/s00256-002-0611-z PG 4 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 698ZN UT WOS:000184030900005 PM 12851789 ER PT J AU Das, J Das, S AF Das, J Das, S TI Trust, learning, and vaccination: a case study of a North Indian village SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE vaccination; information; learning; trust; India AB For US $17 a child can be immunized against six major illnesses. Even at this price, a country such as India would have to spend half its health budget on providing vaccinations. Given the wide variation in immunization costs it may be possible to decrease this cost to more sustainable levels, but to do so we need to arrive at a more thorough understanding of factors affecting household demand for vaccination. Using data on vaccination and pre-natal care collected by the authors in the Garhwal region of India, we explore one aspect of the demand for vaccination in some detail. We show that informational constraints play an important role in the household decision to seek vaccination, and moreover, that learning about the efficacy of vaccinations only through empirical observation may be hard even in environments with variation in vaccination and the high incidence of vaccine-preventable diseases. We argue that when learning about vaccination is inefficient, households use concurrent interventions with easily observable outcomes to evaluate the veracity of a provider's claim regarding preventive care. Hence, the success of immunization programs becomes crucially linked to the success of parallel programs by the same provider. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 World Bank, Dev Res Grp, Washington, DC 20433 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Cambridge, MA USA. RP Das, J (reprint author), World Bank, Dev Res Grp, MSM MC3-311 DECRG, Washington, DC 20433 USA. NR 24 TC 12 Z9 12 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD JUL PY 2003 VL 57 IS 1 BP 97 EP 112 AR PII S0277-9536(02)00302-7 DI 10.1016/S0277-9536(02)00302-7 PG 16 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 684ED UT WOS:000183191700008 PM 12753819 ER PT J AU Shah, MK Burke, DT Shah, SH AF Shah, MK Burke, DT Shah, SH TI Upper-extremity deep vein thrombosis SO SOUTHERN MEDICAL JOURNAL LA English DT Article DE deep vein thrombosis; treatment; upper extremity ID SUBCLAVIAN VENOUS THROMBOSIS; AXILLARY VEIN; CLINICAL-EXPERIENCE; PULMONARY-EMBOLISM; GREENFIELD FILTERS; RISK-FACTORS; DIAGNOSIS; MANAGEMENT; PLETHYSMOGRAPHY; CATHETERS AB Upper-extremity deep vein thrombosis (UEDVT) was an understudied disease until recently. Previously thought of as benign, UEDVT has been shown in recent studies to pose a significant risk for pulmonary embolus and death. This article reviews the epidemiology, risk factors, clinical features, diagnostic tests, treatment options, complications, and prevention strategies for patients with UEDVT. C1 Harvard Univ, Spaulding Rehabil Hosp, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Shah, MK (reprint author), 10 Summer St,Suite 303S, Malden, MA 02148 USA. EM mrugshah@hotmail.com NR 39 TC 8 Z9 8 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD JUL PY 2003 VL 96 IS 7 BP 669 EP 672 DI 10.1097/01.SMJ.0000066659.65762.02 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 831CE UT WOS:000222169700010 PM 12940317 ER PT J AU Atlas, SJ AF Atlas, SJ TI Back to work: Predictors of return to work among patients with back disorders certified as sick - Point of view SO SPINE LA English DT Editorial Material ID PAIN; DISABILITY C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Atlas, SJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD JUL 1 PY 2003 VL 28 IS 13 BP 1473 EP 1474 PG 2 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 699KM UT WOS:000184056100020 ER PT J AU de Crespigny, A AF de Crespigny, A TI Mismatch or misconception? SO STROKE LA English DT Editorial Material ID CEREBRAL BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; MAGNETIC-RESONANCE; COMBINED DIFFUSION; ISCHEMIC STROKE; TISSUE; VOLUME; MRI C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. RP de Crespigny, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 2003 VL 34 IS 7 BP 1683 EP 1685 DI 10.1161/01.STR.0000082062.93106.23 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 697NH UT WOS:000183949200036 PM 12817096 ER PT J AU Eckman, MH Rosand, J Knudsen, KA Singer, DE Greenberg, SM AF Eckman, MH Rosand, J Knudsen, KA Singer, DE Greenberg, SM TI Can patients be anticoagulated after intracerebral hemorrhage? A decision analysis SO STROKE LA English DT Article DE atrial fibrillation; decision support techniques; intracerebral hemorrhage; Markov chains; warfarin ID CEREBRAL AMYLOID ANGIOPATHY; RANDOMIZED CONTROLLED-TRIALS; APOLIPOPROTEIN-E GENOTYPE; QUALITY-OF-LIFE; ATRIAL-FIBRILLATION; ANTITHROMBOTIC THERAPY; INTRACRANIAL HEMORRHAGE; RISK-FACTORS; STROKE PREVENTION; BRAIN HEMORRHAGE AB Background and Purpose - Warfarin increases both the likelihood and the mortality of intracerebral hemorrhage (ICH), particularly in patients with a history of prior ICH. In light of this consideration, should a patient with both a history of ICH and a clear indication for anticoagulation such as nonvalvular atrial fibrillation be anticoagulated? In the absence of data from a clinical trial, we used a decision-analysis model to compare the expected values of 2 treatment strategies - warfarin and no anticoagulation - for such patients. Methods - We used a Markov state transition decision model stratified by location of hemorrhage ( lobar or deep hemispheric). Effectiveness was measured in quality-adjusted life years (QALYs). Data sources included English language literature identified through MEDLINE searches and bibliographies from selected articles, along with empirical data from our own institution. The base case focused on a 69-year-old man with a history of ICH and newly diagnosed nonvalvular atrial fibrillation. Results - For patients with prior lobar ICH, withholding anticoagulation therapy was strongly preferred, improving quality-adjusted life expectancy by 1.9 QALYs. For patients with prior deep hemispheric ICH, withholding anticoagulation resulted in a smaller gain of 0.3 QALYs. In sensitivity analyses for patients with deep ICH, anticoagulation could be preferred if the risk of thromboembolic stroke is particularly high. Conclusions - Survivors of lobar ICH with atrial fibrillation should not be offered long-term anticoagulation. Similarly, most patients with deep hemispheric ICH and atrial fibrillation should not receive anticoagulant therapy. However, patients with deep hemispheric ICH at particularly high risk for thromboembolic stroke or low risk of ICH recurrence might benefit from long-term anticoagulation. C1 Univ Cincinnati, Med Ctr, Div Gen Internal Med, Cincinnati, OH 45267 USA. Univ Cincinnati, Med Ctr, Ctr Clin Effectiveness, Cincinnati, OH 45267 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Eckman, MH (reprint author), Univ Cincinnati, Med Ctr, Div Gen Internal Med, POB 670535, Cincinnati, OH 45267 USA. NR 40 TC 151 Z9 155 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 2003 VL 34 IS 7 BP 1710 EP 1716 DI 10.1161/01.STR.0000078311.18928.16 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 697NH UT WOS:000183949200041 PM 12805495 ER PT J AU Warshaw, AL Sarr, MG AF Warshaw, AL Sarr, MG TI The now and future world of restricted work hours for surgeons SO SURGERY LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Gen Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg Gastroenterol, Boston, MA 02114 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. RP Warshaw, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Gen Surg, Boston, MA 02114 USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUL PY 2003 VL 134 IS 1 BP 1 EP 2 DI 10.1067/msy.2003.200 PG 2 WC Surgery SC Surgery GA 706MD UT WOS:000184456700001 PM 12874571 ER PT J AU Berger, DH Ko, CY Spain, DA AF Berger, DH Ko, CY Spain, DA CA Social Legislative Issues Comm Soc TI Society of University Surgeons position statement on the volume-outcome relationship for surgical procedures SO SURGERY LA English DT Article ID QUALITY-IMPROVEMENT-PROGRAM; IN-HOSPITAL MORTALITY; NEW-YORK-STATE; CANCER RESECTION; PATIENT OUTCOMES; UNITED-STATES; RISK-FACTORS; HEALTH-CARE; PREDICTORS; OPERATIONS C1 Baylor Coll Med, Houston Vet Affairs Med Ctr, Dept Surg, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. RP Berger, DH (reprint author), Baylor Coll Med, Houston Vet Affairs Med Ctr, Dept Surg, 112 OCL,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 32 TC 22 Z9 22 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUL PY 2003 VL 134 IS 1 BP 34 EP 40 DI 10.1067/msy.2003.157 PG 7 WC Surgery SC Surgery GA 706MD UT WOS:000184456700010 PM 12874580 ER PT J AU Sugarbaker, DJ AF Sugarbaker, DJ TI Lung cancer center dot 6: The case for limited surgical resection in non-small cell lung cancer SO THORAX LA English DT Review ID LOBECTOMY AB The choice between conservative resection or standard anatomical resection for stage I NSCLC depends on the size and biology of the tumour and the age and state of health of the patient. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Div Thorac Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Surg Serv, Boston, MA 02115 USA. RP Sugarbaker, DJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Div Thorac Surg, Boston, MA 02115 USA. NR 10 TC 16 Z9 16 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD JUL PY 2003 VL 58 IS 7 BP 639 EP 641 DI 10.1136/thorax.58.7.639 PG 3 WC Respiratory System SC Respiratory System GA 695CB UT WOS:000183812600019 PM 12832686 ER PT J AU Yunis, EJ Larsen, CE Fernandez-Vina, M Awdeh, ZL Romero, T Hansen, JA Alper, CA AF Yunis, EJ Larsen, CE Fernandez-Vina, M Awdeh, ZL Romero, T Hansen, JA Alper, CA TI Inheritable variable sizes of DNA stretches in the human MHC: conserved extended haplotypes and their fragments or blocks SO TISSUE ANTIGENS LA English DT Review DE alleles; genome, human; genotype; haplotypes; linkage disequilibrium; major histocompatibility complex; models, genetic; polymorphism (genetics); recombination, genetic ID MAJOR HISTOCOMPATIBILITY COMPLEX; SINGLE-NUCLEOTIDE POLYMORPHISMS; CLASS-II REGION; CLOZAPINE-INDUCED AGRANULOCYTOSIS; DIFFERENT ETHNIC-GROUPS; ALPHA GENE PROMOTER; HLA-CLASS-I; LINKAGE DISEQUILIBRIUM; UNRELATED INDIVIDUALS; GAMETIC DISEQUILIBRIUM AB The difference in sizes of conserved stretches of DNA sequence within the major histocompatibility complex (MHC) in human individuals constitutes an underappreciated genetic diversity that has many practical implications. We developed a model to describe the variable sizes of stretches of conserved DNA in the MHC using the known frequencies of four different kinds of small (<0.2 Mb) blocks of relatively conserved DNA sequence: HLA-Cw/B; TNF; complotype; and HLA-DR/DQ. Each of these small blocks is composed of two or more alleles of closely linked loci inherited as one genetic unit. We updated the concept of the conserved extended haplotype (CEH) using HLA allele identification and TNF microsatellites to show that specific combinations of the four blocks form single genetic units (greater than or equal to1.5 Mb) with a total haplotype frequency in the Caucasian population of 0.30. Some CEHs extend to the HLA-A and -DPB1 loci forming fixed genetic units of up to at least 3.2 Mb of DNA. Finally, intermediate fragments of CEHs also exist, which are, nevertheless, larger than any of the four small blocks. This complexity of genetic fixity at various levels should be taken into account in studies of genetic disease association, immune response control, and human diversity. This knowledge could also be used for matching CEHs and their fragments for patients undergoing allotransplantation. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Georgetown Univ, Dept Oncol, Natl Naval Med Res Inst, Kensington, MD USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Med, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Yunis, EJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA18029]; NHLBI NIH HHS [HL59838, HL29583]; NIAID NIH HHS [AI49213, AI33484] NR 93 TC 110 Z9 118 U1 0 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD JUL PY 2003 VL 62 IS 1 BP 1 EP 20 DI 10.1034/j.1399-0039.2003.00098.x PG 20 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 700JA UT WOS:000184107800001 PM 12859592 ER PT J AU Bertino, AM Qi, XQ Li, J Xia, Y Kuter, DJ AF Bertino, AM Qi, XQ Li, J Xia, Y Kuter, DJ TI Apoptotic markers are increased in platelets stored at 37 degrees C SO TRANSFUSION LA English DT Article ID CYTOCHROME-C; IN-VIVO; CASPASE FAMILY; STORAGE; 22-DEGREES-C; PROTEIN; ACTIVATION; VIABILITY; APAF-1; SPECIFICITIES AB BACKGROUND: PLTs for transfusion lose viability during storage in blood banking. This loss of viability is accelerated at 37 degreesC, as is the risk of bacterial contamination, and has led to the selection of 22 degreesC as the routine storage temperature. Because PLTs contain an intact apoptotic mechanism, we sought to determine whether PLTs undergo apoptosis during storage and whether storage at 37 degreesC accelerated this process. STUDY DESIGN AND METHODS: PLT-rich plasma from PLT concentrates was stored at 37 or 22 degreesC in small aliquots or whole bags, with and without cell-permeable caspase inhibitors. Number of PLTs, pH, LDH level, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H- tetrazolium activity were analyzed over time. PLT lysates were prepared and tested for the presence and activation of apoptotic proteins by enzyme assay and Western blotting. RESULTS: PLT viability was greatly reduced after 1 to 2 days of storage at 37 degreesC; however, signs of apoptosis were evident by 3 hours after temperature shift. In temperature-stressed PLTs only, a gradual rise in caspase-3 activity was detected that correlated with the appearance of the 17- to 20-kDa cleavage products of caspase-3. Gelsolin, a caspase-3 substrate, underwent cleavage within the same time frame. Bcl-x(L) and caspase-2 also declined significantly; caspase-9 activity rose. Specific caspase inhibitors could prevent caspase activation but did not improve PLT cellular viability at 37 degreesC. CONCLUSIONS: PLTs contain apoptotic proteins that are activated during PLT storage at 37 degreesC and may account for the rapid decline in PLT cellular viability. Although ineffective here, inhibition of PLT apoptosis may improve PLT cellular viability. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Hematol & Oncol, Boston, MA USA. RP Kuter, DJ (reprint author), Hematol Unit, COX 640,100 Blossom St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL61222] NR 33 TC 77 Z9 80 U1 0 U2 5 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 2003 VL 43 IS 7 BP 857 EP 866 DI 10.1046/j.1537-2995.2003.t01-4-00431.x PG 10 WC Hematology SC Hematology GA 693KU UT WOS:000183717400007 PM 12823744 ER PT J AU Dzik, WH Corwin, H Goodnough, LT Higgins, M Kaplan, H Murphy, M Ness, P Shulman, IA Yomtovian, R AF Dzik, WH Corwin, H Goodnough, LT Higgins, M Kaplan, H Murphy, M Ness, P Shulman, IA Yomtovian, R TI Patient safety and blood transfusion: New solutions SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID ADVERSE DRUG EVENTS; NEGLIGENT CARE; ERRORS; COLORADO; UTAH; MEDICINE; SYSTEM; AUDIT AB Current risk from transfusion is largely because of noninfectious hazards and defects in the overall process of delivering safe transfusion therapy. Safe transfusion therapy depends on a complex process that requires integration and coordination among multiple hospital services including laboratory medicine, nursing, anesthesia, surgery, clerical support, and transportation. The multidisciplinary hospital transfusion committee has been traditionally charged with oversight of transfusion safety. However, in recent years, this committee may have been neglected in many institutions. Resurgence in hospital oversight of patient safety and transfusion efficacy is an important strategy for change. A new position, the transfusion safety officer (TSO), has been developed in some nations to specifically identify, resolve, and monitor organizational weakness leading to unsafe transfusion practice. New technology is becoming increasingly available to improve the performance of sample labeling and the bedside clerical check. Several technology solutions are in various stages of development and include wireless handheld portable digital assistants, advanced bar coding, radiofrequency identification, and imbedded chip technology. Technology-based solutions for transfusion safety will depend on the larger issue of the technology for patient identification. Devices for transfusion safety hold exciting promise but need to undergo clinical trials to show effectiveness and ease of use. Technology solutions will likely require integration with delivery of pharmaceuticals to be financially acceptable to hospitals. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Blood Transfus Serv, Dept Hematol Pathol, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Dept Intens Care Med, Hanover, NH USA. Barnes Jewish Hosp, Dept Pathol, St Louis, MO 63110 USA. St Johns Hosp, Dept Pathol, Detroit, MI USA. Columbia Presbyterian Med Ctr, Dept Pathol, New York, NY 10032 USA. Natl Blood Serv, Dept Hematol, Oxford, England. Johns Hopkins Med Ctr, Dept Pathol, Baltimore, MD USA. Univ So Calif, Dept Pathol, Los Angeles, CA 90089 USA. Univ Hosp Cleveland, Dept Pathol, Cleveland, OH 44106 USA. RP Dzik, WH (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, Dept Hematol Pathol, J-224,55 Fruit St, Boston, MA 02114 USA. EM sdzik@partners.org NR 30 TC 45 Z9 49 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JUL PY 2003 VL 17 IS 3 BP 169 EP 180 DI 10.1016/S0887-7963(03)00017-8 PG 12 WC Hematology SC Hematology GA 704XR UT WOS:000184367400001 PM 12881778 ER PT J AU Wu, A Yamada, K Ierino, FL Vagefi, PA Sachs, DH AF Wu, A Yamada, K Ierino, FL Vagefi, PA Sachs, DH TI Regulatory mechanism of peripheral tolerance: in vitro evidence for dominant suppression of host responses during the maintenance phase of tolerance to renal allografts in miniature swine SO TRANSPLANT IMMUNOLOGY LA English DT Article DE tolerance; suppression; regulatory cells; transplantation ID T-CELLS; TRANSPLANTATION TOLERANCE; INDUCTION; CYCLOSPORINE; THYMUS; SUBSET; BLOOD AB Background: Studies from our laboratory have demonstrated that a short course of cyclosporine leads to indefinite survival of renal allografts across an MHC class-1 barrier in miniature swine. We have recently reported that a peripheral regulatory mechanism appears to be involved in the maintenance of this tolerance since peripheral blood lymphocytes (PBL), exposed to donor antigen in vitro specifically suppressed the generation of anti-donor cytotoxic activity by recipient-matched naive PBL. We have now further investigated the mechanism of this phenomenon to determine the level at which such regulation occurs, and investigated the phenotypes of the cells involved in maintaining dominant suppression. Materials and methods: PBL from long-term tolerant animals ( > 6 months after renal transplantation) were pre-stimulated in vitro with donor-type PBL. These cells were then incubated with recipient-matched naive responders and donor-type PBL stimulators in MLR assays. The proliferative activity of the cells was measured by [H-3]-thymidine incorporation. Suppression was measured by inhibition of proliferation of naive cells in response to donor PBL when co-cultured with tolerant cells. Flow cytometry was used to study the phenotypes of cells that were present in cell cultures. Results: Primed PBL from tolerant animals markedly suppressed the proliferative response of recipient-matched naive cells to donor-matched stimulators in vitro. No suppression of proliferation was observed in response to third party stimulators, indicating that the suppression was donor-specific. Primed PBL from naive animals stimulated with donor antigen and co-cultured with unprimed recipient-matched naive cells also demonstrated reduced proliferative responses. However, this decrease in proliferation appeared to be due to a 'burn-out' phenomenon, as assessed by kinetic studies, rather than due to true suppression. Expression of CD25 increased on a sub-population of T cells from tolerant animals following priming with donor antigen. These cell then markedly inhibited further activation of CD25 positive cells in co-cultures with naive responder cells, suggesting a possible mechanism of suppression. Conclusion: These results suggest that the mechanism of tolerance to class-l-mismatched renal allografts, involves a population of regulatory cells that are capable of suppressing proliferative anti-donor responses. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Austin & Repatriat Med Ctr, Dept Nephrol, Heidelberg, Vic 3084, Australia. RP Sachs, DH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [2P01 HL18646]; NIAID NIH HHS [2R01 AI31046] NR 16 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0966-3274 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD JUL-SEP PY 2003 VL 11 IS 3-4 BP 367 EP 374 DI 10.1016/S0966-3274(03)00006-6 PG 8 WC Immunology; Transplantation SC Immunology; Transplantation GA 724UD UT WOS:000185504300014 PM 12967789 ER PT J AU Dor, FJMF Gollackner, B Cooper, DKC AF Dor, FJMF Gollackner, B Cooper, DKC TI Can spleen transplantation induce tolerance? A review of the literature SO TRANSPLANT INTERNATIONAL LA English DT Review DE allotransplantation; human; regulatory cells; rodents; spleen; tolerance ID T-SUPPRESSOR CELLS; HEART ALLOGRAFT SURVIVAL; MIXED LEUKOCYTE REACTION; SPLENIC TRANSPLANTATION; GUINEA-PIGS; HOST DISEASE; HEMOPHILIA-A; LETHAL GRAFT; PANCREATICODUODENAL TRANSPLANTATION; PERIOPERATIVE INJECTION AB In some rodent strain combinations, allogeneic spleen transplantation induces tolerance spontaneously to itself and to other donor-specific organs. In other combinations, a state of tolerance has been achieved in the weakened immune system of the recipient. The data indicate that if a balance can be achieved between host-versus-graft and graft-versus-host responses, tolerance develops, possibly due to the development of suppressor/regulatory cells. There have been a number of unsuccessful studies in outbred large animals, but none in MHC-defined donor-recipient pairs, and none in which the protocol specifically aimed at inducing tolerance. Spleen transplantation has been performed in approximately 50 humans for a number of reasons, however no clear immunologic advantage has been reported. Graft-versus-host disease (GVHD) was documented in at least 3 patients, and was lethal in one case, despite excision of the donor spleen. The advantages of tolerance over chronic immunosuppressive therapy are so great that a potentially tolerogenic approach such as spleen transplantation would seem worthy of further investigation in a suitable large animal model. Such a study is ongoing at our center.(1) C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH-E,Bldg 149-9019 13th St, Boston, MA 02129 USA. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 FU NIAID NIH HHS [1P01 AI45897] NR 65 TC 20 Z9 20 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0934-0874 J9 TRANSPLANT INT JI Transpl. Int. PD JUL PY 2003 VL 16 IS 7 BP 451 EP 460 DI 10.1007/s00147-003-0640-0 PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 713JM UT WOS:000184854200001 PM 12851762 ER PT J AU Drummond, I AF Drummond, I TI Making a zebrafish kidney: a tale of two tubes SO TRENDS IN CELL BIOLOGY LA English DT Review ID DORSOVENTRAL PATTERN-FORMATION; INTRAFLAGELLAR TRANSPORT; INTERMEDIATE MESODERM; PRIMARY CILIUM; FAMILY KINASE; CELL-CYCLE; GENE; DISEASE; EXPRESSION; PRONEPHROS AB The kidney can be thought of as the pairing of two tubes: an epithelial tube (the nephron), carrying filtered blood and engaged in ion and water transport; and endothelial tubes (the blood vessels), delivering blood and carrying away recovered solute. The development of the nephron presents several interesting questions. How does an epithelial tube form and how is it patterned into functionally distinct components and segments? What guides the interaction between the vasculature and kidney epithelia? How are epithelial cell shape and lumen diameter maintained, and what goes wrong when kidney tubules balloon into cysts? Here, I outline the progress that has been made in answering these questions using the zebrafish pronephros as a simple, accessible model of nephron development. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. RP Drummond, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK 53093, DK 54711] NR 74 TC 63 Z9 64 U1 0 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD JUL PY 2003 VL 13 IS 7 BP 357 EP 365 DI 10.1016/S0962-8924(03)00124-7 PG 9 WC Cell Biology SC Cell Biology GA 700QX UT WOS:000184123600004 PM 12837606 ER PT J AU Pissios, P Maratos-Flier, E AF Pissios, P Maratos-Flier, E TI Melanin-concentrating hormone: from fish skin to skinny mammals SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID PROTEIN-COUPLED RECEPTOR; MESSENGER-RIBONUCLEIC-ACID; DEPENDENT CALCIUM CHANNELS; MCH RECEPTOR; FOOD-INTAKE; MOLECULAR CHARACTERIZATION; SIGNALING PATHWAYS; CELLS EXPRESS; BODY-WEIGHT; ALPHA-MSH AB In recent years, the key role of melanin-concentrating hormone (MCH) in regulating mammalian energy balance has been confirmed through several lines of evidence. When administered exogenously, MCH leads to a rapid and robust feeding response and chronic infusions result in the development of mild obesity. At the physiological level, it is known that MCH expression changes in states of altered energy balance, such as fasting and obesity. Genetic studies with mice have shown that ablation of either the gene for prepro-MCH or the gene encoding the MCH receptor leads to a lean phenotype. Finally, the administration of MCH antagonists appears to inhibit both feeding and the development of diet-induced obesity. The aim of this article is to review the recent data on MCH and MCH receptors in light of their emerging roles in energy homeostasis. C1 Joslin Diabet Ctr, Obes Sect, Boston, MA 02215 USA. RP Maratos-Flier, E (reprint author), Joslin Diabet Ctr, Obes Sect, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 53978, DK 56113, DK/PP 56116] NR 57 TC 72 Z9 78 U1 0 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD JUL PY 2003 VL 14 IS 5 BP 243 EP 248 DI 10.1016/S1043-2760(03)00079-1 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 700RA UT WOS:000184123900009 PM 12826331 ER PT J AU Guenette, SY AF Guenette, SY TI Astrocytes: a cellular player in A beta clearance and degradation SO TRENDS IN MOLECULAR MEDICINE LA English DT Article ID ALZHEIMERS-DISEASE; NERVOUS-SYSTEM; CELLS; INFLAMMATION; RECEPTORS; PLAQUES; CHEMOKINES; BRAIN AB Astrocytes are thought to play a protective role in Alzheimer's disease (AD) by shielding neurons from the toxic effects of extracellular senile plaques. The mechanisms involved in the recruitment of astrocytes to senile plaques are unclear, and studies examining the astrocyte response to extracellular beta-amyloid (Abeta) are limited. However, recent work has shown that astrocytes migrating towards monocyte chemoattractant protein-1 become immobilized when they encounter Abeta. Once in the presence of Abeta, astrocytes can internalize and degrade it. It is possible that this proposed function for astrocytes is inactivated or overwhelmed in AD. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Ctr Aging Genet & Neurodegenerat, Charlestown, MA 02129 USA. RP Guenette, SY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Ctr Aging Genet & Neurodegenerat, Charlestown, MA 02129 USA. NR 15 TC 30 Z9 30 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD JUL PY 2003 VL 9 IS 7 BP 279 EP 280 DI 10.1016/S1471-4914(03)00112-6 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 714TK UT WOS:000184929400002 PM 12900212 ER PT J AU Krieger, JN Ross, SO Deutsch, LA Fritsche, TR Riley, DE AF Krieger, JN Ross, SO Deutsch, LA Fritsche, TR Riley, DE TI Counting leukocytes in expressed prostatic secretions from patients with chronic prostatitis/chronic pelvic pain syndrome SO UROLOGY LA English DT Article ID NON-BACTERIAL PROSTATITIS; INFLAMMATION; CLASSIFICATION; CYTOKINES; SYMPTOMS; COHORT; FLUID; MEN AB Objectives. The evaluation of WBCs in EPS is recommended for classifying patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) but no agreement has been reached on the optimal method. We sought to determine the relationship between the expressed prostatic secretions (EPS) leukocyte (WBC) count per high-power field (evaluated by a more quantitative wet mount method and the traditional gram-stained smear method used in clinical microbiology laboratories) and the EPS WBC concentration to determine whether quantitative methods are necessary for accurate patient classification. Methods. EPS collected from 94 patients with CP/CPPS were evaluated by gram-stained smear, a standardized wet mount, and a hemocytometer method. Results. The gram-stained smear detected EPS WBCs in 21 (22%) of 94 subjects compared with 78 (83%) by the standardized wet mount and 57 (60%) by the hemocytometer method. The gram-stained EPS WBC count correlated poorly with the WBC concentration by hemocytometer (R-2=0.051, P=0.03). Although the standardized EPS WBC count correlated better with the concentration by hemocytometer, the correlation coefficient remained low (R-2=0.244, P<0.0001). Conclusions. The standardized wet mount proved superior to the gram-stained smear, but both methods lacked precision. Quantitative determination of the EPS WBC concentration by a counting chamber method proved to be the superior evaluation for research studies of CP/CPPS. C1 Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA. RP Krieger, JN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Urol Sect, 112-GU,1660 S Columbian Way,Univ Washington Campu, Seattle, WA 98108 USA. FU NIDDK NIH HHS [R01-DK38955] NR 20 TC 6 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JUL PY 2003 VL 62 IS 1 BP 30 EP 34 DI 10.1016/S0090-4295(03)00237-1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 696NH UT WOS:000183892600010 PM 12837417 ER PT J AU Oh, WK Manola, J Bittmann, L Brufsky, A Kaplan, ID Smith, MR Kaufman, DS Kantoff, PW AF Oh, WK Manola, J Bittmann, L Brufsky, A Kaplan, ID Smith, MR Kaufman, DS Kantoff, PW TI Finasteride and flutamide therapy in patients with advanced prostate cancer: Response to subsequent castration and long-term follow-up SO UROLOGY LA English DT Article ID ANDROGEN DEPRIVATION THERAPY; BICALUTAMIDE MONOTHERAPY; ANTIANDROGEN MONOTHERAPY; COMBINATION FINASTERIDE; DOUBLE-BLIND; CARCINOMA; FAILURE; MEN AB Objectives. To report the efficacy of castration after progression on finasteride and flutamide. Standard androgen deprivation strategies for prostate cancer typically lead to castrate levels of testosterone. One alternative is the use of finasteride and flutamide. Methods. A Phase II trial evaluated the combination of finasteride (5 mg/day) and flutamide (250 mg three times daily) in patients with rising prostate-specific antigen levels after local treatment for prostate cancer or with newly discovered metastatic disease. Patients were followed up for subsequent events, including castration-free, androgen-independent prostate cancer (AIPC)-free, and overall survival. Results. With a median follow-up of 88 months, 5 patients (25%) continued on finasteride and flutamide, and 12 had stopped this combination and subsequently underwent medical or surgical castration. No patients experienced a flutamide withdrawal effect. All patients experienced more than a 50% decline in prostate-specific antigen after castration (mean 89%). The median protocol treatment failure-free survival was 29.9 months, the median castration-free survival was 37 months, and the median AIPC-free survival was 48.6 months. At 5 years, the overall survival rate was 65% (95% confidence interval 47% to 90%); 29% were alive and have not required castration, and 35% were alive and free of AIPC. Conclusions. Finasteride and flutamide have a durable effect in suppressing prostate-specific antigen progression in some men with advanced prostate cancer. Furthermore, castration induces secondary responses that may be of shorter duration than if started initially, although the overall period of hormonally responsive prostate cancer is more than 4 years. C1 Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 22 TC 18 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JUL PY 2003 VL 62 IS 1 BP 99 EP 104 DI 10.1016/S0090-4295(03)00145-6 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 696NH UT WOS:000183892600024 PM 12837431 ER PT J AU Teranishi, K Alwayn, IPJ Buhler, L Gollackner, B Knosalla, C Huck, J Duthaler, R Katopodis, A Sachs, DH Schuurman, HJ Awwad, M Cooper, DKC AF Teranishi, K Alwayn, IPJ Buhler, L Gollackner, B Knosalla, C Huck, J Duthaler, R Katopodis, A Sachs, DH Schuurman, HJ Awwad, M Cooper, DKC TI Depletion of anti-Gal antibodies by the intravenous infusion of Gal type 2 and 6 glycoconjugates in baboons SO XENOTRANSPLANTATION LA English DT Article DE anti-CD154 monoclonal antibody; anti-pig antibody; anti-Gal antibody; BSA-galactose conjugate; pig-to-primate model; xenotransplantation ID HEMATOPOIETIC-CELL TRANSPLANTATION; PORCINE ENDOTHELIAL-CELLS; NATURAL ANTIBODIES; IMMUNE-COMPLEXES; ANTI-GAL-ALPHA-1-3GAL ANTIBODY; THROMBOTIC MICROANGIOPATHY; IMMUNOAFFINITY COLUMN; TOLERANCE INDUCTION; NONHUMAN-PRIMATES; IN-VITRO AB Background: Natural anti-Gal antibodies (NAb) to Gal epitopes play a key role in the rejection of pig cells or organs transplanted into primates. We have investigated the effect on NAb return after extracorporeal immunoadsorption (EIA) of the continuous intravenous (i.v.) infusion of (i) bovine serum albumin conjugated to Gal type 6 oligosaccharides (BSA-Gal) or (ii) a poly l-lysine backbone conjugated to Gal type 2 or 6 oligosaccharides (PLL-Gal). Methods: Porcine mobilized peripheral blood progenitor cells (PBPC) obtained by leukapheresis from MHC-inbred miniature swine (n = 9) were infused intravenously (i.v.) into baboons: Group 1 baboons (n = 4) received whole body and thymic irradiation, splenectomy, antithymocyte globulin, cobra venom factor, cyclosporine, mycophenolate mofetil, anti-CD154mAb, porcine hematopoietic growth factors, and EIA before transplantation of high doses (2 to 4 x 10(10) cells/kg) of PBPC; Group 2 baboons (n = 3) received the Group 1 regimen plus a continuous i.v. infusion of BSA-Gal for up to 30 days; Group 3 baboons (n = 5) received the Group 1 regimen plus a continuous i.v. infusion of PLL-Gal type 2 (n = 2) or both PLL-Gal types 2 and 6 (n = 3) for up to 30 days. Results: Group 1 : NAb returned to pre-PBPC levels within 20-30 days, but there was no induction of antibody to Gal or non-Gal determinants; Group 2 : NAb was undetectable or at very low level during BSA-Gal therapy. In one baboon, however, IgG to Gal type 2, but not to type 6, returned during BSA-Gal therapy; Group 3 : NAb was undetectable or at very low level during PLL-Gal therapy. In two baboons that received PLL-Gal type 2, NAb to Gal type 6, but not to type 2, returned during PLL-Gal treatment. Two of five baboons, however, developed systemic infection. Four of five baboons died within 14 days; autopsy revealed focal hemorrhagic injury to their hearts, lungs, and small intestines, with histologic abnormalities that varied between animals from hemorrhage and/or thrombosis in some organs (heart, lungs, or intestine) to signs of infections (bacteria in intestine, cytomegalovirus in liver). Conclusions: (i) BSA-Gal and PLL-Gal therapy maintained depletion of NAb. (ii) Some heterogeneity in specificity of NAb was identified, indicating that the infusion of a combination of Gal type 2 and 6 glycoconjugates may be required. (iii) The addition of PLL-Gal to the immunosuppressive regimen was associated with a high incidence of morbidity and mortality without a clear histopathologic entity underlying the cause of death. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Immerge Biotherapeut, Charlestown, MA USA. Novartis Pharma, Transplantat Res, Basel, Switzerland. RP Cooper, DKC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [1P01 AI 45897] NR 32 TC 12 Z9 12 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JUL PY 2003 VL 10 IS 4 BP 357 EP 367 DI 10.1034/j.1399-3089.2003.02078.x PG 11 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 688NY UT WOS:000183443200010 PM 12795685 ER PT J AU Teranishi, K Apitz-Castro, R Robson, SC Romano, E Cooper, DKC AF Teranishi, K Apitz-Castro, R Robson, SC Romano, E Cooper, DKC TI Inhibition of baboon platelet aggregation in vitro and in vivo by the garlic derivative, ajoene SO XENOTRANSPLANTATION LA English DT Article DE ajoene; baboon; platelet aggregation; thrombocytopenia; thrombotic microangiopathy; xenotransplantation ID THROMBOTIC MICROANGIOPATHY; ANTIPLATELET COMPOUND; CELL TRANSPLANTATION; NONHUMAN-PRIMATES; XENOTRANSPLANTATION; COMPONENTS AB Background: The infusion of pig growth factor-mobilized peripheral blood leukocytes (containing 1 to 2% progenitor cells) (pPBPC) into baboons is associated with a thrombotic microangiopathy, which results from a direct effect of these pig cells on platelet aggregation. Ajoene is a synthetic derivative of garlic that inhibits aggregation of human platelets induced by all known agents. To assess its potential use in models of xenotransplantation, this agent was tested for its effect on baboon platelet aggregation in vitro and in vivo. Methods: In vitro studies: Baboon platelet aggregation assays, using adenosine diphosphate (ADP) (20 or 40 mum) or collagen (12.5 mug/ml), were performed after incubation with ajoene (0 to 150 mug/ml) or dipyridamole (0 to 200 mug/ml). Platelets were also incubated with pPBPC (5 x 10(6) cells) without or with ajoene in the absence of a known agonist. In vivo studies: Baboons received either a single intravenous dose of ajoene (10 to 25 mg/kg) or dipyridamole (0.8 mg/kg), or repeated doses of both agents at 2 to 3 h intervals. Platelet-rich plasma was obtained for platelet aggregation assays at time points up to 4 h post-drug administration. Results: In vitro, platelet aggregation was inhibited by 95% (ADP assay) and 89% (collagen assay) by ajoene at concentrations of greater than or equal to75 mug/ml. Dipyridamole had no effect at concentrations of <100 mug/ml, but inhibited aggregation almost completely at higher concentrations. Ajoene inhibited the aggregation caused by pPBPC by 33 to 50%. In vivo, platelet aggregation was completely inhibited for 2 h by ajoene at 25 mg/kg. Dipyridamole at 0.8 mg/kg reduced aggregation by 20% for 15 min, but the effect was lost by 60 min. In combination, the two agents prolonged inhibition marginally. Repeated doses of both agents at 2 h intervals maintained complete inhibition of aggregation, but did not do so when the interval between doses was extended to 2.5 or 3 h. Combined therapy was not associated with any bleeding complications. Conclusions: Although ajoene is a powerful inhibitor of platelet aggregation, the need for repeated administration and its partial effect on pPBPC-induced platelet aggregation would suggest that it may be of only limited value in preventing the thrombotic microangiopathy that develops when pPBPC are infused into baboons. However, it would seem worthy of further investigation when used in combination with other agents. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Inst Venezolano Invest Cient, Caracas, Venezuela. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Immunol, Boston, MA 02215 USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [1P01 AI 45897] NR 17 TC 11 Z9 16 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JUL PY 2003 VL 10 IS 4 BP 374 EP 379 DI 10.1034/j.1399-3089.2003.02068.x PG 6 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 688NY UT WOS:000183443200012 PM 12795687 ER PT J AU Reiser, V Raitt, D Saito, H AF Reiser, V Raitt, D Saito, H TI Yeast osmosensor Sln1 and plant cytokinin receptor Cre1 respond to changes in turgor pressure. SO YEAST LA English DT Meeting Abstract CT 21st International Conference on Yeast Genetics and Molecular Biology CY JUL 07-12, 2003 CL GOTHENBURG, SWEDEN C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0749-503X J9 YEAST JI Yeast PD JUL PY 2003 VL 20 SU 1 BP S169 EP S169 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA 701HH UT WOS:000184161800386 ER PT J AU Wong, SL Zhang, LO Goldberg, DS Tong, AH Lesage, G Vidal, M Andrews, B Bussey, H Boone, C Roth, FP AF Wong, SL Zhang, LO Goldberg, DS Tong, AH Lesage, G Vidal, M Andrews, B Bussey, H Boone, C Roth, FP TI Predicting synthetic lethality from a diverse collection of gene and protein relationships. SO YEAST LA English DT Meeting Abstract CT 21st International Conference on Yeast Genetics and Molecular Biology CY JUL 07-12, 2003 CL GOTHENBURG, SWEDEN C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5G 1L6, Canada. Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON M5G 1L6, Canada. McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0749-503X J9 YEAST JI Yeast PD JUL PY 2003 VL 20 SU 1 BP S344 EP S344 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA 701HH UT WOS:000184161800822 ER PT J AU Lingohr, MK Dickson, LM Wrede, CE McCuaig, JF Myers, MG Rhodes, CJ AF Lingohr, MK Dickson, LM Wrede, CE McCuaig, JF Myers, MG Rhodes, CJ TI IRS-3 inhibits IRS-2-mediated signaling in pancreatic beta-cells SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE insulin receptor substrates (IRS); pancreatic beta-cell; mitogenesis; apoptosis; signal transduction ID RECEPTOR SUBSTRATE-3 IRS-3; PROTEIN-KINASE; PHOSPHOTYROSINE PROTEIN; GLUCOSE-HOMEOSTASIS; INSULIN-RESISTANCE; IGF-I; GROWTH; ACTIVATION; MICE; TRANSDUCTION AB IRS-2 plays an important role in the control of pancreatic beta-cell growth, however it is unclear if other IRS family members are also involved. Using recombinant adenoviruses, IRS-1, -2 and -3 expression was varied in the beta-cell line, INS-1. Increased IRS-1 expression had no appreciable effect on beta-cell growth. However, increased IRS-2 expression augmented glucose/IGF-1 induced beta-cell growth mitogenesis and decreased apoptosis due to glucose-deprivation. In contrast, increased IRS-3 expression significantly inhibited mitogenesis and increased apoptosis. IRS-3 was intransiently located to the beta-cell plasma membrane, and appeared to be inert in terms of IGF-1 induced signaling. However, increased IRS-3 expression blocked glucose/IGF-1 induced IRS-2 translocation from the cytosol to the plasma membrane, dampening IRS-2/IGF-1R interaction and subsequent activation of the PI3K/PKB/GSK3 signaling pathway. In contrast, glucose/IGF-1 induced Erk-1/-2 and p70(S6K) activation were unaffected by IRS-3. These data emphasize the importance of IRS-2/PI3K/PKB signal transduction for beta-cell growth and survival. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Pacific NW Res Inst, Seattle, WA 98122 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98122 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Rhodes, CJ (reprint author), Pacific NW Res Inst, 720 Broadway, Seattle, WA 98122 USA. FU NIDDK NIH HHS [DK60266, DK55269] NR 36 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUN 30 PY 2003 VL 204 IS 1-2 BP 85 EP 99 DI 10.1016/S0303-7207(03)00124-2 PG 15 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 703XA UT WOS:000184306400009 PM 12850284 ER PT J AU Lee, HY Srinivas, H Xia, DR Lu, YL Superty, R LaPushin, R Gomez-Manzano, C Gal, AM Walsh, GL Force, T Ueki, K Mills, GB Kurie, JM AF Lee, HY Srinivas, H Xia, DR Lu, YL Superty, R LaPushin, R Gomez-Manzano, C Gal, AM Walsh, GL Force, T Ueki, K Mills, GB Kurie, JM TI Evidence that phosphatidylinositol 3-kinase- and mitogen-activated protein kinase kinase-4/c-Jun NH2-terminal kinase-dependent pathways cooperate to maintain lung cancer cell survival SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-SUPPRESSOR GENE; PROSTATE CARCINOMA-CELLS; G(1) GROWTH ARREST; PHOSPHOINOSITIDE 3-KINASES; SIGNALING PATHWAYS; BREAST CARCINOMAS; GLIOMA-CELLS; CYCLE ARREST; PTEN; RAS AB Cancer cells in which the PTEN lipid phosphatase gene is deleted have constitutively activated phosphatidylinositol 3-kinase (PI3K)-dependent signaling and require activation of this pathway for survival. In non-small cell lung cancer (NSCLC) cells, PI3K-dependent signaling is typically activated through mechanisms other than PTEN gene loss. The role of PI3K in the survival of cancer cells that express wild-type PTEN has not been defined. Here we provide evidence that H1299 NSCLC cells, which express wild-type PTEN, underwent proliferative arrest following treatment with an inhibitor of all isoforms of class I PI3K catalytic activity (LY294002) or overexpression of the PTEN lipid phosphatase. In contrast, overexpression of a dominant-negative mutant of the p85alpha regulatory subunit of PI3K (Deltap85) induced apoptosis. Whereas PTEN and Delta85 both inhibited activation of AKT/protein kinase B, only Deltap85 inhibited c-Jun NH2-terminal kinase (JNK) activity. Cotransfection of the constitutively active mutant Rac-1 (Val(12)), an upstream activator of JNK, abrogated Deltap85-induced lung cancer cell death, whereas constitutively active mutant mitogen-activated protein kinase kinase (MKK)-1 (R4F) did not. Furthermore, LY294002 induced apoptosis of MKK4-null but not wild-type mouse embryo fibroblasts. Therefore, we propose that, in the setting of wild-type PTEN, PI3K- and MKK4/JNK-dependent pathways cooperate to maintain cell survival. C1 Univ Texas, MD Anderson Canc Ctr, Unit 432, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Therapeut, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX 77030 USA. Tufts Univ New England Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. RP Kurie, JM (reprint author), Univ Texas, MD Anderson Canc Ctr, Unit 432, Dept Thorac Head & Neck Med Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. OI Force, Thomas/0000-0002-0450-8659 FU NCI NIH HHS [CA83639, CA80686, CA82716, P50 CA70907] NR 56 TC 49 Z9 52 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 27 PY 2003 VL 278 IS 26 BP 23630 EP 23638 DI 10.1074/jbc.M300997200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 692AR UT WOS:000183638600054 PM 12714585 ER PT J AU Han, WK Sapirstein, A Hung, CC Alessandrini, A Bonventre, JV AF Han, WK Sapirstein, A Hung, CC Alessandrini, A Bonventre, JV TI Cross-talk between cytosolic phospholipase A(2)alpha (cPLA(2 alpha)) and secretory phospholipase A(2) (sPLA(2)) in hydrogen peroxide-induced arachidonic acid release in murine mesangial cells - sPLA(2) regulates cPLA(2)alpha activity that is responsible for arachidonic acid release SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; SMOOTH-MUSCLE-CELLS; P38 MAP KINASE; P388D(1) MACROPHAGES; INDEPENDENT PATHWAYS; SIGNAL-TRANSDUCTION; EPITHELIAL-CELLS; MAST-CELLS; TYROSINE PHOSPHORYLATION; PROSTAGLANDIN PRODUCTION AB Oxidant stress and phospholipase A(2) (PLA(2)) activation have been implicated in numerous proinflammatory responses of the mesangial cell (MC). We investigated the cross-talk between group IValpha cytosolic PLA(2) (cPLA(2)alpha) and secretory PLA(2)s (sPLA(2)s) during H2O2-induced arachidonic acid (AA) release using two types of murine MC: (i) MC+/+, which lack group IIa and V PLA(2)s, and (ii) MC-/-, which lack groups IIa, V, and IValpha PLA(2)s. H2O2-induced AA release was greater in MC+/+ compared with MC-/-. It has been argued that cPLA(2)alpha plays a regulatory role enhancing the activity of sPLA(2)s, which act on phospholipids to release fatty acid. Group IIa, V, or IValpha PLA(2)s were expressed in MC-/- or MC+/+ using recombinant adenovirus vectors. Expression of cPLA(2)alpha in H2O2-treated MC-/- increased AA release to a level approaching that of H2O2-treated MC+/+. Expression of either group IIa PLA(2) or V PLA(2) enhanced AA release in MC+/+ but had no effect on AA release in MC-/-. When sPLA(2) and cPLA(2)alpha are both present, the effect of H2O2 is manifested by preferential release of AA compared with oleic acid. Inhibition of the ERK and protein kinase C signaling pathways with the MEK-1 inhibitor, U0126, and protein kinase C inhibitor, GF 1092030x, respectively, and chelating intracellular free calcium with 1,2-bis(2-aminophenoyl)ethane-N,N,N',N'-tetraacetic acid-AM, which also reduced ERK1/2 activation, significantly reduced H2O2-induced AA release in MC+/+ expressing either group IIa or V PLA(2)s. By contrast, H2O2-induced AA release was not enhanced when ERK1/2 was activated by infection of MC+/+ with constitutively active MEK1-DD. We conclude that the effect of group IIa and V PLA(2)s on H2O2-induced AA release is dependent upon the presence of cPLA(2)alpha and the activation of PKC and ERK1/2. Group IIa and V PLA(2)s are regulatory and cPLA(2)alpha is responsible for AA release. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med & Anesthesia,Med Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med & Anesthesia,Anesthesia Serv, Charlestown, MA 02129 USA. Harvard MIT Div Hlth Sci & Technol, Charlestown, MA 02129 USA. RP Bonventre, JV (reprint author), Brigham & Womens Hosp, MRB4,75 Francis St, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK10036, DK38452, DK39773]; NINDS NIH HHS [NS10828] NR 89 TC 109 Z9 112 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 27 PY 2003 VL 278 IS 26 BP 24153 EP 24163 DI 10.1074/jbc.M300424200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 692AR UT WOS:000183638600121 PM 12676927 ER PT J AU So, H Rho, J Jeong, D Park, R Fisher, DE Ostrowski, MC Choi, Y Kim, N AF So, H Rho, J Jeong, D Park, R Fisher, DE Ostrowski, MC Choi, Y Kim, N TI Microphthalmia transcription factor and PU.1 synergistically induce the leukocyte receptor osteoclast-associated receptor gene expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TNF FAMILY-MEMBER; DIFFERENTIATION FACTOR; OSTEOPETROSIS; LIGAND; ACTIVATION; MOUSE; TRANCE; MICE; PROTEIN; CELLS AB We have recently reported the identification of a novel member of the leukocyte receptor family, osteoclast-associated receptor (OSCAR), which has two Ig-like domains and functions as a bone-specific regulator of osteoclast differentiation. Here, we have cloned the OSCAR promoter region to examine its regulation by transcription factors. The 1.7-kb promoter region of the mouse OSCAR gene contains two potential E-box elements for microphthalmia transcription factor (MITF) and three putative PU.1 sites. MITF or PU.1 alone activates the OSCAR reporter construct 5-6-fold, and the combination of MITF and PU.1 synergistically activates the OSCAR reporter activity up to 110-fold. The mRNA expression patterns of MITF, PU.1, and OSCAR in TRANCE-treated (RAW 264.7) or TRANCE/M-CSF-treated cells (primary osteoclasts) reveal that MITF mRNA expression is induced at a much earlier time point than OSCAR gene expression. In contrast to MITF, PU.1 mRNA levels remain relatively constant at all time points, suggesting that TRANCE-induced MITF, not PU.1 expression, is one of the critical regulatory mechanisms for optimal OSCAR expression during osteoclastogenesis. In addition, we have shown that the combination of MITF and constitutively active MKK6-expressing plasmids synergistically activates OSCAR reporter activity. Taken together, our results strongly suggest that PU.1 and MITF transcription factors synergistically activate OSCAR gene expression. Moreover, the activation of OSCAR gene expression by PU.1/MITF is further enhanced by the TRANCE-induced MKK6/p38 signaling cascade. C1 Univ Penn, Sch Med, Dept Pathol & Lab Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Wonkwang Univ, Sch Med, Vestibulorcochlear Res Ctr, Chonbuk 570749, South Korea. Chungnam Natl Univ, Dept Microbiol, Taejon 305764, South Korea. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Ohio State Univ, Dept Mol Genet, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Kim, N (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Abramson Family Canc Res Inst, Rm 351 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. RI Ostrowski, Michael/H-3108-2011 OI Ostrowski, Michael/0000-0003-2948-6297 FU NIAMS NIH HHS [AR48251, AR045662, R01-AR44719]; PHS HHS [R13-2002-055-00020] NR 40 TC 63 Z9 66 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 27 PY 2003 VL 278 IS 26 BP 24209 EP 24216 DI 10.1074/jbc.M302940200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 692AR UT WOS:000183638600127 PM 12695521 ER PT J AU Richardson, PG Barlogie, B Berenson, J Singhal, S Jagannath, S Irwin, D Rajkumar, SV Srkalovic, G Alsina, M Alexanian, R Siegel, D Orlowski, RZ Kuter, D Limentani, SA Lee, S Hideshima, T Esseltine, DL Kauffman, M Adams, J Schenkein, DP Anderson, KC AF Richardson, PG Barlogie, B Berenson, J Singhal, S Jagannath, S Irwin, D Rajkumar, SV Srkalovic, G Alsina, M Alexanian, R Siegel, D Orlowski, RZ Kuter, D Limentani, SA Lee, S Hideshima, T Esseltine, DL Kauffman, M Adams, J Schenkein, DP Anderson, KC TI A phase 2 study of bortezomib in relapsed, refractory myeloma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PROTEASOME INHIBITOR PS-341; HUMAN MULTIPLE-MYELOMA; NF-KAPPA-B; OVERCOMES DRUG-RESISTANCE; THERAPEUTIC APPLICATIONS; 26S PROTEASOME; PANCREATIC-CANCER; IN-VIVO; CELLS; GROWTH AB BACKGROUND: Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity. METHODS: In this multicenter, open-label, nonrandomized, phase 2 trial, we enrolled 202 patients with relapsed myeloma that was refractory to the therapy they had received most recently. Patients received 1.3 mg of bortezomib per square meter of body-surface area twice weekly for 2 weeks, followed by 1 week without treatment, for up to eight cycles (24 weeks). In patients with a suboptimal response, oral dexamethasone (20 mg daily, on the day of and the day after bortezomib administration) was added to the regimen. The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. RESULTS: Of 193 patients who could be evaluated, 92 percent had been treated with three or more of the major classes of agents for myeloma, and in 91 percent, the myeloma was refractory to the therapy received most recently. The rate of response to bortezomib was 35 percent, and those with a response included 7 patients in whom myeloma protein became undetectable and 12 in whom myeloma protein was detectable only by immunofixation. The median overall survival was 16 months, with a median duration of response of 12 months. Grade 3 adverse events included thrombocytopenia (in 28 percent of patients), fatigue (in 12 percent), peripheral neuropathy (in 12 percent), and neutropenia (in 11 percent). Grade 4 events occurred in 14 percent of patients. CONCLUSIONS: Bortezomib, a member of a new class of anticancer drugs, is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Univ Arkansas, Little Rock, AR 72204 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Northwestern Univ, Med Ctr, Chicago, IL 60611 USA. St Vincents Catholic Med Ctr, New York, NY USA. Alta Bates Canc Ctr, Berkeley, CA USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Carol G Simon Canc Ctr, Morristown, NJ USA. Univ N Carolina, Chapel Hill, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Charlotte Med Clin, Charlotte, NC USA. Millennium Pharmaceut, Cambridge, MA USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,Dana 1B12, Boston, MA 02115 USA. OI Rajkumar, S. Vincent/0000-0002-5862-1833 NR 42 TC 1738 Z9 1830 U1 8 U2 75 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 26 PY 2003 VL 348 IS 26 BP 2609 EP 2617 DI 10.1056/NEJMoa030288 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 693PN UT WOS:000183726400004 PM 12826635 ER PT J AU McGlynn, EA Asch, SM Adams, J Keesey, J Hicks, J DeCristofaro, A Kerr, EA AF McGlynn, EA Asch, SM Adams, J Keesey, J Hicks, J DeCristofaro, A Kerr, EA TI The quality of health care delivered to adults in the United States SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ELDERLY MEDICARE BENEFICIARIES; STANDARDIZED PATIENTS; MANAGED CARE; UNDERUSE; APPROPRIATENESS; OUTCOMES; TRIALS; SYSTEM; HYPERTENSION AB BACKGROUND: We have little systematic information about the extent to which standard processes involved in health care -- a key element of quality -- are delivered in the United States. METHODS: We telephoned a random sample of adults living in 12 metropolitan areas in the United States and asked them about selected health care experiences. We also received written consent to copy their medical records for the most recent two-year period and used this information to evaluate performance on 439 indicators of quality of care for 30 acute and chronic conditions as well as preventive care. We then constructed aggregate scores. RESULTS: Participants received 54.9 percent (95 percent confidence interval, 54.3 to 55.5) of recommended care. We found little difference among the proportion of recommended preventive care provided (54.9 percent), the proportion of recommended acute care provided (53.5 percent), and the proportion of recommended care provided for chronic conditions (56.1 percent). Among different medical functions, adherence to the processes involved in care ranged from 52.2 percent for screening to 58.5 percent for follow-up care. Quality varied substantially according to the particular medical condition, ranging from 78.7 percent of recommended care (95 percent confidence interval, 73.3 to 84.2) for senile cataract to 10.5 percent of recommended care (95 percent confidence interval, 6.8 to 14.6) for alcohol dependence. CONCLUSIONS: The deficits we have identified in adherence to recommended processes for basic care pose serious threats to the health of the American public. Strategies to reduce these deficits in care are warranted. C1 RAND Corp, Santa Monica, CA 90407 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. VA Ann Arbor Hlth Care Syst, VA Ctr Practice Management & Outcomes Res, Ann Arbor, MI USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. RP McGlynn, EA (reprint author), RAND Corp, 1700 Main St,POB 2138, Santa Monica, CA 90407 USA. NR 51 TC 2525 Z9 2548 U1 6 U2 90 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 26 PY 2003 VL 348 IS 26 BP 2635 EP 2645 DI 10.1056/NEJMsa022615 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 693PN UT WOS:000183726400008 PM 12826639 ER PT J AU Larsen, EC Connolly, SA Rosenberg, AE AF Larsen, EC Connolly, SA Rosenberg, AE TI A nine-year-old girl with hepatosplenomegaly and pain in the thigh - Gaucher's disease, type I. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; ENZYME REPLACEMENT THERAPY; CLINICAL-FEATURES; BONE; ABNORMALITIES; LYMPHOMA; CHILDREN; PATIENT C1 Dartmouth Hitchcock Med Ctr, Div Pediat Hematol Oncol, Lebanon, NH 03766 USA. Dartmouth Coll Sch Med, Dept Pediat, Lebanon, NH USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Larsen, EC (reprint author), Dartmouth Hitchcock Med Ctr, Div Pediat Hematol Oncol, Lebanon, NH 03766 USA. NR 31 TC 4 Z9 4 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 26 PY 2003 VL 348 IS 26 BP 2669 EP 2677 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 693PN UT WOS:000183726400011 PM 12826642 ER PT J AU Kramer, HJ Nguyen, QD Curhan, G Hsu, CY AF Kramer, HJ Nguyen, QD Curhan, G Hsu, CY TI Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ARTERIAL-HYPERTENSION; SERUM CREATININE; NEPHROPATHY; MICROALBUMINURIA; PREVALENCE; DISEASE; PREDICTION; STAGE AB Context Kidney disease in type 2 diabetes mellitus (DM) is more heterogeneous than in type 1 DM. Reduced glomerular-filtration rate (GFR) among individuals with type 2 DM may not always be due to classic diabetic glomerulosclerosis, which is associated with albuminuria and retinopathy. Objective To determine the prevalence of chronic renal insufficiency (CRI), defined as a GFR less than 60 mL/min per 1.73 m(2) body surface area (BSA) in the absence of microalbuminuria or macroalbuminuria and diabetic retinopathy among adults with type 2 DM. Design, Setting, and Participants Cross-sectional analysis of adults aged 40 years or older with type 2 DM in the Third National Health and Nutrition Examination Survey, a probability sample of the total civilian US non institutionalized population conducted from 1988-1994. Main Outcome Measures The GFR per 1.73 m(2) BSA, calculated with serum creatinine, urea nitrogen, and serum albumin levels using the Modification of Diet in Renal Disease Study prediction equation; albuminuria, assessed using spot urine albumin/ creatinine ratio; and presence of retinopathy, determined with fundus photography. Results Overall, 13% (sampled n=171) of adults with type 2 DM (n=1197) had CRI with a population estimate of 1.1 million. Among these adults with CRI, diabetic retinopathy was noted in 28% (n=58), while the frequencies of microalbuminuria and macroalbuminuria were 45% (n=64) and 19% (n=47), respectively. Retinopathy and albuminuria (microalbuminuria or macroalbuminuria) were both absent in 30% (n=51) of adults with type 2 DM and CRI. The population estimate of adults with type 2 DM and CRI in the absence of diabetic retinopathy or albuminuria was approximately 0.3 million. Conclusions A substantial burden of CRI among persons with type 2 DM in the United States is likely due to renal parenchymal disease other than classic diabetic glomerulosclerosis. Approaches to screening renal disease in the type 2 DM population should incorporate assessment of GFR in addition to monitoring urine albumin excretion and funduscopic changes to ensure that individuals with type 2 DM and CRI not due to diabetic glomerulosclerosis will receive appropriate intervention. C1 Loyola Univ, Med Ctr, Dept Epidemiol & Prevent Med, Div Nephrol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Med, Div Nephrol, Maywood, IL 60153 USA. Johns Hopkins Med Inst, Wilmer Ophthalmol Inst, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. RP Kramer, HJ (reprint author), Loyola Univ, Med Ctr, Dept Epidemiol & Prevent Med, Div Nephrol, 2160 S 1st Ave, Maywood, IL 60153 USA. OI Kramer, Holly/0000-0002-6374-837X FU NEI NIH HHS [EY13552]; NIDDK NIH HHS [DK52866, DK61520] NR 26 TC 275 Z9 296 U1 0 U2 11 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 JUN 25 PY 2003 VL 289 IS 24 BP 3273 EP 3277 DI 10.1001/jama.289.24.3273 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 693EX UT WOS:000183704600020 PM 12824208 ER PT J AU Watson, GS Peskind, ER Asthana, S Purganan, K Wait, C Chapman, D Schwartz, MW Plymate, S Craft, S AF Watson, GS Peskind, ER Asthana, S Purganan, K Wait, C Chapman, D Schwartz, MW Plymate, S Craft, S TI Insulin increases CSF A beta 42 levels in normal older adults SO NEUROLOGY LA English DT Article ID AMYLOID BETA-PROTEIN; APOLIPOPROTEIN-E GENOTYPE; ALZHEIMERS-DISEASE; DEGRADING ENZYME; CEREBROSPINAL-FLUID; EXTRACELLULAR LEVELS; DIABETES-MELLITUS; A-BETA; DEGRADATION; MEMORY AB Background: Abnormal insulin metabolism may contribute to the clinical symptoms and pathophysiology of AD. In vitro studies show that insulin enhances the release of beta- amyloid protein ( Abeta) or inhibits its degradation, either of which might increase amyloid burden. Methods: On separate mornings, 16 healthy older adults ( 10 women, 6 men; mean age 68.7 years, SD 8.6 years) each underwent two infusions consisting of either saline ( placebo) or insulin ( 1.0 mU. kg(-1).min(-1)) plus dextrose to maintain euglycemia. After 120 minutes of infusion, blood, CSF, and cognitive measures were acquired. Results: As expected, insulin infusion produced an increase in CSF insulin concentration. Insulin infusion also led to an increase in CSF Abeta42 levels, most notably in older subjects. As has been observed previously, insulin infusion facilitated declarative memory, but such facilitation was attenuated in the subjects with the greatest increase in CSF Abeta42 levels. Conclusions: These findings are consistent with recent in vitro studies of insulin effects on Abeta and support the notion that insulin may modulate Abeta42 levels acutely in humans. C1 Washington Univ, Sch Med, VAPSHCS, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Washington Univ, Sch Med, VAPSHCS, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Washington Univ, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. Washington Univ, Sch Med, Dept Med, Seattle, WA 98108 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI USA. Univ Wisconsin, Sch Med, William S Middleton Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, Madison, WI USA. RP Craft, S (reprint author), Washington Univ, Sch Med, VAPSHCS, Ctr Geriatr Res Educ & Clin, S-182,1660 S Columbian Way, Seattle, WA 98108 USA. RI Schwartz, Michael/H-9950-2012 FU NIA NIH HHS [T32 AG00258, R01 AG10880] NR 33 TC 155 Z9 168 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 24 PY 2003 VL 60 IS 12 BP 1899 EP 1903 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 693CF UT WOS:000183696500005 PM 12821730 ER PT J AU MacCollin, M Willett, C Heinrich, B Jacoby, LB Acierno, JS Perry, A Louis, DN AF MacCollin, M Willett, C Heinrich, B Jacoby, LB Acierno, JS Perry, A Louis, DN TI Familial schwannomatosis - Exclusion of the NF2 locus as the germline event SO NEUROLOGY LA English DT Article ID NEUROFIBROMATOSIS TYPE-1; LINKAGE ANALYSIS; GENE; MUTATIONS; TUMORS; HYBRIDIZATION; RECOMBINATION; ABNORMALITIES; ABERRATIONS; DELETIONS AB Background: Schwannomatosis is a recently recognized disorder, defined as multiple pathologically proven schwannomas without vestibular tumors diagnostic of neurofibromatosis 2 ( NF2). Some investigators have questioned whether schwannomatosis is merely an attenuated form of NF2. Methods: The authors identified eight families in which a proband met their diagnostic criteria for schwannomatosis. Archived and prospectively acquired tumor specimens were studied by mutational analysis at the NF2 locus, loss of heterozygosity analysis along chromosome 22, and fluorescent in situ hybridization analysis of NF2 and the more centromeric probe BCR. Linkage analysis could be performed in six of eight families. Results: Clinical characterization of these kindreds showed that no affected family member harbored a vestibular tumor. Molecular analysis of 28 tumor specimens from 17 affected individuals in these kindreds revealed a pattern of somatic NF2 inactivation incompatible with our current understanding of NF2 as an inherited tumor suppressor gene syndrome. Linkage analysis excluded the NF2 locus in two kindreds, and showed a maximum lod score of 6.60 near the more centromeric marker D22S1174. Conclusions: Schwannomatosis shows clinical and molecular differences from NF2 and should be considered a third major form of neurofibromatosis. Further work is needed to identify the inherited genetic element responsible for familial schwannomatosis. C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurosurg, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA USA. Harvard Univ, Sch Med, Harvard Inst Human Genet, Boston, MA USA. Washington Univ, Sch Med, Div Neuropathol, St Louis, MO USA. RP MacCollin, M (reprint author), Ctr Neurosci, MGH E,Bldg 149,13th St, Charlestown, MA 02129 USA. OI Perry, Arie/0000-0002-8300-7261 FU PHS HHS [R01-3587804] NR 35 TC 73 Z9 79 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 24 PY 2003 VL 60 IS 12 BP 1968 EP 1974 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 693CF UT WOS:000183696500016 PM 12821741 ER PT J AU Lammerding, J Kazarov, AR Huang, H Lee, RT Hemler, ME AF Lammerding, J Kazarov, AR Huang, H Lee, RT Hemler, ME TI Tetraspanin CD151 regulates alpha 6 beta 1 integrin adhesion strengthening SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELL-SURFACE RECEPTORS; EXTRACELLULAR-MATRIX; ALPHA-3-BETA-1 INTEGRIN; ENDOTHELIAL-CELLS; ACTIVATION STATE; LIVING CELLS; CYTOSKELETON; MOLECULES; FORCES; FIBRONECTIN AB The tetraspanin CD151 molecule associates specifically with laminin-binding integrins, including alpha6beta1. To probe strength of alpha6beta1-dependent adhesion to laminin-1, defined forces (0-1.5 nN) were applied to magnetic laminin-coated microbeads bound to NIH 3T3 cells. For NIH 3T3 cells bearing wild-type CD151, adhesion strengthening was observed, as bead detachment became more difficult overtime. In contrast, mutant CD151 (with the C-terminal region replaced) showed impaired adhesion strengthening. Static cell adhesion to laminin-1, and detachment of beads coated with fibronectin or anti-alpha6 antibody were all unaffected by CD151 mutation.. Hence, CD151 plays a key role in selectively strengthening alpha6beta1 integrin-mediated adhesion to laminin-1. C1 MIT, Biol Engn Div, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Hemler, ME (reprint author), MIT, Biol Engn Div, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Lammerding, Jan/A-9498-2016 OI Lammerding, Jan/0000-0003-4335-8611 FU NCI NIH HHS [R01-CA42368, R01 CA042368, R01 CA086712, R01-CA86712]; NHLBI NIH HHS [P01 HL064858, P01-HL64858] NR 48 TC 116 Z9 125 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 24 PY 2003 VL 100 IS 13 BP 7616 EP 7621 DI 10.1073/pnas.1337546100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 695TE UT WOS:000183845800039 PM 12805567 ER PT J AU Lugo-Villarino, G Maldonado-Lopez, R Possemato, R Penaranda, C Glimcher, LH AF Lugo-Villarino, G Maldonado-Lopez, R Possemato, R Penaranda, C Glimcher, LH TI T-bet is required for optimal production of IFN-gamma and antigen-specific T cell activation by dendritic cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MOUSE BONE-MARROW; INTERFERON-GAMMA; IN-VIVO; TRANSCRIPTION FACTOR; LINEAGE COMMITMENT; EXPRESSION; RECEPTOR; STAT4; MICE; CD8-ALPHA(+) AB IFN-gamma is well known as the signature cytokine of CD4(+) T helper 1, CD8(+), and natural killer cells, but recent studies demonstrate that antigen-presenting cells, in particular dendritic cells (DCs), are another potent source for this proinflammatory cytokine. T-bet, a transcription factor that controls IFN-gamma expression in CD4(+) T cells, was reported recently to be expressed in human monocytes and myeloid DCs. In this study we investigate the role of T-bet in this important cell type. The development, differentiation, and activation of bone marrow and splenic IDCs were unimpaired in mice lacking T-bet. However, T-bet was essential for the optimal production of IFN-gamma by both CD8alpha(+) and CD8alpha(-) DCs. T-bet-cleficient IDCs were significantly impaired in their capacity to secrete IFN-gamma after both stimulation with IL-12 alone or in combination with IL-18. Further, T-bet(-/-) DCs were impaired in their ability to activate the T helper 1 program of adoptively transferred antigenspecific T cells in vivo. The rapid up-regulation of T-bet by IFN-gamma in DCs coupled with a function for DC-derived IFN-gamma in T cell activation may constitute a positive feedback loop to maximize type 1 immunity. C1 Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ohio Univ, Dept Biol Sci, Athens, OH 45701 USA. RP Glimcher, LH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, FXB205,651 Huntington Ave, Boston, MA 02115 USA. OI Lugo, Geanncarlo/0000-0003-4620-8491 FU NIAID NIH HHS [AI29673, AI32412, R01 AI029673, R01 AI032412, R37 AI029673] NR 49 TC 156 Z9 174 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 24 PY 2003 VL 100 IS 13 BP 7749 EP 7754 DI 10.1073/pnas.1332767100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 695TE UT WOS:000183845800062 PM 12802010 ER PT J AU Majumder, PK Yeh, JJ George, DJ Febbo, PG Kum, J Xue, Q Bikoff, R Ma, HF Kantoff, PW Golub, TR Loda, M Sellers, WR AF Majumder, PK Yeh, JJ George, DJ Febbo, PG Kum, J Xue, Q Bikoff, R Ma, HF Kantoff, PW Golub, TR Loda, M Sellers, WR TI Prostate intraepithelial neoplasia induced by prostate restricted Akt activation: The MPAKT model SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID STEM-CELL ANTIGEN; TUMOR-SUPPRESSOR PROTEIN; SIGNALING PATHWAY; TRANSGENIC MICE; GENE-EXPRESSION; PTEN; CANCER; KINASE; SIZE; MARKER AB To determine whether Akt activation was sufficient for the transformation of normal prostate epithelial cells, murine prostate restricted Akt kinase activity was generated in transgenic mice (MPAKT mice). Akt expression led to p70(S6K) activation, prostatic intraepithelial neoplasia (PIN), and bladder obstruction. mRNA expression profiles from MPAKT ventral prostate revealed similarities to human cancer and an angiogenic signature that included three angiogenin family members, one of which was found elevated in the plasma of men with prostate cancer. Thus, the MPAKT model may be useful in studying the role of Akt in prostate epithelial cell transformation and in the discovery of molecular markers relevant to human disease. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Sellers, WR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, D720C,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA089021, P01 CA89021] NR 37 TC 199 Z9 206 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 24 PY 2003 VL 100 IS 13 BP 7841 EP 7846 DI 10.1073/pnas.1232229100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 695TE UT WOS:000183845800078 PM 12799464 ER PT J AU Collins, TC Petersen, NJ Suarez-Almazor, M Ashton, CM AF Collins, TC Petersen, NJ Suarez-Almazor, M Ashton, CM TI The prevalence of peripheral arterial disease in a racially diverse population SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the Veterans-Affairs-Health-Services-Research-and-Development-Service CY FEB 14, 2002 CL WASHINGTON, D.C. SP Veterans Affairs Hlth Serv Res Dev Serv ID ANKLE-BRACHIAL INDEX; INTERMITTENT CLAUDICATION; DEFINED POPULATION; PREDICTOR; MORTALITY; ADULTS; EVENTS; TRIAL; RISK AB Background: The purpose of this study was to determine the prevalence of peripheral arterial disease (PAD) in white, African American, and English- and Spanish-speaking Hispanic patients. Methods: We screened patients older than 50 years for PAD at 4 primary care clinics located in the Houston Veterans Affairs Medical Center and the Harris County Hospital District. The disease was diagnosed by an ankle-brachial index of less than 0.9. Patients also completed questionnaires to ascertain symptoms of intermittent claudication, walking difficulty, medical history, and quality of life. Results: We enrolled 403 patients (136 whites-, 136 African Americans, and 131 Hispanics, 81 of whom were Spanish speaking). The prevalence of PAD was 13.2% among whites, 22.8% among African Americans, and 13.7% among Hispanics (P=.06). African Americans had a significantly higher prevalence of PAD than whites and Hispanics combined (P=.02). Among all patients who were diagnosed as having PAD on the basis of their ankle-brachial index, only 5 (7.5%) had symptoms of intermittent claudication. Conclusions: Peripheral arterial disease is a prevalent illness in the primary care setting. Its prevalence varies by race and is higher in African Americans than in whites and Hispanics. Relative to the prevalence of PAD, the prevalence of intermittent claudication is low. Since measurement of the ankle-brachial index is not part of the routine clinic visit, many patients with PAD are not diagnosed unless they develop symptoms of intermittent claudication. Because of this, it is likely that many patients remain undiagnosed. Efforts are needed to improve PAD detection in the primary care setting. C1 Dept Vet Affairs, Houston Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. RP Collins, TC (reprint author), Dept Vet Affairs, Houston Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. NR 27 TC 79 Z9 83 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 23 PY 2003 VL 163 IS 12 BP 1469 EP 1474 DI 10.1001/archinte.163.12.1469 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 693FC UT WOS:000183705400012 PM 12824097 ER PT J AU Reiser, V Raitt, DC Saito, H AF Reiser, V Raitt, DC Saito, H TI Yeast osmosensor Sln1 and plant cytokinin receptor Cre1 respond to changes in turgor pressure SO JOURNAL OF CELL BIOLOGY LA English DT Article DE signal transduction; high osmolarity stress; histidine kinase; two-component system; HOG MAPK pathway ID ACTIVATED PROTEIN-KINASE; SACCHAROMYCES-CEREVISIAE; OSMOTIC-STRESS; ESCHERICHIA-COLI; HISTIDINE KINASE; CELL POLARITY; BUDDING YEAST; ARABIDOPSIS; PATHWAY; AHK4 AB Very little is known about how cellular osmosensors monitor changes in osmolarity of the environment. Here, we report that in yeast, Sln1 osmosensor histidine kinase monitors changes in turgor pressures. Reductions in turgor caused by either hyperosmotic stress, nystatin, or removal of cell wall activate MAPK Hog1 specifically through the SLN1 branch, but not through the SHO1 branch of the high osmolarity glycerol pathway. The integrity of the periplasmic region of Sln1 was essential for its sensor function. We found that activity of the plant histidine kinase cytokinin response 1 (Crel) is also regulated by changes in turgor pressure, in a manner identical to that of Sln1, in the presence of cytokinin. We propose that Sln1 and Cre1 are turgor sensors, and that similar turgor-sensing mechanisms might regulate hyperosmotic stress responses both in yeast and plants. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Tokyo 1088639, Japan. RP Saito, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM56699] NR 33 TC 130 Z9 137 U1 1 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 23 PY 2003 VL 161 IS 6 BP 1035 EP 1040 DI 10.1083/jcb.200301099 PG 6 WC Cell Biology SC Cell Biology GA 695JM UT WOS:000183827400005 PM 12821642 ER PT J AU Jiang, SB Pope, C Al Jarrah, KM Kung, JH Bortfeld, T Chen, GTY AF Jiang, SB Pope, C Al Jarrah, KM Kung, JH Bortfeld, T Chen, GTY TI An experimental investigation on intra-fractional organ motion effects in lung IMRT treatments SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID INTENSITY-MODULATED RADIOTHERAPY; RADIATION-THERAPY; DELIVERY; CANCER; ISSUES AB Respiration-induced tumour motion can potentially compromise the use of intensity-modulated radiotherapy (IMRT) as a dose escalation tool for lung tumour treatment. We have experimentally investigated the intra-fractional or-an motion effects in lung IMRT treatments delivered by multi-leaf collimator (MLC). An in-house made motor-driven platform, which moves sinusoidally with an amplitude of 1 cm and a period of 4 s, was used to mimic tumour motion. Tumour motion was simulated along cranial-caudal direction while MLC leaves moved across the patient from left to right, as in most clinical cases. The dose to a point near the centre of the tumour mass was measured according to geometric and dosimetric parameters from two five-field lung IMRT plans. For each field, measurement was done for two dose rates (300 and 500 MU min(-1)), three MLC delivery modes (sliding window, step-and-shoot with 10 and 20 intensity levels) and eight equally spaced starting phases of tumour motion. The dose to the measurement point delivered from all five fields was derived for both a single fraction and 30 fractions by randomly sampling from measured dose values of each field at different initial phases. It was found that the mean dose to a moving tumour differs slightly (<2-3%) from that to a static tumour. The variation in breathing phase at the start of dose delivery results in a maximum variation around the mean dose of greater than 30% for one field. The full width at half maximum for the probability distribution of the point dose is up to 8% for all five fields in a single fraction, but less than 1-2% after 30 fractions. In general, lower dose rate can reduce the motion-caused dose variation and therefore might be preferable for lung IMRT when no motion mitigation techniques are used. From the two IMRT cases we studied where tumour motion is perpendicular to MLC leaf motion, the dose variation was found to be insensitive to the MLC delivery mode. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jiang, SB (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 12 TC 183 Z9 191 U1 1 U2 9 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUN 21 PY 2003 VL 48 IS 12 BP 1773 EP 1784 AR PII S0031-9155(03)59928-6 DI 10.1088/0031-9155/48/12/307 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 699NQ UT WOS:000184063200007 PM 12870582 ER PT J AU Lepine, F Deziel, E Milot, S Rahme, LG AF Lepine, F Deziel, E Milot, S Rahme, LG TI A stable isotope dilution assay for the quantification of the Pseudomonas quinolone signal in Pseudomonas aeruginosa cultures SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE PQS; stable isotope; mass spectrometry; Pseudomonas aeruginosa ID TO-CELL COMMUNICATION; CYSTIC-FIBROSIS; GENE-EXPRESSION; BACTERIAL-CELL; VIRULENCE GENE; DIHYDROSTREPTOMYCIN; MEMBRANE; ELASTASE; SYSTEMS; LAS AB A stable isotope dilution method was developed to analyse 2-heptyl-3,4-dihydroxyquinoline, also called the Pseudomonas quinolone signal (PQS), directly in Pseudomonas aeruginosa cultures by liquid chromatography coupled to mass spectrometry (LC/MS). PQS, along with the isobaric 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), were quantified in various Pseudomonas liquid cultures using a deuterated PQS analog as internal standard. The kinetic of production of these quinolines in a growing culture of P aeruginosa PA14 showed that their production starts at the end of the logarithmic growth phase and is maximal at the onset of the stationary growth phase. The concentration of PQS reached a maximum at 13 mg/l and then decreased, while the HQNO concentration reached 18 mg/l and then remained stable. Culture supernatants of P aeruginosa strains PAO1 and PA14 produced similar concentrations of PQS whereas no PQS or HQNO could be detected in culture supernatants of the P. aeruginosa strain PAK or in the other Pseudomonas species tested, including phytopathogenic pseudomonads. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Univ Quebec, Inst Armand Frappier, INRS, Laval, PQ H7V 1B7, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Shriners Burns Inst, Boston, MA 02114 USA. RP Lepine, F (reprint author), Univ Quebec, Inst Armand Frappier, INRS, 531 Boul Prairies, Laval, PQ H7V 1B7, Canada. RI Deziel, Eric/A-7678-2008 OI Deziel, Eric/0000-0002-4609-0115 NR 25 TC 77 Z9 79 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD JUN 20 PY 2003 VL 1622 IS 1 BP 36 EP 41 DI 10.1016/S0304-4165(03)00103-X PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 728GK UT WOS:000185709300006 PM 12829259 ER PT J AU Gupta, RA Sarraf, P Mueller, E Brockman, JA Prusakiewicz, JJ Eng, C Willson, TM DuBois, RN AF Gupta, RA Sarraf, P Mueller, E Brockman, JA Prusakiewicz, JJ Eng, C Willson, TM DuBois, RN TI Peroxisome proliferator-activated receptor gamma-mediated differentiation - A mutation in colon cancer cells reveals divergent and cell type-specific mechanisms SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR HORMONE RECEPTORS; PPAR-GAMMA; ADIPOCYTE DIFFERENTIATION; ORPHAN RECEPTORS; CO-REPRESSOR; IN-VITRO; GENE; LIGAND; ADIPOGENESIS; EXPRESSION AB Activation of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma) inhibits cell growth and induces differentiation in both adipocyte and epithelial cell lineages, although it is unclear whether this occurs through common or cell-type specific mechanisms. We have identified four human colon cancer cell lines that do no undergo growth inhibition or induce markers of differentiation after exposure to PPARgamma agonists. Sequence analysis of the PPARgamma gene revealed that all four cell lines contain a previously unidentified point mutation in the ninth alpha-helix of the ligand binding domain at codon 422 (K422Q). The mutant receptor did not exhibit any defects in DNA binding or retinoid X receptor heterodimerization and was transcriptionally active in an artificial reporter assay. However, only retroviral transduction of the wild-type (WT), but not mutant, receptor could restore PPARgamma ligand-induced growth inhibition and differentiation in resistant colon cancer cell lines. In contrast, there was no difference in the ability of fibroblast cells expressing WT or K422Q mutant receptor to undergo growth inhibition, express adipocyte differentiation markers, or uptake lipid after treatment with a PPARgamma agonist. Finally, analysis of direct PPARgamma target genes in colon cancer cells expressing the WT or K422Q mutant allele suggests that the mutation may disrupt the ability of PPARgamma to repress the basal expression of a subset of genes in the absence of exogenous ligand. Collectively, these data argue that codon 422 may be a part of a co-factor(s) interaction domain necessary for PPARgamma to induce terminal differentiation in epithelial, but not adipocyte, cell lineages and argues that the receptor induces growth inhibition and differentiation via cell lineage-specific mechanisms. C1 Vanderbilt Univ, Med Ctr, Dept Cellular & Dev Biol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Biochem, Nashville, TN 37232 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Biol, Boston, MA 02115 USA. Psychiat Genom Inc, Gaithersburg, MD 20878 USA. Ohio State Univ, Ctr Comprehens Canc, Human Genet Program, Columbus, OH 43210 USA. GlaxoSmithKline, Nucl Receptor Discovery Res, Res Triangle Pk, NC 27709 USA. RP DuBois, RN (reprint author), Vanderbilt Univ, Med Ctr, Dept Med GI, MCN C-2104,1161 21st Ave S, Nashville, TN 37232 USA. FU NCI NIH HHS [P01CA-77839]; NIDDK NIH HHS [R01DK 47279]; NIEHS NIH HHS [P030 ES-00267-29] NR 47 TC 45 Z9 45 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 20 PY 2003 VL 278 IS 25 BP 22669 EP 22677 DI 10.1074/jbc.M300637200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 689QF UT WOS:000183503900067 PM 12591919 ER PT J AU Garsin, DA Villanueva, JM Begun, J Kim, DH Sifri, CD Calderwood, SB Ruvkun, G Ausubel, FM AF Garsin, DA Villanueva, JM Begun, J Kim, DH Sifri, CD Calderwood, SB Ruvkun, G Ausubel, FM TI Long-lived C-elegans daf-2 mutants are resistant to bacterial pathogens SO SCIENCE LA English DT Article ID CAENORHABDITIS-ELEGANS; SYSTEM; HOST C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RI Begun, Jakob/J-6793-2014 OI Begun, Jakob/0000-0001-5256-7672 FU NIGMS NIH HHS [GM48707] NR 7 TC 280 Z9 286 U1 7 U2 22 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 20 PY 2003 VL 300 IS 5627 BP 1921 EP 1921 DI 10.1126/science.1080147 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 691RN UT WOS:000183619400038 PM 12817143 ER PT J AU Schwartz, CE Wright, CI Shin, LM Kagan, J Rauch, SL AF Schwartz, CE Wright, CI Shin, LM Kagan, J Rauch, SL TI Inhibited and uninhibited infants "grown up": Adult amygdalar response to novelty SO SCIENCE LA English DT Article ID BEHAVIORAL-INHIBITION; SOCIAL PHOBIA; CHILDREN; ASSOCIATION; TEMPERAMENT; ADOLESCENCE; ACTIVATION; DISORDER; ANXIETY; FACES AB Infants with an inhibited temperament tend to develop into children who avoid people, objects, and situations that are novel or unfamiliar, whereas uninhibited children spontaneously approach novel persons, objects, and situations. Behavioral and physiological features of these two temperamental categories are moderately stable from infancy into early adolescence and have been hypothesized to be due, in part, to variation in amygdalar responses to novelty. We found that adults who had been categorized in the second year of life as inhibited, compared with those previously categorized as uninhibited, showed greater functional MRI signal response within the amygdala to novel versus familiar faces. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Dev Psychopathol Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Psychiat Neuroimaging Res Program, Charlestown, MA 02129 USA. MGH, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. MGH, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Neurol, Brigham Behav Neurol Grp, Boston, MA 02115 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Schwartz, CE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Dev Psychopathol Res Grp, 13th St,Bldg 149,CNY-9, Charlestown, MA 02129 USA. NR 27 TC 299 Z9 303 U1 2 U2 17 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 20 PY 2003 VL 300 IS 5627 BP 1952 EP 1953 DI 10.1126/science.1083703 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 691RN UT WOS:000183619400049 PM 12817151 ER PT J AU Lipsitch, M Cohen, T Cooper, B Robins, JM Ma, S James, L Gopalakrishna, G Chew, SK Tan, CC Samore, MH Fisman, D Murray, M AF Lipsitch, M Cohen, T Cooper, B Robins, JM Ma, S James, L Gopalakrishna, G Chew, SK Tan, CC Samore, MH Fisman, D Murray, M TI Transmission dynamics and control of severe acute respiratory syndrome SO SCIENCE LA English DT Article AB Severe acute respiratory syndrome (SARS) is a recently described illness of humans that has spread widely over the past 6 months. With the use of detailed epidemiologic data from Singapore and epidemic curves from other settings, we estimated the reproductive number for SARS in the absence of interventions and in the presence of control efforts. We estimate that a single infectious case of SARS will infect about three secondary cases in a population that has not yet instituted control measures. Public-health efforts to reduce transmission are expected to have a substantial impact on reducing the size of the epidemic. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Minist Hlth, Epidemiol & Dis Control Div, Singapore 169854, Singapore. Univ Utah, Dept Med, Salt Lake City, UT 84132 USA. McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON L8N 3Z5, Canada. City Hamilton Publ Hlth & Community Serv Dept, Hamilton, ON L8R 3L5, Canada. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Murray, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM mmurray@hsph.harvard.edu RI Cohen, Ted/G-8101-2011; OI Cooper, Ben/0000-0002-9445-7217; Lipsitch, Marc/0000-0003-1504-9213 FU NIAID NIH HHS [K08 AI055985, K08 AI055985-01A1, R01 AI 32475, R01 AI 46669, R01 AI 48935, R21 AI 55825, T32 AI07433] NR 11 TC 499 Z9 540 U1 6 U2 43 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 20 PY 2003 VL 300 IS 5627 BP 1966 EP 1970 DI 10.1126/science.1086616 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 691RN UT WOS:000183619400053 PM 12766207 ER PT J AU Pion, M Sanchez, G Liska, V Bettendroffer, L Candotti, D Chenine, AL Gondois-Rey, F Tamalet, C Vigne, R Ruprecht, RM Agut, H Hirsch, I AF Pion, M Sanchez, G Liska, V Bettendroffer, L Candotti, D Chenine, AL Gondois-Rey, F Tamalet, C Vigne, R Ruprecht, RM Agut, H Hirsch, I CA French ALT Study Grp TI Truncated forms of human and simian immunodeficiency virus in infected individuals and rhesus macaques are unique or rare quasispecies SO VIROLOGY LA English DT Article DE defective SIV and HIV-1; truncated HIV-1 DNA; truncated SIV DNA; HIV-1 replication in vivo; lymphoid tissue ID CIS-ACTING SEQUENCES; DEFECTIVE PARTICLES; LYMPHOID-TISSUE; HIV-1; REPLICATION; TYPE-1; DNA; VECTOR; CELLS; INTERFERENCE AB Truncated proviruses of variable sizes are present in peripheral blood mononuclear cells (PBMC) of human immunodeficiency virus type 1 (HIV-1)-infected persons and simian immunodeficiency virus (SIV)-infected rhesus macaques. Here, we investigated whether the highly deleted HIV and SIV proviruses are present in infected organisms as multiple copies or whether each truncated provirus is unique. Using end-point dilution, multiple long-distance (LD) DNA PCR assays were run in parallel using DNA extracted from PBMC of seropositive, treatment-naive persons and from lymph nodes of a rhesus monkey inoculated with cloned, full-length SIVmac239 DNA. The PCR products were titrated and mapped. Most truncated proviruses were present in the DNA samples tested as single, nonintegrated molecules that differed from one another in size and/or nucleotide sequence. These results indicate that truncated primate lentiviral sequences found in infected tissues are unique or rare quasispecies that do not replicate significantly. (C) 2003 Elsevier Science (USA). All rights reserved. C1 INSERM U372, Lab Pathogen Infect Lentivirus, F-13276 Marseille 9, France. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Hop La Pitie Salpetriere, CERVI, Virol Lab, EA 2387, F-75651 Paris 13, France. Hop Enfants La Timone, Virol Lab, F-13007 Marseille, France. RP Hirsch, I (reprint author), INSERM U372, Lab Pathogen Infect Lentivirus, 163 Ave Luminy,BP 178, F-13276 Marseille 9, France. RI Pion, Marjorie/D-8139-2012; Hirsch, Ivan/J-7726-2015; OI Pion, Marjorie/0000-0002-6406-747X; Hirsch, Ivan/0000-0003-1701-1438 FU NCRR NIH HHS [RR14180] NR 34 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 20 PY 2003 VL 311 IS 1 BP 157 EP 168 DI 10.1016/S0042-6822(03)00188-0 PG 12 WC Virology SC Virology GA 699EL UT WOS:000184042900017 PM 12832213 ER PT J AU Martemyanov, KA Hopp, JA Arshavsky, VY AF Martemyanov, KA Hopp, JA Arshavsky, VY TI Specificity of G protein-RGS protein recognition is regulated by affinity adapters SO NEURON LA English DT Article ID GAMMA-SUBUNIT; EFFECTOR COMPLEX; GTPASE ACTIVITY; TRANSDUCIN; PHOTORECEPTORS; EXPRESSION; BINDING; RAT; ACTIVATION; CHANNELS AB RGS proteins regulate the duration of cell signaling by modulating the lifetime of activated G proteins. The specificity of RGS-G protein mutual recognition is critical for meeting unique timing requirements of numerous G protein-mediated pathways. Our study of two splice isoforms of RGS9 expressed in different types of neurons revealed a novel mechanism whereby this specificity is determined by specialized protein domains or subunits acting as affinity adapters. The long RGS9 isoform contains a C-terminal domain that provides high-affinity interaction with its target G protein. The lack of this domain in the short RGS9 isoform is compensated by the action of a G protein effector subunit that is structurally similar to this C-terminal domain. This allows the short isoform to specifically target the complex between the G protein and its effector. Thus, the specific timing needs of different signaling pathways can be accommodated by affinity adapters positioned at various pathway components. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab Ophthalmol, Boston, MA 02114 USA. RP Arshavsky, VY (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab Ophthalmol, Boston, MA 02114 USA. FU NEI NIH HHS [EY 12859] NR 39 TC 38 Z9 38 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN 19 PY 2003 VL 38 IS 6 BP 857 EP 862 DI 10.1016/S0896-6273(03)00320-9 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 693AA UT WOS:000183691400006 PM 12818172 ER PT J AU Demchenko, IT Atochin, DN Boso, AE Astern, J Huang, PL Piantadosi, CA AF Demchenko, IT Atochin, DN Boso, AE Astern, J Huang, PL Piantadosi, CA TI Oxygen seizure latency and peroxynitrite formation in mice lacking neuronal or endothelial nitric oxide synthases SO NEUROSCIENCE LETTERS LA English DT Article DE hyperbaric oxygen; oxygen seizures; knockout mice; cerebral blood flow; nitric oxide; peroxynitrite ID HYPERBARIC-OXYGEN; TOXICITY; BRAIN; GENE AB Nitric oxide (NO) from endothelial or neuronal NO synthases (eNOS or nNOS) may contribute both to the cerebrovascular responses to oxygen and potentially to the peroxynitrite-mediated toxic effects of hyperbaric oxygen (HBO2) on the central nervous system (CNS O-2 toxicity). In mice lacking eNOS or nNOS (-/-), regional cerebral blood flow (rCBF) and 3-nitrotyrosine (3-NT), a biochemical marker for peroxynitrite (ONOO-) formation, were measured in the brain during HBO2 exposure. These variables were then correlated with EEG spiking activity related to CNS O-2 toxicity. In wild-type (WT) mice, HBO2 exposure transiently reduced rCBF, but by 60 min rCBF was restored to baseline levels and above, followed by EEG spikes. Mice lacking nNOS also showed initial depression of rCBF followed by hyperemia but the delay in the onset of EEG discharges was greater. In contrast, in eNOS-deficient mice rCBF did not decrease and hyperemia was less pronounced during HBO2. EEG spike latency was longer in eNOS(-/-) compared to WT or nNOS(-/-) mice. 3-NT gradually increased in all strains during HBO2 but accumulation was slower in nNOS(-/-) mice, consistent with less ONOO- production. These results indicate that NOS-deficient mice have different cerebrovascular responses and tolerance to HBO2 depending on which enzyme isoform is affected. The data suggest a key role for eNOS-dependent NO production in cerebral vasoconstriction and in the development of hyperoxic hyperemia preceding O-2 seizures, whereas neuronal NO may mediate toxic effects of HBO2 mainly by its reaction with superoxide to generate the stronger oxidant, peroxynitrite. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Duke Univ, Med Ctr, Ctr Hyperbar Med & Environm Physiol, Durham, NC 27710 USA. Russian Acad Sci, Inst Evolut Physiol & Biochem, St Petersburg 194223, Russia. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Piantadosi, CA (reprint author), Duke Univ, Med Ctr, Ctr Hyperbar Med & Environm Physiol, Box 3315, Durham, NC 27710 USA. RI Atochin, Dmitriy/Q-3150-2016 FU NHLBI NIH HHS [HL4244-08]; NINDS NIH HHS [NS533335] NR 26 TC 47 Z9 51 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 19 PY 2003 VL 344 IS 1 BP 53 EP 56 DI 10.1016/S0304-3940(03)00432-4 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 687KJ UT WOS:000183375300014 PM 12781920 ER PT J AU Harisinghani, MG Barentsz, J Hahn, PF Deserno, WM Tabatabaei, S van de Kaa, CH de la Rosette, J Weissleder, R AF Harisinghani, MG Barentsz, J Hahn, PF Deserno, WM Tabatabaei, S van de Kaa, CH de la Rosette, J Weissleder, R TI Noninvasive detection of clinically occult lymph-node metastases in prostate cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SUPERPARAMAGNETIC IRON-OXIDE; PELVIC LYMPHADENECTOMY; RADICAL PROSTATECTOMY; CONTRAST AGENT; MRI; SPECTROSCOPY; DIAGNOSIS; CARCINOMA; THERAPY AB BACKGROUND: Accurate detection of lymph-node metastases in prostate cancer is an essential component of the approach to treatment. We investigated whether highly lymphotropic superparamagnetic nanoparticles, which gain access to lymph nodes by means of interstitial-lymphatic fluid transport, could be used in conjunction with high-resolution magnetic resonance imaging (MRI) to reveal small nodal metastases. METHODS: Eighty patients with presurgical clinical stage T1, T2, or T3 prostate cancer who underwent surgical lymph-node resection or biopsy were enrolled. All patients were examined by MRI before and 24 hours after the intravenous administration of lymphotropic superparamagnetic nanoparticles (2.6 mg of iron per kilogram of body weight). The imaging results were correlated with histopathological findings. RESULTS: Of the 334 lymph nodes that underwent resection or biopsy, 63 (18.9 percent) from 33 patients (41 percent) had histopathologically detected metastases. Of these 63 nodes, 45 (71.4 percent) did not fulfill the usual imaging criteria for malignancy. MRI with lymphotropic superparamagnetic nanoparticles correctly identified all patients with nodal metastases, and a node-by-node analysis had a significantly higher sensitivity than conventional MRI (90.5 percent vs. 35.4 percent, P<0.001) or nomograms. CONCLUSIONS: High-resolution MRI with magnetic nanoparticles allows the detection of small and otherwise undetectable lymph-node metastases in patients with prostate cancer. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Med Ctr, Nijmegen, Netherlands. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Bldg 149,13th St,Rm 5403, Charlestown, MA 02129 USA. RI Barentsz, Jelle/D-3515-2009; Hulsbergen-van de Kaa, C.A./L-4399-2015 FU NCI NIH HHS [R01CA59649] NR 37 TC 1140 Z9 1188 U1 14 U2 129 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 19 PY 2003 VL 348 IS 25 BP 2491 EP U5 DI 10.1056/NEJMoa022749 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 690YC UT WOS:000183577200003 PM 12815134 ER PT J AU Wolfe, LC Harris, NL Weinstein, HJ Ferry, JA Ebb, DH Roberts, AE AF Wolfe, LC Harris, NL Weinstein, HJ Ferry, JA Ebb, DH Roberts, AE TI A five-day-old girl with leukocytosis and a worsening rash from birth - Transient myeloproliferative disorder associated with mosaicism for trisomy 21 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CONGENITAL LEUKEMOID REACTION; DOWN-SYNDROME; NORMAL NEWBORN; INFANT C1 Tufts New England Med Ctr, Floating Childrens Canc Ctr, Div Pediat Hematol Oncol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Pediat, Boston, MA 02111 USA. Massachusetts Gen Hosp Children, Div Pediat Hematol & Oncol, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wolfe, LC (reprint author), Tufts New England Med Ctr, Floating Childrens Canc Ctr, Div Pediat Hematol Oncol, Boston, MA 02111 USA. NR 26 TC 9 Z9 10 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 19 PY 2003 VL 348 IS 25 BP 2557 EP 2566 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 690YC UT WOS:000183577200011 PM 12815142 ER PT J AU Reddy, VY Neuzil, P Taborsky, M Ruskin, JN AF Reddy, VY Neuzil, P Taborsky, M Ruskin, JN TI Short-term results of substrate mapping and radiofrequency ablation of ischemic ventricular tachycardia using a saline-irrigated catheter SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; MYOCARDIAL-INFARCTION; HEART-DISEASE; SINUS RHYTHM; DEFIBRILLATOR; ELECTROGRAMS; ARRHYTHMIAS; THERAPY; SUCCESS; REENTRY AB OBJECTIVES We evaluated the safety and acute procedural efficacy of a combined electrophysiologic and anatomic approach to ablation of all inducible ventricular tachycardias (VT) during sinus rhythm using an irrigated radiofrequency (RF) ablation catheter. BACKGROUND Ventricular tachycardia associated with chronic myocardial infarction (MI) is frequently hemodynamically intolerable and associated with multiple electrocardiographic morphologies. Because traditional mapping techniques are contingent on hemodynamic stability for adequate VT mapping, VT ablation therapy for many patients has been disappointing. METHODS High-density electroanatomic mapping was performed during either sinus rhythm in 11 consecutive patients with a history of MI and ventricular arrhythmias. The RF ablation was performed using an irrigated-tip ablation catheter. All inducible VTs were targeted for catheter ablation during sinus rhythm. RESULTS The RF ablation lesions were placed in a linear fashion traversing the border zones of infarcted and normal tissue (mean of 3.4 linear lesions/patient). With this strategy, the target. VT was eliminated in 9 of 11 patients (82%). Furthermore, when targeting all inducible monomorphic VTs, complete procedural success was achieved in 7 of 11 patients (64%). During the follow-up period (mean 13.1 +/- 1.9 weeks), spontaneous VT was only noted in the two patients with no acute procedural benefit. CONCLUSIONS By identifying potentially arrhythmogenic tissue during sinus rhythm, substrate mapping can guide the ablation of a majority of inducible VTs using an irrigated RF ablation catheter. This emerging therapeutic paradigm may be considered in the management of patients with multiple hemodynamically unstable monomorphic VTs. (J Am Coll Cardiol 2003;41: 2228-36) (C) 2003 by the American College of Cardiology Foundation. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Na Homolce Hosp, Div Cardiol, Electrophysiol Sect, Prague, Czech Republic. RP Reddy, VY (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Dept Med, 32 Fruit St, Boston, MA 02114 USA. NR 24 TC 67 Z9 70 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 18 PY 2003 VL 41 IS 12 BP 2228 EP 2236 DI 10.1016/S0735-1097(03)00492-3 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 690RW UT WOS:000183563600022 PM 12821253 ER PT J AU Sisk, JE Whang, W Butler, JC Sneller, VP Whitney, CG AF Sisk, JE Whang, W Butler, JC Sneller, VP Whitney, CG TI Cost-effectiveness of vaccination against invasive pneumococcal disease among people 50 through 64 years of age: Role of comorbid conditions and race SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID POLYSACCHARIDE VACCINE; UNITED-STATES; REVACCINATION; MORTALITY; HEALTH; CARE; ERA AB Background: Guidelines are increasingly recommending preventive services starting at 50 years of age, and policymakers are considering such a recommendation for pneumococcal polysaccharide vaccination. The finding that pneumococcal vaccination is cost-saving for people 65 years of age or older raises the question of the vaccination's implications for other older adults, especially black people, whose disease incidence exceeds that of nonblack people, and those with high-risk conditions. Objective: To assess the implications of vaccinating black and nonblack people 50 through 64 years of age against invasive pneumococcal disease. Design: Cost-effectiveness analysis. Data Sources: Published literature for vaccination effectiveness and cost estimates; data on disease incidence and case-fatality rates from the Centers for Disease Control and Prevention. Target Population: Hypothetical cohort 50 through 64 years of age with the 1995 U.S. age distribution. Time Horizon: Lifetime. Perspective: Societal. Intervention: Pneumococcal polysaccharide vaccination compared with no vaccination. Outcome Measures: Incremental medical costs and health effects, in quality-adjusted life-years per vaccinee. Results of Base-Case Analysis: vaccination saved medical costs and improved health among high-risk black people ($27.55 savings per vaccinee) and nonblack people ($5.92 savings per vaccinee), excluding survivors' future costs. For low-risk black and nonblack people and the overall general population, vaccination cost $2477, $8195, and $3434, respectively, to gain 1 year of healthy life. Results of Sensitivity Analysis: Excluding survivors' future costs, in the general immunocompetent population, cost per quality-adjusted life-year in global worst-case results ranged from $21 513 for black people to $68 871 for nonblack people; in the high-risk population, cost ranged from $11 548 for black people to $39 000 for nonblack people. In the global best case, vaccination was cost-saving for black and nonblack people in the general immunocompetent and high-risk populations, excluding survivors' future costs. The cost-effectiveness range was narrower in probabilistic sensitivity analyses, with 95% probabilistic intervals ranging from cost-saving to $1594 for black people and from cost-saving to $12 273 for nonblack people in the general immunocompetent population. Costs per quality-adjusted life-year for low-risk people with case-fatality rates from 1998 were $2477 for black people and $8195 for nonblack people, excluding survivors' medical costs. Conclusions: These results support the current recommendation to vaccinate high-risk people and provide useful information for considering extending the recommendation to the general population 50 through 64 years of age. Lack of evidence about the effectiveness of revaccination for people 65 years of age or older, when disease risks are higher, argues for further research to guide vaccination policy. C1 CUNY Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10029 USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Ctr Dis Control & Prevent, Anchorage, AK USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Sisk, JE (reprint author), CUNY Mt Sinai Sch Med, Dept Hlth Policy, Room 2-34,1425 Madison Ave, New York, NY 10029 USA. NR 30 TC 80 Z9 80 U1 1 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 17 PY 2003 VL 138 IS 12 BP 960 EP 968 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 690YM UT WOS:000183578100003 PM 12809452 ER PT J AU Garnovskaya, MN Mukhin, YV Turner, JH Vlasova, TM Ullian, ME Raymond, JR AF Garnovskaya, MN Mukhin, YV Turner, JH Vlasova, TM Ullian, ME Raymond, JR TI Mitogen-induced activation of Na+/H+ exchange in vascular smooth muscle cells involves Janus kinase 2 and Ca2+/calmodulin SO BIOCHEMISTRY LA English DT Article ID SODIUM-PROTON EXCHANGE; ANGIOTENSIN-II; PROTEIN-KINASE; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; GROWTH-FACTOR; H+ EXCHANGER; LYSOPHOSPHATIDIC ACID; INTRACELLULAR CALCIUM; 5-HT1A RECEPTOR AB The sodium/proton exchanger type 1 (NHE-1) plays an important role in the proliferation of vascular smooth muscle cells (VSMC). We have examined the regulation of NHE-1 by two potent mitogens, serotonin (5-HT, 5-hydroxytryptamine) and angiotensin II (Ang II), in cultured VSMC derived from rat aorta. 5-HT and Ang II rapidly activated NHE-1 via their G protein-coupled receptors (5-HT2A and AT(1)) as assessed by proton microphysiometry of quiescent cells and by measurements of intracellular pH on a FLIPR (fluorometric imaging plate reader). Activation of NHE-1 was blocked by inhibitors of phospholipase C, CaM, and Jak2 but not by pertussis toxin or inhibitors of protein kinase C. Immunoprecipitation/immunoblot studies showed that 5-HT and Ang II induce phosphorylation of Jak2 and induce the formation of signal transduction complexes that included Jak2, CaM, and NHE-1. The cell-permeable Ca2+ chelator BAPTA-AM blocked activation of Jak2, complex formation between Jak2 and CaM, and tyrosine phosphorylation of CaM, demonstrating that elevated intracellular Ca2+ is essential for those events. Thus, mitogen-induced activation of NHE-1 in VSMC is dependent upon elevated intracellular Ca2+ and is mediated by the Jak2-dependent tyrosine phosphorylation of CaM and subsequent increased binding of CaM to NHE-1, similar to the pathway previously described for the bradykinin B-2 receptor in inner medullary collecting duct cells of the kidney [Mukhin, Y. V., et al. (2001) J. Biol. Chem. 276, 17339-17346]. We propose that this pathway represents a fundamental mechanism for the rapid regulation of NHE-1 by G(q/11) protein-coupled receptors in multiple cell types. C1 Med Univ S Carolina, Med Serv, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Res Serv, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. RP Garnovskaya, MN (reprint author), Med Univ S Carolina, Med Serv, Ralph H Johnson Vet Affairs Med Ctr, 96 Jonathan Lucas St,Room 829 CSB,POB 250623, Charleston, SC 29425 USA. FU NCRR NIH HHS [S10RR013005]; NIDDK NIH HHS [K01-DK02694, DK52448] NR 58 TC 20 Z9 21 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 17 PY 2003 VL 42 IS 23 BP 7178 EP 7187 DI 10.1021/bi034563+ PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 689FQ UT WOS:000183481300028 PM 12795614 ER PT J AU Keresztes, G Mutai, H Heller, S AF Keresztes, G Mutai, H Heller, S TI TMC and EVER genes belong to a larger novel family, the TMC gene family encoding transmembrane proteins SO BMC GENOMICS LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; HUMAN GENOME; MUTATIONS; DOMINANT; REVEALS AB Background: Mutations in the transmembrane cochlear expressed gene 1 (TMC1) cause deafness in human and mouse. Mutations in two homologous genes, EVER1 and EVER2 increase the susceptibility to infection with certain human papillomaviruses resulting in high risk of skin carcinoma. Here we report that TMC1, EVER1 and EVER2 (now TMC6 and TMC8) belong to a larger novel gene family, which is named TMC for trans membrane channel-like gene family. Results: Using a combination of iterative database searches and reverse transcriptase-polymerase chain reaction (RT-PCR) experiments we assembled contigs for cDNA encoding human, murine, puffer fish, and invertebrate TMC proteins. TMC proteins of individual species can be grouped into three subfamilies A, B, and C. Vertebrates have eight TMC genes. The majority of murine TMC transcripts are expressed in most organs; some transcripts, however, in particular the three subfamily A members are rare and more restrictively expressed. Conclusion: The eight vertebrate TMC genes are evolutionary conserved and encode proteins that form three subfamilies. Invertebrate TMC proteins can also be categorized into these three subfamilies. All TMC genes encode transmembrane proteins with intracellular amino- and carboxyl-termini and at least eight membrane-spanning domains. We speculate that the TMC proteins constitute a novel group of ion channels, transporters, or modifiers of such. C1 Harvard Med Sch, Dept Otolaryngol, Boston, MA 02115 USA. Harvard Med Sch, Neurosci Program, Boston, MA USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Heller, S (reprint author), Harvard Med Sch, Dept Otolaryngol, Boston, MA 02115 USA. EM gabor@epl.meei.harvard.edu; mutai@epl.meei.harvard.edu; hellers@epl.meei.harvard.edu FU NIDCD NIH HHS [DC04563, R01 DC004563] NR 16 TC 59 Z9 73 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JUN 17 PY 2003 VL 4 AR 24 DI 10.1186/1471-2164-4-24 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 703DT UT WOS:000184265300001 PM 12812529 ER PT J AU Ellinor, PT Shin, JT Moore, RK Yoerger, DM MacRae, CA AF Ellinor, PT Shin, JT Moore, RK Yoerger, DM MacRae, CA TI Locus for atrial fibrillation maps to chromosome 6q14-6 SO CIRCULATION LA English DT Article DE arrhythmia; genetics; cardiomyopathy ID DOMINANT DILATED CARDIOMYOPATHY; NATURAL-HISTORY; MUTATION; IDENTIFICATION; EPIDEMIOLOGY; MECHANISMS AB Background-Atrial fibrillation (AF), the most common clinical arrhythmia, is a major cause of morbidity and mortality. Although AF is often associated with other cardiovascular conditions, many patients present without an obvious etiology. Inherited forms of AF exist, but the causative gene has been defined only in a single family. We have identified a large family (family FAF-1) in which AF segregates as a Mendelian trait. Methods and Results-Thirty-four family members were evaluated by 12-lead ECG, echocardiogram, 24-hour Holter monitoring, and laboratory studies. Individuals with electrocardiographically documented AF were defined as affected. Subjects were considered unaffected if they were >60 years of age, had no personal history of AF, and had no offspring with a history of AF. DNA was extracted and genotypic analyses were performed using polymorphic microsatellite markers. Evidence of linkage was obtained on chromosome 6, with a peak 2-point logarithm of the odds (LOD) score of 3.63 (theta=0) at the marker D6S1021. A maximal multipoint LOD score of 4.9 was obtained between D6S286 and D6S1021, indicating odds of approximate to100 000:1 in favor of this interval as the location of the gene defect responsible for AF in this family. The LOD scores were robust to changes in penetrance and allele frequency. Haplotype analyses further supported this minimal genetic interval. Conclusion-We have mapped a novel locus for AF to chromosome 6q14-16. The identification of the causative gene in this interval will be an important step in understanding the fundamental mechanisms of AF. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP MacRae, CA (reprint author), Cardiovasc Res Ctr, 149 13th St,4th Floor, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL71632, R01 HL075431] NR 18 TC 141 Z9 147 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 17 PY 2003 VL 107 IS 23 BP 2880 EP 2883 DI 10.1161/01.CIR.0000077910.80718.49 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 691NQ UT WOS:000183612700003 PM 12782570 ER PT J AU Wang, TJ Larson, MG Levy, D Vasan, RS Leip, EP Wolf, PA D'Agostino, RB Murabito, JM Kannel, WB Benjamin, EJ AF Wang, TJ Larson, MG Levy, D Vasan, RS Leip, EP Wolf, PA D'Agostino, RB Murabito, JM Kannel, WB Benjamin, EJ TI Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality - The Framingham Heart Study SO CIRCULATION LA English DT Article DE arrhythmia; fibrillation, atrial; heart failure; mortality ID PROGNOSTIC-SIGNIFICANCE; SINUS RHYTHM; RISK; CARDIOMYOPATHY; DYSFUNCTION; SURVIVAL; TRIAL AB Background-Atrial fibrillation (AF) and congestive heart failure (CHF) frequently occur together, but there is limited information regarding their temporal relations and the combined influence of these conditions on mortality. Methods and Results-We studied participants in the Framingham Study with new-onset AF or CHF. Multivariable Cox proportional hazards models with time-dependent variables were used to evaluate whether mortality after AF or CHF was affected by the occurrence and timing of the other condition. Hazard ratios (HRs) were adjusted for time period and cardiovascular risk factors. During the study period, 1470 participants developed AF, CHF, or both. Among 382 individuals with both conditions, 38% had AF first, 41% had CHF first, and 21% had both diagnosed on the same day. The incidence of CHF among AF subjects was 33 per 1000 person-years, and the incidence of AF among CHF subjects was 54 per 1000 person-years. In AF subjects, the subsequent development of CHF was associated with increased mortality (men: HR 2.7; 95% CI, 1.9 to 3.7; women: HR 3.1; 95% CI, 2.2 to 4.2). Similarly, in CHF subjects, later development of AF was associated with increased mortality (men: HR 1.6; 95% CI, 1.2 to 2.1; women: HR 2.7, 95% CI, 2.0 to 3.6). Preexisting CHF adversely affected survival in individuals with AF, but preexisting AF was not associated with adverse survival in those with CHF. Conclusions-Individuals with AF or CHF who subsequently develop the other condition have a poor prognosis. Additional studies addressing the pathogenesis, prevention, and optimal management of the joint occurrence of AF and CHF appear warranted. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Neurol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. RP Benjamin, EJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. OI Larson, Martin/0000-0002-9631-1254; Murabito, Joanne/0000-0002-0192-7516; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [K24 HL-04334-01A1, N01-HC-25195]; NINDS NIH HHS [5RO1-NS-17950] NR 27 TC 729 Z9 766 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 17 PY 2003 VL 107 IS 23 BP 2920 EP 2925 DI 10.1161/01.CIR.0000072767.89944.6E PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 691NQ UT WOS:000183612700010 PM 12771006 ER PT J AU Reyes, M Freeman, GL Escobedo, D Lee, SK Steinhelper, ME Feldman, MD AF Reyes, M Freeman, GL Escobedo, D Lee, SK Steinhelper, ME Feldman, MD TI Enhancement of contractility with sustained afterload in the intact murine heart - Blunting of length-dependent activation SO CIRCULATION LA English DT Article DE pressure; afterload; hemodynamics; ontractility; diastole ID CARDIAC TROPONIN-T; FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; PRESSURE-VOLUME RELATIONSHIP; CLOSED-CHEST DOGS; CONDUCTANCE CATHETER; HOMEOMETRIC AUTOREGULATION; CONSCIOUS DOGS; MOUSE; RELAXATION; MUSCLE AB Background-It has been hypothesized that because of its rapid heart rate, the intact murine heart functions near maximal contractility in the basal state. If this hypothesis is correct, then the fast and slow components of myocardial length-dependent activation should be blunted compared with larger mammals. Methods and Results-Mice (n = 24) were anesthetized, and via an open chest, LV pressure-volume relationships were determined by a dual-frequency conductance catheter system. Baseline pressure-volume relationships were determined during transient occlusion of the inferior vena cava, and repeat measurements were made after 1 (n = 10) and 7 (n = 21) minutes of sustained aortic occlusion. Control experiments were performed in a subset of mice (n = 3). For baseline to 1 minute, an increase in afterload (maximal pressure 95 +/- 9 to 126 +/- 7 mm Hg; P < 0.001) and effective arterial elastance (5.9 +/- 3.1 to 9.2 +/- 3.9 mm Hg/μl; P < 0.001) resulted in an increase in end-diastolic volume (31 +/- 8 to 35 +/- 9 muL; P < 0.001). The result was maintenance of stroke volume (17 +/- 6 to 15 +/- 6; P = NS) owing to an increase in contractility (leftward shift in V-100 [the volume of end-systolic elastance at 100 mm Hg], 24 +/- 9 to 16 +/- 5 μL; P < 0.001). No additional augmentation of systolic function was found at 7 minutes. Conclusions-This study demonstrates that the fast phase of length-dependent activation is intact but not the slow phase, consistent with murine myocardium functioning near maximal contractility in the basal state. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Cardiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Feldman, MD (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Cardiol, Room 5-642 U,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NHLBI NIH HHS [HL-67475] NR 39 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 17 PY 2003 VL 107 IS 23 BP 2962 EP 2968 DI 10.1161/01.CIR.0000070964.96190.67 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 691NQ UT WOS:000183612700017 PM 12771002 ER PT J AU Lammert, E Gu, GQ McLaughlin, M Brown, D Brekken, R Murtaugh, LC Gerber, HP Ferrara, N Melton, DA AF Lammert, E Gu, GQ McLaughlin, M Brown, D Brekken, R Murtaugh, LC Gerber, HP Ferrara, N Melton, DA TI Role of VEGF-A in vascularization of pancreatic islets SO CURRENT BIOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; DIFFERENTIATION; PERMEABILITY; RECEPTORS; CELLS; MICE AB Blood vessel endothelium has been recently shown to induce endocrine pancreatic development [1]. Because pancreatic endocrine cells or islets express high levels of vascular endothelial growth factors, VEGFs [2, 3], we investigated the role of a particular VEGF, VEGF-A, on islet vascularization and islet function. By deleting VEGF-A in the mouse pancreas, we show that endocrine cells signal back to the adjacent endothelial cells to induce the formation of a dense network of fenestrated capillaries in islets. Interestingly, VEGF-A is not required for the development of all islet capillaries. However, the few remaining capillaries found in the VEGF-A-deficient islets are not fenestrated and contain an unusual number of caveolae. In addition, glucose tolerance tests reveal that the VEGF-A-induced capillary network is not strictly required for blood glucose control but is essential for fine-tuning blood glucose regulation. In conclusion, we speculate that islet formation takes place in two sequential steps: in the first step, signals from blood vessel endothelium induce islet formation next to the vessels, and in the second step, the islets signal to the endothelium. The second step involves paracrine VEGF-A signaling to elaborate the interaction of islets with the circulatory system. C1 Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany. Harvard Univ, Howard Hughes Med Inst, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dept Surg, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA. Genentech Inc, San Francisco, CA 94080 USA. RP Lammert, E (reprint author), Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany. NR 17 TC 218 Z9 225 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUN 17 PY 2003 VL 13 IS 12 BP 1070 EP 1074 DI 10.1016/S0960-9822(03)00378-6 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 691CV UT WOS:000183588000028 PM 12814555 ER PT J AU Jaeckel, E Klein, L Martin-Orozco, N von Boehmer, H AF Jaeckel, E Klein, L Martin-Orozco, N von Boehmer, H TI Normal incidence of diabetes in NOD mice tolerant to glutamic acid decarboxylase SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE diabetes; NOD mouse; tolerance; GAD65; autoimmunity ID AUTOIMMUNE RESPONSES; TRANSGENIC MICE; T-CELLS; INSULIN; IDENTIFICATION; EXPRESSION; EPITOPES; AUTOANTIGENS; WORKSHOP; LESSONS AB Experiments in nonobese diabetic (NOD) mice that lacked expression of glutamic acid decarboxylase (GAD) in P cells have suggested that GAD represents an autoantigen essential for initiating and maintaining the diabetogenic immune response. Several attempts of inducing GAD-specific recessive tolerance to support this hypothesis have failed. Here we report on successful tolerance induction by expressing a modified form of GAD under control of the invariant chain promoter resulting in efficient epitope display. In spite of specific tolerance insulitis and diabetes occurred with normal kinetics indicating that GAD is not an essential autoantigen in the pathogenesis of diabetes. C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, 44 Binney St, Boston, MA 02115 USA. RI Martin Orozco, Natalia/E-4794-2010; Klein, Ludger/G-8785-2011 NR 30 TC 68 Z9 68 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 16 PY 2003 VL 197 IS 12 BP 1635 EP 1644 DI 10.1084/jem.20030215 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 691RJ UT WOS:000183619000004 PM 12796471 ER PT J AU El Khoury, JB Moore, KJ Means, TK Leung, J Terada, K Toft, M Freeman, MW Luster, AD AF El Khoury, JB Moore, KJ Means, TK Leung, J Terada, K Toft, M Freeman, MW Luster, AD TI CD36 mediates the innate host response to beta-amyloid SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE microglia; scavenger receptor; Alzheimer's disease; chemokine; reactive oxygen species ID MACROPHAGE SCAVENGER RECEPTOR; NITRIC-OXIDE SYNTHASE; ALZHEIMERS-DISEASE; REACTIVE MICROGLIA; TRANSGENIC MICE; SENILE PLAQUES; CELLS; EXPRESSION; ACTIVATION; MONOCYTES AB Accumulation of inflammatory nucroglia in Alzheimer's senile plaques is a hallmark of the innate response to beta-amyloid fibrils and can initiate and propagate neurodegeneration characteristic of Alzheimer's disease (AD). The molecular mechanism whereby fibrillar beta-amyloid activates the inflammatory response has not been elucidated. CD36, a class B scavenger receptor, is expressed on nucroglia in normal and AD brains and binds to beta-amyloid fibrils in vitro. We report here that microglia and macrophages, isolated from CD36 null mice, had marked reductions in fibrillar beta-amyloid-induced secretion of cytokines, chemokines, and reactive oxygen species. Intraperitoneal and stereotaxic intracerebral injection of fibrillar beta-amyloid in CD36 null mice induced significantly less macrophage and microglial recruitment into the peritoneum and brain, respectively, than in wild-type mice. Our data reveal that CD36, a major pattern recognition receptor, mediates microglial and macrophage response to beta-amyloid, and imply that CD36 plays a key role in the proinflammatory events associated with AD. C1 Harvard Univ, Ctr Immunol & Inflammatory Dis, Sch Med, Massachusetts Gen Hosp,Div Rheumatol Allergy & Im, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lipid Met Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv, Charlestown, MA 02129 USA. RP Luster, AD (reprint author), Harvard Univ, Ctr Immunol & Inflammatory Dis, Sch Med, Massachusetts Gen Hosp,Div Rheumatol Allergy & Im, CNY 149,13th St,Room 8301, Charlestown, MA USA. OI Moore, kathryn/0000-0003-2505-2547 FU NHLBI NIH HHS [R01 HL45098, R01 HL045098]; NIA NIH HHS [R01 AG020255, R01AG20255-01]; NIDDK NIH HHS [P01 DK050305, P01 DK50305]; NINDS NIH HHS [K08 NS041330, NS41330] NR 33 TC 206 Z9 209 U1 1 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 16 PY 2003 VL 197 IS 12 BP 1657 EP 1666 DI 10.1084/jem.20021546 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 691RJ UT WOS:000183619000006 PM 12796468 ER PT J AU Ancuta, P Rao, R Moses, A Mehle, A Shaw, SK Luscinskas, FW Gabuzda, D AF Ancuta, P Rao, R Moses, A Mehle, A Shaw, SK Luscinskas, FW Gabuzda, D TI Fractalkine preferentially mediates arrest and migration of CD16+ monocytes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE chemokines; chemokine receptors; chemotaxis; cell adhesion; inflammation ID ADHESION MOLECULE; RECEPTOR CX(3)CR1; LYMPH-NODES; CHEMOKINE; EXPRESSION; SUBSET; GAMMA; MICE; IDENTIFICATION; TRANSMIGRATION AB CD16(+) monocytes represent 5-10% of peripheral blood monocytes in normal individuals and are dramatically expanded in several pathological conditions including sepsis, human immunodeficiency virus 1 infection, and cancer. CD16(+) monocytes produce high levels of proinflammatory cytokines and may represent dendritic cell precursors in vivo. The mechanisms that mediate the recruitment of CD16(+) monocytes into tissues remain unknown. Here we investigate molecular mechanisms of CD16(+) monocyte trafficking and show that migration of CD16(+) and CD16(-) monocytes is mediated by distinct combinations of adhesion molecules and chemokine receptors. In contrast to CD16(-) monocytes, CD16(+) monocytes expressed high CX3CR1 and CXCR4 but low CCR2 and CD62L levels and underwent efficient transendothelial migration in response to fractalkine (FKN; FKN/CX3CL1) and stromal-derived factor 1alpha (CXCL12) but not monocyte chemoattractant protein 1 (CCL2). CD16(+) monocytes arrested on cell surface-expressed FKN under flow with higher frequency compared with CD16(-) monocytes. These results demonstrate that FKN preferentially mediates arrest and migration of CD16(+) monocytes and suggest that recruitment of this proinflammatory monocyte subset to vessel walls via the CX3CR1-FKN pathway may contribute to vascular and tissue injury during pathological conditions. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Canc Immunol & AIDS,Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA. RP Gabuzda, D (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, 44 Binney St,JFB 816, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL56985, HL36028, HL53993, HL65090, P01 HL036028, P50 HL056985, R01 HL053993, R01 HL065090]; NIDA NIH HHS [DA16549, R01 DA016549]; NIDDK NIH HHS [KO1 DK02798]; NINDS NIH HHS [NS37277, R01 NS037277] NR 30 TC 326 Z9 331 U1 0 U2 15 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 16 PY 2003 VL 197 IS 12 BP 1701 EP 1707 DI 10.1084/jem.20022156 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 691RJ UT WOS:000183619000010 PM 12810688 ER PT J AU Michaud, DS Giovannucci, E Willett, WC Colditz, GA Fuchs, CS AF Michaud, DS Giovannucci, E Willett, WC Colditz, GA Fuchs, CS TI Dietary meat, dairy products, fat, and cholesterol and pancreatic cancer risk in a prospective study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cholesterol; dairy products; fats; meat; pancreatic neoplasms ID PAST MEDICAL HISTORY; NUTRITIONAL FACTORS; DIABETES-MELLITUS; PROSTATE-CANCER; NUTRIENT INTAKE; COLON-CANCER; CARCINOGENESIS; ALCOHOL; QUESTIONNAIRE; CONSUMPTION AB Case-control studies suggest that meat and cholesterol intakes may be related to elevated risks of pancreatic cancer. Few prospective studies have examined associations between diet and pancreatic cancer, although in one recent study saturated fat consumption was related to higher risk. In a cohort of US women, the authors confirmed 178 pancreatic cancer cases over 18 years of follow-up. A mailed 61-item food frequency questionnaire was self-administered at baseline, and health and lifestyle variables were updated biennially. Analyses were performed using Cox proportional hazards models to adjust for potential confounders. Intakes of total fat, different types of fats, and cholesterol were not associated with pancreatic cancer risk. Similarly, total meat, red meat, and dairy products were not related to risk. Individual food items contributing to intakes of total meat and dairy products, as well as fish and eggs, did not reveal any specific association. Updating dietary exposures by using questionnaires from 1980, 1984, 1986, and 1990 produced similar findings. The authors' data do not support previous findings that meat or saturated fat intakes are related to pancreatic cancer risk. Future prospective studies should examine the influence of cooking practices as well as other dietary habits on the risk of pancreatic cancer. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. RP Michaud, DS (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS-320 MSC 7232, Rockville, MD 20892 USA. RI Michaud, Dominique/I-5231-2014; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA87969, CA 86102] NR 53 TC 91 Z9 93 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2003 VL 157 IS 12 BP 1115 EP 1125 DI 10.1093/aje/kwg098 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 690BY UT WOS:000183528500009 PM 12796048 ER PT J AU Djousse, L Knowlton, B Hayden, M Almqvist, EW Brinkman, R Ross, C Margolis, R Rosenblatt, A Durr, A Dode, C Morrison, PJ Novelletto, A Frontali, M Trent, RJA McCusker, E Gomez-Tortosa, E Mayo, D Jones, R Zanko, A Nance, M Abramson, R Suchowersky, O Paulsen, J Harrison, M Yang, Q Cupples, LA Gusella, JF MacDonald, ME Myers, RH AF Djousse, L Knowlton, B Hayden, M Almqvist, EW Brinkman, R Ross, C Margolis, R Rosenblatt, A Durr, A Dode, C Morrison, PJ Novelletto, A Frontali, M Trent, RJA McCusker, E Gomez-Tortosa, E Mayo, D Jones, R Zanko, A Nance, M Abramson, R Suchowersky, O Paulsen, J Harrison, M Yang, Q Cupples, LA Gusella, JF MacDonald, ME Myers, RH TI Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Huntington disease; modifier; onset age; trinucleotide repeat; genetics ID TRINUCLEOTIDE REPEAT; MUTANT HUNTINGTIN; OF-ONSET; GENE; INSTABILITY; EXPANSION; LENGTH AB Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have shown that the size of expanded CAG repeat is inversely associated with age at onset (AO) of HD. It is not known whether the normal Huntington allele size influences the relation between the expanded repeat and AO of HD. Data collected from two independent cohorts were used to test the hypothesis that the unexpanded CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD affected persons and in the HD-MAPS cohort of 533 HD affected persons, we found evidence supporting an interaction between the expanded and unexpanded CAG repeat sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The association was statistically significant when both cohorts were combined (P=0.012). The estimated heritability of the AO residual was 0.56 after adjustment for normal and expanded repeats and their interaction. An analysis of tertiles of repeats sizes revealed that the effect of the normal allele is seen among persons with large HD repeat sizes (47-83). These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats. (C) 2003 Wiley-Liss, Inc. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 1M9, Canada. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. Hop La Pitie Salpetriere, Paris, France. Belfast City Hosp, Dept Med Genet, Belfast BT9 7AD, Antrim, North Ireland. Univ Calabria, Dept Cell Biol, I-87036 Arcavacata Di Rende, Italy. CNR, Inst Expt Med, Rome, Italy. Univ Sydney, Dept Med, Sydney, NSW 2006, Australia. Westmead Hosp, Dept Neurol, Sydney, NSW, Australia. Fdn Jimenez Diaz, Serv Neurol & Genet, E-28040 Madrid, Spain. Emory Neurobehav Ctr, Atlanta, GA USA. UCSF Div Med Genet, San Francisco, CA USA. Hennepin Cty Med Ctr, Dept Neurol, Minneapolis, MN 55415 USA. WMS Hall Psychiat Inst, Dept Neuropsychiat & Behav, Columbia, SC USA. Univ Med Clin Foothills, Dept Neurosci, Calgary, AB, Canada. Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. Univ Virginia, Dept Neurol, Charlottesville, VA USA. Boston Univ, Sch Publ Hlth, Dept Biostat & Epidemiol, Boston, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. RP Myers, RH (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St, Boston, MA 02118 USA. RI Yang, Qiong/G-5438-2014; Brinkman, Ryan/B-1108-2008; Hayden, Michael/D-8581-2011; OI Brinkman, Ryan/0000-0002-9765-2990; Hayden, Michael/0000-0001-5159-1419; Yang, Qiong/0000-0002-3658-1375; Cupples, L. Adrienne/0000-0003-0273-7965; Myers, Richard/0000-0002-8365-2674; Novelletto, Andrea/0000-0002-1146-7680 FU NINDS NIH HHS [P50NS016367] NR 29 TC 80 Z9 83 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 0148-7299 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUN 15 PY 2003 VL 119A IS 3 BP 279 EP 282 DI 10.1002/ajmg.a.20190 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 693DH UT WOS:000183699700005 PM 12784292 ER PT J AU Choi, WI Quinn, DA Park, KM Moufarrej, RK Jafari, B Syrkina, O Bonventre, JV Hales, CA AF Choi, WI Quinn, DA Park, KM Moufarrej, RK Jafari, B Syrkina, O Bonventre, JV Hales, CA TI Systemic microvascular leak in an in vivo rat model of ventilator-induced lung injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE microvascular leak; permeability; proteinuria; endothelial nitric oxide synthase; N-nitro-L-arginine methyl ester ID NITRIC-OXIDE SYNTHASE; ENDOTHELIAL GROWTH-FACTOR; RESPIRATORY-DISTRESS SYNDROME; VASCULAR-PERMEABILITY; EPITHELIAL-CELLS; EXPRESSION; PATHWAY; HYPERPERMEABILITY; INHIBITION; ENDOTOXIN AB Positive pressure mechanical ventilation has significant systemic effects, but the systemic effects associated with ventilator-induced lung injury (VILI) are unexplored. We hypothesized that VILI would cause systemic microvascular leak that is dependent on nitric oxide synthase (NOS) expression. Rats were ventilated with room air at 85 breaths/minute for 2 hours with either VT 7 or 20 ml/kg. Kidney microvascular leak, which was assessed by measuring 24-hour urine protein and Evans blue dye, was used as a marker of systemic microvascular leak. A significant microvascular leak occurred in both lung and kidney with large VT (20 ml/kg) ventilation. Injection of 0.9% NaCl corrected the hypotension and the decreased cardiac output related to large VT, but it did not attenuate microvascular leak of lung and kidney. Serum vascular endothelial growth factor was significantly elevated in large VT groups. Endothelial NOS expression significantly increased in the lung and kidney tissue with large VT ventilation but not inducible NOS. The NOS inhibitor, N-nitro-L-arginine methyl ester, attenuated the microvascular leak of lung and kidney and the proteinuria with large VT ventilation. Endothelial NOS may mediate the systemic microvascular leak of the present model of VILI. C1 Massachusetts Gen Hosp, Pulm Crit Care Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hales, CA (reprint author), Massachusetts Gen Hosp, Pulm Crit Care Unit, Dept Med, 55 Fruit St,Bullfinch 148, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL39150, K08 HL03920]; NINDS NIH HHS [NS 10828]; PHS HHS [DR 39773, DR 38452] NR 41 TC 79 Z9 97 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN 15 PY 2003 VL 167 IS 12 BP 1627 EP 1632 DI 10.1164/rccm.200210-1216OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 689CD UT WOS:000183473300008 PM 12663326 ER PT J AU Wallace, MB Block, M Hoffman, BJ Hawes, RH Silvestri, G Reed, CE Mitas, M Ravenel, J Fraig, M Miller, S Jones, ET Boylan, A AF Wallace, MB Block, M Hoffman, BJ Hawes, RH Silvestri, G Reed, CE Mitas, M Ravenel, J Fraig, M Miller, S Jones, ET Boylan, A TI Detection of telomerase expression in mediastinal lymph nodes of patients with lung cancer SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE non-small cell lung cancer; staging; biomarkers; endoscopic ultrasound; micrometastases ID POLYMERASE-CHAIN-REACTION; FINE-NEEDLE ASPIRATION; MINIMAL RESIDUAL DISEASE; QUANTITATIVE RT-PCR; REVERSE-TRANSCRIPTASE; BREAST-CANCER; PROGNOSTIC-SIGNIFICANCE; ENDOSCOPIC ULTRASONOGRAPHY; OCCULT MICROMETASTASES; COMPUTED-TOMOGRAPHY AB Mediastinal lymph nodes are the most common site of tumor spread in non-small cell lung cancer (NSCLC). We hypothesized that micro-metastatic disease could be detected by reverse transcription-polymerase chain reaction (RT-PCR) for expression of human telomerase reverse transcriptase (hTERT) in mediastinal lymph nodes and that a minimally invasive technique (endoscopic ultrasound-guided fine-needle aspiration [EUS-FNA]) is capable of sampling lymph nodes for PCR analysis without surgery. Mediastinal lymph nodes were sampled with EUS-FNA in patients with NSCLC and negative control subjects undergoing EUS for benign disease. Total RNA was harvested from samples, and RT-PCR was performed to detect telomerase gene expression. RNA was available from 87 of 100 lymph node aspirates from 39 patients with NSCLC and from 12 negative control patients. hTERT was expressed in 0 of 14 negative control lymph nodes in 18 of 57 pathologically negative lymph nodes from cancer patients and in 10 of 16 pathologically positive lymph nodes (p < 0.05). Five of 18 (28%) patients with no pathologically evident mediastinal disease expressed telomerase in at least one lymph node. Minimally invasive EUS-FNA with RT-PCR is capable of detecting expression of cancer specific mRNA in lymph nodes. Approximately one-third of pathologically negative mediastinal lymph nodes in NSCLC patients express hTERT mRNA. The clinical significance of this observation is yet to be determined. C1 Med Univ S Carolina, Div Gastroenterol, Ctr Digest Dis, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Surg, Div Pulm Med & Crit Care, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Dept Pathol, Charleston, SC USA. RP Wallace, MB (reprint author), Med Univ S Carolina, Div Gastroenterol, Ctr Digest Dis, 96 Jonathon Lucas St,Suite 210 CSB,POB 250327, Charleston, SC 29425 USA. RI Fraig, Mostafa/I-1670-2016 OI Fraig, Mostafa/0000-0003-1119-3672 FU NCI NIH HHS [R21/R33 CA97875-01] NR 58 TC 38 Z9 41 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN 15 PY 2003 VL 167 IS 12 BP 1670 EP 1675 DI 10.1164/rccm.200211.1297OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 689CD UT WOS:000183473300015 PM 12615614 ER PT J AU Quintana, J Wong, T Ortiz-Portillo, E Marder, SR Mazziotta, JC AF Quintana, J Wong, T Ortiz-Portillo, E Marder, SR Mazziotta, JC TI Right lateral fusiform gyrus dysfunction during facial information processing in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; cognitive deficits; fusiform gyrus; face processing; social cognition ID CEREBRAL-BLOOD-FLOW; DORSOLATERAL PREFRONTAL CORTEX; AUTOMATED IMAGE REGISTRATION; AFFECT RECOGNITION; WORKING-MEMORY; DIFFERENTIAL DEFICIT; ANTERIOR CINGULATE; HUMAN BRAIN; PHYSIOLOGICAL DYSFUNCTION; FUNCTIONAL NEUROANATOMY AB Background: Patients with schizophrenia exhibit facial information processing deficits that likely contribute to their social dysfunction. Whether the deficits involve facial affect and/or identity processing or result from other cognitive abnormalities in schizophrenia remains controversial, and a brain dysfunction specifically related to them has never been reported. If such dysfunction existed, it should be consistently observed across groups of patients and during performance of different facial information processing tasks, independently of whether such tasks demand working memory (WM), semantic, or other cognitive processes. We hypothesized that the right lateral fusiform gyrus (rLFG), one of several human brain areas involved in facial information processing, would consistently show activation abnormalities during both facial affect and identify discrimination in schizophrenia. Methods: We used functional magnetic resonance imaging to measure brain activation in two groups of six chronic, stable schizophrenic outpatients and two of six age- and gender-matched healthy controls. One group of patients and one of controls performed facial affect-with or without semantic processing-and identity discrimination tasks, and the other two groups WM tasks with facial expression cues and varying attentional demands. Results: Patients from either group failed to activate the rLFG when compared to controls in any task. Other activation abnormalities were task-specific (i.e., seen only during performance of one set of tasks) and not consistently observed in both groups of patients, and thus could not be directly and solely linked to facial information discrimination. Conclusions: These results indicate a specific rLFG dysfunction during early facial information-identity or affect-processing, independent from other cognitive deficits, in schizophrenia. C1 Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, W Los Angeles VA Hlth Care Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Brain Mapping Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Radiol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Pharmacol, Los Angeles, CA 90024 USA. RP Quintana, J (reprint author), Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, W Los Angeles VA Hlth Care Ctr, 760 Westwood Plaza,Room C8-846, Los Angeles, CA 90024 USA. FU NCRR NIH HHS [RR08655, RR12169] NR 75 TC 60 Z9 65 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 2003 VL 53 IS 12 BP 1099 EP 1112 DI 10.1016/S0006-3223(02)01784-5 PG 14 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 690YU UT WOS:000183578700004 PM 12814861 ER PT J AU Green, MF Mintz, J Salveson, D Nuechterlein, KH Breitmeyer, B Light, GA Braff, DL AF Green, MF Mintz, J Salveson, D Nuechterlein, KH Breitmeyer, B Light, GA Braff, DL TI Visual masking as a probe for abnormal gamma range activity in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; visual masking; gamma frequency; backward masking; visual processing; neurocognition ID POSTTRAUMATIC-STRESS-DISORDER; TEMPORAL CORRELATION HYPOTHESIS; BACKWARD-MASKING; FEATURE INTEGRATION; OSCILLATIONS; TRANSIENT; CHANNELS; VULNERABILITY; SUPPRESSION; PERFORMANCE AB Background: Visual masking procedures assess very early stages of visual perception. Patients with schizophrenia consistently show deficits on visual masking tasks, and these deficits likely reflect vulnerability to schizophrenia. We conducted two experiments to determine whether visual masking procedures can reveal underlying abnormalities in gamma range oscillations in schizophrenia. Methods: In the first experiment, we conducted nonlinear modeling of visual masking performance data from 89 male schizophrenic patients and 20 male comparison subjects. In the second experiment, electrophysiological recordings of event-related gamma activity were taken during a visual masking task in a subset of eight patients and seven control subjects. Results: In the first experiment, nonlinear modeling of the performance data revealed evidence of oscillations in the gamma range (30 and 35 Hz) for the comparison group but not patients. In the second experiment, the comparison group, but not the patients, showed a burst of gamma range activity 200-400 msec following target presentation. The difference between patients and comparison subjects in this time period was significant (p < .05). Conclusions: Visual masking procedures can serve as a probe for underlying gamma range activity, which appears to be aberrant in schizophrenia. Perceptual problems in schizophrenia may, at least in part, be due to a failure to establish and/or maintain gamma range oscillations. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Houston, Dept Psychol, Houston, TX USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. RP Green, MF (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza,C9-420, Los Angeles, CA 90024 USA. FU NIMH NIH HHS [MH-43292, MH-030911] NR 39 TC 51 Z9 53 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 2003 VL 53 IS 12 BP 1113 EP 1119 DI 10.1016/S0006-3223(02)01813-9 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 690YU UT WOS:000183578700005 PM 12814862 ER PT J AU Thompson, PM Kelley, M Yao, J Tsai, GC van Kammen, DP AF Thompson, PM Kelley, M Yao, J Tsai, GC van Kammen, DP TI Elevated cerebrospinal fluid SNAP-25 in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE SNAP-25; schizophrenia; cerebrospinal fluid; postmortem; synapse; exocytosis; psychosis ID CELL-ADHESION MOLECULE; SEVERE MENTAL-ILLNESS; PREFRONTAL CORTEX; GENE-EXPRESSION; MESSENGER-RNAS; ALTERED LEVELS; SYNAPTIC PATHOLOGY; PROTEIN SNAP-25; DEFICIENT MICE; RAT-BRAIN AB Background: Research suggests an association between abnormal exocytosis and schizophrenia. We previously demonstrated increased synaptosomal associated protein, 25 kDa (SNAP-25), a member of the exocytotic mechanism, in the cerebrospinal fluid (CSF) of schizophrenia subjects. In this study, we explored SNAP-25 level and clinical variables in a new group of subjects. Methods: Twenty-five haloperidol-treated subjects with chronic schizophrenia and twenty-five healthy control subjects participated in the study. Subjects received haloperidol treatment for at least 3 months and then had a lumbar puncture (n = 19). Medication was replaced by placebo, and the lumbar puncture was repeated (n = 25) after 6 weeks or sooner if limited psychotic symptoms occurred. We measured the level of SNAP-25 in the CSF and symptoms with the Brief Psychiatric Rating Scale (BPRS). Results: In both haloperidol (p = .001) and placebo (p = .001) treatment conditions, SNAP-25 was elevated. There was no significant difference in SNAP-25 level between conditions. We identified significant positive correlations among SNAP-25 and the BPRS total score and psychosis and thinking disturbance subscales in subjects on haloperidol. Conclusions: These observations confirm our previous report of elevated CSF SNAP-25 and suggest that synaptic pathology may be linked with the pathophysiology of schizophrenia. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Thompson, PM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 46 TC 29 Z9 30 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 2003 VL 53 IS 12 BP 1132 EP 1137 DI 10.1016/S0006-3223(02)01599-8 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 690YU UT WOS:000183578700007 PM 12814864 ER PT J AU Scadden, DT AF Scadden, DT TI AIDS lymphomas: beginning of an EPOCH? SO BLOOD LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2003 VL 101 IS 12 BP 4647 EP 4647 DI 10.1182/blood-2003-04-1208 PG 1 WC Hematology SC Hematology GA 689FV UT WOS:000183481700001 ER PT J AU Italiano, JE Bergmeier, W Tiwari, S Falet, H Hartwig, JH Hoffmeister, KM Andre, P Wagner, DD Shivdasani, RA AF Italiano, JE Bergmeier, W Tiwari, S Falet, H Hartwig, JH Hoffmeister, KM Andre, P Wagner, DD Shivdasani, RA TI Mechanisms and implications of platelet discoid shape SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR NF-E2; TUBULIN ISOTYPES; BLOOD-PLATELETS; IN-VIVO; POSTTRANSLATIONAL MODIFICATION; P-SELECTIN; MICROTUBULES; MEGAKARYOCYTES; EXPRESSION; SURFACE AB The platelet marginal band consists of a single peripheral microtubule (MT) that is wound in 8 to 12 coils and maintains discoid cell shape. About 90% of beta-tubulin in the marginal band is of the divergent, megakaryocyte (MK)/platelet-restricted beta1 isoform. beta1-tubulin-null mice show reduced proplatelet formation, thrombocytopenia, and platelet spherocytosis. Here, we show that structural abnormalities in resting beta1-tubulin(-/-) platelets include frequent kinks and breaks in the marginal band. Platelets derived from mice lacking the transcription factor GATA1 show similar defects, probably as a direct consequence of ab-sent beta1-tubulin. beta1-tubulin(+/-) platelets have normal ratios of beta-tubulin isotypes but the marginal band is half the normal thickness, which is sufficient to maintain elliptical cell shape. Thus, a threshold 50% or less of the normal amount of beta1-tubulin is required to preserve marginal band integrity and cell shape. beta1-tubulin(-/-) platelets have normal size and contents and show no defects in serotonin release or aggregation. Accordingly, the apparently isolated spherocytosis allows investigation of the role of discoid platelet shape in hemostasis. On agonist stimulation, the disorganized MTs in beta1-tubulin(-/-) platelets fail to condense into central rings and instead are dispersed in short bundles and linear arrays. Nevertheless, intravital microscopy and flow chamber studies demonstrate full functionality of these spherocytic platelets under physiologic shear conditions. Together, these findings highlight the essential requirements of the MK/platelet-restricted beta1-tubulin isoform in platelet structure and suggest that spherocytosis does not impair many aspects of platelet function. (C) 2003 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu RI Tiwari, Sanjay/Q-1853-2016 OI Tiwari, Sanjay/0000-0002-3804-3300 FU NHLBI NIH HHS [P01 HL056949, P01 HL56949, R01HL63143, R01HL68130] NR 48 TC 84 Z9 86 U1 1 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2003 VL 101 IS 12 BP 4789 EP 4796 DI 10.1182/blood-2002-11-3491 PG 8 WC Hematology SC Hematology GA 689FV UT WOS:000183481700030 PM 12586623 ER PT J AU Zhu, AX Chung, RT AF Zhu, AX Chung, RT TI Hepatic steatosis in patients with chronic hepatitis C virus infection - Another risk factor for hepatocellular carcinoma? SO CANCER LA English DT Editorial Material ID CORE PROTEIN; OXIDATIVE STRESS; TRANSGENIC MICE; UNITED-STATES; GENOTYPE-3; DROPLETS; MODEL C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Partners Canc Care, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Zhu, AX (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Cox-640,100 Blossom St, Boston, MA 02114 USA. NR 19 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 2003 VL 97 IS 12 BP 2948 EP 2950 DI 10.1002/cncr.11440 PG 3 WC Oncology SC Oncology GA 686WC UT WOS:000183343100004 PM 12784328 ER PT J AU Kopans, DB Rafferty, E Georgian-Smith, D Yeh, E D'Alessandro, H Moore, R Hughes, K Halpern, E AF Kopans, DB Rafferty, E Georgian-Smith, D Yeh, E D'Alessandro, H Moore, R Hughes, K Halpern, E TI A simple model of breast carcinoma growth may provide explanations for observations of apparently complex phenomena SO CANCER LA English DT Article DE doubling time; ductal carcinoma in situ; growth model; invasive breast carcinoma; breast cancer; screening; mammography ID IN-SITU; CANCER; WOMEN; PREVALENCE; LESIONS; AUTOPSY; MORTALITY; PROJECT; DISEASE; BENIGN AB BACKGROUND. There has been great debate regarding the importance of ductal carcinoma in situ (DCIS) in the breast. Autopsy results that demonstrate a much greater number of these lesions compared with the number of invasive carcinomas, and the numbers of deaths from breast carcinoma each year have been cited as evidence that DCIS rarely leads to invasion and death. These analyses have overlooked the fact that, to sustain a rate of detection each year, there would have to be a reservoir of undetected breast carcinomas growing in the population. The authors developed a simple model that makes this clear. In addition, complex phenomena have been suggested to explain why invasive breast disease may grow more rapidly among very young women and more slowly among the very old. A simple model provides some insight that may simplify the explanation of these observations. METHODS. The simple model of breast carcinoma growth assumes that there are three types of breast carcinoma that begin each year in a cohort of women. It assumes that all breast carcinomas begin as DCIS and take 9 years to go from a single cell to an invasive lesion for the slowest growing lesions, 6 years for intermediate growing DCIS lesions, and 3 years for fast-growing DCIS lesions. Furthermore, once an invasive clone forms, the model assumes that it will double in 60 days for fast-growing lesions, 120 days for intermediate growing lesions, and 180 days for slow-growing lesions. Three new tumors begin to grow in each successive year (one of each type). The model uses simple vectors that are defined by the size of the tumors and the time since tumor initiation, and it assumes that all tumors are detected when they reach 2 cm in greatest dimension. The model can be used to show graphically how many undetected tumors (DCIS as well as invasive carcinomas) there may be in the population to sustain the detection of three invasive tumors each year. RESULTS. Using the assumptions described above, the model showed that, by the time the first slow-growing breast carcinoma reaches 2 cm in greatest dimension, there will be 29 other slow-growing tumors that have not reached that size (9 DCIS and 20 smaller invasive carcinomas), 19 moderately growing tumors (6 DCIS and 13 smaller invasive carcinomas), and 9 fast-growing tumors (3 DCIS and 6 smaller invasive carcinomas). This means that, for every three breast tumors that reach 2 cm, the model predicted that there would be another 57 tumors (39 smaller invasive carcinomas and 18 DCIS) that would be undetected "below the surface". The model showed clearly that faster growing tumors would be expected to predominate among the youngest women, because they are the first to "reach the surface"; and, if the number of newly initiated tumors decreases with age, then there will be more of the slowest growing tumors that are left to reach the surface among the oldest women in the population. CONCLUSIONS. Even if the authors' assumptions are incorrect, their model made it clear that, to diagnose several breast carcinomas per 1000 women each year means that there have to be many more undetected carcinomas in the population to sustain the rate of detection. Although the model did not prove that DCIS may become potentially invasive and lethal, it did demonstrate that, even if all of these in situ lesions become invasive and lethal, many more DCIS lesions would have to be expected in the population than the number of invasive carcinomas detected each year and the number of deaths from breast carcinoma each year. Furthermore, the model provided a simple, purely mechanical illustration that may explain the preponderance of faster growing breast carcinomas among very young women and the preponderance of slower growing tumors among elderly women. (C) 2003 American Cancer Society. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kopans, DB (reprint author), Avon Fdn Comprehens Breast Evaluat Ctr, Wang Ambulatory Care Ctr, Suite 240,15 Parkman St, Boston, MA 02114 USA. OI Hughes, Kevin/0000-0003-4084-6484 NR 32 TC 25 Z9 25 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 2003 VL 97 IS 12 BP 2951 EP 2959 DI 10.1002/cncr.11434 PG 9 WC Oncology SC Oncology GA 686WC UT WOS:000183343100005 PM 12784329 ER PT J AU Bendell, JC Domchek, SM Burstein, HJ Harris, L Younger, J Kuter, I Bunnell, C Rue, M Gelman, R Winer, E AF Bendell, JC Domchek, SM Burstein, HJ Harris, L Younger, J Kuter, I Bunnell, C Rue, M Gelman, R Winer, E TI Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma SO CANCER LA English DT Article DE metastatic breast carcinoma; trastuzumab; central nervous system (CNS) metastases; HER-2/neu ID MONOCLONAL-ANTIBODY; PHASE-II; BRAIN METASTASES; CANCER; CHEMOTHERAPY; SURVIVAL; DISEASE; AUTOPSY; SPREAD AB BACKGROUND. Women with HER-2 overexpressing metastatic breast carcinoma benefit from trastuzumab-based therapy, but trastuzumab does not cross the blood-brain barrier. The authors characterized central nervous system (CNS) disease in these women. METHODS. Using pharmacy records, the authors retrospectively identified 153 women treated with trastuzumab alone or with chemotherapy for HER-2-positive metastatic breast carcinoma at Dana-Farber Partners Cancer Care from June 1998 to December 2000. A study cohort of 122 patients was identified after excluding patients without adequate clinical follow-up or who had CNS disease before trastuzumab treatment. Central nervous system disease was defined as one or more brain metastases or as leptomeningeal carcinomatosis. The median follow-up of this cohort was 23 months. RESULTS. Central nervous system metastases were identified in 34% of patients (95% confidence interval, 26-44%) at a median of 16 months after diagnosis of metastatic breast carcinoma and 6 months from the beginning of trastuzumab therapy. Ninety-three percent of patients with CNS disease presented with clinical symptoms. Five percent of patients with CNS disease had leptomeningeal involvement alone, although 14% had leptomeningeal involvement and parenchymal brain metastases. Fifty percent of patients were responding or had stable disease while receiving trastuzumab at other disease sites at the time of diagnosis of CNS metastasis. The median survival period after CNS metastases was 13 months. Fifty percent of patients died of progressive CNS disease. Patients receiving trastuzumab as first-line therapy for metastatic disease frequently developed brain metastases while responding to or stable on trastuzumab at other disease sites. CONCLUSIONS. Metastatic breast carcinoma to the CNS is common among patients receiving trastuzumab-based therapy, including patients responding to therapy outside the CNS. This may be due either to predilection for the CNS by HER-2-positive tumor cells and/or poor penetration of the CNS by trastuzumab or to improved visceral disease control leading to a longer life and onset of late tumor spread to the CNS. Efforts to characterize other risk factors for development of CNS disease, optimal screening algorithms, and new treatment strategies may be warranted. (C) 2003 American Cancer Society. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Univ Penn, Ctr Canc, Rena Rowan Breast Ctr, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Dept Adult Oncol, Boston, MA 02114 USA. RP Winer, E (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Shields Warren 560,44 Binney St, Boston, MA 02115 USA. RI Rue, Montserrat/B-5663-2009 OI Rue, Montserrat/0000-0002-7862-9365 NR 24 TC 386 Z9 396 U1 1 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 2003 VL 97 IS 12 BP 2972 EP 2977 DI 10.1002/cncr.11436 PG 6 WC Oncology SC Oncology GA 686WC UT WOS:000183343100007 PM 12784331 ER PT J AU Livraghi, T Solbiati, L Meloni, F Ierace, T Goldberg, SN Gazelle, GS AF Livraghi, T Solbiati, L Meloni, F Ierace, T Goldberg, SN Gazelle, GS TI Percutaneous radiofrequency ablation of liver metastases in potential candidates for resection the - "Test-of-time" approach SO CANCER LA English DT Article DE radiofrequency (RF) ablation; colorectal carcinoma (CRC); liver metastases; image-guided therapy ID COLORECTAL-CARCINOMA METASTASES; PERIOPERATIVE BLOOD-TRANSFUSION; HEPATIC METASTASES; TISSUE ABLATION; NATURAL-HISTORY; HEPATOCELLULAR-CARCINOMA; PATIENT SELECTION; THERMAL ABLATION; RADIO-FREQUENCY; LASER PHOTOCOAGULATION AB BACKGROUND. Some surgeons have advocated delaying resection of liver metastases to allow additional metastases which may be present, but are undetected, to be identified. This "test-of-time" approach can limit the number of resections performed on patients who ultimately will develop additional metastases. The current study evaluated the potential role and possible advantages of performing radio-frequency (RF) ablation during the interval between diagnosis and hepatic metastasectomy as part of a test-of-time management approach. METHODS. Eighty-eight consecutive patients with 134 colorectal carcinoma liver metastases were potential candidates for hepatic metastasectomy. They were treated with percutaneous RF ablation using single (101 treatments) or triple-probe cluster (22 treatments) 18-gauge internally cooled electrodes. Treatment was performed under conscious sedation (22 of 119 treatments), anesthesia (14 of 119 treatments), or general anesthesia (83 of 119 treatments). At the time of the initial RF ablation procedure, 49 of 88 patients (56%) were found to have I metastasis, 32 of 88 patients (36%) had 2 metastases, and 7 of 88 patients (8%) had 3 metastases. Metastases ranged from 0.6 to 4.0 cm in greatest dimension (mean, 2.1 cm). Follow-up with serial computed tomography scans scans ranged from 18 to 75 months (median, 33 months) after the initial RF ablation. RESULTS. A total of 119 RF ablations were performed. Complete necrosis was obtained in 53 of 88 patients (60%) and in 85 of 134 lesions (63%). During follow-up of these 53 patients, 16 (30%) remained free of disease and 37 (70%) developed new lesions. New lesions were intrahepatic in 26 of 37 patients (70%), extrahepatic in 4 patients (11%), and both intrahepatic and extrahepatic in 7 patients (19%). Of 26 patients whose new lesions were intrahepatic only, 15 (58%) were retreated with RF and 7 were free of disease at the time of last follow-up (median follow-up, 28 months). Ten additional patients with only intrahepatic new lesions were deemed untreatable and 1 patient underwent resection. Overall, among the 53 patients in whom complete tumor necrosis was achieved after RF ablation therapy, 52 (98%) were spared surgical resection: 23 (44%) because they have remained free of disease and 29 (56%) because they developed disease progression. Among all 88 patients, 21 (24%) underwent resection after RF ablation (8 were free of disease at the time of last follow-up), 23 (26%) remained free of disease after successful RF ablation, and 56 (64%) developed untreatable disease progression (44 after RF alone, 12 after RF and surgery). Lesions in 35 of 88 patients (40%) demonstrated local tumor recurrence on follow-up imaging studies. Twenty of these 35 patients (57%) underwent surgical resection, whereas the remaining 15 patients (43%) developed additional, untreatable metastases. New lesions were intrahepatic in 9 of 15 patients (60%), extrahepatic in I of 15 patients (7%), and both intrahepatic and extrahepatic in 5 of 15 patients (33%). No patient who had been treated with RF ablation became unresectable due to the growth of metastases and there was no evidence of needle track seeding in any patient after RF ablation. Overall, among the 35 patients in whom complete tumor necrosis was not achieved after RF ablation therapy, 15 (43%) were spared surgical resection. CONCLUSIONS. The results of the current study suggest that current RF ablation techniques, when used as part of a test-of-time management approach, can decrease the number of resections performed. The approach results in complete tumor necrosis in some patients and provide an interval for others who ultimately will develop new intrahepatic and/or extrahepatic metastases to do so. (C) 2003 American Cancer Society. C1 Osped Civile, Dept Radiol, Vimercate, MI, Italy. Osped Gen, Dept Radiol, Busto Arsizio, Varese, Italy. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Gazelle, GS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Zero Emerson Pl,Suite 2H, Boston, MA 02114 USA. OI meloni, maria franca/0000-0001-7485-7400; Solbiati, Luigi/0000-0002-3109-1449 NR 91 TC 185 Z9 191 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 2003 VL 97 IS 12 BP 3027 EP 3035 DI 10.1002/cncr.11426 PG 9 WC Oncology SC Oncology GA 686WC UT WOS:000183343100014 PM 12784338 ER PT J AU D'Amico, M Wu, KM Di Vizio, D Reutens, AT Stahl, M Fu, MF Albanese, C Russell, RG Muller, WJ White, M Negassa, A Lee, HW DePinho, RA Pestell, RG AF D'Amico, M Wu, KM Di Vizio, D Reutens, AT Stahl, M Fu, MF Albanese, C Russell, RG Muller, WJ White, M Negassa, A Lee, HW DePinho, RA Pestell, RG TI The role of Ink4a/Arf in ErbB2 mammary gland tumorigenesis SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER CELLS; ARF TUMOR-SUPPRESSOR; CYCLIN D1; P53-DEPENDENT APOPTOSIS; RETINOBLASTOMA-PROTEIN; P16(INK4A) EXPRESSION; EPITHELIAL-CELLS; GENE-EXPRESSION; ACTIVATED NEU; P53 AB Most human tumors display inactivation of the p53 and the p16(INK4)/pRb pathway. The Ink4a/alternative reading frame (ARF) locus encodes the p16(INK4a) and p14(ARF) (murine p19(ARF)) proteins. p16(INK4a) is deleted in 40-60% of breast cancer cell lines, and p16(INK4a) inactivation by DNA methylation occurs in greater than or equal to30% of human breast cancers. In mice genetically heterozygous for p16(INK4a) or Ink4a/Arf, predisposition to specific tumor types is enhanced. Ink4a/Arf(+/-) mice have increased Emu-Myc-induced lymphomagenesis and epidermal growth factor receptor-induced gliomagenesis. ErbB2 (epidermal growth factor receptor-related protein B2) is frequently overexpressed in human breast cancer and is sufficient for mammary tumorigenesis in vivo. We determined the role of heterozygosity at the Ink4a/Arf locus in ErbB2-iriduced mammary tumorigenesis. Compared with mouse mammary tumor virus-ErbB2 Ink4a/Arf(+/-) mice, mouse mammary tumor virus-ErbB2 Ink4a/Arf(+/-) mammary tumors showed increased p16(INK4a), reduced Ki-67 expression, and reduced cyclin D1 protein but increased mammary tumor apoptosis with no significant change in the risk of developing mammary tumors. These studies demonstrate the contribution of Ink4a/Arf heterozygosity to tumor progression is tissue specific in vivo. In view of the important role of Ink4a/Arf in response to chemotherapy, these transgenic mice may provide a useful model for testing breast tumor therapies. C1 Georgetown Univ, Dept Oncol, Lombardi Canc Ctr, Washington, DC 20007 USA. Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10461 USA. McMaster Univ, Dept Pathol, Hamilton, ON L8S 4K1, Canada. UT SW, Med Ctr, Dept Cell Biol, Dallas, TX USA. UT SW, Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX USA. Sungkyunkwan Univ, Div Epidemiol & Biostat, Suwon 440746, South Korea. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pestell, RG (reprint author), Georgetown Univ, Dept Oncol, Lombardi Canc Ctr, Res Bldg,Room E501,3970 Reservoir Rd NW,Box 57146, Washington, DC 20007 USA. EM pestell@georgetown.edu FU NCI NIH HHS [R01CA70896, R01CA75503, R01CA86071, R01CA86072]; NIA NIH HHS [R03AG20337] NR 59 TC 26 Z9 26 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2003 VL 63 IS 12 BP 3395 EP 3402 PG 8 WC Oncology SC Oncology GA 691CG UT WOS:000183586800059 PM 12810676 ER PT J AU Gavrila, A Tsiodras, S Doweiko, J Nagy, GS Brodovicz, K Hsu, W Karchmer, AW Mantzoros, CS AF Gavrila, A Tsiodras, S Doweiko, J Nagy, GS Brodovicz, K Hsu, W Karchmer, AW Mantzoros, CS TI Exercise and vitamin E intake are independently associated with metabolic abnormalities in human immunodeficiency virus-positive subjects: A cross-sectional study SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; COMPUTED-TOMOGRAPHY MEASUREMENT; TYPE-2 DIABETES-MELLITUS; BODY-COMPOSITION; HISTORY QUESTIONNAIRE; INSULIN-RESISTANCE; CONTROLLED TRIAL; FASTING HYPERINSULINEMIA; INTRACELLULAR MAGNESIUM; ANTIRETROVIRAL THERAPY AB We investigated the relationship among habitual exercise, diet, and the presence of metabolic abnormalities (body fat redistribution, dyslipidemia, and insulin resistance) in a cross-sectional study of 120 human immunodeficiency virus (HIV)-infected subjects with use of bivariate and multivariate regression-analysis models. Total and aerobic exercise were significantly and negatively associated with fasting plasma triglyceride levels in the entire sample and in the fat redistribution group. Inverse associations between total or aerobic exercise and insulin resistance were suggestive but did not achieve statistical significance. Diastolic blood pressure was significantly and inversely associated with supplemental or total but not habitual dietary intake of vitamin E. In conclusion, exercise and vitamin E intake were independently and negatively associated with several phenotypic manifestations of HIV-associated metabolic syndrome, whereas other macro- or micronutrients did not have comparable significance. C1 Beth Israel Deaconess Med Ctr, Div Endocrinol & Metab, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Infect Dis, Dept Internal Med, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Merck Res Labs, Blue Bell, PA USA. RP Mantzoros, CS (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol & Metab, 99 Brookline Ave,RN 325, Boston, MA 02215 USA. OI Tsiodras, Sotirios/0000-0002-0463-4321 FU NCRR NIH HHS [M01-RR 01032]; NHLBI NIH HHS [K30 HL04095] NR 59 TC 20 Z9 20 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 15 PY 2003 VL 36 IS 12 BP 1593 EP 1601 DI 10.1086/375225 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 688WJ UT WOS:000183460000015 PM 12802761 ER PT J AU Gandhi, RT Wurcel, A Lee, H McGovern, B Boczanowski, M Gerwin, R Corcoran, CP Szczepiorkowski, Z Toner, S Cohen, DE Sax, PE Ukomadu, C AF Gandhi, RT Wurcel, A Lee, H McGovern, B Boczanowski, M Gerwin, R Corcoran, CP Szczepiorkowski, Z Toner, S Cohen, DE Sax, PE Ukomadu, C TI Isolated antibody to hepatitis B core antigen in human immunodeficiency virus type-1-infected individuals SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HIV-INFECTED PATIENTS; HBC AB We screened 651 human immunodeficiency virus (HIV)-1-infected subjects for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B surface antigen (anti-HBs). Of a total of 387 subjects who tested negative for both HBsAg and anti-HBs, 142 underwent further testing for isolated presence of antibody to hepatitis B core antigen (anti-HBc). Of these 142 subjects, 60 (42%) tested positive for anti-HBc (isolated anti-HBc). Individuals coinfected with HIV-1 and hepatitis C virus (HCV) were more likely to have isolated anti-HBc than were subjects with HIV-1 alone (80% vs. 16%, respectively). Our findings suggest that individuals with HIV-1/HCV coinfection for whom there is no serological evidence for hepatitis B virus when screened with HBsAg and anti-HBs will be positive for anti-HBc in >75% of cases. A screening strategy that tests only for HBsAg and anti-HBs in HIV-1-infected patients will miss a large number of individuals with isolated anti-HBc. C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Lemuel Shattuck Hosp, Boston, MA USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Fenway Community Hlth Ctr, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Gandhi, RT (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, GRJ 504,55 Fruit St, Boston, MA 02114 USA. RI Szczepiorkowski, Zbigniew/A-1359-2007 OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564 NR 12 TC 56 Z9 59 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 15 PY 2003 VL 36 IS 12 BP 1602 EP 1605 DI 10.1086/375084 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 688WJ UT WOS:000183460000016 PM 12802762 ER PT J AU Kemeny, MM Peterson, BL Kornblith, AB Muss, HB Wheeler, J Levine, E Bartlett, N Fleming, G Cohen, HJ AF Kemeny, MM Peterson, BL Kornblith, AB Muss, HB Wheeler, J Levine, E Bartlett, N Fleming, G Cohen, HJ TI Barriers to clinical trial participation by older women with breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COOPERATIVE-ONCOLOGY-GROUP; REPRESENTATION; CHEMOTHERAPY; TOLERANCE; ATTITUDES; PREDICT AB Purpose: Although 48% of breast cancer patients are 65 years old or older, these older patients are severely under-represented in breast cancer clinical trials. This study tested whether older patients were offered trials significantly less often than younger patients and whether older patients who were offered trials were more likely to refuse participation than younger patients. Patients and Methods: In 10 Cancer and Leukemic Group 8 institutions, using a retrospective case-control design, breast cancer patients eligible for an open treatment trial were paired. less than 65 years old and at 65 years old. Each of the 77 Pairs were matched by disease gage and treating physician. Patients were interviewed as to their reasons for participating or refusing to participate in a trial. The treating physicians were also given questionnaires about their reasons for offering or not offering a trial. Results: Sixty-eight percent of younger stage II patients were offered a trial compared with 340% of the older patients (P = .0004). In multivariate, analyses, disease stage and age remained highly significant in predicting trial offering (P = .0008), when controlling for physical functioning and comorbidity. Of those offered a trial, there was no significant difference in participation between younger (56%.) and older (50%) patients (P = .67). Conclusion: In a multivariate analysis including comorbid conditions, age and stage were the only predictors of whether a patient was offered a trial. The greatest impediment to enrolling older women onto trials in the setting of this study was the physicians' perceptions about age and tolerance of toxicity. C1 Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Canc & Leukemia Grp B, Chicago, IL USA. Queens Hosp Ctr, Mt Sinai Sch Med, Canc Ctr Queens, Jamaica, NY USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Canc & Leukemia Grp B Stat Ctr, Durham, NC USA. Canc & Leukemia Grp B Management Ctr, Durham, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Dana Farber Canc Ctr, Boston, MA USA. Vermont Canc Ctr, Burlington, VT USA. Washington Univ, Med Ctr, St Louis, MO USA. RP Kemeny, MM (reprint author), 82-68 164th St, Jamaica, NY 11432 USA. FU NCI NIH HHS [CA31946] NR 23 TC 183 Z9 187 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 15 PY 2003 VL 21 IS 12 BP 2268 EP 2275 DI 10.1200/JCO.2003.09.124 PG 8 WC Oncology SC Oncology GA 690TG UT WOS:000183564800009 PM 12805325 ER PT J AU Fine, HA Wen, PY Maher, EA Viscosi, E Batchelor, T Lakhani, N Figg, WD Purow, BW Borkowf, CB AF Fine, HA Wen, PY Maher, EA Viscosi, E Batchelor, T Lakhani, N Figg, WD Purow, BW Borkowf, CB TI Phase II trial of thalidomide and carmustine for patients with recurrent high-grade gliomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; LEWIS LUNG-CARCINOMA; TUMOR-GROWTH; RADIATION-THERAPY; IN-VIVO; MALIGNANT GLIOMAS; BRAIN-TUMORS; 1ST RELAPSE; ANGIOGENESIS; ANGIOSTATIN AB Purpose: The use of thalidomide as an antiangiogenic agent has met with only limited success in the treatment of malignant gliomas. On the basis of preclinical data demonstrating synergistic antitumor activity when antiangiogenic agents are combined with cytotoxic agents, we explored the clinical activity of the combination of thalidomide and carmustine (BCNU) in patients with recurrent high-grade gliomas. Patients and Methods: Patients with a histologic diagnosis of high-grade glioma and radiographic evidence of tumor progression after standard surgery, radiation, and chemotherapy were eligible for the study. Patients received BCNU 200 mg/m(2) on day 1 of every 6-week cycle, and 800 mg/d of thalidomide that was escalated to a maximal dose of 1,200 mg/d as tolerated. Results: A total of 40 patients (38 with glioblastomas, two with anaplastic gliomas) were accrued to the study. The combination of thalidomide and BCNU was well tolerated; mild myelosuppression and mild to moderate sedation were the most common side effects. The median progression-free survival (100 days) and the objective radiographic response rate (24%) for patients with glioblastoma compared favorably with data from historical controls. Conclusion: This is one of the first clinical trials to evaluate the strategy of combining a putative antiangiogenic agent with a cytotoxic agent in patients with primary brain tumors. Our data demonstrate that thalidomide in combination with BCNU is well tolerated and has antitumor activity in patients with recurrent high-grade gliomas. Although the combination seems to be more active than either agent alone, such conclusions await confirmatory trials. C1 NCI, Neurooncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NCI, Canc Therapeut Branch, NIH, Bethesda, MD 20892 USA. NCI, Canc Prevent Branch, NIH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Dept Neurol, Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Fine, HA (reprint author), NCI, Neurooncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,MSC 1911,Bldg 10,Room 12S245, Bethesda, MD 20892 USA. EM hfine@mail.nih.gov RI Figg Sr, William/M-2411-2016 NR 37 TC 111 Z9 116 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 15 PY 2003 VL 21 IS 12 BP 2299 EP 2304 DI 10.1200/JCO.2003.08.045 PG 6 WC Oncology SC Oncology GA 690TG UT WOS:000183564800014 PM 12805330 ER PT J AU Jaeckle, KA Hess, KR Yung, WKA Greenberg, H Fine, H Schiff, D Pollack, IF Kuhn, J Fink, K Mehta, M Cloughesy, T Nicholas, MK Chang, S Prados, M AF Jaeckle, KA Hess, KR Yung, WKA Greenberg, H Fine, H Schiff, D Pollack, IF Kuhn, J Fink, K Mehta, M Cloughesy, T Nicholas, MK Chang, S Prados, M TI Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma: A North American Brain Tumor Consortium study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TRANS-RETINOIC ACID; CELL-LINES; ANTITUMOR IMIDAZOTETRAZINES; RADIATION-THERAPY; ASTROCYTOMA-CELLS; 1ST RELAPSE; IN-VITRO; PROLIFERATION; CHEMOTHERAPY; XENOGRAFTS AB Purpose: Temozolomide (TMZ) and 13-cis-retinoic acid (cRA) have shown activity in prior single-agent trials of recurrent malignant gliomas (MG). This phase II trial evaluated efficacy and toxicity of combination temozolomide and cRA treatment in recurrent MG. Patients and Methods: Adults with recurrent supratentorial MG for whom surgery, radiation, and/or chemotherapy failed were eligible. Treatment included oral TMZ 150 or 200 mg/m(2)/d, days 1 through 5, and cRA 100 mg/m(2)/d, days 1 to 21, every 28 days. Primary end point was progression-free survival at 6 months (PFS 6); secondary end points included response, survival, and PFS12. Results: Eighty-eight eligible patients (glioblastoma multiforme [n = 40], anaplastic gliomas [n = 48; astrocytoma, 28; oligodendroglioma, 14, mixed glioma, six]) received treatment. PFS 6 was 43% (95% confidence interval [CI], 33% to 54%) and PFS12 was 16% (95% CI, 10% to 26%). Median overall PFS was 19 weeks (95% CI, 16 to 27 weeks), and median overall survival (OS) was 47 weeks (95% CI, 36 to 58 weeks). OS was 46% (95% CI, 36% to 57%) at 52 weeks and 21% (95% CI, 13% to 31%) at 104 weeks. Of 84 assessable patients, there were two (3%) complete responses and eight (12%) partial responses (complete plus partial response, 15%). Among 499 treatment cycles, the most common grade 3/4 events included granulocytopenic (1.8%), thrombocytopenic (1.4%), and hypertriglyceridemia (1.2%). Conclusion: TMZ and cRA were active, exceeding our 20% thresholds for PFS 6 success, assuming 20% improvement over our previously reported database (glioblastoma multiforme: expected, 30%, observed, 32%; anaplastic glioma: expected, 40%; observed, 50%). C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Michigan, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Pittsburgh, PA USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. Univ Wisconsin, Madison, WI USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Chicago, Chicago, IL 60637 USA. RP Jaeckle, KA (reprint author), Mayo Clin Jacksonville, Dept Oncol & Neurol, 4500 San Pablo Blvd, Jacksonville, FL 32224 USA. EM jaeckle.kurt@mayo.edu OI mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [CA16672, CA62399, CA62412, CA62422, CA62426, CA62455, UO1CA62399, UO1CA62405, UO1CA62407-08, UO1CA62421]; NCRR NIH HHS [M01-RR03186, M01-RR00042, M01-RR00633, M01-RR0865, MO1-RR00056] NR 35 TC 100 Z9 103 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 15 PY 2003 VL 21 IS 12 BP 2305 EP 2311 DI 10.1200/JCO.2003.12.097 PG 7 WC Oncology SC Oncology GA 690TG UT WOS:000183564800015 PM 12805331 ER PT J AU Schnipper, LE Atkins, M Beveridge, RA Brenner, D Bunn, P Coleman, E Comis, RL Einhorn, L Emanuel, E Fields, S Forastiere, A Gordon, BG Halberg, F Haluska, F Hortobagyi, G Kolker, A Miller, LL Norton, L Sallan, S Scherr, S Niederhuber, JE Baggstrom, MQ Balducci, L Bosserman, LD Bosworth, LL Brose, M Come, SE Cripe, LD Fisch, M Gesme, D Goldstein, N Gordon, BG Gostout, B Gralow, J Grunberg, SM Haluska, FG Hortobagyi, GN Klimberg, VS Kuzel, T Lessin, LS Pazdur, R Pfister, DG Raghavan, D Runowicz, CD Schnipper, LE Schuchter, LM Schwartz, BS Sigal, EV Stovall, E Ward, JH Zwelling, LA AF Schnipper, LE Atkins, M Beveridge, RA Brenner, D Bunn, P Coleman, E Comis, RL Einhorn, L Emanuel, E Fields, S Forastiere, A Gordon, BG Halberg, F Haluska, F Hortobagyi, G Kolker, A Miller, LL Norton, L Sallan, S Scherr, S Niederhuber, JE Baggstrom, MQ Balducci, L Bosserman, LD Bosworth, LL Brose, M Come, SE Cripe, LD Fisch, M Gesme, D Goldstein, N Gordon, BG Gostout, B Gralow, J Grunberg, SM Haluska, FG Hortobagyi, GN Klimberg, VS Kuzel, T Lessin, LS Pazdur, R Pfister, DG Raghavan, D Runowicz, CD Schnipper, LE Schuchter, LM Schwartz, BS Sigal, EV Stovall, E Ward, JH Zwelling, LA CA Amer Soc Clin Oncology TI American Society of Clinical Oncology policy statement: Oversight of clinical research SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article AB Well-publicized lapses in the review or implementation of clinical research studies have raised public questions about the integrity of the clinical research process. Public trust in the integrity of research is critical not only for funding and participation in clinical trials but also for confidence in the treatments that result from the trials. The questions raised by these unfortunate cases pose an important opportunity to reassess the clinical trials oversight system to ensure the integrity of clinical research and the safety of those who enroll in clinical trials. Since its inception, the American Society of Clinical Oncology (ASCO) has worked for the advancement of cancer treatments through clinical research and to help patients gain prompt access to scientifically excellent and ethically unimpeachable clinical trials. As an extension of its mission, ASCO is affirming with this policy statement the critical importance of a robust review and oversight system to ensure that clinical trials participants give fully informed consent and that their safety is a top priority. Ensuring the integrity of research cannot be stressed enough because of its seminal connection to the advancement of clinical cancer treatment. The overall goal of this policy is to enhance public trust in the cancer clinical trials process. To achieve this, the following elements are essential: 1. Ensure safety precautions for clinical trial participants and their fully informed consent. 2. Ensure the validity and integrity of scientific research. 3. Enhance the educational training of clinical scientists and research staff to ensure the highest standards of research conduct. 4. Promote accountability and responsibility among all those involved in clinical research (not just those serving on institutional review boards [IRBs], but also institutional officials, researchers, sponsors, and participants) and ensure support for an effective oversight process. 5. Enhance the professional and public understanding of clinical research oversight. 6. Enhance the efficiency and cost-effectiveness of the clinical research oversight system. This policy statement makes recommendations in several areas that serve as principles to support an improved system of oversight for clinical research. ASCO will work with all parties involved in the clinical research system to develop the steps necessary to implement these recommendations. Centralized Trial Review: A large percentage of oncology clinical trials are coordinated through the National Cancer Institute's (NCI) system of cooperative groups, which already incorporates centralized scientific review. As such, there is a tremendous opportunity to employ a centralized mechanism to provide ethical review by highly trained IRB members, allowing local IRBs to take advantage of the financial and time efficiencies that central review provides. Centralized review boards (CRBs) would also contribute consistency and efficiency to the process. Once successfully completed, the review would represent an approval to open the protocol at all of the institutions that have subscribed to the centralized review system. Local IRBs would be able to devote time usually spent on initial review to ongoing monitoring of the trial taking place at their institution. Considering the enormous size and complexity of the clinical research enterprise, ASCO envisions multiple CRBs, which could be distributed as regional review boards. Central review will use a single protocol and consent form, and monitor and evaluate adverse events (AEs) on a global basis, eliminating many of the time-consuming steps for the local IRB. Global monitoring and assessment of AEs has real potential to enhance trial participants' safety by giving local institutions more information on the overall trial and enabling them to devote more time to ongoing review of the trial onsite. Use of a CRB also has real potential to reduce the costs of clinical trial oversight by allowing local IRBs to eliminate the costs of initial review. These efficiencies will likely lead to institutions redirecting funds toward monitoring ongoing trials. Although a CRB has potential to improve the efficiency of the process, a CRB could also have tremendous ability to delay valuable trials. Checks and balances must be included in the newly devised system to ensure timely review and appeals of CRB actions. ASCO proposes the advent of a new pilot program for centralizing review of clinical trials. It requires clear engagement of all stakeholders in planning the experiment, clear articulation of the goals, and assurance of federal regulatory protection for institutions choosing to participate. If successful, this CRB pilot project could be expanded to include multi-institutional industry-sponsored research. Education and Training. Education and training are critical to the ultimate success of an improved oversight system. All members of the research team should receive comprehensive education on conducting scientifically and ethically valid clinical research. The curriculum should also include information an the prevailing local and federal regulations that pertain to the clinical trials process. IRB members should also receive ongoing education and training in the review of clinical research protocols. IRB training should pay particular attention to nonscientific members to give them the toots necessary to speak on behalf of research participants. ASCO should develop a curriculum that focuses on the proper conduct of human research and emphasize ethically sound clinical research in the context of its Annual Meeting. Informed Consent: Investigators and review boards have specific roles to play in ensuring the education of trial participants through the informed consent process, both when they are considering trial enrollment and as they participate in the trial. Review boards and investigators should focus primarily on the informed consent process, rather than the informed consent documents. Federal Oversight: The federal government has an important role to play in the oversight of clinical research. This role should be expanded to cover all research, not just that which is funded by the federal government or conducted with the oversight of the Food and Drug Administration (FDA). The Department of Health and Human Services (HHS) Office for Human Research Protections (OHRP) and the FDA should provide dear regulatory support and guidance for local institutions that choose to employ a CRB. In the case, of the pilot CRB discussed in this policy statement, it should serve as the preferred option for the cancer cooperative group clinical trials. Ideally, the federal government should unify and streamline its regulations for the oversight of clinical research. Resources Supporting Clinical Research Infrastructure: An effective oversight process demands the highest quality scientific and ethical review and onsite monitoring of the safety of trial participants. This can only be accomplished by the involvement of an experienced IRB that receives funding, resources, and institutional support enabling it to fulfill its mandate. Conflict of interest: Critical to the integrity of research is the absence of bias in the process. ASCO strongly recommends the adoption of standards for the identification, management, and, where appropriate, elimination of conflicts of interests, whether they are actual, potential, or apparent. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Inova Fairfax Hosp, Alexandria, VA USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Univ Colorado, Ctr Canc, Denver, CO 80262 USA. Canc Care Inc, New York, NY USA. Eastern Cooperat Oncol Grp, Philadelphia, PA USA. Indiana Univ, Canc Pavil, Indianapolis, IN 46204 USA. NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Johns Hopkins Univ, Ctr Oncol, Baltimore, MD 21205 USA. Univ Nebraska, Med Ctr, Omaha, NE USA. Marin Canc Inst, Greenbrae, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Ovarian Canc Natl Alliance, Washington, DC USA. Pharmacia Corp, Peapack, NJ USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Natl Coalit Canc Survivorship, Silver Spring, MD USA. Amer Soc Clin Oncol Canc Policy & Clin Affairs, Alexandria, VA 22314 USA. NR 11 TC 32 Z9 33 U1 1 U2 15 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 JUN 15 PY 2003 VL 21 IS 12 BP 2377 EP 2386 DI 10.1200/JCO.2003.04.026 PG 10 WC Oncology SC Oncology GA 690TG UT WOS:000183564800025 ER PT J AU Bruinooge, SS AF Bruinooge, SS CA ASCO TI American Society of Clinical Oncology policy statement update: Genetic testing for cancer susceptibility SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INFORMED CONSENT; ADOLESCENTS; EXPRESSION; EDUCATION; CHILDREN; TISSUE AB As the leading organization representing cancer specialists involved in patient care and clinical research, the American Society of Clinical Oncology (ASCO) reaffirms its commitment to integrating cancer risk assessment and management, including molecular analysis of cancer predisposition genes, into the practice of oncology and preventive medicine. The primary goal of this effort is to foster expanded access to, and continued advances in, medical care provided to patients and families affected by hereditary cancer syndromes. The 1996 ASCO Statement on Genetic Testing for Cancer Susceptibility set forth specific recommendations relating to clinical practice, research needs, educational opportunities, requirement for informed consent, indications for genetic testing, regulation of laboratories, and protection from discrimination, as well as access to and reimbursement for cancer genetics services. In updating this Statement, ASCO endorses the following principles: Indications for Genetic Testing: ASCO recommends that genetic testing be offered when 1) the individual has personal or family history features suggestive of a genetic cancer susceptibility condition, 2) the test can be adequately interpreted, and 3) the results will aid in diagnosis or influence the medical or surgical management of the patient or family members at hereditary risk of cancer. ASCO recommends that genetic testing only be done in the setting of pre- and post-test counseling, which should include discussion of possible risks and benefits of cancer early detection and prevention modalities. Special Issues in Testing Children for Cancer Susceptibility: ASCO recommends that the decision to offer testing to potentially affected children should take into account the availability of evidence-based risk-reduction strategies and the probability of developing a malignancy during childhood. Where risk-reduction strategies are available or cancer predominantly develops in childhood, ASCO believes that the scope of parental authority encompasses the eight to decide for or against testing. In the absence of increased risk of a childhood malignancy, ASCO recommends delaying genetic testing until an individual is of sufficient age to make an informed decision regarding such tests. As in other areas of pediatric care, the clinical cancer genetics professional should be an advocate for the best interests of the child. Counseling About Medical Management After Testing. ASCO recommends that oncologists include in pre- and post-test counseling the discussion of possible risks and benefits of cancer early-detection and prevention modalities, some of which have presumed but unproven efficacy for individuals at increased hereditary risk of cancer. Regulation of Genetic Testing: ASCO recommends strengthening regulatory oversight of laboratories that provide clinical cancer predisposition tests. These quality assurance mechanisms should include oversight of the reagents used in genetic testing, interlaboratory comparisons of reference samples, standardization of laboratory genetic test reports, and proficiency testing. Protection From Insurance and Employment Discrimination: ASCO supports establishing a federal law to prohibit discrimination by health insurance providers and employers on the basis of an individual's inherited susceptibility to cancer. Protections against genetic discrimination should apply to those with group coverage, those with individual health insurance policies, and the uninsured. Coverage of Services: ASCO supports efforts to ensure that all individuals at significantly increased risk of hereditary cancer have access to appropriate genetic counseling, testing, screening, surveillance, and all related medical and surgical interventions, which should be covered without penalty by public and private third-party payers. Confidentiality and Communication of Familial Risk. ASCO recommends that providers make concerted efforts to protect the confidentiality of genetic information. However, they should remind patients of the importance of communicating test results to family members, as part of pretest counseling and informed consent discussions. ASCO believes that the cancer care provider's obligations (if any) to at-risk relatives are best fulfilled by communication of familial risk to the person undergoing testing, emphasizing the importance of sharing this information with family members so that they may also benefit. Educational Opportunities in Genetics: ASCO is committed to continuing to provide educational opportunities for physicians and other health care providers regarding the methods of cancer risk assessment, the clinical characteristics of hereditary cancer susceptibility syndromes, and the range of issues related to genetic testing, including pre- and post-test genetic counseling, and risk management, so that health professionals may responsibly integrate the care of persons at increased genetic risk of cancer into the practice of clinical and preventive oncology. Special Issues Relating to Genetic Research on Human Tissues. ASCO recommends that all researchers proposing to use or store human biologic specimens for genetic studies should consult either the responsible institutional review board (IRS) or a comparable body specifically constituted to assess human tissue research, to determine the requirements for protection specific to the study under consideration. This consultation should take place before the project is initiated. The determination of the need for informed consent or authorization in such studies should depend on whether the research involves tests for genetic markers of known clinical significance and whether research data will be linked to protected health information, as well as other considerations specific to the study proposed. Special attention should also be paid to 1) whether future research findings Will be disclosed to the research participants, 2) whether future contact of participants is planned, 3) whether and how protected health information about the tissue donors will, be stared, and what will happen to study specimens after the trial ends. In addition, ASCO affirms the right of people contributing tissue to a databank to rescind their permission, in accordance with federal privacy regulations. C1 Amer Soc Clin Oncol, Alexandria, VA 22314 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Albert Einstein Coll Med, Oakland, CA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, NIH, Rockville, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. Marin Canc Inst, Greenbrae, CA USA. James Canc Hosp & Res Inst, Columbus, OH USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Amer Coll Med Genet, Bethesda, MD USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. RP Bruinooge, SS (reprint author), Amer Soc Clin Oncol, 1900 Duke St,Suite 200, Alexandria, VA 22314 USA. NR 24 TC 367 Z9 373 U1 1 U2 22 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 JUN 15 PY 2003 VL 21 IS 12 BP 2397 EP 2406 DI 10.1200/JCO.2003.03.189 PG 10 WC Oncology SC Oncology GA 690TG UT WOS:000183564800028 ER PT J AU Ferreri, AJM Abrey, LE Blay, JY Borisch, B Hochman, J Neuwelt, EA Yahalom, J Zucca, E Cavalli, F Armitage, J Batchelor, T AF Ferreri, AJM Abrey, LE Blay, JY Borisch, B Hochman, J Neuwelt, EA Yahalom, J Zucca, E Cavalli, F Armitage, J Batchelor, T TI Summary statement on primary central nervous system lymphomas from the Eighth International Conference on Malignant Lymphoma, Lugano, Switzerland, June 12 to 15, 2002 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PRIMARY CNS LYMPHOMA; HIGH-DOSE METHOTREXATE; NON-HODGKINS-LYMPHOMA; BLOOD-BRAIN-BARRIER; B-CELL LYMPHOMA; INTRAOCULAR LYMPHOMA; IMMUNOCOMPETENT PATIENTS; RADIATION-THERAPY; CEREBROSPINAL-FLUID; CONSOLIDATION RADIOTHERAPY AB Under the sponsorship of the International Extranodal Lymphoma Study Group, a Multidisciplinary Workshop on primary CNS lymphoma (PCNSL) with over 50 participants from Europe, North America, Israel, and Australia was held as part of the Eighth International Conference on Malignant Lymphoma in Lugano, Switzerland (June 12 to 15, 2002). The main purposes of the Workshop were to exchange the latest scientific information, to analyze methodologic issues in the design of clinical trials, to reach a consensus on treatment recommendations and prognostic factors, to discuss clinical and molecular targets for future studies, and to establish an international collaborative group to conduct laboratory and clinical investigations in PCNSL. This article summarizes the contents of the Workshop, analyzes the current knowledge on the most relevant biologic and clinical issues in PCNSL, and focuses on fundamental challenges to be addressed in future studies. C1 San Raffaele H Sci Inst, Dept Radiochemotherapy, I-20132 Milan, Italy. Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. Oregon Hlth & Sci Univ, Dept Neurol & Neurosurg, Portland, OR 97201 USA. Univ Nebraska, Med Ctr, Coll Med, Omaha, NE USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Hop Edouard Herriot, Unite Cytokines & Canc, Lyon, France. Ctr Leon Berard, F-69373 Lyon, France. Univ Geneva, Dept Pathol, CH-1211 Geneva, Switzerland. Osped San Giovanni Bellinzona, Div Med Oncol, Oncol Inst So Switzerland, Bellinzona, Switzerland. Hebrew Univ Jerusalem, Inst Life Sci, Dept Cell & Anim Biol, IL-91904 Jerusalem, Israel. RP Ferreri, AJM (reprint author), San Raffaele H Sci Inst, Dept Radiochemotherapy, Via Olgettina 60, I-20132 Milan, Italy. RI Ferreri, Andres Jose Maria/A-6662-2013; Blay, Jean-Yves/N-3966-2016 OI Ferreri, Andres Jose Maria/0000-0001-9606-6124; Blay, Jean-Yves/0000-0001-7190-120X NR 76 TC 110 Z9 124 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 15 PY 2003 VL 21 IS 12 BP 2407 EP 2414 DI 10.1200/JCO.2003.01.135 PG 8 WC Oncology SC Oncology GA 690TG UT WOS:000183564800029 PM 12805341 ER PT J AU Back, AL Arnold, RM Tulsky, JA Baile, WF Fryer-Edwards, KA AF Back, AL Arnold, RM Tulsky, JA Baile, WF Fryer-Edwards, KA TI Teaching communication skills to medical oncology fellows SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHYSICIANS C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Med Hist & Eth, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Pittsburgh, Dept Med, Sect Med Eth & Palliat Care, Pittsburgh, PA USA. Vet Affairs Med Ctr, Program Med Encounter & Palliat Care, Durham, NC USA. Duke Univ, Dept Med, Durham, NC USA. Duke Univ, Inst Care End Life, Durham, NC USA. Univ Texas, MD Anderson Canc Ctr, Sect Psychiat, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. RP Back, AL (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-111, Seattle, WA 98108 USA. FU NCI NIH HHS [R25 CA92055] NR 5 TC 119 Z9 120 U1 0 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 15 PY 2003 VL 21 IS 12 BP 2433 EP 2436 DI 10.1200/JCO.2003.09.073 PG 4 WC Oncology SC Oncology GA 690TG UT WOS:000183564800031 PM 12805343 ER PT J AU Brown, JR Wieczorek, TJ Shaffer, K Salgia, R AF Brown, JR Wieczorek, TJ Shaffer, K Salgia, R TI Small-cell cancers, and an unusual reaction to chemotherapy - Case 1. Extrapulmonary small-cell carcinoma arising in the prostate SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID THERAPY C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Brown, JR (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. OI Shaffer, Kitt/0000-0001-6488-6988 NR 11 TC 6 Z9 6 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 JUN 15 PY 2003 VL 21 IS 12 BP 2437 EP 2439 DI 10.1200/JCO.2003.081.03 PG 3 WC Oncology SC Oncology GA 690TG UT WOS:000183564800032 PM 12805344 ER PT J AU Shapiro, MD Hanken, J Rosenthal, N AF Shapiro, MD Hanken, J Rosenthal, N TI Developmental basis of evolutionary digit loss in the Australian lizard Hemiergis SO JOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL EVOLUTION LA English DT Article ID SONIC-HEDGEHOG; LIMB BUD; FEEDBACK LOOP; EXPRESSION; VERTEBRATE; SHH; REDUCTION; CHICK; HETEROCHRONY; APOPTOSIS AB Loss of limb skeletal elements is a recurring theme in tetrapod evolution, but the developmental mechanisms underlying this phenomenon remain largely unknown. The Australian lizard genus Hemiergis offers an excellent model system to study limb reduction among closely related, naturally occurring populations with different numbers of digits. Evolutionary digit loss in Hemiergis does not result from simple truncation of a pentadactyl skeletal developmental program. Rather, the duration of embryonic expression of the patterning molecule Sonic hedgehog (SHH) is shortened in limbs with reduced numbers of digits, and is correlated with decreased cell proliferation in the posterior aspect of the limb. Moreover, this comparative analysis suggests an early role for SHH in specification of digit identity and later importance in maintaining cell proliferation and survival. Subtle changes in spatial or temporal regulation of SHH may alter proliferation and patterning of the developing limb, thereby effecting divergence in adult limb morphology among closely related species. In contrast, expression of MSX and Distal-less proteins were similar among embryos from different populations. (C) 2003 Wiley Liss, Inc. C1 Harvard Univ, Dept Organ & Evolutionary Biol, Cambridge, MA 02138 USA. Harvard Univ, Museum Comparat Zool, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Shapiro, MD (reprint author), Stanford Univ, Sch Med, Dept Dev Biol, 279 Campus Dr, Stanford, CA 94305 USA. EM mshapiro@cmgm.stanford.edu RI Self, Casey/B-6871-2011 NR 40 TC 79 Z9 80 U1 2 U2 15 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-5007 J9 J EXP ZOOL PART B JI J. Exp. Zool. Part B PD JUN 15 PY 2003 VL 297B IS 1 BP 48 EP 56 DI 10.1002/jez.b.00019 PG 9 WC Evolutionary Biology; Developmental Biology; Zoology SC Evolutionary Biology; Developmental Biology; Zoology GA 687DW UT WOS:000183361600005 PM 12955843 ER PT J AU Grey, ST Longo, C Shukri, T Patel, VI Csizmadia, E Daniel, S Arvelo, MB Tchipashvili, V Ferran, C AF Grey, ST Longo, C Shukri, T Patel, VI Csizmadia, E Daniel, S Arvelo, MB Tchipashvili, V Ferran, C TI Genetic engineering of a suboptimal islet graft with A20 preserves beta cell mass and function SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ZINC-FINGER PROTEIN; FACTOR-KAPPA-B; INSULIN-SECRETION; INHIBITS APOPTOSIS; MEDIATED APOPTOSIS; PANCREATIC-ISLETS; ENDOTHELIAL-CELLS; MICE; TRANSPLANTATION; ACTIVATION AB Transplantation of an excessive number of islets of Langerhans (two to four pancreata per recipient) into patients with type I diabetes is required to restore euglycemia. Hypoxia, nutrient deprivation, local inflammation, and the beta cell inflammatory response (up-regulation of NF-kappaB-dependent genes such as inos) result in beta cell destruction in the early post-transplantation period. Genetic engineering of islets with anti-inflammatory and antiapoptotic genes may prevent beta cell loss and primary, nonfunction. We have shown in vitro that A20 inhibits NF-kappaB activation in islets and protects from cytokine- and death receptor-mediated apoptosis. In vivo, protection of newly transplanted islets would reduce the number of islets required for successful transplantation. Transplantation of 500 B6/AF(1) mouse islets into syngeneic, diabetic recipients resulted in a cure rate of 100% within 5 days. Transplantation of 250 islets resulted in a cure rate of only 20%. Transplantation of 250 islets overexpressing A20 resulted in a cure rate of 75% with a mean time to cure of 5.2 days, comparable to that achieved with 500 islets. A20-expressing islets preserve functional beta cell mass and are protected from cell death. These data demonstrate that A20 is an ideal cytoprotective gene therapy candidate for islet transplantation. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Immunobiol Res Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg & Med, Boston, MA 02215 USA. Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. RP Grey, ST (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Immunobiol Res Ctr, 99 Brookline Ave, Boston, MA 02215 USA. RI Grey, Shane/B-3020-2008 OI Grey, Shane/0000-0003-2160-1625 FU NIDDK NIH HHS [P01DK53087-05, R21DK062601] NR 48 TC 68 Z9 71 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2003 VL 170 IS 12 BP 6250 EP 6256 PG 7 WC Immunology SC Immunology GA 688AZ UT WOS:000183411100054 PM 12794157 ER PT J AU Kalayjian, RC Landay, A Pollard, RB Taub, DD Gross, BH Francis, IR Sevin, A Pu, MY Spritzler, J Chernoff, M Namkung, A Fox, L Martinez, A Waterman, K Fiscus, SA Sha, B Johnson, D Slater, S Rousseau, F Lederman, MM AF Kalayjian, RC Landay, A Pollard, RB Taub, DD Gross, BH Francis, IR Sevin, A Pu, MY Spritzler, J Chernoff, M Namkung, A Fox, L Martinez, A Waterman, K Fiscus, SA Sha, B Johnson, D Slater, S Rousseau, F Lederman, MM CA Adult AIDS Clin Trials Grp 5015 5113 TI Age-related immune dysfunction in health and in human immunodeficiency virus (HIV) disease: Association of age and HIV infection with naive CD8(+) cell depletion, reduced expression of CD28 on CD8(+) cells, and reduced thymic volumes SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 14th International AIDS Conference CY JUL 07-12, 2001 CL BARCELONA, SPAIN ID ACTIVE ANTIRETROVIRAL THERAPY; T-CELLS; LYMPHOCYTE SUBSETS; PERIPHERAL-BLOOD; ACTIVATION; APOPTOSIS; AIDS; SURVIVAL; ADULTS; SEROCONVERSION AB Older age is a strong predictor of accelerated human immunodeficiency virus (HIV) disease progression. We investigated the possible immunologic basis of this interaction by comparing older (greater than or equal to45 years) and younger (less than or equal to30 years) HIV-infected adults with simultaneously enrolled, aged-matched, healthy volunteers. Cross-sectional comparisons suggested age-associated reductions in naive CD8(+) cells and in the expression of CD28(+) on CD8(+) cells among both HIV-infected subjects and control subjects. Opposite patterns of CD4(+) and CD8(+) cell differences were apparent between these subject groups. HIV infection, but not age, was associated with impairments in delayed-type hypersensitivity responses, lymphoproliferation, and spontaneous apoptosis and with alterations in expression of chemokine receptors CCR5 and CXCR4. Reduced thymic volumes were associated with age and with HIV infection among younger, but not older, subjects. Because of their common association with age and HIV disease, naive CD8(+) cell depletion, diminished CD28 expression on CD8(+) cells, and reduced thymic volumes are possible correlates of the interaction of age with HIV disease. C1 Metrohlth Med Ctr, Div Infect Dis, Cleveland, OH 44109 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Rush Med Coll, Chicago, IL 60612 USA. Univ Calif Davis, Sacramento, CA 95817 USA. Univ So Calif, Los Angeles, CA USA. NIA, Baltimore, MD 21224 USA. NIA, Rockville, MD USA. NIH, Div AIDS, Rockville, MD USA. Social & Sci Syst, Rockville, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas, Galveston, TX 77555 USA. Univ N Carolina, Chapel Hill, NC USA. Triangle Pharmaceut Inc, Durham, NC 27707 USA. RP Kalayjian, RC (reprint author), Metrohlth Med Ctr, Div Infect Dis, 2500 Metrohlth Dr, Cleveland, OH 44109 USA. FU NCRR NIH HHS [M01 RR00080]; NIAID NIH HHS [AI-38858, AI-36219, AI-25879] NR 47 TC 81 Z9 82 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 15 PY 2003 VL 187 IS 12 BP 1924 EP 1933 DI 10.1086/375372 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 693NA UT WOS:000183722600012 PM 12792869 ER PT J AU South, SM Kohno, T Kaspar, BK Hegarty, D Vissel, B Drake, CT Ohata, M Jenab, S Sailer, AW Malkmus, S Masuyama, T Horner, P Bogulavsky, J Gage, FH Yaksh, TL Woolf, CJ Heinemann, SF Inturrisi, CE AF South, SM Kohno, T Kaspar, BK Hegarty, D Vissel, B Drake, CT Ohata, M Jenab, S Sailer, AW Malkmus, S Masuyama, T Horner, P Bogulavsky, J Gage, FH Yaksh, TL Woolf, CJ Heinemann, SF Inturrisi, CE TI A conditional deletion of the NR1 subunit of the NMDA receptor in adult spinal cord dorsal horn reduces NMDA currents and injury-induced pain SO JOURNAL OF NEUROSCIENCE LA English DT Article DE NMDA receptor; conditional knock-out; Cre-loxP; formalin pain; spinal cord dorsal horn; synaptic transmission; central sensitization ID D-ASPARTATE RECEPTOR; SUBSTANTIA-GELATINOSA NEURONS; MU-OPIOID RECEPTOR; NERVOUS-SYSTEM; FORMALIN TEST; CENTRAL SENSITIZATION; SYNAPTIC PLASTICITY; GLUTAMATE RECEPTORS; MESSENGER-RNAS; TISSUE-INJURY AB To determine the importance of the NMDA receptor (NMDAR) in pain hypersensitivity after injury, the NMDAR1 (NR1) subunit was selectively deleted in the lumbar spinal cord of adult mice by the localized injection of an adenoassociated virus expressing Cre recombinase into floxed NR1 mice. NR1 subunit mRNA and dendritic protein are reduced by 80% in the area of the virus injection, and NMDA currents, but not AMPA currents, are reduced 86 - 88% in lamina II neurons. The spatial NR1 knock-out does not alter heat or cold paw-withdrawal latencies, mechanical threshold, or motor function. However, injury-induced pain produced by intraplantar formalin is reduced by 70%. Our results demonstrate conclusively that the postsynaptic NR1 receptor subunit in the lumbar dorsal horn of the spinal cord is required for central sensitization, the central facilitation of pain transmission produced by peripheral injury. C1 Cornell Univ, Weill Med Coll, Dept Pharmacol, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Neurosci, New York, NY 10021 USA. Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Salk Inst Biol Studies, Lab Gen & Mol Neurobiol, La Jolla, CA 92037 USA. Univ Calif San Diego, Dept Anesthesiol, La Jolla, CA 92093 USA. RP Inturrisi, CE (reprint author), Cornell Univ, Weill Med Coll, Dept Pharmacol, 1300 York Ave, New York, NY 10021 USA. RI Kaspar, Brian/E-6490-2010; Yaksh, Tony/D-4119-2009; Kaspar, Brian/E-3349-2011; Inturrisi, Charles/E-7365-2013 FU NIDA NIH HHS [DA00198, DA01457, DA07274]; NINDS NIH HHS [NS38253, NS39518, NS41073] NR 57 TC 114 Z9 121 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 15 PY 2003 VL 23 IS 12 BP 5031 EP 5040 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 696MY UT WOS:000183891700029 PM 12832526 ER PT J AU Piqueras, L Tache, Y Martinez, V AF Piqueras, L Tache, Y Martinez, V TI Somatostatin receptor type 2 mediates bombesin-induced inhibition of gastric acid secretion in mice SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID ENTEROCHROMAFFIN-LIKE CELLS; SUBTYPE-2 KNOCKOUT MICE; ISOLATED MOUSE STOMACH; GASTROINTESTINAL-TRACT; MONOCLONAL-ANTIBODY; HISTAMINE-RELEASE; ANTAGONIST ANALOG; RAT STOMACH; NEURONS; PEPTIDE AB Studies in isolated mouse stomach showed that bombesin releases somatostatin. We characterized the effects of exogenous bombesin on gastric acid secretion in mice and determined the involvement of somatostatin and somatostatin receptor type 2 (SSTR2) by using somatostatin immunoneutralization, the SSTR2 antagonist, PRL-2903, and SSTR2 knockout mice. Gastric acid secretion was monitored under basal and pentagastrin-, histamine- or bethanechol-stimulated conditions in urethane-anaesthetized mice. Bombesin (10-40 mug kg(-1) h(-1)) and somatostatin-14 (20 mug kg(-1) h(-1)) were infused I.V. 10 and 30 min after PRL-2903 or somatostatin antibody pretreatment, respectively. Urethane-anaesthetized wild-type mice had low basal acid secretion ( 0.12 +/- 0.01 mumol (10 min)(-1)) compared with SSTR2 knockout mice (1.43 +/- 0.10 mumol (10 min)(-1)). Somatostatin antibody and PRL-2903 increased basal secretion in wild-type mice but not in SSTR2 knockout animals. In wildtype mice, bombesin inhibited secretagogue-stimulated acid secretion in a dose-dependent manner, and somatostatin-14 inhibited pentagastrin-stimulated secretion. In wild-type mice pretreated with somatostatin antibody or PRL-2903 and in SSTR2 knockout mice, bombesin and somatostatin-14 I.V. infusion did not alter the increased gastric acid secretion. These results indicate that, in mice, bombesin inhibits gastric acid secretion through the release of somatostatin and the activation of SSTR2. These observations strengthen the important role of SSTR2 in mediating somatostatin inhibitory actions on gastric acid secretion. C1 Cardenal Herrera CEU Univ, Dept Physiol Pharmacol & Toxicol, Valencia, Spain. Univ Calif Los Angeles, Dept Med, VA Greater Los Angeles Hlth Care Syst, CURE,Digest Dis Res Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90024 USA. RP Martinez, V (reprint author), AstraZeneca R&D Molndal, Dept Integrat Pharmacol, S-43183 Molndal, Sweden. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-30110, DK-41301, P30 DK041301] NR 50 TC 22 Z9 24 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 JUN 15 PY 2003 VL 549 IS 3 BP 889 EP 901 DI 10.1113/jphysiol.2003.039750 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 695DE UT WOS:000183815200021 PM 12692184 ER PT J AU Stone, ME AF Stone, ME TI The Merck manual of medical information. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 3 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD JUN 15 PY 2003 VL 128 IS 11 BP 64 EP 64 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 688XZ UT WOS:000183463700023 ER PT J AU Horan, WP Goldstein, G AF Horan, WP Goldstein, G TI A retrospective study of premorbid ability and aging differences in cognitive clusters of schizophrenia SO PSYCHIATRY RESEARCH LA English DT Article DE schizophrenia; cognitive functioning; Wisconsin Card Sorting Test ID NEUROPSYCHOLOGICALLY NORMAL SCHIZOPHRENIA; HETEROGENEITY; DECLINE; AGE; IMPAIRMENTS; HALOPERIDOL; QUETIAPINE; YOUNG AB This retrospective, cross-sectional study evaluated whether age-related differences in patterns of cognitive deficit exist among four cognitively based schizophrenia subgroups. These subgroups had previously been identified through cluster analyses of a battery of abstraction and problem-solving tests in large samples. Evaluation of estimated premorbid intellectual ability and postmorbid cognitive functioning stratified by decade from the twenties through the fifties revealed different patterns across the schizophrenia subgroups and a clinical comparison sample. A near normal cognitive subgroup demonstrated relatively high premorbid intellectual ability and a pattern of age differences similar to the comparison sample, with the exception of deficits on the Wisconsin Card Sorting Test that were detectable in the twenties and remained stable thereafter. In contrast, a subgroup characterized by severe, pervasive cognitive deficit demonstrated low premorbid intellectual ability and extremely low test scores across the four decades studied. The remaining clusters were characterized by moderate cognitive impairment and showed age differences suggestive of a decline in cognitive function around the time of illness onset that remained stable. Results provide further support for the validity of these subgroups and encourage continued efforts to identify cognitively based candidate schizophrenia subtypes. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr,151R, Pittsburgh, PA 15206 USA. NR 47 TC 17 Z9 18 U1 2 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUN 15 PY 2003 VL 118 IS 3 BP 209 EP 221 DI 10.1016/S0165-1781(03)00078-7 PG 13 WC Psychiatry SC Psychiatry GA 700LB UT WOS:000184112500002 PM 12834815 ER PT J AU Gollackner, B Dor, FJMF Knosalla, C Buhler, L Duggan, M Huang, CA Houser, SL Sachs, DH Kawai, T Ko, DSC Cooper, DKC AF Gollackner, B Dor, FJMF Knosalla, C Buhler, L Duggan, M Huang, CA Houser, SL Sachs, DH Kawai, T Ko, DSC Cooper, DKC TI Spleen transplantation in miniature swine: Surgical technique and results in major histocompatibility complex-matched donor and recipient pairs SO TRANSPLANTATION LA English DT Article ID LARGE-ANIMAL-MODEL; MIXED CHIMERISM; TOLERANCE AB Background. Spleen transplantation (Tx) between some strains of rodents can lead to donor-specific tolerance either spontaneously or after a short course of immunosuppression. This study developed a surgical technique for spleen Tx in miniature swine to investigate its immunologic impact in a large animal model. Methods. The preferred surgical technique of spleen Tx (n=8) involved excision of the donor spleen with its vascular pedicle to the aorta and portal vein. Carrel patches of donor aorta and portal vein were anastomosed to the abdominal aorta and inferior vena cava, respectively, of the (splenectomized) recipient. The results in four major histocompatibility complex-matched pairs that were mismatched for the porcine allelic antigen are reported. Two recipients were untreated, one received a 12-day course of cyclosporine A (CsA) alone, and one received thymic irradiation (700 cGy) and CsA. Hematopoietic cell chimerism was followed by fluorescence-activated cell sorter, and graft survival was assessed by histology. Results. Spleen Tx was technically successful. In two untreated pigs, chimerism was detected in the blood (maximum 5% for 17 and 25 days) and lymph nodes (maximum 6% for 28 and 56 days), but both grafts showed histologic rejection by day 28. In two treated pigs, chimerism was present in the blood for 47 and 57 days, and rejection was prevented, with follow-up for 57 and 217 days, respectively. Conclusion. Spleen Tx in major histocompatibility complex-matched pairs treated with CsA thymic irradiation results in prolonged chimerism and is associated with the development of in vivo unresponsiveness to the transplanted spleen. C1 Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp East, Sch Med, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Transplant Unit, Boston, MA USA. RP Cooper, DKC (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp East, Sch Med, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 FU PHS HHS [1P01 A145897] NR 17 TC 16 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 15 PY 2003 VL 75 IS 11 BP 1799 EP 1806 DI 10.1097/01.TP.0000063220.19441.5C PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 692XE UT WOS:000183684900005 PM 12811237 ER PT J AU Zhao, Y Rodriguez-Barbosa, JI Shimizu, A Sachs, DH Sykes, M AF Zhao, Y Rodriguez-Barbosa, JI Shimizu, A Sachs, DH Sykes, M TI Despite efficient intrathymic negative selection of host-reactive T cells, autoimmune disease may develop in porcine thymus-grafted athymic mice: Evidence for failure of regulatory mechanisms suppressing autoimmunity SO TRANSPLANTATION LA English DT Article ID FETAL PIG THYMUS; TOLERANCE INDUCTION; THYMECTOMIZED MICE; XENOGENEIC BARRIER; POSITIVE SELECTION; ANTIGEN RECEPTOR; TRANSGENIC MICE; IN-VIVO; MHC; TRANSPLANTATION AB Background. CD4 T-cell reconstitution and xenogeneic tolerance is achieved in T cell-depleted, thymectomized C57BL/6 (B6) mice and nude mice by grafting of fetal pig thymus (FP THY). Sixty percent of grafted nude mice and 10% of grafted thymectomized B6 mice develop a clinical illness resembling chronic graft-versus-host disease. Methods. Negative selection of mouse T cells in FP THY grafts was studied in "AND" TCR transgenic mice with a negative selecting MHC. Pathologic and immunohistochemical examinations and adoptive transfer assays were performed to determine the role of mouse CD4(+) cells in the occurrence of autoimmune disease in this model. Results. Marked clonal deletion of mouse thymocytes bearing a transgenic TCR ("AND"), which recognizes H2(s) expressed by host hematopoietic cells, was observed in FP THY grafts. Pathologic and immunohistochemical examinations of the liver, skin, lungs, and kidneys of mice with wasting syndrome showed marked mouse CD4(+) T-cell infiltration without detectable pig cells. After adoptive transfer of splenocytes, but not of CD4(+) cell-depleted splenocytes, from sick mice along with B6 bone marrow cells to lethally irradiated syngeneic B6 mice, the secondary recipients developed a similar autoimmune syndrome as the donors. Cotransfer of naive syngeneic splenocytes prevented the occurrence of autoimmune disease in secondary recipients of splenocytes from healthy FP THY-grafted BALB/c nude mice. Conclusion. These results demonstrate a key role for mouse CD4(+) T cells in causing autoimmune disease in this model and suggest the importance of regulatory mechanisms in addition to intrathymic clonal deletion for the maintenance of tolerance to recipient antigens. C1 Harvard Univ, Bone Marrow Transplantat Sect, Massachusetts Gen Hosp, Dept Surg,Med Sch,Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Bone Marrow Transplantat Sect, Massachusetts Gen Hosp, Dept Surg,Med Sch,Transplantat Biol Res Ctr, MGH E Bldg,149-5102,13th St, Boston, MA 02129 USA. RI RODRIGUEZ-BARBOSA, JOSE IGNACIO/C-7808-2011 FU NHLBI NIH HHS [HL186461]; NIAID NIH HHS [P01-AI39755] NR 30 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 15 PY 2003 VL 75 IS 11 BP 1832 EP 1840 DI 10.1097/01.TP.0000065292.20062.F0 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 692XE UT WOS:000183684900010 PM 12811242 ER PT J AU Gollackner, B Mueller, NJ Houser, S Qawi, I Soizic, D Knosalla, C Buhler, L Dor, FJMF Awwad, M Sachs, DH Cooper, DKC Robson, SC Fishman, JA AF Gollackner, B Mueller, NJ Houser, S Qawi, I Soizic, D Knosalla, C Buhler, L Dor, FJMF Awwad, M Sachs, DH Cooper, DKC Robson, SC Fishman, JA TI Porcine cytomegalovirus and coagulopathy in pig-to-primate xenotransplantation SO TRANSPLANTATION LA English DT Article ID DISSEMINATED INTRAVASCULAR COAGULATION; TISSUE FACTOR ACTIVITY; ENDOTHELIAL-CELLS; THROMBOTIC MICROANGIOPATHY; INFECTION; BABOONS; ACTIVATION; PERFUSION; KIDNEY; VIRUS AB Background. A rapidly progressive disorder termed consumptive coagulopathy (CC) has been observed frequently in pig-to-baboon renal xenotransplantation. CC may be initiated by endothelial activation and induction of procoagulant factors after immunologic injury or infection, or by molecular incompatibilities between porcine coagulation proteins and primate clotting factors. The activation of porcine (P) cytomegalovirus (PCMV) and baboon (B) CMV infections has been documented in pig-to-primate xenotransplantation. The purpose of this study was to determine the contribution of PCMV and BCMV to CC. Methods. Endothelial activation was assessed by means of measurement of porcine tissue factor (pTF) in a functional assay in primary porcine aortic endothelial cells (PAEC) in vitro. Renal xenografts and native kidneys were studied by immunohistochemistry in immunosuppressed swine and baboons. BCMV and PCMV DNA was measured by quantitative molecular assays using real-time polymerase chain reaction. Results. In vitro, infection of PAEC with PCMV resulted in a significant increase of pTF expression. In vivo, pTF increase occurred without the activation of PCMV in two xenografts, and in four grafts no pTF was detected despite PCMV activation. All animals with graft pTF increase developed CC. BCMV activation in the baboon xenograft recipients did not correlate with CC or pTF increase. Control pigs and baboons had activation of PCMV and BCMV, respectively, but without coagulation abnormalities. Conclusions. PCMV induces endothelial cell activation in vitro with procoagulant expression. However, in vivo, CC and pTF induction has an uncertain relationship to increased replication of PCMV within a xenograft. Although the data do not exclude a contributory role of PCMV in CC, other mechanisms are also likely to contribute to coagulopathies observed in pig-to-primate xenotransplantation. C1 Massachusetts Gen Hosp, Infect Dis Div, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Ctr Immunobiol,Sandoz Ctr Immunol, Boston, MA USA. Immerge BioTherapeut Inc, Charlestown, MA USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Infect Dis Div, 55 Fruit St,GRJ504, Boston, MA 02114 USA. RI Dor, Frank/E-1032-2013; Mueller, Nicolas/B-6864-2013 OI Dor, Frank/0000-0001-7845-3075; Mueller, Nicolas/0000-0002-1059-3191 FU PHS HHS [5T32-A107529-04, P01 A045897] NR 28 TC 41 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 15 PY 2003 VL 75 IS 11 BP 1841 EP 1847 DI 10.1097/01.TP.0000065806.90840.C1 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 692XE UT WOS:000183684900011 PM 12811243 ER PT J AU Moran, ST Haider, K Ow, Y Milton, P Chen, LJ Pillai, S AF Moran, ST Haider, K Ow, Y Milton, P Chen, LJ Pillai, S TI Protein kinase C-associated kinase can activate NF kappa B in both a kinase-dependent and a kinase-independent manner SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR-INTERACTING PROTEIN; RIP-LIKE KINASE; DEATH DOMAIN; SRC FAMILY; CELL-DEATH; PHOSPHORYLATION; APOPTOSIS; IDENTIFICATION; PATHWAYS; CLONING AB Protein kinase C-associated kinase (PKK, also known as RIP4/DIK) activates NFkappaB when overexpressed in cell lines and is required for keratinocyte differentiation in vivo. However, very little is understood about the factors upstream of PKK or how PKK activates NFkappaB. Here we show that certain catalytically inactive mutants of PKK can activate NFkappaB, although to a lesser degree than wild type PKK. The deletion of specific domains of wild type PKK diminishes the ability of this enzyme to activate NFkappaB; the same deletions made on a catalytically inactive PKK background completely ablate NFkappaB activation. PKK may be phosphorylated by two specific mitogen-activated protein kinase kinase kinases, MEKK2 and MEKK3, and this interaction may in part be mediated through a critical activation loop residue, Thr(184). Catalytically inactive PKK mutants that block phorbol ester-induced NFkappaB activation do not interfere with, but unexpectedly enhance, the activation of NFkappaB by these two mitogen-activated protein kinase kinase kinases. Taken together, these data indicate that PKK may function in both a kinase-dependent as well as a kinase-independent manner to activate NFkappaB. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. RP Pillai, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIAID NIH HHS [AI 33507]; NIDDK NIH HHS [DK 43351] NR 36 TC 19 Z9 21 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 13 PY 2003 VL 278 IS 24 BP 21526 EP 21533 DI 10.1074/jbc.M301575200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 687AT UT WOS:000183354200028 PM 12676934 ER PT J AU Takeyama, K Aguiar, RCT Gu, LQ He, CY Freeman, GJ Kutok, JL Aster, JC Shipp, MA AF Takeyama, K Aguiar, RCT Gu, LQ He, CY Freeman, GJ Kutok, JL Aster, JC Shipp, MA TI The BAL-binding protein BBAP and related deltex family members exhibit ubiquitin-protein isopeptide ligase activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RING; FINGER; REGULATOR; GENE; BRCA1-BARD1; DOMAIN; MDM2 AB Members of the DTX (Deltex) family act as Notch signaling modifiers and may also regulate transcription through interactions with specific transcription factors. DTX proteins have a basic N terminus; a central proline-rich region; and a C-terminal RING finger domain, a motif often found in ubiquitin-protein isopeptide ligases (E3). Recently, we identified and characterized a unique diffuse large B-cell lymphoma risk-related gene named BAL (B aggressive lymphoma). Using a yeast two-hybrid screen for BAL-binding partners, we have now identified a novel protein termed BBAP (B-lymphoma- and BAL-associated protein). Although BBAP has a unique N terminus, the C-terminal region is highly homologous to that of DTX family members. Herein, we report that BBAP and the human family of DTX proteins (DTX1, DTX2, and DTX3) function as E3 ligases based on their capacity for self-ubiquitination. DTX family members homodimerize and heterodimerize in vivo, suggesting that physical interactions between various DTX family members modify E3 activity and/or substrate availability. Consistent with this idea, BBAP and DTX1 associate via their unique N termini, resulting in enhanced self-ubiquitination. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 33 TC 55 Z9 60 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 13 PY 2003 VL 278 IS 24 BP 21930 EP 21937 DI 10.1074/jbc.M301157200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 687AT UT WOS:000183354200078 PM 12670957 ER PT J AU Ghosh-Choudhury, NG Abboud, SL Mahimainathan, L Chandrasekar, B Choudhury, GG AF Ghosh-Choudhury, NG Abboud, SL Mahimainathan, L Chandrasekar, B Choudhury, GG TI Phosphatidylinositol 3-kinase regulates bone morphogenetic protein-2 (BMP-2)-induced myocyte enhancer factor 2A-dependent transcription of BMP-2 gene in cardiomyocyte precursor cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLOMERULAR MESANGIAL CELLS; C-FOS; PHOSPHOINOSITIDE 3-KINASE; RETINOBLASTOMA PROTEIN; MUSCLE DIFFERENTIATION; MEF2 PROTEINS; DNA-SYNTHESIS; KINASE; GROWTH; ACTIVATION AB The growth and differentiation factor bone morphogenetic protein-2 (BMP-2) regulates cardiac development during vertebrate embryogenesis. In cardiac precursor cells, BMP-2 has recently been shown to induce expression of cardiac transcription factors, including myocyte enhancer factor 2A (MEF-2A). The specific signal transduction mechanism by which BMP-2 regulates these actions is not known. We investigated the role of phosphatidylinositol (PI) 3-kinase in regulating these processes in cardiomyocyte precursor CL6 cells. BMP-2 increased PI 3-kinase activity in these cells in a time-dependent manner, resulting in increased expression of sarcomeric myosin heavy chain (MHC) and MEF-2A. Inhibition of PI 3-kinase abolished these actions of BMP-2, indicating the involvement of PI 3-kinase in these processes. Furthermore, BMP-2 stimulated specific protein.DNA complex formation when an MEF-2 DNA recognition element was used as probe. Antibody supershift assay confirmed the presence of MEF-2A in this protein.DNA complex. Inhibition of PI 3-kinase activity completely prevented the MEF-2A.DNA complex formation. BMP-2 also increased transcription of a reporter gene driven by an MEF-2-specific DNA element in a PI 3-kinase-dependent manner. Ectopic expression of MEF-2A increased BMP-2 transcription to the same extent induced by BMP-2, indicating that MEF-2A may participate in BMP-2 autoregulation in CL6 cells. Expression of dominant negative PI 3-kinase completely abolished BMP-2-induced as well as MEF-2A-mediated BMP-2 transcription. Furthermore expression of MEF-2A increased MHC expression in a PI 3-kinase-dependent manner. Together these data provide the first evidence that BMP-2-induced PI 3-kinase signaling regulates MEF-2A expression and define a mechanism of MEF-2A-dependent BMP-2 transcription. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Ghosh-Choudhury, NG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. OI /0000-0001-5077-3552 FU NHLBI NIH HHS [HL 68020]; NIAMS NIH HHS [AR 42306]; NIDDK NIH HHS [R01 DK 55815] NR 50 TC 27 Z9 29 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 13 PY 2003 VL 278 IS 24 BP 21998 EP 22005 DI 10.1074/jbc.M302277200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 687AT UT WOS:000183354200086 PM 12663654 ER PT J AU Szostak, JW AF Szostak, JW TI Molecular messages SO NATURE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. NR 4 TC 36 Z9 39 U1 3 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 12 PY 2003 VL 423 IS 6941 BP 689 EP 689 DI 10.1038/423689a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 688PA UT WOS:000183443400022 PM 12802312 ER PT J AU Lehmann, LE Anupindi, S Harris, NL AF Lehmann, LE Anupindi, S Harris, NL TI Case 18-2003: A 15-year-old girl with pain in the left leg and back, pruritus, and thoracic lymphadenopathy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID NON-HODGKINS-LYMPHOMA; REED-STERNBERG CELLS; SOLITARY BONE-TUMOR; CENTER B-CELLS; MEDICAL PROGRESS; DISEASE; CHILDHOOD; REPRESENT; EXPANSION C1 Childrens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Lehmann, LE (reprint author), Childrens Hosp, Dept Med, Boston, MA 02115 USA. NR 21 TC 0 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 12 PY 2003 VL 348 IS 24 BP 2443 EP 2451 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 688HU UT WOS:000183428900011 PM 12802031 ER PT J AU Hariharan, IK Haber, DA AF Hariharan, IK Haber, DA TI Yeast, flies, worms, and fish in the study of human disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID AUTOSOMAL-DOMINANT HEMOCHROMATOSIS; CELL-DIVISION CYCLE; CAENORHABDITIS-ELEGANS; GENETIC SCREENS; DROSOPHILA-MELANOGASTER; HUMAN HOMOLOG; CANCER; MUTATIONS; ZEBRAFISH; DESIGN C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 59 TC 25 Z9 27 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 12 PY 2003 VL 348 IS 24 BP 2457 EP 2463 DI 10.1056/NEJMon023158 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 688HU UT WOS:000183428900014 PM 12802034 ER PT J AU Goldman, DP Berry, SH McCabe, MS Kilgore, ML Potosky, AL Schoenbaum, ML Schonlau, M Weeks, JC Kaplan, R Escarce, JJ AF Goldman, DP Berry, SH McCabe, MS Kilgore, ML Potosky, AL Schoenbaum, ML Schonlau, M Weeks, JC Kaplan, R Escarce, JJ TI Incremental treatment costs in National Cancer Institute-sponsored clinical trials SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BREAST-CANCER; MEDICAL ONCOLOGISTS; BARRIERS; CARE; CHEMOTHERAPY; MULTICENTER; KNOWLEDGE; ATTITUDES AB Context Concern about additional costs for direct patient care impedes efforts to enroll patients in clinical trials. But generalizable evidence substantiating these concerns is lacking. Objective To assess the additional cost of treating cancer patients in the National Cancer Institute (NCI)-sponsored clinical trials in the United States across a range of trial phases, treatment modalities, and patient care settings. Design Retrospective cost study using a multistage, stratified, random sample of patients enrolled in 1 of 35 active phase 3 trials or phase 1 or any phase 2 trials between October 1, 1998, and December 31, 1999. Unadjusted and adjusted costs were compared and related to trial phase, institution type, and vital status. Setting and Participants A representative sample of 932 cancer patients enrolled in nonpediatric, NCI-sponsored clinical trials and 696 nonparticipants with a similar stage of disease not enrolled in a research protocol from 83 cancer clinical research institutions across the United States. Main Outcome Measures Direct treatment costs as measured using a combination of medical records, telephone survey, and Medicare claims data. Administrative and other research costs were excluded. Results The incremental costs of direct care in trials were modest. Over approximately a 2.5-year period, adjusted costs were 6.5% higher for trial participants than nonparticipants ($35418 vs $33248; P=.11). Cost differences for phase 3 studies were 3.5% (P=.22), lower than for phase 1 or 2 trials (12.8%; P=.20). Trial participants who died had higher costs than nonparticipants who died (17.9%; $39420 vs $33432, respectively; P=15). Conclusions Treatment costs for nonpediatric clinical trial participants are on average 6.5% higher than what they would be if patients did not enroll. This implies total incremental treatment costs for NCI-sponsored trials of $16 million in 1999. Incremental costs were higher for patients who died and who were in early phase studies although these findings deserve further scrutiny. Overall, the additional treatment costs of an open reimbursement policy for government-sponsored cancer clinical trials appear minimal. C1 RAND Corp, Hlth, Santa Monica, CA 90407 USA. RAND Corp, Stat, Santa Monica, CA 90407 USA. NCI, Off Educ & Special Initiat, Div Canc Control & Populat Sci, Washington, DC USA. NCI, Clin Invest Branch, Natl Canc Therapy Evaluat Program, Washington, DC USA. Univ Alabama, Dept Hlth Care Org & Policy, Birmingham, AL USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. RP Goldman, DP (reprint author), RAND Corp, Hlth, 1700 Main St, Santa Monica, CA 90407 USA. NR 34 TC 34 Z9 34 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 JUN 11 PY 2003 VL 289 IS 22 BP 2970 EP 2977 DI 10.1001/jama.289.22.2970 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 687XZ UT WOS:000183403400020 PM 12799405 ER PT J AU Walsh, DM Fadeeva, JV LaVoie, MJ Paliga, K Eggert, S Kimberly, WT Wasco, W Selkoe, DJ AF Walsh, DM Fadeeva, JV LaVoie, MJ Paliga, K Eggert, S Kimberly, WT Wasco, W Selkoe, DJ TI gamma-Secretase cleavage and binding to FE65 regulate the nuclear translocation of the intracellular C-terminal domain (ICD) of the APP family of proteins SO BIOCHEMISTRY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; BETA-PROTEIN; ALZHEIMERS-DISEASE; CYTOPLASMIC DOMAIN; MOLECULAR-CLONING; CDNA CLONING; CELLS; IDENTIFICATION; EXPRESSION; NOTCH AB Regulated intramembrane proteolysis (RIP) of the amyloid precursor protein (APP) produces amyloid beta-protein (A), the probable causative agent of Alzheimer's disease (AD), and is therefore an important target for therapeutic intervention. However, there is a burgeoning consensus that gamma-secretase, one of the proteases that generates Abeta, is also critical for the signal transduction of APP and a growing list of other receptors. APP is a member of a gene family that includes two amyloid precursor-like proteins, APLP1 and APLP2. Although APP and the APLPs undergo similar proteolytic processing, there is little information about the role of their gamma-secretase-generated intracellular domains (ICDs). Here, we show that APLP1 and 2 undergo presenilin-dependent RIP similar to APP, resulting in the release of a similar to6 kDa ICD for each protein. Each of the ICDs are degraded by an insulin degrading enzyme-like activity, but they can be stabilized by members of the FE65 family and translocate to the nucleus. Given that modulation of APP processing is a therapeutic target and that the APLPs are processed in a manner similar to APP, any strategy aimed at altering APP proteolysis will have to take into account possible effects on signaling by APLP 1 and 2. C1 Harvard Univ, Inst Med, Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Max Planck Inst Expt Endocrinol, D-730625 Hannover, Germany. Ctr Mol Biol, D-69120 Heidelberg, Germany. RP Selkoe, DJ (reprint author), Harvard Univ, Inst Med, Ctr Neurol Dis, Dept Neurol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NIA NIH HHS [AG06173] NR 61 TC 83 Z9 85 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 10 PY 2003 VL 42 IS 22 BP 6664 EP 6673 DI 10.1021/bi027375c PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 685YW UT WOS:000183293100005 PM 12779321 ER PT J AU Ansari, M Shlipak, MG Heidenreich, PA Van Ostaeyen, D Pohl, EC Browner, WS Massie, BM AF Ansari, M Shlipak, MG Heidenreich, PA Van Ostaeyen, D Pohl, EC Browner, WS Massie, BM TI Improving guideline adherence - A randomized trial evaluating strategies to increase beta-blocker use in heart failure SO CIRCULATION LA English DT Article DE heart failure; drugs; trials ID PRIMARY-CARE; MANAGEMENT; PHYSICIANS; COMPUTER; OUTCOMES; QUALITY; INTERVENTION; IMPROVEMENT; INFORMATION; REMINDERS AB Background-The dissemination of clinical practice guidelines often has not been accompanied by desired improvements in guideline adherence. This study evaluated interventions for implementing a new practice guideline advocating the use of beta-blockers for heart failure patients. Methods and Results-This was a randomized controlled trial involving heart failure patients (n = 169) with an ejection fraction less than or equal to45% and no contraindications to beta-blockers. Patients' primary providers were randomized in a stratified design to 1 of 3 interventions: (1) control: provider education; (2) provider and patient notification: computerized provider reminders and patient letters advocating beta-blockers; and (3) nurse facilitator: supervised nurse to initiate and titrate beta-blockers. The primary outcome, the proportion of patients who were initiated or uptitrated and maintained on beta-blockers, analyzed by intention to treat, was achieved in 67% (36 of 54) of patients in the nurse facilitator group compared with 16% (10 of 64) in the provider/patient notification and 27% (14 of 51) in the control groups (P < 0.001 for the comparisons between the nurse facilitator group and both other groups). The proportion of patients on target β-blocker doses at the study end (median follow-up, 12 months) was also highest in the nurse facilitator group (43%) compared with the control (10%) and provider/patient notification groups (2%) (P < 0.001). There were no differences in adverse events among groups. Conclusions-The use of a nurse facilitator was a successful approach for implementing a beta-blocker guideline in heart failure patients. The use of provider education, clinical reminders, and patient education was of limited value in this setting. C1 San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Palo Alto VA Med Ctr, Div Cardiol, San Francisco, CA USA. Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. RP Massie, BM (reprint author), VAMC, Cardiol Div 111C, 4150 Clement St, San Francisco, CA 94121 USA. OI Heidenreich, Paul/0000-0001-7730-8490 NR 29 TC 102 Z9 102 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 10 PY 2003 VL 107 IS 22 BP 2799 EP 2804 DI 10.1161/01.CIR.0000070952.08969.5B PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 687WT UT WOS:000183400500008 PM 12756157 ER PT J AU Takahashi, T Aoki, M Tateyama, M Kondo, E Mizuno, T Onodera, Y Takano, R Kawai, H Kamakura, K Mochizuki, H Shizuka-Ikeda, M Nakagawa, M Yoshida, Y Akanuma, J Hoshino, K Saito, H Nishizawa, M Kato, S Saito, K Miyachi, T Yamashita, H Kawai, M Matsumura, T Kuzuhara, S Ibi, T Sahashi, K Nakai, H Kohnosu, T Nonaka, I Arahata, K Brown, RH Saito, H Itoyama, Y AF Takahashi, T Aoki, M Tateyama, M Kondo, E Mizuno, T Onodera, Y Takano, R Kawai, H Kamakura, K Mochizuki, H Shizuka-Ikeda, M Nakagawa, M Yoshida, Y Akanuma, J Hoshino, K Saito, H Nishizawa, M Kato, S Saito, K Miyachi, T Yamashita, H Kawai, M Matsumura, T Kuzuhara, S Ibi, T Sahashi, K Nakai, H Kohnosu, T Nonaka, I Arahata, K Brown, RH Saito, H Itoyama, Y TI Dysferlin mutations in Japanese Miyoshi myopathy - Relationship to phenotype SO NEUROLOGY LA English DT Article ID GIRDLE MUSCULAR-DYSTROPHY; SKELETAL-MUSCLE; CHROMOSOME 2P; GENE; LOCUS; 2B; PROTEIN; LGMD2B AB Objective: To study dysferlin gene mutations and genotype-phenotype correlations in Japanese patients with Miyoshi myopathy ( MM). Background: MM is an autosomal recessive distal muscular dystrophy that arises from mutations in the dysferlin gene. This gene is also mutated in families with limb girdle muscular dystrophy 2B. Methods: The authors examined 25 Japanese patients with MM. Genomic DNA was extracted from the peripheral lymphocytes of the patients. The PCR products of each of 55 exons were screened by single strand conformation polymorphism or direct sequencing from the PCR fragments. Results: The authors identified 16 different mutations in 20 patients with MM; 10 were novel. Mutations in Japanese patients are distributed along the entire length of the gene. Conclusions: Four mutations (C1939G, G3370T, 3746delG, and 4870delT) are relatively more prevalent in this population, accounting for 60% of the mutations in this study. This study revealed that the G3370T mutation was associated with milder forms of MM and the G3510A mutation was associated with a more severe form. C1 Tohoku Univ, Dept Neurol, Sch Med, Sendai, Miyagi 9808574, Japan. Nishitaga Natl Hosp, Dept Neurol, Sendai, Miyagi, Japan. Nishitaga Natl Hosp, Div Clin Res, Sendai, Miyagi, Japan. Takamatsu City Hosp, Kagawa, Japan. Natl Def Med Coll, Dept Internal Med 3, Saitama, Japan. Gunma Univ, Dept Neurol, Maebashi, Gumma, Japan. Kagoshima Univ, Dept Internal Med 3, Kagoshima 890, Japan. Fukushima Med Univ, Dept Neurol, Fukushima, Japan. Toho Univ, Dept Pediat 1, Tokyo, Japan. Akita Red Cross Hosp, Akita, Japan. Jichi Med Sch, Dept Neurol, Tochigi, Japan. Shin Fuji Hosp, Shizuoka, Japan. Tokyo Womens Med Univ, Dept Pediat, Tokyo, Japan. Hiroshima Univ, Dept Internal Med 3, Hiroshima 730, Japan. Natl Ctr Hosp Mental Nervous & Muscular Disorders, Tokyo, Japan. NCNP, Dept Neuromuscular Res, Natl Inst Neurosci, Tokyo, Japan. Mie Univ, Dept Neurol, Tsu, Mie, Japan. Aichi Med Univ, Dept Neurol, Aichi, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Aoki, M (reprint author), Tohoku Univ, Dept Neurol, Sch Med, 1-1 Seiryo Machi, Sendai, Miyagi 9808574, Japan. NR 33 TC 42 Z9 44 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 10 PY 2003 VL 60 IS 11 BP 1799 EP 1804 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 688DT UT WOS:000183418400015 PM 12796534 ER PT J AU Zipfel, WR Williams, RM Christie, R Nikitin, AY Hyman, BT Webb, WW AF Zipfel, WR Williams, RM Christie, R Nikitin, AY Hyman, BT Webb, WW TI Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MAST-CELL SECRETION; EXCITATION; SEROTONIN; MICE; RAT; LOCALIZATION; SPECTROSCOPY; DITYROSINE; METABOLISM; EXPRESSION AB Multicolor nonlinear microscopy of living tissue using two- and three-photon-excited intrinsic fluorescence combined with second harmonic generation by supermolecular structures produces images with the resolution and detail of standard histology without the use of exogenous stains. Imaging of intrinsic indicators within tissue, such as nicotinamide adenine dinucleotide, retinol, in-doleamines, and collagen provides crucial information for physiology and pathology. The efficient application of multiphoton microscopy to intrinsic imaging requires knowledge of the nonlinear optical properties of specific cell and tissue components. Here we compile and demonstrate applications involving a range of intrinsic molecules and molecular assemblies that enable direct visualization of tissue morphology, cell metabolism, and disease states such as Alzheimer's disease and cancer. C1 Cornell Univ, Dept Appl & Engn Phys, Ithaca, NY 14853 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. Cornell Univ, Dept Biomed Sci, Ithaca, NY 14853 USA. RP Webb, WW (reprint author), Cornell Univ, Dept Appl & Engn Phys, Ithaca, NY 14853 USA. EM www2@cornell.edu RI Webb, Watt/B-5905-2011; Wunder, Stephanie/B-5066-2012; Zdilla, Michael/B-4145-2011; Zipfel, Warren/B-4059-2016 OI Zipfel, Warren/0000-0003-2640-329X FU NCI NIH HHS [BC991016, CA96823-01, PC010342, R01 CA096823, R56 CA096823]; NIA NIH HHS [AG08487, R01 AG008487]; NIBIB NIH HHS [9-P41-EB0011976-16]; PHS HHS [R33-645644] NR 41 TC 995 Z9 1003 U1 12 U2 148 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 10 PY 2003 VL 100 IS 12 BP 7075 EP 7080 DI 10.1073/pnas.0832308100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 689LC UT WOS:000183493500035 PM 12756303 ER PT J AU Dombeck, DA Kasischke, KA Vishwasrao, HD Ingelsson, M Hyman, BT Webb, WW AF Dombeck, DA Kasischke, KA Vishwasrao, HD Ingelsson, M Hyman, BT Webb, WW TI Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NEURONAL POLARITY; HIPPOCAMPAL-NEURONS; HARMONIC-GENERATION; AXON; TRANSPORT; SYSTEM; ORIENTATION; MIGRATION; PROTEINS; MITOSIS AB Microtubule (MT) ensemble polarity is a diagnostic determinant of the structure and function of neuronal processes. Here, polarized MT structures are selectively imaged with second-harmonic generation (SHG) microscopy in native brain tissue. This SHG is found to colocalize with axons in both brain slices and cultured neurons. Because SHG arises only from noninversion symmetric structures, the uniform polarity of axonal MTs leads to the observed signal, whereas the mixed polarity in dendrites leads to destructive interference. SHG imaging provides a tool to investigate the kinetics and function of MT ensemble polarity in dynamic native brain tissue structures and other subcellular motility structures based on polarized MTs. C1 Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14853 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimers Dis Res Ctr, Charlestown, MA 02129 USA. RP Webb, WW (reprint author), Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14853 USA. RI Webb, Watt/B-5905-2011 FU NCRR NIH HHS [P412RR04224]; NIA NIH HHS [AG08487, R01 AG008487]; NIGMS NIH HHS [GM08267, T32 GM008267] NR 46 TC 167 Z9 170 U1 3 U2 20 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 10 PY 2003 VL 100 IS 12 BP 7081 EP 7086 DI 10.1073/pnas.0731953100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 689LC UT WOS:000183493500036 PM 12766225 ER PT J AU Handschin, C Rhee, J Lin, JD Tarr, PT Spiegelman, BM AF Handschin, C Rhee, J Lin, JD Tarr, PT Spiegelman, BM TI An autoregulatory loop controls peroxisome proliferator-activated receptor gamma coactivator 1 alpha expression in muscle SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SKELETAL-MUSCLE; MITOCHONDRIAL BIOGENESIS; TRANSCRIPTIONAL COACTIVATOR; 1-ALPHA PGC-1-ALPHA; GENE-EXPRESSION; PROTEIN-KINASE; PGC-1; EXERCISE; MEF2; GLUCONEOGENESIS AB Skeletal muscle adapts to chronic physical activity by inducing mitochondrial biogenesis and switching proportions of muscle fibers from type II to type I. Several major factors involved in this process have been identified, such as the calcium/calmodulin-dependent protein kinase IV (CaMKIV), calcineurin A (CnA), and the transcriptional component peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha). Transgenic expression of PGC-1alpha recently has been shown to dramatically increase the content of type I muscle fibers in skeletal muscle, but the relationship between PGC-1alpha expression and the key components in calcium signaling is not clear. in this report, we show that the PGC-1alpha promoter is regulated by both CaMKIV and CnA activity. CaMKIV activates PGC-1alpha largely through the binding of cAMP response element-binding protein to the PGC-1alpha promoter. Moreover, we show that a positive feedback loop exists between PGC-1alpha and members of the myocyte enhancer factor 2 (MEF2) family of transcription factors. MEF2s bind to the PGC-1alpha promoter and activate it, predominantly when coactivated by PGC-1alpha. MEF2 activity is stimulated further by CnA signaling. These findings imply a unified pathway, integrating key regulators of calcium signaling with the transcriptional switch PGC-1alpha. Furthermore, these data suggest an autofeedback loop whereby the calcium-signaling pathway may result in a stable induction of PGC-1alpha, contributing to the relatively stable nature of muscle fiber-type determination. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. RI Handschin, Christoph/E-6886-2015 OI Handschin, Christoph/0000-0003-0603-1097 FU NIDDK NIH HHS [DK54477, R01 DK054477, R56 DK054477] NR 32 TC 385 Z9 397 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 10 PY 2003 VL 100 IS 12 BP 7111 EP 7116 DI 10.1073/pnas.1232352100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 689LC UT WOS:000183493500041 PM 12764228 ER PT J AU Secomb, TW Konerding, MA West, CA Su, M Young, AJ Mentzer, SJ AF Secomb, TW Konerding, MA West, CA Su, M Young, AJ Mentzer, SJ TI Microangiectasias: Structural regulators of lymphocyte transmigration SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE microcirculation; inflammation; microscopy; ultrastructure; cell movement ID EFFERENT LYMPH; BLOOD-FLOW; MICROCIRCULATION; ENDOTHELIUM; OXAZOLONE; ULTRASTRUCTURE; ADHESION; LFA-1 AB The migration of lymphocytes into inflammatory tissue requires the migrating cell to overcome mechanical forces produced by blood flow. A generally accepted hypothesis is that these forces are overcome by a multistep sequence of adhesive interactions between lymphocytes and endothelial cells. This hypothesis has been recently challenged by results demonstrating wall shear stress on the order of 20 dyn/cm(2) in vivo and infrequent lymphocyte-endothelial adhesion at wall shear stress >1-2 dyn/cm(2) in vitro. Here, we show that lymphocyte slowing and transmigration in the skin is associated with microangiectasias, i.e., focal structural dilatations of microvessel segments. Microangiectaslas are inducible within 4 days of the onset of inflammation and lead to a greater than 10-fold local reduction in wall shear stress. These findings support the hypothesis that a preparatory step to lymphocyte transmigration involves structural adaptations in the inflammatory microcirculation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunophysiol Lab,Harvard Surg Res Labs, Boston, MA 02115 USA. Univ Arizona, Dept Physiol, Tucson, AZ 85724 USA. Univ Mainz, Dept Anat, D-55099 Mainz, Germany. RP Secomb, TW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunophysiol Lab,Harvard Surg Res Labs, 44 Binney St, Boston, MA 02115 USA. OI Secomb, Timothy/0000-0002-0176-5502 FU NHLBI NIH HHS [HL34555, R01 HL034555, R01 HL047078, HL47078] NR 21 TC 23 Z9 23 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 10 PY 2003 VL 100 IS 12 BP 7231 EP 7234 DI 10.1073/pnas.1232173100 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 689LC UT WOS:000183493500061 PM 12782790 ER PT J AU Braun, A Zhang, SW Miettinen, HE Ebrahim, S Holm, TM Vasile, E Post, MJ Yoerger, DM Picard, MH Krieger, JL Andrews, NC Simons, M Krieger, M AF Braun, A Zhang, SW Miettinen, HE Ebrahim, S Holm, TM Vasile, E Post, MJ Yoerger, DM Picard, MH Krieger, JL Andrews, NC Simons, M Krieger, M TI Probucol prevents early coronary heart disease and death in the high-density lipoprotein receptor SR-BI/apolipoprotein E double knockout mouse SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE atherosclerosis; heart failure; myocardial infarction; unesterified cholesterol ID B TYPE-I; APOLIPOPROTEIN E-DEFICIENT; HERITABLE HYPERLIPIDEMIC RABBIT; CHOLESTERYL ESTER TRANSFER; NITRIC-OXIDE SYNTHASE; SCAVENGER RECEPTOR; HDL RECEPTOR; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; LIPID TRANSPORT AB Mice with homozygous null mutations in the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type 1) and apolipoprotein E genes fed a low-fat diet exhibit a constellation of pathologies shared with human atherosclerotic coronary heart disease (CHID): hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarctions, cardiac dysfunction (heart enlargement, reduced systolic function and ejection fraction, and ECG abnormalities), and premature death (mean age 6 weeks). They also exhibit a block in RBC maturation and abnormally high plasma unesterified-to-total cholesterol ratio (0.8) with associated abnormal lipoprotein morphology (lamellar/vesicular and stacked discoidal particles reminiscent of those in lecithin/cholesterol acyltransferase deficiency and cholestasis). Treatment with the lipid-lowering, antiatherosclerosis, and antioxidation drug probucol extended life to as long as 60 weeks (mean 36 weeks), and at 5-6 weeks of age, virtually completely reversed the cardiac and most RBC pathologies and corrected the unesterified to total cholesterol ratio (0.3) and associated distinctive abnormal lipoprotein morphologies. Manipulation of the timing of administration and withdrawal of probucol could control the onset of death and suggested that critical pathological changes usually occurred in untreated double knockout mice between approximate to3 (weaning) and 5 weeks of age and that probucol delayed heart failure even after development of substantial CHD. The ability of probucol treatment to modulate pathophysiology in the double knockout mice enhances the potential of this murine system for analysis of the pathophysiology of CHD and preclinical testing of new approaches for the prevention and treatment of cardiovascular disease. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dartmouth Coll Sch Med, Angiogenesis Res Ctr, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Sect Cardiol, Lebanon, NH 03756 USA. Massachusetts Gen Hosp, Dept Med, Cardiol Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Krieger, M (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Simons, Michael/G-8553-2014; OI Simons, Michael/0000-0003-0348-7734; Andrews, Nancy/0000-0003-0243-4462; Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [HL66105, HL53793, HL63609, HL64737, P01 HL066105, P50 HL063609, R01 HL053793, R01 HL064737] NR 62 TC 82 Z9 91 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 10 PY 2003 VL 100 IS 12 BP 7283 EP 7288 DI 10.1073/pnas.1237725100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 689LC UT WOS:000183493500070 PM 12771386 ER PT J AU Wannamethee, SG Camargo, CA Manson, JAE Willett, WC Rimm, EB AF Wannamethee, SG Camargo, CA Manson, JAE Willett, WC Rimm, EB TI Alcohol drinking patterns and risk of type 2 diabetes mellitus among younger women SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID INSULIN SENSITIVITY; MEXICAN-AMERICANS; GLUCOSE-TOLERANCE; LIFE-STYLE; CONSUMPTION; MEN; POPULATION; QUESTIONNAIRE; HEALTH; SEX AB Objective: To examine the relationship between alcohol consumption and the incidence of type 2 diabetes mellitus among relatively young and middle-aged women. Methods: In a prospective study, 109 690 women, aged 25 to 42 years, without a history of coronary heart disease, stroke, cancer, or diabetes mellitus completed a detailed lifestyle and medical history questionnaire in 1989. During 10 years of follow-up, we documented 935 incident cases of type 2 diabetes mellitus. Results: We found a nonlinear relationship between alcohol consumption and risk of type 2 diabetes mellitus after adjustment for multiple confounders, including body mass index, smoking, physical activity, and family history of diabetes mellitus (quadratic trend P=.003). Compared with lifelong abstainers, the adjusted relative risks (95% confidence intervals) were 0.80 (0.66-0.96) for those consuming 0.1 to 4.9 g/d, 0.67 (0.50-0.89) for those consuming 5.0 to 14.9 g/d, 0.42 (0.20-0.90) for those consuming 15.0 to 29.9 g/d, and 0.78 (0.34-1.78) for those consuming 30.0 g/d or more. Further adjustment for dietary factors, including glycemic load, trams-fatty acid, polyunsaturated fat, and total fiber intake, did not appreciably alter these findings. The inverse association with light to moderate drinking was most apparent in women who reported wine or beer drinking. Women who reported 30.0 g/d or more of liquor intake showed a significantly increased risk of diabetes mellitus compared with those who did not report liquor intake (adjusted relative risk, 2.50; 95% confidence interval, 1:00-6.23). Conclusion: Light to moderate alcoholic beverage consumption may be associated with a lower risk of type 2 diabetes mellitus among women aged 25 to 42 years, although this benefit.may not- persist at higher levels. C1 UCL Royal Free & Univ Coll, Sch Med, Dept Primary Care & Populat Sci, London NW3 2PF, England. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Channing Labs, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. RP Wannamethee, SG (reprint author), UCL Royal Free & Univ Coll, Sch Med, Dept Primary Care & Populat Sci, Rowland Hill St, London NW3 2PF, England. EM goya@pcps.ucl.ac.uk OI Wannamethee, Sasiwarang/0000-0001-9484-9977 FU NCI NIH HHS [CA50385]; NHLBI NIH HHS [HL-03804]; NIAAA NIH HHS [AA-11181] NR 33 TC 110 Z9 115 U1 1 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 9 PY 2003 VL 163 IS 11 BP 1329 EP 1336 DI 10.1001/archinte.163.11.1329 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 687RN UT WOS:000183390600010 PM 12796069 ER PT J AU Hettiaratchy, S Butler, PEM AF Hettiaratchy, S Butler, PEM TI Extending the boundaries of transplantation - Recent hand transplants may herald a new era SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID TISSUE ALLOGRAFTS; FOLLOW-UP; TOLERANCE; INDUCTION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg,Transplantat Biol Res Ctr, Boston, MA 02114 USA. Royal Free Hosp, Dept Plast & Reconstruct Surg, London NW3 2QG, England. RP Hettiaratchy, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg,Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 13 TC 12 Z9 14 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD JUN 7 PY 2003 VL 326 IS 7401 BP 1226 EP 1227 DI 10.1136/bmj.326.7401.1226 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 689FJ UT WOS:000183480700004 PM 12791714 ER PT J AU Prince, S Kolehmainen, V Kaipio, JP Franceschini, MA Boas, D Arridge, SR AF Prince, S Kolehmainen, V Kaipio, JP Franceschini, MA Boas, D Arridge, SR TI Time-series estimation of biological factors in optical diffusion tomography SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID ELECTRICAL-IMPEDANCE TOMOGRAPHY; NEAR-INFRARED SPECTROSCOPY; DYNAMIC INVERSE PROBLEMS; FINITE-ELEMENT-METHOD; IN-PROCESS TOMOGRAPHY; IMAGE-RECONSTRUCTION; SCATTERING MEDIA; STATE-ESTIMATION; EFFICIENT ALGORITHMS; HUMAN BRAIN AB We apply state space estimation techniques to the time-varying reconstruction problem in optical tomography. We develop a stochastic model for describing the evolution of quasi-sinusoidal medical signals such as the heartbeat, assuming these are represented as a known frequency with randomly varying amplitude and phase. We use the extended Kalman filter in combination with spatial regularization techniques to reconstruct images from highly under-determined time-series data. This system also naturally segments activity belonging to different biological processes. We present reconstructions of simulated data and of real data recorded from the human motor cortex (Franceschini et al 2000 Optics Express 6 49-57). It is argued that the application of these time-series techniques improves both the fidelity and temporal resolution of reconstruction in optical tomography. C1 Natl Univ Singapore, Dept Elect & Comp Engn, Singapore 113576, Singapore. Univ Kuopio, Dept Appl Phys, FIN-70211 Kuopio, Finland. Tufts Univ, Bioengn Ctr, Dept Elect & Comp Sci, Medford, MA 02155 USA. Harvard Univ, Massachusetts Gen Hosp, Harvard Med Sch, NMR Ctr, Charlestown, MA USA. UCL, Dept Comp Sci, London WC1E 6BT, England. RP Prince, S (reprint author), Natl Univ Singapore, Dept Elect & Comp Engn, 4 Engn Dr 3, Singapore 113576, Singapore. EM ucacarr@cs.ucl.ac.uk RI Kolehmainen, Ville/K-1963-2012; OI Kolehmainen, Ville/0000-0002-5621-795X; Kaipio, Jari/0000-0002-7392-5149 FU NIBIB NIH HHS [R01 EB001954] NR 38 TC 72 Z9 72 U1 1 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUN 7 PY 2003 VL 48 IS 11 BP 1491 EP 1504 AR PII S0031-9155(03)57708-9 DI 10.1088/0031-9155/48/11/301 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 690RD UT WOS:000183562000001 PM 12817933 ER PT J AU Maillot, C Wang, LX Million, M Tache, Y AF Maillot, C Wang, LX Million, M Tache, Y TI Intraperitoneal corticotropin-releasing factor and urocortin induce Fos expression in brain and spinal autonomic nuclei and long lasting stimulation of colonic motility in rats SO BRAIN RESEARCH LA English DT Article DE CRF; Fos; colonic motility; urocortin; lumbosacral spinal cord; central amygdala; parabrachial nucleus; locus coeruleus; area postrema; nucleus tractus solitarius ID PHASEOLUS-VULGARIS LEUKOAGGLUTININ; SACRAL PARASYMPATHETIC NUCLEUS; DORSAL MOTOR NUCLEUS; C-FOS; SOLITARY TRACT; EFFERENT PROJECTIONS; AREA POSTREMA; PARAVENTRICULAR NUCLEUS; PARABRACHIAL NUCLEUS; NERVOUS-SYSTEM AB CRF injected intraperitoneally (i.p.) stimulates colonic, motor function and induces Fos expression in colonic myenteric neurons. We investigated central and spinal Fos expression and changes. in colonic motility in response to i.p. injection of CRF and urocortin. Ovine CRF9-33 that is devoid of intrinsic activity at the CRF receptors, was used as control peptide. Myoelectrical activity was monitored for I h before and after peptide injection (10 mug/kg, i.p.) in conscious non fasted rats with chronically implanted intraparietal electrodes in the cecum and proximal colon. Brain and lumbosacral spinal cord were processed for Fos immunohistochemistry at I h postinjection. CRF and urocortin elicited defecation and a new pattern of ceco-colonic clustered spike bursts that peaked within, 15 m,in and lasted for the I h experimental period while CRF9-33 did not modify baseline myoelectrical activity and defecation. CRF increased significantly Fos expression in the central nucleus of the amygdala (lateral part), parabrachial nucleus (external lateral subnucleus), area postrema, nucleus tractus solitarius, locus coeruleus, paraventricular nucleus of the hypothalamus, the intermediolateral column and area I-VII, X at the L6-S1 level of the spinal cord by 11-, 6.5-, 5.3-, 5.0-, 4.7-, 2.7- and 1.4-fold, respectively compared with i.p. CRF9-33 injected rats that had little Fos expression. Urocortin induced a similar pattern of Fos response in the brain and the spinal cord. These results indicate that i.p. CRF and urocortin induce a peptide specific activation of brain nuclei receiving viscerosensory inputs and involved in autonomic circuitries whose effector limbs may impact on visceral function. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, Vet Adm Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, Dept Med,Digest Dis Div, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Vet Adm Greater Los Angeles Healthcare Syst, Brain Res Inst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), Univ Calif Los Angeles, Vet Adm Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, Dept Med,Digest Dis Div, 11301 Wilshire Blvd,Bldg 115,Rm 117, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK 57238-01A1S1, DK-41301, DK-57238] NR 83 TC 31 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 6 PY 2003 VL 974 IS 1-2 BP 70 EP 81 DI 10.1016/S0006-8993(03)02553-8 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 684NV UT WOS:000183214200007 PM 12742625 ER PT J AU Harendza, S Lovett, DH Panzer, U Lukacs, Z Kuhnl, P Stahl, RAK AF Harendza, S Lovett, DH Panzer, U Lukacs, Z Kuhnl, P Stahl, RAK TI Linked common polymorphisms in the gelatinase A promoter are associated with diminished transcriptional response to estrogen and genetic fitness SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MATRIX METALLOPROTEINASE-2 GENE; GLOMERULAR MESANGIAL CELLS; IV COLLAGENASE GENE; BREAST-CANCER CELLS; A-DEFICIENT MICE; EXPRESSION; ACTIVATION; ANGIOGENESIS; ELEMENTS; YB-1 AB Gelatinase A ( matrix metalloproteinase- 2) plays a prominent role in multiple biologic processes. Prior studies have established critical roles for gelatinase A transcriptional regulation by defined enhancer elements. To determine possible functional single nucleotide polymorphisms within these elements, we determined the single nucleotide polymorphism distribution within 1,665 bp of the gelatinase A 5'-flanking region, using a healthy homogeneous Caucasian study group of 463 individuals. Among the polymorphisms detected, a G -->A transition at bp - 1575 was located immediately 5' to a half-palindromic potential estrogen receptor binding site. In estrogen receptor-positive MCF-7 cells the - 1575G allele functioned as an enhancer, whereas the - 1575A allele reduced transcription activity significantly. Gel shift assays confirmed that the differences in allelic expression affected binding of the estrogen receptor-alpha to this region. Cotransfection experiments with an estrogen receptor-alpha expression vector in MDA-MB-231 cells, which do not constitutively express an estrogen receptor, revealed that estrogen receptor is absolutely required for enhancing activity. Allelic distribution analysis indicated that a previously reported C-->T transition within an Sp1 binding site at - 1306 was in linkage disequilibrium with the - 1575G 3 A transition. Luciferase reporter studies of the linked variant - 1575A - 1306T allele versus the wild type - 1575G - 1306C allele demonstrated an additive reduction in estrogen-dependent reporter activity. The frequency of the - 1575G 3 A transition deviated significantly from the expected Hardy-Weinberg distribution in two independently assembled study populations consisting of healthy adult blood donors and newborns of Caucasian origin, both with a calculated 21% reduction in genetic fitness. Gelatinase A is a known estrogen-responsive gene and the demonstration of a loss of function polymorphism within an operational estrogen receptor binding site associated with a decrease in genetic fitness underscores the biologic significance of promoter polymorphism analyses. C1 Univ Hamburg, Dept Med, D-20246 Hamburg, Germany. Univ Hamburg, Div Nephrol, D-20246 Hamburg, Germany. Univ Hamburg, Dept Pediat, D-20246 Hamburg, Germany. Univ Hamburg, Dept Transfus Med & Transplantat Immunol, D-20246 Hamburg, Germany. Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Harendza, S (reprint author), Univ Klinikum Hamburg Eppendorf, Zentrum Innere Med, Med Klin 4, Pavillon N26,Martinistr 52, D-20246 Hamburg, Germany. FU NIDDK NIH HHS [DK39776] NR 41 TC 52 Z9 54 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 6 PY 2003 VL 278 IS 23 BP 20490 EP 20499 DI 10.1074/jbc.M211536200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 684WY UT WOS:000183230500008 PM 12657623 ER PT J AU Yehuda, R Halligan, SL Yang, RK Guo, LS Makotkine, I Singh, B Pickholtz, D AF Yehuda, R Halligan, SL Yang, RK Guo, LS Makotkine, I Singh, B Pickholtz, D TI Relationship between 24-hour urinary-free cortisol excretion and salivary cortisol levels sampled from awakening to bedtime in healthy subjects SO LIFE SCIENCES LA English DT Article DE saliva; urine; cortisol; methodology ID ORAL DIFFUSION SINK; SERUM CORTISOL; RECOVERY AB The utility of repeated salivary cortisol sampling as a substitute for 24-hour urinary-free cortisol (UFC) assessment was examined. Forty-four participants completed both 24-hour collections and 6 salivary collections at wake-up, 08:00, 12:00, 16:00, 20:00 and bedtime, during the same 24-hour period. The results demonstrated that mean, maximum, and amplitude (maximum minus minimum) for salivary cortisol all correlated positively with urinary cortisol, but the associations of these variables with urinary-free cortisol excretion were relatively small. Furthermore, a single salivary sample taken at wake-up was as good an indicator of overall cortisol production as the measures derived from multiple salivary samples. An examination of subject compliance indicated that many subjects failed to collect the timed salivary collections as instructed. The authors conclude that diurnal salivary cortisol sampling versus 24-hour urinary cortisol collections are likely to provide different information about ambient hypothalamic-pituitary-adrenal productivity, and therefore these measures should not be used interchangeably. In addition, subject compliance is a serious consideration in designing studies that employ home salivary collections. Published by Elsevier Science Inc. C1 Mt Sinai Sch Med, Psychiat OOMH, Bronx, NY 10468 USA. Bronx Vet Affairs Med Ctr, Bronx, NY 10468 USA. Univ Reading, Sch Psychol, Reading RG6 6AH, Berks, England. RP Yehuda, R (reprint author), Mt Sinai Sch Med, Psychiat OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. OI Halligan, Sarah/0000-0002-3436-3358 FU NIMH NIH HHS [MH-49555, MH 64104] NR 22 TC 43 Z9 45 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUN 6 PY 2003 VL 73 IS 3 BP 349 EP 358 DI 10.1016/S0024-3205(03)00286-8 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 682VX UT WOS:000183114000010 PM 12757842 ER PT J AU Du, KY Herzig, S Kulkarni, RN Montminy, M AF Du, KY Herzig, S Kulkarni, RN Montminy, M TI TRB3: A tribbles homolog that inhibits Akt/PKB activation by insulin in liver SO SCIENCE LA English DT Article ID PROTEIN-KINASE-B; GLYCOGEN-SYNTHASE KINASE-3; NEGATIVE REGULATOR; DROSOPHILA; MORPHOGENESIS; INACTIVATION; GLUCOSE; CELLS; PKB; RESISTANCE AB Insulin resistance is a major hallmark in the development of type II diabetes, which is characterized by the failure of insulin to promote glucose uptake in muscle and to suppress glucose production in liver. The serine-threonine kinase Akt (PKB) is a principal target of insulin signaling that inhibits hepatic glucose output when glucose is available from food. Here we show that TRB3, a mammalian homolog of Drosophila tribbles, functions as a negative modulator of Akt. TRB3 expression is induced in liver under fasting conditions, and TRB3 disrupts insulin signaling by binding directly to Akt and blocking activation of the kinase. Amounts of TRB3 RNA and protein were increased in livers of db/db diabetic mice compared with those in wild-type mice. Hepatic overexpression of TRB3 in amounts comparable to those in db/db mice promoted hyperglycemia and glucose intolerance. Our results suggest that, by interfering with Akt activation, TRB3 contributes to insulin resistance in individuals with susceptibility to type II diabetes. C1 Salk Inst Biol Studies, Peptide Biol Labs, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Montminy, M (reprint author), Salk Inst Biol Studies, Peptide Biol Labs, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. OI Herzig, Stephan/0000-0003-3950-3652 NR 24 TC 476 Z9 499 U1 3 U2 32 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 6 PY 2003 VL 300 IS 5625 BP 1574 EP 1577 DI 10.1126/science.1079817 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 686QU UT WOS:000183333100056 PM 12791994 ER PT J AU Wirth, S Yanike, M Frank, LM Smith, AC Brown, EN Suzuki, WA AF Wirth, S Yanike, M Frank, LM Smith, AC Brown, EN Suzuki, WA TI Single neurons in the monkey hippocampus and learning of new associations SO SCIENCE LA English DT Article ID CONDITIONAL OCULOMOTOR ASSOCIATIONS; SUPPLEMENTARY EYE FIELD; PERIRHINAL NEURONS; CORTEX; MEMORY; ACQUISITION; RESPONSES; TASK AB The medial temporal lobe is crucial for the ability to learn and retain new declarative memories. This form of memory includes the ability to quickly establish novel associations between unrelated items. To better understand the patterns of neural activity during associative memory formation, we recorded the activity of hippocampal neurons of macaque monkeys as they learned new associations. Hippocampal neurons signaled learning by changing their stimulus-selective response properties. This change in the pattern of selective neural activity occurred before, at the same time as, or after learning, which suggests that these neurons are involved in the initial formation of new associative memories. C1 NYU, Ctr Neural Sci, New York, NY 10003 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Anesthesia & Crit Care, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02114 USA. RP Suzuki, WA (reprint author), NYU, Ctr Neural Sci, New York, NY 10003 USA. OI Frank, Loren/0000-0002-1752-5677 NR 20 TC 191 Z9 192 U1 1 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 6 PY 2003 VL 300 IS 5625 BP 1578 EP 1581 DI 10.1126/science.1084324 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 686QU UT WOS:000183333100057 PM 12791995 ER PT J AU Acker, JP Lu, XM Young, V Cheley, S Bayley, H Fowler, A Toner, M AF Acker, JP Lu, XM Young, V Cheley, S Bayley, H Fowler, A Toner, M TI Measurement of trehalose loading of mammalian cells porated with a metal-actuated switchable pore SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE gas chromatography (GC); alpha-hemolysin; intracellular trehalose; anhydrobiosis; biopreservation ID LONG-TERM STORAGE; DESICCATION TOLERANCE; INTRACELLULAR TREHALOSE; STABILIZATION; PRESERVATION; MEMBRANES; ANHYDROBIOSIS; SACCHARIDE; STABILITY; LIPOSOMES AB Efforts to improve the tolerance of mammalian cells to desiccation have focused on the role that sugars have in protecting cells from lethal injury. Among the key determinants of desiccation tolerance is the intracellular trehalose concentration, and thus quantifying the amount and rate of trehalose accumulation has now become very critical to the success of these desiccation approaches. We introduced trehalose into 3T3 fibroblasts, human keratinocytes, and rat hepatocytes using a genetically engineered mutant of the pore-forming a-hemolysin from Staphylococcus aureus. Manipulating the extracellular Zn2+ concentration selectively opens and closes this pore (similar to2 nm) and enables controlled loading of cells with sugars. We quantified intracellular trehalose using gas chromatography-mass spectroscopy (GC-MS) to examine the trimethylsilyl derivative of intracellular trehalose. Using the GC-MS method, we demonstrate that the switchable characteristics of H5 alpha-hemolysin permit controlled loading of the high concentrations of trehalose (up to 0.5 M) necessary for engineering desiccation tolerance in mammalian cells. (C) 2003 Wiley Periodicals, Inc. C1 Harvard Univ, Sch Med, Ctr Engn Med & Surg Serv, Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Hosp Children, Sch Med, Ctr Engn Med & Surg Serv, Massachusetts Gen Hosp, Boston, MA 02114 USA. Texas A&M Univ, Dept Med Biochem & Genet, College Stn, TX USA. MIT, Sch Sci, Human Nutr Lab, Cambridge, MA USA. MIT, Clin Res Ctr, Cambridge, MA USA. Univ Massachusetts, Dept Engn Mech, Dartmouth, MA USA. RP Toner, M (reprint author), Harvard Univ, Sch Med, Ctr Engn Med & Surg Serv, Massachusetts Gen Hosp, 51 Blossom St,Room 266, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK46270]; NINDS NIH HHS [NS26760] NR 44 TC 35 Z9 37 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD JUN 5 PY 2003 VL 82 IS 5 BP 525 EP 532 DI 10.1002/bit.10599 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 669QQ UT WOS:000182362300004 PM 12652476 ER PT J AU Kampman, KM Pettinati, H Lynch, KG Sparkman, T O'Brien, CP AF Kampman, KM Pettinati, H Lynch, KG Sparkman, T O'Brien, CP TI A pilot trial of olanzapine for the treatment of cocaine dependence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine; olanzapine; clinical trial; double-blind ID D2 DOPAMINE ANTAGONISTS; PATTERN-MIXTURE MODELS; CRACK COCAINE; RISPERIDONE; RAT; HALOPERIDOL; REINFORCEMENT; SCHEDULES; D-1; D1 AB Background: Multiple lines of evidence suggest both dopaminergic and serotonergic involvement in the reinforcing effects of cocaine. Medications such as olanzapine, which block dopamine D2 receptors, as well as serotonin receptors 5HT2A and 5HT2C may be able to reduce cocaine use in cocaine dependent patients by reducing the euphoric effects of cocaine and attenuating cocaine craving. Methods: This was a 12-week, double blind, placebo controlled, pilot trial involving 30 cocaine dependent subjects. Subjects received either olanzapine (10 mg/day) or identical placebo. Outcome measures included treatment retention, qualitative urine benzoylecgonine tests, cocaine craving, clinical global impression scores, and results from the addiction severity index. Results: Treatment retention was slightly, but significantly, better in the placebo-treated subjects. Placebo-treated subjects were more likely to be abstinent from cocaine during the trial compared to olanzapine-treated subjects, based on urine benzoylecgonine results. Olanzapine was not superior to placebo in any outcome measure. Conclusions: The results of this trial do not support the usefulness of olanzapine for the treatment of cocaine dependence. In fact, olanzapine may worsen cocaine treatment outcome. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Penn, Sch Med, Treatment Res Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Kampman, KM (reprint author), Univ Penn, Sch Med, Treatment Res Ctr, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. NR 43 TC 57 Z9 58 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN 5 PY 2003 VL 70 IS 3 BP 265 EP 273 DI 10.1016/S0376-8716(03)00009-7 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 690WC UT WOS:000183572600005 PM 12757964 ER PT J AU Ghosh-Choudhury, N Abboud, SL Chandrasekar, B Choudhury, GG AF Ghosh-Choudhury, N Abboud, SL Chandrasekar, B Choudhury, GG TI BMP-2 regulates cardiomyocyte contractility in a phosphatidylinositol 3 kinase-dependent manner SO FEBS LETTERS LA English DT Article DE cardiomyocyte contraction; bone morphogenetic protein-2; phosphatidylinositol 3 kinase ID BONE MORPHOGENETIC PROTEINS; PHOSPHOINOSITIDE 3-KINASE; OSTEOBLAST DIFFERENTIATION; SIGNALING PATHWAYS; CARDIAC MYOCYTES; MESANGIAL CELLS; ACTIVATION; HYPERTROPHY; HEART; SMAD AB Bone morphogenetic protein-2 (BMP-2) regulates development of heart during vertebrate embryogenesis. In vitro BMP-2 induces differentiation of precardiac cells into mature cardiomyocytes by inducing the expression of cardiac-specific genes. However, the role of BMP-2 and its signaling in other cardiac functions have not been studied. We examined the action of phosphatidylinositol (PI) 3 kinase in isolated adult rat cardiomyocytes. Incubation of rat ventricular cardiomyocytes with BMP-2 increased the PI 3 kinase activity. Ly294002, a pharmacological inhibitor of PI 3 kinase, blocked BMP-2-induced PI 3 kinase activity completely. To investigate the contractility of isolated cardiomyocytes, fractional shortening was examined. BMP-2 significantly increased the percent fractional shortening of the cardiomyocytes. Inhibition of PI 3 kinase activity completely abolished this action of BMP-2. These data indicate that PI 3 kinase regulates BMP-2-induced myocyte contractility. To further confirm this observation, we used adenovirus-mediated gene transfer to express a constitutively active myristoylated catalytic subunit of PI 3 kinase in rat cardiomyocytes. Infection of cardiomyocytes with the adenovirus vector increased the expression of constitutively active PI 3 kinase within 24 h. Expression of constitutively active PI 3 kinase significantly increased cardiomyocyte contractility. Together, these data show for the first time that the growth and differentiation factor, BMP-2, stimulates cardiomyocyte contractility. Also we provide the first evidence that BMP-2-induced PI 3 kinase activity regulates this cardiomyocyte function. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX USA. GRECC, San Antonio, TX USA. RP Ghosh-Choudhury, N (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NHLBI NIH HHS [HL68020]; NIAMS NIH HHS [AR-42306]; NIDDK NIH HHS [R01 DK55815] NR 39 TC 21 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 5 PY 2003 VL 544 IS 1-3 BP 181 EP 184 DI 10.1016/S0014-5793(03)00507-6 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 687TR UT WOS:000183393500033 PM 12782312 ER PT J AU Medrano, FJ Wenck, MA Engel, JC Craig, SP AF Medrano, FJ Wenck, MA Engel, JC Craig, SP TI Analysis of 6-(2,2-dichloroacetamido)chrysene interaction with the hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID GUANINE PHOSPHORIBOSYLTRANSFERASE; HPRT AB Selective inhibition is needed for drugs targeting the hypoxanthine phosphoribosyltransferase of Trypanosoma cruzi, etiologic agent of Chagas' disease. 6-(2,2-Dichloroacetamido)chrysene, was shown herein to be a selective inhibitor of the trypanosomal enzyme. SAR analysis revealed that the 6-amido moiety was essential, but the dichloroaceto moiety was not essential for achieving the low K-i for this inhibitor. Understanding the molecular basis for these interactions could facilitate the design of selective inhibitors without a chrysene moiety. C1 Univ Connecticut, Lab Mol Parasitol & Drug Design, Dept Mol & Cell Biol, Storrs, CT 06269 USA. San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Craig, SP (reprint author), Univ Connecticut, Lab Mol Parasitol & Drug Design, Dept Mol & Cell Biol, Storrs, CT 06269 USA. OI Medrano, Francisco/0000-0002-8185-9751 FU NIAID NIH HHS [P01-AI35707, R01-AI45021] NR 12 TC 9 Z9 9 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 5 PY 2003 VL 46 IS 12 BP 2548 EP 2550 DI 10.1021/jm030061i PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 684RM UT WOS:000183220400030 PM 12773058 ER PT J AU Perkins, BA Ficociello, LH Silva, KH Finkelstein, DM Warram, JH Krolewski, AS AF Perkins, BA Ficociello, LH Silva, KH Finkelstein, DM Warram, JH Krolewski, AS TI Regression of microalbuminuria in type 1 diabetes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ALBUMIN EXCRETION; FILTRATION-RATE; RENAL-DISEASE; NEPHROPATHY; MELLITUS; PROTEINURIA; RISK; COMPLICATIONS; PROGRESSION; PREVALENCE AB BACKGROUND: In the present study, we aimed to determine the frequency of a significant reduction in urinary albumin excretion and factors affecting such reduction in patients with type 1 diabetes and microalbuminuria. METHODS: The study included 386 patients with persistent microalbuminuria, indicated by repeated measurements of urinary albumin excretion (estimated on the basis of albumin-to-creatinine ratios) in the range of 30 to 299 microg per minute during an initial two-year evaluation period. Subsequent measurements during the next six years were grouped into two-year periods, averaged, and analyzed for regression of microalbuminuria, which was defined as a 50 percent reduction in urinary albumin excretion from one two-year period to the next. RESULTS: Regression of microalbuminuria was frequent, with a six-year cumulative incidence of 58 percent (95 percent confidence interval, 52 to 64 percent). The use of angiotensin-converting-enzyme inhibitors was not associated with the regression of microalbuminuria. However, microalbuminuria of short duration, salutary levels of glycosylated hemoglobin (less than 8 percent), low systolic blood pressure (less than 115 mm Hg), and low levels of both cholesterol and triglycerides (less than 198 mg per deciliter [5.12 mmol per liter] and 145 mg per deciliter [1.64 mmol per liter], respectively) were independently associated with the regression of microalbuminuria. Patients with salutary levels of all modifiable factors had a hazard ratio for regression of 3.0 (95 percent confidence interval, 1.5 to 6.0), as compared with patients with no salutary levels of any modifiable factor. CONCLUSIONS: Frequent regression of microalbuminuria in patients with type 1 diabetes indicates that elevated urinary albumin excretion does not imply inexorably progressive nephropathy. Identification of the multiple determinants of the regression of microalbuminuria has implications for current theories about the mechanisms of early diabetic nephropathy. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu FU NIDDK NIH HHS [R01-DK41526] NR 42 TC 387 Z9 409 U1 2 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 5 PY 2003 VL 348 IS 23 BP 2285 EP 2293 DI 10.1056/NEJMoa021835 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 686AA UT WOS:000183296300003 PM 12788992 ER PT J AU Engel, S Martinez, H Shamoon, H Engel, H Dahms, W Mayer, L Pendegras, S Zegarra, H Miller, D Singerman, L Smith-Brewer, S Genuth, S Brillon, D Lackaye, M Heinemann, M Reppuci, V Lee, T Whitehouse, F Kruger, D Galpern, A Carey, JD Bergenstal, R Johnson, M Kendall, D Spencer, M Noller, D Morgan, K Etzwiler, D Jacobson, A Golden, E Sharuk, G Arrigg, P Baeser, R Ganda, O Rosenzweig, J Wolpert, H Economides, P Handy, O Rand, L Nathan, D Fritz, S Godine, J McKitrick, C Lou, P Service, FJ Ziegler, G Pach, J Lindsey, J Colwell, J Wood, D Mayfield, R Hermayer, K Szpiech, M Lyons, T Parker, J Farr, A Elsing, S Thompson, T Selby, J Bracey, M Molitch, M Schaefer, B Jampol, L Weinberg, D Lyon, A Strugula, Z Shankle, J Astlesford, P Kolterman, O Lorenzi, G Goldbaum, M Sivitz, W Bayless, M Zeither, R Weingeist, T Stone, E Boidt, HC Gehres, K Russell, S Counts, D Kowarski, A Ostrowski, D Donner, T Steidl, S Jones, B Herman, W Greene, D Martin, C Stevens, MJ Vine, AK Elner, S Bantle, J Rogness, B Olsen, T Steuer, E Goldstein, D Hitt, S Giangiacomo, J Hainsworth, D Schade, D Burge, M Canady, J Schluter, M Das, A Hornbeck, D Schwartz, S Bourne, PA Maschak-Carey, BJ Baker, L Braunstein, S Brucker, A Orchard, T Silvers, N Songer, T Doft, B Olson, S Bergren, RL Lobes, L Fineman, M Drash, A Malone, J Vaccaro-Kish, J Berger, C Gstalder, R Pavan, PR Morrison, A Dagogo-Jack, S Schussler, S Kitabchi, A Lambeth, H Murphy, MB Moser, S Meyer, D Iannacone, A Bryer-Ash, M Raskin, P Strowig, S Edwards, A Alappatt, J Wilson, C Park, S He, Y Zinman, B Barnie, A MacLean, S Devenyi, R Mandelcorn, M Brent, M Palmer, J Catton, S Kinyoun, J Van Ottingham, L Ginsberg, J Dupre, J Harth, J Canny, C Nicolle, D May, M Lorenz, R Lipps, J Survant, L Feman, S Tawansy, K Agarwal, A Adkins, T White, N Santiago, J Levandoski, L Boniuk, I Grand, G Thomas, M Burgess, D Joseph, D Blinder, K Shah, G Tamborlane, W Gatcomb, P Stoessel, K Taylor, K Dahms, B Trail, R Quin, J Lachin, J Cleary, P Kenny, D Backlund, J Diminick, L Determan, A Klump, K Hawkins, M Cowie, C Fradkin, J Siebert, C Eastman, R Davis, M Hubbard, L Geithman, P Kastorff, L Neider, M Badal, D Esser, B Miner, K Wabers, H Glander, K Joyce, J Robinson, N Hurtenbach, C Hannon, C Steffes, M Bucksa, J Chavers, B O'Leary, D Funk, L Polak, J Crow, R O'Donnell, C Gloeb, B Thomas, S Detrano, R Wong, N Fox, M Kim, L Oudiz, R Weir, G Clark, C D'Agostino, R Espeland, M Klein, B Manolio, T Rand, L Singer, D Stern, M Garvey, WT Lyons, TJ Jenkins, A Klein, R Lopes-Virella, M Virella, G Jaffa, AA Zheng, D Lackland, D McGee, D Mayfield, RK Brabham, M Boright, A Paterson, A Scherer, S Zinman, B Brunzell, J Hokanson, J Marcovina, S Purnell, J Sibley, S Deeb, S Edwards, K Nathan, D AF Engel, S Martinez, H Shamoon, H Engel, H Dahms, W Mayer, L Pendegras, S Zegarra, H Miller, D Singerman, L Smith-Brewer, S Genuth, S Brillon, D Lackaye, M Heinemann, M Reppuci, V Lee, T Whitehouse, F Kruger, D Galpern, A Carey, JD Bergenstal, R Johnson, M Kendall, D Spencer, M Noller, D Morgan, K Etzwiler, D Jacobson, A Golden, E Sharuk, G Arrigg, P Baeser, R Ganda, O Rosenzweig, J Wolpert, H Economides, P Handy, O Rand, L Nathan, D Fritz, S Godine, J McKitrick, C Lou, P Service, FJ Ziegler, G Pach, J Lindsey, J Colwell, J Wood, D Mayfield, R Hermayer, K Szpiech, M Lyons, T Parker, J Farr, A Elsing, S Thompson, T Selby, J Bracey, M Molitch, M Schaefer, B Jampol, L Weinberg, D Lyon, A Strugula, Z Shankle, J Astlesford, P Kolterman, O Lorenzi, G Goldbaum, M Sivitz, W Bayless, M Zeither, R Weingeist, T Stone, E Boidt, HC Gehres, K Russell, S Counts, D Kowarski, A Ostrowski, D Donner, T Steidl, S Jones, B Herman, W Greene, D Martin, C Stevens, MJ Vine, AK Elner, S Bantle, J Rogness, B Olsen, T Steuer, E Goldstein, D Hitt, S Giangiacomo, J Hainsworth, D Schade, D Burge, M Canady, J Schluter, M Das, A Hornbeck, D Schwartz, S Bourne, PA Maschak-Carey, BJ Baker, L Braunstein, S Brucker, A Orchard, T Silvers, N Songer, T Doft, B Olson, S Bergren, RL Lobes, L Fineman, M Drash, A Malone, J Vaccaro-Kish, J Berger, C Gstalder, R Pavan, PR Morrison, A Dagogo-Jack, S Schussler, S Kitabchi, A Lambeth, H Murphy, MB Moser, S Meyer, D Iannacone, A Bryer-Ash, M Raskin, P Strowig, S Edwards, A Alappatt, J Wilson, C Park, S He, Y Zinman, B Barnie, A MacLean, S Devenyi, R Mandelcorn, M Brent, M Palmer, J Catton, S Kinyoun, J Van Ottingham, L Ginsberg, J Dupre, J Harth, J Canny, C Nicolle, D May, M Lorenz, R Lipps, J Survant, L Feman, S Tawansy, K Agarwal, A Adkins, T White, N Santiago, J Levandoski, L Boniuk, I Grand, G Thomas, M Burgess, D Joseph, D Blinder, K Shah, G Tamborlane, W Gatcomb, P Stoessel, K Taylor, K Dahms, B Trail, R Quin, J Lachin, J Cleary, P Kenny, D Backlund, J Diminick, L Determan, A Klump, K Hawkins, M Cowie, C Fradkin, J Siebert, C Eastman, R Davis, M Hubbard, L Geithman, P Kastorff, L Neider, M Badal, D Esser, B Miner, K Wabers, H Glander, K Joyce, J Robinson, N Hurtenbach, C Hannon, C Steffes, M Bucksa, J Chavers, B O'Leary, D Funk, L Polak, J Crow, R O'Donnell, C Gloeb, B Thomas, S Detrano, R Wong, N Fox, M Kim, L Oudiz, R Weir, G Clark, C D'Agostino, R Espeland, M Klein, B Manolio, T Rand, L Singer, D Stern, M Garvey, WT Lyons, TJ Jenkins, A Klein, R Lopes-Virella, M Virella, G Jaffa, AA Zheng, D Lackland, D McGee, D Mayfield, RK Brabham, M Boright, A Paterson, A Scherer, S Zinman, B Brunzell, J Hokanson, J Marcovina, S Purnell, J Sibley, S Deeb, S Edwards, K Nathan, D CA Diabet Control Complications Trial TI Intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BLOOD-GLUCOSE CONTROL; INSULIN-RESISTANCE ATHEROSCLEROSIS; CORONARY-ARTERY-DISEASE; WALL THICKNESS; COMPLICATIONS TRIAL; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; RISK-FACTOR; PROGRESSION; ULTRASOUND AB BACKGROUND: Cardiovascular disease causes severe morbidity and mortality in type 1 diabetes, although the specific risk factors and whether chronic hyperglycemia has a role are unknown. We examined the progression of carotid intima-media thickness, a measure of atherosclerosis, in a population with type 1 diabetes. METHODS: As part of the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the long-term follow-up of the Diabetes Control and Complications Trial (DCCT), 1229 patients with type 1 diabetes underwent B-mode ultrasonography of the internal and common carotid arteries in 1994-1996 and again in 1998-2000. We assessed the intima-media thickness in 611 subjects who had been randomly assigned to receive conventional diabetes treatment during the DCCT and in 618 who had been assigned to receive intensive diabetes treatment. RESULTS: At year 1 of the EDIC study, the carotid intima-media thickness was similar to that in an age- and sex-matched nondiabetic population. After six years, the intima-media thickness was significantly greater in the diabetic patients than in the controls. The mean progression of the intima-media thickness was significantly less in the group that had received intensive therapy during the DCCT than in the group that had received conventional therapy (progression of the intima-media thickness of the common carotid artery, 0.032 vs. 0.046 mm; P=0.01; and progression of the combined intima-media thickness of the common and internal carotid arteries, -0.155 vs. 0.007; P=0.02) after adjustment for other risk factors. Progression of carotid intima-media thickness was associated with age, and the EDIC base-line systolic blood pressure, smoking, the ratio of low-density lipoprotein to high-density lipoprotein cholesterol, and urinary albumin excretion rate and with the mean glycosylated hemoglobin value during the mean duration (6.5 years) of the DCCT. CONCLUSIONS: Intensive therapy during the DCCT resulted in decreased progression of intima-media thickness six years after the end of the trial. C1 DCCT EDIC Res Grp, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Cornell Univ, Med Ctr, Ithaca, NY 14853 USA. Henry Ford Hlth Syst, Detroit, MI USA. Int Diabet Ctr, Minneapolis, MN USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Med Univ S Carolina, Mol Risk Factors Program Project, Charleston, SC 29425 USA. Northwestern Univ, Evanston, IL 60208 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Iowa, Iowa City, IA 52242 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Missouri, Columbia, MO 65211 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ S Florida, Tampa, FL 33620 USA. Univ Tennessee, Knoxville, TN 37996 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Toronto, Toronto, ON, Canada. Univ Western Ontario, London, ON N6A 3K7, Canada. Vanderbilt Univ, Nashville, TN USA. Washington Univ, St Louis, MO USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. George Washington Univ, Ctr Biostat, Washington, DC 20052 USA. NIDDKD, Program Off, Bethesda, MD 20892 USA. Univ Wisconsin, Cent Fundus Photog Reading Ctr, Madison, WI 53706 USA. Univ Minnesota, Cent Biochem Lab, Minneapolis, MN 55455 USA. Tufts Univ New England Med Ctr, Cent Carotid Ultrasound Unit, Boston, MA 02111 USA. Univ Minnesota, Cent Electrocardiog Reading Unit, Minneapolis, MN 55455 USA. Harbor UCLA Res & Educ Int, Comp Tomog Reading Ctr, Torrance, CA USA. Hosp Sick Children, Genet Studies Grp, Toronto, ON M5G 1X8, Canada. Univ Washington, Lipoprot Distribut Obes Grp, Seattle, WA 98195 USA. RP Engel, S (reprint author), DCCT EDIC Res Grp, Box NDIC DCCT, Bethesda, MD 20892 USA. EM dnathan@partners.org RI Zinman, Bernard/E-7266-2013; Paterson, Andrew/A-4088-2011; OI Paterson, Andrew/0000-0002-9169-118X; orchard, trevor/0000-0001-9552-3215; Lachin, John/0000-0001-9838-2841 NR 48 TC 463 Z9 472 U1 2 U2 11 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 5 PY 2003 VL 348 IS 23 BP 2294 EP 2303 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 686AA UT WOS:000183296300004 ER PT J AU Thompson, CA Nasseri, BA Makower, J Houser, S McGarry, M Lamson, T Pomerantseva, I Chang, JY Gold, HK Vacanti, JP Oesterle, SN AF Thompson, CA Nasseri, BA Makower, J Houser, S McGarry, M Lamson, T Pomerantseva, I Chang, JY Gold, HK Vacanti, JP Oesterle, SN TI Percutaneous transvenous cellular cardiomyoplasty - A novel nonsurgical approach for myocardial cell transplantation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID GENE-TRANSFER; DELIVERY; HEART; BONE; RECONSTRUCTION; CARDIOMYOCYTES; ISCHEMIA AB OBJECTIVES The study evaluated a nonsurgical means of intramyocardial cell introduction using the I coronary venous system for direct myocardial access and cell delivery. BACKGROUND Direct myocardial cell repopulation has been proposed as a potential method to treat heart failure. METHODS We harvested bone marrow from Yorkshire swine (n = 6; 50 to 60 kg), selected culture-flask adherent cells, labeled them with the gene for green fluorescence protein, expanded them in culture, and resuspended them in a collagen hydrogel. Working through the coronary sinus, a specialized catheter system was easily delivered to the anterior interventricular coronary vein. The composite catheter system (TransAccess) incorporates a phased-array ultrasound tip for guidance and a sheathed, extendable nitinol needle for transvascular myocardial access. A microinfusion (IntraLume) catheter was advanced through the needle, deep into remote, myocardium, and the autologous cell-hydrogel suspension was injected into normal heart. Animals were sacrificed at days 0 (n = 2), 14 (n = 1, + 1 control/collagen biogel only), and 28 (n = 2), and the hearts were excised and examined. RESULTS We gained widespread intramyocardial access to the anterior, lateral, septal, apical,, and inferior walls from the anterior interventicular coronary vein. No death, cardiac tamponade, ventricular arrhythmia, or other procedural complications occurred. Gross inspection demonstrated no evidence of myocardial perforation, and biogel/black tissue dye was well localized to sites corresponding to fluoroscopic landmarks for delivery. Histologic analysis demonstrated needle and microcatheter tracts and accurate cell-biogel delivery. CONCLUSIONS Percutancous intramyocardial access is safe and feasible by a transvenous approach through the coronary venous system. The swine offers an opportunity to refine approaches used for cellular cardiomyoplasty. (C) 2003 by the American College of Cardiology Foundation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Cardiac Catheterizat & Intervent,Cardiovasc D, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tissue Engn Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. TransVasc Inc, Menlo Pk, CA USA. RP Thompson, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Cardiac Catheterizat & Intervent,Cardiovasc D, 55 Fruit St,Blake 950, Boston, MA 02114 USA. NR 23 TC 106 Z9 123 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 4 PY 2003 VL 41 IS 11 BP 1964 EP 1971 DI 10.1016/S0735-1097(03)00397-8 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 684QY UT WOS:000183219100010 PM 12798567 ER PT J AU Massie, BM AF Massie, BM TI Natriuretic peptide measurements for the diagnosis of "nonsystolic" heart failure - Good news and bad SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID PRESERVED SYSTOLIC FUNCTION; EMERGENCY DIAGNOSIS; EJECTION FRACTION; DYSFUNCTION; AGE; COMMUNITY; IMPACT; HEALTH C1 San Francisco Vet Affairs Med Ctr, Div Cardiol, San Francisco, CA USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA USA. RP Massie, BM (reprint author), VA Hosp, Cardiol 111C,4150 Clement St, San Francisco, CA 94121 USA. NR 20 TC 15 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 4 PY 2003 VL 41 IS 11 BP 2018 EP 2021 DI 10.1016/S0735-1097(03)00395-4 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 684QY UT WOS:000183219100018 PM 12798575 ER PT J AU Stratton, JR Levy, WC Caldwell, JH Jacobson, A May, J Matsuoka, D Madden, K AF Stratton, JR Levy, WC Caldwell, JH Jacobson, A May, J Matsuoka, D Madden, K TI Effects of aging on cardiovascular responses to parasympathetic withdrawal SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HEART-RATE-VARIABILITY; POSTMENOPAUSAL WOMEN; SYMPATHETIC-STIMULATION; VAGAL-STIMULATION; BLOOD-PRESSURE; HEALTHY-YOUNG; OLDER MEN; AGE; EXERCISE; GENDER AB OBJECTIVES The study was done to determine whether the effects of parasympathetic withdrawal on heart rate, blood pressure (BP), and systolic and diastolic function are altered with normal aging. BACKGROUND Cardiac responses to beta-adrenergic sympathetic stimulation decline with aging as does the heart rate response to parasympathetic withdrawal, but the extent to which other responses to parasympathetic withdrawal decrease is less clear. METHODS Heart rate, BP, systolic function, and diastolic filling responses to parasympathetic withdrawal induced by atropine (0.02 mg/kg) were compared in 50 healthy subjects, 28 older (ages 65 to 80 years, mean 70 years; 18 females all on estrogen) and 22 young (age 18 to 32 years, mean 26 years; 12 females) subjects, using radionuclide angiography. RESULTS Parasympathetic withdrawal in the older group caused less of an increase in heart rate (+33 vs. +48 beats/min), cardiac index (+0.6 vs. +1.5 l/m(2)), systolic blood pressure (-1 vs. +7 mm Hg), and early diastolic filling rate (+1.7 vs. +2.4 end-diastolic volumes/s) (all p less than or equal to 0.01). At similar declines in the diastolic filling period, end-diastolic volume index (EDVI) fell substantially more in the older group (-11.6 vs. -2.4 ml/m(2), p < 0.001). The only gender difference was in diastolic filling rate, which was similar in the young males and females, but significantly less in older males than in older females. CONCLUSIONS The responses to parasympathetic withdrawal as well as sympathetic stimulation decline with aging, and both contribute to the reduced cardiovascular responses to stress with advancing age. (C) 2003 by the American College of Cardiology Foundation. C1 VA Puget Sound Healthcare Syst, Seattle, WA 98108 USA. Univ Washington, Div Cardiol, Seattle, WA 98195 USA. Univ Washington, Div Nucl Med, Seattle, WA 98195 USA. RP Stratton, JR (reprint author), VA Puget Sound Healthcare Syst, Cardiol S111C,1660 S Columbian Way, Seattle, WA 98108 USA. EM jrs@u.washington.edu FU NHLBI NIH HHS [HL 50293]; NIA NIH HHS [R01 AG 15462, K12 AG 00503] NR 41 TC 34 Z9 35 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 4 PY 2003 VL 41 IS 11 BP 2077 EP 2083 DI 10.1016/S0735-1097(03)00418-2 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 684QY UT WOS:000183219100028 PM 12798585 ER PT J AU Schernhammer, ES Laden, F Speizer, FE Willett, WC Hunter, DJ Kawachi, I Fuchs, CS Colditz, GA AF Schernhammer, ES Laden, F Speizer, FE Willett, WC Hunter, DJ Kawachi, I Fuchs, CS Colditz, GA TI Night-shift work and risk of colorectal cancer in the Nurses' Health Study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CELLS IN-VITRO; BREAST-CANCER; COLON CARCINOGENESIS; MELATONIN; WOMEN; MCF-7; TUMORS; LIGHT; RATS; 1,2-DIMETHYLHYDRAZINE AB Exposure to light at night suppresses the physiologic production of melatonin, a hormone that has antiproliferative effects on intestinal cancers. Although observational studies have associated night-shift work with an increased risk of breast cancer, the effect of night-shift work on the risk of other cancers is not known. We prospectively examined the relationship between working rotating night shifts and the risk of colorectal cancers among female participants in the Nurses' Health Study. We documented 602 incident cases of colorectal cancer among 78 586 women who were followed up from 1988 through 1998. Compared with women who never worked rotating night shifts, women who worked 1-14 years or 15 years or more on rotating night shifts had multivariate relative risks of colorectal cancer of 1.00 (95% confidence interval [CI] = 0.84 to 1.19) and 1.35 (95% CI = 1.03 to 1.77), respectively (P-trend = .04). These data suggest that working a rotating night shift at least three nights per month for 15 or more years may increase the risk of colorectal cancer in women. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Kaiser Franz Josef Spital, Ludwig Boltzmann Inst Appl Canc Res, Vienna, Austria. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Ctr Canc, Program Epidemiol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Ctr Canc Prevent, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Canc Prevent, Harvard Canc Ctr, Boston, MA USA. Harvard Canc Ctr, Program Epidemiol, Dana Farber Canc Inst, Boston, MA USA. RP Schernhammer, ES (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA87969, CA/ES62984] NR 37 TC 362 Z9 381 U1 3 U2 21 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 4 PY 2003 VL 95 IS 11 BP 825 EP 828 PG 4 WC Oncology SC Oncology GA 686LP UT WOS:000183323500013 PM 12783938 ER PT J AU Assendelft, WJJ Morton, SC Yu, EI Suttorp, MJ Shekelle, PG AF Assendelft, WJJ Morton, SC Yu, EI Suttorp, MJ Shekelle, PG TI Spinal manipulative therapy for low back pain - A meta-analysis of effectiveness relative to other therapies SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID RANDOMIZED CLINICAL-TRIAL; SYSTEMATIC REVIEWS; MANUAL THERAPY; NECK COMPLAINTS; FOLLOW-UP; OUTCOME MEASURES; PRIMARY-CARE; HEALTH-CARE; CONSERVATIVE TREATMENT; MULTICENTER TRIAL AB Background: Low back pain is a costly illness for which spinal manipulative therapy is commonly recommended. Previous systematic reviews and practice guidelines have reached discordant results on the effectiveness of this therapy for low back pain. Purpose: To resolve the discrepancies related to use of spinal manipulative therapy and to update previous estimates of effectiveness by comparing spinal manipulative therapy with other therapies and then incorporating data from recent high-quality randomized, controlled trials (RCTs) into the analysis. Data Sources: MEDLINE, EMBASE, CINAHL, the Cochrane Controlled Trials Register, and previous systematic reviews. Study Selection: Randomized, controlled trials of patients with low back pain that evaluated spinal manipulative therapy with at least 1 day of follow-up and at least one clinically relevant outcome measure. Data Extraction: Two authors, who served as the reviewers for all stages of the meta-analysis, independently extracted data from unmasked articles. Comparison treatments were classified into the following seven categories: sham, conventional general practitioner care, analgesics, physical therapy, exercises, back school, or a collection of therapies judged to be ineffective or even harmful (traction, corset, bed rest, home care, topical gel, no treatment, diathermy, and minimal massage). Data Synthesis: Thirty-nine RCTs were identified. Meta-regression models were developed for acute or chronic pain and short-term and long-term pain and function. For patients with acute low back pain, spinal manipulative therapy was superior only to sham therapy (10-mm difference [95% CI, 2 to 17 mm] on a 100-mm visual analogue scale) or therapies judged to be ineffective or even harmful. Spinal manipulative therapy had no statistically or clinically significant advantage over general practitioner care, analgesics, physical therapy, exercises, or back school. Results for patients with chronic low back pain were similar. Radiation of pain, study quality, profession of manipulator, and use of manipulation alone or in combination with other therapies did not affect these results. Conclusions: There is no evidence that spinal manipulative therapy is superior to other standard treatments for patients with acute or chronic low back pain. C1 RAND Corp, Santa Monica, CA 90407 USA. Cochrane Back Review Grp, Toronto, ON, Canada. Dutch Coll Gen Practitioners, Utrecht, Netherlands. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Shekelle, PG (reprint author), RAND Corp, 1700 Main St,POB 2138, Santa Monica, CA 90407 USA. RI Assendelft, W.J.J./H-8008-2014 NR 117 TC 184 Z9 187 U1 0 U2 15 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 3 PY 2003 VL 138 IS 11 BP 871 EP 881 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 686AB UT WOS:000183296400002 PM 12779297 ER PT J AU Cherkin, DC Sherman, KJ Deyo, RA Shekelle, PG AF Cherkin, DC Sherman, KJ Deyo, RA Shekelle, PG TI A review of the evidence for the effectiveness, safety, and cost of acupuncture, massage therapy, and spinal manipulation for back pain SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED TRIALS; FOLLOW-UP; SYSTEMATIC REVIEWS; CLINICAL-TRIALS; HEALTH; CARE; PHYSIOTHERAPISTS; COMPLICATIONS; EXPECTATIONS; MANAGEMENT AB Background: Few treatments for back pain are supported by strong scientific evidence. Conventional treatments, although widely used, have had limited success. Dissatisfied patients have, therefore, turned to complementary and alternative medical therapies and providers for care for back pain. Purpose: To provide a rigorous and balanced summary of the best available evidence about the effectiveness, safety, and costs of the most popular complementary and alternative medical therapies used to treat back pain. Data Sources: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. Study Selection: Systematic reviews of randomized, controlled trials (RCTs) that were published since 1995 and that evaluated acupuncture, massage therapy, or spinal manipulation for nonspecific back pain and RCTs published since the reviews were conducted. Data Extraction: Two authors independently extracted data from the reviews (including number of RCTs, type of back pain, quality assessment, and conclusions) and original articles (including type of pain, comparison treatments, sample size, outcomes, follow-up intervals, loss to follow-up, and authors' conclusions). Data Synthesis: Because the quality of the 20 RCTs that evaluated acupuncture was generally poor, the effectiveness of acupuncture for treating acute or chronic back pain is unclear. The three RCTs that evaluated massage reported that this therapy is effective for subacute and chronic back pain. A meta-regression analysis of the results of 26 RCTs evaluating spinal manipulation for acute and chronic back pain reported that spinal manipulation was superior to sham therapies and therapies judged to have no evidence of a benefit but was not superior to effective conventional treatments. Conclusions: Initial studies have found massage to be effective for persistent back pain. Spinal manipulation has small clinical benefits that are equivalent to those of other commonly used therapies. The effectiveness of acupuncture remains unclear. All of these treatments seem to be relatively safe. Preliminary evidence suggests that massage, but not acupuncture or spinal manipulation, may reduce the costs of care after an initial course of therapy. C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Seattle, WA 98195 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. RP Cherkin, DC (reprint author), Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. FU AHRQ HHS [R01 HS 09989]; NCCIH NIH HHS [AT00606, AT00622] NR 47 TC 195 Z9 201 U1 5 U2 17 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 3 PY 2003 VL 138 IS 11 BP 898 EP 906 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 686AB UT WOS:000183296400005 PM 12779300 ER PT J AU Wang, TJ Levy, D Benjamin, EJ Vasan, RS AF Wang, TJ Levy, D Benjamin, EJ Vasan, RS TI The epidemiology of "asymptomatic" left ventricular systolic dysfunction: Implications for screening SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID BRAIN NATRIURETIC PEPTIDE; CONGESTIVE-HEART-FAILURE; IDIOPATHIC DILATED CARDIOMYOPATHY; CONVERTING ENZYME-INHIBITORS; MYOCARDIAL-INFARCTION; DIASTOLIC DYSFUNCTION; GENERAL-PRACTICE; PROGNOSTIC IMPLICATIONS; CARDIOVASCULAR HEALTH; CLINICAL IMPLICATIONS AB Congestive heart failure is a progressive disorder that is frequently preceded by asymptomatic left ventricular systolic dysfunction. We reviewed the epidemiology, diagnosis, and natural history of asymptomatic left ventricular systolic dysfunction and evaluated community-wide screening for this condition as a potential strategy to reduce the incidence of heart failure. Asymptomatic left ventricular systolic dysfunction has an estimated prevalence of 3% to 6%, and is at least as common in the community as systolic heart failure. Because it often occurs in the absence of known cardiovascular disease, this condition may go unrecognized and undertreated. In randomized trials, individuals with asymptomatic left ventricular systolic dysfunction have high rates of incident heart failure and death. However, little is known about the prognosis of individuals with this condition in the community, who have a substantially lower prevalence of myocardial infarction, have milder degrees of systolic dysfunction, and are older than patients enrolled in clinical trials. Current evidence is inadequate to support community-wide screening for asymptomatic left ventricular systolic dysfunction, either with echocardiography or with assays for natriuretic peptides. Given the increasing prevalence of heart failure, additional studies are needed to develop effective strategies to detect and optimally manage individuals with asymptomatic left ventricular dysfunction in the community. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston Med Ctr, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NHLBI, Bethesda, MD USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, 73 Mt Wayne Ave,Suite 2, Framingham, MA 01702 USA. OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [1U01-HL-66582, K24 HL-04334-01A1, N01-HC-25195] NR 82 TC 114 Z9 117 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 3 PY 2003 VL 138 IS 11 BP 907 EP 916 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 686AB UT WOS:000183296400006 PM 12779301 ER PT J AU Siscovick, DS Lemaitre, RN Mozaffarian, D AF Siscovick, DS Lemaitre, RN Mozaffarian, D TI The fish story - A diet-heart hypothesis with clinical implications: n-3 polyunsaturated fatty acids, myocardial vulnerability, and sudden death SO CIRCULATION LA English DT Editorial Material DE editorials; fish oils; fatty acids, n-3 polyunsaturated; diet; sudden death ID PRIMARY CARDIAC-ARREST; RISK; DISEASE; CONSUMPTION; HEALTH; WOMEN C1 Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Siscovick, DS (reprint author), CHRU, 1730 Minor Ave 1360, Seattle, WA 98101 USA. RI Mozaffarian, Dariush/B-2276-2008 NR 18 TC 44 Z9 45 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 3 PY 2003 VL 107 IS 21 BP 2632 EP 2634 DI 10.1161/01.CIR.0000074779.11379.62 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 685UE UT WOS:000183281000001 PM 12782612 ER PT J AU Cannon, CP Turpie, AGG AF Cannon, CP Turpie, AGG TI Unstable angina and non-ST-elevation myocardial infarction - Initial antithrombotic therapy and early invasive strategy SO CIRCULATION LA English DT Article ID ACUTE CORONARY SYNDROMES; CARDIAC TROPONIN-I; GLYCOPROTEIN IIB/IIIA INHIBITORS; LONG-TERM MORTALITY; TIMI RISK SCORE; ARTERY DISEASE; RANDOMIZED TRIAL; NATRIURETIC PEPTIDE; PROGNOSTIC VALUE; ISCHEMIC EVENTS C1 Brigham & Womens Hosp, Div Cardiovasc, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. McMaster Univ, Hamilton, ON, Canada. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, Dept Med, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. NR 49 TC 13 Z9 15 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 3 PY 2003 VL 107 IS 21 BP 2640 EP 2645 DI 10.1161/01.CIR.0000072246.69344.2D PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 685UE UT WOS:000183281000004 PM 12782615 ER PT J AU Leaf, A Kang, JX Xiao, YF Billman, GE AF Leaf, A Kang, JX Xiao, YF Billman, GE TI Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils SO CIRCULATION LA English DT Review DE fatty acids; arrhythmia; death, sudden; action potentials; antiarrhythmia agents ID SODIUM-CHANNEL INACTIVATION; RAT VENTRICULAR MYOCYTES; MYOCARDIAL-INFARCTION; LONG-CHAIN; EICOSAPENTAENOIC ACID; NA+ CHANNELS; ISCHEMIA; RISK; FIBRILLATION; REPERFUSION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. Ohio State Univ, Dept Physiol & Cell Biol, Columbus, OH 43210 USA. RP Leaf, A (reprint author), Bldg 149,13th St, Charlestown, MA 02129 USA. RI Billman, George/E-2758-2011 FU NHLBI NIH HHS [HL62284]; NIDDK NIH HHS [DK38165] NR 38 TC 379 Z9 400 U1 4 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 3 PY 2003 VL 107 IS 21 BP 2646 EP 2652 DI 10.1161/01.CIR.0000069566.78305.33 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 685UE UT WOS:000183281000005 PM 12782616 ER PT J AU Varo, N Vicent, D Libby, P Nuzzo, R Calle-Pascual, AL Bernal, MR Fernandez-Cruz, A Veves, A Jarolim, P Varo, JJ Goldfine, A Horton, E Schonbeck, U AF Varo, N Vicent, D Libby, P Nuzzo, R Calle-Pascual, AL Bernal, MR Fernandez-Cruz, A Veves, A Jarolim, P Varo, JJ Goldfine, A Horton, E Schonbeck, U TI Elevated plasma levels of the atherogenic mediator soluble CD40 ligand in diabetic patients - A novel target of thiazolidinediones SO CIRCULATION LA English DT Article DE atherosclerosis; diabetes mellitus; inflammation; immunology ID GAMMA PPAR-GAMMA; INSULIN-RESISTANCE; METABOLIC SYNDROME; IN-VITRO; ATHEROSCLEROSIS; DISEASE; ASSOCIATION; EXPRESSION; INTERLEUKIN-6; INFLAMMATION AB Background - Considerable evidence implicates the proinflammatory cytokine CD40 ligand (CD40L) in atherosclerosis and accumulating data link type 1 and 2 diabetes, conditions associated with accelerated atherosclerosis, to inflammation. This study therefore evaluated the hypothesis that diabetic patients have elevated plasma levels of soluble CD40L (sCD40L) and that treatment with the insulin-sensitizing thiazolidinediones lowers this index of inflammation. Methods and Results - Subjects with type 1 (n = 49) or type 2 diabetes (n = 48) had higher (P < 0.001) sCD40L plasma levels (6.56 +/- 3.27 and 6.67 +/- 2.90 ng/mL, respectively) compared with age-matched control groups (1.40 +/- 2.21 and 1.32 +/- 2.68 ng/mL, respectively). Multiple regression analysis demonstrated a significant (P < 0.001) association between plasma sCD40L and type 1 as well as type 2 diabetes, independent of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, blood pressure, body mass index, gender, C-reactive protein, and soluble intracellular adhesion molecule-1. Furthermore, in a pilot study, administration of troglitazone ( 12 weeks, 600 mg/day), but not placebo, to type 2 diabetics ( n = 68) significantly (P < 0.001) diminished sCD40L plasma levels by 29%. The thiazolidinedione lowered plasma sCD40L in type 2 diabetic patients with long-standing disease ( >3 years) with or without macrovascular complications (-34% and -29%, respectively) as well as in type 2 diabetic patients with more recent (<3 years) onset of the disease ( -27%; all P < 0.05). Conclusions - This study provides new evidence that individuals with type 1 or 2 diabetes have a proinflammatory state as indicated by elevated levels of plasma sCD40L. Troglitazone treatment of type 2 diabetic patients diminishes sCD40L levels, suggesting a novel antiinflammatory mechanism for limiting diabetes-associated arterial disease. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Hosp Carlos III, Madrid, Spain. Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Navarra, Fac Med, E-31080 Pamplona, Spain. Hosp Univ San Carlos, Madrid, Spain. RP Libby, P (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, 221 Longwood Ave, Boston, MA 02115 USA. RI Bernal-Lopez, Rosa/F-3548-2011; Vicent, David/O-2255-2014 OI Vicent, David/0000-0002-6663-0350 FU NCRR NIH HHS [RR01032]; NHLBI NIH HHS [HL-66086] NR 35 TC 155 Z9 164 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 3 PY 2003 VL 107 IS 21 BP 2664 EP 2669 DI 10.1161/01.CIR.0000074043.46437.44 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 685UE UT WOS:000183281000009 PM 12742991 ER PT J AU Reddy, VY Neuzil, P Taborsky, M Kralovec, S Sediva, L Ruskin, JN AF Reddy, VY Neuzil, P Taborsky, M Kralovec, S Sediva, L Ruskin, JN TI Electroanatomic mapping of cardiac resynchronization therapy SO CIRCULATION LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Na Homolce Hosp, Prague, Czech Republic. RP Reddy, VY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 3 PY 2003 VL 107 IS 21 BP 2761 EP 2763 DI 10.1161/01.CIR.0000067884.98471.0A PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 685UE UT WOS:000183281000024 PM 12782617 ER PT J AU Ongur, D Ferry, AT Price, JL AF Ongur, D Ferry, AT Price, JL TI Architectonic subdivision of the human orbital and medial prefrontal cortex SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE orbital and medial prefrontal cortex; prefrontal cortex; human brain; macaque brain ID HUMAN CEREBRAL-CORTEX; PRIMATE ORBITOFRONTAL CORTEX; CALCIUM-BINDING PROTEINS; HUMAN CINGULATE CORTEX; SURFACE-BASED ATLAS; MACAQUE MONKEYS; CORTICAL PROJECTIONS; MOOD DISORDERS; FRONTAL-CORTEX; ACETYLCHOLINESTERASE-RICH AB The structure of the human orbital and medial prefrontal cortex (OMPFC) was investigated using five histological and immunohistochemical stains and was correlated with a previous analysis in macaque monkeys [Carmichael and Price (1994) J. Comp. Neurol. 346:366-402]. A cortical area was recognized if it was distinct with at least two stains and was found in similar locations in different brains. All of the areas recognized in the macaque OMPFC have counterparts in humans. Areas 11, 13, and 14 were subdivided into areas 11m, 111, 13a, 13b, 13m, 131, 14r, and 14c. Within area 10, the region corresponding to area 10m in monkeys was divided into 10m and 10r, and area 10o (orbital) was renamed area 10p (polar). Areas 47/12r, 47/12m, 47/12l, and 47/12s occupy the lateral orbital cortex, corresponding to monkey areas 12r, 12m, 121, and 12o. The agranular insula (areas lam, Iapm, Iai, and Ial) extends onto the caudal orbital surface and into the horizontal ramus of the lateral sulcus. The growth of the frontal pole in humans has pushed area 25 and area 32pl, which corresponds to the prelimbic area 32 in Brodmann's monkey brain map, caudal and ventral to the genu of the corpus callosum. Anterior cingulate areas 24a and 24b also extend ventral to the genu of the corpus callosum. Area 32ac, corresponding to the dorsal anterior cingulate area 32 in Brodmann's human brain map, is anterior and dorsal to the genu. The parallel organization of the OMPFC in monkeys and humans allows experimental data from monkeys to be applied to studies of the human cortex. (C) 2003 Wiley-Liss, Inc. C1 Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. Rush Med Coll, Chicago, IL 60612 USA. Massachusetts Gen Hosp, McLean Hosp, Boston, MA 02114 USA. RP Price, JL (reprint author), Washington Univ, Sch Med, Dept Anat & Neurobiol, Campus Box 8108, St Louis, MO 63110 USA. FU NIDCD NIH HHS [R01 DC00093] NR 77 TC 479 Z9 488 U1 7 U2 33 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 JUN 2 PY 2003 VL 460 IS 3 BP 425 EP 449 DI 10.1002/cne.10609 PG 25 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 672AV UT WOS:000182499100008 PM 12692859 ER PT J AU Betancourt, JR AF Betancourt, JR TI Cross-cultural medical education: Conceptual approaches and frameworks for evaluation SO ACADEMIC MEDICINE LA English DT Article ID PATIENT-PHYSICIAN RELATIONSHIP; HEALTH-CARE; STUDENTS; RACE; SENSITIVITY; COMPETENCE; RECOMMENDATIONS; DISPARITIES; AWARENESS; SCHOOL AB Given that understanding the sociocultural dimensions underlying a patient's health values, beliefs, and behaviors is critical to a successful clinical encounter, crosscultural curricula have been incorporated into undergraduate medical education. The goal of these curricula is to prepare students to care for patients from diverse social and cultural backgrounds, and to recognize and appropriately address racial, cultural, and gender biases in health care delivery. Despite progress in the field of cross-cultural medical education, several challenges exist. Foremost among these is the need to develop strategies to evaluate the impact of these curricular interventions. This article provides conceptual approaches for crosscultural medical education, and describes a framework for student evaluation that focuses on strategies to assess attitudes, knowledge, and skills, and the impact of curricular interventions on health outcomes. C1 Inst Hlth Policy, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Betancourt, JR (reprint author), 50 Staniford St,Suite 942, Boston, MA 02114 USA. NR 41 TC 191 Z9 193 U1 7 U2 20 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUN PY 2003 VL 78 IS 6 BP 560 EP 569 DI 10.1097/00001888-200306000-00004 PG 10 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 711LE UT WOS:000184741400004 PM 12805034 ER PT J AU Chew, LD Watanabe, JM Buchwald, D Lessler, DS AF Chew, LD Watanabe, JM Buchwald, D Lessler, DS TI Junior faculty's perspectives on mentoring SO ACADEMIC MEDICINE LA English DT Article ID ACADEMIC MEDICINE; WOMEN AB The prevalence and characteristics of mentorship among junior faculty in clinician-scientist and clinician-educator tracks were evaluated. Comprehensive improvement strategies are needed. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. RP Chew, LD (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Ctr Excellence, S-152,1660 S Columbian Way, Seattle, WA 98108 USA. NR 3 TC 37 Z9 37 U1 0 U2 5 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUN PY 2003 VL 78 IS 6 BP 652 EP 652 DI 10.1097/00001888-200306000-00022 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 711LE UT WOS:000184741400016 PM 12805052 ER PT J AU Roeber, D Achari, A Takai, T Okumura, Y Scott, DL AF Roeber, D Achari, A Takai, T Okumura, Y Scott, DL TI Crystallization and preliminary X-ray analysis of Der f 2, a potent allergen derived from the house dust mite (Dermatophagoides farinae) SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID HISTAMINE-RELEASING ACTIVITY; MOLECULAR REPLACEMENT; IGE-BINDING; DER-P-2; DER-F-2; MUTATION; F-2 AB Although a number of allergens have been identified and isolated, the underlying molecular basis for the potent immune response is poorly understood. House dust mites (Dermatophagoides sp.) are ubiquitous contributors to atopy in developed countries. The rhinitis, dermatitis and asthma associated with allergic reactions to these arthropods are frequently caused by relatively small (125-129 amino acids) mite proteins of unknown biological function. Der f 2, a major allergen from the mite D. farinae, has been recombinantly expressed, characterized and crystallized. The crystals belong to the tetragonal space group I4(1)22, with unit-cell parameters a = b = 95.2, c = 103.3 Angstrom. An essentially complete ( 97.2%) data set has been collected to 2.4 Angstrom at a synchrotron source. Attempts to solve the crystal structure of Der f 2 by molecular replacement using the NMR coordinates for either Der f 2 or Der p 2 ( the homologous protein from D. pteronyssinus) failed, but preliminary searches using the crystalline Der p 2 atomic coordinates appear to be promising. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. NASA, Struct Biol Lab, MSFC, Huntsville, AL 35812 USA. Asahi Brewery Co Ltd, Biosci Res & Dev Lab, Moriya, Ibaraki, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Struct Biol Ctr, Charlestown, MA 02129 USA. RP Scott, DL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, 149 13th St, Charlestown, MA 02129 USA. RI Takai, Toshiro/K-5690-2013 NR 19 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JUN PY 2003 VL 59 BP 1046 EP 1048 DI 10.1107/S0907444903004438 PN 6 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 681PC UT WOS:000183043700013 PM 12777769 ER PT J AU Fagan, P Eisenberg, M Frazier, L Stoddard, AM Avrunin, JS Sorensen, G AF Fagan, P Eisenberg, M Frazier, L Stoddard, AM Avrunin, JS Sorensen, G TI Employed adolescents and beliefs about self-efficacy to avoid smoking SO ADDICTIVE BEHAVIORS LA English DT Article DE self-efficacy; social influences; smoking; nicotine dependence ID NICOTINE DEPENDENCE; CESSATION; SMOKERS; PROGRAMS; HEALTH AB This paper examines self-efficacy to avoid cigarette smoking and its association with smoking and quitting behavior, peer and worksite influences, nicotine dependence, and socio-dernographic variables among employed adolescents. A cross-sectional survey was used to collect data from employed adolescents ages 15-18 who worked in 10 participating grocery stores in Massachusetts. Eighty-three percent of workers (n = 379), completed the survey. Results from the multivariate model indicate that daily smokers were less confident in their ability to avoid smoking than those who smoked less frequently. As nicotine dependence increased, self-efficacy beliefs decreased. In addition, as friends' encouragement to quit increased, self-efficacy beliefs also increased. Work-related variables were not associated with self-efficacy beliefs among smokers. This study suggests that smoking frequency, nicotine dependence, and friends' encouragement to quit are associated with self-efficacy to avoid smoking. Researchers may tailor interventions for daily and less-than-daily smokers, build on peer networks that encourage quitting and help smokers resist pressures to smoke, and enhance strategies for coping with nicotine dependence. in high-risk situations. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Univ Massachusetts, Amherst, MA 01003 USA. RP Fagan, P (reprint author), NCI, Div Canc Control & Populat Sci, Tobacco Control Res Branch, Execut Plaza N,Room 4042,6130 Ex Blvd,MSC 7337, Bethesda, MD 20892 USA. FU NINR NIH HHS [R01 NR04748] NR 27 TC 21 Z9 23 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JUN PY 2003 VL 28 IS 4 BP 613 EP 626 DI 10.1016/S0306-4603(02)00227-7 PG 14 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 678VX UT WOS:000182888300001 PM 12726779 ER PT J AU Huynh-Hohnbaum, ALT Damron-Rodriguez, J Washington, DL Villa, V Harada, N AF Huynh-Hohnbaum, ALT Damron-Rodriguez, J Washington, DL Villa, V Harada, N TI Exploring the diversity of women veterans' identity to improve the delivery of veterans' health services SO AFFILIA-JOURNAL OF WOMEN AND SOCIAL WORK LA English DT Article DE health care; qualitative research; veteran identity; women veterans ID CARE AB This qualitative study explored the domains of gender, ethnicity, and military association in a population of women veterans as these domains related to the women's access to and use of health care services and assessed barriers to the use of health services and suggestions for improving them. The study found that a significant proportion of the participants had experienced some form of gender discrimination in the military, through segregation or sexual harassment, and that their perceptions of the Veterans Administration health care system were framed by their military, ethnic/racial, and gender experiences. C1 Univ Calif Los Angeles, Sch Publ Policy & Social Res, Dept Social Welf, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, VA Hlth Serv Res & Dev Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Huynh-Hohnbaum, ALT (reprint author), Univ Calif Los Angeles, Sch Publ Policy & Social Res, Dept Social Welf, 3250 Publ Policy Bldg, Los Angeles, CA 90095 USA. NR 13 TC 5 Z9 5 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0886-1099 J9 AFFILIA J WOM SOC WO JI Affil. J. Women Soc. Work PD SUM PY 2003 VL 18 IS 2 BP 165 EP 176 DI 10.1177/0886109903251422 PG 12 WC Social Work; Women's Studies SC Social Work; Women's Studies GA 666FV UT WOS:000182167200006 ER PT J AU Netti, PA Travascio, F Jain, RK AF Netti, PA Travascio, F Jain, RK TI Coupled macromolecular transport and gel mechanics: Poroviscoelastic approach SO AICHE JOURNAL LA English DT Article ID ARTICULAR-CARTILAGE; SOLID TUMORS; DELIVERY; DIFFUSION; TISSUE; COMPRESSION; RELAXATION; CONVECTION; HYDROGELS; MATRICES AB Designing drug delivery devices or drug delivery protocols poses problems because they are considered to operate in a mechanically static environment. It should consider, however, transport processes in these cases occur in a mechanically dynamic environment since mechanical stimuli may strongly influence transport within soft hydrated materials. A general framework combines fluid and macromolecular transport with the mechanics of hydrated polymer gels or tissue. As an example, the model equations have been created for a spherical geometry to describe the distribution of macromolecules within the gel resulting from a constant pressure or a constant flow infusion source. The model describes the overall average profiles of the interstitial fluid pressure, velocity and solid matrix dilatation, displacement, and stress, as well as macromolecular distribution. The basic theory provides new insight into understanding the transport of macromolecules within mechanically stimulated polymeric gets and tissues and, therefore, represents a valuable tool for designing and engineering novel drug delivery systems, as well as optimization of drug delivery protocols to be used in detection and treatments. C1 Univ Naples Federico II, Dept Mat & Prod Engn, I-80125 Naples, Italy. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Univ Naples Federico II, Dept Mat & Prod Engn, I-80125 Naples, Italy. RI Kipke, Daryl/A-2167-2009; OI NETTI, PAOLO/0000-0002-2435-7181 NR 40 TC 27 Z9 27 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-1541 EI 1547-5905 J9 AICHE J JI AICHE J. PD JUN PY 2003 VL 49 IS 6 BP 1580 EP 1596 DI 10.1002/aic.690490621 PG 17 WC Engineering, Chemical SC Engineering GA 691HH UT WOS:000183599700020 ER PT J AU Sandborn, WJ Sands, BE Wolf, DC Valentine, JF Safdi, M Katz, S Isaacs, KL Wruble, LD Katz, J Present, DH Loftus, EV Graeme-Cook, F Odenheimer, DJ Hanauer, SB AF Sandborn, WJ Sands, BE Wolf, DC Valentine, JF Safdi, M Katz, S Isaacs, KL Wruble, LD Katz, J Present, DH Loftus, EV Graeme-Cook, F Odenheimer, DJ Hanauer, SB TI Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis: a randomized, double-blind, placebo-controlled, dose-escalation trial SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID RECOMBINANT HUMAN INTERLEUKIN-10; INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; 5-AMINOSALICYLIC ACID; EFFICACY; MODELS; SAFETY; RATS AB Background: Repifermin (keratinocyte growth factor-2) has been shown to reduce inflammation in animal models of colitis. Aim: To evaluate repifermin for the treatment of active ulcerative colitis. Methods: Eighty-eight patients with active ulcerative colitis were enrolled in a 6-week, double-blind trial. Patients were randomized to receive treatment for five consecutive days with intravenous repifermin at a dose of 1, 5, 10, 25 or 50 mug/kg, or placebo. The primary objective of the study was to evaluate the safety of repifermin. The primary efficacy outcome was clinical remission at week 4, defined as a score of zero on the endoscopic appearance and stool blood components of the Mayo score and a score of zero or unity on the stool frequency and physician's global assessment components. Results: At week 4, the rates of clinical remission in the 1, 5, 10, 25 and 50 mug/kg repifermin groups were 19%, 9%, 0%, 0% and 0%, respectively, and 11% for the placebo group (P = 0.32 for repifermin vs. placebo). The frequencies of commonly occurring adverse events and severe adverse events were similar in both groups. Conclusions: Intravenous repifermin at a dose of 1-50 mug/kg was very well tolerated, but there was no evidence that repifermin was effective for the treatment of active ulcerative colitis at these doses. An additional study to determine the efficacy of repifermin at doses of > 50 mug/kg or for a longer treatment duration may be warranted, as the maximally tolerated dose was not reached in the present study. C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Atlanta Gastroenterol Associates, Atlanta, GA USA. Univ Florida, Gainesville, FL USA. Gainesville Vet Adm Med Ctr, Gainesville, FL USA. Consultants Clin Res, Cincinnati, OH USA. Long Isl Clin Res Associates, Great Neck, NY USA. Univ N Carolina, Chapel Hill, NC USA. Memphis Gastroenterol Grp, Memphis, TN USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Mt Sinai Sch Med, New York, NY USA. Human Genome Sci Inc, Rockville, MD USA. Univ Chicago, Chicago, IL 60637 USA. RP Sandborn, WJ (reprint author), Mayo Clin & Mayo Fdn, 200 1st St SW, Rochester, MN 55905 USA. RI Loftus, Edward/E-8304-2011 NR 19 TC 60 Z9 69 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JUN 1 PY 2003 VL 17 IS 11 BP 1355 EP 1364 DI 10.1046/j.1365-2036.2003.01589.x PG 10 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 685TB UT WOS:000183278400003 PM 12786629 ER PT J AU Stafford, RS AF Stafford, RS TI Feedback intervention to reduce routine electrocardiogram use in primary care SO AMERICAN HEART JOURNAL LA English DT Article ID LABORATORY TESTS; RESTING ELECTROCARDIOGRAM; GUIDELINES; BEHAVIOR; PATTERNS AB Background Although physicians frequently order non-essential diagnostic tests, including screening tests such as electrocardiograms (ECGs), effective strategies for achieving evidence-based test-ordering are not proven. Our objective was to evaluate the impact of a feedback intervention designed to reduce the rate of screening ECG use and its variation. Methods A non-randomized pre-post intervention trial assessed the ordering of ECGs among primary care providers affiliated with Massachusetts General Hospital. Among outpatients visiting providers, those with cardiac diagnoses or symptoms were excluded, as were providers with <120 annual visits. Data were available on 117 providers, 105,682 patients, and 5 1,328 patient visits. During a 9-month intervention, providers received periodic case-mix-adjusted peer-comparisons of their screening ECG use. Two computerized billing systems tracked baseline (December 1996 to March 1998), intervention (April 1998 to December 1998), and post-intervention (January 1999 to September 1999) ECG use. Our outcome measures were: 1) the likelihood of ECG ordering at office visits and 2) provider practice variation, indicated by coefficient of variation and interquartile range. Results ECGs were ordered in 4.6% of visits before the intervention. Provider variation in case-mix adjusted ECG ordering was substantial (coefficient of variation, 101.6%; interquartile range, 3.2% [1.5%-4.7%]). ECG ordering averaged 3.5% during the intervention and 2.8% post-intervention (P < .001). Variation in ECG ordering narrowed considerably (coefficient of variation, 92.5%; interquartile range, 2.0% [1.0%-3.0%]) after the intervention. Multivariate analysis confirmed a persistent impact of the intervention. Conclusions Feedback to primary care providers successfully reduced ECG use and its variation. This approach may be applicable to other physician behaviors that remain contrary to evidence, but are not questioned because peer comparisons are unavailable. C1 Stanford Univ, Stanford Ctr Res Dis Prevent, Palo Alto, CA 94304 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Primary Care Operat Improvement Team,Inst Hlth Po, Boston, MA USA. RP Stafford, RS (reprint author), Stanford Univ, Stanford Ctr Res Dis Prevent, 1000 Welch Rd, Palo Alto, CA 94304 USA. FU NHLBI NIH HHS [K08-HL03548] NR 27 TC 7 Z9 7 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2003 VL 145 IS 6 BP 979 EP 985 DI 10.1016/S0002-8703(03)00107-8 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 690NW UT WOS:000183556100009 PM 12796752 ER PT J AU Kopjar, B Sales, AEB Pineros, SL Sun, HL Li, YF Hedeen, AN AF Kopjar, B Sales, AEB Pineros, SL Sun, HL Li, YF Hedeen, AN TI Comparison of characteristics of patients with coronary heart disease receiving lipid-lowering therapy versus those not receiving such therapy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article C1 Univ Washington, Dept Hlth Serv, Ctr Cost & Outcome Res, Hlth Sci Ctr H688, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Dev Ctr Excellence, Seattle, WA USA. RP Kopjar, B (reprint author), Univ Washington, Dept Hlth Serv, Ctr Cost & Outcome Res, Hlth Sci Ctr H688, Box 357660, Seattle, WA 98195 USA. OI Sales, Anne/0000-0001-9360-3334 NR 2 TC 2 Z9 2 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 2003 VL 91 IS 11 BP 1352 EP 1354 DI 10.1016/S0002-9149(03)00329-1 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 685EE UT WOS:000183247200015 PM 12767433 ER PT J AU Misra, M Soyka, LA Miller, KK Grinspoon, S Levitsky, LL Klibanski, A AF Misra, M Soyka, LA Miller, KK Grinspoon, S Levitsky, LL Klibanski, A TI Regional body composition in adolescents with anorexia nervosa and changes with weight recovery SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE anorexia nervosa; body composition; lean body mass; fat mass; trunk fat; extremity fat; adolescents; eating disorders ID GROWTH-HORMONE SECRETION; FAT DISTRIBUTION; SHORT-TERM; BONE MASS; GH REPLACEMENT; WOMEN; INSULIN; GIRLS; GAIN; PREDICTORS AB Background: Studies of regional fat distribution in adults with anorexia nervosa (AN) have shown decreased extremity fat at baseline and increased trunk fat with weight recovery, resulting in truncal adiposity. Little is known about fat distribution in adolescents with AN, especially with weight recovery. Objective: We sought to determine whether regional fat distribution in adolescents with AN is comparable with that in healthy adolescents and whether weight recovery results in increased trunk fat and truncal adiposity. Design: In 21 adolescent girls with AN and 21 control subjects matched for age and pubertal stage, we measured body-composition variables with dual-energy X-ray absorptiometry at baseline, 6 mo, and 12 mo. Weight recovery was defined as a greater than or equal to 10% increase in body mass index. Results: At baseline, the girls with AN had a lower percentage of trunk fat than did the control subjects, whereas the percentage of extremity fat was not significantly different between the groups. Weight recovery in 13 subjects with AN resulted in an increased percentage of trunk fat and an increased ratio of trunk fat to extremity fat; however, this ratio did not exceed that of control subjects. Conclusions: In adolescents with AN, trunk fat rather than extremity fat is reduced. Weight recovery is associated with increased trunk fat and an increased ratio of trunk fat to extremity fat. In contrast with previous findings in adults, this most likely represents normalization of fat distribution rather than development of truncal adiposity. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA. RP Klibanski, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, BUL 457B,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [DK07703] NR 42 TC 50 Z9 50 U1 0 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2003 VL 77 IS 6 BP 1361 EP 1367 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 682GY UT WOS:000183084400005 PM 12791610 ER PT J AU Sesso, HD Gaziano, JM Liu, S Buring, JE AF Sesso, HD Gaziano, JM Liu, S Buring, JE TI Flavonoid intake and the risk of cardiovascular disease in women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE flavonoids; cardiovascular disease; diet; nutrition; women; primary prevention ID CORONARY HEART-DISEASE; MYOCARDIAL-INFARCTION; TEA CONSUMPTION; DIETARY FLAVONOIDS; ANTIOXIDANT FLAVONOLS; DENSITY-LIPOPROTEIN; CATECHIN CONTENTS; MALE SMOKERS; SOY PROTEIN; HEALTH AB Background: Despite emerging evidence of the role of flavonoids in cardiovascular disease (CVD) prevention, the association remains unclear. Objective: We examined whether flavonoids and selected flavonols and flavones or their food sources are associated with CVD risk. Design: Women (n = 38 445) free of CVD and cancer participated in a prospective study with a mean follow-up of 6.9 y. On the basis of a food-frequency questionnaire, total flavonoids and selected flavonols and flavones were categorized into quintiles, and food sources were categorized into 4 groups. Relative risks were computed for important vascular events (519 events; excluding revascularizations) and CVD (729 events),, including myocardial infarction, stroke, revascularization, and CVD death. Results: The mean flavonoid intake was 24.6 +/- 18.5 mg/d, primarily as quercetin (70.2%). For both CVD and important vascular events, no significant linear trend was observed across quintiles of flavonoid intake (P = 0.63 and 0.80, respectively). No individual flavonol or flavone was associated with CVD. Broccoli and apple consumption were associated with nonsignificant reductions in CVD risk: 25-30% and 13-22%, respectively. A small proportion of women (n = 1185) consuming greater than or equal to4 cups (946 ML) tea/d had a reduction in the risk of important vascular events but with a nonsignificant linear trend (P = 0.07). Conclusions: Flavonoid intake was not strongly associated with a reduced risk of CVD. The nonsignificant inverse associations for broccoli, apples, and tea with CVD were not mediated by flavonoids and warrant further study. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Sesso, HD (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. RI Liu, Simin/I-3689-2014 OI Liu, Simin/0000-0003-2098-3844 FU NCI NIH HHS [CA-47988]; NHLBI NIH HHS [HL-65727, HL-43851]; NIA NIH HHS [AG-15933]; NINDS NIH HHS [NS-34108] NR 48 TC 170 Z9 185 U1 0 U2 19 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2003 VL 77 IS 6 BP 1400 EP 1408 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 682GY UT WOS:000183084400011 PM 12791616 ER PT J AU Oh, WK Kaplan, ID Febbo, P Prisby, J Manola, J Kaufman, DS Kantoff, PW AF Oh, WK Kaplan, ID Febbo, P Prisby, J Manola, J Kaufman, DS Kantoff, PW TI Neoadjuvant doxil chemotherapy prior to androgen ablation plus radiotherapy for high-risk localized prostate cancer - Feasibility and toxicity SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE prostate cancer; chemotherapy; neoadjuvant ID PEGYLATED LIPOSOMAL DOXORUBICIN; RADICAL PROSTATECTOMY; ANTITUMOR-ACTIVITY; CARCINOMA; PHARMACOKINETICS AB Patients with clinical T3 or T4 prostate cancer or with elevated serum prostate-specific antigen (PSA) levels greater than 40 ng/ml are at high risk of failure with primary treatment. Chemotherapy administered at the time of diagnosis may decrease the risk of recurrence. Patients with, high risk localized prostate cancer were treated with two cycles of liposomal doxorubicin (Doxil) at 50 mg/m(2) every 28 days. Patients were assessed for response by digital rectal examination (DRE), PSA, and endorectal magnetic resonance imaging (MRI) (erMRI). Patients were then treated with androgen ablative therapy and prostate radiotherapy. Seven patients were treated. Three patients had 73 disease, and 4 patients had T2b disease with either PSA greater than 40 ng/ml or erMRI evidence of seminal vesicle involvement or extracapsular disease. Median PSA was 29.4 ng/hil. None of the seven patients experienced a significant response, as measured by changes in DRE, PSA, or erMRI. Toxicity was significant, with 4 of 7 patients developing skin toxicity. All seven patients responded to androgen ablative therapy and prostate irradiation. Neoadjuvant liposomal doxorubicin demonstrates no apparent activity and significant toxicity. New strategies are needed to improve outcomes in high-risk prostate cancer. C1 Dana Farber Canc Inst, Dept Adult Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Dept Adult Oncol, Boston, MA USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 17 TC 4 Z9 4 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD JUN PY 2003 VL 26 IS 3 BP 312 EP 316 DI 10.1097/00000421-200306000-00021 PG 5 WC Oncology SC Oncology GA 689RG UT WOS:000183506300021 PM 12796607 ER PT J AU Nasser, SM Faquin, WC Dayal, Y AF Nasser, SM Faquin, WC Dayal, Y TI Expression of androgen, estrogen, and progesterone receptors in salivary gland tumors - Frequent expression of androgen receptor in a subset of malignant salivary gland tumors SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE salivary gland; androgen; progesterone; estrogen; receptors; hormones ID EX-PLEOMORPHIC ADENOMA; DUCT CARCINOMA; CYSTIC CARCINOMA; PAROTID-GLAND; C-ERBB-2; OVEREXPRESSION; ADENOCARCINOMA; PROSTATE; PROTEIN AB The expression of sex hormone receptors in some tumors suggests a role for these receptors in tumor pathogenesis and therapy. Previous studies of the expression of estrogen and progesterone receptors in salivary gland tumors have reported conflicting results. We evaluated the immunohistochemical expression of androgen, estrogen, and progesterone receptors (AR, ER, and PR) in a series of 78 formalin-fixed, paraffin-embedded salivary gland tumors. Immunoreactivity for AR was seen in 14 of 14 carcinoma ex pleomorphic adenomas, 6 of 6 salivary duct carcinomas, and 2 of 2 basal cell adenocarcinomas but in only 2 of 10 acinic cell carcinomas, mucoepidermoid carcinomas, and adenoid cystic carcinomas each. AR expression was distributed evenly between the sexes. ER and PR were expressed in only a few cases of salivary gland tumors. All 26 benign salivary gland tumors were negative for AR, ER, and PR. The uniform expression of AR exclusively in a subset of malignant salivary gland tumors suggests a possible role for AR in the histogenesis and possibly in the clinical management of these malignant salivary gland tumors. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. RP Dayal, Y (reprint author), Tufts Univ, New England Med Ctr Hosp, Dept Pathol, 750 Washington St, Boston, MA 02111 USA. NR 33 TC 84 Z9 87 U1 0 U2 1 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUN PY 2003 VL 119 IS 6 BP 801 EP 806 DI 10.1309/RVTP1G0Q727WJUQD PG 6 WC Pathology SC Pathology GA 683WC UT WOS:000183173200004 PM 12817426 ER PT J AU Freed, LA Acierno, JS Dai, D Leyne, M Marshall, JE Nesta, F Levine, RA Slaugenhaupt, SA AF Freed, LA Acierno, JS Dai, D Leyne, M Marshall, JE Nesta, F Levine, RA Slaugenhaupt, SA TI A locus for autosomal dominant mitral valve prolapse on chromosome 11p15.4 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; MULTILOCUS LINKAGE ANALYSIS; GENERAL-POPULATION; PSEUDOXANTHOMA ELASTICUM; MOLECULAR-GENETICS; CONNECTIVE-TISSUE; CLINICAL-FEATURES; MARFAN-SYNDROME; COLLAGEN GENES; FOLLOW-UP AB Mitral valve prolapse (MVP) is a common cardiovascular abnormality in the United States, occurring in similar to2.4% of the general population. Clinically, patients with MVP exhibit fibromyxomatous changes in one or both of the mitral leaflets that result in superior displacement of the leaflets into the left atrium. Although often clinically benign, MVP can be associated with important accompanying sequelae, including mitral regurgitation, bacterial endocarditis, congestive heart failure, atrial fibrillation, and even sudden death. MVP is genetically heterogeneous and is inherited as an autosomal dominant trait that exhibits both sex- and age-dependant penetrance. In this report, we describe the results of a genome scan and show that a locus for MVP maps to chromosome 11p15.4. Multipoint parametric analysis performed by use of GENEHUNTER gave a maximum LOD score of 3.12 for the chromosomal region immediately surrounding the four-marker haplotype D11S4124-D11S2349-D11S1338-D11S1323, and multipoint nonparametric analysis (NPL) confirms this finding (NPL = 38.59; P = .000397). Haplotype analysis across this region defines a 4.3-cM region between the markers D11S1923 and D11S1331 as the location of a new MVP locus, MMVP2, and confirms the genetic heterogeneity of this disorder. The discovery of genes involved in the pathogenesis of this common disease is crucial to understanding the marked variability in disease expression and mortality seen in MVP. C1 Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Inst Human Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. RP Slaugenhaupt, SA (reprint author), Harvard Inst Med, Room 422,77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NHLBI NIH HHS [K24 HL067434, K24 HL67434, R01 HL038176, R01 HL38176] NR 63 TC 61 Z9 65 U1 3 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 2003 VL 72 IS 6 BP 1551 EP 1559 DI 10.1086/375452 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 685QV UT WOS:000183275500018 PM 12707861 ER PT J AU Makita, Y Moczulski, DK Bochenski, J Smiles, AM Warram, JH Krolewski, AS AF Makita, Y Moczulski, DK Bochenski, J Smiles, AM Warram, JH Krolewski, AS TI Methylenetetrahydrofolate reductase gene polymorphism and susceptibility to diabetic nephropathy in type 1 diabetes SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE diabetic nephropathy; type 1 diabetes; methylenetetrahydrofolate reductase (MTHFR) polymorphism; end-stage renal disease (ESRD); follow-up; mortality ID RISK FACTOR; PLASMA HOMOCYSTEINE; VASCULAR-DISEASE; COMMON MUTATION; HYPERHOMOCYSTEINEMIA; PREVALENCE; MTHFR; MICROALBUMINURIA; OUTCOMES; MELLITUS AB Bagkground The T allele of the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with elevated plasma homocysteine levels, and it has been postulated to be a risk factor for the development of diabetic nephropathy. We examined this hypothesis in both a case-control and a follow-up study in individuals with type 1 diabetes. Methods., In the case-control study, the control group included 310 subjects with normoalbuminuria and diabetes duration of 15 years or greater, and the case group included 88 prevalent cases with end-stage renal disease (ESRD). The follow-up study included 235 subjects with overt proteinuria followed up for 6 years (on average), during which time ESRD developed in 69 subjects. DNA from each individual was genotyped for the C677T MTHFR polymorphism. Results: The frequency of TT homozygotes did not vary significantly among the four groups: 10% in controls, 15% in prevalent cases of ESRD, 13% in cases with new-onset ESRD, and 11% in those who remained proteinuric during follow-up (P = 0.9, 6 df). Similarly, frequency of the T allele varied little among the same groups (range, 33% to 36%; P = 0.9, 3 df) During follow-up, 52 of 323 individuals with diabetic nephropathy died. Total mortality rates were 4.3/100 person-years in TT homozygotes, 2.4/100 person-years in CT heterozygotes, and 3.0/100 person-years in CC homozygotes (P = 0.55, 2 df). Conclusion Using both a large case-control and a follow-up study, we found no evidence that the C677T MTHFR polymorphism has a significant role in the development of diabetic nephropathy in type 1 diabetes. C1 Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. L Warynski Silesian Med Acad, Dept Internal Med Diabetol & Nephrol, Zabrze, Poland. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 41526] NR 30 TC 15 Z9 15 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUN PY 2003 VL 41 IS 6 BP 1189 EP 1194 DI 10.1016/S0272-6386(03)00350-0 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 685JJ UT WOS:000183259000011 PM 12776270 ER PT J AU Kramer, HM Curhan, G Singh, A AF Kramer, HM Curhan, G Singh, A CA HELP Study Grp TI Hemodialysis and estrogen levels in postmenopausal (HELP) patients: The Multicenter HELP study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE hemodialysis (HD); menopause; estrogen ID STAGE RENAL-DISEASE; POST-MENOPAUSAL WOMEN; BONE-MINERAL DENSITY; SERUM SEX-HORMONES; ENDOMETRIAL CANCER; ELDERLY WOMEN; HIP FRACTURE; RISK; ANDROSTENEDIONE; OSTEOPOROSIS AB Background: Low serum estrogen levels are associated with increased risk for hip fractures in healthy Postmenopausal women. Although the rate of hip fractures is 4- to 24-fold greater in postmenopausal hemodialysis-dependent women (PHDW) compared with the general population, no published study has examined the prevalence of low serum estrogen levels or factors associated with low serum estrogen levels in this population. Methods: We measured serum estrone (E-1) and total estradiol (E-2) levels in PHDW and investigated the independent association between serum estrogen levels and demographic and dialysis-related factors. Results: Of 186 PHDW not administered postmenopausal hormones, 44% and 30% had low serum E-1 (<15 pg/mL [55.50 pmol/L]) and total E-2 levels (<5 pg/mL [18.35 pmol/L]) respectively. Serum E-1 and total E-2 levels were significantly lower In Caucasian women compared with non-Caucasian women and in women with a body mass index (BMI) less than 25 kg/m(2) versus 25 kg/m(2) or greater. After adjusting for age, BMI, dialysis vintage, dialysis dose, and history of bilateral oophorectomy, Caucasian race was associated with an increased risk for low serum E-1 (odds ratio [OR], 3.42; 95% confidence interval [CI], 1.63 to 7.19) and total E-2 levels (OR, 2.47; 95% Cl, 1.11 to 5.49) compared with non-Caucasians. In addition, we noted a significant and independent association between BMI and serum estrogen levels. For every 1-kg/m(2) increase in BMI, risk for low serum E-1 and total E-2 levels decreased by 12% (OR, 0.88; 95% Cl, 0.83 to 0.94) and 15% (OR, 0.85; 95% Cl, 0.80 to 0.91), respectively. No significant association was noted between age, dialysis vintage, or dialysis dose and low serum E-1 or total E-2 levels. Conclusion: A substantial number of PHDW have low serum estrogen levels. Caucasian race and low BMI are independently associated with low serum estrogen levels in PHDW, whereas dialysis-related factors are not. C1 Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Loyola Univ, Med Ctr, Dept Prevent Med & Epidemiol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Med, Div Nephrol, Maywood, IL 60153 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. RP Singh, A (reprint author), Brigham & Womens Hosp, Div Renal, 75 Francis St, Boston, MA 02115 USA. NR 27 TC 10 Z9 11 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUN PY 2003 VL 41 IS 6 BP 1240 EP 1246 DI 10.1016/S0272-6386(03)00357-3 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 685JJ UT WOS:000183259000018 PM 12776277 ER PT J AU Asch, DA Jepson, C Hershey, JC Baron, J Ubel, PA AF Asch, DA Jepson, C Hershey, JC Baron, J Ubel, PA TI When money is saved by reducing healthcare costs, where do US primary care physicians think the money goes? SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article AB Background: Physician willingness to reduce medical costs is mixed. Some physicians, might be unwilling to reduce medical costs because they are concerned about where the savings would go. Objective: To determine whether primary care physicians might be less willing to choose a less expensive, less effective cancer screening alternative if they believe that the money saved goes to insurance companies. Design: Anonymous mailed survey. Participants: A total of 865 US primary care physicians. Main Outcome Measures: Responses to one of several clinical vignettes presenting a choice between a less expensive, less effective cancer screening option and a more expensive, more effective alternative and responses to where physicians thought the savings might go if they chose the cheaper alternative. Results: Fifty-three percent of physicians chose the most expensive screening alternative. in aggregate, physicians responded that more of any money saved would go to the managers or owners of insurance companies than to increased clinical services or reduced insurance premiums. Physicians choosing the more expensive screening test were more likely to believe that money saved from choosing the less expensive test would go to insurance company profits and salaries rather than to increased clinical services or reduced premiums (P < .001). Conclusions: Although US primary care physicians vary in where they think money saved in healthcare goes, most believe that more of it goes to the salaries of insurance company executives and the profits of insurance company owners than to improved clinical services or reduced premiums. The more physicians believe that this is where the money goes, the less willing they are to reduce healthcare costs. C1 Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Ann Arbor, MI USA. Univ Michigan, Div Gen Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Program Improving Hlth Care Decis, Ann Arbor, MI 48109 USA. RP Asch, DA (reprint author), Leonard Davis Inst Hlth Econ, 3641 Locust Walk, Philadelphia, PA 19104 USA. FU NCI NIH HHS [R01-CA78052-01] NR 6 TC 5 Z9 5 U1 0 U2 0 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUN PY 2003 VL 9 IS 6 BP 438 EP 442 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 690XC UT WOS:000183574900003 PM 12816173 ER PT J AU Scheid, R Preul, C Gruber, O Wiggins, C von Cramon, DY AF Scheid, R Preul, C Gruber, O Wiggins, C von Cramon, DY TI Diffuse axonal injury associated with chronic traumatic brain injury: Evidence from T2*-weighted gradient-echo imaging at 3 T SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Deutschen-Gesellschaft-fur-Neurologie CY SEP 27, 2002 CL MANNHEIM, GERMANY SP Deutschen Gesellschaft Neurologie ID AMYLOID PRECURSOR PROTEIN; NONMISSILE HEAD-INJURY; CEREBRAL MICROBLEEDS; CORPUS-CALLOSUM; PRACTICAL SCALE; FOCAL LESIONS; MRI EVIDENCE; FIELD MR; HEMORRHAGE; DIAGNOSIS AB BACKGROUND AND PURPOSE: Diffuse axonal injury is frequently accompanied by tissue tear hemorrhages. We examined whether high field strength T2*-weighted gradient-echo imaging performed during the chronic stage of traumatic brain injury may have advantages in the evaluation of diffuse axonal injury as compared with T1- and T2-weighted MR imaging. METHODS: Prospective MR imaging of 66 patients (age range, 17-57 years) was performed using a 3-T system 3 to 292 months (median, 23.5 months) after traumatic brain injury. T1-, T2-, T2*-hypointense and T2-hyperintense foci of 1- to 15-mm diameter were registered in 10 brain regions by two readers separately. Foci that appeared hypointense both on the T1- and T2- and/or on the T2*-weighted images were defined as traumatic microbleeds. RESULTS: For 46 (69.7%) of the patients, T2*-weighted gradient-echo imaging revealed traumatic microbleeds. Hyperintense foci were observed on the T2-weighted images of only 15 (22.7%) patients. T2*-weighted imaging showed significantly more traumatic microbleeds (P = .000) than did T1- and T2-weighted imaging. Interobserver agreement was strong (kappa = 0.79, tau = 0.749, P = .000). For 14 (21.2%) of the patients, T2*-weighted gradient-echo imaging revealed traumatic microbleeds in the corpus callosum, whereas for only two (3%), hyperintense callosal lesions were seen on the T2-weighted images. Although a significant correlation existed between the total amount and callosal appearance of traumatic microbleeds and Glasgow Coma Scale scores (P = .000), no correlation existed with extended Glasgow Outcome Scale scores. CONCLUSION: T2*-weighted gradient-echo imaging at high field strength is a useful tool for the evaluation of diffuse axonal injury during the chronic stage of traumatic brain injury. Diffuse axonal injury-related brain lesions are mainly hemorrhagic. The relevance of diffuse axonal injury for long-term clinical outcome is uncertain. C1 Univ Leipzig, Day Clin Cognit Neurol, D-04103 Leipzig, Germany. Max Planck Inst Cognit Neurosci, Leipzig, Germany. Univ Ulm, Dept Psychiat, Ulm, Germany. Massachusetts Gen Hosp, MGH NMR Ctr, Charlestown, MA USA. RP Scheid, R (reprint author), Univ Leipzig, Day Clin Cognit Neurol, Liebigstr 22A, D-04103 Leipzig, Germany. NR 47 TC 144 Z9 152 U1 0 U2 3 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JUN-JUL PY 2003 VL 24 IS 6 BP 1049 EP 1056 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 691TB UT WOS:000183620600006 PM 12812926 ER PT J AU Lev, MH Romero, JM Goodman, DNF Bagga, R Kim, HYK Clerk, NA Ackerman, RH Gonzalez, RG AF Lev, MH Romero, JM Goodman, DNF Bagga, R Kim, HYK Clerk, NA Ackerman, RH Gonzalez, RG TI Total occlusion versus hairline residual lumen of the internal carotid arteries: Accuracy of single section helical CT angiography SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID GADOLINIUM-ENHANCED MR; MAGNETIC-RESONANCE ANGIOGRAPHY; CONVENTIONAL ANGIOGRAPHY; PSEUDO-OCCLUSION; SPIRAL CT; STRING SIGN; STENOSIS; DISEASE; BIFURCATION; DIAGNOSIS AB BACKGROUND AND PURPOSE: Routine carotid sonography and MR angiography cannot reliably detect the markedly reduced flow velocities associated with very severe carotid stenosis. In this study, we sought to evaluate the accuracy of single row detector helical CT angiography in distinguishing hairline residual lumen from total occlusion of severely stenosed internal carotid arteries (ICAs). METHODS: From our departmental data base of single row detector CT angiography studies performed for evaluation of ICA occlusive disease, 21 cases were identified with evidence of either hairline residual lumen or total occlusion on correlative conventional catheter radiographic arteriograms; these included seven cases of proved hairline residual lumen and 14 cases of proved total occlusion. Two neuroradiologists, blinded to the radiographic arteriography results, graded the diseased ICA on each CT angiogram as definitely occluded, probably occluded, indeterminate, probably patent, or definitely patent: Receiver operating characteristic curves were generated for each neuroradiologist. RESULTS: At an operating point on the receiver operating characteristic curve corresponding to 90% sensitivity, the first reader achieved 95% specificity and the second reader achieved 80% specificity for distinguishing hairline residual lumen from total occlusion. Absolute accuracy rates were 95% and 85%, respectively. No significant difference in accuracy was observed between the two readers (P = .28, two-tailed t test). CONCLUSION: Single row detector CT angiography can distinguish total ICA occlusion from hairline residual lumen with a high degree of accuracy. In equivocal cases, conventional catheter arteriography may be desirable to confirm the diagnosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Univ Chicago, Sch Med, Chicago, IL 60637 USA. RP Lev, MH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Neuroradiol, Boston, MA 02114 USA. NR 36 TC 41 Z9 44 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JUN-JUL PY 2003 VL 24 IS 6 BP 1123 EP 1129 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 691TB UT WOS:000183620600017 PM 12812937 ER PT J AU Guido, R Schiffman, M Solomon, D Burke, L AF Guido, R Schiffman, M Solomon, D Burke, L CA ALTS Grp TI Postcolposcopy management strategies for women referred with low-grade squamous intraepithelial lesions or human papillomavirus DNA-positive atypical squamous cells of undetermined significance: A two-year prospective study SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cervical intraepithelial neoplasia grade 1; cervix; clinical management; colposcopy; cytology; human papillomavirus ID RANDOMIZED TRIAL AB OBJECTIVE: This study was undertaken to compare postcolposcopy management strategies for women referred for low-grade squamous intraepithelial lesions (LSIL) or oncogenic human papillomavirus (HPV) DNA-positive atypical squamous cells of undetermined significance (ASCUS), with cervical intraepithelial neoplasia (CIN) grade 1 or less found at initial colposcopy. STUDY DESIGN: A 2-year prospective follow-up of 1539 women was designed to assess the percentage sensitivity of different postcolposcopy management strategies to detect subsequent CIN grade 2 or 3 and percentage referral to repeat colposcopy. RESULTS: HPV testing at 12 months was sensitive (92.2%) for detection of CIN grade 2 or 3 with a referral rate to repeat colposcopy of 55.0%. Repeat semiannual cytology with referral to colposcopy at an ASCUS threshold demonstrated similar sensitivity (88.0%) but with a higher rate of referral to colposcopy (63.6%). Combining cytology and HPV testing did not increase sensitivity and hurt specificity. Baseline viral load and colposcopic impression were not helpful. CONCLUSION: The most efficient test for identifying women with CIN grade 2 or 3 after colposcopy might be an HPV test alone at 12 months. C1 NCI, Breast & Gynecol Canc Res Grp, Div Canc Prevent, NIH,DHHS, Bethesda, MD USA. NIH, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD 20852 USA. Univ Pittsburgh, Magee Womens Hosp, Hlth Care Syst, Pittsburgh, PA 15260 USA. Beth Israel Deaconess Med Ctr Hosp, Boston, MA USA. RP Solomon, D (reprint author), NCI, Breast & Gynecol Canc Res Grp, Div Canc Prevent, NIH,DHHS, Execut Pl N,Room 2130,6130 Execut Blvd, Rockville, MD 20852 USA. FU NCI NIH HHS [CA-55157, CA-55154, CA-55159, CA-55153, CA-55105, CA-55156, CA-55155, CA-55158] NR 10 TC 117 Z9 121 U1 1 U2 6 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUN PY 2003 VL 188 IS 6 BP 1401 EP 1405 DI 10.1067/mob.2003.456 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 694QC UT WOS:000183784600004 PM 12824969 ER PT J AU Mendes, F Schaumberg, DA Navon, S Steinert, R Sugar, J Holland, EJ Dana, MR AF Mendes, F Schaumberg, DA Navon, S Steinert, R Sugar, J Holland, EJ Dana, MR TI Assessment of visual function after corneal transplantation: The quality of life and psychometric assessment after corneal transplantation (Q-PACT) study SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PSEUDOPHAKIC BULLOUS KERATOPATHY; PENETRATING KERATOPLASTY; VF-14 INDEX; ACUITY; ASTIGMATISM; IMPAIRMENT; GRAFT AB PURPOSE: Many patients with successful corneal grafts have poor vision postoperatively. This study evaluates changes in vision,related quality of life after penetrating keratoplasty (PK). DESIGN: Multicenter prospective cohort study. METHODS: Penetrating keratoplasty candidates from the university-affiliated ophthalmology clinics of four participating centers were enrolled and followed up prospectively. We used the PK-VFQ, a modified version of the Visual Function Index-14, combined with clinical examinations before and at 6 and 12 months after PK. We used multivariate linear regression models to examine predictors of change in PK-VFQ scores. RESULTS: We studied 74 grafts in 71 eyes of 67 patients aged 23 to 91 (mean, 61) years who were followed up for at least 6 months. Indications for surgery included bullous keratopathy (27%), scarring (16%), keratoconus (16%), dystrophies (16%), and regrafts (15%). Median preoperative visual acuity was 20/200 in the graft candidate and 20/30 in the best eye. Median best-corrected postoperative visual acuity in the operated eyes was 20/60 at 6 months. PK-VFQ scores improved at 6 months in 79% by an average of 13.0 points (range, - 16.7 to 67.5). Improvement in PK-VFQ scores was associated with younger age (P =.04), poorer preoperative visual acuity in the best eye (P =.001), and postoperative contact lens use (P =.04) but not with postoperative acuity in the grafted eye (P =.49). Postoperatively, 80% of patients were moderately to very satisfied with their vision, and 97% of patients stated they would have the surgery again. CONCLUSIONS: Improvement in visual function is inversely associated with visual acuity in the better-seeing eye but does not correlate with the postoperative acuity in the grafted eye. Although most keratoplasties are done unilaterally in the setting of good visual acuity in the contralateral eye, for the majority of patients visual function improves after PK. (C) 2003 by Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med,Dept Med, Boston, MA 02114 USA. Carolina Eye Associates, Charlotte, NC USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Ophthalmol Consultants Boston, Boston, MA USA. Univ Illinois, Eye & Ear Infirm, Chicago, IL 60612 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. RP Dana, MR (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA. NR 24 TC 30 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN PY 2003 VL 135 IS 6 BP 785 EP 793 DI 10.1016/S0002-9394(02)02278-X PG 9 WC Ophthalmology SC Ophthalmology GA 686GF UT WOS:000183312500005 PM 12788117 ER PT J AU Dadras, SS Paul, T Bertoncini, J Brown, LF Muzikansky, A Jackson, DG Ellwanger, U Garbe, C Mihm, MC Detmar, M AF Dadras, SS Paul, T Bertoncini, J Brown, LF Muzikansky, A Jackson, DG Ellwanger, U Garbe, C Mihm, MC Detmar, M TI Tumor lymphangiogenesis - A novel prognostic indicator for cutaneous melanoma metastasis and survival SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; LYMPH-NODE METASTASIS; MALIGNANT-MELANOMA; FACTOR-C; VEGF-C; ANGIOGENESIS; CANCER; VASCULARITY; EXPRESSION; THICKNESS AB Malignant melanomas of the skin are distinguished by their propensity for early metastatic spread via lymphatic vessels to regional lymph nodes, and lymph node metastasis is a major determinant for the staging and clinical management of melanoma. However, the importance of tumor-induced lymphangiogenesis for lymphatic melanoma spread has remained unclear. We investigated whether tumor lymphangiogenesis occurs in human malignant melanomas of the skin and whether the extent of tumor lymphangiogenesis may be related to the risk for lymph node metastasis and to patient survival, using double immunostains for the novel lymphatic endothelial marker LYVE-1 and for the panvascular marker CD31. Tumor samples were obtained from clinically and histologically closely matched cases of primary melanomas with early lymph node metastasis (n = 18) and from non-metastatic melanomas (n = 19). Hot spots of proliferating intratumoral and peritumoral lymphatic vessels were detected in a large number of melanomas. The incidence of intratumoral lymphatics was significantly higher in metastatic melanomas and correlated with poor disease-free survival. Metastatic melanomas had significantly more and larger tumor-associated lymphatic vessels, and a relative lymphatic vessel area of >1.5% was significantly associated with poor disease-free and overall survival. In contrast, no differences in the density of tumor-associated blood vessels were found. Vascular endothelial growth factor and vascular endothelial growth factor-C expression was equally detected in a minority of cases in both groups. Our results reveal tumor lymphangiogenesis as a novel prognostic indicator for the risk of lymph node metastasis in cutaneous melanoma. (Am J Pathol 2003, 162:1951-1960) C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Dermatol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. John Radcliffe Hosp, Inst Mol Med, Oxford OX3 9DU, England. Univ Tubingen, Sch Med, Dept Dermatol, Tubingen, Germany. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA92644, 5T32CA09216, CA69184, CA86410, P01 CA092644, R01 CA069184, R01 CA086410, T32 CA009216] NR 57 TC 325 Z9 343 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2003 VL 162 IS 6 BP 1951 EP 1960 DI 10.1016/S0002-9440(10)64328-3 PG 10 WC Pathology SC Pathology GA 682FM UT WOS:000183081100020 PM 12759251 ER PT J AU Schneeberger, EE AF Schneeberger, EE TI Claudins form ion-selective channels in the paracellular pathway. Focus on "Claudin extracellular domains determine paracellular charge selectively and resistance but not tight junction fibril architecture" SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Editorial Material ID ZONULAE-OCCLUDENTES; MEMBRANE-PROTEIN; EPITHELIAL-CELLS; OCCLUDIN; COMPONENT; STRANDS; PERMEABILITY; BARRIER C1 Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, Charlestown, MA 02129 USA. RP Schneeberger, EE (reprint author), Mol Pathol Unit, Rm 7147,149 13th St, Charlestown, MA 02129 USA. NR 23 TC 11 Z9 11 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUN PY 2003 VL 284 IS 6 BP C1331 EP C1333 DI 10.1152/ajpcell.00037.2003 PG 3 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 675DP UT WOS:000182678000001 PM 12734103 ER PT J AU Egan, JM Meneilly, GS Elahi, D AF Egan, JM Meneilly, GS Elahi, D TI Effects of 1-mo bolus subcutaneous administration of exendin-4 in type 2 diabetes SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulinotropic effect; glucose disposal; glucagon; C-peptide; hemoglobin A(1C) ID GLUCAGON-LIKE PEPTIDE-1; DEPENDENT INSULINOTROPIC POLYPEPTIDE; ENERGY-INTAKE; BETA-CELL; PROMOTES SATIETY; ZUCKER RATS; FOOD-INTAKE; 7-36 AMIDE; IN-VITRO; GLUCOSE AB A gut insulinotropic peptide, glucagon-like peptide-1 (GLP-1), when given continuously subcutaneously, has been shown to be an effective agent to treat type 2 diabetes. Because of inactivation by dipeptidyl peptidase IV ( DPP IV), it has a very short half-life (90-120 s), hence the need for continuous administration. Exendin-4 is an agonist of the GLP-1 receptor. It is not a substrate for DPP IV, and we previously demonstrated that intravenous administration has potent insulinotropic properties in type 2 diabetic volunteers. We evaluated the efficacy of bolus subcutaneous exendin-4 in insulin-naive type 2 diabetic volunteers. Ten patients aged 44-72 yr with mean fasting glucose levels of 11.4 +/- 0.9 mmol/l were enrolled, and daily or twice-daily bolus subcutaneous exendin-4 was self-administered for 1 mo. Glycosylated hemoglobin, multiple daily capillary blood glucose, beta-cell sensitivity to glucose, and peripheral tissue sensitivity to insulin were compared before and after treatment. The greatest decline in capillary blood glucose was seen before bed, with a drop from 15.5 to 9.2 mmol/l (P < 0.0001). Glycosylated hemoglobin improved significantly with treatment, from 9.1 to 8.3% (P = 0.009). β-Cell sensitivity to glucose was improved, as assessed by C-peptide levels during a hyperglycemic clamp. No significant adverse effects were noted or reported. Our data suggest that, even with this short duration of therapy, exendin-4 treatment had a significant effect on glucose homeostasis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Geriatr Res Lab, Boston, MA 02114 USA. Univ British Columbia, Dept Med, Vancouver, BC V6T 2B5, Canada. NIA, Diabet Sect, NIH, Baltimore, MD 21224 USA. RP Elahi, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Geriatr Res Lab, GRB SB 0015,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR-02719] NR 29 TC 60 Z9 63 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN PY 2003 VL 284 IS 6 BP E1072 EP E1079 DI 10.1152/ajpendo.00315.2002 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 675NA UT WOS:000182700400003 PM 12475750 ER PT J AU Segal-Lieberman, G Trombly, DJ Juthani, V Wang, XM Maratos-Flier, E AF Segal-Lieberman, G Trombly, DJ Juthani, V Wang, XM Maratos-Flier, E TI NPY ablation in C57BL/6 mice leads to mild obesity and to an impaired refeeding response to fasting SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE neuropeptide Y; C57BL/6 background ID MELANIN-CONCENTRATING HORMONE; RECEPTOR-DEFICIENT MICE; NEUROPEPTIDE-Y; FEEDING-BEHAVIOR; ENERGY HOMEOSTASIS; FOOD-INTAKE; MELANOCORTIN-4 RECEPTOR; PARAVENTRICULAR NUCLEUS; RATS MIMICS; BODY-WEIGHT AB Neuropeptide Y (NPY) is an orexigenic (appetite-stimulating) peptide that plays an important role in regulating energy balance. When administered directly into the central nervous system, animals exhibit an immediate increase in feeding behavior, and repetitive injections or chronic infusions lead to obesity. Surprisingly, initial studies of Npy(-/-) mice on a mixed genetic background did not reveal deficits in energy balance, with the exception of an attenuation in obesity seen in ob/ob mice in which the NPY gene was also deleted. Here, we show that, on a C57BL/6 background, NPY ablation is associated with an increase in body weight and adiposity and a significant defect in refeeding after a fast. This impaired refeeding response in Npy(-/-) mice resulted in a deficit in weight gain in these animals after 24 h of refeeding. These data indicate that genetic background must be taken into account when the biological role of NPY is evaluated. When examined on a C57BL/6 background, NPY is important for the normal refeeding response after starvation, and its absence promotes mild obesity. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Maratos-Flier, E (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-56113, R01 DK-53978, R01 DK-56116] NR 44 TC 50 Z9 54 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN PY 2003 VL 284 IS 6 BP E1131 EP E1139 DI 10.1152/ajpendo.00491.2002 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 675NA UT WOS:000182700400011 PM 12582011 ER PT J AU Bruder, ED Ball, DL Goodfriend, TL Raff, H AF Bruder, ED Ball, DL Goodfriend, TL Raff, H TI An oxidized metabolite of linoleic acid stimulates corticosterone production by rat adrenal cells SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE steroidogenesis; glucocorticoid; fatty acid; zona fasciculata; epoxide ID INDUCED INSULIN-RESISTANCE; ACUTE REGULATORY PROTEIN; STAR PROTEIN; IN-VITRO; KINASE-C; ALDOSTERONE; STEROIDOGENESIS; ACTIVATION; ACTH; INVOLVEMENT AB Oxidized derivatives of linoleic acid have the potential to alter steroidogenesis. One such derivative is 12,13-epoxy-9-keto-10-( trans)-octadecenoic acid (EKODE). To evaluate the effect of EKODE on corticosterone production, dispersed rat zona fasciculata/reticularis ( subcapsular) cells were incubated for 2 h with EKODE alone or together with rat ACTH ( 0, 0.2, or 2.0 ng/ml). In the absence of ACTH, EKODE ( 26 muM) increased corticosterone production from 5.3 +/- 2.3 to 14.7 +/- 5.0 ng . 10(6) cells . h(-1). The stimulatory effect of ACTH was increased threefold in the presence of EKODE (26.0 muM). Cholesterol transport/P-450scc activity was assessed by measuring basal and cAMP-stimulated pregnenolone production in the presence of cyanoketone (1.1 muM). EKODE (13.1 and 26.0 muM) significantly increased basal and cAMP-stimulated (0.1 mM) pregnenolone production. In contrast, EKODE decreased the effect of 1.0 mM cAMP. EKODE had no effect on early or late-pathway activity in isolated mitochondria. We conclude that EKODE stimulates corticosterone biosynthesis and amplifies the effect of ACTH. Increased levels of fatty acid metabolites may be involved in the increased glucocorticoid production observed in obese humans. C1 St Lukes Hosp, Endocrine Res Lab, Milwaukee, WI 53215 USA. William S Middleton Mem Vet Adm Med Ctr, Dept Med, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Dept Pharmacol, Madison, WI 53705 USA. Univ Wisconsin, Madison, WI 53705 USA. Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. RP Raff, H (reprint author), Endocrinol & Metab, St Lukes Phys Off Bldg,2801 W KK River Pkwy,Suite, Milwaukee, WI 53215 USA. FU NIDDK NIH HHS [DK-54685] NR 30 TC 10 Z9 10 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JUN PY 2003 VL 284 IS 6 BP R1631 EP R1635 DI 10.1152/ajpregu.00753.2002 PG 5 WC Physiology SC Physiology GA 675MW UT WOS:000182700000037 PM 12689852 ER PT J AU Thongboonkerd V Klein, JB Pierce, WM Jevans, AW Arthur, JM AF Thongboonkerd, V Klein, JB Pierce, WM Jevans, AW Arthur, JM TI Sodium loading changes urinary protein excretion: a proteomic analysis SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE urine; tubular transport ID 2-DIMENSIONAL ELECTROPHORESIS; RENAL-CORTEX; HIGH-SALT; EXPRESSION; RATS; AQUAPORIN-2; MEDULLA AB Plasma sodium concentration is maintained even when sodium intake is altered. Sodium homeostasis may involve changes in renal tubular protein expression that are reflected in the urine. We used proteomic analysis to investigate changes in urinary protein excretion in response to acute sodium loading. Rats were given deionized water followed by hypertonic (2.7%) saline for 28 h each. Urinary protein expression was determined during the final 4 h of each treatment. Acute sodium loading increased urinary sodium excretion (4.53 +/- 1.74 vs. 1.70 +/- 0.27 mmol/day, P = 0.029). Urinary proteins were separated by two-dimensional PAGE and visualized by Sypro ruby staining. Differentially expressed proteins were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry followed by peptide mass fingerprinting. The abundance of a total of 45 protein components was changed after acute sodium loading. Neutral endopeptidase, solute carrier family 3, meprin 1alpha, diphor-1, chaperone heat shock protein 72, vacuolar H(+)-ATPase, ezrin, ezrin/radixin/moesin-binding protein, glutamine synthetase, guanine nucleotide-binding protein, Rho GDI-1, and chloride intracellular channel protein 1 were decreased, whereas albumin and alpha-2u globulin were increased. Some of these proteins have previously been shown to be associated with tubular transport. These data indicate that alterations in the excretion of several urinary proteins occur during acute sodium loading. C1 Univ Louisville, Dept Med, Kidney Dis Program, Core Proteom Lab, Louisville, KY 40202 USA. Univ Louisville, Dept Biochem & Mol Biol, Louisville, KY 40202 USA. Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40202 USA. Vet Affairs Med Ctr, Louisville, KY 40202 USA. Jewish Hosp, Dept Pathol, Louisville, KY 40202 USA. Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Thongboonkerd V (reprint author), Univ Louisville, Dept Med, Kidney Dis Program, Core Proteom Lab, 570 S Preston St,Suite 102, Louisville, KY 40202 USA. EM visith.thongboonkerd@louisville.edu RI THONGBOONKERD, VISITH /C-6920-2009; Klein, Jon/B-9833-2013 FU NHLBI NIH HHS [R01-HL-66358-01]; NIDDK NIH HHS [21-DK-629686-01] NR 30 TC 29 Z9 32 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUN PY 2003 VL 284 IS 6 BP F1155 EP F1163 DI 10.1152/ajprenal.00140.2002 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 675MY UT WOS:000182700200004 PM 12582004 ER PT J AU Wilhelm, S Deckersbach, T Coffey, BJ Bohne, A Peterson, AL Baer, L AF Wilhelm, S Deckersbach, T Coffey, BJ Bohne, A Peterson, AL Baer, L TI Habit reversal versus supportive psychotherapy for Tourette's disorder: A randomized controlled trial SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT World Congress of Behavioral and Cognitive Therapy CY JUL 17-21, 2001 CL TORONTO, CANADA AB Objective: The authors investigated the efficacy of habit reversal for Tourette's disorder, which is characterized by multiple motor and vocal tics. Method: Thirty-two patients with Tourette's disorder were randomly assigned to 14 sessions of either habit reversal or supportive psychotherapy. Habit reversal consisted of awareness training, self-monitoring, relaxation training, competing response training, and contingency management. Changes in severity of Tourette's disorder and psychosocial impairment were investigated over the course of the 14-session treatment for the 29 patients who completed at least eight treatment sessions. Results: In contrast to the 13 patients in the supportive psychotherapy group, the 16 patients in the habit reversal group improved significantly. The habit reversal patients remained significantly improved over pretreatment at 10-month follow-up. Conclusions: Habit reversal may be an effective behavioral treatment for Tourette's disorder. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. Wilford Hall USAF Med Ctr, Lackland AFB, TX 78236 USA. RP Wilhelm, S (reprint author), Massachusetts Gen Hosp E, OCD Clin, 149 13th St, Charlestown, MA 02129 USA. NR 7 TC 86 Z9 88 U1 3 U2 8 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 2003 VL 160 IS 6 BP 1175 EP 1177 DI 10.1176/appi.ajp.160.6.1175 PG 3 WC Psychiatry SC Psychiatry GA 685BK UT WOS:000183240800024 PM 12777279 ER PT J AU Jackson, DJ Lang, JM Swartz, WH Ganiats, TG Fullerton, J Ecker, J Nguyen, U AF Jackson, DJ Lang, JM Swartz, WH Ganiats, TG Fullerton, J Ecker, J Nguyen, U TI Outcomes, safety, and resource utilization in a collaborative care birth center program compared with traditional physician-based perinatal care SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CLINICAL-DATA SET; RISK DIFFERENCES; REGRESSION; RATIOS AB Objective. We compared outcomes, safety, and resource utilization in a collaborative management birth center model of perinatal care versus traditional physician-based care. Methods. We studied 2957 low-risk, low-income women: 1808 receiving collaborative care and 1149 receiving traditional care. Results. Major antepartum (adjusted risk difference [RD]=-0.5%; 95% confidence interval [Cl]=-2.5, 1.5), intrapartum (adjusted RD=0.8%; 95% Cl =-2.4, 4.0), and neonatal (adjusted RD=-1.8%; 95% Cl=-3.8, 0.1) complications were similar, as were neonatal intensive care unit admissions (adjusted RD=-1.3%; 95%CI=-3.8, 1.1). Collaborative care had a greater number of normal spontaneous vaginal deliveries (adjusted RD = 14.9%; 95% Cl = 11.5, 18.3) and less use of epidural anesthesia (adjusted RD=-35.7%;95%CI=-39.5,-31.8). Conclusions. For low-risk women, both scenarios result in safe outcomes for mothers and babies. However, fewer operative deliveries and medical resources were used in collaborative care. C1 Univ Western Cape, Sch Publ Hlth, ZA-8018 Cape Town, South Africa. BirthPlace Res Dept, San Diego, CA USA. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. Univ Texas El Paso, Sch Nursing, El Paso, TX USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. RP Jackson, DJ (reprint author), Univ Western Cape, Sch Publ Hlth, POB 16239, ZA-8018 Cape Town, South Africa. FU AHRQ HHS [R01-HS07161] NR 26 TC 64 Z9 64 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2003 VL 93 IS 6 BP 999 EP 1006 DI 10.2105/AJPH.93.6.999 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 685ZJ UT WOS:000183294800036 PM 12773368 ER PT J AU Barnewolt, CE Jaramillo, D Taylor, GA Dunning, PS AF Barnewolt, CE Jaramillo, D Taylor, GA Dunning, PS TI Correlation of contrast-enhanced power Doppler sonography and conventional angiography of abduction-induced hip ischemia in piglets SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CONGENITAL DISLOCATION; PAVLIK HARNESS; FEMORAL-HEAD; US; REDUCTION AB OBJECTIVE. The purpose of this study was to determine if enhanced power Doppler sonography can detect early ischemia of the capital femoral epiphysis induced by hip hyper-abduction in piglets and to correlate these findings with angiography. MATERIALS AND METHODS. Proximal femoral perfusion was evaluated in 18 studies of 10 piglet hips with unenhanced power Doppler sonography, enhanced power Doppler sonography with IV contrast agent, and digital angiography, in neutral position, hyperabduction, and after release to neutral position. Enhancement ratios between pixel intensities of power Doppler sonography and enhanced power Doppler images in each position were calculated. Angiograms were analyzed for differences in flow with changes in hip position. RESULTS. With the piglet in neutral position, power Doppler sonography revealed few vessels in the femoral head. Contrast administration resulted in a temporary marked increase in the visualization of vessels in the femoral head. Quantitative enhanced power Doppler sonography revealed a marked decrease in pixel intensity with abduction (p < 0.001) that was not apparent on unenhanced studies (p = 0.28). The enhancement ratio decreased from 0.45 (mean +/- SD, +/- 0.26) in neutral position to 0.10 (+/- 0.21) after abduction; it returned to 0.41 (+/- 0.14) after release of abduction (p < 0.001 for each comparison). Angiographic studies in hyperabduction revealed a variable level of ischemia. CONCLUSION. Enhanced power Doppler sonography can be used to visualize the vascular supply to the cartilaginous femoral head in piglets and can detect reversible ischemia induced by hip hyperabduction. These differences correlate with digital angiographic evidence of ischemia. C1 Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Taylor, GA (reprint author), Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. FU NIAMS NIH HHS [AR 42396-05] NR 21 TC 7 Z9 7 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2003 VL 180 IS 6 BP 1731 EP 1735 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 683LE UT WOS:000183149200040 PM 12760952 ER PT J AU Deshpande, V Rosenberg, AE O'Connell, JX Nielsen, GP AF Deshpande, V Rosenberg, AE O'Connell, JX Nielsen, GP TI Epithelioid angiosarcoma of the bone - A series of 10 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE epithelioid angiosarcoma; bone neoplasms ID SOFT-TISSUE; HEMANGIOENDOTHELIOMA; HEMANGIOMA; MISTAKEN AB The clinical and pathologic features of 10 epithelioid angiosarcomas of bone were analyzed. There were eight males and two females who ranged in age from 26 to 83 years (mean 62 years). Four tumors were solitary and six were multifocal. In two consultation cases, the submitted diagnosis was metastatic carcinoma. Microscopically, the tumor cells were arranged in solid and infiltrative sheets, and in most cases vascular channels or cystically dilated spaces were present. The neoplastic cells had abundant eosinophilic cytoplasm and large nuclei with open chromatin and prominent eosinophilic nucleoli. Intratumoral hemorrhage, neutrophilic infiltrates, and intracytoplasmic lumina were frequently present. All 10 tumors stained positive for one or more endothelial markers, with CD31 being the most sensitive marker. Seven cases stained positive for cytokeratin. Ultrastructural examination in three tumors confirmed their endothelial differentiation. In the absence of obvious vascular differentiation, abundant intratumoral hemorrhage and intratumoral neutrophils are useful ancillary morphologic features that may suggest a vascular origin. Six patients are dead of disease, one is alive with metastasis, and two patients are currently disease free. Epithelioid angiosarcoma of bone should be included in the differential diagnosis of epithelioid neoplasms of bone, and endothelial markers should be a part of their immunohistochemical analysis to avoid the misdiagnosis of a metastatic carcinoma because of the significant differences in the treatment and clinical outcomes of these entities. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Surrey Mem Hosp, Dept Pathol, Surrey, BC, Canada. RP Nielsen, GP (reprint author), Massachusetts Gen Hosp, Dept Pathol Warren 2, 55 Fruit St, Boston, MA 02114 USA. NR 22 TC 42 Z9 47 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUN PY 2003 VL 27 IS 6 BP 709 EP 716 DI 10.1097/00000478-200306000-00001 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 683KW UT WOS:000183148200001 PM 12766574 ER PT J AU Yantiss, RK Odze, RD Farraye, FA Rosenberg, AE AF Yantiss, RK Odze, RD Farraye, FA Rosenberg, AE TI Solitary versus multiple carcinoid tumors of the ileum - A clinical and pathologic review of 68 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 91st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 23-MAR 01, 2002 CL CHICAGO, ILLINOIS SP US & Canadian Acad Pathol DE small intestine; endocrine tumor; carcinoid tumor; multiple; prognosis ID COMPARATIVE GENOMIC HYBRIDIZATION; GASTROINTESTINAL-TRACT; ENDOCRINE TUMORS; NEUROENDOCRINE TUMORS; ALLELIC DELETIONS; ILEAL CARCINOIDS; SMALL-INTESTINE; MANAGEMENT; NEOPLASMS; DUODENUM AB It is well known that small intestinal carcinoid tumors may occur as solitary or multiple lesions. However, the biologic significance of multiple carcinoid tumors has not been clearly defined. The purpose of this study was to compare the clinical and pathologic features and prognosis of patients with solitary versus multiple carcinoid tumors of the ileum. Sixty-eight patients, including 50 with solitary and 18 with multiple carcinoid tumors, were included in the study. Hematoxylin and eosin-stained slides from routinely processed tumor resection specimens of the ileum were evaluated for a variety of histologic features such as tumor size, depth of invasion, tumor stage, and venous, perineural, and lymphovascular invasion. Follow-up and clinical data, such as patient age, gender, presenting complaints, presence of synchronous or metachronous malignancies. and presence of the carcinoid syndrome, were obtained and the results were compared between the two patient groups. Fifty patients with solitary carcinoid tumors (male/female ratio, 27:23) and 18 patients with multiple tumors (male/female ratio, 7: 11) were identified. Patients with multiple carcinoid tumors were significantly younger than patients with solitary tumors at the time of diagnosis (55 years vs 63 years, p = 0.006). There was a high association between multiple carcinoid tumors and the carcinoid syndrome (4 of 18 vs 1 of 50, p = 0.004) as compared with patients with solitary carcinoid tumors. There was also an association between tumor multiplicity and venous invasion, but this relationship was not statistically significant (p = 0.07). The follow-up period was similar for both groups (mean 36 months, median 26 months, range 1-139 months). A significantly higher proportion of patients with multiple carcinoid tumors were either alive with disease or died of disease (56%) compared with those with solitary carcinoid tumors (18%. p = 0.002), and this relationship persisted in multivariate analysis (p = 0.02). Overall, no significant differences were observed between these two patient groups with respect to other clinicopathologic features such as tumor size, depth of invasion, presence of distant metastases, lymphatic or perineural invasion, or presence of an associated malignancy (p >0.05). In conclusion, we found that patients with multiple carcinoid tumors are younger, have a significantly greater risk of developing the carcinoid syndrome, and have a poorer prognosis than patients with solitary tumors. C1 UMass Mem Hlth Care, Dept Pathol, Worcester, MA 01655 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Boston Med Ctr, Gastroenterol Sect, Boston, MA USA. RP Yantiss, RK (reprint author), UMass Mem Hlth Care, Dept Pathol, 55 Lake Ave N, Worcester, MA 01655 USA. NR 32 TC 32 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUN PY 2003 VL 27 IS 6 BP 811 EP 817 DI 10.1097/00000478-200306000-00013 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 683KW UT WOS:000183148200013 PM 12766586 ER PT J AU Racusen, LC Colvin, RB Solez, K Mihatsch, MJ Halloran, PF Campbell, PM Cecka, MJ Cosyns, JP Demetris, AJ Fishbein, MC Fogo, A Furness, P Gibson, IW Glotz, D Hayry, P Hunsickern, LN Kashgarian, M Kerman, R Magil, AJ Montgomery, R Morozumi, K Nickeleit, V Randhawa, P Regele, H Seron, D Seshan, S Sund, S Trpkov, K AF Racusen, LC Colvin, RB Solez, K Mihatsch, MJ Halloran, PF Campbell, PM Cecka, MJ Cosyns, JP Demetris, AJ Fishbein, MC Fogo, A Furness, P Gibson, IW Glotz, D Hayry, P Hunsickern, LN Kashgarian, M Kerman, R Magil, AJ Montgomery, R Morozumi, K Nickeleit, V Randhawa, P Regele, H Seron, D Seshan, S Sund, S Trpkov, K TI Antibody-mediated rejection criteria - an addition to the Banff '97 Classification of Renal Allograft Rejection SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE antibody; Banff; pathology; rejection ID ACUTE HUMORAL REJECTION; CORONARY-ARTERY-DISEASE; PATHOLOGICAL FEATURES; KIDNEY-TRANSPLANTATION; C4D DEPOSITION; RECIPIENTS; BIOPSIES; INJURY AB Antibody-mediated rejection (AbAR) is increasingly recognized in the renal allograft population, and successful therapeutic regimens have been developed to prevent and treat AbAR, enabling excellent outcomes even in patients highly sensitized to the donor prior to transplant. It has become critical to develop standardized criteria for the pathological diagnosis of AbAR. This article presents international consensus criteria for and classification of AbAR developed based on discussions held at the Sixth Banff Conference on Allograft Pathology in 2001. This classification represents a working formulation, to be revisited as additional data accumulate in this important area of renal transplantation. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Alberta, Edmonton, AB, Canada. Univ Basel, Basel, Switzerland. Univ Calif Los Angeles, Los Angeles, CA USA. Catholic Univ Louvain, Sch Med, Brussels, Belgium. Univ Pittsburgh, Pittsburgh, PA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Vanderbilt Univ, Nashville, TN USA. Univ Leicester, Leicester, Leics, England. Hlth Sci Ctr, Winnipeg, MB, Canada. Hop Europeen Georges Pompidou, Paris, France. Univ Helsinki, Helsinki, Finland. Univ Iowa, Iowa City, IA USA. Yale Univ, New Haven, CT USA. Univ Texas, Houston, TX USA. St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. Nagoya City Univ, Nagoya, Aichi, Japan. Univ N Carolina, Chapel Hill, NC USA. Univ Vienna, Vienna, Austria. Univ Barcelona, Barcelona, Spain. Cornell Med Ctr, New York, NY USA. Natl Hosp, Oslo, Norway. Rockyview Gen Hosp, Calgary, AB, Canada. RP Racusen, LC (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. RI Halloran, Philip/J-1390-2012 OI Halloran, Philip/0000-0003-1371-1947 NR 25 TC 698 Z9 754 U1 0 U2 4 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2003 VL 3 IS 6 BP 708 EP 714 DI 10.1034/j.1600-6143.2003.00072.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 693NN UT WOS:000183723800011 PM 12780562 ER PT J AU Knechtle, SJ Pirsch, JD Fechner, JH Becker, BN Friedl, A Colvin, RB Lebeck, LK Chin, LT Becker, YT Odorico, JS D'Alessandro, AM Kalayoglu, M Hamawya, MM Hu, HZ Bloom, DD Sollinger, HW AF Knechtle, SJ Pirsch, JD Fechner, JH Becker, BN Friedl, A Colvin, RB Lebeck, LK Chin, LT Becker, YT Odorico, JS D'Alessandro, AM Kalayoglu, M Hamawya, MM Hu, HZ Bloom, DD Sollinger, HW TI Campath-1H induction plus rapamycin monotherapy for renal transplantation: Results of a pilot study SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Campath-1H; depletion; renal transplant ID DONOR BONE-MARROW; DOSE CYCLOSPORINE MONOTHERAPY; ACUTE HUMORAL REJECTION; ALLOGRAFT RECIPIENTS; T-CELL; TOLERANCE; DISEASE; 1H AB Campath-1H, an anti-CD52 monoclonal antibody, was used as induction therapy (40 mg i.v. total dose) in 29 primary human renal transplants, and the patients were maintained on rapamycin monotherapy (levels 8-15 ng/mL) post-transplant. Campath-1H profoundly depletes lymphocytes long-term and more transiently depletes B cells and monocytes. All patients are alive and well at 3-29 months of follow up. One graft was lost because of rejection. There have been no systemic infections and no malignancies. Eight of 29 patients have experienced rejection, which was successfully treated in seven of eight patients. Five of these patients had pathological evidence of a humoral component of their rejection. Seven of the 29 patients were converted to standard triple therapy on account of rejection. Rapamycin was generally well tolerated in that there were no significant wound-healing problems; two lymphoceles required surgical drainage; and most patients were treated with a lipid-lowering agent. Flow crossmatch testing post-transplant revealed evidence of alloantibody in two patients tested with previous combined cellular and humoral rejection. Biopsies have shown no chronic allograft nephropathy to date. In view of the relatively high incidence of early humoral rejection, we plan to modify the immunosuppressive regimen in subsequent pilot studies. This clinical trial provides insight into the use of Campath-1H induction in combination with rapamycin maintenance monotherapy. C1 Univ Wisconsin, Sch Med, Dept Surg, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI USA. Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. RP Knechtle, SJ (reprint author), Univ Wisconsin, Sch Med, Dept Surg, Madison, WI 53706 USA. RI Fechner, John/C-5962-2016 OI Fechner, John/0000-0002-8220-7237 FU NIAID NIH HHS [R01 AI50938] NR 15 TC 267 Z9 276 U1 0 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2003 VL 3 IS 6 BP 722 EP 730 DI 10.1034/j.1600-6143.2003.00120.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 693NN UT WOS:000183723800013 PM 12780564 ER PT J AU Shin, JJ Hartnick, CJ AF Shin, JJ Hartnick, CJ TI Pediatric endoscopic transnasal adenoid ablation SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE adenoidectomy; endoscopy; suction diathermy ID SURGERY; OBSTRUCTION AB We describe a technique in which suction diathermy is used for adenoid ablation through a solely endoscopic transnasal approach in the older pediatric population. This procedure has proved to be both effective and convenient during other transnasal endoscopic procedures, as it provides excellent visualization of both the superior and inferior parts of the nasopharynx and results in minimal to no bleeding in the adenoid bed. In all cases to date, there has been complete resolution of preoperative problems of infection, pain, and bleeding. All patients had good control of postoperative pain. There has been no evidence of postoperative nasopharyngeal stenosis and no velopharyngeal insufficiency. Although transnasal adenoid ablation is not appropriate for the entire pediatric population, this procedure has multiple benefits when another endoscopic sinonasal procedure is planned, when there is neck instability, or when enhanced visualization of the nasopharynx is desired. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. RI Shin, Jennifer/A-3169-2016 NR 17 TC 13 Z9 17 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JUN PY 2003 VL 112 IS 6 BP 511 EP 514 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 689MR UT WOS:000183497600005 PM 12834118 ER PT J AU May, JW AF May, JW TI Aesthetic surgery 101: Resident education in aesthetic surgery, the MGH experience SO ANNALS OF PLASTIC SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP May, JW (reprint author), Massachusetts Gen Hosp, Suite 453,15 Parkman St, Boston, MA 02114 USA. NR 8 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD JUN PY 2003 VL 50 IS 6 BP 561 EP 566 DI 10.1097/01.SAP.0000069074.93280.78 PG 6 WC Surgery SC Surgery GA 687BW UT WOS:000183356800001 PM 12782999 ER PT J AU Hilgenberg, AD AF Hilgenberg, AD TI Fate of coronary ostial anastomoses after the modified Bentall procedure - Invited commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. RP Hilgenberg, AD (reprint author), Massachusetts Gen Hosp, Dept Thorac Surg, 55 Fruit St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 2003 VL 75 IS 6 BP 1802 EP 1802 AR PII S0003-4975(03)00354-0 DI 10.1016/S0003-4975(03)00354-0 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 686FU UT WOS:000183311400026 ER PT J AU Schwaber, MJ Graham, CS Sands, BE Gold, HS Carmeli, Y AF Schwaber, MJ Graham, CS Sands, BE Gold, HS Carmeli, Y TI Treatment with a broad-spectrum cephalosporin versus piperacillin-tazobactam and the risk for isolation of broad-spectrum cephalosporin-resistant Enterobacter species SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIBIOTIC-RESISTANCE; ECONOMIC OUTCOMES; EMERGENCE; HEALTH AB Receipt of a broad-spectrum cephalosporin is a strong risk factor for isolation of broad-spectrum cephalosporin-resistant Enterobacter species, and yet the risk from other broad-spectrum beta-lactams hydrolyzed by group 1 beta-lactamases has not been well characterized. We compared the risk conferred by broad-spectrum cephalosporins to that conferred by piperacillin-tazobactam, alone or in combination with an aminoglycoside or a fluoroquinolone. A retrospective cohort was monitored from treatment onset until a broad-spectrum cephalosporin-resistant Enterobacter strain was isolated or the patient was discharged. There were 447 patients in the piperacillin-tazobactam group and 2,341 patients in the broad-spectrum cephalosporin group. Groups were similar in age (mean, 62.5 years). The piperacillin-tazobactam group had a smaller percentage of men (32% versus 44%, P < 0.001) and a lower rate of intensive care unit stay (25% versus 38%, P < 0.001) but a higher rate of surgery (41% versus 26%, P < 0.001). Groups differed in the distribution of comorbidities. Resistant Enterobacter strains were isolated from 62 patients, 2% in each group (hazard ratio [RR] = 1.02 [P = 0.95]). In multivariable analysis, risk was similar among treatment groups (RR = 0.71 [P = 0.32]). Intensive care unit stay and surgery were associated with increased risk (RR = 4.53 [P < 0.001] and RR = 1.97 [P = 0.015], respectively), fluoroquinolones were protective (RR = 0.24 [P = 0.003]), and aminoglycosides did not affect risk (RR = 0.98 [P = 0.95]). The protective effect of fluoroquinolones against isolation of broad-spectrum cephalosporin-resistant Enterobacter spp. and the equivalence in risk associated with piperacillin-tazobactam and broad-spectrum cephalosporins may have important clinical and epidemiologic implications. C1 Tel Aviv Sourasky Med Ctr, Epidemiol Unit, IL-64239 Tel Aviv, Israel. Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schwaber, MJ (reprint author), Tel Aviv Sourasky Med Ctr, Epidemiol Unit, 6 Weizmann St, IL-64239 Tel Aviv, Israel. FU ODCDC CDC HHS [TO1/CCU111438] NR 13 TC 30 Z9 31 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 2003 VL 47 IS 6 BP 1882 EP 1886 DI 10.1128/AAC.47.6.1882-1886.2003 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 684BD UT WOS:000183184800015 PM 12760862 ER PT J AU Kukoski, R Blonigen, B Macri, E Renshaw, AA Hoffman, M Loda, M Datta, MW AF Kukoski, R Blonigen, B Macri, E Renshaw, AA Hoffman, M Loda, M Datta, MW TI p27 and cyclin E/D2 associations in testicular germ cell tumors - Implications for tumorigenesis SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY LA English DT Article DE testis; germ cell tumor; cyclins; p27; cell cycle ID IN-SITU HYBRIDIZATION; DEPENDENT KINASE; INHIBITOR P27; BREAST-CANCER; EXPRESSION; TESTIS; OVEREXPRESSION; P27(KIP1); CHROMOSOME-12; I(12P) AB The cyclins are key regulators of cell cycle progression and cellular proliferation. We have previously shown that in testicular germ cell tumors, cyclin E expression correlates with more aggressive tumors, higher clinical stage, and the presence of pulmonary metastases. Here, we have examined the association between cyclin activation and the proliferative rate of the pluripotential testicular tumor cell. We have shown that in a panel of 30 testicular germ cell tumors, 15 cases (50%) expressed the cyclin dependent kinase inhibitor p27; of note, 13 of 14 embryonal carcinomas (93%) coexpressed cyclin E and p27, suggesting inhibition of this cyclin. We show that 25 of 30 (83%) of the testicular germ cell tumors express cyclin D2. Using immunoprecipitation assays from the embryonal carcinoma cell line NTera2 or from tumor cell extracts, we have shown that cyclin D2 is complexed with p27, consistent with its known ability to sequester and block the cyclin E inhibitory function of p27. From these results, we propose a model in testicular germ cell tumors, in particular embryonal carcinomas, whereby the overexpression of cyclin D2, a gene localized on chromosome 12p-a region of DNA amplification in germ cell tumors-leads to the functional sequestration of p27 in the presence of cyclin E and cyclin D2, thus favoring cellular proliferation. C1 Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. Baptist Hosp Miami, Dept Pathol, Miami, FL USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Tumor Biol, Boston, MA 02115 USA. RP Datta, MW (reprint author), Med Coll Wisconsin, Dept Pathol, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. NR 38 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-3345 J9 APPL IMMUNOHISTO M M JI Appl. Immunohistochem. PD JUN PY 2003 VL 11 IS 2 BP 138 EP 143 PG 6 WC Anatomy & Morphology; Medical Laboratory Technology; Pathology SC Anatomy & Morphology; Medical Laboratory Technology; Pathology GA 687FX UT WOS:000183366700008 PM 12777997 ER PT J AU Hebden, JC Boas, DA George, JS Durkin, AJ AF Hebden, JC Boas, DA George, JS Durkin, AJ TI Topics in biomedical optics: Introduction SO APPLIED OPTICS LA English DT Editorial Material AB The field of biomedical optics is experiencing tremendous growth. Biomedical technologies contribute in the creation of devices used in healthcare of various specialties (ophthalmology, cardiology, anesthesiology, and immunology, etc.). Recent research in biomedical optics is discussed. Overviews of meetings held at the 2002 Optical Society of America Biomedical Topical Meetings are presented. (C) 2003 Optical Society of America. C1 UCL, Dept Med Phys, London WC1E 6JA, England. Univ Calif Irvine, Beckman Laser Inst & Med Clin, Irvine, CA 92612 USA. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Massachusetts Gen Hosp, Radiol NMR Ctr, Charlestown, MA 02129 USA. RP UCL, Dept Med Phys, 11-20 Capper St, London WC1E 6JA, England. EM adurkin@laser.bli.uci.edu OI Durkin, Anthony/0000-0001-9124-6388 NR 0 TC 6 Z9 6 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD JUN 1 PY 2003 VL 42 IS 16 BP 2869 EP 2870 DI 10.1364/AO.42.002869 PG 2 WC Optics SC Optics GA 685HL UT WOS:000183256600001 ER PT J AU Fabbri, F Franceschini, MA Fantini, S AF Fabbri, F Franceschini, MA Fantini, S TI Characterization of spatial and temporal variations in the optical properties of tissuelike media with diffuse reflectance imaging SO APPLIED OPTICS LA English DT Article; Proceedings Paper CT Biomedical Topical Meeting of the Optical-Society-of-America CY 2002 CL MIAMI BEACH, FL SP Optl Soc Amer ID FLUORESCENT CONTRAST AGENTS; IN-VIVO; QUANTITATIVE-DETERMINATION; ABSORPTION-COEFFICIENTS; LIGHT-PROPAGATION; TURBID MEDIA; SCATTERING; TUMORS; CORTEX; MODEL AB We describe a method to characterize spatial or temporal changes in the optical properties of turbid media using diffuse reflectance images acquired under broad-beam illumination conditions. We performed experiments on liquid phantoms whose absorption (mu(alpha)) and reduced scattering (mu(S)') coefficients were representative of those of biological tissues in the near infrared. We found that the relative diffuse reflectance R depends on mu(alpha) and mu(S)' only through the ratio and that dependence can be well described with an analytical expression previously reported in the literature [S. L. Jacques, Kluwer Academic Dordrecht (1996)]. We have found that this expression for R deviates from experimental values by no more than 8% for various illumination and detection angles within the range 0degrees-30degrees. Therefore, this analytical expression for R holds with good approximation even if the investigated medium presents curved or irregular surfaces. Using this expression, it is possible to translate spatial or temporal changes in the relative diffuse reflectance from a turbid medium into quantitative estimates of the corresponding changes of ( L/VL)(1/2). In the case of media with optical properties similar to those of tissue in the near infrared, we found that the changes of R/L should occur over a volume approximately 2 mm deep and 4 mm x 4 mm wide to apply this expression. (C) 2003 Optical Society of America. C1 Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA. Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02129 USA. RP Tufts Univ, Dept Biomed Engn, 4 Colby St, Medford, MA 02155 USA. EM francesco.fabbri@tufts.edu FU NIMH NIH HHS [R01 MH062854, R01 MH062854-03, MH-62854, R01 MH062854-02] NR 54 TC 21 Z9 24 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD JUN 1 PY 2003 VL 42 IS 16 BP 3063 EP 3072 DI 10.1364/AO.42.003063 PG 10 WC Optics SC Optics GA 685HL UT WOS:000183256600025 PM 12790458 ER PT J AU Milstein, AB Oh, S Webb, KJ Bouman, CA Zhang, Q Boas, DA Millane, RP AF Milstein, AB Oh, S Webb, KJ Bouman, CA Zhang, Q Boas, DA Millane, RP TI Fluorescence optical diffusion tomography SO APPLIED OPTICS LA English DT Article; Proceedings Paper CT Biomedical Topical Meeting of the Optical-Society-of-America CY 2002 CL MIAMI BEACH, FL SP Optl Soc Amer ID INDOCYANINE GREEN; CONTRAST AGENTS; SCATTERING MEDIA; TUMOR-DETECTION; RECONSTRUCTION; LIFETIME; OPTIMIZATION; CALIBRATION; ALGORITHM; BREAST AB A nonlinear, Bayesian optimization scheme is presented for reconstructing fluorescent yield and lifetime, the absorption coefficient, and the diffusion coefficient in turbid media, such as biological tissue. The method utilizes measurements at both the excitation and the emission wavelengths to reconstruct all unknown parameters. The effectiveness of the reconstruction algorithm is demonstrated by simulation and by application to experimental data from a tissue phantom containing the fluorescent agent Indocyanine Green. (C) 2003 Optical Society of America. C1 Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Univ Canterbury, Dept Elect & Comp Engn, Christchurch, New Zealand. RP Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. EM webb@ecn.purdue.edu NR 46 TC 196 Z9 200 U1 0 U2 9 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD JUN 1 PY 2003 VL 42 IS 16 BP 3081 EP 3094 DI 10.1364/AO.42.003081 PG 14 WC Optics SC Optics GA 685HL UT WOS:000183256600027 PM 12790460 ER PT J AU Barnett, AH Culver, JP Sorensen, AG Dale, A Boas, DA AF Barnett, AH Culver, JP Sorensen, AG Dale, A Boas, DA TI Robust inference of baseline optical properties of the human head with three-dimensional segmentation from magnetic resonance imaging SO APPLIED OPTICS LA English DT Article; Proceedings Paper CT Biomedical Topical Meeting of the Optical-Society-of-America CY 2002 CL MIAMI BEACH, FL SP Optl Soc Amer ID TIME-RESOLVED REFLECTANCE; 2-LAYERED TURBID MEDIA; IN-VIVO; DIFFUSION TOMOGRAPHY; PHOTON MIGRATION; HUMAN BRAIN; HETEROGENEOUS TISSUES; RECONSTRUCTION; SPECTROSCOPY; BREAST AB We model the capability of a small (6-optode) time-resolved diffuse optical tomography (DOT) system to infer baseline absorption and reduced scattering coefficients of the tissues of the human head (scalp, skull, and brain). Our heterogeneous three-dimensional diffusion forward model uses tissue geometry from segmented magnetic resonance (MR) data. Handling the inverse problem by use of Bayesian inference and introducing a realistic noise model, we predict coefficient error bars in terms of detected photon number and assumed model error. We demonstrate the large improvement that a MR-segmented model can provide: 2-10% error in brain coefficients (for 2 x 10(6) photons, 5% model error). We sample from the exact posterior and show robustness to numerical model error. This opens up the possibility of simultaneous DOT and MR for quantitative cortically constrained functional neuroimaging. (C) 2003 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. EM barnett@cims.nyu.edu RI Dale, Anders/A-5180-2010 NR 74 TC 50 Z9 50 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD JUN 1 PY 2003 VL 42 IS 16 BP 3095 EP 3108 DI 10.1364/AO.42.003095 PG 14 WC Optics SC Optics GA 685HL UT WOS:000183256600028 ER PT J AU Kilmer, ME Miller, EL Barbaro, A Boas, D AF Kilmer, ME Miller, EL Barbaro, A Boas, D TI Three-dimensional shape-based imaging of absorption perturbation for diffuse optical tomography SO APPLIED OPTICS LA English DT Article; Proceedings Paper CT Biomedical Topical Meeting of the Optical-Society-of-America CY 2002 CL MIAMI BEACH, FL SP Optl Soc Amer ID RECONSTRUCTION; FRAMEWORK AB We present a shape-based approach to three-dimensional image reconstruction from diffuse optical data. Our approach differs from others in the literature in that we jointly reconstruct object and background characterization and localization simultaneously, rather than sequentially process for optical properties and postprocess for edges. The key to the efficiency and robustness of our algorithm is in the model we propose for the optical properties of the background and anomaly: We use a low-order parameterization of the background and another for the interior of the anomaly, and we use an ellipsoid to describe the boundary of the anomaly. This model has the effect of regularizing the inversion problem and provides a natural means of including additional physical properties if they are known a priori. A Gauss-Newton-type algorithm with line search is implemented to solve the underlying nonlinear least-squares problem and thereby determine the coefficients of the parameterizations and the descriptors of the ellipsoid. Numerical results show the effectiveness of this method. (C) 2003 Optical Society of America. C1 Tufts Univ, Dept Math, Medford, MA 02155 USA. Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. Tufts Univ, Medford, MA 02155 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Tufts Univ, Dept Math, Medford, MA 02155 USA. EM misha.kilmer@tufts.edu RI Miller, Eric/B-2546-2008 OI Miller, Eric/0000-0002-3156-6002 NR 25 TC 41 Z9 42 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD JUN 1 PY 2003 VL 42 IS 16 BP 3129 EP 3144 DI 10.1364/AO.42.003129 PG 16 WC Optics SC Optics GA 685HL UT WOS:000183256600031 PM 12790464 ER PT J AU Stott, JJ Culver, JP Arridge, SR Boas, DA AF Stott, JJ Culver, JP Arridge, SR Boas, DA TI Optode positional calibration in diffuse optical tomography SO APPLIED OPTICS LA English DT Article; Proceedings Paper CT Biomedical Topical Meeting of the Optical-Society-of-America CY 2002 CL MIAMI BEACH, FL SP Optl Soc Amer ID PHOTON DENSITY WAVES; BREAST-TISSUE; SPECTROSCOPY; ABSORPTION; TIME; BRAIN AB Although diffuse optical tomography is a highly promising technique used to noninvasively image blood volume and oxygenation, the reconstructed data are sensitive to systemic differences between the forward model and the actual experimental conditions. In particular, small changes in optode location or in the optode-tissue coupling coefficient significantly degrade the quality of the reconstruction images. Accurate system calibration therefore is an essential part of any experimental protocol. We present a technique for simultaneously calibrating optode positions and reconstructing images that significantly improves image quality, as we demonstrate with simulations and phantom experiments. (C) 2003 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MIT,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. UCL, Dept Comp Sci, London WC1E 6BT, England. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, MIT,Athinoula A Martinos Ctr Biomed Imaging, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM jstott@nmr.mgh.harvard.edu; dboas@nmr.mgh.harvard.edu FU NCI NIH HHS [R01-CA97305] NR 22 TC 22 Z9 22 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD JUN 1 PY 2003 VL 42 IS 16 BP 3154 EP 3162 DI 10.1364/AO.42.003154 PG 9 WC Optics SC Optics GA 685HL UT WOS:000183256600033 PM 12790466 ER PT J AU Taneja, A Trehan, M Taylor, CR AF Taneja, A Trehan, M Taylor, CR TI 308-nm excimer laser for the treatment of psoriasis - Induration-based dosimetry SO ARCHIVES OF DERMATOLOGY LA English DT Article AB Objective: To determine the response of stubborn psoriatic plaques to the 308-nm excimer laser. Design: Controlled study with a before-after design. Setting: A university-based clinical research center. Patients: Adult subjects with recalcitrant plaque psoriasis that have not responded to other therapies for at least 2 months. Interventions: Selected psoriatic plaques were treated with the 308-nm excimer laser. One lesion was left as a control. Each plaque was treated 2 times a week, with an initial dose based solely on the induration component of the modified Psoriasis Area and Severity Index score for that lesion. Subsequent treatments were twice a week with dosage increments up to 50%, based on the change in induration. Four final consolidation doses were given once the induration score was reduced to zero. Results: Eighteen subjects were treated. There were 4 dropouts because of various scheduling problems. In the remaining 14 subjects, 44 plaques received a mean of 10 treatments (range, 4-14). Treatments were quick and well tolerated. The mean cumulative dose was 8.8J/cm(2) (range, 2.2-22.8J/cm(2)). Compared with controls, treated plaques showed significant improvement (P<.001). The only adverse event was a mild sunburn-like reaction in 2 subjects after I treatment. Conclusions: Selective targeting of laser-generated 308-nm excimer radiation with this convenient subblistering dosage schedule based on induration allows for individualized treatment plans for each plaque. Clearing of stubborn psoriatic lesions occurs rapidly and safely. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Gange Photomed Res Ctr, Dept Dermatol, Boston, MA 02114 USA. RP Taylor, CR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Gange Photomed Res Ctr, Dept Dermatol, Bartlett 622,55 Fruit St, Boston, MA 02114 USA. NR 11 TC 27 Z9 28 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUN PY 2003 VL 139 IS 6 BP 759 EP 764 DI 10.1001/archderm.139.6.759 PG 6 WC Dermatology SC Dermatology GA 689EE UT WOS:000183478000009 PM 12810507 ER PT J AU Anderson, RR AF Anderson, RR TI Fire and ice SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Anderson, RR (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 55 Fruit St,MGH BHX 630, Boston, MA 02114 USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUN PY 2003 VL 139 IS 6 BP 787 EP 788 DI 10.1001/archderm.139.6.787 PG 2 WC Dermatology SC Dermatology GA 689EE UT WOS:000183478000013 PM 12810511 ER PT J AU Szanto, K Mulsant, BH Houck, P Dew, MA Reynolds, CF AF Szanto, K Mulsant, BH Houck, P Dew, MA Reynolds, CF TI Occurrence and course of suicidality during short-term treatment of late-life depression SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID PSYCHOLOGICAL AUTOPSY; COMPLETED SUICIDE; ELDERLY PATIENTS; DOUBLE-BLIND; IDEATION; BEHAVIOR; NORTRIPTYLINE; POPULATION; PAROXETINE; INPATIENTS AB Background: Elderly persons (greater than or equal to65 years) have the highest rate of suicide; still, little is known about the occurrence, course, and responsivity of suicidal ideation during treatment of depression in late life and how suicidality affects treatment response. Methods: This study was undertaken to determine (1) how suicidal ideation changes during short-term depression treatment and (2) whether treatment response differs among 3 groups of patients based on their levels of suicidality at baseline and during treatment (those with a recent suicide attempt or current suicidal ideation [high-risk group; n=46], those with recurrent thoughts of death [moderate-risk group; n=143], or those with no suicide attempt, suicidal ideation, or thoughts of death [low-risk group; n=206]). This is a secondary analysis of pooled data from 3 treatment studies of late-life major depression. Participants were 395 elderly persons with a current major depressive episode, treated as inpatients or outpatients under protocolized conditions with paroxetine hydrochloride or nortriptyline hydrochloride, with or without interpersonal psychotherapy. Changes in suicidal ideation over time, rate of responses, and time to response in each group were compared. Results: Suicidal ideation decreased rapidly early in the course of treatment, with more gradual change thereafter. At the beginning of treatment, 77.5% of the patients reported suicidal ideation, thoughts of death, or feelings that life is empty. After 12 weeks of treatment, suicidal ideation had resolved in all treated patients; 4.6% still reported thoughts of death. However, 6-week (P=.001) and 12-week (P=.02) rates of response were significantly lower in high-fisk patients than in low- and moderate-risk patients. High- and moderate-risk patients needed a significantly (P<.001) longer time to respond than low-risk patients (median time to response, 6 and 5 vs; 3 weeks). Conclusions: While suicidal ideation resolves rapidly, the resolution of thoughts about death is more gradual. Suicidal elderly persons with depression require special attention during depression treatment because they have a lower response rate and need a longer. time to respond. C1 VA Pittsburgh Healthcare Syst, Dept Psychiat, Intervent Res Ctr Study Late Life Mood Disorders, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Dept Psychiat, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Mulsant, BH (reprint author), Western Psychiat Inst & Clin, 3811 OHara St,Room E-837, Pittsburgh, PA 15213 USA. RI Szanto, Katalin/B-8389-2014 FU NIA NIH HHS [AG05133]; NIMH NIH HHS [K05 MH00295, MH01613, MH37869, MH43832, MH52247] NR 34 TC 82 Z9 82 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 2003 VL 60 IS 6 BP 610 EP 617 DI 10.1001/archpsyc.60.6.610 PG 8 WC Psychiatry SC Psychiatry GA 688GB UT WOS:000183424900008 PM 12796224 ER PT J AU Seddon, JM Cote, J Davis, N Rosner, B AF Seddon, JM Cote, J Davis, N Rosner, B TI Progression of age-related macular degeneration - Association with body mass index, waist circumference, and waist-hip ratio SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID BEAVER-DAM-EYE; CORONARY HEART-DISEASE; BLUE-MOUNTAINS EYE; RISK-FACTORS; DIETARY-FAT; CARDIOVASCULAR-DISEASE; CLASSIFICATION-SYSTEM; FAMILIAL AGGREGATION; HORMONE REPLACEMENT; CIGARETTE-SMOKING AB Background: Individuals with early or intermediate stages of age-related macular degeneration (AMD) make up a large and growing segment of our elderly population. To advise these high-risk patients regarding preventive measures, we evaluated anthropomorphic, behavioral, and medical factors associated with progression to the advanced stages of AMD associated with visual loss. Methods: The design was a prospective cohort study in a hospital-based retinal practice. The 261 participants were 60 years or older, with some sign of nonadvanced AMD and visual acuity of 20/200 or better in at least 1 eye. The average follow-up time was 4.6 years, and the total person-years of follow-up was 1198. Factors associated with rates of progression to advanced AMD were assessed by the Cox proportional hazards model. Outcome Measures: Progression to geographic atrophy and neovascular disease. Results: Higher body mass index (calculated as weight in kilograms divided by the square of height in meters) increased the risk for progression to the advanced forms of AMD. Relative risk (RR) was 2.35 (95% confidence interval [CI], 1.27-4.34) for a body mass index of at least 30, and 2.32 (95% CI, 1.32-4.07) for a body mass index of 25 to 29, relative to the lowest category, (<25) after controlling for other factors (P=.007 for trend). Higher waist circumference was associated with a 2-fold increased risk for progression (RR for the highest tertile compared with the lowest, 2.04; 95% CI, 1.12-3.72), with a significant trend for increasing risk with a greater waist circumference (P=.02). Higher waist-hip ratio also increased the risk for progression (RR, 1.84; 95% CI, 1.07-3.15) for the highest tertile compared with lowest (P=.02 for trend). More physical activity tended to be associated with a reduced rate of progression (25% reduction for 3 times per week vigorous activity vs none, P=.05 to P=.07). Relative risks for smoking ranged from 1.48 to 1.99, but were not statistically significant. Conclusions: Results provide new information regarding modifiable factors for individuals with the early or intermediate stages of this disease. Overall and abdominal obesity increased the risk for progression to advanced AMD, and more physical activity tended to decrease risk. These preventive measures deserve additional research and greater emphasis. C1 Massachusetts Eye & Ear Infirm, Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Harvard Univ, Sch Med, Dept Med Biostat, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Seddon, JM (reprint author), Massachusetts Eye & Ear Infirm, Epidemiol Unit, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY 11309] NR 54 TC 178 Z9 188 U1 0 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 2003 VL 121 IS 6 BP 785 EP 792 DI 10.1001/archopht.121.6.785 PG 8 WC Ophthalmology SC Ophthalmology GA 687ZY UT WOS:000183408600004 PM 12796248 ER PT J AU Arroyo, JG Michaud, N Jakobiec, FA AF Arroyo, JG Michaud, N Jakobiec, FA TI Choroidal neovascular membranes treated with photodynamic therapy SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID MACULAR DEGENERATION C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Retina Serv, Boston, MA 02114 USA. RP Arroyo, JG (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Retina Serv, 243 Charles St,12th Floor, Boston, MA 02114 USA. FU PHS HHS [K-23] NR 9 TC 11 Z9 12 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 2003 VL 121 IS 6 BP 898 EP 903 DI 10.1001/archopht.121.6.898 PG 6 WC Ophthalmology SC Ophthalmology GA 687ZY UT WOS:000183408600023 PM 12796267 ER PT J AU Kim, SK Andreoli, CM Rizzo, JF Golden, MA Bradbury, MJ AF Kim, SK Andreoli, CM Rizzo, JF Golden, MA Bradbury, MJ TI Optic neuropathy secondary to sub-tenon anesthetic injection in cataract surgery SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID LOCAL-ANESTHESIA C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Rizzo, JF (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 4 TC 18 Z9 18 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 2003 VL 121 IS 6 BP 907 EP 909 DI 10.1001/archopht.121.6.907 PG 3 WC Ophthalmology SC Ophthalmology GA 687ZY UT WOS:000183408600027 PM 12796271 ER PT J AU Bsoul, S Terezhalmy, G Abboud, H Woodruff, K Abboud, SL AF Bsoul, S Terezhalmy, G Abboud, H Woodruff, K Abboud, SL TI PDGF BB and bFGF stimulate DNA synthesis and upregulate CSF-1 and MCP-1 gene expression in dental follicle cells SO ARCHIVES OF ORAL BIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Oral-Medicine CY APR 23-28, 2002 CL FT LAUDERDALE, FLORIDA SP Amer Acad Oral Med DE CFS-1; MCP-1; gene expression; PDGF; bFGF; dental follicle cells ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; TOOTH ERUPTION MOLECULES; IMMEDIATE-EARLY GENE; GROWTH-FACTOR; FACTOR-I; STROMAL CELLS; MESSENGER-RNA; RAT MOLARS; MOUSE; BONE AB CSF-1 and MCP-1, released by dental follicle cells, stimulate the influx of monocytes into the follicle sac and enhance the formation of osteoclasts that, in turn, resorb alveolar bone for the eruption pathway. PDGF and bFGF, released by cells adjacent to the follicle or by activated monocytes, are prime candidates that may regulate CSF-1 and MCP-1 gene expression. The present study demonstrates that PDGF and bFGF are mitogens for dental follicle cells and stimulate CSF-1 and MCP-1 mRNA, but with different time course kinetics. Peak induction of CSF-1 mRNA was observed at 6-8 h, while maximal MCP-1 induction was observed at 2 h. These findings suggest that MCP-1 is an early chemotactic signal for monocytes and that subsequent release of CSF-1 may act synergistically with MCP-1 to enhance monocyte influx. Further understanding of the molecular mechanisms by which cytokines regulate CSF-1 and MCP-1 may lead to more effective treatment regimens for disorders associated with abnormal tooth eruption. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RP Abboud, SL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIAMS NIH HHS [AR42306]; NIDCR NIH HHS [R01 DE015857] NR 34 TC 9 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD JUN PY 2003 VL 48 IS 6 BP 459 EP 465 DI 10.1016/S0003-9969(03)00084-0 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 689CN UT WOS:000183474200007 PM 12749918 ER PT J AU Pulsifer, MB Salorio, CF Niparko, JK AF Pulsifer, MB Salorio, CF Niparko, JK TI Developmental, audiolopaical, and speech perception functioning in children after cochlear implant surgery SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID DEAF-CHILDREN; LANGUAGE-DEVELOPMENT; HEARING IMPAIRMENTS; COMMUNICATION; PERFORMANCE; BEHAVIOR; AGE; ACQUISITION; EXPERIENCE AB Objectives: To examine changes in audiological, speech perception, and developmental functioning subsequent to cochlear implantation in children with severe to profound hearing impairment, and to identify factors related to those changes. Design: Prospective, longitudinal analysis to compare functioning of pediatric patients who underwent cochlear implantation before and I year after surgery. Setting: Outpatient pediatric cochlear implantation program in an academic institution (The Listening Center, The Johns Hopkins University School of Medicine, Baltimore, Md). Patients: Forty consecutive pediatric patients between 11/2 and 9 years of age who received a cochlear implant between April 1, 1996, and August 31, 1998, and who also underwent psychological, audiological, and speech perception evaluations immediately before and 1 year after implantation. Main Outcome Measure: Scores on the Bayley Scales of Infant Development-Second Edition, Stanford-Binet Intelligence Scale-Fourth Edition, Developmental Profile 11, Child Behavior Checklist, speech perception categories, and audiological pure-tone thresholds. Results: Mean (SD) duration of hearing impairment was 37.78 (27.94) months, mean (SD) age at surgery was 50.72 (27.66) months. Significant improvements were found I year after surgery in audiological, speech perception, and developmental functioning, but not in nonverbal intelligence or behavior. Greater benefits in audiological and developmental functioning were associated with younger age (< 48 months) at implantation. Conclusions: Patients showed significant improvement in audiological status, overall developmental functioning, and speech perception skills in a short time after surgery. Greatest improvement in speech perception was for children with the least initial impairment, and greatest developmental gains were associated with young age at implantation. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Otolaryngol, Baltimore, MD 21205 USA. RP Pulsifer, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 5 Emerson Pl,Suite 105, Boston, MA 02114 USA. NR 38 TC 20 Z9 22 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JUN PY 2003 VL 157 IS 6 BP 552 EP 558 DI 10.1001/archpedi.157.6.552 PG 7 WC Pediatrics SC Pediatrics GA 688AB UT WOS:000183408900008 PM 12796235 ER PT J AU zur Wiesch, JS Schmitz, H Borowski, E Borowski, P AF zur Wiesch, JS Schmitz, H Borowski, E Borowski, P TI The proteins of the Hepatitis C virus: Their features and interactions with intracellular protein phosphorylation SO ARCHIVES OF VIROLOGY LA English DT Review ID DEPENDENT RNA-POLYMERASE; INTERNAL RIBOSOME ENTRY; AMINO-ACID-SEQUENCE; CORE GENE-PRODUCTS; NS5A PROTEIN; NONSTRUCTURAL PROTEIN-3; ENVELOPE PROTEIN; NS3 PROTEIN; KINASE-A; NUCLEOSIDE TRIPHOSPHATASE AB Chronic infection with Hepatitis C virus (HCV) often results in cirrhosis and enhances the probability of developing hepatocellular carcinoma (HCC). The underlying mechanisms that lead to malignant transformation of infected cells, however, remain unclear. Observations made with isolated HCV antigens and/or with HCV subgenomic replicon systems demonstrated that the products encoded in the HCV genome interfere with and disturb intracellular signal transduction, often by phosphorylation of cellular proteins. Moreover, some of the HCV-encoded proteins seem to serve as substrates for host cell protein kinases. These phosphorylations affect the biological functions of the antigens. In many cases it could be demonstrated that only short stretches of the linear sequence of the viral or cellular proteins are involved and play a crucial role for these phosphorylation events. The identification of these small polypeptide elements and the subsequent development of strategies to inhibit protein-protein interactions involving them may be the first step towards reducing the chronicity and/or of the carcinogenicity of the virus. This review summarizes current knowledge of intracellular phosphorylation processes that are affected by HCV. C1 Bernhard Nocht Inst Trop Med, Abt Virol, D-20359 Hamburg, Germany. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. RP Borowski, P (reprint author), Bernhard Nocht Inst Trop Med, Abt Virol, Bernhard Nocht Str 74, D-20359 Hamburg, Germany. NR 122 TC 19 Z9 20 U1 0 U2 3 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD JUN PY 2003 VL 148 IS 7 BP 1247 EP 1267 DI 10.1007/s00705-003-0115-8 PG 21 WC Virology SC Virology GA 694MZ UT WOS:000183779500001 ER PT J AU Wolfe, F Michaud, K Gefeller, O Choi, HK AF Wolfe, F Michaud, K Gefeller, O Choi, HK TI Predicting mortality in patients with rheumatoid arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID IMPACT MEASUREMENT SCALES; HEALTH-STATUS; LONG-TERM; QUESTIONNAIRE; DISEASE; METHOTREXATE; DISABILITY; TIME AB Objective. A number of different variables have been proposed as risk factors for mortality in patients with rheumatoid arthritis (RA), but limited prospective information on the magnitude of their effects is available. This study was undertaken to evaluate the relative predictive strength and usefulness of a wide range of variables on the risk of mortality in a large, long-term, prospectively studied cohort of patients with RA. Methods. Over a 20-year period of followup beginning in 1981, 1,387 consecutive RA patients were seen in a single clinic. A wide range of clinical and demographic assessments were recorded and entered into a computer database at the time of each clinical assessment. Assessment of predictive strength included determination of standardized and fourth-versus-first-quartile odds ratios (ORs), goodness-of-fit measures, contributing fraction. Results. The Health Assessment Questionnaire (HAQ) disability index was the strongest clinical predictor of mortality. A 1-SD change in the HAQ resulted in a much larger increase in the odds ratio for mortality compared with a 1-SD change in global disease severity, the next most powerful predictor of mortality (OR 2.31 versus 1.83).. Considering the contributing fraction, mortality would be reduced by 50% for the HAQ and by 33% for global disease severity if patients in the fourth quartile for these variables could be switched to the first quartile. Global disease severity, pain, depression, anxiety, and laboratory and radiographic features were significantly weaker predictors. Disease duration, nodules, and tender joint count were clinical variables that provided very little predictive information. In multivariable analyses, HAQ and other patient self-report measures were significantly better predictors than were radiographic and laboratory variables. A single baseline observation provided the least information, with substantially increasing predictive ability associated with 1-year, 2-year, and all-time point followup observations (time-varying covariates). Conclusion. In this large 20-year study from routine clinical practice, the HAQ was the most powerful predictor of mortality, followed by other patient self-report variables. Laboratory, radiographic, and physical examination data were substantially weaker in predicting mortality. We recommend that clinicians collect patient self-report data, since they produce more useful clinical outcome information than other available clinical measures. C1 Arthrit Res Ctr Fdn, Natl Data Bank Rheumat Dis, Wichita, KS 67214 USA. Univ Kansas, Sch Med, Wichita, KS 67214 USA. Univ Erlangen Nurnberg, D-8520 Erlangen, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wolfe, F (reprint author), Arthrit Res Ctr Fdn, Natl Data Bank Rheumat Dis, 1035 N Emporia,Suite 230, Wichita, KS 67214 USA. OI Michaud, Kaleb/0000-0002-5350-3934; Gefeller, Olaf/0000-0002-8985-7582 NR 43 TC 176 Z9 185 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 2003 VL 48 IS 6 BP 1530 EP 1542 DI 10.1002/art.11024 PG 13 WC Rheumatology SC Rheumatology GA 688AQ UT WOS:000183410300011 PM 12794820 ER PT J AU Sherman, SJ Atri, A Hasselmo, ME Stern, CE Howard, MW AF Sherman, SJ Atri, A Hasselmo, ME Stern, CE Howard, MW TI Scopolamine impairs human recognition memory: Data and modeling SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID RECEIVER-OPERATING CHARACTERISTICS; HUMAN THETA-OSCILLATIONS; DUAL-PROCESS MODEL; LAYER-II NEURONS; ENTORHINAL CORTEX; INTRAVENOUS DIAZEPAM; TASK DEPENDENCE; FREE-RECALL; FAMILIARITY; HYOSCINE AB Eight subjects studied a set of complex visual images after administration of 0.4 mg scopolamine. Another 8 subjects performed the same task without drug administration. On a subsequent item recognition test, subjects rated. on a 5-point scale, their confidence that the studied pictures and an equal number of unstudied lures were actually presented. Results showed that scopolamine affected responses to studied items, but not unstudied lures, demonstrating an unambiguous effect of scopolamine on recognition memory. To describe the scopolamine-injected subjects' data, the authors constructed a new model of 2-process recognition that includes the A. P. Yonelinas (1994) model as a limiting case. The model analysis suggests that scopolamine affected both familiarity and recollection. In particular. scopolamine did not affect the frequency with which recollection took place, but rather. affected the amount of recollected information. C1 Boston Univ, Ctr Mind & Brain, Dept Psychol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stern, CE (reprint author), Boston Univ, Ctr Mind & Brain, Dept Psychol, 2 Cummington St, Boston, MA 02215 USA. RI Howard, Marc/E-2518-2012; OI Atri, Alireza/0000-0003-4405-6973; Hasselmo, Michael/0000-0002-9925-6377; Sherman, Seth/0000-0003-3667-9898 FU NINDS NIH HHS [R01 NS41636] NR 60 TC 53 Z9 54 U1 1 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD JUN PY 2003 VL 117 IS 3 BP 526 EP 539 DI 10.1037/0735-7044.117.3.526 PG 14 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 682CQ UT WOS:000183073600012 PM 12802881 ER PT J AU Hinton, D Hsia, C Um, K Otto, MW AF Hinton, D Hsia, C Um, K Otto, MW TI Anger-associated panic attacks in Cambodian refugees with PTSD; a multiple baseline examination of clinical data SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE anger; stress disorder; post-traumatic; panic; cognition; Cambodia; refugees ID ANXIETY SENSITIVITY; DISORDER; FEAR; PREVALENCE; INSTRUMENT; STRESS AB Despite the increasing recognition of the importance of anger as a key aspect of post-traumatic stress disorder (PTSD), the presence of anger-induced panic attacks has been understudied in traumatized groups. The present investigation determines the prevalence of anger-associated panic attacks among Cambodian refugees suffering from PTSD. Specific characteristics of these episodes that were examined included frequency, symptoms, and cognitions (in particular, fear of death from bodily dysfunction). In a survey of 100 Khmer patients suffering PTSD, 58% reported anger-associated panic attacks in the last month. These attacks occurred at a mean rate of 6.2 attacks a month and were characterized by extreme arousal and in 81% of these cases, fears of death due to bodily dysfunction during the anger-induced panic. Mechanisms for this high rate of fear of death during anger arousal are discussed with a focus on culture-specific catastrophic cognitions. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Revere, MA 02151 USA. Harvard Univ, Sch Med, Revere, MA USA. N Suffolk Mental Hlth Assoc, SE Asian Community Clin, Revere, MA 02151 USA. Arbour Counseling Ctr, Lowell, MA USA. Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. RP Hinton, D (reprint author), Massachusetts Gen Hosp, Revere, MA 02151 USA. NR 29 TC 22 Z9 23 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD JUN PY 2003 VL 41 IS 6 BP 647 EP 654 DI 10.1016/S0005-7967(02)00035-9 PG 8 WC Psychology, Clinical SC Psychology GA 679QB UT WOS:000182932500002 PM 12732373 ER PT J AU Yialamas, MA Hayes, FJ AF Yialamas, MA Hayes, FJ TI Androgens and the ageing male and female SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article DE testosterone; ageing; osteoporosis; sarcopenia; libido; post-menopausal ID DENSITY LIPOPROTEIN CHOLESTEROL; FOLLICLE-STIMULATING-HORMONE; HUMAN CHORIONIC-GONADOTROPIN; CLINICAL RESEARCH-CENTER; OBSTRUCTIVE SLEEP-APNEA; ESTROGEN PLUS PROGESTIN; CORONARY HEART-DISEASE; BONE-MINERAL DENSITY; MIDDLE-AGED MEN; POSTMENOPAUSAL WOMEN AB Androgens play a number of important physiological roles in the human. In the male, testosterone is required for virilization, normal sexual function, and both stimulation and maintenance of bone and muscle mass. Epidemiological studies have shown a progressive decline in testosterone levels with ageing in men. The clinical significance of this decline is still unclear, and there is controversy as to whether a specific syndrome of androgen deficiency or 'andropause' exists. The benefits of testosterone supplementation in this age group have yet to be equivocally established, and long-term safety data on testosterone administration in this setting are lacking. In the female, a decline in testosterone levels with ageing has been less clearly established due, at least in part, to the absence of sensitive assays. Available data suggest that the major role of testosterone replacement after menopause may be in those women who have had an oophorectomy. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Hayes, FJ (reprint author), Massachusetts Gen Hosp, Bartlett Hall Extens 5,55 Fruit St, Boston, MA 02114 USA. NR 88 TC 19 Z9 22 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-690X J9 BEST PRACT RES CL EN JI Best Pract. Res. Clin. Endoc. Metab. PD JUN PY 2003 VL 17 IS 2 BP 223 EP 236 DI 10.1053/ybeem.2003.251 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 692NT UT WOS:000183667700004 PM 12787549 ER PT J AU Ko, CW Lee, SR AF Ko, CW Lee, SR TI Biliary sludge and cholecystitis SO BEST PRACTICE & RESEARCH IN CLINICAL GASTROENTEROLOGY LA English DT Article DE biliary sludge; cholelithiasis; cholecystitis; cholecystectomy ID ACUTE ACALCULOUS CHOLECYSTITIS; POSITIVE-PRESSURE VENTILATION; CHOLESTEROL CRYSTAL-FORMATION; TOTAL PARENTERAL-NUTRITION; BONE-MARROW TRANSPLANT; HIGH-RISK PATIENTS; PERCUTANEOUS CHOLECYSTOSTOMY; GALLSTONE FORMATION; GALLBLADDER SLUDGE; LIPID SECRETION AB Biliary sludge develops commonly in critically ill patients and may be associated with biliary colic, acute pancreatitis or acute cholecystitis. Sludge often resolves upon resolution of the underlying pathogenetic factor. It is generally diagnosed on sonography. Treatment of sludge itself is unnecessary unless further complications develop. Acute acalculous cholecystitis also develops frequently in critically ill patients. It may be difficult to diagnose in these patients, manifesting only as unexplained fever, leukocytosis or sepsis. Sonography and hepatobiliary scintigraphy are the most useful diagnostic tests. Management decisions should take into account the underlying co-morbid conditions. For many patients, percutaneous cholecystostomy may be the best management option. Cholecystostomy may also provide definitive drainage as patients recover and underlying critical illness resolves. C1 Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Ko, CW (reprint author), Univ Washington, Dept Med, Div Gastroenterol, Box 356424, Seattle, WA 98195 USA. NR 74 TC 8 Z9 8 U1 0 U2 1 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6918 J9 BEST PRACT RES CL GA JI Best Pract. Res. Clin. Gastroenterol. PD JUN PY 2003 VL 17 IS 3 BP 383 EP 396 DI 10.1053/ybega.2003.384 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 687VD UT WOS:000183396900006 PM 12763503 ER PT J AU Ramesh, V AF Ramesh, V TI Aspects of tuberous sclerosis complex (TSC) protein function in the brain SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE ezrin/radixin/moeisin (ERM); hamartin; hamartomas; neurofilament light chain (NF-L); tuberin; tuberous sclerosis complex (TSC) ID GROWTH CONE MORPHOLOGY; ALLELIC LOSS; EKER RAT; GENE; HAMARTOMAS; HETEROZYGOSITY; MOTILITY; RADIXIN; KIDNEY; INACTIVATION AB Tuberous sclerosis complex (TSC), an autosomal dominant disease caused by mutations in either TSC1 or TSC2, is characterized by the development of hamartomas in a variety of organs. Concordant with the tumour-suppressor model, loss of heterozygosity (LOH) is known to occur in these hamartomas at both TSC1 and TSC2 loci. LOH has been documented in renal angiomyolipomas, but loss of the wild-type allele in cortical tubers appears very uncommon. we analysed 24 hamartomas from 10 patients for second-hit mutations by several methods, and found no evidence for the inactivation of the second allele in many of the central nervous system (CNS) lesions, including tumours that appear to be clonally derived. We believe that somatic mutations in TSC1 and TSC2 resulting in the loss of wild-type alleles may not be necessary in some tumour types, and other mechanisms may contribute to tumorigenesis in this setting. We have shown that hamartin interacts with neurofilament light chain (NF-L) and could integrate the neuronal cytoskeleton through its direct interaction with NF-L and ERM (ezrin/radixin/moeisin) proteins. Our unpublished work further documents the binding of tuberin with Pam, a protein associated with c-Myc, which is enriched in brain. All these observations suggest that the tuberin-hamartin complex is likely to have distinct functions in the CNS. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Ramesh, V (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS41917, NS24279] NR 24 TC 18 Z9 18 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD JUN PY 2003 VL 31 BP 579 EP 583 DI 10.1042/BST0310579 PN 3 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 691TX UT WOS:000183622500019 PM 12773159 ER PT J AU Biederman, J AF Biederman, J TI Pediatric bipolar disorder coming of age SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID MANIC-DEPRESSIVE ILLNESS; PREPUBERTAL CHILDREN; ADOLESCENTS; SYMPTOMS; ONSET; ADHD; CHILDHOOD; MISTAKEN; BEHAVIOR C1 Harvard Univ, Massachusetts Gen Hosp,Stanley Ctr Treatment Pedi, Sch Med,Clin & Res Program,Pediat Bipolar Disorde, Pediat Psychopharmacol Unit ACC 725,J&J Ctr Pedia, Boston, MA 02114 USA. RP Biederman, J (reprint author), Harvard Univ, Massachusetts Gen Hosp,Stanley Ctr Treatment Pedi, Sch Med,Clin & Res Program,Pediat Bipolar Disorde, Pediat Psychopharmacol Unit ACC 725,J&J Ctr Pedia, 15 Parkman St, Boston, MA 02114 USA. NR 23 TC 14 Z9 15 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2003 VL 53 IS 11 BP 931 EP 934 DI 10.1016/S0006-3223(03)00297-X PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 686UT UT WOS:000183339900001 PM 12788236 ER PT J AU Wozniak, J Monuteaux, M Richards, J Lail, KE Faraone, SV Biederman, J AF Wozniak, J Monuteaux, M Richards, J Lail, KE Faraone, SV Biederman, J TI Convergence between structured diagnostic interviews and clinical assessment on the diagnosis of pediatric-onset mania SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Pediatric Bipolar Disorder CY MAR, 2002 CL BOSTON, MASSACHUSETTS DE structured interview; bipolar disorder; pediatric clinical interview ID DEFICIT HYPERACTIVITY DISORDER; JUVENILE MANIA; CHILD-BEHAVIOR; RATING-SCALE; RELIABILITY; YOUNG; SYMPTOMS; ADHD AB Background: Uncertainties remain as to the utility of structured diagnostic methodology to aid in the diagnosis of manic symptomatology in youth. To this end, this study compared structured diagnostic interview based diagnoses of mania in children and adolescents with that of an expert clinician. Methods: We separately and independently assessed 69 youths recruited for a study of mania in childhood, all but 2 of whom experienced mania, with a structured diagnostic interview administered by trained psychometricians and a clinical assessment by a board-certified child and adolescent psychiatrist (JW) who was blind to the structured interview results. Results: Structured interviews and clinical evaluations converged in all but two cases (67 of 69 or 97% agreement). In one discrepant case, the structured interview diagnosed a full case of mania, but the clinical interview diagnosed cyclothymia/subthreshold mania; in the other discrepant case, the structured interview failed to diagnose mania, but the clinical interview did diagnose mania. Conclusions: In children referred for evaluation of suspected bipolar disorder, a structured interview diagnosis of mania is very likely to be corroborated by a clinical interview. (C) 2003 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Wozniak, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Psychiat Serv, 15 Parkman St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K08 MH 01503] NR 25 TC 35 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2003 VL 53 IS 11 BP 938 EP 944 DI 10.1016/S0006-3223(03)00344-5 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 686UT UT WOS:000183339900003 PM 12788238 ER PT J AU Biederman, J Mick, E Wozniak, J Monuteaux, MC Galdo, M Faraone, SV AF Biederman, J Mick, E Wozniak, J Monuteaux, MC Galdo, M Faraone, SV TI Can a subtype of conduct disorder linked to bipolar disorder be identified? Integration of findings from the Massachusetts General Hospital Pediatric Psychopharmacology Research Program SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Pediatric Bipolar Disorder CY MAR, 2002 CL BOSTON, MASSACHUSETTS DE mania; bipolar disorder; conduct disorder; children ID ATTENTION-DEFICIT HYPERACTIVITY; ADOLESCENT SUBSTANCE-ABUSERS; PROSPECTIVE FOLLOW-UP; LA-TOURETTES SYNDROME; AGGRESSIVE-CHILDREN; DOUBLE-BLIND; PSYCHIATRIC-DISORDERS; GENETIC-RELATIONSHIP; MULTIPLE THRESHOLDS; ADHD CHILDREN C1 Harvard Univ, Pediat Psychopharmacol Unit, Dept Psychiat, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. Massachusetts Gen Hosp, Johnson & Johnson Ctr Pediat Psychopathol, Boston, MA USA. Massachusetts Gen Hosp, Stanley Ctr Pediat Mania, Boston, MA 02114 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. RP Biederman, J (reprint author), Harvard Univ, Pediat Psychopharmacol Unit, Dept Psychiat, Massachusetts Gen Hosp,Med Sch, ACC 725,Fruit St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [R01HD036317, R01HD37694, R01HD37999]; NIMH NIH HHS [R01 MH050657] NR 55 TC 39 Z9 40 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2003 VL 53 IS 11 BP 952 EP 960 DI 10.1016/S0006-3223(03)00009-X PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 686UT UT WOS:000183339900005 PM 12788240 ER PT J AU Faraone, SV Glatt, SJ Tsuang, MT AF Faraone, SV Glatt, SJ Tsuang, MT TI The genetics of pediatric-onset bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Pediatric Bipolar Disorder CY MAR, 2002 CL BOSTON, MASSACHUSETTS DE bipolar disorder; mania; genetics; neurobiology; epidemiology ID DEFICIT HYPERACTIVITY DISORDER; CARDIO-FACIAL SYNDROME; EARLY ADOLESCENT BIPOLARITY; ALZHEIMERS-DISEASE LOCUS; MANIC-DEPRESSIVE ILLNESS; TRINUCLEOTIDE-REPEAT; MOOD DISORDERS; FAMILIAL TRANSMISSION; PSYCHIATRIC-DISORDERS; PREPUBERTAL CHILDREN AB Although bipolar disorder in adults has been extensively studied, early-onset forms of the disorder have received less attention. We review several lines of evidence indicating that pediatric- and early adolescent- onset bipolar disorder cases may prove the most useful for identifying susceptibility genes. Family studies have consistently found a higher rate of bipolar disorder among the relatives of early-onset bipolar disorder patients than in relatives of later-onset cases, which supports the notion of a larger genetic contribution to the early-onset cases. Comorbid pediatric bipolar disorder and attention-deficit/ hyperactivity disorder (ADHD) may also define a familial subtype of ADHD or bipolar disorder that is strongly influenced by genetic factors and may, therefore, be useful in molecular genetic studies. There are no twin and adoption studies of pediatric bipolar disorder, but the heritability of this subtype is expected to be high given the results from family studies. Thus, pediatric- and early adolescent- onset bipolar disorder may represent a genetically loaded and homogeneous subtype of-bipolar disorder, which, if used in genetic linkage and association studies, should increase power to detect risk loci and alleles. (C) 2003 Society of Biological Psychiatry. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Johnson & Johnson Ctr Pediat Psychopathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stanley Ctr Pediat Mania, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Faraone, SV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, WACC 725,15 Parkham St, Boston, MA 02114 USA. OI Glatt, Stephen/0000-0002-0360-7567; Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [R01HD37694]; NIMH NIH HHS [R25 MH60485, R01 MH43518, R01 MH57934, R01MH59624, R01MH60485, R13 MH59126] NR 74 TC 94 Z9 94 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2003 VL 53 IS 11 BP 970 EP 977 DI 10.1016/S0006-3223(02)01893-0 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 686UT UT WOS:000183339900007 PM 12788242 ER PT J AU Hirshfeld-Becker, DR Biederman, J Calltharp, S Rosenbaum, ED Faraone, SV Rosenbaum, JF AF Hirshfeld-Becker, DR Biederman, J Calltharp, S Rosenbaum, ED Faraone, SV Rosenbaum, JF TI Behavioral inhibition and disinhibition as hypothesized precursors to psychopathology: Implications for pediatric bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Pediatric Bipolar Disorder CY MAR, 2002 CL BOSTON, MASSACHUSETTS DE behavioral inhibition; behavioral disinhibition temperament; disruptive behavior disorders; attention-deficit/hyperactivity disorder; pediatric bipolar disorder ID DEFICIT HYPERACTIVITY DISORDER; MACARTHUR LONGITUDINAL TWIN; AGE 3 YEARS; ANXIETY DISORDERS; YOUNG-CHILDREN; NOVELTY SEEKING; PANIC DISORDER; SOCIAL ANXIETY; RECEPTOR GENE; FOLLOW-UP AB Attention has been devoted over the past two decades to the identification of temperamental risk factors for child psychopathology. These qualities, evident in toddlerhood or earlier, have the advantage of being measurable in standardized laboratory observations well before children reach the age of onset or diagnosis of. psychiatric disorders. Our group's programmatic research over the past 15 years, and that of others, has provided evidence linking "behavioral inhibition to the unfamiliar" in toddlerhood or early childhood with later social anxiety disorder. In addition, recent results by our group have suggested that "behavioral disinhibition" in early childhood, measured by the same laboratory methods, may be linked with later disruptive behavior and comorbid mood disorders. In this article, we discuss our approach to the study of temperamental precursors to disorders in high-risk children, summarize the literature linking behavioral inhibition and disinhibition to later psychopathology, and suggest directions to take in applying this methodology to the search for temperamental precursors to pediatric. bipolar disorder. (C) 2003 Society of Biological Psychiatry. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. Massachusetts Mental Hlth Ctr, Dept Psychiat, Cambridge, MA USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Cambridge, MA 02138 USA. RP Hirshfeld-Becker, DR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Program, 185 Alewife Brook Pkwy,Suite 2100, Cambridge, MA 02138 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-47077-08, MH-01538-05] NR 133 TC 56 Z9 60 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2003 VL 53 IS 11 BP 985 EP 999 DI 10.1016/S0006-3223(03)00316-0 PG 15 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 686UT UT WOS:000183339900009 PM 12788244 ER PT J AU Mick, E Biederman, J Pandina, G Faraone, SV AF Mick, E Biederman, J Pandina, G Faraone, SV TI A preliminary meta-analysis of the child behavior checklist in pediatric bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Pediatric Bipolar Disorder CY MAR, 2002 CL BOSTON, MASSACHUSETTS DE bipolar disorder; disruptive behavior disorders; assessment; children ID DEFICIT HYPERACTIVITY DISORDER; JUVENILE MANIA; SYMPTOMS; SCALES; CBCL; METAANALYSIS; ADOLESCENTS; ADHD; TRF AB Background: A possible explanation for the ongoing controversy surrounding pediatric bipolar disorder is that differences in assessment methodologies lead to conflicting results. One way to address methodological differences in assessment across studies is to use a single standardized assessment of psychopathology to calibrate the findings reported in different studies. To this end, we conducted a meta-analysis of several studies that have employed the Child Behavior Checklist in the assessment of children with a diagnosis of bipolar disorder. Methods: MEDLINE was searched for all publications that utilized the Child Behavior Checklist in addition to structured diagnostic interviews to assess pediatric bipolar disorder. Random effects models were used to calculate combined estimates of Child Behavior Checklist clinical subscales. Results: Children with bipolar disorder had scaled scores of >70 in the Aggression, Attention Problems, and Anxious/Depressed subscales of the Child Behavior Checklist. The Child Behavior Checklist was useful in distinguishing bipolar from attention-deficit/hyperactivity disorder subjects. Conclusions: While there was a significant heterogeneity in estimates between studies, a consistent pattern Of elevations in inattention/hyperactivity, depression/anxiety, and aggression was identified. (C) 2003 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Janssen Pharmaceut Prod LP, CNS, Clin Dev Div, Titusville, NJ USA. RP Mick, E (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, 15 Parkman St,WACC 725, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K01-MH065523] NR 30 TC 109 Z9 111 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2003 VL 53 IS 11 BP 1021 EP 1027 DI 10.1016/S0006-3223(03)00234-8 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 686UT UT WOS:000183339900012 PM 12788247 ER PT J AU Sachs, GS Thase, ME Otto, MW Bauer, M Miklowitz, D Wisniewski, SR Lavori, P Lebowitz, B Rudorfer, M Frank, E Nierenberg, AA Fava, M Bowden, C Ketter, T Marangell, L Calabrese, J Kupfer, D Rosenbaum, JF AF Sachs, GS Thase, ME Otto, MW Bauer, M Miklowitz, D Wisniewski, SR Lavori, P Lebowitz, B Rudorfer, M Frank, E Nierenberg, AA Fava, M Bowden, C Ketter, T Marangell, L Calabrese, J Kupfer, D Rosenbaum, JF TI Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD) SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Pediatric Bipolar Disorder CY MAR, 2002 CL BOSTON, MASSACHUSETTS DE bipolar disorder; effectiveness research; bipolar depression; relapse prevention ID RATING-SCALE; DEPRESSION; LITHIUM; ILLNESS; PROPHYLAXIS; COMORBIDITY; PREDICTORS; STRATEGIES; INVENTORY; SUICIDE AB The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was conceived in response to a National Institute of Mental Health initiative seeking a public health intervention model that could generate externally valid answers to treatment effectiveness questions related to bipolar disorder. STEP-BD, like all effectiveness research, faces many design challenges, including how to do the following: recruit a representative sample of patients for studies of readily available treatments; implement a common intervention strategy across diverse settings; determine outcomes for patients in multiple phases of illness; make provisions for testing as yet undetermined new treatments; integrate adjunctive psychosocial interventions; and avoid biases due to subject drop-out and last-observation-carried-forward data analyses. To meet these challenges, STEP-BD uses a hybrid design to collect longitudinal data as patients make transitions between naturalistic studies and randomized clinical trials. Bipolar patients of every subtype with age greater than or equal to 15 years are accessioned into a study registry. All patients receive a systematic assessment battery at entry and are treated by a psychiatrist (trained to deliver care and measure outcomes in patients with bipolar disorder) using a series of model practice procedures consistent with expert recommendations. At every follow-up visit, treating psychiatrist completes a standardized assessment and assigns an operationalized clinical status based on DSM-IV criteria. Patients have independent evaluations at regular intervals throughout the study and remain under the, care of the same treating psychiatrist while making transitions between randomized care studies and the standard care treatment pathways. This article reviews the methodology used for the selection and certification of the clinical treatment centers, training study personnel, the general approach to clinical management, and the sequential treatment strategies offered in the STEP-BD standard and randomized care pathways for bipolar depression and relapse prevention. (C) 2003 Society of Biological Psychiatry. C1 Harvard Univ, Partners Bipolar Treatment Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. Brown Univ, Dept Psychiat, Providence, RI 02912 USA. Univ Colorado, Dept Psychiat, Boulder, CO 80309 USA. Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. NIMH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. RP Sachs, GS (reprint author), Harvard Univ, Partners Bipolar Treatment Ctr, Massachusetts Gen Hosp, Sch Med, 50 Stanford St,5th Floor, Boston, MA 02114 USA. OI Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [N01MH80001] NR 50 TC 338 Z9 341 U1 4 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2003 VL 53 IS 11 BP 1028 EP 1042 DI 10.1016/S0006-3223(03)00165-3 PG 15 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 686UT UT WOS:000183339900013 PM 12788248 ER PT J AU Daly, A McAfee, S Dey, B Colby, C Schulte, L Yeap, B Sackstein, R Tarbell, NJ Sachs, D Sykes, M Spitzer, TR AF Daly, A McAfee, S Dey, B Colby, C Schulte, L Yeap, B Sackstein, R Tarbell, NJ Sachs, D Sykes, M Spitzer, TR TI Nonmyeloablative bone marrow transplantation: Infectious complications in 65 recipients of HLA-identical and mismatched transplants SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE bone marrow transplantation; complications; nonmyeloablative; infection; cytomegalovirus; fungal infection ID STEM-CELL TRANSPLANTATION; CYTOMEGALOVIRUS-INFECTION; MYELOABLATIVE THERAPY; BACTERIAL-INFECTIONS; CONTROLLED TRIAL; ACUTE-LEUKEMIA; DOUBLE-BLIND; ENGRAFTMENT; GANCICLOVIR; DISEASES AB Infections are a common complication of allogeneic bone marrow transplantation and the leading cause of transplantation-related mortality. It had been hypothesized that transplantation following nonmyeloablative preparative regimens would result in fewer infections by causing less mucosal injury, less graft-versus-host disease, and allowing earlier immune reconstitution. We have retrospectively reviewed the infectious complications of 65 consecutive patients with advanced hematologic malignancies who underwent bone marrow transplantation using a novel preparative regimen consisting of cyclophosphamide, thymic irradiation, and in vivo T-cell depletion. Cytomegalovirus (CMV) infection occurred in 52% of cases in which the donor or recipient had evidence of prior CAW exposure. Using a strategy of preemptive therapy and secondary prophylaxis with ganciclovir, no CMV disease occurred. Infections with gram-positive bacteria predominated over the first 100 days after bone marrow transplantation. Thereafter, the relative proportion of gram-negative infections increased without a significant increase in episodes of neutropenia. The rate of bacterial infections was not influenced by relapse of the underlying malignancy. Seven patients developed infections with Aspergillus species, which was the most common infectious cause of death in these patients. Infections with viruses other than CAW (n=10) and with protozoan organisms (n=2) also occur-red. The use of BILA-mismatched donors, the occurrence of grade II-IV acute graft-versus-host disease, and treatment with corticosteroids did not influence the risk of CAW or bacterial or fungal infections in patients who underwent transplantation following this preparative regimen. Overall, the incidence and spectrum of infections in this series was similar to the reported incidence of infections following conventional myeloablative allogeneic stem cell transplantation. We conclude that a quantitative T-cell deficiency in these extensively T-cell depleted patients may be a risk factor for infection, even in the absence of graft-versus-host disease. (C) 2003 American Society for Blood and Marrow Transplantation. C1 Univ Toronto, Princess Margaret Hosp, Allogen Bone Marrow Transplant Program, Hlth Network, Toronto, ON M5G 2M9, Canada. Univ Toronto, Toronto, ON M5G 2M9, Canada. Massachusetts Gen Hosp, Bone Marrow Transplant Program, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Daly, A (reprint author), Princess Margaret Hosp, Dept Med Oncol & Hematol, 610 Univ Ave, Toronto, ON M5G 2M9, Canada. NR 27 TC 46 Z9 48 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2003 VL 9 IS 6 BP 373 EP 382 DI 10.1016/S1083-8791(03)00100-9 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 697QX UT WOS:000183955700003 PM 12813445 ER PT J AU Lee, SJ Loberiza, FR Rizzo, JD Soiffer, RJ Antin, JH Weeks, JC AF Lee, SJ Loberiza, FR Rizzo, JD Soiffer, RJ Antin, JH Weeks, JC TI Optimistic expectations and survival after hematopoietic stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE stem cell transplantation; quality of life; state optimism ID BONE-MARROW TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; CANCER-PATIENTS; DISEASE; HEALTH; TRUTH; PREDICTORS; PHYSICIANS; PROGNOSIS; REMISSION AB An optimistic attitude is hypothesized to be beneficial when facing a life-threatening medical condition. However, the actual relationship of high expectations for treatment success and medical outcome is controversial. Using a prospective cohort of 313 autologous and allogeneic hematopoietic stem cell transplant patients enrolled July 1996 through November 1999, we tested whether patient-reported expectations before transplantation were associated with survival and quality of life following the procedure. Before transplantation, patients with higher expectations that the transplant procedure would go well had better mental and emotional functioning, but similar physical status and medical condition to patients with less optimistic expectations. In the first 2 months after transplantation, optimistic expectations were associated with better survival (92% v 84%; relative risk for mortality 0.45, 95% confidence interval 0.22-0.92; P=.03) controlling for other physical and mental characteristics. However, by 6 months posttransplantation, survival and quality of life were indistinguishable between patients with initially higher and lower expectations. Our data suggest an association between more optimistic expectations and early survival following hematopoietic stem cell transplantation, but this association is not present by 6 months posttransplantation. (C) 2003 American Society for Blood and Marrow Transplantation. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Boston, MA 02115 USA. Med Coll Wisconsin, Hlth Policy Inst, Milwaukee, WI 53226 USA. RP Lee, SJ (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 75267-04] NR 33 TC 28 Z9 28 U1 0 U2 3 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2003 VL 9 IS 6 BP 389 EP 396 DI 10.1016/S1083-8791(03)00103-4 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 697QX UT WOS:000183955700005 PM 12813447 ER PT J AU Pitsillides, CM Joe, EK Wei, XB Anderson, RR Lin, CP AF Pitsillides, CM Joe, EK Wei, XB Anderson, RR Lin, CP TI Selective cell targeting with light-absorbing microparticles and nanoparticles SO BIOPHYSICAL JOURNAL LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; MONOCLONAL-ANTIBODIES; PHOTODYNAMIC THERAPY; LASER-PULSES; INACTIVATION; PHOTOTHERMOLYSIS; MICROSURGERY; ABSORPTION; RADIATION; CANCER AB We describe a new method for selective cell targeting based on the use of light-absorbing microparticles and nanoparticles that are heated by short laser pulses to create highly localized cell damage. The method is closely related to chromophore-assisted laser inactivation and photodynamic therapy, but is driven solely by light absorption, without the need for photochemical intermediates (particularly singlet oxygen). The mechanism of light-particle interaction was investigated by nanosecond time-resolved microscopy and by thermal modeling. The extent of light-induced damage was investigated by cell lethality, by cell membrane permeability, and by protein inactivation. Strong particle size dependence was found for these interactions. A technique based on light to target endogenous particles is already being exploited to treat pigmented cells in dermatology and ophthalmology. With exogenous particles, phamacokinetics and biodistribution studies are needed before the method can be evaluated against photodynamic therapy for cancer treatment. However, particles are unique, unlike photosensitizers, in that they can remain stable and inert in cells for extended periods. Thus they may be particularly useful for prelabeling cells in engineered tissue before implantation. Subsequent irradiation with laser pulses will allow control of the implanted cells (inactivation or modulation) in a noninvasive manner. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02137 USA. RP Lin, CP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, BHX 630,40 Blossom St, Boston, MA 02114 USA. NR 29 TC 443 Z9 457 U1 5 U2 105 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 2003 VL 84 IS 6 BP 4023 EP 4032 PG 10 WC Biophysics SC Biophysics GA 683CL UT WOS:000183129800046 PM 12770906 ER PT J AU Malo, MS Husain, Z AF Malo, MS Husain, Z TI Positive selection vectors for high-fidelity PCR cloning SO BIOTECHNIQUES LA English DT Article ID PFU DNA-POLYMERASE; CONSTRUCTION; SEQUENCES; GENE AB The power of PCR cloning of a target DNA fragment is limited by polymerase-induced mutations. While high-fidelity PCR products can be achieved by reducing the number of PCR cycles, the cloning of the very small amount of DNA thus amplified should give only a few recombinant clones (carrying an insert), which would be very difficult to screen from thousands of background false-positive clones generated by all the currently available vectors, including the positive selection vectors. False-positive clones are mostly generated by the recircularization of linearized vectors that have lost some bases at their ends due to digestion with contaminating exonuclease activities present in restriction enzymes, ligases, polymerases, and other reagents. To overcome this problem, two positive selection vectors, pRGR1Ap and pREM5Tc, have been developed, based on the principles of reporter gene reconstruction and regulatory element modulation, respectively. A PCR primer carrying a vecto-specific sequence at its 5' end is used in PCR. When the resultant PCR products are ligated to the specific vector an antibiotic resistance gene is expressed, thus donating positive selection capability to the harboring cells in a specific selection medium. These vectors cloned PCR fragments generated from less than a femtomole quantity of Escherichia coli genomic DNA after only three cycles of PCR amplification, thus greatly reducing the number of recombinant clones containing polymerase-induced mutations. C1 SynthGen Syst, Medford, MA USA. RP Malo, MS (reprint author), Massachusetts Gen Hosp, Jackson 812,55 Fruit St, Boston, MA 02114 USA. NR 15 TC 4 Z9 4 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUN PY 2003 VL 34 IS 6 BP 1250 EP + PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 688JB UT WOS:000183429700020 PM 12813893 ER PT J AU Tohen, M Baldessarini, RJ AF Tohen, M Baldessarini, RJ TI Introduction to special issue on treatment of bipolar disorder SO BIPOLAR DISORDERS LA English DT Editorial Material C1 Lilly Res Labs, Indianapolis, IN 46225 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Int Consortium Bipolar Disorder Res, Belmont, MA USA. Massachusetts Gen Hosp, Bipolar & Psychot Disorders Program, McLean Div, Belmont, MA USA. RP Tohen, M (reprint author), Lilly Res Labs, 525 S Meridian St, Indianapolis, IN 46225 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2003 VL 5 IS 3 BP 153 EP 155 DI 10.1034/j.1399-5618.2003.00035.x PG 3 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 683NZ UT WOS:000183156800001 ER PT J AU Baldessarini, RJ Tondo, L Hennen, J AF Baldessarini, RJ Tondo, L Hennen, J TI Treatment-latency and previous episodes: relationships to pretreatment morbidity and response to maintenance treatment in bipolar I and II disorders SO BIPOLAR DISORDERS LA English DT Article DE bipolar I and II disorders; course of illness; duration of illness; episode count; lithium; maintenance treatment; manic-depressive illness; treatment delay; treatment latency; treatment response ID RECURRENT AFFECTIVE-DISORDERS; PROSPECTIVE FOLLOW-UP; LONG-TERM LITHIUM; SUICIDE RISK; MOOD STABILIZERS; PROPHYLAXIS; ILLNESS; MANIA; HOSPITALIZATION; CARBAMAZEPINE AB Objective: To clarify relationships of treatment delay and pretreatment episode count with pretreatment morbidity and responses to maintenance treatments in bipolar disorders. Methods: In 450 DSM-IV bipolar I (n = 293) or II (n = 157) patients (280 women, 170 men), we evaluated correlations of latency from illness-onset to starting maintenance treatment and pretreatment episode counts with pretreatment morbidity and treatment response. We considered morbidity measures before and during treatment, and their differences. Results: Latency averaged 7.8 years, with 9.0 episodes per patient, before various maintenance treatments started. Morbidity (percentage of time-ill, episodes per year, first wellness-interval, or proportion of subjects hospitalized or having no recurrences) during maintenance treatment averaging 4.2 years was unrelated to treatment latency or pretreatment episode count. However, pretreatment morbidity was greater with shorter latency, resulting in larger relative reduction of morbidity after earlier treatment. Conclusions: Greater treatment latency and pretreatment episode count were not followed by greater morbidity during treatment, although longer delay yielded smaller during-versus-before treatment reduction in morbidity. Predictions that longer treatment delay or more pretreatment episodes lead to poorer responses to various maintenance treatments in bipolar I or II disorder were not supported. C1 Harvard Univ, Sch Med,Consolidated Dept Psychiat, Int Consortium Bipolar Disorder Res,Bipolar & Psy, Massachusetts Gen Hosp,McLean Div, Belmont, MA 02178 USA. Univ Cagliari, Dept Psychol, Lucio Bini Stanley Inst, Ctr Psychiat Res, Cagliari, Sardinia, Italy. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 306, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-47370] NR 53 TC 62 Z9 64 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2003 VL 5 IS 3 BP 169 EP 179 DI 10.1034/j.1399-5618.2003.00030.x PG 11 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 683NZ UT WOS:000183156800003 PM 12780871 ER PT J AU Harvey, EA Coull, BA Holmes, LB AF Harvey, EA Coull, BA Holmes, LB TI Anticonvulsant teratogenesis 5: Observer bias in a cohort study SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article ID PHYSICAL FEATURES; PREDICTIVE VALUE; MINOR ANOMALIES; MALFORMATIONS; ASSOCIATION; EPILEPSY; WOMEN AB The most common physical effects of prenatal exposure to the anticonvulsant drugs phenytoin and phenobarbital are midface and digit hypoplasia. These features are subjective in nature, which makes their detection vulnerable to any bias the examiner has, such as an increased expectation that the infant being examined has been exposed prenatally to an anticonvulsant drug. The purpose of this analysis was to determine whether or not there was evidence of observer bias in the detection of presumed anticonvulsant drug-related physical features. METHODS:The presence or absence of three groups of features were compared: 1) midface hypoplasia, such as anteverted nostrils; 2) digit hypoplasia, e.g., tapered fingers, and 3) other features, e.g., prominent occiput, not known to be affected by exposure to anticonvulsants. These infants were examined by one masked physician examiner, using a study protocol, in three time periods: in two similar time periods, the masked examiner knew that one in four (25%) of the infants to be examined had been exposed to an anticonvulsant drugs; in the third time period, the chance was 50%. RESULTS: The frequencies of the subjective features of midface (odds ratio [OR] = 2.6) and digit hypoplasia (OR = 3.9), but not the other features, were significantly more common in the time periods when the masked examiner knew that there was a 50% chance of exposure to anticonvulsant drugs, compared to the time periods when there was a 25% chance. CONCLUSIONS: The findings suggest the effect of observer bias. In addition, there was evidence of context bias, meaning that a study that focuses on determining the presence of specific features will identify them more often. (C) 2003 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Holmes, LB (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Warren 801,55 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS 24125] NR 13 TC 8 Z9 8 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 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JUN PY 2003 VL 67 IS 6 BP 452 EP 456 DI 10.1002/bdra.10055 PG 5 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 720XG UT WOS:000185287100008 PM 12962290 ER PT J AU Fisler, RE Cohen, A Ringer, SA Lieberman, E AF Fisler, RE Cohen, A Ringer, SA Lieberman, E TI Neonatal outcome after trial of labor compared with elective repeat cesarean section SO BIRTH-ISSUES IN PERINATAL CARE LA English DT Article ID RESPIRATORY-DISTRESS SYNDROME; VAGINAL BIRTH; EPIDURAL ANALGESIA; INTRAPARTUM FEVER; MATERNAL FEVER; TERM INFANTS; MORBIDITY; NEWBORN; PLASMA AB Background: Trial of labor after cesarean section has been an important strategy for lowering the rate of cesarean delivery in the United States, but concerns regarding its safety remain. The purpose of this study was to evaluate the outcome of newborns delivered by elective repeat cesarean section compared to delivery following a trial of labor after cesarean. Methods: All low-risk mothers with 1 or 2 previous cesareans and no prior vaginal deliveries, who delivered at our institution from December 1994 through July 1995, were identified. Neonatal outcomes were compared between 136 women who delivered by elective repeat cesarean section and 313 women who delivered after a trial of labor. To investigate reasons for differences in outcome between these groups, neonatal outcomes within the trial of labor group were then compared between those mothers who had received epidural analgesia (n = 230) and those who did not (n = 83). Results: Infants delivered after a trial of labor had increased rates of sepsis evaluation (23.3% vs 12.5%, p = 0.008); antibiotic treatment (11.5% vs 4.4%, p = 0.02); intubation to evaluate for the presence of meconium below the cords (11.5% vs 1.5%, p < 0.001); and mild bruising (8.0% vs 1.5%, p = 0.008). Within the trial of labor group, infants of mothers who received epidural analgesia were more likely to have received diagnostic tests and therapeutic interventions including sepsis evaluation (29.6% vs 6.0%, p = 0.001) and antibiotic treatment (13.9% vs 4.8%, p = 0.03) than within the no-epidural analgesia group. Conclusions: Infants born to mothers after a trial of labor are twice as likely to undergo diagnostic tests and therapeutic interventions than infants born after an elective repeat cesarean section, but the increase occurred only in the subgroup of infants whose mothers received epidural analgesia for pain relief during labor. The higher rate of intervention could relate to the well-documented increase in intrapartum fever that occurs with epidural use. C1 Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Program Neonatol, Boston, MA 02115 USA. RP Lieberman, E (reprint author), Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 20 TC 11 Z9 11 U1 0 U2 7 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0730-7659 J9 BIRTH-ISS PERINAT C JI Birth-Issue Perinat. Care PD JUN PY 2003 VL 30 IS 2 BP 83 EP 88 DI 10.1046/j.1523-536X.2003.00225.x PG 6 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA 676WJ UT WOS:000182775300002 PM 12752164 ER PT J AU Bauer, KA AF Bauer, KA TI TFPI and venous thrombosis SO BLOOD LA English DT Editorial Material C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Bauer, KA (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2003 VL 101 IS 11 BP 4228 EP 4229 PG 2 WC Hematology SC Hematology GA 682CJ UT WOS:000183072800004 ER PT J AU Andersson, G Illigens, BMW Johnson, KW Calderhead, D LeGuern, C Benichou, G White-Scharf, ME Down, JD AF Andersson, G Illigens, BMW Johnson, KW Calderhead, D LeGuern, C Benichou, G White-Scharf, ME Down, JD TI Nonmyeloablative conditioning is sufficient to allow engraftment of EGFP-expressing bone marrow and subsequent acceptance of EGFP-transgenic skin grafts in mice SO BLOOD LA English DT Article ID GREEN FLUORESCENT PROTEIN; STEM-CELL TRANSPLANTATION; LONG-TERM ENGRAFTMENT; IN-VIVO PERSISTENCE; GENE-THERAPY; IMMUNE-RESPONSES; HEMATOPOIETIC-CELLS; DENDRITIC CELLS; MIXED CHIMERISM; C57BL/6 MICE AB Immunologic reactions against gene therapy products may prove to be a frequent problem in clinical gene therapy protocols. Enhanced green fluorescence protein (EGFP) is commonly used as a marker in gene transfer protocols, and immune responses against EGFP-expressing cells have been documented. The present study was designed to investigate the effect of a pharmacologic, nonmyeloablative, conditioning regimen on the development of EGFP(+) donor/recipient mixed bone marrow chimerism and ensuing tolerance to EGFP-expressing transplants. To this end, C57BL/6J (136) mice were treated with soluble formulations of either busulfan (Busulfex) or the closely related compound treosulfan, followed by transplantation of bone marrow cells from EGFP-transgenic (B6-EGFR.Tg) donor mice. Such conditioning regimens resulted in long-term persistence of donor EGFP(+) cells among various hematopoietic lineages from blood, bone marrow, and thymus. Stable hematopoietic chimeras transplanted at 10 to 17 weeks after bone marrow transplantation (BMT) with B6-EGFP.Tg skin grafts all accepted their transplants, whereas non-EGFP chimeric B6 control animals were able to mount rejection of the EGFP(+) B6 skin grafts. Control third-party grafts from major histocompatibility complex (MHC)-mismatched mice were rejected within 20 days, indicating that acceptance of EGFP-expressing skin grafts was the result of specific immune tolerance induction by the transplantation of EGFP-transgenic bone marrow. Long-term tolerance to EGFP in chimeric recipients was confirmed by the absence of anti-EGFP-reactive T cells and antibodies. These results broaden the therapeutic potential for using hematopoietic molecular chimerism in nonmyeloablated recipients as a means of preventing rejection of genetically modified cells. (C) 2003 by The American Society of Hematology. C1 BioTransplant Inc, Boston, MA 02129 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Cellular & Mol Immunol Lab, Boston, MA USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Down, JD (reprint author), BioTransplant Inc, Charlestown Navy Yard, Boston, MA 02129 USA. FU NCI NIH HHS [1R43CA090097-1A1] NR 48 TC 40 Z9 40 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2003 VL 101 IS 11 BP 4305 EP 4312 DI 10.1182/blood-2002-06-1649 PG 8 WC Hematology SC Hematology GA 682CJ UT WOS:000183072800022 PM 12576326 ER PT J AU Fonseca, R Blood, E Rue, M Harrington, D Oken, MM Kyle, RA Dewald, GW Van Ness, B Van Wier, SA Henderson, KJ Bailey, RJ Greipp, PR AF Fonseca, R Blood, E Rue, M Harrington, D Oken, MM Kyle, RA Dewald, GW Van Ness, B Van Wier, SA Henderson, KJ Bailey, RJ Greipp, PR TI Clinical and biologic implications of recurrent genomic aberrations in myeloma SO BLOOD LA English DT Article ID IN-SITU HYBRIDIZATION; COOPERATIVE-ONCOLOGY-GROUP; CANCER CELL-LINES; HIGH-DOSE THERAPY; HEAVY-CHAIN GENE; MULTIPLE-MYELOMA; CHROMOSOME-13 ABNORMALITIES; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; SYSTEMIC AMYLOIDOSIS AB Nonrandom recurrent chromosomal abnormalities are ubiquitous in multiple myeloma (MM) and include, among others, translocations of the immunoglobulin heavy chain locus (IgH). IgH translocations in MM result in the up-regulation of oncogenes, and include more commonly t(11;14)(q13;q32), t(4;14)(p16;q32), and t(14;16)(q32;q23). Based on the recurrent nature of these translocations and their finding since the early stages of the plasma cell (PC) disorders, we hypothesized that they would confer biologic and clinical variability. In addition, deletions of 13q14 and 17p13 have also been associated with a shortened survival. We used cytoplasmic Ig-enhanced interphase fluorescent in situ hybridization to detect deletions (13q14 and 17p13.1), and translocations involving IgH in 351 patients treated with conventional chemotherapy entered into the Eastern Cooperative Oncology Group clinical trial E9486/9487. Translocations were frequently unbalanced with loss of one of the derivative chromosomes. The presence of t(4; 14)(p16;q32) (n = 42; 26 vs 45 months, P < .001), t(l 4;1 6)(q32;q23) (n = 15; 16 vs 41 months, P = .003), -17p13 (n 37; 23 vs 44 months, P = .005), and 13q14 (n = 176; 35 VS 51 months, P = .028) were associated with shorter survival. A stratification of patients into 3 distinct categories allowed for prognostication: poor prognosis group (t(4;14)(p16;q32), t(14; 16)(q32;q23), and -17p13), intermediate prognosis (-13q14), and good prognosis group (all others), with median survivals of 24.7, 42.3, and 50.5 months, respectively (P < .001). This molecular cytogenetic classification identifies patients into poor, intermediate, and good risk categories. More importantly it provides further compelling evidence that MM is composed of subgroups of patients categorized according to their underlying genomic aberrations. (C) 2003 by The American Society of Hematology. C1 Mayo Clin, Div Hematol, Dept Lab Med & Pathol, Rochester, MN USA. Dana Farber Canc Inst, Ctr Stat, ECOG, Boston, MA 02115 USA. Virginia Piper Canc Inst, Minneapolis, MN USA. Univ Minnesota, Minneapolis, MN USA. RP Fonseca, R (reprint author), Mayo Clin & Mayo Fdn, Div Hematol & Internal Med, Stabile 6-22, Rochester, MN 55905 USA. RI Rue, Montserrat/B-5663-2009; OI Rue, Montserrat/0000-0002-7862-9365; Fonseca, Rafael/0000-0002-5938-3769 FU NCI NIH HHS [P01 CA62242, R01 CA83724-01]; PHS HHS [A21115-25C] NR 46 TC 370 Z9 398 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2003 VL 101 IS 11 BP 4569 EP 4575 DI 10.1182/blood-2002-10.3017 PG 7 WC Hematology SC Hematology GA 682CJ UT WOS:000183072800058 PM 12576322 ER PT J AU Jemtland, R Divieti, P Lee, K Segre, GV AF Jemtland, R Divieti, P Lee, K Segre, GV TI Hedgehog promotes primary osteoblast differentiation and increases PTHrP mRNA expression and iPTHrP secretion SO BONE LA English DT Article DE osteoblast; hedgehog; PTHrP; bone; differentiation ID HORMONE-RELATED PROTEIN; INDIAN HEDGEHOG; SONIC HEDGEHOG; BONE-FORMATION; PTH/PTHRP RECEPTOR; LINEAGE; CELLS; PROLIFERATION; PATHWAYS AB We used both clonal osteoblast-like cells and primary calvarial osteoblastic cells to examine the role of Hedgehog in osteoblast biology. Primary osteoblasts and several clonal osteoblast-like cell lines express Indian hedgehog (Ihh), and genes encoding both components of its receptor. patched (Ptc) and smoothened (Smo). Moreover, Hilt is relatively increased in phenotypically mature clonal cells and it increases by fivefold in primary osteoblasts as they mature in culture. Recombinant N-terminal Sonic Hedgehog (rSHH-N) upregulates Ptc and Gli-1 in osteoblasts, classical transcriptional targets. Furthermore; in response to rSHH-N, immunoreactive parathyroid hormone-related peptide (iPTHrP) secretion is transiently increased in medium conditioned by primary osteoblasts. Changes in PTHrP expression mirror those of iPTHrP. except in late cultures, when mRNA levels remain relatively elevated in response to rSHH-N. Gli-1, but not Ptc, becomes resistant to treatment with rSHH-N over a time course paralleling that of PTHrP, suggesting that mechanisms regulated by Gli-1 affect PTHrP. Last, rSHH-N increases formation of mineralized bone nodules and it accelerates expression of alkaline phosphatase, alkaline phosphatase activity. and mineralization. Taken together, these data suggest a functional role for Hedgehog protein in osteoblast recruitment and differentiation. which includes stimulation of PTHrP expression and secretion. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit,Dept Med, Boston, MA 02114 USA. RP Segre, GV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit,Dept Med, 32 Fruit St,Wellman 501, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK 11794] NR 31 TC 36 Z9 48 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JUN PY 2003 VL 32 IS 6 BP 611 EP 620 DI 10.1016/S8756-3282(03)00092-9 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 692DK UT WOS:000183645200004 PM 12810168 ER PT J AU Burstein, HJ Demetri, GD Mueller, E Sarraf, P Spiegelman, BM Winer, EP AF Burstein, HJ Demetri, GD Mueller, E Sarraf, P Spiegelman, BM Winer, EP TI Use of the peroxisome proliferator-activated receptor (PPAR) gamma ligand troglitazone as treatment for refractory breast cancer: a phase II study SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer clinical trials; peroxisome proliferator-activated receptor (PPAR); thiazolidinediones; troglitazone ID HUMAN PROSTATE-CANCER; IN-VITRO; CELLS; THIAZOLIDINEDIONES; DIFFERENTIATION; CARCINOGENESIS; CARCINOMA; GROWTH AB Purpose. To evaluate the therapeutic effects of the peroxisome proliferator-activated receptor (PPAR). activating ligand, troglitazone, in patients with refractory metastatic breast cancer. Experimental design. Patients with advanced breast cancer refractory to at least one chemotherapy regimen (ER negative tumors) or two hormonal regimens (ER positive tumors) were treated with troglitazone at 800 mg PO QD until disease progression, to determine the percentage of patients free of progression at 6 months. Tumor response, toxicity, and changes in serum tumormarkers (CEA, CA27.29) that might reflect alteration in tumor differentiation, were also examined. Results. Twenty-two patients were enrolled before suspension of protocol accrual and treatment when troglitazone was withdrawn from commercial availability following FDA warnings on hepatic toxicity. No objective responses (CR or PR) were observed; only three patients had SD at 8 weeks. Patients came off study for PD (16), DLT (1), FDA withdrawal (2), or other (3) reasons. No patients took troglitazone for more than 20 weeks; all had experienced disease progression or began other systemic therapy within 6 months. All patients with elevated serum tumor markers (CEA and CA27.29) at baseline had rising tumor markers within 8 weeks. Conclusions. While clinical trials among different patient populations might uncover subtle effects on tumor differentiation, PPAR. activation by troglitazone has little apparent clinical value among patients with treatment-refractory metastatic breast cancer. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 22 TC 148 Z9 156 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2003 VL 79 IS 3 BP 391 EP 397 DI 10.1023/A:1024038127156 PG 7 WC Oncology SC Oncology GA 686KU UT WOS:000183321600011 PM 12846423 ER PT J AU Kyle, RA Child, JA Anderson, K Barlogie, B Bataille, R Bensinger, W Blade, J Boccadoro, M Dalton, W Dimopoulos, M Djulbegovic, B Drayson, M Durie, B Facon, T Fonseca, R Gahrton, G Greipp, P Harousseau, JL Harrington, D Hussein, M Joshua, D Ludwig, H Morgan, G Oken, M Powles, R Richardson, P Roodman, D San Miguel, J Shimizu, K Shustik, C Sirohi, B Sonneveld, P Tricot, G Turesson, I Van Ness, B Vesole, D Weber, D Westin, J Wheatley, K AF Kyle, RA Child, JA Anderson, K Barlogie, B Bataille, R Bensinger, W Blade, J Boccadoro, M Dalton, W Dimopoulos, M Djulbegovic, B Drayson, M Durie, B Facon, T Fonseca, R Gahrton, G Greipp, P Harousseau, JL Harrington, D Hussein, M Joshua, D Ludwig, H Morgan, G Oken, M Powles, R Richardson, P Roodman, D San Miguel, J Shimizu, K Shustik, C Sirohi, B Sonneveld, P Tricot, G Turesson, I Van Ness, B Vesole, D Weber, D Westin, J Wheatley, K CA Int Myeloma Working Grp TI Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE classification; monoclonal; gammopathies; multiple myeloma ID PLASMA-CELL LEUKEMIA; 20-YEAR FOLLOW-UP; UNDETERMINED SIGNIFICANCE; MALIGNANT-TRANSFORMATION; SOLITARY PLASMACYTOMA; PROGNOSTIC-FACTORS; ADULT-POPULATION; NATURAL-HISTORY; M-COMPONENTS; LONG-TERM AB The monoclonal gammopathies are a group of disorders associated with monoclonal proliferation of plasma cells. The characterization of specific entities is an area of difficulty in clinical practice. The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations. In monoclonal gammopathy of undetermined significance (MGUS) or monoclonal gammopathy, unattributed/unassociated (MG[u]), the monoclonal protein is < 30 g/l and the bone marrow clonal cells < 10% with no evidence of multiple myeloma, other B-cell proliferative disorders or amyloidosis. In asymptomatic (smouldering) myeloma the M-protein is greater than or equal to 30 g/l and/or bone marrow clonal cells greater than or equal to 10% but no related organ or tissue impairment (ROTI)(end-organ damage), which is typically manifested by increased calcium, renal insufficiency, anaemia, or bone lesions (CRAB) attributed to the plasma cell proliferative process. Symptomatic myeloma requires evidence of ROTI. Non-secretory myeloma is characterized by the absence of an M-protein in the serum and urine, bone marrow plasmacytosis and ROTI. Solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas (+/- recurrent) are also defined as distinct entities. The use of these criteria will facilitate comparison of therapeutic trial data. Evaluation of currently available prognostic factors may allow better definition of prognosis in multiple myeloma. C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Leeds Teaching Hosp, Leeds, W Yorkshire, England. Dana Farber Canc Ctr, Boston, MA USA. Univ Arkansas, Fayetteville, AR 72701 USA. Univ Nantes, F-44035 Nantes, France. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Hosp Clin Barcelona, IDIBAPS, Barcelona, Spain. Univ Turin, I-10124 Turin, Italy. Univ S Florida, Tampa, FL 33620 USA. Univ Athens, GR-10679 Athens, Greece. Univ Birmingham, Birmingham B15 2TT, W Midlands, England. Cedars Sinai Canc Ctr, Los Angeles, CA USA. Univ Lille, Lille, France. Karolinska Inst, S-10401 Stockholm, Sweden. Harvard Univ, Cambridge, MA 02138 USA. Cleveland Clin, Cleveland, OH 44106 USA. Univ S Wales, Sydney, NSW, Australia. Wilhelmenia Hosp, Vienna, Austria. Virginia Piper Canc Ctr, Minneapolis, MN USA. Royal Marsden Canc Hosp, London, England. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Salamanca, E-37008 Salamanca, Spain. Nagoya Univ, Nagoya, Aichi, Japan. McGill Univ, Montreal, PQ H3A 2T5, Canada. Univ Rotterdam, Rotterdam, Netherlands. Malmo Gen Hosp, S-21401 Malmo, Sweden. Univ Minnesota, Minneapolis, MN 55455 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Lund Univ, S-22100 Lund, Sweden. RP Kyle, RA (reprint author), Mayo Clin & Mayo Fdn, 200 1st St SW, Rochester, MN 55905 USA. EM kyle.robert@mayo.edu RI Djulbegovic, Benjamin/I-3661-2012; FACON, THIERRY/M-9736-2014; OI Djulbegovic, Benjamin/0000-0003-0671-1447; FACON, THIERRY/0000-0001-7705-8460; Fonseca, Rafael/0000-0002-5938-3769 NR 32 TC 968 Z9 995 U1 10 U2 42 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2003 VL 121 IS 5 BP 749 EP 757 PG 9 WC Hematology SC Hematology GA 684FA UT WOS:000183193700008 ER PT J AU Maecker, B Anderson, KS von Bergwelt-Baildon, MS Weller, E Vonderheide, RH Richardson, PG Schlossman, RL Menezes, IA Xia, ZN Munshi, NC Anderson, KC Nadler, LM Schultze, JL AF Maecker, B Anderson, KS von Bergwelt-Baildon, MS Weller, E Vonderheide, RH Richardson, PG Schlossman, RL Menezes, IA Xia, ZN Munshi, NC Anderson, KC Nadler, LM Schultze, JL TI Viral antigen-specific CD8(+) T-cell responses are impaired in multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE T cells; multiple myeloma; tetramer ID EPSTEIN-BARR-VIRUS; LYMPHOCYTES; BLOOD; EXPRESSION; TRANSPLANTATION; INFLUENZA; PROTEIN; COMPLEX; TRIAL AB Multiple myeloma (MM) is associated with defects of humoral and cellular immunity, however, little is known about the frequency and function of antigen-specific CD8(+) T cells. Such information might be critical for the development of immunotherapy for MM patients. As a model, we assessed the frequency and proliferation of CD8(+) T cells specific for HLA-A*0201-restricted immunodominant epitopes from influenza A (Inf A) and Epstein-Barr virus (EBV). Experiments in identical twins demonstrated reduced numbers of antigen-specific T cells after ex-vivo antigenic challenge in the MM twin when compared with the healthy twin. Similarly, the proliferation and frequency of EBV- and Inf A-specific T cells was also significantly reduced in a cohort of 24 previously untreated or conventionally treated MM patients when compared with 19 healthy individuals. In contrast, MM patients studied after receiving an autologous stem cell transplantation showed strikingly higher frequencies of EBV-specific T cells with potential to proliferate ex vivo , suggesting that EBV-specific T cells are readily expandable under these circumstances. These data identify an impaired response of CD8(+) T cells in MM patients, which might in part explain the relatively limited success of anti-MM immunisations. Prospective studies will determine whether such immune assessment strategies may identify patients more likely to benefit from cancer immunotherapy. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Schultze, JL (reprint author), Univ Klinikum Koln, Joseph Stelzmann Str 9 Haus 16, D-50924 Cologne, Germany. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 FU NCI NIH HHS [K08 CA 88444-01, P01 CA 66996, P01 CA 78378] NR 25 TC 28 Z9 29 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2003 VL 121 IS 6 BP 842 EP 848 DI 10.1046/j.1365-2141.2003.04375.x PG 7 WC Hematology SC Hematology GA 686DK UT WOS:000183305700003 PM 12786794 ER PT J AU Nishioka, NS AF Nishioka, NS TI Optical biopsy using tissue spectroscopy and optical coherence tomography SO CANADIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT 15th International Course on Therapeutic Endoscopy CY OCT 09-12, 2002 CL TORONTO, CANADA DE laser; optical coherence tomography; optics; spectroscopy ID LASER-INDUCED FLUORESCENCE; GASTROINTESTINAL-TRACT; GI TRACT; DIAGNOSIS; ESOPHAGUS; STOMACH; MUCOSA; COLON AB 'Optical biopsy' or 'optical diagnostics' is a technique whereby light energy is used to obtain information about the structure and function of tissues without disrupting them. In fluorescence spectroscopy, tight energy (usually provided by a laser) is used to excite tissues and the resulting fluorescence provides information about the target tissue. Its major gastrointestinal application has been in the evaluation of colonic polyps, in which it can reliably distinguish malignant from benign lesions. Optical coherence tomography (OCT) has been used in the investigation of Barrett's epithelium (and dysplasia), although a variety of other applications are feasible. For example, OCT could assist in the identification and staging of mucosal and submucosal neoplasms, the grading of inflammation in the stomach and intestine, the diagnosis of biliary tumours and the assessment of villous architecture. OCT differs from endoscopic ultrasound, a complementary modality, in that it has a much higher resolution but lesser depth of penetration. The images correlate with the histopathological appearance of tissues, and the addition of Doppler methods may enable it to evaluate the vascularity of tumours and the amount of blood flow in varices. Refinements in these new optical techniques will likely make them valuable in clinical practice, although their specific roles have yet to be determined. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nishioka, NS (reprint author), Massachusetts Gen Hosp, Blake 4,55 Fruit St, Boston, MA 02114 USA. NR 28 TC 6 Z9 6 U1 0 U2 0 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 0835-7900 J9 CAN J GASTROENTEROL JI Can. J. Gastroenterol. PD JUN PY 2003 VL 17 IS 6 BP 376 EP 380 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 695QP UT WOS:000183842000004 PM 12813604 ER PT J AU Dreicer, R Manola, J Schneider, DJ Schwerkoske, JF George, CS Roth, BJ Wilding, G AF Dreicer, R Manola, J Schneider, DJ Schwerkoske, JF George, CS Roth, BJ Wilding, G TI Phase II trial of gemcitabine and docetaxel in patients with advanced carcinoma of the urothelium - A trial of the eastern cooperative oncology group SO CANCER LA English DT Article DE gemcitabine; docetaxel; urothelial carcinoma; phase II trial ID TRANSITIONAL-CELL CARCINOMA; PROGNOSTIC FACTORS; CISPLATIN; CANCER; CHEMOTHERAPY; IFOSFAMIDE; PACLITAXEL; METHOTREXATE; COMBINATION; VINBLASTINE AB BACKGROUND. Gemcitabine and docetaxel are active agents in advanced urothelial carcinoma. A Phase II trial of this combination was performed to determine the activity and toxicity of these agents in a multiinstitutional setting in patients previously treated with one prior chemotherapy regimen. METHODS. Twenty-nine eligible patients with advanced urothelial carcinoma were treated with docetaxel at a dose of 40 mg/m(2) over 1 hour followed by gemcitabine, 800 mg/m(2), over 30 minutes, both intravenously (i.v.) on Days 1 and 8. Cycles were repeated every 21 days until disease progression or a maximum of 6 cycles. RESULTS. Five patients obtained an objective response for an overall response rate of 17% (90% confidence interval, 7-33%). One patient achieved a complete clinical response. The median overall survival of the group was 7.7 months. Toxicity was moderate with granulocytopenia, anorexia, and fatigue being the most commonly noted side effects. CONCLUSIONS. Gemcitabine and docetaxel is an active second-line combination in patients with advanced urothelial carcinoma. Responses in visceral, lymph node, and soft tissues sites were observed. Granulocytopenia without fever, fatigue, and anorexia was common. Thromboembolic symptoms were reported and are of concern. The combination of gemcitabine and docetaxel has the potential to palliate a subset of previously treated patients with an adequate performance status. (C) 2003 American Cancer Society. C1 Cleveland Clin Fdn, Dept Hematol & Oncol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Inst Urol, Cleveland, OH 44195 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Abbott NW Hosp, Minneapolis, MN USA. United Hosp, St Paul, MN USA. Riverside Methodist Hosp, Columbus, OH 43214 USA. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. Univ Wisconsin, Ctr Clin Canc, Madison, WI USA. RP Dreicer, R (reprint author), Cleveland Clin Fdn, Dept Hematol & Oncol, 9500 Euclid Ave,R35, Cleveland, OH 44195 USA. FU NCI NIH HHS [CA23318, CA17145, CA66636, CA21115] NR 18 TC 29 Z9 29 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 2003 VL 97 IS 11 BP 2743 EP 2747 DI 10.1002/cncr.11413 PG 5 WC Oncology SC Oncology GA 681DR UT WOS:000183022100006 PM 12767086 ER PT J AU Roth, AJ Rosenfeld, B Kornblith, AB Gibson, C Scher, HI Curley-Smart, T Holland, JC Breitbart, W AF Roth, AJ Rosenfeld, B Kornblith, AB Gibson, C Scher, HI Curley-Smart, T Holland, JC Breitbart, W TI The memorial anxiety scale for prostate cancer - Validation of a new scale to measure anxiety in men with prostate cancer SO CANCER LA English DT Article DE anxiety; cancer; prostate; scale development ID QUALITY-OF-LIFE; PSYCHOSOCIAL MORBIDITY; RADICAL PROSTATECTOMY; FUNCTIONAL ASSESSMENT; PSYCHOLOGIC DISTRESS; HOSPITAL ANXIETY; DEPRESSION SCALE; RADIATION; THERAPY; CARCINOMA AB BACKGROUND. The psychological difficulties facing men with prostate cancer are 2 acknowledged widely, yet identifying men who may benefit from mental health treatment has proven to be a challenging task. The authors developed the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) to facilitate the identification and assessment of men with prostate cancer-related anxiety. This scale consists of three subscales that measure general prostate cancer anxiety, anxiety related to prostate specific antigen (PSA) levels in particular, and fear of recurrence. METHODS. Ambulatory men with prostate cancer (n = 385 patients) were recruited from clinics throughout the United States. Prior to routine PSA tests, participants completed a baseline assessment packet that included the Hospital Anxiety and Depression Scale; the Distress Thermometer; the Functional Assessment of Cancer Therapy Scale, Prostate Module; and measures of role functioning, sleep, and urinary functioning. PSA values from the last three tests also were collected. Follow-up evaluation was completed within 2 weeks after patients learned of their PSA test result using a subset of these scales. RESULTS. Analysis of the MAX-PC revealed a high degree of internal consistency and test-retest reliability for the total score and for the three subscales, although reliability was somewhat weaker for the PSA Anxiety Scale. Concurrent validity was demonstrated by correlations between the MAX-PC and measures of anxiety. 5 Overall changes in PSA levels were correlated only modestly with changes in MAX-PC scores (correlation coefficient, 0.13; P = 0.02). CONCLUSIONS. The MAX-PC appears to be a valid and reliable measure of anxiety in men with prostate cancer receiving ambulatory care. (C) 2003 American Cancer Society. C1 Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Nursing, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Med Oncol Serv, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fordham Univ, Dept Psychol, Bronx, NY 10458 USA. RP Roth, AJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, Box 421,1242 2nd Ave, New York, NY 10021 USA. NR 34 TC 100 Z9 100 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 2003 VL 97 IS 11 BP 2910 EP 2918 DI 10.1002/cncr.11386 PG 9 WC Oncology SC Oncology GA 681DR UT WOS:000183022100027 PM 12767107 ER PT J AU Chan, AT AF Chan, AT TI Aspirin, non-steroidal anti-inflammatory drugs and colorectal neoplasia: future challenges in chemoprevention SO CANCER CAUSES & CONTROL LA English DT Editorial Material ID FAMILIAL ADENOMATOUS POLYPOSIS; LONG-TERM USE; SPONTANEOUS INTESTINAL ADENOMAS; TRANSIENT ISCHEMIC ATTACK; PROSTAGLANDIN E-2 LEVELS; COLON-CANCER CELLS; MIN MOUSE MODEL; RANDOMIZED-TRIAL; LARGE-BOWEL; CYCLOOXYGENASE-2 LEVELS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. RP Chan, AT (reprint author), Channing Labs, 3rd Floor,181 Longwood Ave, Boston, MA 02115 USA. FU NIDDK NIH HHS [T32DK07191] NR 77 TC 25 Z9 27 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 2003 VL 14 IS 5 BP 413 EP 418 DI 10.1023/A:1024986220526 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 705VU UT WOS:000184417300002 PM 12946035 ER PT J AU Jain, RK Duda, DG AF Jain, RK Duda, DG TI Role of bone marrow-derived cells in tumor angiogenesis and treatment SO CANCER CELL LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; HEMATOPOIETIC STEM-CELLS; TRANSPLANTATION; ISCHEMIA AB The role of bone marrow-derived cells in tumor neovascularization is currently the subject of intense research and debate. Two recent studies (De Palma et al., 2003 and Garcia-Barros et al., 2003) offer novel yet somewhat conflicting evidence for the role of these cells in tumor growth and neovascularization. These results have significant implications for tumor biology and treatment. At the same time, they raise many questions, which must be addressed for translating these important findings into new, improved treatment strategies. C1 Massachusetts Gen Hosp, EL Steele Lab Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, EL Steele Lab Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA. NR 13 TC 48 Z9 50 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUN PY 2003 VL 3 IS 6 BP 515 EP 516 DI 10.1016/S1535-6108(03)00138-7 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 694TN UT WOS:000183790600002 PM 12842078 ER PT J AU Kasum, CM Blair, CK Folsom, AR Ross, JA AF Kasum, CM Blair, CK Folsom, AR Ross, JA TI Non-steroidal anti-inflammatory drug use and risk of adult leukemia SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COLORECTAL-CANCER; BREAST-CANCER; OLDER WOMEN; ASPIRIN USE; SMOKING; HEALTH AB Epidemiological studies have suggested that regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may be associated with reduced risk of some types of malignancy. Leukemia incidence and self-reported aspirin, as well as other NSAID use, was examined in a prospective cohort of >28,000 postmenopausal women. Eighty-one incident leukemia cases occurred during the period 1993-2000. The multivariate-adjusted relative risk of leukemia was 0.45 (95% confidence interval: 0.27-0.75) for women who reported using aspirin two or more times per week compared with women who reported no use. Similar inverse associations were observed for the two subtypes of leukemia analyzed. In contrast, for women who reported using nonaspirin NSAIDs, the multivariate-adjusted relative risk of leukemia was 1.31 (95% confidence interval: 0.77-2.22). Analyses that excluded cases diagnosed before 1995 did not notably alter results. To our knowledge, this is the first prospective study to examine the association between NSAID use and incident adult leukemia. Although preliminary, the notable differences observed in leukemia risk between aspirin and nonaspirin NSAID use warrant further investigation. C1 Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55454 USA. Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. RP Ross, JA (reprint author), Univ Minnesota, Ctr Canc, MMC 422,554 CCRB,420 Delaware St SE, Minneapolis, MN 55455 USA. FU NCI NIH HHS [T32 CA09607, R01 CA39742] NR 22 TC 30 Z9 32 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2003 VL 12 IS 6 BP 534 EP 537 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 692PZ UT WOS:000183670600010 PM 12814999 ER PT J AU Smith, MR AF Smith, MR TI Management of treatment-related osteoporosis in men with prostate cancer SO CANCER TREATMENT REVIEWS LA English DT Review ID BONE-MINERAL DENSITY; ANDROGEN-DEPRIVATION THERAPY; SEX STEROID-LEVELS; OLDER MEN; HORMONE AGONISTS; VITAMIN-D; AROMATASE DEFICIENCY; RANCHO BERNARDO; WOMEN; CARCINOMA AB Osteoporosis is an important and preventable adverse effect of androgen deprivation therapy for prostate cancer. Androgen deprivation therapy by either bilateral orchiectomies or administration of a gonadotropin-releasing hormone agonist decreases bone mineral density and increases fracture risk. Treatment-related osteoporosis can be prevented by intermittent administration of either intravenous pamidronate or zoledronic acid. Pamidronate (60 mg intravenously every 3 months) prevents bone loss during androgen deprivation therapy. Zoledronic acid (4 mg intravenously every 3 months) not only prevents bone loss but also increases bone mineral density. Alendronate and other oral bisphosphonates may be effective but have not been evaluated in men with castrate testosterone levels. Oestrogen replacement therapy and treatment with selective ooestrogen receptor modulators may prevent bone loss during androgen deprivation therapy. Bicalutamide ( 150 mg daily) monotherapy increases serum ooestrogen levels and maintains bone mineral density. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Haematol Oncol Div, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Haematol Oncol Div, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 57 TC 20 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD JUN PY 2003 VL 29 IS 3 BP 211 EP 218 DI 10.1016/S0305-7372(03)00076-8 PG 8 WC Oncology SC Oncology GA 695QW UT WOS:000183842600007 PM 12787715 ER PT J AU Lowe, HC Jang, IK Yoerger, DM MacGillivray, TE de Moor, M Palacios, IF AF Lowe, HC Jang, IK Yoerger, DM MacGillivray, TE de Moor, M Palacios, IF TI Compassionate use of the amplatzer ASD closure device for residual postinfarction ventricular septal rupture following surgical repair SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE VSR; myocardial infarction; TTE ID TRANSCATHETER CLOSURE; DEFECT; INFARCTION; OCCLUDER AB We report successful transcatheter closure of a post-MI ventricular septal rupture acutely following unsuccessful surgical repair. Catheter closure was accomplished by the use of a 26-mm Amplatzer atrial septal occluder. Initial attempts to close the defect with the use of 28-mm and 33-mm CARDIOSEAL were unsuccessful. Closure technique, immediate and long-term follow-up outcomes are reported. (C) 2003 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02144 USA. Harvard Univ, Sch Med, Boston, MA 02144 USA. Massachusetts Gen Hosp, Cardiac Surg Div, Boston, MA 02144 USA. Massachusetts Gen Hosp, Div Pediat Cardiol, Boston, MA 02144 USA. RP Palacios, IF (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Bullfinch 105, Boston, MA 02144 USA. NR 9 TC 4 Z9 5 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 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUN PY 2003 VL 59 IS 2 BP 230 EP 233 DI 10.1002/ccd.10525 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 685ZM UT WOS:000183295100017 PM 12772247 ER PT J AU Caviness, VS Goto, T Tarui, T Takahashi, T Bhide, PG Nowakowski, RS AF Caviness, VS Goto, T Tarui, T Takahashi, T Bhide, PG Nowakowski, RS TI Cell output, cell cycle duration and neuronal specification: a model of integrated mechanisms of the neocortical proliferative process SO CEREBRAL CORTEX LA English DT Article ID MURINE CEREBRAL WALL; GABAERGIC NEURONS; MICE LACKING; G1 PHASE; ORIGIN; CORTEX; NEURONOGENESIS; P27(KIP1); FATE; HYPERPLASIA AB The neurons of the neocortex are generated over a 6 day neuronogenetic interval that comprises 11 cell cycles. During these 11 cell cycles, the length of cell cycle increases and the proportion of cells that exits (12) versus re-enters (P) the cell cycle changes systematically. At the same time, the fate of the neurons produced at each of the 11 cell cycles appears to be specified at least in terms of their laminar destination. As a first step towards determining the causal interrelationships of the proliferative process with the process of laminar specification, we present a two-pronged approach. This consists of (i) a mathematical model that integrates the output of the proliferative process with the laminar fate of the output and predicts the effects of induced changes in 0 and P during the neuronogenetic interval on the developing and mature cortex and (ii) an experimental system that allows the manipulation of 0 and P in vivo. Here we show that the predictions of the model and the results of the experiments agree. The results indicate that events affecting the output of the proliferative population affect both the number of neurons produced and their specification with regard to their laminar fate. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Keio Univ, Sch Med, Dept Pediat, Tokyo 1608582, Japan. RP Nowakowski, RS (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, 675 Hoes Lane, Piscataway, NJ 08854 USA. RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670 FU NINDS NIH HHS [NS33433, NS12005, R01 NS012005] NR 33 TC 119 Z9 120 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUN PY 2003 VL 13 IS 6 BP 592 EP 598 DI 10.1093/cercor/13.6.592 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 681CL UT WOS:000183019300008 PM 12764033 ER PT J AU Au, DH Udris, EM Fan, VS Curtis, JR McDonell, MB Fihn, SD AF Au, DH Udris, EM Fan, VS Curtis, JR McDonell, MB Fihn, SD TI Risk of mortality and heart failure exacerbations associated with inhaled beta-adrenoceptor agonists among patients with known left ventricular systolic dysfunction SO CHEST LA English DT Article DE adreaergic beta-agonists; COPD; echocardiography; heart failure; mortality ID IDIOPATHIC DILATED CARDIOMYOPATHY; ADRENERGIC-RECEPTOR BLOCKADE; PHARMACY RECORDS; MERIT-HF; METOPROLOL; TERBUTALINE; RESPONSES; DISEASE; DENSITY; TRIAL AB Objectives: Recent studies suggest that myocardial beta(2)-adrenoceptors may be important in chronic heart failure. We sought to determine if use of selective beta(2)-agonists was associated with hospitalization for heart failure and all-cause mortality. Methods: We studied a cohort of patients with left ventricular systolic dysfunction (LVSD). The outcome was the first hospitalization with a primary diagnosis of chronic heart failure or death from any cause. The exposure was the average number of R-agonist canisters filled per month in the 90 days prior to and 15 days after enrollment. Results: Among 1,529 subjects, the relative risk (RR) of chronic heart failure hospital admission associated with inhaled beta-agonists followed a dose-response relationship: RR for one canister per month, 1.4 (95% confidence interval [CI], 0.9 to 2.0), RR for two canisters per month, 1.7 (95% CI, 1.2 to 2.5), and RR for three canisters per month, 2.1 (95% CI, 1.4 to 3.1). The RR of death demonstrated a similar finding: RR for one canister per month, 0.9 (95% CI, 0.5 to 1.5), RR for two canisters per month, 1.3 (95% CI, 0.9 to 2.1), and RR for three canisters per month, 2.0 (95% CI, 1.3 to 3.1). Adjusting for potential confounding factors did not affect the estimates, Conclusion: Among subjects with LVSD, inhaled beta-agonists were associated with an increased risk of heart failure hospitalization, and all-cause mortality. Clinicians should carefully consider the etiology of dyspnea when prescribing beta-agonists to patients with LVSD. C1 VA Puget Sound Hlth Care Syst, Div Pulm & Crit Care Med, NW Ctr Excellence, Dept Vet Affairs, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Au, DH (reprint author), VA Puget Sound Hlth Care Syst, Div Pulm & Crit Care Med, NW Ctr Excellence, Dept Vet Affairs, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 31 TC 69 Z9 69 U1 1 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2003 VL 123 IS 6 BP 1964 EP 1969 DI 10.1378/chest.123.6.1964 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 689XV UT WOS:000183519000031 PM 12796175 ER PT J AU Cuajungco, MP Ando, Y Axelrod, FB Biaggioni, I Goldstein, DS Guttmacher, AE Gwinn-Hardy, K Hahn, MK Hilz, MJ Jacob, G Jens, J Kennedy, WR Liggett, SB O'Connor, DT Peltzer, SR Robertson, D Rubin, BY Scudder, Q Smith, LJ Sonenshein, GE Svejstrup, JQ Xu, Y Slaugenhaupt, SA AF Cuajungco, MP Ando, Y Axelrod, FB Biaggioni, I Goldstein, DS Guttmacher, AE Gwinn-Hardy, K Hahn, MK Hilz, MJ Jacob, G Jens, J Kennedy, WR Liggett, SB O'Connor, DT Peltzer, SR Robertson, D Rubin, BY Scudder, Q Smith, LJ Sonenshein, GE Svejstrup, JQ Xu, Y Slaugenhaupt, SA TI Hereditary dysautonomias: current knowledge and collaborations for the future SO CLINICAL AUTONOMIC RESEARCH LA English DT Review DE autonomic nervous system; catecholamine; neuropathy; amyloidosis ID FAMILIAL AMYLOIDOTIC POLYNEUROPATHY; INHIBITORY PEPTIDE CATESTATIN; NOREPINEPHRINE-TRANSPORTER DEFICIENCY; IDIOPATHIC ORTHOSTATIC INTOLERANCE; POLYMERASE-II HOLOENZYME; RENIN-ANGIOTENSIN SYSTEM; MOUSE IKBKAP GENE/; B KINASE COMPLEX; CATECHOLAMINE RELEASE; PARKINSON-DISEASE AB The hereditary dysautonomias (H-Dys) are a large group of disorders that affect the autonomic nervous system. Research in the field of H-Dys is very challenging, because the disorders involve interdisciplinary, integrative, and "mind-body" connections. Recently, medical scientists, NIH/NINDS representatives, and several patient support groups gathered for the first time in order to discuss recent findings and future directions in the H-Dys field. The H-Dys workshop was instrumental in promoting interactions between basic science and clinical investigators. It also allowed attendees to have an opportunity to meet each other, understand the similarities between the various forms of dysautonomia, and experience the unique perspective offered by patients and their families. Future advances in H-Dys research will depend on a novel multi-system approach by investigators from different medical disciplines, and it is hoped that towards a common goal, novel "bench-to-bedside" therapeutics will be developed to improve the lives of, or even cure, patients suffering from dysautonomic syndromes. C1 Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Charlestown, MA USA. Kumamoto Univ, Sch Med, Dept Lab Med, Kumamoto 860, Japan. NYU, Sch Med, Dept Pediat, New York, NY USA. NYU, Sch Med, Dept Neurol, New York, NY USA. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. NINDS, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Ctr Med, Ctr Mol Neurosci, Dept Pharmacol, Nashville, TN 37232 USA. Univ Erlangen Nurnberg, Dept Neurol, D-8520 Erlangen, Germany. Rambam Med Ctr, Jacob Recanati Autonom Dysfunct Ctr, Haifa, Israel. Humboldt Univ, Franz Volhard Clin Res Ctr, Berlin, Germany. Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. Univ Cincinnati, Div Pulm & Crit Care Med, Dept Internal Med, Cincinnati, OH USA. Univ Calif San Diego, Dept Nephrol, San Diego, CA 92103 USA. Familial Dysautonomia Hope Fdn, Newton, NC USA. Vanderbilt Univ, Med Ctr, Clin Res Ctr, Nashville, TN USA. Fordham Univ, Dept Biol Sci, Bronx, NY 10458 USA. RP Slaugenhaupt, SA (reprint author), Harvard Inst Human Genet, 77 Ave Louis Pasteur HIM Bldg,Rm 422, Boston, MA 02115 USA. RI Gwinn, Katrina/C-2508-2009; Cuajungco, Math/B-2647-2008; liggett, stephen/E-7453-2012; OI Cuajungco, Math/0000-0003-0749-9564; Svejstrup, Jesper/0000-0003-4964-6147 NR 123 TC 0 Z9 0 U1 0 U2 1 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD JUN PY 2003 VL 13 IS 3 BP 180 EP 195 DI 10.1007/s10286-003-0098-2 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 701CT UT WOS:000184151000005 PM 12822040 ER PT J AU Borden, EC Baker, LH Bell, RS Bramwell, V Demetri, GD Eisenberg, BL Fletcher, CDM Fletcher, JA Ladanyi, M Meltzer, P O'Sullivan, B Parkinson, DR Pisters, PWT Saxman, S Singer, S Sundaram, M van Oosterom, AT Verweij, J Waalen, J Weiss, SW Brennan, MF AF Borden, EC Baker, LH Bell, RS Bramwell, V Demetri, GD Eisenberg, BL Fletcher, CDM Fletcher, JA Ladanyi, M Meltzer, P O'Sullivan, B Parkinson, DR Pisters, PWT Saxman, S Singer, S Sundaram, M van Oosterom, AT Verweij, J Waalen, J Weiss, SW Brennan, MF TI Soft tissue sarcomas of adults: State of the translational science SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT State of the Science Conference CY FEB 04-06, 2002 CL BETHESDA, MARYLAND ID GASTROINTESTINAL STROMAL TUMORS; POSITRON-EMISSION-TOMOGRAPHY; DOXORUBICIN PLUS IFOSFAMIDE; FUSION TRANSCRIPT STRUCTURE; ELECTRON-BEAM RADIOTHERAPY; KINASE INHIBITOR STI571; ABL TYROSINE KINASE; RADIATION-THERAPY; SYNOVIAL SARCOMA; GENE-EXPRESSION AB Sarcomas-like leukemias, which are also mesodermal malignancies-carry biological significance disproportionate to their clinical frequency. Identification of mutations and translocations associated with these tumors has illuminated aberrant signaling pathways that cause these diseases, determine their behavior, and are therapeutic targets. Activated receptor-associated tyrosine kinase c-kit, mutated in most gastrointestinal stromal tumors, has proven a clinically effective target for enzyme inhibition. A translocation involving a single gene family, consisting of EWS and related genes, has been identified in five different sarcomas, and its chimeric protein products could prove similarly amenable to inhibitors. Resolution of the histopathological complexity is being aided by data from molecular and chromosomal characterization. Improvements in imaging, definition of prognostic factors, and surgical and radiotherapeutic treatment have resulted in improved local control. Continued progress will depend on further adapting the rapidly evolving technologies of genomics and proteomics. It will also depend upon accurate histopathological diagnosis based on validated reagents and consistent methodologies applied to adequate tissue samples derived from patients with complete clinical data. Finally, multicenter, coordinated trials, such as those that occurred with assessment of imatinib mesylate in metastatic gastrointestinal stromal tumors, will assure the most rapid reductions in morbidity and mortality. C1 Cleveland Clin Fdn, Ctr Canc Drug Discovery & Dev, Cleveland, OH 44195 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. London Reg Canc Ctr, London, ON N6A 4L6, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NHGRI, Bethesda, MD 20892 USA. Novartis Pharmaceut, E Hanover, NJ USA. NCI, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. Univ Ziekenhuizen Gasthuisberg, Louvain, Belgium. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. Scripps Res Inst, La Jolla, CA USA. Emory Univ, Atlanta, GA 30322 USA. RP Borden, EC (reprint author), Cleveland Clin Fdn, Ctr Canc Drug Discovery & Dev, 9500 Euclid Ave,Room 40, Cleveland, OH 44195 USA. NR 129 TC 170 Z9 177 U1 0 U2 7 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 JUN PY 2003 VL 9 IS 6 BP 1941 EP 1956 PG 16 WC Oncology SC Oncology GA 687PP UT WOS:000183386000001 PM 12796356 ER PT J AU Kelly, WK Zhu, AX Scher, H Curley, T Fallon, M Slovin, S Schwartz, LN Larson, S Tong, W Hartley-Asp, B Pellizzoni, C Rocchetti, M AF Kelly, WK Zhu, AX Scher, H Curley, T Fallon, M Slovin, S Schwartz, LN Larson, S Tong, W Hartley-Asp, B Pellizzoni, C Rocchetti, M TI Dose escalation study of intravenous estramustine phosphate in combination with paclitaxel and carboplatin in patients with advanced prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID PLASMA-CONCENTRATIONS; PHARMACOKINETICS; TAXOL; BONE; 3A4 AB Purpose: The purpose is to determine a safe weekly dose of i.v. estramustine phosphate (EMP) to combine with weekly paclitaxel and monthly carboplatin in patients with advanced prostate cancer. Experimental Design: Patients with advanced prostate cancer (castrate and noncastrate) were administered escalating doses of weekly 1-h infusion of i.v. EMP (500-1000-1500 mg/m(2)) in combination with weekly paclitaxel (100 mg/m(2) over 1 h) and i.v. carboplatin (area under the curve 6 mg/ml-min every 4 weeks). Four weeks of therapy were considered one cycle. In the first three cohorts; EMP was given i.v. 3 h before paclitaxel. Cohorts 4 and 5 reversed the administration order: EMP (doses 1000-1500 mg/m(2)) was given immediately after the end of paclitaxel infusion. Plasma levels of EMP and its metabolites, estramustine and estromustine, were monitored at time 0, at 120 min, and approximately at 20, 21, and 168 h from the start of EMP infusion. Paclitaxel concentrations were determined at basal (0), 30, 60, 90, and 120 min and 18 h after the start of paclitaxel infusion, and a concentration-time curve was estimated. Pharmacokinetic evaluation was performed in cycles 1 and 2 during the first week of therapy. Results: Nineteen patients were entered on the initial three dose levels (cohorts 1-3). Dose-limiting transient hepatic toxicity was encountered in cohort 3 (EMP = 1500 mg/m(2)). An additional 13 patients were treated with paclitaxel(100 mg/m(2)) first, followed by i.v. EMP at 1000 mg/m(2) (cohort 4), and 1500 mg/m(2) (cohort 5). No dose-limiting toxicities were seen, and cohort 5 was determined safe for Phase H studies. Thromboembolic events were observed in 9% of patients (no prophylactic coumadin was used). Plasma concentrations of EMP and metabolites increased proportionally with dose. In all cohorts, there was a slight decrease in EMP and estramustine plasma concentrations between cycles 1 and 2. Although not significant, higher levels of estromustine at cycle 2 were observed in comparison to cycle 1. Decreased clearance of paclitaxel leading to higher than expected paclitaxel plasma concentrations was observed during the first cycle of therapy. Paclitaxel plasma concentrations were lower during cycle 2. In 17 patients with androgen-independent disease, 59% had greater than or equal to50% posttherapy decline in PSA and 22% showed measurable disease regression. Conclusions: The regimen of weekly i.v. EMP in combination with paclitaxel and carboplatin can be safely administered with hepatic toxicity being transient and reversible. Pharmacokinetic results suggest that EMP competitively inhibits the biotransformation of paclitaxel after the first administration. This effect is counterbalanced, after repeated administrations, by a possible induction of the metabolic system caused by EMP. Phase II testing is ongoing to evaluate the efficacy of this combination. C1 Mem Sloan Kettering Canc Ctr, Div Solid Tumor, Genitourinary Oncol Serv, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Nursing, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Div Epidemiol & Biostat, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Pharmacol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Nucl Med, New York, NY 10021 USA. Cornell Univ, Joan & Sanford Weill Med Coll, Dept Med, New York, NY USA. Massachusetts Gen Hosp, Dana Farber Partners Canc, Boston, MA 02114 USA. Pharmacia Corp, Peapack, NJ USA. RP Kelly, WK (reprint author), Mem Sloan Kettering Canc Ctr, Div Solid Tumor, Genitourinary Oncol Serv, Dept Med, 1275 York Ave, New York, NY 10021 USA. NR 22 TC 10 Z9 10 U1 0 U2 0 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 JUN PY 2003 VL 9 IS 6 BP 2098 EP 2107 PG 10 WC Oncology SC Oncology GA 687PP UT WOS:000183386000019 PM 12796374 ER PT J AU Battle, TE Wierda, WG Rassenti, LZ Zahrieh, D Neuberg, D Kipps, TJ Frank, DA AF Battle, TE Wierda, WG Rassenti, LZ Zahrieh, D Neuberg, D Kipps, TJ Frank, DA TI In vivo activation of signal transducer and activator of transcription 1 after CD154 gene therapy for chronic lymphocytic leukemia is associated with clinical and immunologic response SO CLINICAL CANCER RESEARCH LA English DT Article ID APOPTOTIC PATHWAY; CELL-DEATH; IFN-GAMMA; T-CELLS; EXPRESSION; STAT1; SURVIVAL; PROTEINS; CASPASES AB Purpose: Signal transducer and activator of transcription (STAT) proteins are important regulators of physiological stimuli in lymphocytes. Biological therapies directed at lymphocytic malignancies such as chronic lymphocytic leukemia (CLL) may be mediated by these transcription factors. One such approach, CD154 (CD40-ligand) gene therapy, involves expressing CD154 on malignant B cells from CLL patients by transduction with an adenovirus vector after which the cells are reinfused into the patients. To determine the intracellular signaling pathways that underlie the clinical and immunological responses observed in patients from a Phase I study of CD154 gene therapy, CLL cells from these patients were examined for changes in STAT signaling events. Experimental Design: CLL cells from patients who underwent CD154 gene therapy were analyzed for changes in STAT signaling by Western blot analysis and electrophoretic mobility shift assay. Activation of STAT1 was correlated with patient response to therapy. Results: Tyrosine phosphorylation of STAT1 was detected in the nontransduced CLL cells in 9 of 11 patients 24 h after infusion, but not before. Activation of STAT1 was associated with clinical response, as measured by decreased absolute lymphocyte count, and immunological response, as measured by elevated plasma levels of IFN-gamma. Conclusion: This study indicates that STAT signaling may be an important mediator of biological treatments, such as CD154 gene therapy, and that early STAT1 activation may predict response to this novel treatment. C1 Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA. MD Anderson Canc Ctr, Leukemia Dept, Houston, TX USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Frank, DA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA81534, CA93053, CA79547] NR 27 TC 17 Z9 19 U1 0 U2 0 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 JUN PY 2003 VL 9 IS 6 BP 2166 EP 2172 PG 7 WC Oncology SC Oncology GA 687PP UT WOS:000183386000027 PM 12796382 ER PT J AU Dinovo, EC Singh, M Renner, SW Baria, AM Schieffer, B Korobkin, S Naliboff, BD AF Dinovo, EC Singh, M Renner, SW Baria, AM Schieffer, B Korobkin, S Naliboff, BD TI Comparison of opiate test results obtained from the LX20, AxSYM, REMEDi HS and the RapidOne Oxy testing systems with prescribed medications. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-Clinical-Chemiatry CY JUL 20-24, 2003 CL PHILADELPHIA, PENNSYLVANIA C1 VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2003 VL 49 IS 6 SU S BP A77 EP A77 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 682JP UT WOS:000183088700241 ER PT J AU Molano, ID Redmond, S Sekine, H Zhang, XK Reilly, C Hutchison, F Ruiz, P Gilkeson, GS AF Molano, ID Redmond, S Sekine, H Zhang, XK Reilly, C Hutchison, F Ruiz, P Gilkeson, GS TI Effect of genetic deficiency of terminal deoxynucleotidyl transferase on autoantibody production and renal disease in MRL/lpr mice SO CLINICAL IMMUNOLOGY LA English DT Article DE MRLMpJ/Fas(lpr); MRL/lpr; TdT; N additions; autoimmune; autoantibodies; lupus; nephritis; albuminuria; CDR3 sequence ID ANTI-DNA ANTIBODIES; SYSTEMIC LUPUS-ERYTHEMATOSUS; MRL-LPR MICE; BACTERIAL-DNA; AUTOIMMUNE ANTIBODIES; T-CELLS; B-CELLS; SPECIFICITY; NEPHRITIS; MODEL AB Terminal deoxynucleotidyl transferase (TdT) places non-template-coded nucleotides (N additions) in the VH CDR3 of T cell receptors and immunoglobulins. Amino acids coded for by N additions are important in autoantibody binding of dsDNA in lupus. We hypothesized that a genetic lack of TdT would modulate disease in lupus-prone mice. To test this hypothesis, we derived TdT-deficient MRL/lpr mice. Serum levels of anti-dsDNA antibodies and anti-dsDNA producing splenocytes were significantly lower in the TdT(-) versus TdT(+) littermates. Albuminuria, glomerular IgG deposition, and pathologic renal disease were significantly reduced in the TdT(-) mice. Sequence analysis of anti-dsDNA hybridomas derived from TdT(-) mice revealed a lack of N additions, short VH CDR3 segments, yet the presence of VH CDR3 arginines. Thus, the genetic absence of TdT reduces autoantibody production and clinical disease in MRL/lpr mice, confirming the importance of N additions in the autoimmune response in these mice. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Med Univ S Carolina, Ralph H Johnson VAMC, Med Res Serv, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Univ Miami, Med Ctr, Dept Pathol, Miami, FL 33136 USA. RP Gilkeson, GS (reprint author), 96 Jonathan Lucas Blvd,Ste 912,POB 250623, Charleston, SC 29425 USA. FU NIAMS NIH HHS [R01 AR056670, R03 AR054546] NR 36 TC 11 Z9 11 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUN PY 2003 VL 107 IS 3 BP 186 EP 197 DI 10.1016/S1521-6616(03)00035-4 PG 12 WC Immunology SC Immunology GA 692MR UT WOS:000183665300007 PM 12804532 ER PT J AU Rodriguez, EK Hornicek, FJ Gebhardt, MC Mankin, HJ AF Rodriguez, EK Hornicek, FJ Gebhardt, MC Mankin, HJ TI Metachronous osteosarcoma: A report of five cases SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID OSTEO-SARCOMA; NEOADJUVANT CHEMOTHERAPY; MULTIFOCAL OSTEOSARCOMA; EXPERIENCE; METASTASES AB Five patients with primary osteosarcoma who were treated effectively with chemotherapy and resective surgery and in whom a metachronous tumor subsequently developed in another site but who never had evidence of pulmonary metastases are described. The original bone scans of the five patients showed only the primary site as being involved. After diagnosis and treatment of the initial tumor, at intervals ranging from 12 to 78 months (average, 39 months) another osteosarcoma developed in the patients at a distant bony site. After diagnosis and treatment of the second osteosarcoma, followup of these patients for a mean of 77 months (range, 24-96 months) after the appearance of the metachronous tumor and for a mean of 118 months (range, 99-150 months) after the diagnosis of the primary lesion showed that none had pulmonary metastases develop. No recurrences of the local tumors have occurred and four of the patients currently are alive and free of disease. One of the patients had a fatal acute myelogenous leukemia develop 144 months after the discovery of the primary osteosarcoma and 86 months after the appearance of the metachronous disease. At the time of her death, however she had no evidence of osteosarcoma in any site. C1 Massachusetts Gen Hosp, Orthopaed Oncol Serv, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Orthopaed Serv, Gray 604, Boston, MA 02114 USA. NR 27 TC 1 Z9 1 U1 0 U2 1 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 JUN PY 2003 IS 411 BP 227 EP 235 DI 10.1097/01.blo.0000069887.31220.cf PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 687LW UT WOS:000183379000027 PM 12782879 ER PT J AU Roemer, L Orsillo, SM AF Roemer, L Orsillo, SM TI Mindfulness: A promising intervention strategy in need of further study SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Article DE acceptance; mindfulness; cognitive-behavioral therapy ID GENERALIZED ANXIETY DISORDER; COGNITIVE THERAPY; DEPRESSION; PREVENTION; MEDITATION; LIFE AB Baer (2003; this issue) has provided a thoughtful conceptual and empirical review of mindfulness-based clinical interventions, emphasizing the need for further research. In this commentary we elaborate on some of the areas needing further study. The promising initial data suggest a need for basic experimental and treatment outcome research in order to determine active ingredients and mechanisms of action in mindfulness-based interventions. In addition, questions remain regarding the optimal mode of delivery of this treatment, as well as how to integrate the nonstriving aspect of mindfulness into clinical intervention. C1 Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. Boston VA Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Roemer, L (reprint author), Univ Massachusetts, Dept Psychol, 100 Morrissey Blvd, Boston, MA 02125 USA. EM lizabeth.roemer@umb.edu OI Roemer, Lizabeth/0000-0002-2453-5435 NR 40 TC 62 Z9 64 U1 0 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0969-5893 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD SUM PY 2003 VL 10 IS 2 BP 172 EP 178 DI 10.1093/clipsy/bpg020 PG 7 WC Psychology, Clinical SC Psychology GA 680PJ UT WOS:000182986300006 ER PT J AU Leung, JY Abraczinskas, DR Bhan, AK Terella, AM Pascual, M Cosimi, AB Chung, RT AF Leung, JY Abraczinskas, DR Bhan, AK Terella, AM Pascual, M Cosimi, AB Chung, RT TI Recurrent allograft HCV presenting as acute cellular rejection: successful management with interferon and ribavirin alone SO CLINICAL TRANSPLANTATION LA English DT Article DE acute cellular rejection; interferon; recurrent HCV; ribavirin ID LIVER-TRANSPLANT RECIPIENTS; HEPATITIS-C; VIRUS-INFECTION; CELLS AB Hepatitis C (HCV) is currently the leading indication worldwide for orthotopic liver transplantation. However, the majority of patients receiving transplant for HCV eventually develop histopathologic evidence of recurrent allograft HCV and approximately 10% die or require retransplantation within the first 5 post-operative years because of accelerated graft injury and cirrhosis. Traditional induction immunosuppressive regimens and intensive immunosuppression used to treat episodes of acute cellular rejection (ACR) are associated with enhanced viral replication and higher likelihood and severity of recurrent HCV. At our institution, therefore, we have used low-dose steroid therapy in an effort to limit HCV replication. However, this practice has been associated with frequent early presentations consistent with ACR. Here, we present three cases consistent with histologic ACR treated with conventional antirejection therapy that improved transiently, but evolved rapidly to progressive HCV. A fourth patient with a similar presentation experienced dramatic improvement in aminotransferases when treated solely with interferon and ribavirin. We propose that histologic characteristics traditionally associated with ACR may, in fact, represent early recurrent HCV as both processes share common immunopathogenetic mechanisms, or alternatively, that both ACR and recurrent HCV may be present simultaneously. We conclude that in cases suggestive of ACR, careful consideration should be given to treatment for recurrent HCV in lieu of or in concert with intensive immunosuppression. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. NR 17 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PD JUN PY 2003 VL 17 IS 3 BP 275 EP 283 DI 10.1034/j.1399-0012.2003.00049.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 682DW UT WOS:000183076900018 PM 12780680 ER PT J AU Otto, MW Reilly-Harrington, NA Kogan, JN Winett, CA AF Otto, MW Reilly-Harrington, NA Kogan, JN Winett, CA TI Treatment contracting in cognitive-behavior therapy SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID MAINTENANCE PROGRAM; BIPOLAR DISORDER; VICTIMS AB Consistent with the goal of providing reviews of core strategies and principles used in cognitive-behavior therapy (Albano, 2003), this article is devoted to a discussion of the philosophy, elements, and potential benefits of treatment contracting. Treatment contracting is discussed as a way of formalizing the goals, responsibilities, and strategies to be employed in treatment by therapists, patients, and the patient's support network. In particular, we discuss the potential value of contracts for enhancing motivation and eliciting adaptive behaviors from patients, particularly at. moments of high stress or high risk when these behaviors are most needed. In addition, we comment on how contracts can serve as an agreement of advocacy for patients who may fail to take appropriate action for themselves during acute distress. We provide an example of a treatment contract for use with adults with posttraumatic stress disorder (PTSD). This contract most directly focuses on enhancing motivation for treatment and engendering self-care, and is embedded in the context Of an informational worksheet detailing common patterns in PTSD. C1 Massachusetts Gen Hosp, Cognit Behav Therapy Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Otto, MW (reprint author), Massachusetts Gen Hosp, Cognit Behav Therapy Program, WACC-812,15 Parkman St, Boston, MA 02114 USA. EM motto@partners.org NR 21 TC 5 Z9 5 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD SUM PY 2003 VL 10 IS 3 BP 199 EP 203 DI 10.1016/S1077-7229(03)80031-7 PG 5 WC Psychology, Clinical SC Psychology GA 918NW UT WOS:000228550900002 ER PT J AU Orsillo, SM Roemer, L Barlow, DH AF Orsillo, SM Roemer, L Barlow, DH TI Integrating acceptance and mindfulness into existing cognitive-behavioral treatment for GAD: A case study SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID GENERALIZED ANXIETY DISORDER; STATE WORRY QUESTIONNAIRE; PSYCHOMETRIC PROPERTIES; APPLIED RELAXATION; CLINICAL ANXIETY; PANIC DISORDER; THERAPY; PSYCHOTHERAPY; MODEL; EFFICACY AB Generalized anxiety disorder (GAD) is a chronic, pervasive disorder associated with significant impairment in functioning. While cognitive-behavioral interventions appear to be relatively efficacious in reducing GAD symptoms, the Proportion of treated individuals who reach desired levels of end-state functioning is less than ideal. A number of recent theoretical and empirical advances in the field have Led to the development of novel, experimental treatments for GAD. The current paper describes the integration of acceptance and mindfulness techniques into an existing cognitive-behavioral group treatment for GAD. Data from 4 clients suggest that further refinement of acceptance and mindfulness methods may facilitate improvement in the quality of life and psychosocial functioning of individuals diagnosed with GAD. C1 Boston VA Healthcare Syst, Natl Ctr PTSD Womens Hlth Serv Div, Boston, MA 02130 USA. Boston Univ, Boston, MA 02215 USA. Univ Massachusetts, Boston, MA 02125 USA. Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA USA. RP Orsillo, SM (reprint author), Boston VA Healthcare Syst, Natl Ctr PTSD Womens Hlth Serv Div, 116B-3,150 S Huntington Ave, Boston, MA 02130 USA. EM susan.orsillo@med.va.gov OI Roemer, Lizabeth/0000-0002-2453-5435 NR 64 TC 26 Z9 28 U1 8 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD SUM PY 2003 VL 10 IS 3 BP 222 EP 230 DI 10.1016/S1077-7229(03)80034-2 PG 9 WC Psychology, Clinical SC Psychology GA 918NW UT WOS:000228550900005 ER PT J AU Brickman, AM Buchsbaum, MS Shihabuddin, L Hazlett, EA Borod, JC Mohs, RC AF Brickman, AM Buchsbaum, MS Shihabuddin, L Hazlett, EA Borod, JC Mohs, RC TI Striatal size, glucose metabolic rate, and verbal learning in normal aging SO COGNITIVE BRAIN RESEARCH LA English DT Article DE FDG; positron emission tomography (PET); normal aging; striatum (caudate and putamen); regional glucose metabolism; verbal learning ID POSITRON EMISSION TOMOGRAPHY; BRAIN DOPAMINE ACTIVITY; CEREBRAL BLOOD-FLOW; AGE-RELATED-CHANGES; PARKINSONS-DISEASE; BASAL GANGLIA; HEALTHY-MEN; IN-VIVO; MEDICATED SCHIZOPHRENICS; SEX-DIFFERENCES AB The striatum has recently been implicated as an area that may mediate age-associated cognitive decline because of diminution of volume and functional activity. We used F-18-fluorodeoxyglucose (FDG) with positron emission tomography (PET) and high-resolution magnetic resonance imaging (MRI) to examine the effects of age on striatal glucose metabolic rate and size in 70 healthy, normal subjects. During the FDG tracer uptake period, subjects performed a serial verbal learning task, based on the California Verbal Learning Test. PET images were co-registered to the MR images. The interrelations among striatal glucose metabolic rate, size, and performance on the verbal learning task were examined with repeated-measures analysis of variance and correlational analysis. As age increased, relative glucose metabolic rate (GMR) increased in the putamen and decreased in the caudate. Female subjects had lower relative GMR than male subjects in the caudate, but equal in the putamen. Striatal size remained relatively constant across the lifespan in men but was lower in women aged 50-70 than in men. While there were significant associations between striatal activity and performance on the uptake task, these findings were mostly accounted for by age. The findings are consistent with our earlier report on the same cohort that demonstrated an age-related shift from anterior to posterior cortical metabolism, as the putamen receives primarily posterior cortical input and the caudate receives relatively more anterior cortical input. Findings of significant involvement of striatal functioning in verbal learning are most likely accounted for by age and suggest an age-related shift from anterior to posterior circuitry in the human telencephalon. Published by Elsevier Science B.V. C1 Mt Sinai Sch Med, Neurosci PET Lab, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Psychiat Serv, Bronx, NY 10468 USA. CUNY Queens Coll, Dept Psychol, Flushing, NY 11367 USA. CUNY Ctr, Flushing, NY 11367 USA. Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Brickman, AM (reprint author), Mt Sinai Sch Med, Neurosci PET Lab, Dept Psychiat, Box 1505,1 Gustave L Levy Pl, New York, NY 10029 USA. NR 63 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD JUN PY 2003 VL 17 IS 1 BP 106 EP 116 DI 10.1016/S0926-6410(03)00085-5 PG 11 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA 733CP UT WOS:000185982600011 ER PT J AU Kuperberg, GR Sitnikova, T Caplan, D Holcomb, PJ AF Kuperberg, GR Sitnikova, T Caplan, D Holcomb, PJ TI Electrophysiological distinctions in processing conceptual relationships within simple sentences SO COGNITIVE BRAIN RESEARCH LA English DT Article DE semantics; pragmatics; syntax; animacy; proposition; language; sentences; thematic roles; P600; N400; ERP; event related potentials; verb-argument structure; context ID EVENT-RELATED POTENTIALS; SYNTACTIC POSITIVE SHIFT; BRAIN POTENTIALS; LANGUAGE; INFORMATION; INTEGRATION; VIOLATIONS; ERPS; DEPENDENCIES; EXPECTANCY AB The aim of this study was to determine whether or not the brain distinguishes between two types of conceptual relationships between noun-phrases (NPs) and verbs during online processing of simple, unambiguous English sentences. A total of 15 participants read and made plausibility judgments on sentences that were presented word-by-word. Event-related potentials elicited by critical verbs were measured. In all cases, the critical verb assigned a thematic role of 'agent' to its subject NP. In non-violated sentences (e.g. "For breakfast the boys would only eat... "), the preceding NP was animate ("boys") and was a likely agent for a given verb ("eat") given its preceding context ("For breakfast"). In both types of conceptually violated sentences, the NPs were unlikely agents for the verbs given their preceding contexts. In 'thematic role animacy violations' (e.g. "For breakfast the eggs would only eat... "), the NP was inanimate ("eggs") and was therefore more likely to occupy the role of 'theme' than 'agent', i.e. eggs, being inanimate, cannot eat but they can be eaten. In 'non-thematic role pragmatic violations' (e.g. "For breakfast the boys would only bury... "), the thematic role of agent assigned by the verb ("bury") to its preceding NP ("boys") is inherently acceptable (boys can bury), but the sentence is still pragmatically incongruous given the preceding context ("At breakfast"). As expected, the non-thematic role pragmatic violations elicited a significant N400 effect. The thematic role animacy violations elicited a smaller N400 effect that only approached significance across all participants. The thematic role animacy violations, however, elicited a significant P600 effect-an ERP component that is most commonly associated with processing syntactic information during language comprehension. We discuss the possibility that the P600 was elicited by the thematic role animacy violations (but not by the non-thematic role pragmatic violations) because, in the former but not the latter, there was an online attempt to structurally repair and make sense of the sentences by reassigning the thematic role of the NP that preceded the critical verb from 'agent' to 'theme'. Our findings suggest a qualitative neural distinction in processing these two types of conceptual anomalies within simple, unambiguous sentences. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. Tufts Univ, Dept Psychol, Neurocognit Lab, Medford, MA 02155 USA. RP Kuperberg, GR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 44 TC 178 Z9 184 U1 3 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD JUN PY 2003 VL 17 IS 1 BP 117 EP 129 DI 10.1016/S0926-6410(03)00086-7 PG 13 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA 733CP UT WOS:000185982600012 ER PT J AU Brooks, WW Conrad, CH Nedder, AP Bing, OHL Slawsky, MT AF Brooks, WW Conrad, CH Nedder, AP Bing, OHL Slawsky, MT TI Thoracic massage permits use of echocardiography in unanesthetized rats SO COMPARATIVE MEDICINE LA English DT Article ID CARDIAC-FUNCTION; ANESTHESIA; MICE AB Purpose: The objective of the study reported here was to investigate whether massage-like stroking of the thorax and cranial portion of the abdomen might relax unanesthetized rats sufficiently to permit in vivo echocardiography. Methods: Nine-month-old spontaneously hypertensive rats (SHR) were first conditioned to being held by hand for 10 to 15 min twice a day for seven to 10 days. During each session, the animal was placed in supine position, and the thorax and cranial abdominal area were gently stroked (approx. 5 cm/s, 12 to 14 times/min). After the conditioning period, echocardiography was initiated. We obtained serial transthoracic two-dimensional (2-D) and M-mode echocardiograms from nine-month-old SHR that were treated with isoproterenol. (60 mg/kg of body weight, s.c., x 1, followed by 30 mg/kg/d x3), and from old (20 to 24 months old) SHR, studied when labored breathing, suggestive of heart failure, was evident (SHR-F). Measurements included end-diastolic volume (EDV) and end-systolic volume (ESV). Results: In the isoproterenol-treated SHR, mean +/- SD echocardiographicallyderived EDV (2-D, 0.29 +/- 0.05; M-mode, 0.28 +/- 0.01 ml) was not significantly different from volume at necropsy (0.33 +/- 0.04 ml). Measurements of EDV and ESV by use of M-mode and 2-D echocardiography were significantly correlated (EDV R-2 = 0.48, P = 0.05; ESV R-2 = 0.39, P = 0.02). Echocardiography revealed pleuropericardial effusions (4/6), atrial thrombi (5/6), and left and right ventricular enlargement (6/6). The EDV and ESV were increased fivefold (P < 0.01) and threefold (P < 0.05), respectively, versus values for SHR not in heart failure (SHR-NF). Left ventricular ejection fraction of hearts from SHR-F was markedly decreased, compared with that in SHR-NF (44 +/- 7 versus 74 +/- 2%, respectively; P < 0.05). The presence or absence of left atrial thrombi and fluid in the thoracic cavity was confirmed at necropsy in SHR-F and SHR-NF. Conclusion: Thoracic massage permits use of echocardiography in unanesthetized rats, thereby providing a simple, non-invasive technique for assessment of cardiac structure and function in rats without the potentially adverse effects of anesthesia. C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Brooks, WW (reprint author), VA Boston Healthcare Syst, Boston, MA 02130 USA. NR 9 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD JUN PY 2003 VL 53 IS 3 BP 288 EP 292 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 697FW UT WOS:000183932400012 PM 12868574 ER PT J AU Akita, H Sowa, J Makiura, M Akamatsu, H Matsunaga, K AF Akita, H Sowa, J Makiura, M Akamatsu, H Matsunaga, K TI Maculopapular drug eruption due to the Japanese herbal medicine Kakkonto (kudzu or arrowroot decoction) SO CONTACT DERMATITIS LA English DT Editorial Material DE cutaneous adverse drug reaction; herbal medicine; Kakkonto; kudzu decoction; patch test C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Fujita Hlth Univ, Sch Med, Dept Dermatol, Toyoake, Aichi 47011, Japan. RP Akita, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St,BHX-630, Boston, MA 02114 USA. NR 5 TC 3 Z9 5 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-1873 J9 CONTACT DERMATITIS JI Contact Dermatitis PD JUN PY 2003 VL 48 IS 6 BP 348 EP 349 DI 10.1034/j.1600-0536.2003.00151.x PG 2 WC Allergy; Dermatology SC Allergy; Dermatology GA 737LD UT WOS:000186231100022 PM 14531887 ER PT J AU Nierenberg, AA Trivedi, M Ritz, L Wisniewski, S Quitkin, F Stegman, D Burroughs, D Greist, J Fava, M Rush, AJ AF Nierenberg, AA Trivedi, M Ritz, L Wisniewski, S Quitkin, F Stegman, D Burroughs, D Greist, J Fava, M Rush, AJ TI STAR*D safety monitoring: Lessons from a large hybrid study of depression SO CONTROLLED CLINICAL TRIALS LA English DT Meeting Abstract CT Joint International Conference of the International-Society-for-Clinical-Biostatistics/Society-for-Clinical-Tr ials CY JUL 20-24, 2003 CL LONDON, ENGLAND SP Int Soc Clin Biostat, Soc Clin Trials C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD JUN PY 2003 VL 24 SU 3 MA P15 BP 100S EP 100S PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 686TP UT WOS:000183337300119 ER PT J AU Render, ML Kim, HM Welsh, DE Timmons, S Johnston, J Hui, S Connors, AF Wagner, D Daley, J Hofer, TP AF Render, ML Kim, HM Welsh, DE Timmons, S Johnston, J Hui, S Connors, AF Wagner, D Daley, J Hofer, TP CA Invest TI Automated intensive care unit risk adjustment: Results from a National Veterans Affairs study SO CRITICAL CARE MEDICINE LA English DT Article DE intensive care unit; mortality; severity adjustment; outcome; informatics ID III PROGNOSTIC SYSTEM; APACHE-II; SEVERITY; MORTALITY; ILLNESS; MODELS; PREDICTIONS; SURGERY; QUALITY; LENGTH AB Context. Comparison of outcome among intensive care units (ICUs) requires risk adjustment for differences in severity of illness and risk of death at admission to the ICU, historically obtained by costly chart review and manual data entry. Objective: To accurately estimate patient risk of death in the ICU using data easily available in hospital electronic databases to permit automation. Design and Setting: Cohort study to develop and validate a model to predict mortality at hospital discharge using multivariate logistic regression with a split derivation (17,731) and validation (11,646) sample formed from 29,377 consecutive first ICU admissions to medical, cardiac, and surgical ICUs in 17 Veterans' Health Administration hospitals between February 1996 and July 1997. Main Outcome Measures: Mortality at hospital discharge adjusted for age, laboratory data, diagnosis, source of ICU admission, and comorbid illness. Results. The overall hospital death rate was 11.3%. In the validation sample, the model separated well between survivors and nonsurvivors (area under the receiver operating characteristic curve = 0.885). Examination of the observed vs. the predicted mortality across the range of mortality showed the model was well calibrated. Conclusions., Automation could broaden access to risk adjustment of ICU outcomes with only a small trade-off in discrimination. Broader use might promote valid evaluation of ICU outcomes, encouraging effective practices and improving ICU quality. C1 VAMC, Cincinnati, OH 45220 USA. VA Ann Arbor HSR&D, Ctr Excellence, Ann Arbor, MI USA. Univ Cincinnati, Dept Med, Div Pulm Crit Care, Cincinnati, OH 45221 USA. Univ Cincinnati, Dept Med, Sect Hlth Outcomes, Cincinnati, OH 45221 USA. Roudebusch VAMC, Regienstrieff Inst, Indianapolis, IN USA. Harvard Univ, Sch Med, Inst Hlth Policy, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Univ Virginia, Sch Med, Dept Hlth Eval Sci, Charlottesville, VA 22903 USA. Univ Michigan, Dept Med, Ctr Stat Consultat & Res, Ann Arbor, MI 48109 USA. RP Render, ML (reprint author), VAMC, Cincinnati, OH 45220 USA. NR 32 TC 52 Z9 52 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 JUN PY 2003 VL 31 IS 6 BP 1638 EP 1646 DI 10.1097/01.CCM.0000055372.08235.09 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 691DC UT WOS:000183588700005 PM 12794398 ER PT J AU Trocme, SD Leiferman, KM George, T Bonini, S Foster, CS Smit, EE Sra, SK Grabowski, LR Dohlman, CH AF Trocme, SD Leiferman, KM George, T Bonini, S Foster, CS Smit, EE Sra, SK Grabowski, LR Dohlman, CH TI Neutrophil and eosinophil participation in atopic and vernal keratoconjunctivitis SO CURRENT EYE RESEARCH LA English DT Article DE atopic keratoconjunctivitis; conjunctival epithelium; eosinophil major basic protein; neutrophil elastase; vernal keratoconjunctivitis ID MAJOR BASIC-PROTEIN; EXTRACELLULAR DEPOSITION; CONJUNCTIVAL DEPOSITION; CATIONIC PROTEIN; GRANULE; DISEASE; ELASTASE; DEGRANULATION; LOCALIZATION; ACTIVATION AB Purpose. A retrospective study was conducted at three centers to examine the participation of neutrophils and eosinophils in the inflammatory processes associated with atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC). Methods. Conjunctival specimens were obtained from four patients with AKC, six with VKC, and five normal subjects. Indirect immunofluoreseent staining was used to localize neutrophil elastase (NE) and eosinophil granule major basic protein (MBP) in serial sections of all specimens. Results. Specimens from both AKC and VKC patients revealed extracellular deposition of NE and MBP, Control specimens showed no or minimal extracellular NE, and no MBP. Statistical analysis demonstrated significantly greater extracellular MBP deposition in AKC specimens compared to controls (p = 0.009), and VKC specimens showed significantly greater staining for both extracellular MBP (p = 0.005) and NE (p = 0.006). Conclusions. These results suggest that neutrophils, in addition to eosinophils, play an active role in the pathogenesis of AKC and VKC as evidenced by the extracellular deposition of their specific granule proteins. C1 Univ Texas, Med Branch, Dept Ophthalmol & Visual Sci, Galveston, TX 77555 USA. Univ Utah, Hlth Sci Ctr, Dept Dermatol, Salt Lake City, UT USA. Univ Roma Tor Vergata, Dept Ophthalmol, Rome, Italy. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Cambridge, MA 02138 USA. RP Trocme, SD (reprint author), Univ Texas, Med Branch, Dept Ophthalmol & Visual Sci, 700 Univ Blvd, Galveston, TX 77555 USA. RI Bonini, Stefano/A-2250-2012 OI Bonini, Stefano/0000-0002-7787-2144 FU NIAID NIH HHS [AI 34577]; NIAMS NIH HHS [AR 36008] NR 34 TC 19 Z9 22 U1 0 U2 3 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD JUN PY 2003 VL 26 IS 6 BP 319 EP 325 DI 10.1076/ceyr.26.5.319.15437 PG 7 WC Ophthalmology SC Ophthalmology GA 705MF UT WOS:000184398300002 PM 12868012 ER PT J AU Wang, JH Eck, MJ AF Wang, JH Eck, MJ TI Assembling atomic resolution views of the immunological synapse SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID T-CELL ACTIVATION; MHC CLASS-II; CRYSTAL-STRUCTURE; SH2 DOMAIN; INTEGRIN ALPHA-V-BETA-3; EXTRACELLULAR SEGMENT; ENCODING GENE; HUMAN CD4; COMPLEX; ADHESION AB Antigen-dependent T-cell activation is initiated by the organized interactions of a host of cell-surface receptors in the interface between the T cell and an antigen-presenting cell. Recent structural studies of many of the receptors that comprise this 'immunological synapse', including integrins, cadherins and costimulatory molecules, reveal in detail the molecular interactions that bridge the synapse. Additionally, structural analyses of the cytoplasmic tails of integrins and co-stimulatory receptors in complex with intracellular signaling proteins are providing insight into the mechanisms that couple receptor clustering on the cell surface with the initiation of cytoplasmic signaling. C1 Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Wang, JH (reprint author), Harvard Univ, Sch Med, Dept Pediat, 44 Binney St, Boston, MA 02115 USA. NR 56 TC 4 Z9 4 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2003 VL 15 IS 3 BP 286 EP 293 DI 10.1016/S0952-7915(03)00055-4 PG 8 WC Immunology SC Immunology GA 689GT UT WOS:000183483800008 PM 12787753 ER PT J AU Menzies, BE AF Menzies, BE TI The role of fibronectin binding proteins in the pathogenesis of Staphylococcus aureus infections SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review DE Staphylococcus aureus; fibronectin; adherence; invasion ID ENDOTHELIAL-CELLS; NUCLEOTIDE-SEQUENCE; EPITHELIAL-CELLS; FNB GENES; ADHERENCE; INVASION; INTERNALIZATION; ENDOCARDITIS; EXPRESSION; APOPTOSIS AB Purpose of review Staphylococcus aureus; produces two closely-related fibronectin-binding proteins (FnBPs) that facilitate attachment by this versatile pathogen. Recent studies of staphylococcal FnBP have increased our understanding of the molecular mechanisms that are critical in bacterial-host cell interactions and in infection. Recent findings This review will summarize current knowledge of the role of the FnBPs of Staphylococcus aureus in the pathogenesis of infection. The FnBPs, which facilitate attachment of this pathogen to host cells and to fibronectin-coated biomaterials, are important mediators of infection in experimental endocarditis. In addition, recent vaccine studies utilizing FnBP derivatives have shown partial protection in animals. FnBPs also act as invasins permitting uptake of the staphylococcus by cultured non-professional phagocytes using host fibronectin to bridge with integrins on the cell surface. However, the precise role of FnBP in tissue invasion and the relevance of intracellular invasion in disease remain to be elucidated. Summary FnBP is one of many adhesins expressed by S. aureus; that influence host tissue adherence by binding to host fibronectin. FnBP-based vaccine strategies and novel anti-adherence tools based upon FnBP derivatives are in the early stages of investigation but may show promise in preventing staphylococcal infections. C1 VA Puget Sound Hlth Care Syst, Infect Dis Sect, Seattle, WA 98108 USA. Univ Washington, Washington, DC USA. RP Menzies, BE (reprint author), VA Puget Sound Hlth Care Syst, Infect Dis Sect, 111-1D,1660 S Columbia Way, Seattle, WA 98108 USA. NR 37 TC 72 Z9 74 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD JUN PY 2003 VL 16 IS 3 BP 225 EP 229 DI 10.1097/01.qco.0000073771.11390.75 PG 5 WC Infectious Diseases SC Infectious Diseases GA 688KP UT WOS:000183434100007 PM 12821812 ER PT J AU Brodsky, AS Johnston, AP Trau, M Silver, PA AF Brodsky, AS Johnston, AP Trau, M Silver, PA TI Analysis of RNA-protein interactions by flow cytometry SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article DE flow cytometry; functional genomics; microbeads; microspheres; RNA-protein interactions ID REAL-TIME MEASUREMENTS; DNA HYBRIDIZATION; BINDING PROTEINS; MESSENGER-RNAS; PROBE DENSITY; SYSTEM; ASSAY; IDENTIFICATION; LIBRARIES; ARRAYS AB Flow cytometry, in combination with advances in bead coding technologies, is maturing as a powerful high-throughput approach for analyzing molecular interactions. Applications of this technology include antibody assays and single nucleotide polymorphism mapping. This review describes the recent development of a microbead flow cytometric approach to analyze RNA-protein interactions and discusses emerging bead coding strategies that together will allow genome-wide identification of RNA-protein complexes. The microbead flow cytometric approach is flexible and provides new opportunities for functional genomic studies and small-molecule screening. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Univ Queensland, Dept Chem, Ctr Nanotechnol & Biomat, St Lucia, Qld 4072, Australia. RP Brodsky, AS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 1 Jimmy Fund Way,SM 922, Boston, MA 02115 USA. RI Johnston, Angus/A-9254-2011; Trau, Matt/E-3944-2015 OI Johnston, Angus/0000-0001-5611-4515; NR 42 TC 4 Z9 5 U1 0 U2 2 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD JUN PY 2003 VL 5 IS 3 BP 235 EP 240 PG 6 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 698XJ UT WOS:000184024600004 PM 12870432 ER PT J AU Zhang, H Azevedo, RBR Lints, R Doyle, C Teng, YQ Haber, D Emmons, SW AF Zhang, H Azevedo, RBR Lints, R Doyle, C Teng, YQ Haber, D Emmons, SW TI Global regulation of Hox gene expression in C-elegans by a SAM domain protein SO DEVELOPMENTAL CELL LA English DT Article ID POLYCOMB GROUP PROTEIN; CAENORHABDITIS-ELEGANS; VULVAL INDUCTION; CELL; EVOLUTION; PATTERNS; HOMOLOG; PROLIFERATION; REPRESSION; GERMLINE AB Polycomb group (PcG)-mediated repression of C. elegrans Hox genes has not been demonstrated, and genes homologous to components of one of the PcG complexes (PRC1) have not been identified in the C. elegans genome. We find that a mechanism of general Hox gene repression exists in C. elegans, carried out in part by SOP-2, a protein related to, but not orthologous with, any PcG protein. sop-2 mutations lead to widespread ectopic expression of Hox genes and homeotic transformations. SOP-2 contains a SAM domain, a self-associating protein domain found in other repressors, including a core component of PRC1 and ETS transcription factors. Phylogenetic analysis indicates that this domain is more closely related to those of the ETS family than to those of PcG proteins. The results suggest that global repression of Hox genes has been taken over by a different branch of the SAM domain family during the evolution of nematodes. C1 Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Emmons, SW (reprint author), Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. OI Lints, Robyn/0000-0002-1403-2121 FU NCI NIH HHS [2T32CA09216, CA58596]; NIGMS NIH HHS [GM39353] NR 46 TC 34 Z9 53 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUN PY 2003 VL 4 IS 6 BP 903 EP 915 DI 10.1016/S1534-5807(03)00136-9 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 687NK UT WOS:000183383100014 PM 12791274 ER PT J AU Newmyer, SL Christensen, A Sever, S AF Newmyer, SL Christensen, A Sever, S TI Auxilin-dynamin interactions link the uncoating ATPase chaperone machinery with vesicle formation SO DEVELOPMENTAL CELL LA English DT Article ID CLATHRIN-MEDIATED ENDOCYTOSIS; GTPASE-ACTIVATING PROTEINS; RATE-LIMITING STEP; COATED VESICLES; IN-VIVO; DOMAIN; HSC70; BINDING; CELLS; MECHANISM AB The large GTPase dynamin is required for budding of clathrin-coated vesicles from the plasma membrane, after which the clathrin coat is removed by the chaperone Hsc70 and its cochaperone auxilin. Recent evidence suggests that the GTP-bound form of dynamin may recruit factors that execute the fission reaction. Here, we show that dynamin:GTP binds to Hsc70 and auxilin. We mapped two domains within auxilin that interact with dynamin, and these domains inhibit endocytosis when overexpressed in HeLa cells or when added in a permeable cell assay. The inhibition is not due to impairment of clathrin uncoating or to altered clathrin distribution in cells. Thus, in addition to its requirement for clathrin uncoating, our results show that auxilin also acts during the early steps of clathrin-coated vesicle formation. The data suggest that dynamin regulates the action of molecular chaperones in vesicle budding during endocytosis. C1 Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02129 USA. Univ Calif San Francisco, George Williams Hooper Fdn, San Francisco, CA 94143 USA. RP Sever, S (reprint author), Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02129 USA. NR 58 TC 57 Z9 60 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUN PY 2003 VL 4 IS 6 BP 929 EP 940 DI 10.1016/S1534-5807(03)00157-6 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 687NK UT WOS:000183383100016 PM 12791276 ER PT J AU El-Haschimi, K Dufresne, SD Hirshman, MF Flier, JS Goodyear, LJ Bjorbaek, C AF El-Haschimi, K Dufresne, SD Hirshman, MF Flier, JS Goodyear, LJ Bjorbaek, C TI Insulin resistance and lipodystrophy in mice lacking ribosomal S6 kinase 2 SO DIABETES LA English DT Article ID ACTIVATED PROTEIN-KINASE; EPIDERMAL GROWTH-FACTOR; COFFIN-LOWRY-SYNDROME; SKELETAL-MUSCLE; SIGNAL-TRANSDUCTION; MENTAL-RETARDATION; GLYCOGEN-SYNTHASE; GLUCOSE-UPTAKE; MESSENGER-RNA; MAPK PATHWAY AB The p90 ribosomal S6 kinase 2 (RSK2) is a serine/threonine kinase with high expression levels in adipose tissue. Numerous in vitro studies show that RSK2 is activated by a broad number of cellular stimuli and suggest that RSK2 is involved in the regulation of a variety of cellular processes. However, the physiological role of RSK2 still remains elusive. We therefore generated rsk2 knockout (KO) mice to better understand the function of RSK2 in vivo. Birth weights of RSK2 KO mice are normal, but the body weight is reduced with age, as compared with wild-type littermates. We found that the difference in body weight was largely caused by a specific loss of white adipose tissue that is accompanied by reduced serum levels of the adipocyte-derived peptide, leptin. KO mice also have impaired glucose tolerance and elevated fasting insulin and glucose levels that are restored following administration of low amounts of leptin, which do not affect food intake. We conclude that RSK2 plays a novel and an important role in regulation of adipose mass in mice and speculate that the reduction in fat tissue may negatively affect insulin sensitivity, as observed in human lipodystrophy, through reduced levels of adipocyte-derived factors, such as leptin. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Hosp Magdeburg, Magdeburg, Germany. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Bjorbaek, C (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,RN 325, Boston, MA 02215 USA. FU NIAMS NIH HHS [AR 42238]; NIDDK NIH HHS [P30 DK 36836] NR 64 TC 25 Z9 25 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2003 VL 52 IS 6 BP 1340 EP 1346 DI 10.2337/diabetes.52.6.1340 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683UD UT WOS:000183167600005 PM 12765942 ER PT J AU Peppa, M He, CJ Hattori, M McEvoy, R Zheng, F Vlassara, H AF Peppa, M He, CJ Hattori, M McEvoy, R Zheng, F Vlassara, H TI Fetal or neonatal low glycotoxin environment prevents autoimmune diabetes in NOD mice SO DIABETES LA English DT Article ID ADVANCED GLYCATION ENDPRODUCTS; ADVANCED GLYCOSYLATION; GLYCOXIDATION PRODUCTS; DIETARY GLYCOTOXINS; DIABETOGENIC GENE; OXIDATIVE STRESS; IMMUNE TOLERANCE; RISK FACTOR; BETA-CELLS; BB RATS AB Advanced glycation end products (AGES) are implicated in beta-cell oxidant stress. Diet-derived AGE (dAGE) are shown to contribute to end-organ toxicity attributed to diabetes. To assess the role of dAGE on type 1 diabetes, NOD mice were exposed to a high-AGE diet (H-AGE) and to a nutritionally similar diet with approximate fivefold-lower levels of N-epsilon-carboxymethyllysine (CML) and methylglyoxal-derivatives (MG) (L-AGE). Suppression of serum CML and MG in L-AGE-fed mice was marked by suppression of diabetes (H-AGE mice >94% vs. L-AGE mice 33% in founder [F](0), 14% in F-1, and 13% in F-2 offspring, P < 0.006) and by a delay in disease onset (4-month lag). Survival for L-AGE mice was 76 vs. 0% after 44 weeks of H-AGE mice. Reduced insulitis in L-AGE versus H-AGE mice (P < 0.01) was marked by GAD- and insulin-unresponsive pancreatic interleukin (IL)-4-positive CD4+ cells compared with the GAD-and insulin-responsive interferon (IFN)-gamma-positive T-cells from H-AGE mice (P < 0.005). Splenocytes from L-AGE mice consisted of GAD- and insulin-responsive IL-10-positive CD4+ cells compared with the IFN-gamma-positive T-cells from H-AGE mice (P < 0.005). Therefore, high AGE intake may provide excess antigenic stimulus for T-cell-mediated diabetes or direct beta-cell injury in NOD mice; both processes are ameliorated by maternal or neonatal exposure to L-AGE nutrition. C1 Mt Sinai Sch Med, Div Expt Diabet & Aging, Dept Geriatr, New York, NY 10029 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Peppa, M (reprint author), Mt Sinai Sch Med, Div Expt Diabet & Aging, Dept Geriatr, Box 1640, New York, NY 10029 USA. RI e-, a/F-9947-2012 NR 50 TC 68 Z9 69 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2003 VL 52 IS 6 BP 1441 EP 1448 DI 10.2337/diabetes.52.6.1441 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683UD UT WOS:000183167600018 PM 12765955 ER PT J AU Rana, JS Mukamal, KJ Morgan, JP Muller, JE Mittleman, MA AF Rana, JS Mukamal, KJ Morgan, JP Muller, JE Mittleman, MA TI Circadian variation in the onset of myocardial infarction - Effect of duration of diabetes SO DIABETES LA English DT Article ID CARDIAC AUTONOMIC NEUROPATHY; BLOOD-PRESSURE VARIATION; HEART-RATE-VARIABILITY; Q-WAVE INFARCTION; SYMPTOM ONSET; CARDIOVASCULAR-DISEASE; MORNING INCREASE; QTC DISPERSION; MELLITUS; RISK AB There are conflicting reports regarding circadian variation in the onset of acute myocardial infarction (MI) among patients with diabetes. We therefore, studied the circadian pattern of the incidence of acute MI in patients (n = 3,882) who were enrolled in the Onset Study stratified by the presence, type, and duration of diabetes. The Onset Study was conducted at 64 U.S. medical centers between August 1989 and September 1996. We used harmonic regression model to evaluate the circadian variation of MI symptom onset in patients with and without diabetes. Subgroup analysis was performed according to the presence, type, and duration of diabetes by the X-2 test (dividing the day into four 6-h intervals). Patients without diabetes exhibited a prominent morning peak in the incidence of acute MI symptom onset (P < 0.001). In contrast, patients with type 1 diabetes and type 2 diabetes greater than or equal to5 years had a marked attenuation of the morning peak. Patients who had type 2 diabetes diagnosed within the previous 5 years had a pattern of onset of acute MI similar to patients without diabetes. Patients with type 1 diabetes and those with type 2 diabetes greater than or equal to5 years have an attenuation of the morning peak in acute MI. Inconsistency in observation of such an effect in patients with diabetes in the past may well have been due to difference in the duration of diabetes and thus the variable extent of underlying autonomic dysfunction. Diabetes 52:1464-1468, 2003. C1 Beth Israel Deaconess Med Ctr, Div Cardiovasc, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Dept Med, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Mittleman, MA (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc, Dept Med, 1 Autumn St,5th Floor, Boston, MA 02215 USA. FU NHLBI NIH HHS [HL 41016, T32 HL 07374-22] NR 48 TC 26 Z9 26 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2003 VL 52 IS 6 BP 1464 EP 1468 DI 10.2337/diabetes.52.6.1464 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683UD UT WOS:000183167600021 PM 12765958 ER PT J AU Meigs, JB Muller, DC Nathan, DM Blake, DR Andres, R AF Meigs, JB Muller, DC Nathan, DM Blake, DR Andres, R TI The natural history of progression from normal glucose tolerance to type 2 diabetes in the Baltimore Longitudinal Study of Aging SO DIABETES LA English DT Article ID INSULIN SECRETORY DYSFUNCTION; IMPAIRED FASTING GLUCOSE; DIAGNOSTIC-CRITERIA; LIFE-STYLE; BETA-CELL; HIGH-RISK; RESISTANCE; MELLITUS; NIDDM; PREVENTION AB The natural history of progression from normal glucose tolerance (NOT), to impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes is riot well defined. We studied this progression using biennial oral glucose, tolerance tests performed in the Baltimore Longitudinal Study of Aging, and. survival analysis to assess progression from NGT to abnormal fasting plasma glucose (FPG; greater than or equal to6.1 mmol/l), abnormal 2-h plasma. glucose (2hPG; greater than or equal to7.8. mmol/l), IFG (FPG 6.1-6.9 mmol/l, 2hPG less than or equal to7.8 mmol/l), and IGT (FPG <6.1 mmol/l; 2hPG-7.8-11.0 mmol/l), and from IFG-IGT to diabetes (FPG greater than or equal to7.0 mmol/l or 2hPG greater than or equal to11.1 mmol/l). At baseline, the 815 subjects had a mean age of 57 years, 35% were women, and 60% had NOT. Of the 488 subjects with NOT, over half were followed for at least 10 years. By 10 years, 14% had progressed to abnormal FPG and 48% to abnormal 2hPG. Of the 267 subjects who progressed to IFG-IGT, 216 had additional follow-up. By 10 years, 8% of these progressed to diabetes by FPG whereas 27% progressed by 2hPG. In subsidiary analyses, we defined "abnormal" FPG as greater than or equal to5.55 mmol/l and "diabetic". FPG as greater than or equal to6.1. mmol/l; making the baseline prevalence of IFG similar to that of IGT.. By these criteria, 43% progressed to abnormal FPG and 43% to abnormal 2hPG by 10 years of follow-up; among subjects developing impaired FPG or 2hPG, 22% progressed to diabetes by FPG whereas 17% progressed by 2hPG at 10 years. Nonetheless, 42% of subjects developing abnormal FPG did not develop abnormal 2hPG, and vice versa. We conclude that, although phenotypic differences in rates of progression are partly a function of diagnostic thresholds, fasting and postchallenge hyperglycemia may represent phenotypes with distinct natural histories in the evolution of type 2 diabetes. Diabetes 52: 1415-1484,2003. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. NIA, Baltimore, MD 21224 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. NR 35 TC 158 Z9 165 U1 1 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2003 VL 52 IS 6 BP 1475 EP 1484 DI 10.2337/diabetes.52.6.1475 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683UD UT WOS:000183167600023 PM 12765960 ER PT J AU Kulkarni, RN Almind, K Goren, HJ Winnay, JN Ueki, K Okada, T Kahn, CR AF Kulkarni, RN Almind, K Goren, HJ Winnay, JN Ueki, K Okada, T Kahn, CR TI Impact of genetic background on development of hyperinsulinemia and diabetes in insulin receptor/insulin receptor substrate-1 double heterozygous mice SO DIABETES LA English DT Article ID MULTIFACTORIAL MOUSE MODEL; MOLECULAR MECHANISMS; RESISTANCE; MELLITUS; EXPRESSION; LACKING; SENSITIVITY; KNOCKOUT; STRAINS; OBESITY AB Type 2 diabetes is a complex disease in which genetic and environmental factors interact to produce alterations in insulin action and insulin secretion, leading to hyperglycemia. To evaluate the influence of genetic background on development of diabetes in a genetically susceptible host, we generated mice that are double heterozygous (DH) for knockout of the insulin receptor and insulin receptor substrate-1 on three genetic backgrounds (C57BL/6 [B6], 129Sv, and DBA). Although DH mice on all backgrounds showed insulin resistance, their phenotypes were dramatically different. B6 DH mice exhibited marked hyperinsulinemia and massive islet hyperplasia and developed early hyperglycemia, with 85% overtly diabetic by 6 months. By contrast, 1295v DH mice showed mild hyperinsulinemia and minimal islet hyperplasia, and <2% developed diabetes. DBA mice had slower development of hyperglycemia, intermediate insulin levels, and evidence of islet degeneration, with 64% developing diabetes. Thus, mice carrying the same genetic defects on different backgrounds exhibited the full spectrum of abnormalities observed in humans with type 2 diabetes, which allowed for identification of potential loci that promote development of the diabetic phenotype. Diabetes 52:1528-1534, 2003. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 02885, DK 31036] NR 34 TC 77 Z9 77 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2003 VL 52 IS 6 BP 1528 EP 1534 DI 10.2337/diabetes.52.6.1528 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683UD UT WOS:000183167600029 PM 12765966 ER PT J AU Almind, K Kulkarni, RN Lannon, SM Kahn, CR AF Almind, K Kulkarni, RN Lannon, SM Kahn, CR TI Identification of interactive loci linked to insulin and leptin in mice with genetic insulin resistance SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; UNCOUPLING PROTEIN-2; GLUCOSE-METABOLISM; SKELETAL-MUSCLE; OBESITY-PRONE; PATHOGENESIS; EXPRESSION; MAP; DISRUPTION; ADIPOSE AB Mice double heterozygous (DH) for deletion of insulin receptor and insulin receptor substrate-1 are lean, insulin resistant, and have a phenotype that strongly depends on the genetic background of the mouse. On the C57BL/6 (B6) background, DH mice develop marked hyperinsulinemia and diabetes, whereas on the 12956 background, DH mice exhibit only mild elevations of insulin and remain free of diabetes. F2 male mice created by an intercross between these two strains exhibit a 60% incidence of diabetes and a bell-shaped distribution of insulin levels as related to glucose, reminiscent of that in humans with type 2 diabetes. These mice also exhibit a wide range of leptin levels as related to body weight. A genome-wide scan of F2 mice reveals a quantitative trait locus (QTL) related to hyperinsulinemia on chromosome 14 (D14Mit55) with a peak logarithm of odds (LOD) score of 5.6, accounting for up to 69% of this trait. A QTL with a LOD score of 3.7 related to hyperleptinemia is present on chromosome 7 at D12Mit38 (a marker previously assigned to chromosome 12) in the area of the uncoupling protein 2/3 gene cluster. This locus also interacts synergistically with D14Mit55 in development of hyperinsulinemia and with a QTL on chromosome 12 (D12Mit231) related to hyper-glycemia. These data demonstrate how multiple genetic modifiers can interact and influence the development of diabetes and the phenotype of animals with genetically programmed insulin resistance and provide evidence as to the location and nature of these genes. Diabetes 52: 1535-1543,2003. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Almind, K (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [K08 DK 02885-02, DK 31036, DK 45935] NR 47 TC 34 Z9 34 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2003 VL 52 IS 6 BP 1535 EP 1543 DI 10.2337/diabetes.52.6.1535 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683UD UT WOS:000183167600030 PM 12765967 ER PT J AU Karamohamed, S Demissie, S Volcjak, J Liu, CY Heard-Costa, N Liu, J Shoemaker, CM Panhuysen, CI Meigs, JB Wilson, P Atwood, LD Cupples, LA Herbert, A AF Karamohamed, S Demissie, S Volcjak, J Liu, CY Heard-Costa, N Liu, J Shoemaker, CM Panhuysen, CI Meigs, JB Wilson, P Atwood, LD Cupples, LA Herbert, A TI Polymorphisms in the insulin-degrading enzyme gene are associated with type 2 diabetes in men from the NHLBI Framingham Heart Study SO DIABETES LA English DT Article ID LINKAGE DISEQUILIBRIUM; HUMAN GENOME; LOCUS; SCAN; PEDIGREES; DISEASE; BLOCKS; MICE AB Linkage studies have mapped a susceptibility gene for type 2 diabetes to the long arm of chromosome 10, where we have previously identified a quantitative trait locus that affects fasting blood glucose within the Framingham Heart Study cohort. One candidate gene in this region is the insulin-degrading enzyme (IDE), which, in the GK rat model, has been associated with nonobese type 2 diabetes. Single nucleotide polymorphisms (SNPs) were used to map a haplotype block in the 3' end of IDE, which revealed association with HbA(1c), fasting plasma glucose (FPG), and mean fasting plasma glucose (mFPG) measured over 20 years. The strongest associations were found in a sample of unrelated men. The lowest trait values were associated with a haplotype (TT, fsimilar to0.32) containing the minor allele of rs2209772 and the major allele of the rs1887922 SNP (FPG P < 0.001, mFPG P < 0.003, HbA(1c) P < 0.025). Another haplotype (CC, fsimilar to0.16) was associated with elevated HbA(1c) (P < 0.002) and type 2 diabetes (P < 0.001, odds ratio 1.96, 95% CI 1.28-3.00). The evidence presented supports the possibility that IDE is a susceptibility gene for diabetes in populations of European descent. Diabetes 52:1562-1567, 2003. C1 Boston Univ, Sch Med, Dept Neurol, Framingham Heart Study,Genet Lab, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Med, Gen Internal Med Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Clin Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Herbert, A (reprint author), Boston Univ, Sch Med, Dept Neurol, Framingham Heart Study,Genet Lab, 715 Albany St, Boston, MA 02118 USA. FU NHLBI NIH HHS [M01 HC 38083, N01 HC 25195] NR 20 TC 69 Z9 73 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2003 VL 52 IS 6 BP 1562 EP 1567 DI 10.2337/diabetes.52.6.1562 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683UD UT WOS:000183167600034 PM 12765971 ER PT J AU Magre, J Delepine, M Van Maldergem, L Robert, JJ Maassen, JA Meier, M Panz, VR Kim, CA Tubiana-Rufi, N Czernichow, P Seemanova, E Buchanan, CR Lacombe, D Vigouroux, C Lascols, O Kahn, CR Capeau, J Lathrop, M AF Magre, J Delepine, M Van Maldergem, L Robert, JJ Maassen, JA Meier, M Panz, VR Kim, CA Tubiana-Rufi, N Czernichow, P Seemanova, E Buchanan, CR Lacombe, D Vigouroux, C Lascols, O Kahn, CR Capeau, J Lathrop, M TI Prevalence of mutations in AGPAT2 among human lipodystrophies SO DIABETES LA English DT Article ID SEIP CONGENITAL LIPODYSTROPHY; LYSOPHOSPHATIDIC ACID ACYLTRANSFERASES; LIPOATROPHIC DIABETES-MELLITUS; GENETIC EXCLUSION; CODING MUTATIONS; CDNA CLONING; EXPRESSION; IDENTIFICATION; LOCALIZATION AB Berardinelli-Seip congenital lipodystrophy (BSCL) is a heterogeneous genetic disease characterized by near absence of adipose tissue and severe insulin resistance. We have previously identified mutations in the seipin gene in a subset of our patients' cohort. Recently, disease-causing mutations in AGPAT2 have been reported in BSCL patients. In this study, we have performed mutation screening in AGPAT2 and the related AGPAT1 in patients with BSCL or other forms of lipodystrophy who have no detectable mutation in the seipin gene. We found 38 BSCL patients from 30 families with mutations in AGPAT2. Three of the known mutations were frequently found in our families. Of the eight new alterations, six are null mutations and two are missense mutations (Glu172Lys and Ala238Gly). All the patients harboring AGPAT2 mutations presented with typical features of BSCL. We did not find mutations in patients with other forms of lipodystrophies, including the syndromes of Lawrence, Dunnigan, and Barraquer-Simons, or with type A insulin resistance. In conclusion, mutations in the seipin gene and AGPAT2 are confined to the BSCL phenotype. Because we found mutations in 92 of the 94 BSCL patients studied, the seipin gene and AGPAT2 are the two major genes involved in the etiology of BSCL. Diabetes 52:1573-1578, 2003. C1 Univ Paris 06, INSERM, U402, Fac Med St Antoine, F-75571 Paris, France. Natl Ctr Genotyping, Evry, France. Inst Pathol & Genet, Ctr Human Genet, Loverval, Belgium. Hop Necker Enfants Malad, Dept Pediat Diabetol, Paris, France. Leiden Univ, Sylvius Lab, Med Ctr, Leiden, Netherlands. Univ Witwatersrand, Dept Med, ZA-2001 Johannesburg, South Africa. Univ Sao Paulo, Crianca Inst, Dept Pediat, Sao Paulo, Brazil. Hop Robert Debre, Dept Pediat Endocrinol, F-75019 Paris, France. Charles Univ, Dept Child Hlth, Prague, Czech Republic. Pellegrin Enfants Hosp, Dept Med Genet, Bordeaux, France. Harvard Univ, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Magre, J (reprint author), Univ Paris 06, INSERM, U402, Fac Med St Antoine, 27 Rue Chaligny, F-75571 Paris, France. RI MAGRE, Jocelyne/D-4788-2015 NR 25 TC 53 Z9 54 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2003 VL 52 IS 6 BP 1573 EP 1578 DI 10.2337/diabetes.52.6.1573 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683UD UT WOS:000183167600036 PM 12765973 ER PT J AU LeMaster, JW Sugarman, JR Baumgardner, G Reiber, GE AF LeMaster, JW Sugarman, JR Baumgardner, G Reiber, GE TI Motivational brochures increase the number of Medicare-eligible persons with diabetes making therapeutic footwear claims SO DIABETES CARE LA English DT Article ID POSTCARD REMINDERS; MAMMOGRAPHY USE; INTERVENTIONS; BENEFICIARIES; PREVENTION; VACCINE; SHOES; TRIAL; RATES; CARE AB OBJECTIVE - This study tests the hypothesis that Medicare beneficiaries at high risk of foot complications who are mailed a motivational brochure describing the Medicare diabetes-related therapeutic footwear benefit will increase their therapeutic footwear-related Medicare claims. RESEARCH DESIGN AND METHODS - in this quasi-experimental study, a motivational brochure was mailed in the summer of 1997 to 5,872 Medicare beneficiaries in Washington, Alaska, and Idaho who were identified as being at high risk for foot-related claims on the basis of their prior Medicare claims history. Beneficiaries were identified through footwear claims made in these states-and also in three comparison states (Oregon, Montana, and Wyoming) during the 18 months before and after the mailing. Linear regression was used to compare the number of persons making claims in the intervention states with the comparison states before, at the time of, and after the mailing. RESULTS - Before the intervention, the number of persons making claims was increasing in the nonintervention states and decreasing in the intervention states. During the first month after the intervention mailing, the number of persons making claims remained nearly the same in nonintervention states, but increased 13 persons per month in intervention states (95% Cl 3.5-11 persons/month). After the intervention, the number of persons making claims continued to increase similarly in both intervention and nonintervention states. CONCLUSIONS - Mailed motivational brochures were associated with an increase in the number of persons making therapeutic footwear claims. Randomized trials should confirm these findings. C1 Univ Missouri, Dept Family & Community Med, Columbia, MO 65212 USA. Qualis Hlth, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Dept Vet Affairs, VA Puget Sound Hlth Care Syst, Hlth Serv & Rehabil Res & Dev, Seattle, WA USA. RP LeMaster, JW (reprint author), Univ Missouri, Dept Family & Community Med, 1 Hosp Dr, Columbia, MO 65212 USA. FU PHS HHS [500-99-WA02] NR 19 TC 1 Z9 1 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2003 VL 26 IS 6 BP 1679 EP 1684 DI 10.2337/diacare.26.6.1679 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UR UT WOS:000185505500003 PM 12766093 ER PT J AU Sheehan, P Jones, P Caselli, A Giurini, JM Veves, A AF Sheehan, P Jones, P Caselli, A Giurini, JM Veves, A TI Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial SO DIABETES CARE LA English DT Article ID VENOUS ULCERS; RISK-FACTORS; MANAGEMENT; MULTICENTER; COST AB OBJECTIVE - To assess the ability of the 4-week healing rate to predict complete healing over a 12-week period in a large prospective multicenter trial of diabetic patients with foot ulceration. RESEARCH DESIGN AND METHODS - We examined the change in ulcer area over a 4-week period as a predictor of wound healing within 12 weeks in patients who were seen weekly in a prospective, randomized controlled trial. RESULTS - Wound area measurements at baseline and after 4 weeks were performed in 203 patients. The midpoint between the percentage area reduction from baseline at 4 weeks in patients healed versus those not healed at 12 weeks was found to be 53%. Subjects with a reduction in ulcer area greater than the 4-week median had a 12-week healing rate of 58%, whereas those with reduction in ulcer area less than the 4-week median had a healing rate of only 9% (P < 0.01). The absolute change in ulcer area at 4 weeks was significantly greater in healers versus nonhealers (1.5 vs. 0.8 cm(2), p < 0.02). The percent change in wound area at 4 weeks in those who healed was 82% (95% CI 70-94), whereas in those who failed to heal, the percent change in wound area was 25% (15-35; P < 0.001). CONCLUSIONS - The percent change in foot ulcer area after 4 weeks of observation is a robust predictor of healing at 12 weeks. This simple tool may serve as a pivotal clinical decision point in the care of diabetic foot ulcers for early identification of patients who may not respond to standard care and may need additional treatment. C1 Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA. NYU, Hosp Joint Dis, Sch Med, Diabet Foot & Ankle Ctr,Orthopaed Inst, New York, NY 10003 USA. With Confidence Ltd, Surrey, England. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg,Microcirculat Lab, Boston, MA 02215 USA. RP Veves, A (reprint author), Joslin Beth Israel Deaconess Foot Ctr, 1 Deaconess Rd, Boston, MA 02215 USA. NR 22 TC 194 Z9 197 U1 1 U2 8 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 JUN PY 2003 VL 26 IS 6 BP 1879 EP 1882 DI 10.2337/diacare.26.6.1879 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UR UT WOS:000185505500037 PM 12766127 ER PT J AU Freemark, M Levitsky, LL AF Freemark, M Levitsky, LL TI Screening for celiac disease in children with type 1 diabetes - Two views of the controversy SO DIABETES CARE LA English DT Editorial Material ID GLUTEN-FREE DIET; INFLAMMATORY-BOWEL-DISEASE; BONE-MINERAL DENSITY; CLINICAL CHARACTERISTICS; CEREBRAL CALCIFICATIONS; HIGH PREVALENCE; SMALL-INTESTINE; UNITED-STATES; FOLLOW-UP; RISK C1 Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Endocrine Unit, Boston, MA USA. RP Freemark, M (reprint author), Duke Univ, Med Ctr, Dept Pediat, Box 3080, Durham, NC 27710 USA. NR 74 TC 56 Z9 58 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2003 VL 26 IS 6 BP 1932 EP 1939 DI 10.2337/diacare.26.6.1932 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UR UT WOS:000185505500048 PM 12766138 ER PT J AU Pildal, J Lajer, M Hansen, SK Almind, K Ambye, L Borch-Johnsen, K Carstensen, B Hansen, T Pedersen, O AF Pildal, J Lajer, M Hansen, SK Almind, K Ambye, L Borch-Johnsen, K Carstensen, B Hansen, T Pedersen, O TI Studies of variability in the islet amyloid polypeptide gene in relation to Type 2 diabetes SO DIABETIC MEDICINE LA English DT Article DE Type 2 diabetes; IAPP; amylin; mutation analysis; polymorphism ID IMPAIRED GLUCOSE-TOLERANCE; PANCREATIC AMYLIN; INSULIN; MELLITUS; SECRETION; MUTATION; POLYMORPHISM; JAPANESE; PROMOTER; RELEASE AB Aims To explore whether the coding region of the islet amyloid polypeptide (IAPP) gene contains genetic variants associated with Type 2 diabetes and whether a previously reported association of the promoter variant -132g-->a with Type 2 diabetes could be reproduced in Danish Caucasians. Methods The coding region was analyzed using single strand conformation polymorphism (SSCP) and heteroduplex analysis in 192 Type 2 diabetic patients. Restriction fragment length polymorphism (RFLP) was employed to screen for the promoter variant in 414 Type 2 diabetic patients and 182 glucose-tolerant control subjects. Results The SSCP analysis identified an IVS+75a-->g variant in two patients. The frequency of heterozygous carriers of the promoter variant in the case-control study was 4.1% (17/414) and 7.1% (13/182), respectively. Odds ratio of the prevalence of Type 2 diabetes in carriers compared with non-carriers was estimated to be 0.47 (95% confidence interval 0.19, 1.15). Conclusine Neither variability in the coding region of the IAPP gene nor the -132g-->a promoter variant was associated with Type 2 diabetes among the studied Danish Caucasians. C1 Prof Oluf Pedersen, Steno Diabet Ctr, DK-2820 Gentofte, Denmark. Hagedorn Res Inst, Copenhagen, Denmark. Joslin Diabet Ctr, Boston, MA 02215 USA. Copenhagen Univ Hosp, Dept Clin Biochem, Hvidovre, Denmark. Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark. RP Pildal, J (reprint author), Prof Oluf Pedersen, Steno Diabet Ctr, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark. NR 20 TC 7 Z9 7 U1 0 U2 1 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 JUN PY 2003 VL 20 IS 6 BP 491 EP 494 DI 10.1046/j.1464-5491.2003.00951.x PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 684JU UT WOS:000183203300012 PM 12786686 ER PT J AU Nurgalieva, ZZ Graham, DY AF Nurgalieva, ZZ Graham, DY TI Pearls and pitfalls of assessing Helicobacter pylori status SO DIGESTIVE AND LIVER DISEASE LA English DT Article DE Helicobacter pylori; stool antigen; urea breath test ID C-13-UREA BREATH TEST; CITRIC-ACID; INFECTION; ERADICATION; COHORT C1 VA Med Ctr, Dept Med, Houston, TX 77211 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Graham, DY (reprint author), VA Med Ctr, Dept Med, Houston, TX 77211 USA. NR 14 TC 13 Z9 13 U1 0 U2 0 PU PACINI EDITORE PI PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE OSPEDALETTO, 56121 PISA, ITALY SN 1590-8658 J9 DIGEST LIVER DIS JI Dig. Liver Dis. PD JUN PY 2003 VL 35 IS 6 BP 375 EP 377 DI 10.1016/S1590-8658(03)00166-X PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 700LY UT WOS:000184114500001 PM 12868671 ER PT J AU Frank, SR Parisi, T Taubert, S Fernandez, P Fuchs, M Chan, HM Livingston, DM Amati, B AF Frank, SR Parisi, T Taubert, S Fernandez, P Fuchs, M Chan, HM Livingston, DM Amati, B TI MYC recruits the TIP60 histone acetyltransferase complex to chromatin SO EMBO REPORTS LA English DT Article ID C-MYC; ACETYLASE COMPLEX; ESSENTIAL COFACTOR; ONCOGENIC TRANSFORMATION; TRANSCRIPTION; TRRAP; ACTIVATION; YEAST; ONCOPROTEINS; PROMOTER AB The transcription factor MYC binds specific DNA sites in cellular chromatin and induces the acetylation of histones H3 and H4. However, the histone acetyltransferases (HATs) that are responsible for these modifications have not yet been identified. MYC associates with TRRAP, a subunit of distinct macromolecular complexes that contain the HATs GCN5/PCAF or TIP60. Although the association of MYC with GCN5 has been shown, its interaction with TIP60 has never been analysed. Here, we show that MYC associates with TIP60 and recruits it to chromatin in vivo with four other components of the TIP60 complex: TRRAP, p400, TIP48 and TIP49. Overexpression of enzymatically inactive TIP60 delays the MYC-induced acetylation of histone H4, and also reduces the level of MYC binding to chromatin. Thus, the TIP60 HAT complex is recruited to MYC-target genes and, probably with other other HATs, contributes to histone acetylation in response to mitogenic signals. C1 DNA Res Inst, Palo Alto, CA 94304 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. European Inst Oncol, Dept Expt Oncol, I-20141 Milan, Italy. RP Amati, B (reprint author), DNA Res Inst, 901 Calif Ave, Palo Alto, CA 94304 USA. RI Taubert, Stefan/A-8104-2015 OI Taubert, Stefan/0000-0002-2432-7257 NR 27 TC 209 Z9 212 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD JUN PY 2003 VL 4 IS 6 BP 575 EP 580 DI 10.1038/sj.embor.embor861 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 686BA UT WOS:000183299600012 PM 12776177 ER PT J AU Makihira, S Yan, WQ Murakami, H Furukawa, M Kawai, T Nikawa, H Yoshida, E Hamada, T Okada, Y Kato, Y AF Makihira, S Yan, WQ Murakami, H Furukawa, M Kawai, T Nikawa, H Yoshida, E Hamada, T Okada, Y Kato, Y TI Thyroid hormone enhances aggrecanase-2/ADAM-TS5 expression and proteoglycan degradation in growth plate cartilage SO ENDOCRINOLOGY LA English DT Article ID BOVINE ARTICULAR-CARTILAGE; SERUM-FREE CULTURE; PARATHYROID-HORMONE; CHONDROCYTE CULTURES; TERMINAL DIFFERENTIATION; POSTNATAL-DEVELOPMENT; RECEPTOR-BETA; MATRIX METALLOPROTEINASE-2; INTERGLOBULAR DOMAIN; ADAMTS FAMILY AB Effects of thyroid hormone on proteoglycan degradation in various regions of cartilage were investigated. In propylthiouracil-treated rats with hypothyroidism, proteoglycan degradation in epiphyseal cartilage during endochondral ossification was markedly suppressed. However, injections of T-4 reversed this effect of propylthiouracil on proteoglycan degradation. In pig growth plate explants, T-3 also induced breakdown of proteoglycan. T-3 increased the release of aggrecan monomer and core protein from the explants into the medium. Accordingly, the level of aggrecan monomer remaining in the tissue decreased after T-3 treatment, and the monomer lost hyaluronic acid-binding capacity, suggesting that the cleavage site is in the interglobular domain The aggrecan fragment released from the T-3-exposed explants underwent cleavage at Glu(373)-Ala(374). the major aggrecanase-cleavage site. The stimulation of proteoglycan degradation by T-3 was less prominent in resting cartilage explants than in growth plate explants and was barely detectable in articular cartilage explants. Using rabbit growth plate chondrocyte cultures, we explored proteases that may be involved in T-3-induced aggrecan degradation and found that T-3 enhanced the expression of aggrecanase-2/ADAM-TS5 (a disintegrin and a metalloproteinase domain with thrombospondin type I domains) mRNA, whereas we could not detect any enhancement of stromelysin, gelatinase, or collagenase activities or any aggrecanase-1/ADAM-TS4 mRNA expression. We also found that the aggrecanse-2 mRNA level, but not aggrecanase-1, increased at the hypertrophic stage during endochondral ossification. These findings suggest that aggrecanse-2/ADAM-TS5 is involved in aggrecan breakdown during endochondral ossification, and that thyroid hormone stimulates the aggrecan breakdown partly via the enhancement of aggrecanase-2/ADAM-TS5. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. Hiroshima Univ, Dept Prosthet Dent, Fac Dent, Minami Ku, Hiroshima 7348553, Japan. Hiroshima Univ, Dept Biochem, Fac Dent, Minami Ku, Hiroshima 7348553, Japan. Osaka City Univ, Dept Pediat, Sch Med, Abeno Ku, Osaka 5458585, Japan. Keio Univ, Dept Pathol, Sch Med, Shinjuku Ku, Tokyo 1608582, Japan. RP Makihira, S (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. RI Okada, Yasunori/B-5550-2014 OI Okada, Yasunori/0000-0001-9208-4755 FU NIDCR NIH HHS [DE-1455] NR 56 TC 29 Z9 31 U1 0 U2 3 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 JUN PY 2003 VL 144 IS 6 BP 2480 EP 2488 DI 10.1210/en.2002-220746 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683KH UT WOS:000183146900041 PM 12746310 ER PT J AU Lee, AV Zhang, P Ivanova, M Bonnette, S Oesterreich, S Rosen, JM Grimm, S Hovey, RC Vonderhaar, BK Kahn, CR Torres, D George, J Mohsin, S Allred, DC Hadsell, DL AF Lee, AV Zhang, P Ivanova, M Bonnette, S Oesterreich, S Rosen, JM Grimm, S Hovey, RC Vonderhaar, BK Kahn, CR Torres, D George, J Mohsin, S Allred, DC Hadsell, DL TI Developmental and hormonal signals dramatically alter the localization and abundance of insulin receptor substrate proteins in the mammary gland SO ENDOCRINOLOGY LA English DT Article ID BREAST-CANCER CELLS; END BUD FORMATION; GROWTH-FACTOR-I; PROLACTIN RECEPTOR; IGF-I; DUCTAL MORPHOGENESIS; PROGESTERONE RECEPTORS; NUCLEAR TRANSLOCATION; TARGETED DISRUPTION; POSTNATAL-GROWTH AB Insulin receptor substrates (IRS) are central integrators of hormone, cytokine, and growth factor signaling. IRS proteins can be phosphorylated by a number of signaling pathways critical to normal mammary gland development. Studies in transgenic mice that overexpress IGF-I in the mammary gland suggested that IRS expression is important in the regulation of normal postlactational mammary involution. The goal of these studies was to examine IRS expression in the mouse mammary gland and determine the importance of IRS-1 to mammary development in the virgin mouse. IRS-1 and -2 show distinct patterns of protein expression in the virgin mouse mammary gland, and protein abundance is dramatically increased during pregnancy and lactation, but rapidly lost during involution. Consistent with hormone regulation, IRS-1 protein levels are reduced by ovariectomy, induced by combined treatment with estrogen and progesterone, and vary considerably throughout the estrous cycle. These changes occur without similar changes in mRNA levels, suggesting post-transcriptional control. Mammary glands from IRS-1 null mice have smaller fat pads than wild-type controls, but this reduction is proportional to the overall reduction in body size. Development of the mammary duct (terminal endbuds and branch points) is not altered by the loss of IRS-1, and pregnancy-induced proliferation is not changed. These data indicate that IRS undergo complex developmental and hormonal regulation in the mammary gland, and that IRS-1 is more likely to regulate mammary function in lactating mice than in virgin or pregnant mice. C1 Baylor Coll Med, Breast Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Breast Ctr, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Baylor Coll Med, Breast Ctr, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Breast Ctr, Dept Pathol, Houston, TX 77030 USA. ARS, USDA, Childrens Nutr Res Ctr, Bethesda, MD 20892 USA. NCI, Mol & Cellular Endocrinol Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA. RP Lee, AV (reprint author), Baylor Coll Med, Breast Ctr, Dept Med, Room N1110,1 Baylor Plaza,MS 600, Houston, TX 77030 USA. FU NCI NIH HHS [CA-94118]; NIDDK NIH HHS [DK-52197] NR 61 TC 31 Z9 31 U1 0 U2 3 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 JUN PY 2003 VL 144 IS 6 BP 2683 EP 2694 DI 10.1210/en.2002-221103 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683KH UT WOS:000183146900064 PM 12746333 ER PT J AU Axelrod, L AF Axelrod, L TI Perioperative management of patients treated with glucocorticoids SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID PITUITARY-ADRENOCORTICAL FUNCTION; CORTICOTROPIN-RELEASING HORMONE; ACTH TEST; ADRENAL INSUFFICIENCY; SHORT-TERM; THERAPY; RESPONSES; PROSTACYCLIN; HYPOGLYCEMIA; SUPPRESSION AB Hypothatamic-pituitary-adrenal (HPA) suppression is a common consequence of glucocorticoid therapy. Overt secondary adrenal insufficiency from this treatment is a rare but life-threatening condition. This article addresses the following issues in patients previously treated with glucocorticoids: the pathogenesis of hypotension, the incidence of perioperative adrenal insufficiency, the time course of development of HPA suppression, the time course of recovery from HPA suppression, management of HPA suppression, preoperative assessment, and perioperative management. The short adrenocorticotropic hormone test is the preferred study for preoperative assessment of adrenocortical function. Recommendations for perioperative glucocorticoid coverage of patients with HPA suppression, with lower doses than in the past, now reflect the normal physiologic response to surgical stress and consider the duration and severity of the surgical procedure. C1 Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Axelrod, L (reprint author), Massachusetts Gen Hosp, Diabet Unit, Bulfinch 408,55 Fruit St, Boston, MA 02114 USA. NR 51 TC 37 Z9 42 U1 1 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD JUN PY 2003 VL 32 IS 2 BP 367 EP + DI 10.1016/S0889-8529(03)00008-2 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 685BE UT WOS:000183240300005 PM 12800537 ER PT J AU Brain, JD Kavet, R McCormick, DL Poole, C Silverman, LB Smith, TJ Valberg, PA Van Etten, RA Weaver, JC AF Brain, JD Kavet, R McCormick, DL Poole, C Silverman, LB Smith, TJ Valberg, PA Van Etten, RA Weaver, JC TI Childhood leukemia: Electric and magnetic fields as possible risk factors SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE childhood leukemia; contact currents; contact voltages; electric and magnetic fields; EMT; review ID TOXICITY ONCOGENICITY EVALUATION; ACUTE MYELOID-LEUKEMIA; LOW-FREQUENCY; ELECTROMAGNETIC-FIELDS; BIOLOGICAL MAGNETITE; POOLED ANALYSIS; THERMAL NOISE; MICE; CANCER; CELLS AB Numerous epidemiologic studies have reported associations between measures of power-line electric or magnetic fields (EMTs) and childhood leukemia. The basis for such associations remains unexplained. In children, acute lymphoblastic leukemia represents approximately three-quarters of all U.S. leukemia types. Some risk factors for childhood leukemia have been established, and others are suspected. Pathogenesis, as investigated in animal models, is consistent with the multistep model of acute leukemia development. Studies of carcinogenicity in animals, however, are overwhelmingly negative and do not support the hypothesis that EMF exposure is a significant risk factor for hematopoietic neoplasia. We may fail to observe effects from EMFs because, from a mechanistic perspective, the effects of EMFs on biology are very weak. Cells and organs function despite many sources of chemical "noise" (e.g., stochastic, temperature, concentration, mechanical, and electrical noise), which exceed the induced EMF "signal" by a large factor. However, the inability to detect EMF effects in bioassay systems may be caused by the choice made for "EMF exposure." "Contact currents" or "contact voltages" have been proposed as a novel exposure metric, because their magnitude is related to measured power-line magnetic fields. A contact current occurs when a person touches two conductive surfaces at different voltages. Modeled analyses support contact currents as a plausible metric because of correlations with residential magnetic fields and opportunity for exposure. The possible role of contact currents as an explanatory variable in the reported associations between EMFs and childhood leukemia will need to be clarified by further measurements, biophysical analyses, bioassay studies, and epidemiology. C1 Gradient Corp, Hlth Risk Assessment, Cambridge, MA 02142 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. EMF Hlth Assessment, Elect Power Res Inst, Palo Alto, CA USA. IIT, Res Inst, Chicago, IL 60616 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Ctr Blood Res, Dept Genet, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Valberg, PA (reprint author), Gradient Corp, Hlth Risk Assessment, 238 Main St, Cambridge, MA 02142 USA. NR 66 TC 23 Z9 25 U1 1 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 2003 VL 111 IS 7 BP 962 EP 970 DI 10.1289/ehp.6020 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 689ND UT WOS:000183498900036 PM 12782499 ER PT J AU Oster, J Doherty, C Grant, PE Simon, M Cole, AJ AF Oster, J Doherty, C Grant, PE Simon, M Cole, AJ TI Diffusion-weighted imaging abnormalities in the splenium after seizures SO EPILEPSIA LA English DT Article DE splenium; diffusion-weighted imaging; magnetic resonance imaging ID STATUS EPILEPTICUS; CORPUS-CALLOSUM; RAT-BRAIN; COEFFICIENT; LESION; WATER; MRI AB Purpose: Transient increased T-2 signal in the splenium of the corpus callosum after seizures has been reported and sometimes attributed to a postulated toxicity of anticonvulsant medications (AEDs). Methods: We describe two patients with bitemporal epilepsy. Results: Transiently increased T2 signal (in one) and decreased apparent diffusion coefficient (ADC) (in both) in the splenium appeared to be related directly to acute seizures. Conclusions: These cases illustrate an unusual acute postictal imaging finding, highlight involvement of an important commissural pathway, and suggest that seizures per se, and not their treatment, are the cause of transient white-matter abnormalities in these cases. C1 Massachusetts Gen Hosp, MGH Epilepsy Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Cole, AJ (reprint author), Massachusetts Gen Hosp, MGH Epilepsy Serv, VBK-830,Fruit St, Boston, MA 02114 USA. NR 12 TC 57 Z9 58 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 PD JUN PY 2003 VL 44 IS 6 BP 852 EP 854 DI 10.1046/j.1528-1157.2003.40902.x PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 695PW UT WOS:000183840300016 PM 12790901 ER PT J AU Bauer, M Forsthoff, A Baethge, C Adli, M Berghofer, A Dopfmer, S Bschor, T AF Bauer, M Forsthoff, A Baethge, C Adli, M Berghofer, A Dopfmer, S Bschor, T TI Lithium augmentation therapy in refractory depression - Update 2002 SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE major depression; lithium augmentation; treatment resistant depression; response prediction; refractory depression ID TREATMENT-RESISTANT-DEPRESSION; UNIPOLAR MAJOR DEPRESSION; PLACEBO-CONTROLLED TRIAL; COMBINED DEX/CRH TEST; DOUBLE-BLIND; TRIIODOTHYRONINE AUGMENTATION; ANTIDEPRESSANT MEDICATION; TRICYCLIC ANTIDEPRESSANTS; CARBONATE AUGMENTATION; HEALTHY-SUBJECTS AB Lithium has been used to augment the efficacy of antidepressant medications for more than 20 years. The present study examines whether evidence exists to support,the clinical efficacy of lithium augmentation in refractory, treatment resistant depression. Studies were identified by searching Medline (1980 to August 2002) and by scanning the references of published reviews and standard textbooks. Studies were selected if they were open-labeled or double-blind, placebo-controlled or comparator trials that involved patients who had not responded to conventional antidepressants. 27 prospective studies were identified that included a total of 803 depressed patients displaying the following designs: 10 double-blind, placebo-controlled trials, 2 randomized, double-blind comparator trials, 2 randomized, open comparator trials, and 13 open-label trials. The majority of randomized controlled trials has demonstrated substantial efficacy of lithium augmentation in partial and non responders to antidepressant treatment. In the placebo-controlled trials, the response rate in the lithium group was 45 % and in the placebo group 18 % (p < 0.001). Summarizing all open and controlled studies, approximately 50 % of patients responded to lithium augmentation within 4 weeks. In conclusion, lithium is the foremost and most well-documented augmentation strategy in refractory depression. Therefore, it should be considered a first-line treatment strategy in patients with major depression who do not adequately respond to standard antidepressants. C1 Humboldt Univ, Klin Psychiat & Psychotherapie, Charite, D-10117 Berlin, Germany. Univ Munich, Dept Psychiat, D-8000 Munich, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, McLean Div,Consolidated Dept Psychiat, Belmont, MA 02178 USA. Humboldt Univ, Inst Social Med Epidemiol & Hlth Econ, Charite, D-10117 Berlin, Germany. Tech Univ Dresden, Dept Psychiat, D-8027 Dresden, Germany. RP Bauer, M (reprint author), Humboldt Univ, Klin Psychiat & Psychotherapie, Charite, Campus Mitte,Schumannstr 20-21, D-10117 Berlin, Germany. NR 63 TC 56 Z9 56 U1 0 U2 3 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0940-1334 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD JUN PY 2003 VL 253 IS 3 BP 132 EP 139 DI 10.1007/s00406-003-0430-9 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 710PF UT WOS:000184688100005 PM 12904977 ER PT J AU Baethge, C Bschor, T AF Baethge, C Bschor, T TI Wrist fracture in a patient undergoing electroconvulsive treatment monitored using the "cuff" method SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE electroconvulsive therapy; cuff method; fracture; osteoporosis; depression ID BONE-FRACTURES; THERAPY; OSTEOPOROSIS; DEPRESSION AB We report on a case of a 64-year-old female patient who received electroconvulsive treatment for major depression. The patient sustained a fracture to the distal radius of the arm blocked by the "cuff" method (Smith fracture). Subsequent investigations revealed that she was suffering from osteoporosis. This case report underlines the importance of special treatment procedures for osteoporotic patients and other patient groups at risk for fractures. We recommend screening for osteoporosis in routine pre-ECT evaluation, even in younger patients, and propose not attaching the cuff to the arm in those at risk for fractures. In our patient, electroconvulsive therapy was safely continued using higher doses of succinylcholine and without the cuff method. C1 Harvard Univ, Sch Med,Bipolar & Psychot Disorders Program, Massachusetts Gen Hosp, McLean Div,Mailman Res Ctr,Dept Psychiat, Belmont, MA 02478 USA. Free Univ Berlin, Klinikum Benjamin Franklin, Klin Psychiat & Psychotherapie, D-1000 Berlin, Germany. Tech Univ Dresden, Klinikum Carl Gustav Carus, Klin & Poliklin Psychiat & Psychotherapie, Dresden, Germany. RP Baethge, C (reprint author), Harvard Univ, Sch Med,Bipolar & Psychot Disorders Program, Massachusetts Gen Hosp, McLean Div,Mailman Res Ctr,Dept Psychiat, 115 Mill St, Belmont, MA 02478 USA. NR 15 TC 6 Z9 6 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0940-1334 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD JUN PY 2003 VL 253 IS 3 BP 160 EP 162 DI 10.1007/s00406-003-0432-7 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 710PF UT WOS:000184688100009 PM 12904981 ER PT J AU Krause, MHJ D'Amico, DJ AF Krause, MHJ D'Amico, DJ TI Ablation of vitreous tissue with a high repetition rate erbium : YAG laser SO EUROPEAN JOURNAL OF OPHTHALMOLOGY LA English DT Article DE laser surgery-methods; lasers-therapeutic use; vitrectomy methods; vitreous body surgery; vitreous body-radiation effects ID ER-YAG; VITREORETINAL SURGERY; EXTRACELLULAR-MATRIX; CLINICAL-EXPERIENCE; THERMAL-DAMAGE; MU-M; VITRECTOMY; IRRADIATION; SHAPE AB PURPOSE. To quantify erbium (Er):YAG laser ablation of vitreous in relation to different pulse repetition rates less than or equal to 200 Hz, in order to examine the feasibility of laser for removal of vitreous gel (photovitrectomy) in clinically acceptable times. METHODS. Fresh porcine vitreous samples and saline controls were ablated in air with an Er:YAG laser connected to a sapphire fiber at pulse energies between 1.0 and 21.2 mJ and at pulse repetition rates between 10 and 200 Hz. Net ablation rates were determined by weight measurement. RESULTS. Reproducible and constant ablation rates were found for given laser parameters. Net ablation rates increased linearly with pulse repetition rate and nonlinearly with pulse energy. Expanded laser parameter domains permitted vitreous ablation rates as low as 1 mug/s to as high as 1031 mug/s. Ablation rates did not differ significantly between vitreous and saline. CONCLUSIONS. The study documents clinically useful vitreous ablation rates that scale linearly with high repetition rates of Er:YAG laser, and suggests directions for further development of laser technology for enhanced removal of vitreous and other tissues. However, nonlinear effects of pulse energy also exist, indicating need for careful examination of ablation characteristics in various instruments. C1 Univ Saarland, Dept Ophthalmol, D-66424 Homburg, Saar, Germany. Univ Saarland, Hosp Eye, Homburg, Saar, Germany. Harvard Univ, Sch Med, Retina Serv, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Laser Res Lab,Dept Ophthalmol, Boston, MA 02115 USA. RP Krause, MHJ (reprint author), Univ Saarland, Dept Ophthalmol, Kirrberger Str 1, D-66424 Homburg, Saar, Germany. NR 35 TC 4 Z9 4 U1 0 U2 1 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 JUN PY 2003 VL 13 IS 5 BP 424 EP 432 PG 9 WC Ophthalmology SC Ophthalmology GA 701CZ UT WOS:000184151800002 PM 12841564 ER PT J AU Kulke, MH AF Kulke, MH TI Recent developments in the pharmacological treatment of advanced pancreatic cancer SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE chemotherapy; gemcitabine; pancreatic cancer; systemic therapy ID PHASE-II TRIAL; COLONY-STIMULATING FACTOR; HIGH-DOSE LEUCOVORIN; FIRST-LINE THERAPY; RANDOMIZED TRIAL; CONTINUOUS-INFUSION; GEMCITABINE; ADENOCARCINOMA; CISPLATIN; FLUOROURACIL AB Metastatic pancreatic cancer is one of the leading causes of cancer-related death in North America and Europe. The high mortality rate associated with pancreatic cancer is related to the fact that the vast majority of patients develop incurable, metastatic disease. Such patients have, in the past, had few treatment options. In recent years, however, the systemic administration of gemcitabine has been accepted as a standard first-line treatment for patients with advanced pancreatic cancer. While treatment with gemcitabine has been shown to result in both clinical benefit and in prolongation of survival, objective tumour responses following therapy with gemcitabine are relatively uncommon and median survival times remain short. Current efforts have, therefore, focused on evaluating chemotherapy regimens in which gemcitabine is combined with a second cytotoxic agent. Several such combinations appear to be associated with higher objective response rates than single-agent gemcitabine and have been well-tolerated in early clinical trials. Ongoing, prospectively randomised clinical trials will help better define the efficacy of these new combinations and will determine if they result in a significant benefit when compared to gemcitabine monotherapy. A number of novel chemotherapeutic and biological agents also appear promising and are likely to play a future role in the treatment of patients with advanced pancreatic cancer. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM matthew_kulke@dfci.harvard.edu NR 63 TC 8 Z9 8 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1354-3784 EI 1744-7658 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JUN PY 2003 VL 12 IS 6 BP 983 EP 992 DI 10.1517/13543784.12.6.983 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 689DM UT WOS:000183476400007 PM 12783602 ER PT J AU Olson, SL Ledoux, WR Ching, RP Sangeorzan, BJ AF Olson, SL Ledoux, WR Ching, RP Sangeorzan, BJ TI Muscular imbalances resulting in a clawed hallux SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE toes; hammer toe syndrome; foot; biomechanics; pressure ID FOOT PRESSURE; RISK-FACTORS; TENDON; FORCE; MANAGEMENT; MODEL AB A clawed hallux is a deformity of the great toe resulting from a muscular imbalance. Using a cadaveric foot-loading frame, we quantitatively assessed the role of the peroneus longus (PL), extensor hallucis longus (EHL), and flexor hallucis longus (FHL) on position and pressure distribution of the first ray by simulating muscle imbalances. The experimental protocol included applying seven different combinations of simulated disproportionate loads ("overpulls") for these three muscles using midstance force values derived from the literature. This study quantified the angular change in the joints of the first ray and measured the plantar pressure beneath the head of the first metatarsal and the hallux. The results indicated that the peroneus longus was statistically the greatest contributor to the elevation of plantar pressure beneath the first metatarsal, while the EHL and FHL were primarily responsible for the angular changes resuilting in the clawed hallux deformity. C1 VA Puget Sound Hlth Care Syst, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Dept Vet Affairs, Seattle, WA 98108 USA. Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. RP Ledoux, WR (reprint author), VA Puget Sound Hlth Care Syst, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Dept Vet Affairs, MS 151,1660 S Columbian Way, Seattle, WA 98108 USA. RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 NR 22 TC 22 Z9 22 U1 0 U2 1 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD JUN PY 2003 VL 24 IS 6 BP 477 EP 485 PG 9 WC Orthopedics SC Orthopedics GA 695ME UT WOS:000183834000005 PM 12854668 ER PT J AU Sonnenberg, A Fennerty, MB AF Sonnenberg, A Fennerty, MB TI Medical decision analysis of chemoprevention against esophageal adenocarcinoma SO GASTROENTEROLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; HIGH-GRADE DYSPLASIA; BARRETTS-ESOPHAGUS; COLORECTAL-CANCER; CYCLOOXYGENASE-2 EXPRESSION; ENDOSCOPIC SURVEILLANCE; ASPIRIN USE; RISK; PREVENTION; MANAGEMENT AB Background & Aims: Chemoprevention of esophageal adenocarcinoma using nonsteroldal anti-inflammatory drugs (NSAIDs) may reduce the risk of cancer in patients with Barrett's esophagus. The aim of the study was to assess the cost-effectiveness of this strategy. Metho The Incremental cost-effectiveness ratio (ICER) of chemoprevention (compared with endoscopic surveillance or with no surveillance) was analyzed with a computer model of a Markov process. Results: Under baseline conditions for all patients with Barrett's esophagus (neoplastic and nonneoplastic), the ICER of chemoprevention ranges between $12,700 and $18,500 per life-year saved. However, these cost values are sensitive to variations in the costs of chemoprevention, incidence of cancer in patients with Barrett's esophagus, and efficacy of NSAlDs in reducing the incidence of cancer, which can shift the ICER into a cost range that is prohibitively expensive. Conversely, in those patients with Barrett's esophagus and high-grade dysplasia, the ICER ranges between $3900 and $5000. Chemoprevention remains a cost-effective option even under rather unfavorable conditions, such as higher cost and lower efficacy of chemoprevention and lower incidence of cancer. Conclusions. This model suggests that a high incidence of esophageal adenocarcinoma in high-grade dysplasia renders chemoprevention cost-effective even in the presence of less-favorable conditions. However, chemoprevention may not be a cost-effective measure in the general population of all patients with Barrett's esohagus, depending on unknown factors such as cost and efficacy of chemoprevention as well as true incidence of cancer. C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Div Gastroenterol Hepatol, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Oregon Hlth Sci Univ, Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. NR 33 TC 26 Z9 27 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2003 VL 124 IS 7 BP 1758 EP 1766 DI 10.1016/S0016-5085(03)00393-7 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 684ZK UT WOS:000183236200008 PM 12806608 ER PT J AU Otte, JM Rosenberg, IM Podolsky, DK AF Otte, JM Rosenberg, IM Podolsky, DK TI Intestinal myofibroblasts in innate immune responses of the intestine SO GASTROENTEROLOGY LA English DT Article ID COLONIC SUBEPITHELIAL MYOFIBROBLASTS; TOLL-LIKE RECEPTORS; PROTEIN-KINASE KINASE; NF-KAPPA-B; INTERLEUKIN-1 RECEPTOR; SIGNAL-TRANSDUCTION; MESENCHYMAL CELLS; SKIN FIBROBLASTS; GENE-EXPRESSION; LIPOPOLYSACCHARIDE AB Background & Aims. Intestinal myofibroblasts are known to respond to Inflammatory signals and may play a role in Crohn's disease-associated fibrosis. However, putative involvement by myofibroblasts in innate immune responses as part of intestinal host defense has not been characterized. We therefore analyzed expression and regulation of toll-like receptors (TLRs) in colonic human myofibroblasts (CCD-18) and primary human colonic myofibroblasts in comparison with human lung myofibroblasts (CCD-37). Methods Expression of TLRs (1-10) and NOD :L and 2 was assessed before and after stimulation with either lipopolysaccharide (LPS) or lipotelchoic acid (LTA) by using a custom microarray, reverse-transcription polymerase chain reaction, Northern blot and Western blot analysis, and immunohistochemistry. Activation of signaling pathways, translocation of p65, and secretion of interleukin (IL)-8 were determined. Results; Messenger RNAs encoding for TLR1-9, as well as NOD:1 and NOD2, were amplified from cultured and primary human intestinal myofibroblasts. After stimulation with LIPS or LTA, a 1.5-4.2-fold up-regulation of TLRs (2, 3, 4, 6, 7) and elements of the signaling cascade (MyD88, TIR domain-containing adapter protein [TIRAP]) was observed. CCD-18 and CCD-37 cells expressed TLR 2 and 4 protein, which were located primarily on the cell membrane. Stimulation with LTA or LPS resulted in activation of the mitogen-activated protein kinases pathway, nuclear translocation of p65, and significantly increased IL-8 secretion. Conclusions: Bacterial components directly activate Intestinal myofibroblasts expressing TLRs. These cells may therefore participate in Innate immune responses by sensing and responding to bacterial products that have penetrated into the subepithelial compartment. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, GI Unit,Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, GI Unit,Ctr Study Inflammatory Bowel Dis, GRJ719,32 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [P30 DK 43351, R01 DK 60049] NR 53 TC 141 Z9 145 U1 0 U2 6 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 JUN PY 2003 VL 124 IS 7 BP 1866 EP 1878 DI 10.1016/S0016-5085(03)00403-7 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 684ZK UT WOS:000183236200019 PM 12806620 ER PT J AU Somsouk, MA Lauer, GM Casson, D Terella, A Day, CL Walker, BD Chung, RT AF Somsouk, MA Lauer, GM Casson, D Terella, A Day, CL Walker, BD Chung, RT TI Spontaneous resolution of chronic hepatitis C virus disease after withdrawal of immunosuppression SO GASTROENTEROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LIVER FIBROSIS PROGRESSION; T-CELL RESPONSE; IMMUNE-RESPONSES; NATURAL-HISTORY; INFECTION; THERAPY AB Approximately 85% of acute cases of hepatitis C infection result in chronic hepatitis. Spontaneous clearance of hepatitis C virus has been thought to occur exclusively after acute infection and is associated with a robust cellular immune response. We describe here a case of a renal transplant recipient who acquired posttransplant hepatitis C virus infection with rapid histological, progression but who subsequently experienced spontaneous viral clearance along with histological remission after removal of immunosuppression. Immunologic studies showed persistently strong cellular immune responses. This case underscores the importance of restoration of the immune system in the control of hepatitis C virus viremia and disease progression and the need to minimize or obviate immunosuppression in organ transplant recipients. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, GRJ 825, Boston, MA 02114 USA. RI Day, Cheryl/J-9844-2012 FU NIDDK NIH HHS [R01 DK 57857] NR 12 TC 32 Z9 33 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2003 VL 124 IS 7 BP 1946 EP 1949 DI 10.1016/S0016-5085(03)00391-3 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 684ZK UT WOS:000183236200026 PM 12806627 ER PT J AU Kearney, DJ Crump, C Maynard, C Boyko, EJ AF Kearney, DJ Crump, C Maynard, C Boyko, EJ TI A case-control study of endoscopy and mortality from adenocarcinoma of the esophagus or gastric cardia in persons with GERD SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID GASTROESOPHAGEAL REFLUX DISEASE; BARRETTS-ESOPHAGUS; SURVEILLANCE; POPULATION; DYSPLASIA; SURVIVAL; EFFICACY; RECORDS; CANCER; STAGE AB Background. This study assessed whether EGD reduces mortality from adenocarcinoma of the esophagus or gastric cardia for patients with gastroesophageal reflux. Methods: A case-control study was performed. A total of 245 incident cases of death caused by adenocarcinoma of the esophagus or gastric cardia (1995-1999) in which reflux was present were identified using Veterans Health Administration databases. A total of 980 controls with reflux but no death from adenocarcinoma were frequency matched for age, gender, and race. The occurrences of EGD from 1990 onward were compared for cases and controls. Logistic regression analysis with adjustment for potential confounding factors was performed. Results: All the subjects were men. Cases were significantly less likely to have had an EGD in the time period of interest as compared with controls (adjusted odds ratio 0.66: 95% Cl [0.45, 0.96], p = 0.03). This negative association was as strong for any EGD performed within 1 to 8 years before diagnosis as for a more recent EGD. However, there were no controls that included esophagectomy and no controls with a nonfatal diagnosis of adenocarcinoma, raising the question of whether EGD and reduced mortality are causally linked. The risk of dying from adenocarcinoma was significantly lower for men with a diagnosis of GERD as an inpatient relative to men in whom the diagnosis was made as an outpatient (adjusted odds ratio 0.21: 95% Cl [0.15, 0.31], p < 0.01). Conclusions: For patients with GERD, performing an EGD is associated with reduced mortality from adenocarcinoma of the esophagus or gastric cardia, but whether this is a causative association remains unclear. C1 VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Vet Affairs Epidemiol Res & Informat Ctr, Seattle, WA USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Kearney, DJ (reprint author), Univ Washington, Gastroenterol Sect, VAMC 111G1, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 39 TC 21 Z9 21 U1 0 U2 3 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 JUN PY 2003 VL 57 IS 7 BP 823 EP 829 DI 10.1067/mge.2003.249 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 685WP UT WOS:000183287300004 PM 12776027 ER PT J AU Wakimoto, H Johnson, PR Knipe, DM Chiocca, EA AF Wakimoto, H Johnson, PR Knipe, DM Chiocca, EA TI Effects of innate immunity on herpes simplex virus and its ability to kill tumor cells SO GENE THERAPY LA English DT Review ID DIFFUSE LIVER METASTASES; TYPE-1 GLYCOPROTEIN GC; BLOOD-BRAIN-BARRIER; GALACTOSYL NATURAL ANTIBODY; AMPHIPATHIC PEPTIDE ANALOGS; ACTIVATED PROTEIN-KINASE; MANNAN-BINDING PROTEIN; CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; IN-VIVO AB Several clinical trials have or are being performed testing the safety and efficacy of different strains of oncolytic viruses (OV) for malignant cancers. OVs represent either naturally occurring or genetically engineered strains of viruses that exhibit relatively selective replication in tumor cells. Several types of OV have been derived from herpes simplex virus 1 (HSV1). Tumor oncolysis depends on the processes of initial OV infection of tumor, followed by subsequent propagation of OV within the tumor itself. The role of the immune responses in these processes has not been extensively studied. On the contrary, effects of the immune response on the processes of wild-type HSV1 infection and propagation in the central nervous system have been studied and described in detail. The first line of defense against a wild-type HSV1 infection in both naive and immunized individuals is provided by innate humoral (complement, cytokines, chemokines) and cellular (macrophages, neutrophils, NK cells, gammadelta T cells, and interferon-producing cells) responses. These orchestrate the lysis of virions and virus-infected cells as well as provide a link to effective adaptive immunity. The role of innate defenses in curtailing the oncolytic effect of genetically engineered HSV has only recently been studied, but several of the same host responses appear to be operative in limiting anticancer effects by the replicating virus. The importance of this knowledge lies in finding avenues to modulate such initial innate responses, in order to allow for increased oncolysis of tumors while minimizing host toxicity. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv,Mol Neurooncol Labs, Charlestown, MA USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, Southborough, MA USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Chiocca, EA (reprint author), Massachusetts Gen Hosp East, Mol Neurooncol Lab, CNY6, Charlestown, MA 02129 USA. NR 82 TC 76 Z9 78 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD JUN PY 2003 VL 10 IS 11 BP 983 EP 990 DI 10.1038/sj.gt.3302038 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 682YT UT WOS:000183120500008 PM 12756419 ER PT J AU Corey, LL Weirich, CS Benjamin, IJ Kingston, RE AF Corey, LL Weirich, CS Benjamin, IJ Kingston, RE TI Localized recruitment of a chromatin-remodeling activity by an activator in vivo drives transcriptional elongation SO GENES & DEVELOPMENT LA English DT Article DE hsp70; SWI/SNF; heat shock; chromatin; transcription; elongation ID RNA-POLYMERASE-II; HISTONE ACETYLTRANSFERASE COMPLEXES; HEAT-SHOCK FACTOR-1; DROSOPHILA-MELANOGASTER; PROMOTER NUCLEOSOMES; HSP70 PROMOTER; HUMAN SWI/SNF; IN-VITRO; DISRUPTION; GENE AB To understand the role of chromatin-remodeling activities in transcription, it is necessary to understand how they interact with transcriptional activators in vivo to regulate the different steps of transcription. Human heat shock factor 1 (HSF1) stimulates both transcriptional initiation and elongation. We replaced mouse HSF1 in fibroblasts with wild-type and mutant human HSF1 constructs and characterized regulation of an endogenous mouse hsp70 gene. A mutation that diminished transcriptional initiation led to twofold reductions in hsp70 mRNA induction and recruitment of a SWI/SNF remodeling complex. In contrast, a mutation that diminished transcriptional elongation abolished induction of full-length mRNA, SWI/SNF recruitment, and chromatin remodeling, but minimally impaired initiation from the hsp70 promoter. Another remodeling factor, SNF2h, is constitutively present at the promoter irrespective of the genotype of HSF1. These data suggest that localized recruitment of SWI/SNF drives a specialized remodeling reaction necessary for the production of full-length hsp70 mRNA. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Div Cell & Mol Biol, Dallas, TX 75235 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 41 TC 95 Z9 97 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUN 1 PY 2003 VL 17 IS 11 BP 1392 EP 1401 DI 10.1101/gad.1071803 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 687VB UT WOS:000183396700010 PM 12782657 ER PT J AU Xu, YH Stange-Thomann, N Weber, G Bo, RH Dodge, S David, RG Foley, K Beheshti, J Harris, NL Birren, B Lander, ES Meyerson, M AF Xu, YH Stange-Thomann, N Weber, G Bo, RH Dodge, S David, RG Foley, K Beheshti, J Harris, NL Birren, B Lander, ES Meyerson, M TI Pathogen discovery from human tissue by sequence-based computational subtraction (vol 81, pg 329, 2003) SO GENOMICS LA English DT Correction C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Whitehead Inst, MIT, Ctr Genome Res, Cambridge, MA 02142 USA. Brigham & Womens Hosp, Decis Syst Group, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Xu, YH (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 1 TC 1 Z9 1 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 2003 VL 81 IS 6 BP 648 EP 648 DI 10.1016/S0888-7543(02)00088-0 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 689DU UT WOS:000183477000015 ER PT J AU Kier, FJ Molinari, V AF Kier, FJ Molinari, V TI "Do-it-yourself" dementia testing: Issues regarding an Alzheimer's Home Screening Test SO GERONTOLOGIST LA English DT Article ID SMELL IDENTIFICATION TEST; OLFACTORY IDENTIFICATION; COGNITIVE IMPAIRMENT; LONGITUDINAL CHANGES; HIV-INFECTION; FOLLOW-UP; DEFICITS; DISEASE; CARE; SCHIZOPHRENIA C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ S Florida, Louis Parte Florida Mental Hlth Inst, Tampa, FL USA. RP Kier, FJ (reprint author), VA Pittsburgh Healthcare Syst, Highland Dr Div 116 A-H,7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 50 TC 12 Z9 13 U1 3 U2 5 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD JUN PY 2003 VL 43 IS 3 BP 295 EP 301 PG 7 WC Gerontology SC Geriatrics & Gerontology GA 691JY UT WOS:000183603900002 PM 12810892 ER PT J AU Kieseier, BC Pischel, H Neuen-Jacob, E Tourtellotte, WW Hartung, HP AF Kieseier, BC Pischel, H Neuen-Jacob, E Tourtellotte, WW Hartung, HP TI ADAM-10 and ADAM-17 in the inflamed human CNS SO GLIA LA English DT Article DE TNF-alpha; TNFR-2; multiple sclerosis; astrocyte; T lymphocyte ID TUMOR-NECROSIS-FACTOR; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS; FACTOR-ALPHA; MATRIX METALLOPROTEINASES; MEDIATED DEMYELINATION; DISINTEGRIN; EXPRESSION; TNF; PATHOGENESIS AB Inflammatory demyelinating disorders of the CNS, such as multiple sclerosis (MS), are mediated, at least in part, by various cytokines and proteases. In the present study, we investigated the expression of A disintegrin and metalloproteinase (ADAM)-17, an important sheddase for various proteins, including tumor necrosis factor-alpha (TNF-alpha), and the p75- and p55-TNF receptors, as well as ADAM-10, a protease implicated in myelin degradation, in post mortem CNS tissue samples from patients with MS, and normal brain tissue (as control) by immunohistochemistry. ADAM-10 was found to be expressed by astrocytes in all MS and control sections studied; however, in some MS sections, perivascular macrophages were determined as an additional cellular source as well. ADAM-17 could be observed exclusively in acute and chronic active MS plaques and localized to invading T lymphocytes. The staining pattern of ADAM-17 in MS plaques was mirrored in distribution and extent by the pattern obtained with an antibody against the p75-TNF-receptor (TNFR-2), whereas TNF-a was found to be expressed primarily by perivascular macrophages. In studying cerebrospinal fluid (CSF) samples from MS patients, we were able to detect increased protein levels of ADAM-17 as compared with noninflammatory controls. In addition, increased levels of soluble TNFR-2 could be measured, suggestive of an active shedding process mediated by ADAM-17. The stimulation of peripheral blood mononuclear cells (PBMC) obtained from MS patients and healthy individuals corroborated these findings by revealing expression of ADAM-17 by T lymphocytes and ADAM-10 by macrophages in vitro. Our results indicate that ADAM-10 is expressed constitutively by astrocytes in the normal and inflamed human CNS. In contrast, under inflammatory conditions, ADAM-10, expressed by perivascular macrophages, and ADAM-17, expressed by invading T cells, may actively contribute to the pathogenesis of inflammatory disorders of the CNS. (C) 2003 Wiley-Liss, Inc. C1 Univ Dusseldorf, Dept Neurol, Res Grp Clin & Expt Neuroimmunol, D-40225 Dusseldorf, Germany. Univ Dusseldorf, Dept Neuropathol, D-40225 Dusseldorf, Germany. W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Kieseier, BC (reprint author), Univ Dusseldorf, Dept Neurol, Res Grp Clin & Expt Neuroimmunol, Moorenstr 5, D-40225 Dusseldorf, Germany. NR 32 TC 38 Z9 38 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 0894-1491 J9 GLIA JI Glia PD JUN PY 2003 VL 42 IS 4 BP 398 EP 405 DI 10.1002/glia.10226 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 685PH UT WOS:000183272100009 PM 12730960 ER PT J AU Tanaka, S Chu, S Hirokawa, M Montrose, MH Kaunitz, JD AF Tanaka, S Chu, S Hirokawa, M Montrose, MH Kaunitz, JD TI Direct measurement of acid permeation into rat oesophagus SO GUT LA English DT Article ID RABBIT ESOPHAGEAL EPITHELIUM; MUCOSAL BLOOD-FLOW; MUCUS GEL THICKNESS; INTRACELLULAR PH; NITRIC-OXIDE; BARRETTS-ESOPHAGUS; ALKALINE SECRETION; DYNAMIC REGULATION; SPECIAL EMPHASIS; SURFACE PH AB Background and aims: The early responses of the oesophageal mucosa to acid perfusion may predict subsequent pathology. Mucosal responses to luminal acid may result either from acid permeating through the mucosa or from other unknown transduction mechanisms. In order to better understand the dynamics of acid permeation into the oesophageal mucosa, we measured interstitial pH (pH(int)) of the oesophageal basal epithelial layer, pre-epithelial layer thickness, and blood flow in rats in vivo during luminal acid challenge. A novel confocal microscopic technique was used in vitro to measure pH(int) from defined cellular sites in response to luminal and basolateral acidification. Methods: 5-(and-6)-Carboxyfluorescein (CF) and carboxy- seminapthorhodofluor-1 (SNARF-1) fluorescence was used to measure pH(int) by conventional and confocal microscopy, respectively, in urethane anaesthetised rats. Pre-epithelial layer thickness was measured optically with carbon particles as markers. Blood flow was measured with laser Doppler flowmetry. Results: Luminal acidification failed to alter pH(int) in vivo and in vitro, but pH(int) was lowered by modest serosal acidification. Pre-epithelial layer thickness and blood flow increased significantly during luminal surface acid perfusion. Indomethacin had no effect on any acid related response. Conclusion: In this first dynamic measurement of oesophageal acid permeation and pre-epithelial layer thickness, pH(int) was preserved in spite of high luminal acidity by two complementary techniques. Despite the apparent permeability barrier to acid permeation, oesophageal blood flow and thickness responded to luminal acid perfusion. C1 W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. Indiana Univ, Sch Med, Dept Physiol, Indianapolis, IN 46202 USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, Bldg 114,Room 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [R01 DK54940, R01 DK054221, R01 DK54221, R01 DK054940, 5P30DK041301, P30 DK041301] NR 57 TC 22 Z9 24 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JUN PY 2003 VL 52 IS 6 BP 775 EP 783 DI 10.1136/gut.52.6.775 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 676FU UT WOS:000182741300001 PM 12740330 ER PT J AU Russell, AH AF Russell, AH TI All, none, or some? SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material ID CARCINOMA C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Russell, AH (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 305,100 Blossom St, Boston, MA 02114 USA. NR 4 TC 1 Z9 1 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 JUN PY 2003 VL 89 IS 3 BP 341 EP 342 DI 10.1016/S0090-8258(03)00260-9 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 692WB UT WOS:000183682300001 PM 12798693 ER PT J AU Freeman, DM Abnet, CC Hemmert, W Tsai, BS Weiss, TF AF Freeman, DM Abnet, CC Hemmert, W Tsai, BS Weiss, TF TI Dynamic material properties of the tectorial membrane: a summary SO HEARING RESEARCH LA English DT Article DE cochlea; macromechanics; micromechanics; tectorial membrane; osmotic response; polyelectrolyte gel; fixed charge; bulk modulus; viscoelastic; connective tissue; stiffness; point impedance; material property ID COCHLEAR HAIR BUNDLES; GUINEA-PIG; MECHANOELECTRICAL TRANSDUCTION; FREQUENCY-ANALYSIS; STIFFNESS; CELLS; MODEL; ORGAN; CORTI; FORCES AB Dynamic material properties of the tectorial membrane (TM) have been measured at audio frequencies in TMs excised from the apical portions of mouse cochleae. We review, integrate, and interpret recent findings. The mechanical point impedance of the TM in the radial, longitudinal, and transverse directions is viscoelastic and has a frequency dependence of the form 1/(K(j2pif)(alpha)) for 10 less than or equal to f less than or equal to 4000 Hz, where f is frequency, K is a constant, j = root-1 and alpha approximate to 0.66. Comparison with other connective tissues shows that the TM is a relatively lossy viscoelastic material. The median magnitudes of the point impedance at 10 Hz in the radial, longitudinal, and transverse directions are 4.6 X 10(-3) N.s/m, 1.8 X 10(-3) N.s/m, and 2.7 X 10(-3) N.s/m. Consistent with osmotic responses (Freeman et al., 2003), the TM point impedance is anisotropic - the TM is stiffer in the radial than in the longitudinal and transverse directions. The mechanical space constant of the TM is approximately 20 gm. Comparisons reveal that in the apical region of the mouse cochlea, the TM dynamic stiffness at 10 Hz is 10 times larger than the static stiffness of the aggregate hair cells in a mechanical space constant and roughly comparable to the stiffness of the basilar membrane. We conclude that the TM provides a mechanical load on the basilar membrane and that the lability of the TM to changes in endolymph composition may well be reflected in changes in basilar membrane motion. (C) 2003 Elsevier Science B.V. All rights reserved. C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. LLC, Lightwave Instruments, Watertown, MA 02472 USA. Infineon Technol AG, Corp Res, D-81730 Munich, Germany. Baylor Coll Med, Houston, TX 77030 USA. RP Freeman, DM (reprint author), MIT, Dept Elect Engn & Comp Sci, Room 36-889,77 Massachusetts Ave, Cambridge, MA 02139 USA. OI Abnet, Christian/0000-0002-3008-7843 NR 68 TC 32 Z9 32 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JUN PY 2003 VL 180 IS 1-2 BP 1 EP 10 DI 10.1016/S0378-5955(03)00073-X PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 690WU UT WOS:000183574100001 PM 12782348 ER PT J AU Freeman, DM Masaki, K McAllister, AR Wei, JL Weiss, TF AF Freeman, DM Masaki, K McAllister, AR Wei, JL Weiss, TF TI Static material properties of the tectorial membrane: a summary SO HEARING RESEARCH LA English DT Review DE cochlea; macromechanics; micromechanics; tectorial membrane; osmotic response; polyelectrolyte gel; fixed charge; bulk modulus; viscoelastic; connective tissue; stiffness; point impedance; material properties ID POLYELECTROLYTE GEL MODEL; ION-EXCHANGE REACTIONS; GUINEA-PIG COCHLEA; OUTER HAIR-CELLS; INNER-EAR; CHONDROITIN 4-SULFATE; POTASSIUM CONCENTRATION; BINDING PROPERTIES; CALCIUM-BINDING; MECHANICAL-PROPERTIES AB The tectorial membrane (TM) is a polyelectrolyte gel. Hence, its chemical, electrical, mechanical, and osmotic properties are inextricably linked. We review, integrate, and interpret recent findings on these properties in isolated TM preparations. The dimensions of the TM in alligator lizard, chick, and mouse are sensitive to bath ion concentrations of constituents normally present in the cochlear fluids - an increase in calcium concentration shrinks the TM, and an increase in sodium concentration swells the TM in a manner that depends competitively on the calcium concentration. The sodium-induced swelling is specific; it does not occur with other alkali metal cations. We interpret these findings as due to competitive binding of sodium and calcium to TM macromolecules which causes a change in their conformation that leads to a change in mechanical properties. In mouse TM, decreasing the bath pH below 6 or increasing it above 7 results in swelling of the TM. Electric potential measurements are consistent with the notion that the swelling is caused by a pH-driven increase in positive fixed charge at low pH and an increase in the magnitude of the negative fixed charge at high pH which is consistent with the known protonation pattern of TM macromolecules. Increasing the osmotic pressure of the bathing solution with polyethylene glycol shrinks the TM and decreasing the ionic strength of the bathing solution swells the TM. Both results are qualitatively consistent with predictions of a polyelectrolyte gel model of the TM. (C) 2003 Elsevier Science B.V. All rights reserved. C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Polychromix Inc, Woburn, MA 01801 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Freeman, DM (reprint author), MIT, Dept Elect Engn & Comp Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 114 TC 27 Z9 27 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JUN PY 2003 VL 180 IS 1-2 BP 11 EP 27 DI 10.1016/S0378-5955(03)00072-8 PG 17 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 690WU UT WOS:000183574100002 PM 12782349 ER PT J AU Pohle, K Ropers, D Maffert, R Geitner, P Moshage, W Regenfus, M Kusus, M Daniel, WG Achenbach, S AF Pohle, K Ropers, D Maffert, R Geitner, P Moshage, W Regenfus, M Kusus, M Daniel, WG Achenbach, S TI Coronary calcifications in young patients with first, unheralded myocardial infarction: a risk factor matched analysis by electron beam tomography SO HEART LA English DT Article ID ULTRAFAST COMPUTED-TOMOGRAPHY; ARTERY CALCIUM; INTRACORONARY ULTRASOUND; ATHEROSCLEROTIC PLAQUES; ASYMPTOMATIC SUBJECTS; EVENTS; DISEASE; DEATH AB Objective: To compare the presence and extent of coronary calcifications in young patients with first, unheralded acute myocardial infarction with matched controls without a history of coronary artery disease. Methods: In 102 patients under 60 years of age (19-59 years, mean 41 years; 88% male), electron beam tomography was done 1-14 days after acute myocardial infarction, before any coronary intervention. Coronary calcifications were quantified using the Agatston score. Age related calcium centiles were determined based on the Mayo Clinic "epidemiology of coronary calcification" study, and results were compared with a group of 102 controls without coronary artery disease, matched for sex, age, and risk factors. Results: Calcifications were present in 95.1% of patients with acute myocardial infarction and in 59.1% of controls (p = 0.008). The mean (SD) Agatston score was 529 (901) in the infarct patients versus 119 (213) in the controls (p < 0.001). An Agatston score above the 50th centile was present in 87.2% of infarct patients and 47.0% of controls (p = 0.006), and above the 90th centile in 60.7% of infarct patients and only 5.8% of controls (p = 0.001). Conclusions: In young patients with their first, unheralded acute myocardial infarction, the presence and extent of coronary calcium are significantly greater than in matched controls. C1 Univ Erlangen Nurnberg, Dept Cardiol, D-8520 Erlangen, Germany. Klinikum Traunstein, Dept Cardiol, Traunstein, Germany. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. RP Pohle, K (reprint author), Ulmenweg 18, D-91052 Erlangen, Germany. NR 26 TC 33 Z9 33 U1 1 U2 1 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 JUN PY 2003 VL 89 IS 6 BP 625 EP 628 DI 10.1136/heart.89.6.625 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 678FC UT WOS:000182853600011 PM 12748216 ER PT J AU Robertson, P Scadden, DT AF Robertson, P Scadden, DT TI Immune reconstitution in HIV infection and its relationship to cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; SARCOMA-ASSOCIATED HERPESVIRUS; EPSTEIN-BARR-VIRUS; CD4(+) T-CELLS; HUMAN-PAPILLOMAVIRUS INFECTION; RECEPTOR EXCISION CIRCLE; NON-HODGKINS-LYMPHOMA; KAPOSIS-SARCOMA; THYMIC OUTPUT AB HIV infection results in formidable immune dysfunction, widely affecting the immune system, but typified by T lymphopenia. This dysfunction includes a perturbed immune response to several persistent viruses that have a propensity to cause tumors. Effective control of HIV replication by highly active antiretroviral therapy (HAART) results in regeneration of the damaged immune system, and recent advances have allowed this immune reconstitution to be better defined. This article describes the immunodeficiency caused by HIV and the response of the immune system to HAART, with specific reference to the immune response to cancers associated with HIV infection. C1 Harvard Univ, Massachusetts Gen Hosp, Ctr AIDS Res, Sch Med, Boston, MA 02109 USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Regenerat Med, Sch Med, Boston, MA 02109 USA. Harvard Univ, Massachusetts Gen Hosp, Program Immunol, Sch Med, Boston, MA 02109 USA. RP Scadden, DT (reprint author), Harvard Univ, Dept Expt Hematol, Sch Med, 13th ST,Room 5212, Boston, MA 02109 USA. OI Robertson, Paul/0000-0002-6605-2589 NR 105 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 2003 VL 17 IS 3 BP 703 EP + DI 10.1016/S0889-8588(03)00047-9 PG 15 WC Oncology; Hematology SC Oncology; Hematology GA 696VQ UT WOS:000183908600004 PM 12852652 ER PT J AU Papakostas, YG Eftychiadis, A Papakostas, GI Christodoulou, GN AF Papakostas, YG Eftychiadis, A Papakostas, GI Christodoulou, GN TI A historical inquiry into the appropriateness of the term 'panic disorder' SO HISTORY OF PSYCHIATRY LA English DT Article DE anxiety disorder; history; Pan; panic; psychiatry ID DSM-IV; ATTACKS; ANXIETY; AGORAPHOBIA; HYPOTHESIS; SLEEP AB Panic disorder was introduced in the standard psychiatric nosology with the publication of the DSM-III in 1980. The myriad of earlier medical and psychiatric names describing anxiety attacks and related conditions were all abandoned, being housed under the term 'panic attack and panic disorder.' In this paper, the rationale and the appropriateness of this term are critically examined from a historical perspective. First, a brief historical account of anxiety that comes in the episodic form, and the medical and psychiatric terminology that emerged during the last two centuries regarding this condition, are presented. Next, the origins of the concept of panic as a collective or individual fear reaction are traced from a mythological and historical standpoint, up to its current, almost accidental, introduction into the official psychiatric diagnostic systems. Since the word 'panic' has its roots in the Greek god Pan and the unpleasant states inflicted by him, this god is described, as well as St Gilles-also known as St Aegidios, the Athenian-the healing saint for those suffering from panic, horror and phobias. Finally, the current diagnostic features of panic disorder are systematically compared with the corresponding troubles inflicted on people by the mythical god Pan. It is concluded that the introduced term 'panic' appropriately and successfully replaced the old ones. C1 Univ Athens, Sch Med, Dept Med Hist, Athens 11528, Greece. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Univ Athens, Sch Med, Dept Psychiat, GR-11527 Athens, Greece. RP Papakostas, YG (reprint author), Univ Athens, Sch Med, Eginit Hosp, 72-74 Vas Sophias Ave, Athens 11528, Greece. EM gnchrist@compulink.gr RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 NR 46 TC 2 Z9 2 U1 1 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0957-154X J9 HIST PSYCHIATR JI Hist. Psychiatr. PD JUN PY 2003 VL 14 IS 54 BP 195 EP 204 DI 10.1177/0957154X030142004 PN 2 PG 10 WC History Of Social Sciences; Psychiatry SC Social Sciences - Other Topics; Psychiatry GA 768KV UT WOS:000188542900004 PM 14518489 ER PT J AU Lin, FH Chen, YJ Belliveau, JW Wald, LL AF Lin, FH Chen, YJ Belliveau, JW Wald, LL TI A wavelet-based approximation of surface coil sensitivity profiles for correction of image intensity inhomogeneity and parallel imaging reconstruction SO HUMAN BRAIN MAPPING LA English DT Article DE MRI; surface coil; image reconstruction; RF inhomogeneity; wavelet transform; parallel MRI ID PHASED-ARRAY; HUMAN BRAIN; MR-IMAGES; SEGMENTATION; ALGORITHM; SENSE; SMASH AB We evaluate a wavelet-based algorithm to estimate the coil sensitivity modulation from surface coils. This information is used to improve the image homogeneity of magnetic resonance imaging when a surface coil is used for reception, and to increase image encoding speed by reconstructing images from under-sampled (aliased) acquisitions using parallel magnetic resonance imaging (MRI) methods for higher spatiotemporal image resolutions. The proposed algorithm estimates the spatial sensitivity profile of surface coils from the original anatomical images directly without using the body coil for additional reference scans or using coil position markers for electromagnetic model-based calculations. No prior knowledge about the anatomy is required for the application of the algorithm. The estimation of the coil sensitivity profile based on the wavelet transform of the original image data was found to provide a robust method for removing the slowly varying spatial sensitivity pattern of the surface coil image and recovering full FOV images from two-fold acceleration in 8-channel parallel MRI. The results, using bi-orthogonal Daubechies 97 wavelets and other members in this family, are evaluated for T1-weighted and T2-weighted brain imaging. (C) 2003 Wiley-Liss, Inc. C1 MGH, MIT, HMS, Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Cambridge, MA USA. MIT, Dept Civil & Environm Engn, Cambridge, MA 02139 USA. RP Lin, FH (reprint author), MGH, MIT, HMS, Athinoula A Martinos Ctr, Rm 2301 Bldg 149,13th St, Charlestown, MA 02129 USA. EM fhlin@mit.edu RI Lin, Fa-Hsuan/G-6988-2012; Wald, Lawrence/D-4151-2009 OI Lin, Fa-Hsuan/0000-0002-9539-1731; NR 31 TC 42 Z9 44 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 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JUN PY 2003 VL 19 IS 2 BP 96 EP 111 DI 10.1002/hbm.10109 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 688TK UT WOS:000183452100004 PM 12768534 ER PT J AU Caplan, D Waters, G Alpert, N AF Caplan, D Waters, G Alpert, N TI Effects of age and speed of processing on rCBF correlates of syntactic processing in sentence comprehension SO HUMAN BRAIN MAPPING LA English DT Article DE speed of processing; age; syntactic comprehension; rCBF ID VERBAL WORKING-MEMORY; HUMAN-BRAIN; INDIVIDUAL-DIFFERENCES; APHASIC PATIENTS; LANGUAGE; ACTIVATION; LOCALIZATION; COGNITION; FMRI; PET AB Positron emission tomography (PET) was used to determine the effect of age on regional cerebral blood flow (rCBF) during syntactic processing in sentence comprehension. PET activity associated with making plausibility judgments about syntactically more complex subject object (SO) sentences (e.g., The juice that the child spilled stained the rug) was compared to that associated with making judgments about synonymous syntactically simpler object subject (OS) sentences (e.g., The child spilled the juice that stained the rug). In the first study, 13 elderly (70-80-year-old) subjects showed increased rCBF in the left inferior parietal lobe. This result contrasted with previous studies, which have shown activation in Broca's area in this task in young subjects. Elderly subjects were noted to have longer reaction times than young subjects previously tested. A second study found that young subjects whose reaction times were as long as those of the elderly subjects tested in Experiment 1 activated left superior parietal, and not left inferior frontal, structures. A third experiment found that elderly subjects with reaction times as fast as previously tested young subjects activated left inferior frontal structures. The results suggest that the speed of syntactic processing, but not age per se is related to the neural location where one. aspect of syntactic processing is carried out. (C) 2003 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Neuropsychol Lab, Dept Neurol, Boston, MA 02114 USA. Boston Univ, Dept Commun Disorders, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Dept Neurol, Vincent Burnham 827,Fruit St, Boston, MA 02114 USA. EM dcaplan@partners.org FU NIA NIH HHS [AG96610]; NIDCD NIH HHS [DC02146] NR 77 TC 20 Z9 21 U1 3 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JUN PY 2003 VL 19 IS 2 BP 112 EP 131 DI 10.1002/hbm.10107 PG 20 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 688TK UT WOS:000183452100005 PM 12768535 ER PT J AU Brodeur, SR Angelini, F Bacharier, LB Blom, AM Mizoguchi, E Fujiwara, H Plebani, A Notarangelo, LD Dahlback, B Tsitsikov, E Geha, RS AF Brodeur, SR Angelini, F Bacharier, LB Blom, AM Mizoguchi, E Fujiwara, H Plebani, A Notarangelo, LD Dahlback, B Tsitsikov, E Geha, RS TI C4b-binding protein (C4BP) activates B cells through the CD40 receptor SO IMMUNITY LA English DT Article ID NF-KAPPA-B; CLASS-SWITCH RECOMBINATION; LINKED IMMUNOGLOBULIN DEFICIENCY; COMPLEMENT REGULATOR C4BP; AUTOSOMAL RECESSIVE FORM; CYTIDINE DEAMINASE AID; ELEVATED IGM HIGMX-1; AMYLOID-P COMPONENT; GENE-EXPRESSION; ALPHA-CHAIN AB We demonstrate that the a. chain of human C4b binding protein (C4BP) binds directly to CD40 on human B cells at a site that differs from that used by CD40 ligand. C4BP induces proliferation, upregulation of CD54 and CD86 expression, and IL4-dependent IgE isotype switching in normal B cells but not in B cells from patients with CD40 or IKKgamma/NEMO deficiencies. Furthermore, C4BP colocalized with B cells in the germinal centers of human tonsils. These observations suggest that C4BP is an activating ligand for CD40 and establish a novel interface between complement and B cell activation. C1 Harvard Univ, Childrens Hosp, Sch Med, Div Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Lund Univ, Dept Clin Chem, Malmo, Sweden. Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Univ Brescia, Dept Pediat, Brescia, Italy. Univ Brescia, Inst Mol Med Angelo Nocivelli, Brescia, Italy. Univ Roma Tor Vergata, Dept Pediat, Rome, Italy. Washington Univ, Dept Pediat, St Louis, MO 63130 USA. Osaka Univ, Dept Med, Osaka, Japan. RP Geha, RS (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Div Immunol, Boston, MA 02115 USA. RI Plebani, Alessandro/C-8593-2011; Blom, Anna/B-9607-2009; Notarangelo, Luigi/F-9718-2016 OI Blom, Anna/0000-0002-1348-1734; Notarangelo, Luigi/0000-0002-8335-0262 FU NIAID NIH HHS [AI-31451, T32 AI-07512] NR 67 TC 73 Z9 73 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 2003 VL 18 IS 6 BP 837 EP 848 DI 10.1016/S1074-7613(03)00149-3 PG 12 WC Immunology SC Immunology GA 694HB UT WOS:000183767700013 PM 12818164 ER PT J AU Chen, DS Xia, JC Tanaka, Y Chen, HS Koido, S Wernet, O Mukherjee, P Gendler, SJ Kufe, D Gong, JL AF Chen, DS Xia, JC Tanaka, Y Chen, HS Koido, S Wernet, O Mukherjee, P Gendler, SJ Kufe, D Gong, JL TI Immunotherapy of spontaneous mammary carcinoma with fusions of dendritic cells and mucin 1-positive carcinoma cells SO IMMUNOLOGY LA English DT Article ID TRANSGENIC MICE; BREAST-CANCER; ERADICATE TUMORS; T-LYMPHOCYTES; CORE PROTEIN; HUMAN-MILK; TUMORIGENESIS; EXPRESSION; INDUCTION; EPITOPE AB The tumour-associated antigen mucin 1 (MUC1) is a multifunctional protein involved in protection of mucous membranes, signal transduction, and modulation of the immune system. More than 70% of cancers overexpress MUC1, making MUC1 a potential target for immunotherapy. In the present study, MUC1 transgenic mice were crossed with syngeneic strains that express the polyomavirus middle-T oncogene (PyMT) driven by the mouse mammary tumour virus promoter long-terminal repeat (MMTV-LTR). The resultant breed (MMT mice) developed spontaneous MUC1-expressing mammary carcinomas with 100% penetrance at 8-15 weeks of age. As found in human breast cancer, the mammary carcinoma in MMT mice arose in multiple stages. Immunization with fusions of dendritic cells and MUC1-positive tumour cells (FC/MUC1) induced MUC1-specific immune responses that blocked or delayed the development of spontaneous breast carcinomas. In contrast, there was no delay of tumour development in MMT mice immunized with irradiated MC38/MUC1 tumour cells. The efficacy of fusion cells was closely correlated with the timing of initial immunization. Immunization with FC/MUC1 initiated in MMT mice at < 1, 1-2 and 2-3 months of age rendered 33, 5 and 0% of mice free of tumour, respectively, up to 6 months. Whereas mice immunized in the later stage of tumour development succumbed to their disease, immunization resulted in control of tumour progression and prolongation of life. These results indicate that immunization with FC/MUC1 can generate an anti-MUC1 response that is sufficient to delay the development of spontaneous mammary carcinomas and control tumour progression in MMT mice. C1 Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Scottsdale, AZ USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Gong, JL (reprint author), Boston Univ, Sch Med, Dept Med, 88 E Newton St, Boston, MA 02118 USA. FU NCI NIH HHS [R01 CA087057, R01 CA87057] NR 41 TC 58 Z9 66 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 JUN PY 2003 VL 109 IS 2 BP 300 EP 307 DI 10.1046/j.1365-2567.2003.01656.x PG 8 WC Immunology SC Immunology GA 681RQ UT WOS:000183049500015 PM 12757626 ER PT J AU Suzuki, M Hisamatsu, T Podolsky, DK AF Suzuki, M Hisamatsu, T Podolsky, DK TI Gamma interferon augments the intracellular pathway for lipopolysaccharide (LPS) recognition in human intestinal epithelial cells through coordinated up-regulation of LPS uptake and expression of the intracellular toll-like receptor 4-MD-2 complex SO INFECTION AND IMMUNITY LA English DT Article ID NF-KAPPA-B; BACTERIAL LIPOPOLYSACCHARIDE; INNATE IMMUNITY; CROHNS-DISEASE; ULCERATIVE-COLITIS; GOLGI-APPARATUS; BINDING-PROTEIN; FAMILY MEMBER; MICE; ACTIVATION AB Although some intestinal epithelial cell lines are known to respond to lipopolysaccharide (LPS), understanding of the relationship between LPS responsiveness and the expression of LPS receptors or factors regulating LPS responsiveness of intestinal epithelial cell lines is incomplete. In this study, we demonstrate that commonly studied human intestinal epithelial cell lines can be classified into at least three different types on the basis of LPS responsiveness, Toll-like receptor-4 (TLR4) expression, and the effects of gamma interferon (IFN-gamma) on LPS responsiveness. The first phenotype, which includes the HCT-116 and Caco-2 cell lines, is characterized by relative hyporesponsiveness to LPS and diminished expression of TLR4 protein. In these cells, IFN-gamma does not induce LPS responsiveness. The second phenotype, which includes cell line SW480, exhibits a highly LPS-responsive phenotype and surface expression of TLR4 protein even in unprimed conditions. These lines are functionally similar to cells of monocytic lineage. In the third phenotype, which includes the HT-29 and Colo205 cell lines, TLR4 protein is largely present in the cytoplasmic fraction and the cells are hyporesponsive to LPS in an unprimed condition. However, priming of these cells with IFN-gamma can induce LPS responsiveness through augmentation of LPS uptake and expression of MD-2 mRNA and intracellular TLR4 proteins. Finally, these findings suggest that the Th1 cytokine IFN-gamma modulates LPS responsiveness through several mechanisms in intestinal epithelial cells and that these cells may comprise different subpopulations with distinct roles in innate immune responses. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 32 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK43351, DK60049, P30 DK043351, R01 DK060049] NR 43 TC 161 Z9 170 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2003 VL 71 IS 6 BP 3503 EP 3511 DI 10.1128/IAI.71.6.3503-3511.2003 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 682WX UT WOS:000183116300063 PM 12761135 ER PT J AU Reiser, M Lauer, GM AF Reiser, M Lauer, GM TI 20 clinical pearls: Viral hepatitis SO INFECTIONS IN MEDICINE LA English DT Article DE hepatitis E; vaccination; interferon ID C VIRUS-INFECTION; A VACCINE; HEPATOCELLULAR-CARCINOMA; RANDOMIZED TRIAL; INTERFERON-ALPHA; NATURAL-HISTORY; PLUS RIBAVIRIN; LIVER-DISEASE; TRANSMISSION; PROGRESSION AB While prevention of hepatitis A and B can be achieved by means of immunization, no vaccine is currently available for hepatitis C. Transmission of hepatitis C virus (HCV) can therefore only be prevented by minimizing parenteral risk contacts. Treatment of chronic hepatitis B virus infection has advanced with the introduction of new, highly effective antivirals. Most patients with HCV infection have mild or no symptoms. Diagnosis of acute HCV infection is challenging, but early treatment with interferon may be beneficial. In patients with chronic HCV infection, a baseline liver biopsy is useful for prognosis and as the basis for a therapy plan. Most patients with chronic HCV infection can be reassured that progression of fibrosis is mild to moderate and that even in those with progressive disease, it typically takes years to decades to reach the point of irreversible liver disease. C1 Ruhr Univ Bochum, Berufsgenossenschaftliche Kliniken Bergmannsheil, D-4630 Bochum, Germany. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Reiser, M (reprint author), Ruhr Univ Bochum, Berufsgenossenschaftliche Kliniken Bergmannsheil, Univ Str 150, D-4630 Bochum, Germany. NR 25 TC 0 Z9 0 U1 0 U2 0 PU SCP COMMUNICATIONS INC PI NEW YORK PA 134 W 29TH ST, NEW YORK, NY 10001-5304 USA SN 0749-6524 J9 INFECT MED JI Infect. Med. PD JUN PY 2003 VL 20 IS 6 BP 281 EP + PG 6 WC Infectious Diseases SC Infectious Diseases GA 692QW UT WOS:000183672600006 ER PT J AU Thiagarajan, RR Roth, SJ Margossian, S Mackie, AS Neufeld, EJ Laussen, PC Forbess, JM Blume, ED AF Thiagarajan, RR Roth, SJ Margossian, S Mackie, AS Neufeld, EJ Laussen, PC Forbess, JM Blume, ED TI Extracorporeal membrane oxygenation as a bridge to cardiac transplantation in a patient with cardiomyopathy and hemophilia A SO INTENSIVE CARE MEDICINE LA English DT Article DE dilated cardiomyopathy; extracorporeal membrane oxygenation; hemophilia A; factor VIII inhibitor; cardiac transplantation ID CHILDREN; DISEASE AB Objective: To report the use of extracorporeal membrane oxygenation (ECMO) as a bridge to cardiac transplantation in a patient with hemophilia A and dilated cardiomyopathy. Design: Case report. Interventions and results: During ECMO factor VIII concentrate was administered to maintain a factor VIII level close to 50% of normal control both to decrease the risk of bleeding and to allow standard anticoagulation with heparin. The patient developed an inhibitor to exogenous factor VIII during hospitalization, which was successfully managed with a high-dose continuous infusion of factor VIII during ECMO, the transplant operation, and the postoperative period. Conclusions: We report the successful use of ECMO as a bridge to cardiac transplantation in a patient with hemophilia A and low-level factor VIII inhibitors. C1 Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiovasc Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. RP Thiagarajan, RR (reprint author), Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA. EM ravi@cardio.chboston.org RI Neufeld, Ellis/F-9331-2011 FU NHLBI NIH HHS [HL04183-03] NR 15 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD JUN PY 2003 VL 29 IS 6 BP 985 EP 988 DI 10.1007/s00134-003-1748-5 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 697GU UT WOS:000183934800022 PM 12719805 ER PT J AU Feil, D Razani, J Boone, K Lesser, I AF Feil, D Razani, J Boone, K Lesser, I TI Apathy and cognitive performance in older adults with depression SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE executive function; cognition; apathy; geriatric depression; motivation; emotions; neuropsychological tests; Stroop C; Wisconsin Card Sorting ID ACQUIRED BRAIN-DAMAGE; GERIATRIC DEPRESSION; ALZHEIMERS-DISEASE; EXECUTIVE DYSFUNCTION; VASCULAR DEPRESSION; RATING-SCALE; DOUBLE-BLIND; LATE-LIFE; DEMENTIA; VALIDITY AB Objectives Recent studies have linked apathy to frontal lobe dysfunction in persons with dementia, but few studies have explored this relationship in older, depressed persons without dementia. We examined the association between apathy and cognitive function in a group of older persons with major depression using standardized neuropsychological tests. We hypothesized that presence of apathy in depression is associated with poorer frontal executive performance. Methods We analyzed data from 89 older adults with major depression. We defined apathy using four items from the Hamilton Psychiatric Rating Scale for Depression which reflect the clinical state of apathy, including 'diminished work/interest,' 'psychomotor retardation,' 'anergy' and 'lack of insight.' Results Apathy most strongly correlated with two verbal executive measures (Stroop C and FAS), a nonverbal executive measure (Wisconsin Card Sorting Test-Other Responses), and a measure of information processing speed (Stroop B). Apathy was not associated with age, sex, education, medical illness burden, Mini-Mental State Examination score and Full Scale IQ score. Stepwise regression analyses of significant cognitive tests showed that apathy alone or apathy plus depression severity, age, or education accounted for a significant amount of the variance. Conclusions The results of this study provide support for an apathy syndrome associated with poorer executive function in older adults with major depression. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Univ Calif Los Angeles, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. Calif State Univ Northridge, Northridge, CA 91330 USA. Harbor UCLA Med Ctr, Torrance, CA 90509 USA. RP Feil, D (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Hlth Care Syst, 11301 Wilshire Blvd,116-AF,Bldg 500,Room 3416, Los Angeles, CA 90073 USA. FU NCRR NIH HHS [RR-00425]; NIMH NIH HHS [MH43960] NR 56 TC 52 Z9 56 U1 2 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD JUN PY 2003 VL 18 IS 6 BP 479 EP 485 DI 10.1002/gps.869 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 691JN UT WOS:000183603000002 PM 12789667 ER PT J AU Kaban, LB Thurmuller, R Troulis, MJ Giowacki, J Wahl, D Linke, B Rahn, B Perrott, DH AF Kaban, LB Thurmuller, R Troulis, MJ Giowacki, J Wahl, D Linke, B Rahn, B Perrott, DH TI Correlation of biomechanical stiffness with plain radiographic and ultrasound data in an experimental mandibular distraction wound SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 84th Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgeons CY OCT, 2002 CL CHICAGE, ILLINOIS SP Amer Assoc Oral & Maxillofacial Surg DE distraction osteogenesis; biomechanical stiffness; ultrasound ID BONE-FORMATION; SKELETAL DISTRACTION; GRADUAL DISTRACTION; COMPUTED-TOMOGRAPHY; GENE-EXPRESSION; OSTEOGENESIS; GROWTH; MODEL; RAT; TISSUES AB The aim of this study Was to determine the stiffness of a porcine mandibular distraction wound at the end of neutral fixation. Twenty-four Yucatan minipigs underwent unilateral mandibular distraction: zero-day latency, rates of 1, 2, and 4 mm per day, distraction gap of 12 mm. Radiographic and ultrasound bone fill scores at 0, 8, 16 and 24 days of neutral fixation were used to evaluate interval healing. At sacrifice, biomechanical stiffness was determined using an Instron machine to produce a downward force of 2 mm/min at the premolar occlusal surface.. Force (kilo-Newton, kN) and displacement (mm) were recorded at a rate of 10,000 points/second. Stiffness across the distraction wound, plain radiographic and ultrasound bone fill scores all increased with duration of neutral fixation and were highest for the 1 mm per day group at all time points. At the end of fixation, even in the most clinically stable group, stiffness across the distraction wound was only 25.5% of control. Despite clinical stability and high bone fill scores by X-ray and ultrasound, the distraction wound did not achieve normal stiffness at the end of neutral fixation. in this model. This may have implications for the management of patients who undergo large movements by distraction. C1 Massachusetts Gen Hosp, Dept OMFS, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. AO Res Inst, Davos, Switzerland. RP Kaban, LB (reprint author), Massachusetts Gen Hosp, Dept OMFS, Fruit St, Boston, MA 02114 USA. NR 60 TC 24 Z9 25 U1 1 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0901-5027 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD JUN PY 2003 VL 32 IS 3 BP 296 EP 304 DI 10.1054/ijom.2002.0380 PG 9 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 689VP UT WOS:000183513900011 PM 12767878 ER PT J AU Cherukupally, SR Mankarious, LA Faquin, W Cunningham, MJ AF Cherukupally, SR Mankarious, LA Faquin, W Cunningham, MJ TI Pediatric non-orbital pseudotumor of the head and neck SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE pseudotumor; non-orbital pseudotumor; pediatric; head and neck ID INFLAMMATORY DISEASE AB Objective: To evaluate the incidence, sites of presentation, and treatment outcome of non-orbital pseudotumor of the head and neck in the pediatric population. Methods: 10-year retrospective case series at a tertiary care center. All patients 18 years of age and younger with non-orbital pseudotumor of the head and neck evaluated and treated at our institution over the study period (1990-2000) were identified through the Systematic Nomenclature of Medicine (SNOMED) database with the keyword 'pseudotumor'. Results: Among 146 patients identified with head and neck pseudotumor at our institution, 15 (10%) were pediatric patients, only three (20%) of whom had pseudotumor in non-orbital sites (the infratemporal and pterygopalatine fossae, submandibular gland, and masseter space). Four (27%) of the 15 had pseudotumor limited to the lacrimal gland, with the remaining eight (53%) being orbital pseudotumor cases. Conclusions: Similar to cases of orbital pseudotumor, long term systemic steroid therapy proved effective in the management of nonorbital pseudotumor in all three children with eventual disease resolution. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Cunningham, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 14 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD JUN PY 2003 VL 67 IS 6 BP 649 EP 653 DI 10.1016/S0165-5876(03)00037-5 PG 5 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 682VY UT WOS:000183114100011 PM 12745159 ER PT J AU Kim, HK Silver, B Li, SG Neuberg, D Mauch, P AF Kim, HK Silver, B Li, SG Neuberg, D Mauch, P TI Hodgkin's disease in elderly patients (>= 60): Clinical outcome and treatment strategies SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO 99) CY OCT 30-NOV 04, 1999 CL SAN ANTONIO, TEXAS SP Amer Soc Therapeut Radiol & Oncol DE Hodgkin's disease; elderly patients; treatment strategies; clinical outcome ID PROGNOSTIC FACTORS; STAGE-I; AGE; SURVIVAL; THERAPY; MANAGEMENT; YOUNGER; MOPP AB Purpose: Older age is an adverse prognostic factor for survival for patients with Hodgkin's disease. This study assessed the outcome of elderly patients (greater than or equal to60 years) with Hodgkin's disease treated with curative intent in an attempt to identify the optimal treatment strategies for this group of patients. Methods and Materials: Eighty-six patients, 60-93 years old at the time of diagnosis, were treated for Hodgkin's disease with radical intent between 1969 and 1995. All patients underwent radiographic staging of the chest, abdomen, and pelvis, and 17 patients underwent staging laparotomy. Fifty-two patients had early-stage disease (Stage IA-IIA) and 34 had Stage IIB-IV Hodgkin's disease. The median follow-up time was 75 months (range 24-267) for surviving patients. Results: The 10-year actuarial freedom from treatment failure (FFTF) rate for all patients was 62%. The 10-year FFTF rate for patients with Stage IA-IIA and Stage IIB-IV disease was 71% and 49%, respectively (p = 0.03). Patients with early-stage disease treated with chemoradiotherapy had a lower crude rate of treatment failure (20%) than patients treated with either chemotherapy alone (33%) or radiotherapy alone (46%). However, no statistically significant difference was found between the treatment groups in terms of actuarial FFTF or overall survival. The 5- and 10-year overall survival rate (all causes) for all patients was 48% and 30%, respectively. The 10-year survival rate for patients with Stage IA-IIA and Stage IIB-IV disease was 31% and 26%, respectively (p = 0.07). On multiple regression analysis, including age, treatment, and stage in the Cox regression model with respect to overall survival, age was a marginally significant factor (p = 0.08). For FFTF, age was not a significant factor in the model (p = 0.11). We analyzed the subsequent outcome of patients who developed a first recurrence after initial treatment; the 5-year survival rate was only 20% after recurrence of Hodgkin's disease. Initial treatment was reasonably well tolerated. Conclusion: Although more patients died of other causes than Hodgkin's disease, the recurrence of Hodgkin's disease had a significant impact on survival. Thus, we favor the use of chemoradiotherapy in early-stage patients >60 years to minimize the risk of relapse. (C) 2003 Elsevier Inc. C1 Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Kim, HK (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, 330 Brookline Ave, Boston, MA 02215 USA. NR 31 TC 20 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 1 PY 2003 VL 56 IS 2 BP 556 EP 560 DI 10.1016/S0360-3016(02)04596-0 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 678HP UT WOS:000182861500031 PM 12738333 ER PT J AU Seybold, U Draenert, R Goebel, FD AF Seybold, U Draenert, R Goebel, FD TI Adverse events of antiretroviral therapy: aspects of pathogenesis SO INTERNIST LA German DT Article DE HIV-infection; AIDS; metabolic alterations; lipodystrophy; cardiovascular risk ID HIV-INFECTED PATIENTS; HUMAN GROWTH-HORMONE; IMMUNODEFICIENCY-VIRUS-INFECTION; NECROSIS-FACTOR-ALPHA; INSULIN-RESISTANCE; HIV-1-INFECTED PATIENTS; PROTEASE INHIBITORS; FAT REDISTRIBUTION; LIPODYSTROPHY SYNDROME; POSITIVE PATIENTS AB Highly active antiretroviral therapy has resulted in remarkable reduction of morbidity and mortality of HIV infection. With increasing duration of therapy metabolic alterations such as hyperlipidemia diabetes mellitus type 2 and lipodystrophy are encountered which considerably reduced quality of life for the patients. These adverse events are most likely due to protease inhibitors and nucleoside analogues with synergistic effects. The pathogenesis is related to metabolical alterations of the adipocytes with cellular insulin resistance and enhanced apoptosis of these cells caused by adipocytic cytokines such as adiponectin,leptin, TNF-alpha and interleukin 2. Switch of therapy regimens with elimination of the most suspicious substances and certain protease inhibitors can lead to improvement of deranged metabolism. Also symptomatic therapy is possible to cope with hyperlipidemia and diabetes, although no effective treatment is available to reverse already existing lipodystrophy. Our knowledge about the pathogenesis of these alterations might lead to new concepts and causal therapy in the future. C1 Univ Munich Klinikum, Med Poliklin Innenstadt, D-80336 Munich, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div AIDS, Boston, MA USA. RP Goebel, FD (reprint author), Univ Munich Klinikum, Med Poliklin Innenstadt, Pettenkoferstr 8A, D-80336 Munich, Germany. NR 55 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0020-9554 J9 INTERNIST JI Internist PD JUN PY 2003 VL 44 IS 6 BP 701 EP + DI 10.1007/s00108-003-0927-3 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 696XR UT WOS:000183913300004 PM 14567106 ER PT J AU Hong, DH Pawlyk, B Sokolov, M Strissel, KJ Yang, J Tulloch, B Wright, AF Arshavsky, VY Li, TS AF Hong, DH Pawlyk, B Sokolov, M Strissel, KJ Yang, J Tulloch, B Wright, AF Arshavsky, VY Li, TS TI RPGR isoforms in photoreceptor connecting cilia and the transitional zone of motile cilia SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID LINKED RETINITIS-PIGMENTOSA; NUCLEOTIDE-EXCHANGE FACTOR; SUBCELLULAR-LOCALIZATION; EXON ORF15; RETINAL RODS; PROTEIN; MOUSE; IDENTIFICATION; GENE; DEGENERATION AB Purpose. The retinitis pigmentosa guanosine triphosphatase (GTPase) regulator (RPGR) is essential for photoreceptor survival. There is as yet no consensus concerning the subcellular localization of RPGR. This study was undertaken as a comprehensive effort to resolve current controversies. Method. RPGR in mice and other mammalian species was examined by immunofluorescence. RPGR variants were distinguished by using isoform-specific antibodies. Different tissue processing procedures were evaluated. Immunoblot analysis of serial cross-sections of photoreceptors was performed as a complementary approach to subcellular localization. Results.. RPGR was found in the connecting cilia of rods and cones with no evidence for species-dependent variation. RPGR ORF15 was the predominant variant in photoreceptor connecting cilia whereas constitutive RPGR (default) was the sole variant in the transitional zone of motile cilia in airway epithelia. Removal of soluble materials in the interphotoreceptor matrix facilitated detection of RPGR in the connecting cilia in photoreceptors. CONCLUSIONS. RPGR localizes in photoreceptor connecting cilia and in a homologous structure, the transitional zone of motile cilia. These data are important for understanding the multitude of clinical manifestations associated with mutations in RPGR. Interphotoreceptor matrix surrounding the connecting cilia is a key variable for in situ detection of a protein in the connecting cilia. 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, Howe Lab,Dept Ophthalmol, Boston, MA 02114 USA. Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. RP Li, TS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY10309, EY10336] NR 34 TC 124 Z9 125 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 JUN PY 2003 VL 44 IS 6 BP 2413 EP 2421 DI 10.1167/iovs.02-1206 PG 9 WC Ophthalmology SC Ophthalmology GA 682FU UT WOS:000183081700008 PM 12766038 ER PT J AU Shatos, MA Rios, JD Horikawa, Y Hodges, RR Chang, EL Bernardino, CR Rubin, PAD Dartt, DA AF Shatos, MA Rios, JD Horikawa, Y Hodges, RR Chang, EL Bernardino, CR Rubin, PAD Dartt, DA TI Isolation and characterization of cultured human conjunctival goblet cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID EPIDERMAL GROWTH-FACTOR; CORNEAL EPITHELIAL-CELLS; HUMAN OCULAR SURFACE; HUMAN BREAST-CANCER; STEM-CELLS; FACTOR RECEPTOR; EGF RECEPTOR; FACTOR-BETA; TEAR FILM; IN-VITRO AB Purpose. To isolate and characterize goblet cells from normal human conjunctival tissue to determine whether epidermal growth factor (EGF) receptors are present and whether EGF can influence goblet cell proliferation. Methods.. Goblet cells were isolated from explant cultures established from normal conjunctival tissue harvested from patients during periocular surgery. The cells were grown in RPMI culture medium supplemented with 10% fetal bovine serum and characterized using morphology, histochemistry, indirect immunofluorescence microscopy, molecular biology, and biochemistry. Proliferation was determined with a MTT proliferation assay after exposing goblet cells, which had been serum deprived for 48 hours, to increasing concentrations of epidermal growth factor (EGF; 0-80 ng/mL) for 24 hours. Results. Goblet cells were isolated from conjunctival explants by scraping nongoblet cells from the culture dish. Human goblet cells exhibited positive reactivity with alcian blue-periodic acid Schiff (PAS) reagent, goblet cell-specific Cytokeratin-7, HPA lectin, and MUC5AC, but negative reactivity to the stratified squamous epithelial cell marker, cytokeratin-4. The mRNA for MUC5AC was detected using RT-PCR. The presence of the EGF receptors EGFR, ErbB2, and ErbB3 was confirmed through Western blot analysis of cell lysates. EGF elicited a concentration-dependent increase in goblet cell proliferation of 160% +/- 0.5%, 188% +/- 0.45%, 293% +/- 1.3%, and 220% +/- 0.5% of control values with 10, 20, 40, and 80 ng/ml, EGF, respectively. Conclusion. Human goblet cells that retain characteristics of goblet cells in vivo can be cultured. EGF receptors are present in human goblet cells, and EGF stimulates their proliferation. (Invest Ophthalmol Vis Sci. 2003;44:2477-2486) DOI: 10.1167/iovs.02-0550. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Asahikawa Med Coll, Dept Ophthalmol, Asahikawa, Hokkaido, Japan. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Shatos, MA (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. FU NEI NIH HHS [R01 EY009057, EY09057] NR 52 TC 44 Z9 48 U1 1 U2 6 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 JUN PY 2003 VL 44 IS 6 BP 2477 EP 2486 DI 10.1167/iovs.02-0550 PG 10 WC Ophthalmology SC Ophthalmology GA 682FU UT WOS:000183081700016 PM 12766046 ER PT J AU Horikawa, Y Shatos, MA Hodges, RR Zoukhri, D Rios, JD Chang, EL Bernardino, CR Rubin, PAD Dartt, DA AF Horikawa, Y Shatos, MA Hodges, RR Zoukhri, D Rios, JD Chang, EL Bernardino, CR Rubin, PAD Dartt, DA TI Activation of mitogen-activated protein kinase by cholinergic agonists and EGF in human compared with rat cultured conjunctival goblet cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID GROWTH-FACTOR; SECRETION; RABBIT; STIMULATION; RECEPTORS; EPITHELIA; MUCIN; EXPRESSION; NERVES AB Purpose. To compare activation of the p42/p44 mitogen-activated protein kinase (MAPK) by cholinergic agonists and epidermal growth factor (EGF) in cultured human and rat goblet cells. Methods. Conjunctiva was removed from either humans during ocular surgery or male Sprague-Dawley rats and cultured in RPMI medium. These cells were incubated with the cholinergic agonist carbachol (10(-4) M) or EGF (10(-8) M) for various times. Before stimulation, cells were incubated with the EGF receptor (EGFR) inhibitor, AG1478 (10(-7) M) or the muscarinic M-3 receptor inhibitor, 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine hydrochloride (4-DAMP; 10(-5) M) for 10 minutes. Proteins were analyzed by Western blot analysis, using antibodies specific to phosphorylated (activated) p42/44-MAPK or total p42-MAPK. Immunoreactive bands were quantified, and data were expressed as percentage of increase over basal. Results. Carbachol (10(-4) M) increased MAPK activity in human and rat cultured goblet cells in a time-dependent manner, increasing pMAPK with a maximum at 10 minutes. EGF (10(-8) M) activated MAPK in human and rat goblet cells in a time-dependent manner with a maximum at 5 minutes. Carbachol- and EGF-induced activation of pMAPK was completely inhibited by AG1478 in cultured conjunctival goblet cells from both species. Carbachol-induced MAPK activity was also completely inhibited by 4-DAMP in both species. Conclusions. In human and rat cultured conjunctival goblet cells, cholinergic agonists and EGF activate MAPK with a similar time dependency, this activation is receptor mediated, and cholinergic agonists transactivate the EGF receptor. Thus, rat cultured conjunctival goblet cells can be used as a model to study human conjunctival goblet cells. (Invest Ophthalmol Vis Sci. 2003;44:2535-2544) DOI:0.1167/iovs.02-1117. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Asahikawa Med Coll, Dept Ophthalmol, Asahikawa, Hokkaido, Japan. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Dartt, DA (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. OI Zoukhri, Driss/0000-0003-1622-4431 FU NEI NIH HHS [EY09057, R01 EY009057] NR 31 TC 21 Z9 22 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 JUN PY 2003 VL 44 IS 6 BP 2535 EP 2544 DI 10.1167/iovs.02-1117 PG 10 WC Ophthalmology SC Ophthalmology GA 682FU UT WOS:000183081700024 PM 12766054 ER PT J AU Sakurai, E Taguchi, H Anand, A Ambati, BK Gragoudas, ES Miller, JW Adamis, AR Ambati, J AF Sakurai, E Taguchi, H Anand, A Ambati, BK Gragoudas, ES Miller, JW Adamis, AR Ambati, J TI Targeted disruption of the CD18 or ICAM-1 gene inhibits choroidal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; INTERCELLULAR-ADHESION MOLECULE-1; RETINAL-PIGMENT EPITHELIUM; AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; SUBRETINAL NEOVASCULARIZATION; MESSENGER-RNA; LASER PHOTOCOAGULATION; BRUCHS MEMBRANE; CELL-ADHESION AB PURPOSE. To investigate the role of the leukocyte adhesion molecules CD18 and intercellular adhesion molecule (ICAM)-1 in the development of choroidal neovascularization (CNV). METHODS. Laser photocoagulation was used to induce CNV in wild-type C57BL/6J mice and species-specific counterparts with targeted homozygous disruption of the CD18 or ICAM-I gene. Expression of CD18 and ICAM-I after laser injury was assessed by immunostaining. CNV responses were compared on the basis of en masse volumetric measurements Obtained by confocal microscopy 2 weeks after laser injury and by determination of fluorescein angiographic leakage at 1, 2, and 4 weeks after laser injury. RESULTS. The site of laser injury showed upregulation of ICAM-I and invasion by CD18-positive leukocytes within I day of laser injury. Significantly fewer lesions exhibited fluorescein leakage defined to be pathologically significant in CD18-deficient mice at weeks 1, 2, and 4 weeks and in ICAM-1-deficient mice at 1 and 4 weeks, compared with the control. There were a significantly greater number of lesions without fluorescein leakage in CD18-deficient mice than in the other two groups at all time points. The volume of CNV in CD18- and ICAM-1-deficient mice was significantly less than in wild type. CONCLUSIONS. These data suggest a nonredundant role for leukocyte adhesion to vascular endothelium in the development of laser-induced choroidal neovascularization. C1 Univ Kentucky, Dept Ophthalmol, Lexington, KY 40536 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 USA. Eyetech Res Ctr, Woburn, MA USA. RP Ambati, J (reprint author), Univ Kentucky, Dept Ophthalmol, 740 S Limestone St, Lexington, KY 40536 USA. NR 64 TC 84 Z9 96 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 JUN PY 2003 VL 44 IS 6 BP 2743 EP 2749 DI 10.1167/iovs.02-1246 PG 7 WC Ophthalmology SC Ophthalmology GA 682FU UT WOS:000183081700052 PM 12766082 ER PT J AU Zekry, D Epperson, TK Krause, KH AF Zekry, D Epperson, TK Krause, KH TI A role for NOX NADPH oxidases in Alzheimer's disease and other types of dementia? SO IUBMB LIFE LA English DT Review DE ageing (aging); Alzheimer; dementia; NADPH oxidase; reactive oxygen species; neuronal death ID QUALITY STANDARDS SUBCOMMITTEE; SUPEROXIDE-GENERATING OXIDASE; ACADEMY-OF-NEUROLOGY; VASCULAR DEMENTIA; NAD(P)H OXIDASE; CEREBROVASCULAR-DISEASE; INFLAMMATORY MECHANISMS; DIFFERENTIAL-DIAGNOSIS; PRACTICE PARAMETER; MIXED DEMENTIA AB Because of population ageing, dementias are likely to become a major scourge of the 21st century. Causes of dementia include Alzheimer's disease, cerebrovascular disease, and lesser known entities such as frontotemporal dementia or dementia with Lewy bodies. Neuroinflammation is likely to play an important role in the pathogenesis of dementia by the killing of neurons through inflammatory mechanisms. Such a role of neuroinflammation is well documented for Alzheimer's disease, and it is likely to play a role in other types of dementia as well. Reactive oxygen species (ROS) play a key role in inflammatory tissue destruction. The phagocyte NADPH oxidase NOX2 is the best studied ROS-generating system. In the central nervous system, it is expressed in microglia and--to a lesser extent--in neurons. Indeed, there is emerging experimental evidence for a role of NOX2 in Alzheimer's and cerebrovascular disease. Recently, six novel ROS-generating NADPH oxidases with homology to NOX2 have been discovered. Several of them are also expressed in the central nervous system. In this article, we hypothesize a role of NOX-type NADPH oxidases in inflammatory neuronal loss. We review presently available evidence and suggest that NOX-type NADPH oxidases may become promising pharmacological targets for the treatment and prevention of dementia. C1 Univ Hosp Geneva, Dept Geriatr, Geneva, Switzerland. S Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. RP Krause, KH (reprint author), Biol Ageing Lab, 2 Chemin Petit Bel Air, CH-1225 Geneva, Switzerland. RI Krause, Karl-Heinz/E-8030-2011 NR 62 TC 67 Z9 68 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD JUN PY 2003 VL 55 IS 6 BP 307 EP 313 DI 10.1080/1521654031000153049 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 706NP UT WOS:000184460000004 PM 12938732 ER PT J AU Imamura, S Adams, JC AF Imamura, S Adams, JC TI Distribution of gentamicin in the guinea pig inner ear after local or systemic application SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article ID COCHLEAR HAIR-CELLS; AMINOGLYCOSIDE OTOTOXICITY; ETHACRYNIC-ACID; HORSERADISH-PEROXIDASE; GERBIL COCHLEA; HEARING-LOSS; RAT; ANTIBIOTICS; PERILYMPH; DIHYDROSTREPTOMYCIN AB Uptake and retention of gentamicin by cells in the guinea pig inner ear after a single peritoneal injection or local application on the round window were investigated using immunocytochemistry to localize the drug. The cells that accumulated the drug under the two conditions were the same, but staining for the drug was more intense and was often accompanied by widespread cochlear degeneration following local application. Soon after drug administration by either route, there was diffuse staining for the drug throughout all tissue within the labyrinth, including bone. At later times when distinct cell staining became evident, virtually all cell types were found to be positive, with several cell types staining more darkly for the drug than hair cells, indicating that hair cells were not the most avid in accumulating gentamicin. The infracuticular portion of auditory and vestibular hair cells as well as type III fibrocytes of the spiral ligament were positively stained in almost all cases and these sites were found to be positive for as long as six months post administration. In animals with loss of the organ of Corti, there was unusually intense staining for gentamicin in root cells of the spiral ligament, in marginal cells of the stria vascularis, and in cells of the spiral limbus. Dark staining of surviving cells in cases with overt tissue destruction suggests that variability in the extent of damage caused by the drug was determined more by the degree of its local uptake than by differences in animals' capacities to metabolize the drug systemically. The present results show that gentamicin may damage or destroy all cochlear cells following a single round window application. The findings broaden the scope of our knowledge of cochlear gentamicin uptake and damage and have implications for treatment of patients with vestibular disorders by infusion of aminoglycosides into the middle ear, as well as implications for prospects of rehabilitating patients that have been deafened by aminoglycosides. C1 Shinshu Univ, Dept Otolaryngol, Sch Med, Nagano 3908621, Japan. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Adams, JC (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC 03929, R01 DC003929] NR 59 TC 63 Z9 65 U1 0 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1525-3961 J9 JARO JI JARO PD JUN PY 2003 VL 4 IS 2 BP 176 EP 195 DI 10.1007/s10162-002-2036-8 PG 20 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 712DK UT WOS:000184781600006 PM 12943372 ER PT J AU Imamura, S Adams, JC AF Imamura, S Adams, JC TI Changes in cytochemistry of sensory and nonsensory cells in gentamicin-treated cochleas SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE aminoglycoside toxicity; spiral ligament; organ of Corti; immunostaining ID CALCIUM-BINDING PROTEINS; OUTER HAIR-CELLS; INTERMEDIATE FILAMENT PROTEINS; GUINEA-PIG COCHLEA; MEMBRANE CA-ATPASE; INNER-EAR; PLASMA-MEMBRANE; AMINOGLYCOSIDE ANTIBIOTICS; IMMUNOHISTOCHEMICAL LOCALIZATION; CARBONIC-ANHYDRASE AB Effects of a single local dose of gentamicin upon sensory and nonsensory cells throughout the cochlea were assessed by changes in immunostaining patterns for a broad array of functionally important proteins. Cytochemical changes in hair cells, spiral ganglion cells, and cells of the stria vascularis, spiral ligament, and spiral limbus were found beginning 4 days post administration. The extent of changes in immunostaining varied with survival time and with cell type and was not always commensurate with the degree to which individual cell types accumulated gentamicin. Outer hair cells, types I and II fibrocytes of the spiral ligament, and fibrocytes in the spiral limbus showed marked decreases in immunostaining for a number of constituents. In contrast, inner hair cells, type III fibrocytes and root cells of the spiral ligament, cells of the stria vascularis, and interdental cells in the spiral limbus showed less dramatic decreases, and in some cases they showed increases in immunostaining. Results indicate that, in addition to damaging sensory cells, local application of gentamicin results in widespread and disparate disruptions of a variety of cochlear cell types. Only in the case of ganglion cells was it apparent that the changes in nonsensory cells were secondary to loss or damage of hair cells. These results indicate that malfunction of the ear following gentamicin treatment is widespread and far more complex than simple loss of sensory elements. The results have implications for efforts directed toward detecting, preventing, and treating toxic effects of aminoglycosides upon the inner ear. C1 Shinshu Univ, Dept Otolaryngol, Sch Med, Nagano 3908621, Japan. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Adams, JC (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC003929, DC 03929] NR 73 TC 26 Z9 30 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1525-3961 J9 JARO JI JARO PD JUN PY 2003 VL 4 IS 2 BP 196 EP 218 DI 10.1007/s10162-002-2037-7 PG 23 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 712DK UT WOS:000184781600007 PM 12943373 ER PT J AU Harris, WH AF Harris, WH TI "The lysis threshold": An erroneous and perhaps misleading concept? SO JOURNAL OF ARTHROPLASTY LA English DT Article DE lysis threshold; erroneous concept; total hip ID TOTAL HIP-ARTHROPLASTY; LOW-FRICTION ARTHROPLASTY; POLYETHYLENE WEAR DEBRIS; FOLLOW-UP; OSTEOLYSIS; COMPONENTS; CEMENT AB The "lysis threshold" concept suggests that a lower limit of particle generation exists in total hip arthroplasty (THA) below which lysis will not occur or is tolerable. Although this concept is appealing at first, serious reservations arise with more detailed analysis. Five major points challenge this concept: (1) For many of the reports, the duration too short. Ten years is not. the goal for most patients. (2) The definition of lysis is inadequate, listing only "balloon" lysis or endosteal erosion. (3) In most reports of 100 mum/y, lysis does occur. (4) Plain radiographs are not adequate for detection of lysis. (5) Other factors can overwhelm the role of particle volume, such as patch-porous cementless femoral designs. These 5 observations seriously challenge the lysis threshold concept. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. NR 17 TC 12 Z9 12 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD JUN PY 2003 VL 18 IS 4 BP 506 EP 510 DI 10.1016/S0883-5403(03)00153-0 PG 5 WC Orthopedics SC Orthopedics GA 701XD UT WOS:000184193500019 PM 12820096 ER PT J AU Cramer, DW Sluss, PM Powers, RD McShane, P Ginsburg, ES Hornstein, MD Vitonis, AF Barbieri, RL AF Cramer, DW Sluss, PM Powers, RD McShane, P Ginsburg, ES Hornstein, MD Vitonis, AF Barbieri, RL TI Serum prolactin and TSH in an in vitro fertilization population: Is there a link between fertilization and thyroid function? SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS LA English DT Article DE fertilization; IVF; oocytes; prolactin; TSH ID IN-VITRO; OOCYTES; INFERTILITY; MATURATION; THYROXINE; INVITRO AB Purpose: Measurements of TSH and prolactin are generally included in the evaluation of female infertility, but their value in women coming to in vitro fertilization (IVF) has been questioned. Methods: In this study, we sought to investigate whether prolactin or TSH, measured in 509 specimens collected prior to therapy, predicted outcome in a prospective study of couples undergoing IVF between 1994 and 2001. Results: TSH was higher in women whose fertility problem was attributed to a male factor, and prolactin was lower if the measurement was taken during menses. TSH and prolactin were positively correlated (p < 0.0001). Neither TSH nor prolactin levels correlated with overall IVF outcome; however, TSH levels were significantly higher among women who produced oocytes that failed to be fertilized and this finding persisted after adjustment for several covariates, including sperm motility. Among women who had a least one oocyte inseminated, the likelihood that they would have fewer than 50% of their eggs fertilized was significantly related to higher TSH levels in a multivariate model. Conclusion: We conclude that TSH may predict poor fertilization in IVF and reflect the importance of thyroid hormones in oocyte physiology. C1 Brigham & Womens Hosp, Ob Gyn Epidemiol Ctr, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Reprod Endocrinol Unit Lab, Dept Obstet & Gynecol, Boston, MA 02114 USA. Boston IVF, Waltham, MA USA. Deaconess Waltham Hosp, Ctr Reprod Sci, Waltham, MA USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Cramer, DW (reprint author), Brigham & Womens Hosp, Ob Gyn Epidemiol Ctr, Dept Obstet Gynecol & Reprod Biol, 221 Longwood Ave, Boston, MA 02115 USA. FU NICHD NIH HHS [HD 32153-08] NR 20 TC 35 Z9 39 U1 0 U2 8 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1058-0468 J9 J ASSIST REPROD GEN JI J. Assist. Reprod. Genet. PD JUN PY 2003 VL 20 IS 6 BP 210 EP 215 DI 10.1023/A:1024151210536 PG 6 WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology GA 688MY UT WOS:000183440900002 PM 12877251 ER PT J AU Ring, D Gulotta, L Jupiter, JB AF Ring, D Gulotta, L Jupiter, JB TI Unstable nonunions of the distal part of the humerus SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID TOTAL ELBOW ARTHROPLASTY; OPEN FRACTURES; INFECTION AB Background: Some nonunions of the distal part of the humerus are so unstable that the hand and the forelimb cannot be supported against gravity. The purpose of the present retrospective study was to analyze the results of open reduction and internal fixation, joint contracture release, and autogenous bone-grafting in the treatment of these unstable nonunions of the distal part of the humerus. Methods: Fifteen patients (average age, sixty years) with an unstable nonunion of the distal part of the humerus were treated with excision of fibrous and synovial tissues, opening of sclerotic fracture surfaces, internal fixation with multiple plates and screws, and autogenous bone-grafting. The average time from the original fracture to the index treatment of the nonunion was eleven months. Vascularized fibular grafts and supplemental external fixation were necessary in two patients with large bone defects after debridement at the site of a previous infection. Results: Three nonunions failed to heal and were treated with total elbow arthroplasty. Twelve nonunions healed, but six of the twelve required additional surgery because of painful implants, ulnar neuropathy, or elbow contracture. After an average duration of follow-up of fifty-one months (range, twenty-four to 130 months), the twelve patients in whom the nonunion healed had an average arc of ulnohumeral motion of 95degrees, with an average flexion of 117degrees and an average flexion contracture of 22degrees. According to the Mayo Elbow Performance Index, the functional result was rated as excellent in two patients, good in nine, and fair in one. Conclusions: Unstable nonunions of the distal part of the humerus can be treated successfully in most active, healthy patients with use of rigid internal fixation, joint contracture release, and bone-grafting. Level of Evidence: Therapeutic study, Level IV (case series [no, or historical, control group]). See Instructions to Authors for a complete description of levels of evidence. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, ACC 525, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, ACC 527, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, ACC 525, 15 Parkman St, Boston, MA 02114 USA. NR 21 TC 33 Z9 33 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 JUN PY 2003 VL 85A IS 6 BP 1040 EP 1046 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 684LM UT WOS:000183208900008 PM 12783999 ER PT J AU Comunale, ME Maslow, A Robertson, LK Haering, JM Mashikian, JS Lowenstein, E AF Comunale, ME Maslow, A Robertson, LK Haering, JM Mashikian, JS Lowenstein, E TI Effect of site of venous protamine administration, previously alleged risk factors, and preoperative use of aspirin on acute protamine-induced pulmonary vasoconstriction SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE heparin; protamine; aspirin; pulmonary vasoconstriction; thromboxane ID CORONARY-ARTERY DISEASE; AWAKE SHEEP; CARDIOPULMONARY BYPASS; CONTROLLED-TRIALS; UNSTABLE ANGINA; RIGHT ATRIAL; HEPARIN; REVERSAL; HYPERTENSION; HEMODYNAMICS AB Objective: To determine whether the incidence of protamine-induced pulmonary vasoconstriction (PIPV) is influenced by central venous versus peripheral venous infusion of protamine and whether aspirin ingestion within a week of surgery would decrease the incidence of PIPV. Design: Single-institution, prospective, observational, randomized trial. Setting: University teaching hospital. Participants: One thousand four hundred ninety-seven consecutive patients undergoing cardiopulmonary bypass procedures. Intervention: Protamine neutralization of heparin by infusion pump via either central venous or peripheral venous route. Measurements and Main Results: Five previously suspected risk factors (valve surgery, prior protamine exposure, history of pulmonary hypertension, fish allergy, and vasectomy), aspirin ingestion within 7 days of surgery, and demographic information were recorded. PIPV was defined as an abrupt increase in mean PA pressure of 7 mmHg or more with associated right ventricular dysfunction as assessed by observation of the right ventricle in the field and regional wall motion abnormality by transesophageal echocardiogram and hypotension (systolic blood pressure less than or equal to 90 mmHg). Data were collected via continuous strip chart recording. A total of 10 patients (0.6%) developed PIPV during protamine infusion. The incidents were similar with respect to the site of venous administration. Prior exposure to protamine was associated with a greater incidence of PIPV (odds ratio 6.9; p < 0.01). Other previously suspected risk factors did not achieve statistical significance. None of the 766 patients who ingested aspirin experienced PIPV as opposed to 10 of the 731 patients who did not ingest aspirin (odds ratio 0.08; p < 0.001). Conclusions: Although the site of venous protamine administration does not influence incidence of PIPV, aspirin ingestion within 1 week of surgery may decrease it. These data also confirmed other studies suggesting that previous protamine administration predisposes to this protamine reaction. (C) 2003 Elsevier Inc. All rights reserved. C1 St Louis Univ, Sch Med, Dept Anesthesiol, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Boston, MA USA. Brown Med Sch, Dept Anesthesiol, Boston, MA USA. Boston Med Ctr, Dept Anesthesiol, Boston, MA USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Comunale, ME (reprint author), St Louis Univ, Sch Med, Dept Anesthesiol, 3635 Vista Ave & Grand Blvd,POB 15250, St Louis, MO 63110 USA. NR 27 TC 5 Z9 5 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 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD JUN PY 2003 VL 17 IS 3 BP 309 EP 313 DI 10.1016/S1053-0770(03)00055-7 PG 5 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 696BJ UT WOS:000183865000006 PM 12827577 ER PT J AU Reddy, VY Neuzil, P Ruskin, JN AF Reddy, VY Neuzil, P Ruskin, JN TI Extra-ostial pulmonary venous isolation: Use of epicardial ablation to eliminate a point of conduction breakthrough SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; epicardial mapping; pulmonary vein; catheter ablation; radiofrequency; pericardium ID ATRIAL-FIBRILLATION; VENTRICULAR-TACHYCARDIA; CATHETER ABLATION; VEIN; INITIATION AB During catheter ablation of atrial fibrillation, ablation within the pulmonary veins is undesirable due to the risk of pulmonary venous stenosis and the possibility of leaving residual cuffs of arrhythmogenic tissue proximal to the ablation lesion set. An extra-ostial pulmonary vein isolation strategy may circumvent these limitations, but achieving electrical isolation can be technically challenging, even with the use of saline-irrigated radiofrequency energy technology. This report describes the successful use of epicardial radiofrequency ablation in a patient in whom endocardial irrigated radiofrequency ablation failed to achieve extra-ostial pulmonary vein isolation. C1 Harvard Univ, Arrhythmia Serv, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Homolce Hosp, Div Cardiol, Electrophysiol Sect, Prague, Czech Republic. RP Reddy, VY (reprint author), Harvard Univ, Arrhythmia Serv, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Gray Bigelow 109, Boston, MA 02114 USA. NR 13 TC 8 Z9 10 U1 0 U2 0 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JUN PY 2003 VL 14 IS 6 BP 663 EP 666 DI 10.1046/j.1540-8167.2003.03049.x PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 689JZ UT WOS:000183490100019 PM 12875430 ER PT J AU Durante, W AF Durante, W TI Heme oxygenase-1 in growth control and its clinical application to vascular disease SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID SMOOTH-MUSCLE-CELLS; SPONTANEOUSLY HYPERTENSIVE-RATS; SOLUBLE GUANYLYL CYCLASE; CORONARY-ARTERY DISEASE; CARBON-MONOXIDE PATHWAY; PROTEIN-KINASE PATHWAY; HUMAN-SKIN FIBROBLASTS; GENE-TRANSFER; OXIDATIVE STRESS; ENDOTHELIAL-CELLS AB Heme oxygenase-1 (HO-1) catalyzes the degradation of heme to carbon monoxide (CO), iron, and biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Although interest in HO-1 originally centered on its heme-degrading function, recent findings indicate that HO-1 exerts other biologically important actions. Emerging evidence suggests that HO-1 plays a critical role in growth regulation. Deletion of the HO-1 gene or inhibition of HO-1 activity results in growth retardation and impaired fetal development, whereas HO-1 overexpression increases body size. Although the mechanisms responsible for the growth promoting properties of HO-1 are not well established, HO-1 can indirectly influence growth by regulating the synthesis of growth factors and by modulating the delivery of oxygen or nutrients to specific target tissues. In addition, HO-1 exerts important effects on critical determinants of tissue size, including cell proliferation, apoptosis, and hypertrophy. However, the actions of HO-1 are highly variable and may reflect a role for HO-1 in maintaining tissue homeostasis. Considerable evidence supports a crucial role for HO-1 in blocking the growth of vascular smooth muscle cells (SMCs). This antiproliferative effect of HO-1 is mediated primarily via the release of CO, which inhibits vascular SMC growth via multiple pathways. Pharmacologic or genetic approaches targeting HO-1 or CO to the blood vessel wall may represent a promising, novel therapeutic approach in treating vascular proliferative disorders. (C) 2003 Wiley-Liss, Inc. C1 Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. RP Durante, W (reprint author), Baylor Coll Med, VA Med Ctr, Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM wdurante@bcm.tmc.edu FU NHLBI NIH HHS [R01 HL-59976] NR 128 TC 127 Z9 137 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUN PY 2003 VL 195 IS 3 BP 373 EP 382 DI 10.1002/jcp.10274 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 675BV UT WOS:000182673900005 PM 12704646 ER PT J AU Wilens, TE Biederman, J Kwon, A Chase, R Greenberg, L Mick, E Spencer, TJ AF Wilens, TE Biederman, J Kwon, A Chase, R Greenberg, L Mick, E Spencer, TJ TI A systematic chart review of the nature of psychiatric adverse events in children and adolescents treated with selective serotonin reuptake inhibitors SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Review ID OBSESSIVE-COMPULSIVE DISORDER; OPEN-LABEL TREATMENT; CONTROLLED-TRIAL; MAJOR DEPRESSION; FLUVOXAMINE; SERTRALINE; FLUOXETINE; PAROXETINE; 12-YEAR-OLDS; OUTPATIENTS AB Objective: Despite a rapidly growing literature on the efficacy of the selective serotonin reuptake inhibitors (SSRD in the treatment of juvenile psychiatric disorders, relatively little is described about emotional, behavioral, and cognitive adverse effects associated with their use. To this end we completed a retrospective analysis of medical charts to determine the incidence, nature, and clinical correlates of treatment emergent adverse effects in the behavioral, cognitive, and emotional domains. Methods: We systematically evaluated the medical charts of children treated with SSRI for depressive or obsessive-compulsive disorders for a mean (+/-SD) of 26.9 +/- 20.8 months to determine the incidence, nature, and clinical correlates of treatment emergent psychiatric adverse events (PAE). Charts were reviewed for diagnoses, type and dose of SSRI and adjunct medication, specific type of PAE, and time to onset and offset of PAE. Results: In total, 82 charts of children and adolescents (mean age 12.2 +/- 3.2 years) were examined. PAE occurred in 22% of children and were most commonly related to disturbances in mood. PAE were not associated with psychiatric diagnosis(es), age, sex, concurrent medications, doses or specific serotonin reuptake inhibitors. The onset of PAE was observed typically 3 months after SSRI exposure (median = 91 days). Although PAE diminished with SSRI discontinuation, those that emerged early in treatment diminished significantly more rapidly than those that emerged later (median offset was 10 and 49 days, respectively). Re-exposure to an SSRI resulted in another PAE in 44% (n = 18) of the group. Conclusion: Based on the retrospective review of medical charts, youth receiving SSRI appear to be at risk for treatment emergent PAE and recurrence with re-exposure to an SSRI. Prospective longer term studies evaluating the course and prognosis of youths manifesting PAE to SSRI are necessary. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Child Psychiat Serv, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Child Psychiat Serv, Clin & Res Program Pediat Psychopharmacol, ACC 725, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145 FU NIDA NIH HHS [R01 DA12945] NR 26 TC 51 Z9 54 U1 0 U2 0 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. PD SUM PY 2003 VL 13 IS 2 BP 143 EP 152 DI 10.1089/104454603322163862 PG 10 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 694GU UT WOS:000183766700005 PM 12886909 ER PT J AU Carlson, GA Mick, E AF Carlson, GA Mick, E TI Drug-induced disinhibition in psychiatrically hospitalized children SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; RATING-SCALE; ANXIETY DISORDERS; MAJOR DEPRESSION; CLINICAL-TRIAL; ADOLESCENTS; FLUOXETINE; FLUVOXAMINE; SERTRALINE AB Objective: To examine rates and predictors of drug-induced behavioral disinhibition (DIBD) in psychiatrically hospitalized children. Methods: DIBD was examined in 267 children psychiatrically hospitalized for at least 4 weeks. Age, gender, diagnosis, and medication were covariates. DIBD was defined as dramatic increase in aggression identified by increased time-outs while on medicaton. Results: Twenty (7.5%) children met our criteria. Attention deficit hyperactivity disorder, pervasive developmental disorder, and selective serotonin reuptake inhibitor use appeared to increase the risk, and older age and stimulant use decreased the risk (if DIBD. However, it was often difficult to distinguish true DIBD from the behavioral fluctuations of these disturbed children. Fifteen percent of children subsequently improved on the same regimen, 40% improved when the offending drug was stopped and another treatment was started, and the remainder had adverse response to many medications. Conclusions: DIBD is a complex phenomenon that does not lend itself to simple conclusions and requires further study. C1 SUNY Stony Brook, Stony Brook, NY 11794 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Carlson, GA (reprint author), SUNY Stony Brook, Putnam Hall, Stony Brook, NY 11794 USA. OI Mick, Eric/0000-0001-8505-8145 NR 33 TC 27 Z9 27 U1 0 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. PD SUM PY 2003 VL 13 IS 2 BP 153 EP 163 DI 10.1089/104454603322163871 PG 11 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 694GU UT WOS:000183766700006 PM 12880509 ER PT J AU Bo-Abbas, Y Acierno, JS Shagoury, JK Crowley, WF Seminara, SB AF Bo-Abbas, Y Acierno, JS Shagoury, JK Crowley, WF Seminara, SB TI Autosomal recessive idiopathic hypogonadotropic hypogonadism: Genetic analysis excludes mutations in the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PHENOTYPIC CHARACTERIZATION; HOMOZYGOUS MUTATION; CEREBELLAR-ATAXIA; DEFICIENCY; MEN AB Failure of the normal pattern of episodic secretion of GnRH from the hypothalamus results in the clinical syndrome of idiopathic hypogonadotropic hypogonadism (IHH), with failure of pubertal development and infertility. The only gene that has been implicated in normosmic IHH is the GnRH receptor gene (GNRHR), which accounts for 10% of cases. This report presents four families with autosomal recessive IHH, including a consanguineous pedigree from the Middle East. Defects within the genomic coding sequence of the GNRHR, and the GnRH gene itself, GNRH1, were excluded by temperature gradient gel electrophoresis, direct sequencing, and haplotypes created from simple sequence polymorphisms flanking the GNRH1 and GNRHR loci. We concluded that: 1) genetic analysis has excluded sequence variations in GNRH1 and GNRHR in four families with recessive IHH, suggesting the existence of a novel, as-yet-undiscovered gene for this condition, and 2) because mutation analysis of genomic coding sequence will fail to detect mutations deep within introns or regulatory regions, haplotype analysis is the preferred genetic methodology to eliminate the role of specific candidate genes. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Kuwait Univ, Fac Med, Al Jabriyah 13110, Kuwait. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall,Extens 505, Boston, MA 02114 USA. EM seminara.stephanie@mgh.harvard.edu FU NICHD NIH HHS [U54 HD029164, U54 HD028138, R01 HD015788] NR 23 TC 27 Z9 29 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2003 VL 88 IS 6 BP 2730 EP 2737 DI 10.1210/jc.2002-021948 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 686JL UT WOS:000183318200054 PM 12788881 ER PT J AU Jensen, CB Storgaard, H Holst, JJ Dela, F Madsbad, S Vaag, AA AF Jensen, CB Storgaard, H Holst, JJ Dela, F Madsbad, S Vaag, AA TI Insulin secretion and cellular glucose metabolism after prolonged low-gradeintralipid infusion in young men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FREE FATTY-ACIDS; DEPENDENT DIABETES-MELLITUS; LONG-TERM EXPOSURE; SKELETAL-MUSCLE; CARBOHYDRATE-METABOLISM; PANCREATIC-ISLETS; HEALTHY-SUBJECTS; BETA-CELLS; HUMANS; RESISTANCE AB We examined the simultaneous effects of a 24-h low-grade Intralipid infusion on peripheral glucose disposal, intracellular glucose partitioning and insulin secretion rates in twenty young men, by 2-step hyperinsulinemic euglycemic clamp [low insulin clamp (LI), 10 mU/m(2).min; high insulin clamp (HI), 40 mU/m(2).min], 3-(3)H-glucose, indirect calorimetry, and iv glucose tolerance test. Free fatty acid concentrations were similar during basal steady state but 3.7- to 13-fold higher during clamps. P-glucagon increased and the insulin/glucagon ratio decreased at both LI and HI during Intralipid infusion. At LI, glucose oxidation decreased by 10%, whereas glucose disposal, glycolytic flux, glucose storage, and glucose production were not significantly altered. At HI, glucose disposal, and glucose oxidation decreased by 12% and 24%, respectively, during Intralipid infusion. Glycolytic flux, glucose storage, and glucose production were unchanged. Insulin secretion rates increased in response to Intralipid infusion, but disposition indices (DI=insulin action.insulin secretion) were unchanged. In conclusion, a 24-h low-grade Intralipid infusion caused insulin resistance in the oxidative (but not in the nonoxidative) glucose metabolism in young healthy men. Moreover, insulin hypersecretion perfectly countered the free-fatty acid-induced insulin resistance. Future studies are needed to determine the role of a prolonged moderate lipid load in subjects at increased risk of developing diabetes. C1 Hvidovre Univ Hosp, Dept Endocrinol, DK-2650 Hvidovre, Denmark. Hvidovre Univ Hosp, Clin Res Unit, DK-2650 Hvidovre, Denmark. Steno Diabet Ctr, DK-2820 Gentofte, Denmark. Univ Copenhagen, Panum Inst, Dept Med Physiol, DK-2200 Copenhagen N, Denmark. Rigshosp, Copenhagen Muscle Res Ctr, DK-2100 Copenhagen, Denmark. RP Jensen, CB (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM cbjensen@dadlnet.dk RI Dela, Flemming/B-3239-2008; OI Dela, Flemming/0000-0001-9970-9535; Holst, Jens Juul/0000-0001-6853-3805 NR 63 TC 21 Z9 21 U1 2 U2 8 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 JUN PY 2003 VL 88 IS 6 BP 2775 EP 2783 DI 10.1210/jc.2002-021430 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 686JL UT WOS:000183318200060 PM 12788887 ER PT J AU Osgood, D Corella, D Demissie, S Cupples, LA Wilson, PWF Meigs, JB Schaefer, EJ Coltell, O Ordovas, JM AF Osgood, D Corella, D Demissie, S Cupples, LA Wilson, PWF Meigs, JB Schaefer, EJ Coltell, O Ordovas, JM TI Genetic variation at the scavenger receptor class B type I gene locus determines plasma lipoprotein concentrations and particle size and interacts with type 2 diabetes: The Framingham Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; CORONARY HEART-DISEASE; SELECTIVE LIPID UPTAKE; SR-BI; HDL RECEPTOR; APOLIPOPROTEIN-E; INSULIN-RESISTANCE; TARGETED MUTATION; FINNISH FAMILIES; TRANSGENIC MICE AB The scavenger receptor class B type I ( SR- BI) is a key component in the reverse cholesterol transport pathway. We have previously reported three common polymorphisms associated with plasma lipids and body mass index. We hypothesized that diabetic status may interact with these polymorphisms in determining plasma lipid concentrations and particle size. We evaluated this hypothesis in 2463 nondiabetic ( 49% men) and 187 diabetic ( 64% men) participants in the Framingham Study. SR- BI and APOE genotypes, anthropometric, clinical, biochemical, and lifestyle variables were determined. After multivariate adjustment, we found a consistent association between the exon 8 polymorphism and high- density lipoprotein cholesterol concentration and particle size. Interaction effects were not significant for exon 8 and intron 5 polymorphisms. However, we found statistically significant interactions between SR- BI exon 1 genotypes and type 2 diabetes, indicating that diabetic subjects with the less common allele ( allele A) have lower lipid concentrations. For low- density lipoprotein cholesterol, the adjusted means ( +/- SE) were 3.31 +/- 0.03 and 3.29 +/- 0.04 mmol/ liter for G/ G and G/ A or A/ A in nondiabetics, respectively, compared with 3.19 +/- 0.10 and 2.75 +/- 0.01 mmol/ liter for G/ G and G/ A or A/ A in diabetics ( P = 0.03 for interaction). Similar results were obtained for HDL(2)- C. In conclusion, SR- BI gene variation modulates the lipid profile, particularly in type 2 diabetes, contributing to the metabolic abnormalities in these subjects. C1 Tufts Univ, Nutr & Genom Lab, Jean Mayer Human Nutr Res Ctr Aging, USDA, Boston, MA 02111 USA. Tufts Univ, Lipid Metab Lab, Jean Mayer Human Nutr Res Ctr Aging, USDA, Boston, MA 02111 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Gen Internal Med Dept, Boston, MA 02114 USA. RP Ordovas, JM (reprint author), Tufts Univ, Nutr & Genom Lab, Jean Mayer Human Nutr Res Ctr Aging, USDA, 711 Washington St, Boston, MA 02111 USA. EM jose.ordovas@tufts.edu OI Cupples, L. Adrienne/0000-0003-0273-7965; Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [HL54776]; PHS HHS [1-38038] NR 57 TC 74 Z9 79 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2003 VL 88 IS 6 BP 2869 EP 2879 DI 10.1210/jc.2002-021664 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 686JL UT WOS:000183318200074 PM 12788901 ER PT J AU Tritos, NA Kokkinos, A Lampadariou, E Alexiou, E Katsilambros, N Maratos-Flier, E AF Tritos, NA Kokkinos, A Lampadariou, E Alexiou, E Katsilambros, N Maratos-Flier, E TI Cerebrospinal fluid ghrelin is negatively associated with body mass index SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-HORMONE SECRETAGOGUE; ACYLATED PEPTIDE; CIRCULATING GHRELIN; FOOD-INTAKE; HUMANS; STOMACH; OBESITY; SECRETION; APPETITE; RECEPTOR AB Ghrelin is a 28 amino acid peptide hormone, predominantly expressed in the gastric epithelium and, at a lower level, in the hypothalamus. Although several line of evidence indicate that ghrelin has a role in appetite regulation, nevertheless the regulation and role of central ghrelin levels remain unclear. To further characterize the role of ghrelin in the regulation of body adiposity, we investigated the association between fasting cerebrospinal fluid (CSF) ghrelin levels and body mass index (BMI) in humans. We consecutively enrolled 19 adults (aged 21-76 yr, 15 females and 4 males), including 4 obese, 7 overweight and 8 learn subjects, who underwent spinal anesthesia during surgery for non-malignant conditions. We found a negative association between fasting CSF ghrelin levels and BMI (r= -0.048, p=0.035) and a trend towards lower (by 16%) fasting CSF ghrelin levels in the obese (=0.06 for the difference between learn and obese subjects). In conclusion, we found a negative association between fasting CSF ghrelin levels and BMI in humans. Our data suggest that central ghrelin may have a role in the regulation of body adiposity in humans, which requires further study to be fully elucidated. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Athens, Sch Med, Dept Internal Med, GR-11527 Athens, Greece. Univ Athens, Sch Med, Laikon Gen Hosp, GR-11527 Athens, Greece. RP Tritos, NA (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK53978, DK56116, DK56113] NR 22 TC 22 Z9 23 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2003 VL 88 IS 6 BP 2943 EP 2946 DI 10.1210/jc.2003-030300 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 686JL UT WOS:000183318200082 PM 12788909 ER PT J AU Acierno, JS Shagoury, JK Bo-Abbas, Y Crowley, WF Seminara, SB AF Acierno, JS Shagoury, JK Bo-Abbas, Y Crowley, WF Seminara, SB TI A locus for autosomal recessive idiopathic hypogonadotropic hypogonadism on chromosome 19p13.3 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; MUTATIONS; RECEPTOR; FAMILY AB Idiopathic hypogonadotropic hypogonadism (IHH) is traditionally established by 1) the absence of spontaneous pubertal development by age 18 yr and 2) low sex steroids with inappropriately low gonadotropins in the absence of any functional or anatomic cause. To identify a novel disease locus for IHH, a genome wide scan was performed on a large, consanguineous Saudi family with 6 affected individuals. Linkage over a 1.06 Mb interval on chromosome 19p13.3 was established with a maximal two point LOD score of 5.17. Because numerous genes and hypothetical proteins are mapped to this region, further studies will be necessary to determine the precise genetic defect in this family. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Kuwait Univ, Fac Med, Kuwait, Kuwait. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall,Extens 505,Fruit St, Boston, MA 02114 USA. EM seminara_stephaine@mgh.harvard.edu FU NCRR NIH HHS [3M01-RR01066-22S2]; NICHD NIH HHS [U54-HD28138-11, R01 HD015788, U54 HD029164, U54 HD028138, 5R01-HD15788-17, T32 HD007396, P30 HD028138] NR 14 TC 10 Z9 10 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2003 VL 88 IS 6 BP 2947 EP 2950 DI 10.1210/jc.2003-030423 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 686JL UT WOS:000183318200083 PM 12788910 ER PT J AU Hunink, MGM Gazelle, GS AF Hunink, MGM Gazelle, GS TI CT screening: a trade-off of risks, benefits, and costs SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BEAM COMPUTED-TOMOGRAPHY; SERVICES-TASK-FORCE; ABDOMINAL AORTIC-ANEURYSMS; OPEN SURGICAL REPAIR; ELECTRON-BEAM; COLORECTAL-CANCER; CORONARY CALCIFICATION; LUNG-CANCER; DISEASE; COLONOSCOPY C1 Erasmus Univ, Med Ctr, Dept Epidemiol & Biostat, Program Assessment Radiol Technol, NL-3000 DR Rotterdam, Netherlands. Erasmus Univ, Med Ctr, Dept Radiol, NL-3000 DR Rotterdam, Netherlands. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Hunink, MGM (reprint author), Erasmus Univ, Med Ctr, Dept Epidemiol & Biostat, Program Assessment Radiol Technol, Room EE21-40A,POB 1738, NL-3000 DR Rotterdam, Netherlands. NR 31 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2003 VL 111 IS 11 BP 1612 EP 1619 DI 10.1172/JCI200318842 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 686GQ UT WOS:000183313400002 PM 12782661 ER PT J AU Kos, CH Le, TC Sinha, S Henderson, JM Kim, SH Sugimoto, H Kalluri, R Gerszten, RE Pollak, MR AF Kos, CH Le, TC Sinha, S Henderson, JM Kim, SH Sugimoto, H Kalluri, R Gerszten, RE Pollak, MR TI Mice deficient in alpha-actinin-4 have severe glomerular disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; CONGENITAL NEPHROTIC SYNDROME; ALPHA-ACTININ; PROTEIN; NEPHRIN; PODOCYTES; KIDNEY; GENE AB Dominantly inherited mutations in ACTN4, which encodes alpha-actinin-4, cause a form of human focal and segmental glomerulosclerosis (FSGS). By homologous recombination in ES cells, we developed a mouse model deficient in Actn4. Mice homozygous for the targeted allele have no detectable alpha-actinin-4 protein expression. The number of homozygous mice observed was lower than expected under mendelian inheritance. Surviving mice homozygous for the targeted allele show progressive proteinuria, glomerular disease, and typically death by several months of age. Light microscopic analysis shows extensive glomerular disease and proteinaceous casts. Electron microscopic examination shows focal areas of podocyte foot-process effacement in young mice, and diffuse effacement and globally disrupted podocyte morphology in older mice. Despite the widespread distribution of alpha-actinin-4, histologic examination of mice showed abnormalities only in the kidneys. In contrast to the dominantly inherited human form of ACTN4-associated FSGS, here we show that the absence of alpha-actinin-4 causes a recessive form of disease in mice. Cell motility, as measured by lymphocyte chemotaxis assays, was increased in the absence of a-actinin-4. We conclude that alpha-actinin-4 is required for normal glomerular function. We further conclude that the nonsarcomeric forms of alpha-actinin (alpha-actinin-1 and alpha-actinin-4) are not functionally redundant. In addition, these genetic studies demonstrate that the nonsarcomeric alpha-actinin-4 is involved in the regulation of cell movement. C1 Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Dept Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Program Matrix Biol, Div Gastroenterol, Boston, MA 02215 USA. RP Pollak, MR (reprint author), HIM 534,77 Ave Louis Pasteur, Boston, MA 02115 USA. RI Kalluri, Raghu/E-2677-2015 OI Kalluri, Raghu/0000-0002-2190-547X FU NHLBI NIH HHS [HL-07208, HL-65584, R01 HL065584, T32 HL007208]; NIDDK NIH HHS [R01 DK055001, DK-51711, DK-55001, DK-59588, R01 DK059588, R37 DK059588] NR 18 TC 147 Z9 158 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2003 VL 111 IS 11 BP 1683 EP 1690 DI 10.1172/JCI200317988 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 686GQ UT WOS:000183313400012 PM 12782671 ER PT J AU O'Connell, TD Ishizaka, S Nakamura, A Swigart, PM Rodrigo, MC Simpson, GL Cotecchia, S Rokosh, DG Grossman, W Foster, E Simpson, PC AF O'Connell, TD Ishizaka, S Nakamura, A Swigart, PM Rodrigo, MC Simpson, GL Cotecchia, S Rokosh, DG Grossman, W Foster, E Simpson, PC TI The alpha(1A/C)- and alpha(1B)-adrenergic receptors are required for physiological cardiac hypertrophy in the double-knockout mouse SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ARTERIAL BLOOD-PRESSURE; TRANSGENIC MICE; IN-VIVO; GENDER DIFFERENCES; MESSENGER-RNAS; MYOCYTES; RAT; OVEREXPRESSION; GROWTH; NOREPINEPHRINE AB Catecholamines and alpha(1)-adrenergic receptors (alpha(1)-ARs) cause cardiac hypertrophy in cultured myocytes and transgenic mice, but heart size is normal in single KOs of the main alpha(1)-AR subtypes, alpha(1A/C) and alpha(1B). Here we tested whether alpha(1)-ARs are required for developmental cardiac hypertrophy by generating alpha(1A/C) and alpha(1B) double KO (ABKO) mice, which had no cardiac alpha(1)-AR binding. In male ABKO mice, heart growth after weaning was 40% less than in WT, and the smaller heart was due to smaller myocytes. Body and other organ weights were unchanged, indicating a specific effect on the heart. Blood pressure in ABKO mice was the same as in WT, showing that the smaller heart was not due to decreased load. Contractile function was normal by echocardiography in awake mice, but the smaller heart and a slower heart rate reduced cardiac output. alpha(1)-AR stimulation did not activate extracellular signal-regulated kinase (Erk) and downstream kinases in ABKO myocytes, and basal Erk activity was lower in the intact ABKO heart. In female ABKO mice, heart size was normal, even after ovariectomy. Male ABKO mice had reduced exercise capacity and increased mortality with pressure overload. Thus, alpha(1)-ARs in male mice are required for the physiological hypertrophy of normal postnatal cardiac development and for an adaptive response to cardiac stress. C1 San Francisco Vet Affairs Med Ctr, Div Cardiol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Cardiol, Dept Med, San Francisco, CA 94143 USA. Univ Lausanne, Inst Pharmacol & Toxocol, CH-1015 Lausanne, Switzerland. Univ Louisville, Dept Med, Div Cardiol, Louisville, KY 40292 USA. RP Simpson, PC (reprint author), San Francisco Vet Affairs Med Ctr, Div Cardiol, 111C8,4150 Clement St, San Francisco, CA 94121 USA. RI Rokosh, Gregg/J-2730-2013; O'Connell, Timothy/D-5048-2013 FU NHLBI NIH HHS [R01 HL031113, T32 HL007731] NR 33 TC 117 Z9 119 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2003 VL 111 IS 11 BP 1783 EP 1791 DI 10.1172/JCI200316100 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 686GQ UT WOS:000183313400021 PM 12782680 ER PT J AU Sachs, DH AF Sachs, DH TI Tolerance: Of mice and men SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID STAGE RENAL-DISEASE; ALLOGRAFT TOLERANCE; LYMPHOHEMATOPOIETIC CHIMERISM; TRANSPLANTATION TOLERANCE; MULTIPLE-MYELOMA; MINIATURE SWINE; BONE-MARROW; CLASS-I; INDUCTION AB Little is known about the effect of an individual's immune history on his or her response to an allogeneic tissue transplant. An important study (see the related article beginning on page 1887) now reveals that individuals harboring virally-induced memory T cells that are cross reactive with donor alloantigen are resistant to conventional strategies designed to induce transplant tolerance. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH East,Bldg 149-9019,149 13th St, Boston, MA 02129 USA. NR 15 TC 60 Z9 61 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2003 VL 111 IS 12 BP 1819 EP 1821 DI 10.1172/JCI200318926 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 691UH UT WOS:000183623600005 PM 12813017 ER PT J AU Kondo, T Vicent, D Suzuma, K Yanagisawa, M King, GL Holzenberger, M Kahn, CR AF Kondo, T Vicent, D Suzuma, K Yanagisawa, M King, GL Holzenberger, M Kahn, CR TI Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NITRIC-OXIDE SYNTHASE; DEPENDENT DIABETES-MELLITUS; OXYGEN-INDUCED RETINOPATHY; GROWTH-FACTOR-I; GENE-EXPRESSION; PHOSPHATIDYLINOSITOL 3-KINASE; VASO-OBLITERATION; HYPOXIA; STIMULATION; INHIBITION AB Both insulin and IGF-1 have been implicated in control of retinal endothelial cell growth, neovascularization, and diabetic retinopathy. To precisely define the role of insulin and IGF-1 signaling in endothelium in these processes, we have used the oxygen-induced retinopathy model to study mice with a vascular endothelial cell-specific knockout of the insulin receptor (VENIRKO) or IGF-1 receptor (VENIFARKO). Following relative hypoxia, VENIRKO mice show a 57% decrease in retinal neovascularization as compared with controls. This is associated with a blunted rise in VEGF, eNOS, and endothelin-1. By contrast, VENIFARKO mice show only a 34% reduction in neovascularization and a very modest reduction in mediator generation. These data indicate that both insulin and IGF-1 signaling in endothelium play a role in retinal neovascularization through the expression of vascular mediators, with the effect of insulin being most important in this process. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX USA. Hop St Antoine, Croissance Differenciat & Proc Tumoraux, INSERM, Paris, France. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu RI Vicent, David/O-2255-2014 OI Vicent, David/0000-0002-6663-0350 FU NIDDK NIH HHS [DK-33201, DK-31036, DK-53105, R01 DK031036, R01 DK033201, R01 DK053105, R37 DK031036] NR 47 TC 125 Z9 136 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2003 VL 111 IS 12 BP 1835 EP 1842 DI 10.1172/JCI200317455 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 691UH UT WOS:000183623600007 PM 12813019 ER PT J AU Wadler, S Levy, DE Lincoln, ST Soori, GS Schink, JC Goldberg, G AF Wadler, S Levy, DE Lincoln, ST Soori, GS Schink, JC Goldberg, G TI Topotecan is an active agent in the first-line treatment of metastatic or recurrent endometrial carcinoma: Eastern cooperative oncology group study E3E93 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-II TRIAL; DNA TOPOISOMERASE-I; CELL LUNG-CANCER; OVARIAN-CANCER; PACLITAXEL; CISPLATIN; ADENOCARCINOMA; CAMPTOTHECIN; INFUSION; THERAPY AB Purpose : To determine the clinical activity and the toxicity profile of the topoisomerase-I inhibitor, topotecan, in women with recurrent or advanced endometrial carcinoma. Patients and Methods: A prospective, phase 11 clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG). Patients had histologically confirmed advanced or recurrent endometrial carcinoma, measurable disease, no prior cytotoxic therapy, an ECOG performance status of 0 to 2, and evidence of disease progression while on progestins or after radiation therapy. Topotecan was administered at 1.5 mg/m(2) (or 1.2 mg/m(2) for patients with prior pelvic radiation) intravenously daily for 5 days every 3 weeks. Results: A total of 44 patients were enrolled; 42 were eligible. The study was suspended because of unexpected toxicities, primarily sepsis and bleeding. After toxicity review, the study was reopened using lower doses of topotecan (1.0 mg/m(2) or 0.8 mg/m(2) for patients with prior radiation therapy). In addition, prophylactic use of growth factors was allowed after the first cycle, and patients with performance status of 2 were excluded. The major toxicities were hematologic and gastrointestinal. Among the 40 assessable patients, there were three (7.5%) complete responders and five partial responders (12.5%), for an overall response rate of 20%. The median duration of response was 8.0 months and of overall survival was 6.5 months. Conclusion: Topotecan is an active agent for the treatment of advanced endometrial carcinoma. At the doses and schedules initially used, toxicities were unacceptable; however, at the modified doses, toxicities were acceptable and clinical activity was preserved. (C) 2003 by American Society of Clinical Oncology. C1 Cornell Univ, Weill Med Coll, Dept Oncol, Div Hematol Oncol, New York, NY 10021 USA. Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Bergan Mercy Med Ctr, Omaha, NE USA. Univ Wisconsin, Madison, WI USA. RP Wadler, S (reprint author), Cornell Univ, Weill Med Coll, Dept Oncol, Div Hematol Oncol, 525 E 68th St STARR 353, New York, NY 10021 USA. FU NCI NIH HHS [CA21115, CA49883, CA23318, CA13650, CA14958, CA66636] NR 34 TC 22 Z9 26 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 JUN 1 PY 2003 VL 21 IS 11 BP 2110 EP 2114 DI 10.1200/JCO.2003.12.093 PG 5 WC Oncology SC Oncology GA 684MP UT WOS:000183211400010 PM 12775736 ER PT J AU D'Amico, AV Moul, J Carroll, PR Sun, L Lubeck, D Chen, MH AF D'Amico, AV Moul, J Carroll, PR Sun, L Lubeck, D Chen, MH TI Cancer-specific mortality after surgery or radiation for patients with clinically localized prostate cancer managed during the prostate-specific antigen era SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RADICAL PROSTATECTOMY; DISEASE RECURRENCE; THERAPY; BIOPSIES; SURVIVAL; DATABASE; UTILITY; CAPSURE AB Purpose: To determine whether pretreatment risk groups shown to predict time to prostate cancer-specific mortality (PCSM) after treatment at a single institution retained that ability in a multi-institutional setting. Patients and Methods: From 1988 to 2002, 7,316 patients treated in the United States at 44 institutions with either surgery (n = 4,946) or radiation (n = 2,370) for clinical stage T1c-2, N0 or NX, M0 prostate cancer made up the study cohort. A Cox regression analysis was performed to determine the ability of pretreatment risk groups to predict time to PCSM after treatment. The relative risk (RR) of PCSM and 95% confidence intervals (CIs) were calculated for the intermediate- and high-risk groups relative to the low-risk group. Results: Estimates of non-PCSM 8 years after prostate-specific antigen (PSA) failure were 4% v 15% (surgery versus radiation; P-log rank = .002) compared with 13% v 18% (surgery versus radiation; P-log rank = .35) for patients whose age at the time of PSA failure was less than 70 as compared with !: 70 years, respectively. The RR of PCSM after treatment for surgery-managed patients with high- or intermediate-risk disease was 14.2 (95% CI, 5.0 to 23.4; P-Cox < .0001) and 4.9 (95% CI, 1.7 to 8.1; P-Cox = .0037), respectively. These values were 14.3 (95% CI, 5.2 to 24.0; P-Cox < .0001) and 5.6 (95% CI, 2.0 to 9.3; P-Cox = .0012) for radiation-managed patients. Conclusion: This study provided evidence to support the prediction of time to PCSM after surgery or radiation on the basis of pretreatment risk groups for patients with clinically localized prostate cancer managed during the PSA era. (C) 2003 by American Society of Clinical Oncology. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Uniformed Serv Univ Hlth Sci, Dept Surg & Urol Serv, Ctr Prostate Dis Res, Rockville, MD USA. Walter Reed Army Med Ctr, Rockville, MD USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. NR 22 TC 266 Z9 271 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2003 VL 21 IS 11 BP 2163 EP 2172 DI 10.1200/JCO.2003.01.075 PG 10 WC Oncology SC Oncology GA 684MP UT WOS:000183211400016 PM 12775742 ER PT J AU Irie, HY Jaklitsch, MT Shaffer, K Weinstein, M Salgia, R AF Irie, HY Jaklitsch, MT Shaffer, K Weinstein, M Salgia, R TI Unusual problems in breast cancer and a rare lung cancer case - Case 4. Primary lymphoepithelioma-like carcinoma of the lung SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; ASSOCIATION C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Irie, HY (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. OI Shaffer, Kitt/0000-0001-6488-6988 NR 12 TC 0 Z9 1 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2003 VL 21 IS 11 BP 2220 EP 2222 DI 10.1200/JCO.2003.09.088 PG 3 WC Oncology SC Oncology GA 684MP UT WOS:000183211400026 PM 12775751 ER PT J AU van den Brink, GR Hardwick, JCH Nielsen, C Xu, C ten Kate, FJ Glickman, J van Deventer, SJH Roberts, DJ Peppelenbosch, MP AF van den Brink, GR Hardwick, JCH Nielsen, C Xu, C ten Kate, FJ Glickman, J van Deventer, SJH Roberts, DJ Peppelenbosch, MP TI Sonic hedgehog expression correlates with fundic gland differentiation in the adult gastrointestinal tract SO JOURNAL OF CLINICAL PATHOLOGY-MOLECULAR PATHOLOGY LA English DT Article ID LEFT-RIGHT ASYMMETRY; GROWTH-FACTOR-ALPHA; MENETRIERS-DISEASE; TRANSGENIC MICE; INTESTINAL METAPLASIA; HUMAN STOMACH; MOUSE; EPITHELIUM; MORPHOGENESIS; PATHOGENESIS AB Background: Sonic hedgehog (Shh) is an important endodermal morphogenetic signal during the development of the vertebrate gut. It controls gastrointestinal patterning in general, and gastric gland formation in particular. We have previously shown that Shh regulates gastric gland proliferation in the adult but detailed analysis of its expression along the adult gastrointestinal tract has never been undertaken. We therefore studied Shh expression along the normal human and rodent adult gastrointestinal tract as well as in intestinal metaplasia of the stomach, gastric and intestinal metaplasia of the oesophagus, and gastric heterotopia in Meckel's diverticulum. Methods: The studies were performed with in situ hybridisation and by immunohistochemistry using an antibody that recognises the Shh precursor form. Results: We found that in the normal gastrointestinal tract, high levels of Shh were expressed in the fundic glands of the stomach. Shh expression was also found in fundic gland metaplasia and heterotopia. However, Shh expression was lost in intestinal metaplasia of the stomach. Conclusion: We found a strong correlation between Shh expression and fundic gland differentiation. Our current study therefore provides evidence that in addition to its role in gastric epithelial development, Shh plays a unique role in gastric epithelial differentiation in adults. C1 Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med, Lab Expt Internal Med, NL-1105 AZ Amsterdam, Netherlands. Brigham & Womens Hosp, Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02115 USA. Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol, NL-1105 AZ Amsterdam, Netherlands. RP van den Brink, GR (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med, Lab Expt Internal Med, Room G2-130,Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. NR 35 TC 2 Z9 2 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1366-8714 J9 J CLIN PATHOL-MOL PA JI J. Clin. Pathol.-Mol. Pathol. PD JUN PY 2003 VL 56 IS 3 BP 150 EP 155 PG 6 WC Pathology SC Pathology GA 685GU UT WOS:000183254700005 ER PT J AU Koenigsberg, HW Reynolds, D Goodman, M New, AS Mitropoulou, V Trestman, RL Silverman, J Siever, LJ AF Koenigsberg, HW Reynolds, D Goodman, M New, AS Mitropoulou, V Trestman, RL Silverman, J Siever, LJ TI Risperidone in the treatment of schizotypal personality disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID COGNITIVE PERFORMANCE; NEGATIVE SYMPTOMS; SCHIZOPHRENIA; BORDERLINE; HALOPERIDOL; THIOTHIXENE; STRATEGIES; CRITERIA; SCALE AB Objective: Schizotypal personality disorder (SPD) has many phenomenological, genetic, physiologic, and neuroanatomical commonalities with schizophrenia. Patients with the disorder often suffer from marked social and occupational impairment, yet they have been difficult to treat with medications because of their unusual sensitivity to side effects. This study was designed to determine whether low-dose risperidone treatment is acceptable to SPD patients and can reduce characteristic schizotypal symptoms. In addition, if SPD patients respond to an antipsychotic medication, this will provide support for the notion of a commonality in treatment response between SPD and schizophrenia. Method. Twenty-five patients with DSM-IV-defined SPD were entered into a 9-week randomized, double-blind, placebo-controlled study of low-dose risperidone (starting dose of 0.25 mg/day, titrated upward to 2 mg/day) in the treatment of SPD. Patients were rated with the Positive and Negative Syndrome Scale (PANSS), the Schizotypal Personality Disorder Questionnaire, the Hamilton Rating Scale for Depression, and the Clinical Global Impressions scale. Data were collected from 1995 to 2001. Results: The subjects had a low incidence of depression and of comorbid borderline personality disorder. Patients receiving active medication had significantly (p < .05) lower scores on the PANSS negative and general symptom scales by week 3 and on the PANSS positive symptom scale by week 7 compared with patients receiving placebo. Side effects were generally well tolerated, and there was no group difference in dropout rate for side effects. Conclusion: Low-dose risperidone appears to be effective in reducing symptom severity in SPD and is generally well tolerated. C1 Bronx Vet Affairs Med Ctr, Mental Hlth Patient Care Ctr 116A, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Koenigsberg, HW (reprint author), Bronx Vet Affairs Med Ctr, Mental Hlth Patient Care Ctr 116A, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NCRR NIH HHS [5M01 RR00071] NR 27 TC 56 Z9 57 U1 1 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 2003 VL 64 IS 6 BP 628 EP 634 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 693YR UT WOS:000183746400002 PM 12823075 ER PT J AU Croyle, KL Troster, AI Fields, JA Straits-Troster, KA Lyons, KE Pahwa, R AF Croyle, KL Troster, AI Fields, JA Straits-Troster, KA Lyons, KE Pahwa, R TI Presurgical coping, depression, and quality of life in persons with Parkinson's disease SO JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS LA English DT Article DE Parkinson's disease; depression; quality of life; coping; deep brain stimulation ID OF-LIFE; HEALTH; QUESTIONNAIRE; ILLNESS; INDIVIDUALS; INVENTORY; AVOIDANCE; STROKE; IMPACT; STRESS AB This study describes utilization of coping strategies and evaluates the interaction between coping strategies, depression, and quality of life (QOL) in patients with Parkinson's disease (PD) who are being considered for neurosurgical intervention. Eighty patients (mean age 61.7 years) with PD being evaluated for possible deep brain stimulation completed self-report instruments of coping strategies (Coping Responses Inventory), depression (Beck Depression Inventory), and disease-specific QOL (Parkinson's Disease Questionnaire-39). Analyses showed that patients with PD cope with the acute stressor of approaching neurosurgery through a variety of strategies, but particularly avoidant and behavioral strategies. When the correlated but apparently opposing effects of cognitive and behavioral strategies were teased apart, greater use of cognitive strategies was associated with more severe depressive symptomatology (and poorer QOL), while greater use of behavioral strategies appeared to be associated with less depression. Depressive symptomatology, in turn, was associated with poorer QOL. However, coping had minimal direct association with QOL. From this it was concluded that patients with advanced PD generate a variety of coping responses to an acute stressor such as surgery, and the use of behavioral strategies, in particular seeking of alternative enjoyable activities, may be associated with better mood if salutary effects are not overwhelmed by less helpful cognitive coping techniques. The minimization of depressive symptomatology, in turn, is associated with better QOL. C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Texas Pan Amer, Dept Psychol & Anthropol, Edinburg, TX USA. Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle Div, PADRECC, Seattle, WA USA. Univ Miami, Dept Neurol, Miami, FL 33152 USA. Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA. RP Troster, AI (reprint author), Univ Washington, Dept Psychiat & Behav Sci, Box 356560,1959 NE Pacific St,BB1623, Seattle, WA 98195 USA. NR 39 TC 8 Z9 10 U1 1 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9583 J9 J CLIN PSYCHOL MED S JI J. Clin. Psychol. Med. Settings PD JUN PY 2003 VL 10 IS 2 BP 101 EP 107 DI 10.1023/A:1023342021244 PG 7 WC Psychology, Clinical SC Psychology GA 668PD UT WOS:000182301600004 ER PT J AU Pollack, MH Meoni, P Otto, MW Hackett, D AF Pollack, MH Meoni, P Otto, MW Hackett, D TI Predictors of outcome following venlafaxine extended-release treatment of DSM-IV generalized anxiety disorder: A pooled analysis of short- and long-term studies SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; ODDS RATIOS MISLEAD; DOUBLE-BLIND; MAJOR DEPRESSION; NONDEPRESSED OUTPATIENTS; BENZODIAZEPINE USE; CONTROLLED TRIAL; PLACEBO; EFFICACY; BUSPIRONE AB This pooled analysis evaluated potential predictive abilities of baseline demographic factors, psychiatric history, and DSM-IV. diagnostic criteria for short- and long-term outcome after treatment with venlafaxine extended release (XR) or placebo in patients with generalized anxiety disorder (GAD). Pooled data from 1,839 patients in five placebo-controlled studies of venlafaxine XR for GAD were analyzed by logistic regression. Odds ratios (ORs) were used to quantify pretreatment factors' abilities to predict response (50% reduction, baseline Hamilton Rating Scale for Anxiety [HAM-A] severity) and remission (total HAM-A score less than or equal to7) following venlafaxine XR or placebo treatment. All analyzed factors showed statistically significant outcome associations after 8 or 24 weeks of treatment, or both, in placebo- or venlafaxine-XR-treated patients or both. Substance abuse history, DSM-IV diagnostic criteria of sleep disturbances, difficulty concentrating, and restlessness had the strongest associations with outcome. Sleep disturbances predicted significant positive response in both groups, but more so in the placebo group. Restlessness consistently predicted poor response and lack of remission with either treatment; difficulty concentrating predicted short-term remission with placebo only. Substance abuse history predicted positive outcomes with placebo only. Sex, age, depression history, panic disorder history, prior benzodiazepine and nonbenzodiazepine use, being easily fatigued, muscle tension, and irritability were modestly outcome-predictive or showed treatment condition interactions. In the largest pooled analysis to date, pretreatment factors were associated with treatment outcome in patients with GAD receiving venlafaxine XR or placebo. The strongest trends emerged for history of substance abuse or dependence and symptoms of restlessness, sleep disturbance, and difficulty concentrating. C1 Massachusetts Gen Hosp, Anxiety Disorders Program, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Wyeth Res, Philadelphia, PA USA. Wyeth Pharmaceut, Philadelphia, PA USA. Wyeth Res, Paris, France. Wyeth Pharmaceut, Paris, France. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Anxiety Disorders Program, Dept Psychiat, WAC-812,15 Parkman St, Boston, MA 02114 USA. NR 40 TC 29 Z9 30 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 2003 VL 23 IS 3 BP 250 EP 259 DI 10.1097/00004714-200306000-00006 PG 10 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 697GM UT WOS:000183934200006 PM 12826987 ER PT J AU Sachs, GS AF Sachs, GS TI Unmet clinical needs in bipolar disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT International Meeting on Improvement Without Impairment in Psychotic and Mood Disorders CY JUN 20-21, 2001 CL MONTREUX, SWITZERLAND ID DOUBLE-BLIND; LITHIUM PROPHYLAXIS; DEPRESSIVE-ILLNESS; SUICIDE RISK; I DISORDER; FOLLOW-UP; MANIA; EFFICACY; PLACEBO; LAMOTRIGINE AB Bipolar disorder is a complex, chronic condition associated with considerable morbidity and mortality, including a high rate of suicide. Currently available treatment options for bipolar disorder fail to adequately address many of the important needs of bipolar patients. Long-term maintenance therapy with lithium has been shown to prevent further episodes of mania and depression and to decrease the likelihood of suicide. However, many patients stop lithium treatment after only a few weeks, because of either untoward side effects or other factors, such as the belief that they no longer require medication. Even when lithium is taken regularly and at adequate doses, many patients continue to exhibit severe functional disability and also fail to achieve remission. Bipolar depression is also poorly understood and difficult to treat. A number of adjunctive medications are used in combination with lithium, but residual symptoms and recurring episodes of mania and depression remain common. Recently, atypical antipsychotics, such as olanzapine, risperidone, and quetiapine, have been evaluated for the treatment of bipolar disorder. Although considerable research is still needed, preliminary findings suggest that some of these agents may act as mood stabilizers, improving the acute symptoms of mania without inducing depression or rapid cycling. The role of atypical antipsychotics in maintenance therapy for bipolar disorder is currently being evaluated in a number of large clinical trials. C1 Massachusetts Gen Hosp, Harvewrd Bipolar Res Program, Boston, MA 02114 USA. RP Sachs, GS (reprint author), Massachusetts Gen Hosp, Harvewrd Bipolar Res Program, 50 Staniford St,5th Floor, Boston, MA 02114 USA. NR 44 TC 29 Z9 34 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 2003 VL 23 IS 3 SU 1 BP S2 EP S8 DI 10.1097/00004714-200306001-00002 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 699AH UT WOS:000184033400002 PM 12832943 ER EF