FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Niederman, R Richards, D Matthews, D Shugars, D Worthington, H Shaw, W AF Niederman, R Richards, D Matthews, D Shugars, D Worthington, H Shaw, W TI International standards for clinical trial conduct and reporting SO JOURNAL OF DENTAL RESEARCH LA English DT Editorial Material DE clinical trials; diagnosis; practice guidelines; literature review ID CONSORT STATEMENT; RANDOMIZED TRIALS; QUALITY C1 Forsyth Inst, Ctr Evidence Based Dent, Boston, MA 02115 USA. Boston Univ, Dept Hlth Policy & Hlth Serv Res, Boston, MA 02115 USA. Univ Oxford, Inst Hlth Sci, Ctr Evidence Based Dens, Oxford OX1 2JD, England. Dalhousie Univ, Canadian Collaborat Clin Practice Guidelines Dent, Halifax, NS, Canada. Univ N Carolina, Chapel Hill, NC USA. Univ Manchester, Oral Hlth Grp, Cochrane Collaborat, Manchester M13 9PL, Lancs, England. RP Niederman, R (reprint author), Forsyth Inst, Ctr Evidence Based Dent, 140 Fenway, Boston, MA 02115 USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2003 VL 82 IS 6 BP 415 EP 416 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 682AC UT WOS:000183066700002 PM 12766190 ER PT J AU Barrow, SY Mijares, DQ Tavares, M Legeros, JP Legeros, AR Legeros, RZ AF Barrow, S. -Y. Mijares, D. Q. Tavares, M. Legeros, J. P. Legeros, A. R. Legeros, R. Z. TI Oral health behavior/status: Perception, access, insurance class. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NYU, New York, NY USA. Forsyth Inst, Boston, MA USA. NYU, Coll Dent, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2003 VL 82 SI B MA 0695 BP B99 EP B99 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V42UY UT WOS:000202893600691 ER PT J AU Bertuzzo, C Goodson, JM Mager, D Pilatti, GL Santos, JR Silveira, GM Stadler, CC Kozlowski, VA AF Bertuzzo, C. Goodson, J. M. Mager, D. Pilatti, G. L. Santos, J. R. Silveira, G. M. Stadler, C. C. Kozlowski, V. A., Jr. TI Salivary cadmium levels associated with smoking. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2003 VL 82 SI B MA 1775 BP B233 EP B233 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V42UY UT WOS:000202893602216 ER PT J AU Bogren, A Haffajee, AD Wennstrom, J Lindhe, J Kent, R Goodson, JM Socransky, SS AF Bogren, A. Haffajee, A. D. Wennstrom, J. Lindhe, J. Kent, R. Goodson, J. M. Socransky, S. S. TI Effects of a local drug delivery system and home care on periodontal maintenance therapy. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Gothenburg Univ, S-41124 Gothenburg, Sweden. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2003 VL 82 SI B MA 0611 BP B89 EP B89 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V42UY UT WOS:000202893600607 ER PT J AU Goodson, JM Haffajee, AD Smith, C Yaskell, T Japlit, M Wennstrom, J Lindhe, J Van Dyke, TE Kent, R Socransky, SS AF Goodson, J. M. Haffajee, A. D. Smith, C. Yaskell, T. Japlit, M. Wennstrom, J. Lindhe, J. Van Dyke, T. E. Kent, R. Socransky, S. S. TI Subgingival microbiota in Swedish and USA subjects with different periodontal status. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. Univ Gothenburg, Gothenburg, Sweden. Boston Univ, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2003 VL 82 SI B MA 1896 BP B248 EP B248 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V42UY UT WOS:000202893602334 ER PT J AU Haffajee, AD Smith, C Yaskell, T Japlit, M Wennstrom, J Lindhe, J Van Dyke, TE Kent, R Goodson, JM Socransky, SS AF Haffajee, A. D. Smith, C. Yaskell, T. Japlit, M. Wennstrom, J. Lindhe, J. Van Dyke, T. E. Kent, R. Goodson, J. M. Socransky, S. S. TI Differences in the subgingival microbiota between Swedish and USA subjects. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. Univ Gothenburg, Gothenburg, Sweden. Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2003 VL 82 SI B MA 1897 BP B248 EP B248 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V42UY UT WOS:000202893602335 ER PT J AU Hasturk, H Stan, E Davey, M Warbington, M Guerrero, DM Kantarci, A Goodson, JM Van Dyke, TE AF Hasturk, H. Stan, E. Davey, M. Warbington, M. Guerrero, D. M. Kantarci, A. Goodson, J. M. Van Dyke, T. E. TI Evaluation of monocyte-mediated cytokine production in treatment of chronic periodontitis. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Boston Univ, Boston, MA 02215 USA. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2003 VL 82 SI B MA 2849 BP B366 EP B366 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V42UY UT WOS:000202893603513 ER PT J AU Heitz-Mayfield, LJA Tonetti, M Cortellini, P Haffajee, AD Socransky, SS Buergin, WB Lang, NP AF Heitz-Mayfield, L. J. A. Tonetti, M. Cortellini, P. Haffajee, A. D. Socransky, S. S. Buergin, W. B. Lang, N. P. TI Subgingival microbiota in advanced chronic periodontitis following initial therapy: Single intrabony defects vs. patient profiles. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 UCL, London WC1E 6BT, England. Univ Bern, CH-3012 Bern, Switzerland. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2003 VL 82 SI B MA 2440 BP B315 EP B315 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V42UY UT WOS:000202893603106 ER PT J AU Mager, D Haffajee, AD Devlin, P Norris, CM Posner, MA Goodson, JM AF Mager, D. Haffajee, A. D. Devlin, P. Norris, C. M. Posner, M. A. Goodson, J. M. TI Effects of periodontitis smoking, and oral cancer on oral mucous membrane microbiotas. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2003 VL 82 SI B MA 0117 BP B27 EP B27 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V42UY UT WOS:000202893600116 ER PT J AU Papas, AS Russell, D Singh, ML Winston, A Triol, C Kent, RL AF Papas, A. S. Russell, D. Singh, M. L. Winston, A. Triol, C. Kent, R. L. TI Caries prevention in a head-and-neck-irradiated population. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Tufts Sch Dent Med, Boston, MA USA. Church & Dwight Co Inc, Princeton, NJ USA. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2003 VL 82 SI B MA 2410 BP B312 EP B312 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V42UY UT WOS:000202893603077 ER PT J AU Quick, DL Perciaccante, VJ Krishnan, DG Dodson, TB AF Quick, D. L. Perciaccante, V. J. Krishnan, D. G. Dodson, T. B. TI Prognostic variables associated with clinical outcomes in children with maxillofacial infections. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Emory Univ, Sch Med, Atlanta, GA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2003 VL 82 SI B MA 0789 BP B111 EP B111 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V42UY UT WOS:000202893601003 ER PT J AU Roberts, A Socransky, SS Matthews, J Chapple, I AF Roberts, A. Socransky, S. S. Matthews, J. Chapple, I. TI Growth responses of periodontal pathogens to adrenaline. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Birmingham Dent Sch, Birmingham, W Midlands, England. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2003 VL 82 SI B MA 1676 BP B221 EP B221 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V42UY UT WOS:000202893602117 ER PT J AU Soukos, N Som, S Goodson, JM AF Soukos, N. Som, S. Goodson, J. M. TI Visible spectrum light selectively kills black-pigmented bacteria of human dental plaque. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2003 VL 82 SI B MA 3090 BP B396 EP B396 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V42UY UT WOS:000202893603751 ER PT J AU Susarla, S Dodson, TB AF Susarla, S. Dodson, T. B. TI How well do clinicians estimate mandibular third molar extraction difficulty?. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Harvard Sch Dent Med, Boston, MA USA. Massachusetts Gen Hosp, Harvard Sch Dent Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2003 VL 82 SI B MA 1335 BP B179 EP B179 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V42UY UT WOS:000202893601546 ER PT J AU Taubman, MA Smith, DJ Lees, A AF Taubman, M. A. Smith, D. J. Lees, A. TI Preparation and immunogenicity of monoepitopic and polyepitopic tetanus toxoid (TT)-Glucosyltransferase (GTF) peptide conjugate vaccines. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. Biosynexus Inc, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2003 VL 82 SI B MA 0227 BP B41 EP B41 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V42UY UT WOS:000202893600226 ER PT J AU Torresyap, G Socransky, SS Haffajee, AD Bogren, A Wennstrom, J Lindhe, J Van Dyke, TE Kent, R Goodson, JM AF Torresyap, G. Socransky, S. S. Haffajee, A. D. Bogren, A. Wennstrom, J. Lindhe, J. Van Dyke, T. E. Kent, R. Goodson, J. M. TI Prevalence of smoking among Swedish and USA subjects with different periodontal disease status. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Gothenburg, Gothenburg, Sweden. Boston Univ, Boston, MA 02215 USA. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2003 VL 82 SI B MA 2449 BP B317 EP B317 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V42UY UT WOS:000202893603115 ER PT J AU Philips, N Smith, J Keller, T Gonzalez, S AF Philips, N Smith, J Keller, T Gonzalez, S TI Predominant effects of Polypodium leucotomos on membrane integrity, lipid peroxidation, and expression of elastin and matrixmetalloproteinase-1 in ultraviolet radiation exposed fibroblasts, and keratinocytes SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Article DE Polypodium leucotomos; ultraviolet radiation; extracellular matrix; keratinocytes; fibroblasts ID HUMAN SKIN FIBROBLASTS; CULTURED HUMAN KERATINOCYTES; HUMAN DERMAL FIBROBLASTS; ANTIOXIDANT DEFENSE; ANIMAL-MODEL; IN-VITRO; COLLAGENASE; EXTRACT; TROPOELASTIN; INHIBITION AB Background: Polypodium leucotomos has been reported to have antioxidant, anti-inflammatory and photoprotective properties. Exposure of skin to ultraviolet (UV) radiation can Lead to deposition of excessive etastotic material, reduction in collagen, and increased expression of matrix metalloproteinases (MMPs). Objective: The goal of this research was to determine the effects of P leucotomos in the absence or presence of UVA or UVB radiation on membrane damage, Lipid peroxidation, and expression of elastin and MMP-1 in fibroblasts and keratinocytes, respectively. Methods: Fibroblasts and keratinocytes, respectively, were irradiated by a single exposure to UVA (0.6, 1.8 or 3.6 J) or UVB radiation (0.75, 2.5 or 7.5 mJ), and then incubated with, or without, P leucotomos (0.01, 0.1 and 1%) and examined for membrane damage, lipid peroxidation, expression of elastin (protein levels) and MMP-1 (protein Levels or MMP-1 promoter activity). Results: UV radiation did not significantly alter membrane integrity, lipid peroxidation or MMP-1 expression, but increased elastin expression. P leucotomos significantly improved membrane integrity, inhibited lipid peroxidation, increased elastin expression, and inhibited MMP-1 expression in both fibroblasts, and keratinocytes. The effects of P leucotomos predominated in the presence of UVA or UVB in both fibroblasts and keratinocytes, respectively, with the exception of inhibition of MMP-1 protein Levels in fibroblasts only in combination with UV radiation. Conclusion: Lower concentration of P leucotomos (Lower than 0.1%), may be beneficial in preventing photoaging by improving membrane integrity and inhibiting MMP-1, without increasing elastin expression. Higher concentration (greater than 0.1%) of P leucotomos may reverse the loss of normal elastic fibers associated with intrinsic aging. (C) 2003 Japanese Society for Investigative Dermatology. Published by Elsevier Science Ireland Ltd. ALL rights reserved. C1 Georgian Court Coll, Dept Biol, Lakewood, NJ 08701 USA. Georgian Court Coll, Dept Chem Biochem, Lakewood, NJ USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Philips, N (reprint author), Georgian Court Coll, Dept Biol, Lakewood, NJ 08701 USA. NR 26 TC 49 Z9 56 U1 1 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD JUN PY 2003 VL 32 IS 1 BP 1 EP 9 DI 10.1016/S0923-1811(03)00042-2 PG 9 WC Dermatology SC Dermatology GA 691DD UT WOS:000183588800001 PM 12788523 ER PT J AU Kwolek, CJ Matthews, MR Hartford, JM Minion, DJ Schwarcz, TH Quick, R Endean, E AF Kwolek, CJ Matthews, MR Hartford, JM Minion, DJ Schwarcz, TH Quick, R Endean, E TI Endovascular repair of external iliac artery occlusion after hip prosthesis migration SO JOURNAL OF ENDOVASCULAR THERAPY LA English DT Article DE hip arthroplasty; hip prosthesis; external iliac artery; arterial injury; arterial thrombosis; prosthetic migration; thrombolysis; SMART stent ID ARTHROPLASTY; SECONDARY AB Purpose: To report emergent endovascular intervention to restore lower extremity arterial patency after migration of a hip prosthesis caused thrombosis of the external iliac artery (EIA). Case Report: Nine months following left hip revision arthroplasty, a 66-year-old woman presented to the Emergency Department with the complaints of an acutely painful left lower extremity for over 6 hours. Imaging showed the metallic acetabular portion of the hip prosthesis in the iliac fossa, with severe external compression of the EIA. After thrombolysis to remove clot from the EIA, an 8X60-mm self-expanding Smart stent was deployed in the left EIA from a contralateral access. The procedure was successful, and the patient was discharged. An infected wound from a compartment fasciotomy delayed revision of the hip prosthesis. Nine weeks after stenting, the patient returned with a cold, pulseless left limb; a femorofemoral bypass was constructed to restore perfusion. Conclusions: While stent placement restored flow for 9 weeks after the initial ischemic event, the recurrent thrombosis could have been prevented by earlier revision of the migrated prosthesis. C1 Univ Kentucky, Dept Surg, Vasc Sect, Lexington, KY USA. Univ Kentucky, Dept Orthoped Surg, Lexington, KY USA. RP Kwolek, CJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, WAC-458,15 Parkman St, Boston, MA 02114 USA. NR 9 TC 3 Z9 3 U1 0 U2 0 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1526-6028 J9 J ENDOVASC THER JI J. Endovascular Ther. PD JUN PY 2003 VL 10 IS 3 BP 668 EP 671 DI 10.1583/1545-1550(2003)010<0668:EROEIA>2.0.CO;2 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 721FK UT WOS:000185306200039 PM 12932185 ER PT J AU Asch, SM Kilbourne, AM Gifford, AL Burnam, MA Turner, B Shapiro, MF Bozzette, SA AF Asch, SM Kilbourne, AM Gifford, AL Burnam, MA Turner, B Shapiro, MF Bozzette, SA TI Underdiagnosis of depression in HIV - Who are we missing? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE depression; HIV; diagnosis ID HUMAN-IMMUNODEFICIENCY-VIRUS; NATIONAL PROBABILITY SAMPLES; LOW-PREVALENCE DISEASES; MAJOR DEPRESSION; MENTAL-HEALTH; UNITED-STATES; PRIMARY-CARE; ANTIRETROVIRAL THERAPY; SERVICES UTILIZATION; PATIENT ADHERENCE AB OBJECTIVE: To determine the sociodemographic and service delivery correlates of depression underdiagnosis in HIV. DESIGN: Cross-sectional survey. PATIENTS/PARTICPANTS: National probability sample of HIV-infected persons in care in the contiguous United States who have available medical record data. MEASUREMENTS AND MAIN RESULTS: We interviewed patients using the Composite International Diagnostic Interview (CIDI) survey from the Mental Health Supplement. Patients also provided information regarding demographics, socioeconomic status, and HIV disease severity. We extracted patient medical record data between July 1995 and December 1997, and we defined depression underdiagnosis as a diagnosis of major depressive disorder based on the CIDI and no recorded depression diagnosis by their principal health care provider in their medical records between July 1995 and December 1997. Of the 1,140 HIV Cost and Services Utilization Study patients with medical record data who completed the CIDI, 448 (37%) had CIDI-defined major depression, and of these, 203 (45%) did not have a diagnosis of depression documented in their medical record. Multiple logistic regression analysis revealed that patients who had less than a high school education (P < .05) were less likely to have their depression documented in the medical record compared to those with at least a college education. Patients with Medicare insurance coverage compared to those with private health insurance (P < .01) and those with greater than or equal to3 outpatient visits (P < .05) compared to <3 visits were less likely to have their depression diagnosis missed by providers. CONCLUSIONS: Our results suggest that providers should be more attentive to diagnosing comorbid depression in HIV-infected patients. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. Ctr Hlth Equity Res & Promot & VA, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. VA San Diego Healthcare Syst, San Diego, CA USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. Univ Penn, Gen Internal Med Sect, Philadelphia, PA 19104 USA. RP Asch, SM (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd 111G, Los Angeles, CA 90073 USA. FU AHRQ HHS [U-01HS08578, U01 HS008578] NR 59 TC 109 Z9 110 U1 2 U2 9 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2003 VL 18 IS 6 BP 450 EP 460 DI 10.1046/j.1525-1497.2003.20938.x PG 11 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 694VP UT WOS:000183796100006 PM 12823652 ER PT J AU Weintraub, D Streim, JE Datto, CJ Katz, IR DiFilippo, SD Oslin, DW AF Weintraub, D Streim, JE Datto, CJ Katz, IR DiFilippo, SD Oslin, DW TI Effect of increasing the dose and duration of sertraline trial in the treatment of depressed nursing home residents SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE sertraline; elderly; depression ID ANTIDEPRESSANT TRIAL; SCALE AB There has been limited research into defining what constitutes an adequate first-line antidepressant trial in elderly patients. The authors report the outcome of extended, high-dosage sertraline treatment in a sample of nursing home residents experiencing residual significant depressive symptoms after 10 weeks of treatment with sertraline at a final dosage of 100 mg/day, Subjects who had a Hamilton Depression Rating Scale score : 12 after 10 weeks of treatment with sertraline were eligible for the 8-week open-label extension phase, which involved titrating the sertraline dosage to 200 mg/day. The cumulative response rate was 52% for the extension phase, compared. with 37% for the acute phase. Examining acute phase nonresponders, 39% responded during the extension phase. Rates of discontinuation due to adverse events were comparable in the 2 phases. Our findings suggest that an extended trial or high dosages of sertraline may benefit some depressed elderly patients with persistent depression after acute treatment. C1 Univ Penn, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Weintraub, D (reprint author), Univ Penn, Sect Geriatr Psychiat, 3535 Market St,Room 3003, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu FU NIMH NIH HHS [1-37MH 52147-06] NR 12 TC 6 Z9 6 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD JUN PY 2003 VL 16 IS 2 BP 109 EP 111 DI 10.1177/0891988703252546 PG 3 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 847GI UT WOS:000223380300008 PM 12801161 ER PT J AU Marin, RS Butters, MA Mulsant, BH Pollock, BG Reynolds, CF AF Marin, RS Butters, MA Mulsant, BH Pollock, BG Reynolds, CF TI Apathy and executive function in depressed elderly SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE apathy; executive cognitive function; major depression; geriatrics; executive inter-view; cardiovascular risk factors ID DEFINED VASCULAR DEPRESSION; GERIATRIC DEPRESSION; DYSFUNCTION; DISEASE; RELIABILITY; DISABILITY; DISORDERS; VALIDITY; SCALE AB Apathy and executive cognitive dysfunction (ECD) are important though conceptually different aspects of late-life depression. The primary objective of this study was to evaluate the relationship of apathy to ECD. The authors also evaluated the relationship of apathy and ECD to global cognitive impairment and word generation. Fifty-two elderly subjects with major depression and MMSE scores of 15 or greater were evaluated with apathy-related items from the Hamilton rating scale for depression (ApHRSD), the Executive Interview (EXIT), the Dementia Rating Scale (DRS), and the Controlled Oral Word Association test (COWA). ApHRSD scores were not significantly correlated with any of these variables. EXIT scores were correlated significantly with DRS and COWA. The results suggest that apathy and ECD may be independent of each other in some samples of elderly with late-life depression. Correlations may have been reduced by low variance for the variables of interest and by psychometric limitations of the ApHRSD. C1 Univ Pittsburgh, Sch Med, Intervent Res Ctr Study Late Life Mood Disorders, Dept Psychiat, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Marin, RS (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. EM rmarin@pitt.edu FU NIMH NIH HHS [MH01613, MH01509, P30 MH52247, MH01684, K05 MH00295] NR 36 TC 26 Z9 27 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD JUN PY 2003 VL 16 IS 2 BP 112 EP 116 DI 10.1177/0891988702250593 PG 5 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 847GI UT WOS:000223380300009 PM 12801162 ER PT J AU Schiff, ER Dienstag, JL Karayalcin, S Grimm, IS Perrillo, RP Husa, P de Man, RA Goodman, Z Condreay, LD Crowther, LM Woessner, MA McPhillips, PJ Brown, NA AF Schiff, ER Dienstag, JL Karayalcin, S Grimm, IS Perrillo, RP Husa, P de Man, RA Goodman, Z Condreay, LD Crowther, LM Woessner, MA McPhillips, PJ Brown, NA CA Int Lamivudine Investigator Grp TI Lamivudine and 24 weeks of lamivudine/interferon combination therapy for hepatitis B e antigen-positive chronic hepatitis B in interferon nonresponders SO JOURNAL OF HEPATOLOGY LA English DT Article DE lamivudine; interferon; hepatitis B; hepatitis B e antigen; chronic hepatitis; interferon nonresponder ID TERM FOLLOW-UP; RANDOMIZED CONTROLLED TRIAL; ALPHA-INTERFERON; PROGNOSTIC FACTORS; INFECTION; VIRUS; SURVIVAL; ALFA; RETREATMENT; MULTICENTER AB Background/Aims: Lamivudine is effective in treatment-naive patients with chronic hepatitis B, but its role in interferon nonresponders has not been described. We assessed lamivudine treatment, with or without added interferon, in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had failed interferon therapy previously. Methods: Patients were randomized to lamivudine (100 mg) or placebo for 52 weeks or to a 24-week regimen of lamivudine plus interferon. Primary treatment comparisons were at week 52, with a 16-week posttreatment follow-up period. Measurements included histology (primary endpoint), HBeAg response, normalization of alanine aminotransferase, reduction of hepatitis B virus (HBV) DNA, and safety. Results: Among 238 patients, histologic response was significantly more common in patients treated with lamivudine (52 versus placebo 25%, P = 0.002) or the combination regimen (32%, P = 0.01). HBeAg loss was also more common with lamivudine (33 versus 13 versus 21%), as were virologic and alanine aminotransferase responses. Among 28 subjects with HBeAg loss/seroconversion, 71% had durable responses 16 weeks posttreatment. Conclusions: Lamivudine for 52 weeks is as effective in interferon nonresponders as in previously reported treatment-naive patients; however, a combination of lamivudine for 24 weeks and interferon for 16 weeks was not effective in this population. (C) 2003 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved. C1 Univ Miami, Div Hepatol, Miami, FL 33136 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Ankara Univ, Sch Med, TR-06100 Ankara, Turkey. Univ N Carolina, Chapel Hill, NC USA. Ochsner Clin & Alton Ochsner Med Fdn, New Orleans, LA USA. Clin Infect Dis, Brno, Czech Republic. Acad Ziekenhuis Dijkzigt Rotterdam, Rotterdam, Netherlands. Armed Forces Inst Pathol, Washington, DC 20306 USA. GlaxoSmithKline, Res Triangle Pk, NC USA. GlaxoSmithKline, Greenford, Middx, England. RP Schiff, ER (reprint author), Univ Miami, Div Hepatol, Jackson Med Towers,1500 NW 12th Ave,Suite 1101, Miami, FL 33136 USA. OI Grimm, Ian/0000-0001-9083-5930 FU NCRR NIH HHS [M01RR01066] NR 41 TC 82 Z9 94 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD JUN PY 2003 VL 38 IS 6 BP 818 EP 826 DI 10.1016/S0168-8278(03)00076-X PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 681ZJ UT WOS:000183065200016 PM 12763376 ER PT J AU Anikeeva, N Lebedeva, T Sumaroka, M Kalams, SA Sykulev, Y AF Anikeeva, N Lebedeva, T Sumaroka, M Kalams, SA Sykulev, Y TI Soluble HIV-specific T cell receptor: expression, purification and analysis of the specificity SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE soluble T cell receptor; MHC tetramer; drosophila expression system; receptor-ligand interactions; binding assay ID PEPTIDE-MHC; ANTIGEN RECEPTOR; BETA-CHAIN; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; RECOGNITION; ALPHA; TCR; BINDING; ASSAY AB We have produced soluble T cell receptor (TCR) derived from a human CD8(+) cytotoxic T lymphocyte (CTL) clone D3 that recognizes the immunodominant HIV Gag peptide SLYNTVATL (SL9) in association with major histocompatibility complex (MHC) class I protein HLA-A2. Drosophila Schneider cells (S2) were used to express genes coding the TCR alpha and beta chains under an inducible promoter. Both chains were labeled with two different tags: a (His)(6) was introduced at the C-terminal end of a chain, while chain was terminated by c-myc. Since an isolated a chain is unstable unless it is associated with a 0 chain, this design permits rapid separation of alpha,beta-heterodimer from unpaired beta chain in a single step of Ni-NTA Agarose chromatography yielding 90% pure alpha,beta-TCR. Introduction of the c-myc epitope to the beta chain allows capture of soluble D3 from the culture supernatant by immobilized anti-c-myc antibody, without the need for receptor purification. The TCR specificity was then examined by analyzing the binding of peptide-HLA-A2/tetramer in an ELISA assay. Using this assay, we have also evaluated the binding of monomeric SL9-HLA-A2 complex to the immobilized D3 TCR and determined that the affinity measurement of the D3-SL9-HLA-A2 reaction is similar to that obtained by a biosensor instrument. We propose that the approach described here is generally useful for purification of other soluble TCRs and will allow rapid analysis of their specificity. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Thomas Jefferson Univ, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Kimmel Canc Inst, Philadelphia, PA 19107 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sykulev, Y (reprint author), Thomas Jefferson Univ, Dept Microbiol & Immunol, BLSB 650, Philadelphia, PA 19107 USA. FU NIAID NIH HHS [AI43254, AI39966, 5-T32-AI07523] NR 32 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUN 1 PY 2003 VL 277 IS 1-2 BP 75 EP 86 DI 10.1016/S0022-1759(03)00179-0 PG 12 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 692LD UT WOS:000183661800007 PM 12799041 ER PT J AU Hewison, M Freeman, L Hughes, SV Evans, KN Bland, R Eliopoulos, AG Kilby, MD Moss, PAH Chakraverty, R AF Hewison, M Freeman, L Hughes, SV Evans, KN Bland, R Eliopoulos, AG Kilby, MD Moss, PAH Chakraverty, R TI Differential regulation of vitamin D receptor and its ligand in human monocyte-derived dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; D-3 1-ALPHA-HYDROXYLASE GENE; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; 1,25-DIHYDROXYVITAMIN D-3; IN-VITRO; IL-12 PRODUCTION; PHORBOL ESTER; T-CELLS; MATURATION; EXPRESSION AB The functions of dendritic cells (DCs) are tightly regulated such that protective immune responses are elicited and unwanted immune responses are prevented. 1alpha25-dihydroxyvitamin D-3 (1alpha25(OH)(2)D-3) has been identified as a major factor that inhibits the differentiation and maturation of DCs, an effect dependent upon its binding to the nuclear vitamin D receptor (VDR). Physiological control of 1alpha25(OH)(2)D-3 levels is critically dependent upon 25-hydroxyvitamin D-3-1alpha-hydroxylase (1alphaOHase), a mitochondrial cytochrome P450 enzyme that catalyzes the conversion of inactive precursor 25-hydroxyvitamin D3 (25(OH)D3) to the active metabolite 1alpha25(OH)(2)D-3. Using a human monocyte-derived DC (moDC) model, we have examined the relationship between DC VDR expression and the impact of exposure to its ligand, 1alpha25(OH)(2)D-3. We show for the first time that moDCs are able to synthesize 1alpha25(OH)(2)D-3, in vitro as a consequence of increased 1alphaOHase expression. Following terminal differentiation induced by a diverse set of maturation stimuli, there is marked transcriptional up-regulation of IaOHase leading to increased laOHase enzyme activity. Consistent with this finding is the observation that the development and function of moDCs is inhibited at physiological concentrations of the inactive metabolite 25(OH)D-3. In contrast to 1alphaOHase, VDR expression is down-regulated as monocytes differentiate into immature DCs. Addition of 1alpha25(OH)(2)D-3 to moDC cultures at different time points indicates that its inhibitory effects are greater in monocyte precursors than in immature DCs. In conclusion, differential regulation of endogenous 1alpha25(OH)(2)D-3 ligand and its nuclear receptor appear to be important regulators of DC biology and represent potential targets for the manipulation of DC function. C1 Univ Birmingham, Dept Med Sci, Birmingham, W Midlands, England. Univ Birmingham, Dept Hematol, Birmingham, W Midlands, England. Univ Birmingham, Dept Canc Studies, Birmingham, W Midlands, England. Univ Birmingham, Dept Reprod & Child Hlth, Birmingham, W Midlands, England. RP Chakraverty, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplant Biol Res Ctr, Massachusetts Gen Hosp E,Bone Marrow Transplantat, Bldg 149-5102,13th St, Boston, MA 02129 USA. NR 49 TC 236 Z9 245 U1 0 U2 7 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 1 PY 2003 VL 170 IS 11 BP 5382 EP 5390 PG 9 WC Immunology SC Immunology GA 681UY UT WOS:000183055000007 PM 12759412 ER PT J AU Zhao, Y Ohdan, H Manilay, JO Sykes, M AF Zhao, Y Ohdan, H Manilay, JO Sykes, M TI NK cell tolerance in mixed allogeneic chimeras SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; BONE-MARROW ALLOGRAFTS; H-2-DEFICIENT LYMPHOMA VARIANTS; DEFICIENT HEMATOPOIETIC-CELLS; NONLETHAL PREPARATIVE REGIMEN; CLASS-I MHC; GRAFT-REJECTION; STEM-CELLS; T-CELLS; PECULIAR IMMUNOBIOLOGY AB Alterations in inhibitory receptor expression on NK cells have been detected in mixed allogeneic chimeras and in mosaic MHC class I-expressing transgenic mice. However, it is not known whether or not NK cells are tolerant to host and donor Ags in mixed chimeras. In vitro studies have shown a lack of mutual tolerance of separated donor and host NK cells obtained from mixed chimeras. Using BALB/c-->B6 fully MHC-mismatched mixed chimeras, we have now investigated this question in vivo. Neither donor nor host NK cells in mixed chimeras showed evidence for activation, as indicated by expression of B220 and Thy-1.2 on NK cells in chimeric mice at levels similar to those in nonchimeric control mice. Lethally irradiated, established mixed BALB/c-->B6 chimeras rejected a low dose of 162-microglobulin-deficient bone marrow cells (BMC) efficiently but did not reject BALB/c or B6 BMCs. In contrast, similarly conditioned B6 mice rejected both BALB/c and beta(2)-microglobulin-deficient BMCs. Thus, NK cells were specifically tolerant to the donor and the host in mixed allogeneic chimeras. The similar growth of RMA lymphoma cells in both chimeric and control B6 mice further supports the conclusion that donor BALB/c NK cells are tolerant to B6 Ags in chimeras. Administration of a high dose of exogenous IL-2 could not break NK cell tolerance in chimeric mice, suggesting that NK cell tolerance in chimeras is not due to a lack of activating cytokine. No reduction in the level of expression of the activating receptor Ly-49D, recognizing a donor MHC molecule, was detected among recipient NK cells in mixed chimeras. Thus, the present studies demonstrate that NK cells in mixed chimeras are stably tolerant to both donor and host Ags, by mechanisms that are as yet unexplained. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, MGH E,Transplantat Biol Res Ctr,Surg Serv, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, MGH E,Transplantat Biol Res Ctr,Surg Serv, Bldg 149,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [5 R01 CA79986-03]; NHLBI NIH HHS [5 R01 HL49915-01] NR 54 TC 47 Z9 48 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 1 PY 2003 VL 170 IS 11 BP 5398 EP 5405 PG 8 WC Immunology SC Immunology GA 681UY UT WOS:000183055000009 PM 12759414 ER PT J AU Hamblin, MR Zahra, T Contag, CH McManus, AT Hasan, T AF Hamblin, MR Zahra, T Contag, CH McManus, AT Hasan, T TI Optical monitoring and treatment of potentially lethal wound infections in vivo SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 8th International-Photodynamic-Association Congress CY JUN 08, 2001 CL VANCOUVER, CANADA SP Int Photodynam Assoc ID PHOTODYNAMIC THERAPY; ESCHERICHIA-COLI; IN-VIVO; BACTERIA; MODEL; MICE; UNIT AB We report on the use of optical techniques to monitor and treat Pseudomonas aeruginosa wound infections in mice. Bioluminescent bacteria transduced with a plasmid containing a bacterial lux gene operon allow the infection in excisional mouse wounds to be imaged by use of a sensitive charge-coupled device camera. Photodynamic therapy (PDT) targeted bacteria, by use of a polycationic photosensitizer conjugate, which is designed to penetrate the gram-negative cell wall and was topically applied to the wound and was followed by red-light illumination. There was a rapid light dose-dependent loss of luminescence, as measured by image analysis, in the wounds treated with conjugate and light, a loss that was not seen in untreated wounds, wounds treated with light alone, or wounds treated with conjugate alone. P. aeruginosa was invasive in our mouse model, and all 3 groups of control mice died within 5 days; in contrast, 90% of PDT-treated mice survived. PDT-treated wounds healed significantly faster than did silver nitrate-treated wounds, and this was not due to either inhibition of healing by silver nitrate or stimulation of healing by PDT. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. Ft Sam Houston, Inst Surg Res, San Antonio, TX USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 50 Blossom St, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01AI050879, R01 AI050875] NR 32 TC 105 Z9 112 U1 1 U2 7 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 1 PY 2003 VL 187 IS 11 BP 1717 EP 1725 DI 10.1086/375244 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 685TK UT WOS:000183279200006 PM 12751029 ER PT J AU Maslow, JN Brar, I Smith, G Newman, GW Mehta, R Thornton, C Didier, P AF Maslow, JN Brar, I Smith, G Newman, GW Mehta, R Thornton, C Didier, P TI Latent infection as a source of disseminated disease caused by organisms of the Mycobacterium avium complex in simian immunodeficiency virus-infected rhesus macaques SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID FIELD GEL-ELECTROPHORESIS; AIDS; BACTEREMIA; TUBERCULOSIS; SENSITIN; MONKEYS; WATER; RETROVIRUS; INDUCTION; STRAIN AB Whether infection with Mycobacterium avium complex (MAC) among patients with acquired immune deficiency syndrome results from recent exposure to virulent strains or reactivation of latent infection acquired years earlier is unknown. To address this question, tissue samples from 47 simian immunodeficiency virus (SIV)-infected and 63 SIV-uninfected rhesus macaques were cultured. MAC was cultured from 14 SIV-uninfected macaques (22.2%) and 32 SIV-infected macaques (68.1%); median bacterial burdens were 33.3 and 998.7 cfu/g, respectively. Genetically distinct strains of MAC were identified for 13 SIV-uninfected macaques (20.6%) and 15 SIV-infected macaques (31.9%). A genetically identical MAC strain (K128A) was identified for 25 SIV-infected macaques (53.2%) and 1 SIV-uninfected macaque (1.6%). Multivariate analysis identified infection with SIV/Delta(B670), diagnosis of an SIV-related tumor or opportunistic infection, and birth on site as risks for MAC infection. SIV-uninfected and SIV-infected macaques yielding unique strains of MAC were considered to have latent and reactivation infection, respectively, whereas animals infected with strain K128A were considered to have recent infection, demonstrating that both mechanisms occur among rhesus macaques. C1 Dept Vet Affairs Med Ctr, Res Serv, Div Infect Dis, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Sect Epidemiol & Publ Hlth, Kennett Sq, PA 19348 USA. Henry Ford Hosp, Dept Med, Div Infect Dis, Detroit, MI 48202 USA. Morehouse Sch Med, Dept Microbiol Biochem & Immunol, Atlanta, GA 30310 USA. Quest Diagnost, Integrated Res Technol, Baltimore, MD USA. Tulane Reg Primate Ctr, Dept Pathol, Covington, LA USA. Tulane Univ, Sch Med, Covington, LA USA. RP Maslow, JN (reprint author), Dept Vet Affairs Med Ctr, Res Serv, Div Infect Dis, Univ & Woodland Aves, Philadelphia, PA 19104 USA. NR 37 TC 15 Z9 16 U1 0 U2 0 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 1 PY 2003 VL 187 IS 11 BP 1748 EP 1755 DI 10.1086/374985 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 685TK UT WOS:000183279200009 PM 12751032 ER PT J AU Dallalio, G Means, RT AF Dallalio, G Means, RT TI Effects of oxidative stress on human erythroid colony formation: Modulation by gamma-interferon SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Hematology CY DEC 07-11, 2001 CL ORLANDO, FLORIDA SP Amer Soc Hematol ID IMMUNODEFICIENCY-VIRUS-INFECTION; PROGRAMMED CELL-DEATH; TUMOR-NECROSIS-FACTOR; FORMING-UNITS; CHRONIC DISEASE; THIOREDOXIN; APOPTOSIS; CERAMIDE; ANEMIA; INHIBITION AB Evidence of increased oxidative stress is a hallmark of many chronic diseases associated with anemia. The current study was undertaken to evaluate the effects of oxidative stress on erythroid colony formation in vitro by bone marrow light density mononuclear cells (LDMN) and by peripheral blood derived cells enriched for erythroid colony forming units (CFU-E), and how these effects can be modified by a cytokine implicated in the anemia of chronic disease. When blood-derived and marrow cells were cultured with 50 muM H2O2, CFU-E colony formation by blood-derived cells but not by marrow cells was significantly inhibited, suggesting a protective effect of marrow accessory cells. This inhibitory effect on peripheral blood-derived CFU-E was shown to be caspase-dependent. rhgammaIFN at concentrations which did not inhibit CFU-E colony formation sensitized LDMN marrow cells to inhibition by H2O2. Exposure of LDMN marrow cells to rhgammaIFN at concentrations of 10U/mL or higher significantly decreased the concentration of thioredoxin (Trx) in cell supernatant. Addition of recombinant Trx to LDMN marrow cells cultured with H2O2 and rhgammaIFN partially (although not completely) reversed inhibition of CFU-E colony formation. These findings suggest that inflammatory cytokines implicated in the pathogenesis of the anemia of chronic disease may exert their effects at least in part through modulation of oxidative stress. C1 Med Univ S Carolina, Div Hematol Oncol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Div Hematol Oncol, Charleston, SC 29425 USA. RP Means, RT (reprint author), Med Univ S Carolina, Div Hematol Oncol, 903 CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. RI Means, Robert/A-4454-2008 FU NHLBI NIH HHS [HL-53703] NR 43 TC 5 Z9 5 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD JUN PY 2003 VL 141 IS 6 BP 395 EP 400 DI 10.1016/S0022-2143(03)00041-6 PG 6 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 693LF UT WOS:000183718500005 PM 12819637 ER PT J AU Lee, PL Yiannoutsos, CT Ernst, T Chang, L Marra, CM Jarvik, JG Richards, TL Kwok, EW Kolson, DL Simpson, D Tang, CY Schifitto, G Ketonen, LM Meyerhoff, DJ Lenkinski, RE Gonzalez, RG Navia, BA AF Lee, PL Yiannoutsos, CT Ernst, T Chang, L Marra, CM Jarvik, JG Richards, TL Kwok, EW Kolson, DL Simpson, D Tang, CY Schifitto, G Ketonen, LM Meyerhoff, DJ Lenkinski, RE Gonzalez, RG Navia, BA CA HIV MRS Consortium TI A multi-center H-1 MRS study of the AIDS dementia complex: validation and preliminary analysis SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE AIDS dementia complex (ADC); MRS; HIV infection; spectroscopy; neuroimaging ID HUMAN-IMMUNODEFICIENCY-VIRUS; MAGNETIC-RESONANCE SPECTROSCOPY; HIV-INFECTION; SEROPOSITIVE INDIVIDUALS; NEOCORTICAL DAMAGE; HUMAN BRAIN; PROTON MRS; METABOLITES; THERAPY; ABNORMALITIES AB Purpose: To demonstrate the technical feasibility and reliability of a multi-center study characterizing regional levels of the brain metabolite ratios choline (Cho)/creatine (Cr) and myoinositol (MI)/Cr, markers of glial cell activity, and N-acetyl aspartate (NAA)/Cr, a marker of mature neurons, in subjects with AIDS dementia complex (ADC). Materials and Methods: Using an automated protocol (GE PROBE-P). short echo time spectra (TE = 35 msec) were obtained at eight sites from uniformly prepared phantoms and from three brain regions (frontal white matter, basal ganglia. and parietal cortex) of normal volunteers and ADC and HIV-negative subjects. Results: A random-effects model of the phantom and volunteer data showed no significant inter-site differences. Feasibility of a multi-center study was further validated by detection of significant differences between the metabolite ratios of ADC subjects and HIV-negative controls. ADC subjects exhibited significantly higher Cho/Cr and MI/Cr in the basal ganglia and significantly reduced NAA/Cr and significantly higher MI/Cr in the frontal white matter. These results are consistent with the predominantly subcortical distribution of the pathologic abnormalities associated with ADC. Conclusion: This is the first study to ascertain and validate the reliability and reproducibility of a short echo time H-1-MRS acquisition sequence from multiple brain regions in a multi-center setting. It should now be possible to examine the regional effects of HIV infection in the brain in a large number of subjects and to study the metabolic effects of new therapies for the treatment of ADC in a clinical trial setting. C1 Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harbor UCLA Med Ctr, Torrance, CA 90509 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Univ Rochester, Dept Radiol, Rochester, MN USA. Mt Sinai Med Ctr, Dept Radiol, New York, NY 10029 USA. Univ Texas, Dept Radiol, Galveston, TX 77555 USA. Univ Calif San Francisco, DVA Med Ctr, San Francisco, CA 94143 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Tufts Univ New England Med Ctr, Dept Neurol & Psychiat, Boston, MA 02111 USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149 13th St, Charlestown, MA 02129 USA. RI Lenkinski, Robert/F-9045-2014; OI Lenkinski, Robert/0000-0001-7371-5048 FU NCRR NIH HHS [R01RR13213]; NIAID NIH HHS [AI38855]; NINDS NIH HHS [R01 NS36524, R01NS34626] NR 40 TC 59 Z9 59 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JUN PY 2003 VL 17 IS 6 BP 625 EP 633 DI 10.1002/jmri.10295 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 684TA UT WOS:000183221600001 PM 12766890 ER PT J AU McGibbon, CA Bencardino, J Yeh, ED Palmer, WE AF McGibbon, CA Bencardino, J Yeh, ED Palmer, WE TI Accuracy of cartilage and subchondral bone spatial thickness distribution from MRI SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE cartilage thickness; subchondral bone thickness; three-dimensional thickness; 3D thickness; spatial thickness distribution; arthritis; joint injury; MRI; Faxitron ID SPIN-ECHO MR; ARTICULAR-CARTILAGE; 3-DIMENSIONAL ASSESSMENT; NONINVASIVE TECHNIQUE; COMPUTATIONAL METHOD; IN-VITRO; OSTEOARTHRITIS; KNEE; ARTHROSCOPY; REPRODUCIBILITY AB Purpose: To assess three-dimensional measurement accuracy of articular cartilage (AC) and subchondral bone (SB) thickness from MRI. Materials and Methods: A computer program was used to calculate AC and SB thickness from MRI (three-dimensional spoiled gradient echo (SPGR), .31-mm resolution, 1-mm slice thickness) of six adult femoral heads. Specimens were imaged in five anatomical planes ranging between +30degrees to -30degrees from neutral and cut into 2-mm thick sections along the five anatomical planes. Faxitron x-ray was used to produce microradiographic (.05-mm resolution) images of the sections. Results: In-plane measurement accuracy was. 165+/-.108 mm for AC thickness and .387+/-.174 mm for SB thickness. Taking into account chemical-shift misregistration in SB thickness, accuracy of measurements improved to .213+/-128 mm. Out-of-plane (three-dimensional) thickness accuracy of the model, assessed by numerical simulation, was .015 mm. However, three-dimensional thickness errors in specimens were .319+/-.256 mm for AC and .253+/-.183 mm for SB thickness. Conclusion: Errors in three-dimensional AC thickness were attributed to volume-averaging effects caused by oblique intersection of the image plane with the joint surface. Errors in three-dimensional SB thickness were attributed to chemical-shift artifact. We conclude that accuracy of AC thickness is within clinically acceptable standards but that more sophisticated pulse sequences are needed to improve the measurement of SB thickness. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Biomot Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, NGH Inst Hlth Profess,Grad Programs Phys Therapy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP McGibbon, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Biomot Lab, 55 Fruit St,Ruth Sleeper Hall,Room 010, Boston, MA 02114 USA. EM cmcgibbon@partners.org NR 35 TC 29 Z9 29 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JUN PY 2003 VL 17 IS 6 BP 703 EP 715 DI 10.1002/jmr.10309 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 684TA UT WOS:000183221600011 PM 12766900 ER PT J AU Gruber, A Chen, I Kuhen, KL Wheat, JC Law, P Wong-Staal, F AF Gruber, A Chen, I Kuhen, KL Wheat, JC Law, P Wong-Staal, F TI Generation of dendritic cells from lentiviral vector-transduced CD34(+) cells from HIV+ donors SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE HIV; CD34(+) hematopoietic stem cells; dendritic cells; lentiviral vector ID CD8(+) T-CELLS; PROGENITOR CELLS; INFECTED INDIVIDUALS; MELANOMA PATIENTS; IN-VITRO; MONOCYTES; GENE; LYMPHOCYTES; VACCINATION; MACROPHAGES AB Dendritic cells hold promise as adjuvant for immunotherapy for cancer and infectious diseases. We demonstrate that a significant number of cryopreserved peripheral blood CD34(+) cells from HIV-infected subjects can be transduced with a replication-incompetent lentiviral vector expressing HIV antigens. In addition, untransduced and transduced CD34(+) cells from HIV-infected individuals were able to differentiate into dendritic cells with strong T-cell stimulatory capacity. Thus, cryopreserved CD34(+) cells from HIV-infected subjects may prove useful for immunotherapy for HI/AIDS. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Diego, Blood & Marrow Transplantat Program, La Jolla, CA 92093 USA. Harvard Med Sch, Dept Canc Immunol & AIDS, Boston, MA USA. RP Gruber, A (reprint author), Dana Farber Canc Inst, 44 Binney St,JFB-809, Boston, MA 02115 USA. FU NIAID NIH HHS [AI44372, AI45992] NR 19 TC 6 Z9 6 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUN PY 2003 VL 70 IS 2 BP 183 EP 186 DI 10.1002/jmv.10376 PG 4 WC Virology SC Virology GA 673DC UT WOS:000182564000001 PM 12696103 ER PT J AU McClain, MT Rapp, EC Harley, JB James, JA AF McClain, MT Rapp, EC Harley, JB James, JA TI Infectious mononucleosis patients temporarily recognize a unique, cross-reactive epitope of Epstein-Barr virus nuclear antigen-1 SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE EBV; EBNA-1; autoimmunity; SLE; SM B ' ID INDUCED AUTOIMMUNE RESPONSES; ALANINE REPEATING REGION; AUTOANTIBODIES; IMMUNOGLOBULIN; ANTIBODIES; MIMICKING AB The spectrum of antibodies against Epstein-Barr virus nuclear antigen-1 (EBNA-1) in patients with a recent history of infectious mononucleosis and nonaffected EBV-positive individuals has been characterized by epitope mapping. Sera were evaluated for antibodies to all unique maximally overlapping octapeptides of EBNA-1. Both normal controls and patients with infectious mononucleosis produce IgG antibodies that recognize the glycine-alanine-rich portion of EBNA-1, as previously described. All EBNA-1 IgG-positive infectious mononucleosis patients tested, however, consistently produce IgG specific for an additional epitope (aa 398-412 PPPGRRPFFHPVGEA) near the middle of the EBNA-1 protein. This region was not found to be antigenic in healthy EBV-seropositive individuals. This region does, however, cross-react with the sequence PPPGMRPP from the common lupus spliceosomal autoantigen Sm B' several infectious mononucleosis patient sera. Patients with recent clinical infectious mononucleosis temporarily recognize a unique cross-reactive epitope of EBNA-1 not bound by antibodies from non-infectious mononucleosis EBV-positive sera or those with a distant history of IM. C1 Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. US Dept Vet Affairs, Oklahoma City, OK USA. RP McClain, MT (reprint author), Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA. FU NIAID NIH HHS [AI31584]; NIAMS NIH HHS [AR01981, AR45084, AR45451] NR 12 TC 32 Z9 33 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUN PY 2003 VL 70 IS 2 BP 253 EP 257 DI 10.1002/jmv.10385 PG 5 WC Virology SC Virology GA 673DC UT WOS:000182564000010 PM 12696112 ER PT J AU Willey, CD Balasubramanian, S Rosas, MCR Ross, RS Kuppuswamy, D AF Willey, CD Balasubramanian, S Rosas, MCR Ross, RS Kuppuswamy, D TI Focal complex formation in adult cardiomyocytes is accompanied by the activation of beta 3 integrin and c-Src SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE c-Src; FAK; integrins; focal adhesion complex; cardiomyocytes; hypertrophy ID CARDIAC-HYPERTROPHY; EXTRACELLULAR-MATRIX; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; CYTOPLASMIC DOMAIN; ADHESION KINASE; FAMILY KINASES; GROWTH-CONTROL; SHEAR-STRESS; CELLS AB In pressure-overloaded myocardium, our recent study demonstrated cytoskeletal assembly of c-Src and other signaling proteins which was partially mimicked in vitro using adult feline cardiomyocytes embedded in three-dimensional (3D) collagen matrix and stimulated with an integrin-binding Arg-Gly-Asp (RGD) peptide. In the present study, we improved this model further to activate c-Src and obtain a full assembly of the focal adhesion complex (FAC), and characterized c-Src localization and integrin subtype(s) involved. RGD dose response experiments revealed that c-Src activation occurs subsequent to its cytoskeletal recruitment and is accompanied by p130Cas cytoskeletal binding and focal adhesion kinase (FAK) Tyr925 phosphorylation. When cardiomyocytes expressing hexahistidine-tagged c-Src via adenoviral gene delivery were used for RGD stimulation, the expressed c-Src exhibited relocation: (i) biochemical analysis revealed c-Src movement from the detergent-soluble to the -insoluble cytoskeletal fraction and (ii) confocal microscopic analysis showed c-Src movement from a nuclear/perinuclear to a sarcolemmal region. RGD treatment also caused sarcolemmal co-localization of FAK and vinculin. Characterization of integrin subtypes revealed that beta3, but not beta1, integrin plays a predominant role: (i) expression of cytoplasmic domain of beta1A integrin did not affect the RGD-stimulated FAC formation and (ii) both pressure-overloaded myocardium and RGD-stimulated cardiomyocytes exhibited phosphorylation of beta3 integrin at Tyr773/785 sites but not beta1 integrin at Thr788/789 sites. Together these data indicate that RGD treatment in cardiomyocytes causes beta3 integrin activation and c-Src sarcolemmal localization, that subsequent c-Src activation is accompanied by p130Cas binding and FAK Tyr925 phosphorylation, and that these events might be crucial for growth and remodeling of hypertrophying adult cardiomyocytes. (C) 2003 Elsevier Science Ltd. All fights reserved. C1 Med Univ S Carolina, Div Cardiol, Dept Med, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Univ Calif Los Angeles, Dept Physiol & Med, Gessen Sch Med, Los Angeles, CA 90095 USA. Dept Vet Affairs Med Ctr, Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Kuppuswamy, D (reprint author), Med Univ S Carolina, Div Cardiol, Dept Med, Gazes Cardiac Res Inst, 114 Doughty St, Charleston, SC 29425 USA. EM kuppusd@musc.edu OI Willey, Christopher/0000-0001-9953-0279 FU NHLBI NIH HHS [HL-48788, HL-57872]; NIGMS NIH HHS [GM08716] NR 55 TC 24 Z9 25 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUN PY 2003 VL 35 IS 6 BP 671 EP 683 DI 10.1016/S0022-2828(03)00112-3 PG 13 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 692QZ UT WOS:000183672900014 PM 12788385 ER PT J AU Hilsenroth, MJ Ackerman, SJ Blagys, MD Baity, MR Mooney, MA AF Hilsenroth, MJ Ackerman, SJ Blagys, MD Baity, MR Mooney, MA TI Short-term psychodynamic psychotherapy for depression: An examination of statistical, clinically significant, and technique-specific change SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article; Proceedings Paper CT Winter Meeting of the American-Psychoanalytic-Association CY DEC, 2001 CL NEW YORK, NEW YORK SP Amer Psychoanalyt Assoc ID COLLABORATIVE RESEARCH-PROGRAM; COGNITIVE-BEHAVIORAL THERAPY; MENTAL-HEALTH TREATMENT; BRIEF DYNAMIC THERAPY; INTERPERSONAL PSYCHOTHERAPY; NATIONAL-INSTITUTE; ALLIANCE; METAANALYSIS; RELIABILITY; ADHERENCE AB This study investigates the effectiveness of short-term psychodynamic psychotherapy (STPP) for depression in a naturalistic setting utilizing a hybrid effectiveness/efficacy treatment research model. Twenty-one patients were assessed pre- and post-treatment through clinician ratings and patient self-report on scales representing specific DSM-IV depressive, global symptomatology, relational, social, and occupational functioning. Treatment credibility, fidelity, and satisfaction were examined, all of which were found to be high. All areas of functioning assessed exhibited significant and positive changes. These adaptive changes in functioning demonstrated large statistical effects. Likewise, changes in depressive symptoms evaluated at the patient level utilizing clinical significance methodology were found to be high. A significant direct process/outcome link between STPP therapist techniques and changes in depressive symptoms was observed. Alternative treatment interventions within STPP were evaluated in relation to subsequent improvements in depression and were found to be nonsignificant. The present results demonstrate that robust statistical and Clinically significant improvement can occur in a naturalistic/hybrid model of outpatient STPP for depression. C1 Adelphi Univ, Derner Inst Adv Psycol Studies, Garden City, NY 11530 USA. Austen Riggs Ctr Inc, Erikson Inst Educ & Res, Stockbridge, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA USA. Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Hilsenroth, MJ (reprint author), Adelphi Univ, Derner Inst Adv Psycol Studies, 158 Cambridge Ave,220 Weinberg Bldg, Garden City, NY 11530 USA. NR 45 TC 58 Z9 59 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUN PY 2003 VL 191 IS 6 BP 349 EP 357 DI 10.1097/01.NMD.0000071582.11781.67 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 695DD UT WOS:000183815100001 PM 12826915 ER PT J AU Doyle, AE Biederman, J Monuteaux, M Cohan, SL Schofield, HLT Faraone, SV AF Doyle, AE Biederman, J Monuteaux, M Cohan, SL Schofield, HLT Faraone, SV TI Diagnostic threshold for conduct disorder in girls and boys SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID ATTENTION-DEFICIT DISORDER; DISRUPTIVE BEHAVIOR DISORDERS; OPPOSITIONAL DEFIANT DISORDER; LONGITUDINAL DATA-ANALYSIS; IV FIELD TRIALS; DSM-III-R; HYPERACTIVITY DISORDER; GENDER DIFFERENCES; FAMILIAL SUBTYPE; CHILDREN AB Concerns about gender bias in the diagnostic criteria for conduct disorder (CD) have prompted some researchers to recommend that the diagnostic threshold in girls be lowered. Since CD is a highly familial condition, the authors assessed the diagnostic validity of subthreshold CD in girls using family study methodology. They compared the rates of antisocial disorders (CD and antisocial personality disorder) in relatives of four groups of index children: children with attention deficit hyperactivity disorder (ADHD) and full, subthreshold, or no CD diagnoses and non-ADHD/non-CD control subjects. Results showed no interaction between gender and familiality across the four groups. Furthermore, there was no significant evidence of familiality of subthreshold CD. From a family genetic perspective, the diagnostic threshold for CD does not appear to differ by gender. The current results support the possibility that differential rates of CD reflect actual differences in rates of antisocial behavior across gender. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Johnson & Johnson Psychopathol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. RP Doyle, AE (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Clin & Res Program Pediat Psychopharmacol, ACC-725,15 Parkman St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH41314, R01 MH-50657] NR 37 TC 7 Z9 7 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUN PY 2003 VL 191 IS 6 BP 379 EP 386 DI 10.1097/01.NMD.0000071586.10820.05 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 695DD UT WOS:000183815100005 PM 12826919 ER PT J AU Kim, MJ Cotman, SL Halfter, W Cole, GJ AF Kim, MJ Cotman, SL Halfter, W Cole, GJ TI The heparan sulfate proteoglycan agrin modulates neurite outgrowth mediated by FGF-2 SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE agrin; FGF-2; neurite outgrowth; heparan sulfate proteoglycan ID FIBROBLAST-GROWTH-FACTOR; HIPPOCAMPAL-NEURONS; NERVOUS-SYSTEM; SYNAPSE FORMATION; CORTICAL-NEURONS; FACTOR RECEPTOR; DEFICIENT MICE; FACTOR-BINDING; AXONAL GROWTH; VISUAL-SYSTEM AB Although the role of agrin in the formation of the neuromuscular junction is well established, other functions for agrin have remained elusive. The present study was undertaken to assess the role of agrin in neurite outgrowth mediated by the heparin-binding growth factor basic fibroblast growth factor (FGF-2), which we have shown previously to bind to agrin with high affinity and that has been shown to mediate neurite outgrowth from a number of neuronal cell types. Using both an established neuronal cell line, PC12 cells, and primary chick retina neuronal cultures, we find that agrin potentiates the ability of FGF-2 to stimulate neurite outgrowth. In PC12 cells and retinal neurons agrin increases the efficacy of FGF-2 stimulation of neurite outgrowth mediated by the FGF receptor, as an inhibitor of the FGF receptor abolished neurite outgrowth in the presence of agrin and FGF-2. We also examined possible mechanisms by which agrin may modulate neurite outgrowth, analyzing ERK phosphorylation and c-fos phosphorylation. These studies indicate that agrin augments a transient early phosphorylation of ERK in the presence of FGF-2, and augments and sustains FGF-2 mediated increases in c-fos phosphorylation. These data are consistent with established mechanisms where heparan sulfate proteoglycans such as agrin may increase the affinity between FGF-2 and the FGF receptor. In summary, our studies suggest that neural agrin contributes to the establishment of axon pathways by modulating the function of neurite promoting molecules such as FGF-2. (C) 2003 Wiley Periodicals, Inc. C1 N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC 27606 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15261 USA. RP Cole, GJ (reprint author), N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, 4700 Hillsborough St, Raleigh, NC 27606 USA. FU NINDS NIH HHS [NS 33981] NR 71 TC 41 Z9 42 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD JUN PY 2003 VL 55 IS 3 BP 261 EP 277 DI 10.1002/neu.10213 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 677JP UT WOS:000182804000001 PM 12717697 ER PT J AU Dedeoglu, A Kubilus, JK Yang, LC Ferrante, KL Hersch, SM Beal, MF Ferrante, RJ AF Dedeoglu, A Kubilus, JK Yang, LC Ferrante, KL Hersch, SM Beal, MF Ferrante, RJ TI Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE chemotherapy; creatine; Huntington's disease ID NEURONAL INTRANUCLEAR INCLUSIONS; COENZYME Q(10); MOUSE MODELS; ANIMAL-MODEL; MITOCHONDRIAL; PHOSPHOCREATINE; INCREASES; KINASE; BRAIN; SUPPLEMENTATION AB While there have been enormous strides in the understanding of Huntington's disease (HD) pathogenesis, treatment to slow or prevent disease progression remains elusive. We previously reported that dietary creatine supplementation significantly improves the clinical and neuropathological phenotype in transgenic HD mice lines starting at weaning, before clinical symptoms appear. We now report that creatine administration started after onset of clinical symptoms significantly extends survival in the R6/2 transgenic mouse model of HD. Creatine treatment started at 6, 8, and 10 weeks of age, analogous to early, middle, and late stages of human HD, significantly extended survival at both the 6- and 8-week starting points. Significantly improved motor performance was present in both the 6- and 8-week treatment paradigms, while reduced body weight loss was only observed in creatine-supplemented R6/2 mice started at 6 weeks. Neuropathological sequelae of gross brain and neuronal atrophy and huntingtin aggregates were delayed in creatine-treated R6/2 mice started at 6 weeks. We show significantly reduced brain levels of both creatine and ATP in R6/2 mice, consistent with a bioenergetic defect. Oral creatine supplementation significantly increased brain concentrations of creatine and ATP to wild-type control levels, exerting a neuroprotective effect. These findings have important therapeutic implications, suggesting that creatine therapy initiated after diagnosis may provide significant clinical benefits to HD patients. C1 Bedford VA Med Ctr, GRECC Unit 182B, Ctr Geriatr Res Educ & Clin, Bedford, MA 01730 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Dept Neurol, New York, NY USA. Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Dept Neurosci, New York, NY USA. Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Ferrante, RJ (reprint author), Bedford VA Med Ctr, GRECC Unit 182B, Ctr Geriatr Res Educ & Clin, 200 Springs Rd, Bedford, MA 01730 USA. OI Dedeoglu, Alpaslan/0000-0003-1156-0874 FU NCCIH NIH HHS [AT00613, R01 AT000613, U01 AT000613]; NIA NIH HHS [P01 AG014930-040005, AG12992, AG13846, AG14930, P01 AG012992, P01 AG014930, P01 AG014930-09, P30 AG013846]; NINDS NIH HHS [NS35255, NS37102, NS38180, NS39258, R01 NS039258] NR 44 TC 107 Z9 111 U1 0 U2 6 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2003 VL 85 IS 6 BP 1359 EP 1367 DI 10.1046/j.1471-4159.2003.01706.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 686EK UT WOS:000183308300001 PM 12787055 ER PT J AU Linseman, DA Cornejo, BJ Le, SS Meintzer, MK Laessig, TA Bouchard, RJ Heidenreich, KA AF Linseman, DA Cornejo, BJ Le, SS Meintzer, MK Laessig, TA Bouchard, RJ Heidenreich, KA TI A myocyte enhancer factor 2D (MEF2D) kinase activated during neuronal apoptosis is a novel target inhibited by lithium SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoptosis; cerebellar granule neuron; glycogen synthase kinase; lithium; MEF2 transcription factor; phosphorylation ID CEREBELLAR GRANULE NEURONS; GLYCOGEN-SYNTHASE KINASE-3-BETA; TRANSCRIPTION FACTOR MEF2C; DNA-BINDING ACTIVITY; CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR-I; CASPASE-3 ACTIVATION; BIPOLAR DISORDER; CELL-DEATH; PROTECTION AB Depolarization promotes the survival of cerebellar granule neurons via activation of the transcription factor myocyte enhancer factor 2D (MEF2D). Removal of depolarization induces hyperphosphorylation of MEF2D on serine/threonine residues, resulting in its decreased DNA binding and susceptibility to caspases. The subsequent loss of MEF2-dependent gene transcription contributes to the apoptosis of granule neurons. The kinase(s) that phosphorylates MEF2D during apoptosis is currently unknown. The serine/threonine kinase, glycogen synthase kinase-3beta (GSK-3beta), plays a pro-apoptotic role in granule neurons. To investigate a potential role for GSK-3beta in MEF2D phosphorylation, we examined the effects of lithium, a non-competitive inhibitor of GSK-3beta, on MEF2D activity in cultured cerebellar granule neurons. Lithium inhibited caspase-3 activation and chromatin condensation in granule neurons induced to undergo apoptosis by removal of depolarizing potassium and serum. Concurrently, lithium suppressed the hyperphosphorylation and caspase-mediated degradation of MEF2D. Moreover, lithium sustained MEF2 DNA binding and transcriptional activity in the absence of depolarization. Lithium also attenuated MEF2D hyperphosphorylation and apoptosis induced by calcineurin inhibition under depolarizing conditions, a GSK-3beta-independent model of neuronal death. In contrast to lithium, MEF2D hyperphosphorylation was not inhibited by forskolin, insulin-like growth factor-I, or valproate, three mechanistically distinct inhibitors of GSK-3beta. These results demonstrate that the kinase that phosphorylates and inhibits the pro-survival function of MEF2D in cerebellar granule neurons is a novel lithium target distinct from GSK-3beta. C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Heidenreich, KA (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmacol C236, 4200 E 9th Ave, Denver, CO 80262 USA. FU NINDS NIH HHS [NS38619-01A1] NR 54 TC 31 Z9 31 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2003 VL 85 IS 6 BP 1488 EP 1499 DI 10.1046/j.1471-4159.2003.01790.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 686EK UT WOS:000183308300014 PM 12787068 ER PT J AU Black, DN Taber, KH Hurley, RA AF Black, DN Taber, KH Hurley, RA TI Metachromatic leukodystrophy: A model for the study of psychosis SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID ARYLSULFATASE-A ACTIVITY; WHITE-MATTER; NEUROPSYCHIATRIC DISORDERS; CORPUS-CALLOSUM; SCHIZOPHRENIA; BRAIN; MR; ABNORMALITIES; ANISOTROPY; DTI C1 Univ Vermont, Dept Neurol, Burlington, VT USA. Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. Baylor Coll Med, Dept Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Herbert J Frensley Ctr Imaging Res, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Psychiat Serv, Houston, TX USA. RP Taber, KH (reprint author), Univ Texas, Sch Hlth Informat Sci, 7000 Fannin,UCT 880, Houston, TX 77030 USA. NR 42 TC 20 Z9 20 U1 1 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 2003 VL 15 IS 3 BP 289 EP 293 DI 10.1176/appi.neuropsych.15.3.289 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 715JR UT WOS:000184968800001 PM 12928504 ER PT J AU Berezovska, O Ramdya, P Skoch, J Wolfe, MS Bacskai, BJ Hyman, BT AF Berezovska, O Ramdya, P Skoch, J Wolfe, MS Bacskai, BJ Hyman, BT TI Amyloid precursor protein associates with a nicastrin-dependent docking site on the presenilin 1-gamma-secretase complex in cells demonstrated by fluorescence lifetime imaging SO JOURNAL OF NEUROSCIENCE LA English DT Article DE APP; nicastrin; presenilin; gamma-secretase; docking site; FLIM; spatial paradox ID GAMMA-SECRETASE INHIBITORS; RECEPTOR-RELATED PROTEIN; INTRACELLULAR DOMAIN; ALZHEIMERS-DISEASE; BETA-APP; CLEAVAGE; NOTCH; LOCALIZATION; PROTEOLYSIS; DEFICIENCY AB gamma-Secretase cleavage is the final enzymatic step generating beta-amyloid via intramembranous cleavage of the amyloid precursor protein (APP). Presenilin ( PS), initially identified as a gene in which mutations account for the vast majority of early-onset autosomal dominant Alzheimer's disease, is a major component of gamma-secretase. Enzymatic activity also depends on nicastrin, Aph-1, and Pen-2. We propose a model in which gamma-secretase components assemble, interact with substrates initially at a docking site, and then cleave and release substrates. To test this model, we developed a novel morphological technique on the basis of advanced fluorescence microscopy methods, fluorescence lifetime imaging microscopy (FLIM). FLIM allows us to examine protein - protein "proximity" in intact cells. We show that, although the strongest colocalization of APP and PS1 is in the perinuclear area, the strongest interactions detected by FLIM are at or near the cell surface. We also found that APP - PS1 interactions occur even when gamma-secretase inhibitors or "dominant-negative" PS1 mutations are used to block gamma-secretase activity. Finally, using nicastrin RNA interference, we demonstrate that nicastrin is critical for APP association with PS1. We interpret these results to suggest that there is a noncatalytic docking site closely associated with PS1-gamma-secretase. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Inst Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. RP Berezovska, O (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Alzheimers Dis Res Lab, 114 16th St,Room 2750, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG15379, AG 08487]; NIBIB NIH HHS [EB00768]; NINDS NIH HHS [NS 41355] NR 30 TC 77 Z9 82 U1 0 U2 2 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 1 PY 2003 VL 23 IS 11 BP 4560 EP 4566 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 688PD UT WOS:000183443700019 PM 12805296 ER PT J AU Chang, SM Parney, IF McDermott, M Barker, FG Schmidt, MH Huang, W Laws, ER Lillehei, KO Bernstein, M Brem, H Sloan, AE Berger, M AF Chang, SM Parney, IF McDermott, M Barker, FG Schmidt, MH Huang, W Laws, ER Lillehei, KO Bernstein, M Brem, H Sloan, AE Berger, M CA Glioma Outcomes Investigators TI Perioperative complications and neurological outcomes of first and second craniotomies among patients enrolled in the Glioma Outcome Project SO JOURNAL OF NEUROSURGERY LA English DT Article DE malignant glioma; craniotomy; postoperative complication; outcome ID GLIOBLASTOMA-MULTIFORME; AWAKE CRANIOTOMY; RECURRENT GLIOBLASTOMA; MALIGNANT GLIOMAS; RADIATION-THERAPY; RESECTION; REOPERATION; TUMORS; BRAIN; ASTROCYTOMA AB Object. In many new clinical trials of patients with malignant gliomas surgical intervention is incorporated as an integral part of tumor-directed interstitial therapies such as gene therapy, biodegradable wafer placement, and immunotherapy. Assessment of toxicity is a major component of evaluating these novel therapeutic interventions, but this must be done in light of known complication rates of craniotomy for tumor resection. Factors predicting neurological outcome would also be helpful for patient selection for surgically based clinical trials. Methods. The Glioma Outcome Project is a prospectively compiled database containing information on 788 patients with malignant gliomas that captured clinical practice patterns and patient outcomes. Patients in this series who underwent their first or second craniotomy were analyzed separately for presenting symptoms, tumor and patient characteristics, and perioperative complications. Preoperative and intraoperative factors possibly related to neurological outcome were evaluated. There were 408 patients who underwent first cramotomies (C1 group) and 91 patients who underwent second ones (C2 group). Both groups had similar patient and tumor characteristics except for their median age (55 years in the C I group compared with 50 years in the C2 group; p = 0.006). Headache was more common at presentation in the C1 group, whereas papilledema and an altered level of consciousness were more common at presentation in patients undergoing second surgeries. Perioperative complications occurred in 24% of patients in the C1 group and 33% of patients in the C2 group (p = 0.1). Most patients were the same or better neurologically after surgery, but more patients in the C2 group (18%) displayed a worsened neurological status than those in the C1 group (8%; p = 0.007). The Karnofsky Performance Scale score and, in patients in the C2 group, tumor size were important neurological outcome predictors. Regional complications occurred at similar rates in both groups. Systemic infections occurred more frequently in the C2 group (4.4 compared with 0%; p < 0.0001) as did depression (20 compared with 11%; p = 0.02). The perioperative mortality rate was 1.5% for the C1 group and 2.2% for the C2 group (p = not significant). The median length of the hospital stay was 4 days in each group. Conclusions. Perioperative complications occur slightly more often following a second craniotomy for malignant glioma than after the first craniotomy. This should be considered when evaluating toxicities from intraoperative local therapies requiring craniotomy. Nevertheless, most patients are neurologically stable or improved after either their first or second craniotomy. This data set may serve as a benchmark for neurosurgeons and others in a discussion of operative risks in patients with malignant gliomas. C1 Univ Calif San Francisco, Dept Neurol Surg, Brain Tumor Res Ctr, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Ctr Outcomes Res, Boston, MA 02125 USA. Univ Utah, Dept Neurosurg, Salt Lake City, UT USA. Univ Virginia, Hlth Sci Ctr, Dept Neurol Surg, Charlottesville, VA 22908 USA. Univ Colorado, Div Neurosurg, Denver, CO 80202 USA. Univ Toronto, Div Neurosurg, Toronto, ON, Canada. Johns Hopkins Univ, Dept Neurosurg, Baltimore, MD USA. Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. Wayne State Univ, Dept Neurol Surg, Detroit, MI USA. RP Chang, SM (reprint author), Univ Calif San Francisco, Dept Neurol Surg, Brain Tumor Res Ctr, 400 Parnassus Ave,A808, San Francisco, CA 94143 USA. NR 37 TC 127 Z9 131 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 JUN PY 2003 VL 98 IS 6 BP 1175 EP 1181 DI 10.3171/jns.2003.98.6.1175 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 686TT UT WOS:000183337600005 PM 12816260 ER PT J AU Topcuoglu, MA Ogilvy, CS Carter, BS Buonanno, FS Koroshetz, WJ Singhal, AB AF Topcuoglu, MA Ogilvy, CS Carter, BS Buonanno, FS Koroshetz, WJ Singhal, AB TI Subarachnoid hemorrhage without evident cause on initial angiography studies: diagnostic yield of subsequent angiography and other neuroimaging tests SO JOURNAL OF NEUROSURGERY LA English DT Article DE subarachnoid hemorrhage; magnetic resonance imaging; magnetic resonance angiography; computerized tomography angiography; angiography ID PERIMESENCEPHALIC HEMORRHAGE; REPEAT-ANGIOGRAPHY; CEREBRAL ANEURYSMS; CT ANGIOGRAPHY; TOMOGRAPHY; PATTERN AB Object. The aim of this study was to assess the diagnostic yield of imaging tests performed in patients in whom the cause of subarachnoid hemorrhage (SAH) had not been demonstrated on initial angiography. Methods. By reviewing medical records of 806 patients with SAH who had been admitted during a 6.5-year period, the authors identified 86 in whom initial transfemoral catheter angiography failed to reveal the cause of SAH. Clinical and radiological data were analyzed to determine the diagnostic yield of subsequent catheter angiography, computerized tomography (CT) angiography, magnetic resonance (MR) angiography, and MR imaging of the brain and spine for various subtypes of SAH (bleeding not visualized on CT studies [CT-negative SAH], perimesencephalic SAH, and nonperimesencephalic SAH). Of 41 patients with noriperimesencephalic SAH, 36, 32, and 21 underwent repeated catheter angiography, CT angiography, and MR angiography, respectively; brain MR imaging was performed in 23 patients (18 with Gd and 15 with susceptibility contrast sequences), and spine MR imaging in 17. Of 36 patients with perimesencephalic SAH, 31, 23, and 17 underwent repeated catheter angiography, CT angiography, and MR angiography, respectively; brain MR imaging was performed in 18 patients (17 with Gd and I I with susceptibility contrast sequences), and spine MR imaging in 14. Of nine patients with SAH not visualized on CT scanning, three, one, and six underwent repeated catheter angiography, CT angiography, and MR angiography, respectively; brain MR imaging was performed in eight patients (five with Gd and three with susceptibility contrast sequences), and spine MR imaging in seven. The cause of SAH could be determined in only four patients, all with nonperimesencephalic SAH. The only test that yielded a diagnosis was catheter angiography (three aneurysms on the second and one on the third angiography, all surgically secured). Diffusion-weighted MR imaging demonstrated small, deep infarcts in five patients. Conclusions. Repeated catheter angiography remains the most sensitive test to determine the cause of SAH that is not demonstrated on initial angiography, particularly in the subtype of nonperimesencephalic SAH. Newer, noninvasive imaging techniques provide little diagnostic yield. C1 Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, VBK 802, Boston, MA 02114 USA. NR 27 TC 61 Z9 64 U1 0 U2 0 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 JUN PY 2003 VL 98 IS 6 BP 1235 EP 1240 DI 10.3171/jns.2003.98.6.1235 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 686TT UT WOS:000183337600015 PM 12816270 ER PT J AU Royal, W Dupont, B McGuire, D Chang, L Goodkin, K Ernst, T Post, MJ Fish, D Pailloux, G Poncelet, H Concha, M Apuzzo, L Singer, E AF Royal, W Dupont, B McGuire, D Chang, L Goodkin, K Ernst, T Post, MJ Fish, D Pailloux, G Poncelet, H Concha, M Apuzzo, L Singer, E TI Topotecan in the treatment of acquired immunodeficiency syndrome-related progressive multifocal leukoencephalopathy SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE HIV-1; MRI; polyomavirus; topoisomerases; viral encephalitis ID ACTIVE ANTIRETROVIRAL THERAPY; JC VIRUS LOAD; ALPHA-INTERFERON; NATURAL-HISTORY; DNA-REPLICATION; HIV-INFECTION; AIDS; SURVIVAL; CYTARABINE; CIDOFOVIR AB Progressive multifocal leukoencephalopathy (PML) affects about 1 in 20 individuals with the acquired immunodeficiency syndrome (AIDS) and has been associated with poor survival. This report describes the results of a phase II clinical trial using the drug topotecan, a semisynthetic analogue of camptothecan, administered to a cohort of subjects with AIDS-related PML. Data were evaluated on 11 of 12 subjects enrolled in the study. Three responded to therapy. Additionally, one patient was treated off-protocol and showed a response to treatment. Progression occurred after the first course; however, a partial response was noted after five courses. One study patient died from accidental overdose of topotecan. Overall, responders had higher pretreatment Karnofsky and lower Kurtzke expanded disability status scale scores than non-responders. The most frequent toxicities were hematologic (anemia, neutropenia, and thrombocytopenia). Five patients had dose delays; all delays were due to hematologic adverse events. This study demonstrates that topotecan treatment may be associated with decreased lesion size and prolonged survival from the infection. Because of the small number of subjects in the study, further studies are required to evaluate the efficacy of topotecan in treating this disease. C1 Morehouse Sch Med, Inst Neurosci, Atlanta, GA 30310 USA. Hop Necker Enfants Malad, Paris, France. HIV Inst, San Francisco, CA USA. Brookhaven Inst, Staten Isl, NY USA. Univ Miami, Sch Med, Miami, FL USA. Albany Med Ctr, Albany, NY USA. Hop Inst Pasteur, Paris, France. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Royal, W (reprint author), Morehouse Sch Med, Inst Neurosci, Med Res Bldg,Room 218,720 Westview Dr SW, Atlanta, GA 30310 USA. NR 35 TC 45 Z9 49 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD JUN PY 2003 VL 9 IS 3 BP 411 EP 419 DI 10.1080/13550280390201740 PG 9 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 683XJ UT WOS:000183176100014 PM 12775425 ER PT J AU Kaban, LB Dodson, TB AF Kaban, LB Dodson, TB TI Calcitonin therapy for central giant cell granuloma SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material ID ANTIANGIOGENIC THERAPY; INTERFERON-ALPHA; JAWS; LESIONS C1 Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Kaban, LB (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. NR 12 TC 7 Z9 7 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 JUN PY 2003 VL 61 IS 6 BP 653 EP 654 DI 10.1053/joms.2003.50130 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 685PP UT WOS:000183272700003 ER PT J AU August, M Faquin, WC Troulis, MJ Kaban, LB AF August, M Faquin, WC Troulis, MJ Kaban, LB TI Dedifferentiation of odontogenic keratocyst epithelium after cyst decompression SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID TERM FOLLOW-UP; SURGICAL-MANAGEMENT; RECURRENCE; JAW AB Purpose: Cytokeratin-10 expression by cystic epithelium has been shown in the suprabasilar layers of odontogenic keratocyts (OKCs) but not in dentigerous cysts. Cyst decompression and irrigation result in the loss of keratinization. In this study, we used cytokeratin-10 antibody staining to evaluate changes in OKC epithelium to determine if decompression/irrigation treatment results in an epithelial modulation that may be associated with lower long-term recurrence. Methods: Fourteen OKCs were exteriorized by removal of mucosa and bone. An irrigation port was placed into the cyst for twice-daily irrigations. At 3-month intervals, panoramic radiographs were obtained and cyst-lining cells were sampled and stained for cytokeratin-10. Residual cystectomy was performed when necessary based on clinical and radiographic criteria, and the lining was evaluated by histologic and immunohistochemical examination. Results: There were 6 males and 8 females with a mean age of 32 years. Ten cysts were mandibular, and 4 were maxillary. Average duration of irrigation was 8.4 months (range, 6 to 12 months), and the mean shrinkage of the radiolucency was 65% (range, 5% to 91%). All cytologic samples obtained at 3 and 6 months contained cytokeratin-10-positive epithelial cells. At the time of cystectomy, 9 of 14 cases were cytokeratin-10 negative and no longer showed histologic features of OKCs. Specimens from the remaining 5 patients were histologically consistent with OKC and were cytokeratin-10 positive. Mean treatment time of the cytokeratin-10-positive group was 7 months, and that of the cytokeratin-10-negative group was 9 months. Conclusion: Epithelial dedifferentiation and loss of cytokeratin-10 production were observed in 64% of patients treated by cyst decompression/irrigation after a 9-month average treatment time. Longitudinal follow-tip of these patients will determine whether this change is associated with lower rates of recurrence than alternative OKC therapy. (C) 2003 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP August, M (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren 1201,55 Fruit St, Boston, MA 02114 USA. FU PHS HHS [K23 1200 209103] NR 20 TC 42 Z9 48 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUN PY 2003 VL 61 IS 6 BP 678 EP 683 DI 10.1053/joms.2003.50137 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 685PP UT WOS:000183272700010 PM 12796876 ER PT J AU Fuchs, JR Hannouche, D Terada, S Vacanti, JP Fauza, DO AF Fuchs, JR Hannouche, D Terada, S Vacanti, JP Fauza, DO TI Fetal tracheal augmentation with cartilage engineered from bone marrow-derived mesenchymal progenitor cells SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the Section on Surgery of the American-Academy-of-Pediatrics CY OCT 18-20, 2002 CL BOSTON, MASSACHUSETTS SP Amer Acad Pediat, Sect Surg DE tissue engineering; mesenchymal stem cells; bone marrow-derived stromal cells; cartilage; tracheal malformations; fetal surgery; congenital anomalies; transplantation ID STEM-CELLS; IN-VITRO; TRANSPLANTATION; BLOOD; SHEEP AB Background/Purpose: The authors have described previously the use of engineered fetal cartilage in a large animal model of fetal tracheal repair. This study was aimed at comparing cartilage engineered from bone marrow-derived stromal cells (BMSC) to native and engineered cartilage, in this model. Methods: Ovine BMSC were expanded in vitro, seeded onto biodegradable scaffolds, and maintained in transforming growth factor beta I (TGF-beta1)-supplemented medium for 3 months (group I). Identical scaffolds were seeded with fetal chondrocytes (group II). All constructs were analyzed in vitro, implanted into fetal tracheas, and harvested after birth for further analysis. Results: There were no differences in survival between the groups. All BMSC-based constructs exhibited chondrogenic differentiation. Matrix analyses in vitro showed that both groups had similar levels of glycosaminoglycans (GAG) and type II collagen (C-II), but lower levels of elastin when compared with native fetal cartilage. Yet, compared with group II, group I had higher levels of GAG, equal levels of C-II, and lower levels of elastin. However, remodeling resulted in no differences between the 2 groups in any of these variables in vivo. Conclusions: The bone marrow may be a useful cell source for cartilage engineering aimed at the surgical repair of severe congenital tracheal anomalies, such as tracheal atresia and agenesis, in utero. J Pediatr Surg 38:984-987. (C) 2003 Elsevier Inc. All rights reserved. C1 Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Harvard Ctr Minimally Invas Surg, Ctr Integrat Med & Innovat Technol, Boston, MA 02114 USA. RP Fauza, DO (reprint author), Childrens Hosp, Fegan 3,300 Longwood Ave, Boston, MA 02115 USA. NR 13 TC 58 Z9 73 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 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JUN PY 2003 VL 38 IS 6 BP 984 EP 987 DI 10.1016/S0022-3468(03)00139-8 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 690NU UT WOS:000183555900056 PM 12778408 ER PT J AU Guzman-Marin, R Suntsova, N Stewart, DR Gong, H Szymusiak, R McGinty, D AF Guzman-Marin, R Suntsova, N Stewart, DR Gong, H Szymusiak, R McGinty, D TI Sleep deprivation reduces proliferation of cells in the dentate gyrus of the hippocampus in rats SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID UNBIASED STEREOLOGICAL ESTIMATION; RECURRENT MAJOR DEPRESSION; ADULT-RAT; PARADOXICAL SLEEP; ANTIDEPRESSANT TREATMENT; RECEPTOR ACTIVATION; PHYSICAL EXERCISE; ENERGY-METABOLISM; GROWTH-FACTOR; WATER MAZE AB The dentate gyrus (DG) of the adult hippocampus gives rise to progenitor cells, which have the potential to differentiate into neurons. To date it is not known whether sleep or sleep loss has any effect on proliferation of cells in the DG. Male rats were implanted for polysomnographic recording, and divided into treadmill sleep-deprived (SD), treadmill control (TC) and cage control (CC) groups. SD and TC rats were kept for 96 h on a treadmill that moved either for 3 s on/ 12 s off (SD group) or for 15 min on/60 min off (TC group) to equate total movement but permit sustained rest periods in TC animals. To label proliferating cells the thymidine analogue 5-bromo-2'deoxyuridine (BrdU) was injected after the first 48 h of the experimental procedure in all groups (50 mg kg(-1), I.P.). The percentage of time awake per day was 93.2% in the SD group vs. 59.6% in the TC group and 49.9% in the CC group (P < 0.001). Stereological analysis showed that the number of BrdU-positive cells in the DG of the dorsal hippocampus was reduced by 54% in the SD group in comparison with the TC and by 68% in comparison with the CC group. These results suggest that sleep deprivation reduces proliferation of cells in the DG of the dorsal hippocampus. C1 VA Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA 91343 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Rostov State Univ, AB Kogan Res Inst Neurocybernet, Rostov Na Donu, Russia. RP McGinty, D (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv 151A3, 16111 Plummer St, North Hills, CA 91343 USA. FU NHLBI NIH HHS [HL60296, P50 HL060296]; NIMH NIH HHS [MH 47480, R01 MH047480] NR 85 TC 92 Z9 95 U1 4 U2 13 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 1 PY 2003 VL 549 IS 2 BP 563 EP 571 DI 10.1113/jphysiol.2003.041665 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 692JR UT WOS:000183658400019 PM 12679377 ER PT J AU Proctor, SP White, RF Heeren, T Debes, F Gloerfelt-Tarp, B Appleyard, M Ishoy, T Guldager, B Suadicani, P Gyntelberg, F Ozonoff, DM AF Proctor, SP White, RF Heeren, T Debes, F Gloerfelt-Tarp, B Appleyard, M Ishoy, T Guldager, B Suadicani, P Gyntelberg, F Ozonoff, DM TI Neuropsychological functioning in Danish Gulf War veterans SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Gulf War veterans; cognitive function; environmental exposures ID PERSIAN-GULF; NEUROBEHAVIORAL DEFICITS; SYMPTOMS; HEALTH; EXPOSURES AB Research has shown that Danish Gulf War (GW) veterans reported a significantly higher prevalence of neuropsychological symptoms than did military controls 6 years after GW deployment. To explore the possible central nervous system determinants of these complaints, neuropsychological tests were administered to stratified, random samples of the Danish cohort of 916 GW-deployed veterans and 236 non-GW-deployed participants. Multivariate analyses of covariance were used to analyze neuropsychological test outcomes among the 215 male participants (143 GW-deployed and 72 non-GW-deployed soldiers). No significant differences in neuropsychological test performances were found between the GW-deployed and non-GW-deployed groups. Troops deployed to the GW reported significantly more mood complaints (i.e., fatigue and confusion) than their nondeployed counterparts. Because they were assigned to the Gulf region during the postcombat phase, Danish GW soldiers differed from the majority of American GW-deployed troops in military assignments and possible toxicant exposures. C1 VA Boston Healthcare Syst Med Ctr, Boston Environm Hazards Ctr, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Bispebjerg Hosp, DK-2400 Copenhagen, Denmark. RP Proctor, SP (reprint author), VA Boston Healthcare Syst Med Ctr, Boston Environm Hazards Ctr, 116B-4,150 S Hungtinton Ave, Boston, MA 02130 USA. OI Ozonoff, David/0000-0002-4281-4171 NR 22 TC 10 Z9 10 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD JUN PY 2003 VL 25 IS 2 BP 85 EP 93 DI 10.1023/A:1023390831355 PG 9 WC Psychology, Clinical SC Psychology GA 668QM UT WOS:000182304700002 ER PT J AU Lindem, K Heeren, T White, RF Proctor, SP Krengel, M Vasterling, J Sutker, PB Wolfe, J Keane, TM AF Lindem, K Heeren, T White, RF Proctor, SP Krengel, M Vasterling, J Sutker, PB Wolfe, J Keane, TM TI Neuropsychological performance in Gulf War era veterans: Traumatic stress symptomatology and exposure to chemical-biological warfare agents SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Gulf War syndrome; posttraumatic stress disorder; chemical-biological warfare agents; anxiety disorders; neuropsychological tests ID INTELLECTUAL RESOURCES; DISORDER; MEMORY; ATTENTION; HEALTH; DEFICITS; SYMPTOMS; PTSD; PSYCHOPATHOLOGY; DYSFUNCTION AB Because complaints of diminished concentration and memory are among the most common health symptoms reported by Gulf War (GW) veterans with unexplained illnesses, this study investigated neuropsychological functions among GW veterans and controls. Relationships between neuropsychological performance, severity of posttraumatic stress disorder (PTSD) symptomatology, and exposure to chemical-biological warfare agents (CBW) were assessed. Participants were 225 veterans recruited from three cohorts: GW-deployed veterans from Ft. Devens, MA (n = 141) and New Orleans, LA (n = 37), and Germany-deployed veterans from a Maine National Guard unit (n = 47). A comprehensive evaluation was completed. Severity of subclinical PTSD symptomatology was significantly related to scores on specific neuropsychological tests. PTSD symptom severity in GW-deployed veterans was found to be greater and associated with a broader range of neuropsychological deficits than in Germany-deployed veterans. PTSD severity was associated with lower performance on a range of neuropsychological tasks, whereas CBW exposure contributed to performance deficits on specific cognitive tasks. C1 VA Boston Healthcare Syst Med Ctr, Boston Environm Hazards Ctr, Dept Psychol, Boston, MA 02130 USA. VA Boston Healthcare Syst, Boston Environm Hazards Ctr, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. Univ So Denmark, Odense, Denmark. VA Med Ctr, New Orleans, LA USA. Tulane Univ, Sch Med Psychiat & Neurol, New Orleans, LA USA. Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP White, RF (reprint author), VA Boston Healthcare Syst Med Ctr, Boston Environm Hazards Ctr, Dept Psychol, 150 S Huntington Ave 116B-4, Boston, MA 02130 USA. NR 50 TC 10 Z9 10 U1 1 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD JUN PY 2003 VL 25 IS 2 BP 105 EP 119 DI 10.1023/A:1023394932263 PG 15 WC Psychology, Clinical SC Psychology GA 668QM UT WOS:000182304700004 ER PT J AU Lindem, K Proctor, SP Heeren, T Krengel, M Vasterling, J Sutker, PB Wolfe, J Keane, TM White, RF AF Lindem, K Proctor, SP Heeren, T Krengel, M Vasterling, J Sutker, PB Wolfe, J Keane, TM White, RF TI Neuropsychological performance in Gulf War era veterans: Neuropsychological symptom reporting SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Gulf War syndrome; neuropsychological tests; health symptoms; cognitive symptoms ID POSTTRAUMATIC-STRESS-DISORDER; NEUROBEHAVIORAL DEFICITS; COGNITIVE COMPLAINTS; BASE RATES; HEALTH; EXPOSURES AB Relationships between broad-based health symptoms and neuropsychological performance have been investigated previously in GulfWar (GW) veterans. However, very little has been done to assess relationships between severity of neuropsychological symptom complaints and performance on objective neuropsychological tests. In this study, relationships between level of self-reported neuropsychological symptom severity and objective neuropsychological performance measures were investigated. Participants included 240 veterans from three GW-era cohorts: GW-deployed veterans recruited from Ft. Devens, MA, (n = 142) and from New Orleans, LA (n = 51), and veterans deployed to Germany from a Maine National Guard unit (n = 47). Findings suggest that level of subjective neuropsychological complaints was associated primarily with mood symptoms in GW-era veterans. Among GW-deployed troops, high neuropsychological symptom reporters endorsed more tension, fatigue, and confusion and less vigor than those reporting fewer cognitive complaints. Current findings emphasize the importance of independent assessment of subjective symptoms and objective neuropsychological performance. C1 VA Boston Healthcare Syst Med Ctr, Boston Environ Hazards Ctr, Dept Psychol, Boston, MA 02130 USA. VA Boston Healthcare Syst, Boston Environ Hazards Ctr, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. Univ So Denmark, Odense, Denmark. VA Med Ctr, New Orleans, LA USA. Tulane Univ, Sch Med Psychiat & Neurol, New Orleans, LA 70118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. RP White, RF (reprint author), VA Boston Healthcare Syst Med Ctr, Boston Environ Hazards Ctr, Dept Psychol, 150 S Huntington Ave 116B-4, Boston, MA 02130 USA. NR 40 TC 4 Z9 4 U1 2 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD JUN PY 2003 VL 25 IS 2 BP 121 EP 127 DI 10.1023/A:1023347016334 PG 7 WC Psychology, Clinical SC Psychology GA 668QM UT WOS:000182304700005 ER PT J AU Lindem, K White, RF Heeren, T Proctor, SP Krengel, M Vasterling, J Wolfe, J Sutker, PB Kirkley, S Keane, TM AF Lindem, K White, RF Heeren, T Proctor, SP Krengel, M Vasterling, J Wolfe, J Sutker, PB Kirkley, S Keane, TM TI Neuropsychological performance in Gulf War era veterans: Motivational factors and effort SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Gulf War syndrome; neuropsychological tests; motivation; malingering ID MILD HEAD TRAUMA; NEUROBEHAVIORAL DEFICITS; TEST-SCORES; EXPOSURES; HEALTH; STRESS AB Assuming that the underlying etiology of unexplained health-related symptoms in returning Gulf War (GW) veterans is multifactorial, the possible role of feigning or exaggeration of symptoms is worth consideration as a contributing factor. The present study assessed the relationship between motivation to perform well during neuropsychological assessment and objective neuropsychological test performance. Motivation was measured as the score on a visual memory task (Test of Memory Malingering, TOMM) of low difficulty. Participants included 77 veterans from the cohorts of GW(n = 58) and Germany-deployed (n = 19) GW-era veterans described in two other papers in this issue who were administered the TOMM. Most veterans earned perfect or near-perfect scores on the TOMM (48-50/50). Scores less than or equal to47 were associated with lower scores on neuropsychological tasks assessing attention, executive functions, and memory. Variability in test performance within and between tasks measuring similar functions was also found in participants with lower TOMM scores. C1 VA Boston Healthcare Syst Med Ctr, Boston Environm Hazards Ctr, Dept Psychol, Boston, MA 02130 USA. VA Boston Healthcare Syst, Boston Environm Hazards Ctr, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. Univ So Denmark, Odense, Denmark. VA Med Ctr, New Orleans, LA USA. Tulane Univ, Sch Med Psychiat & Neurol, New Orleans, LA 70118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. RP White, RF (reprint author), VA Boston Healthcare Syst Med Ctr, Boston Environm Hazards Ctr, Dept Psychol, 150 S Huntington Ave 116B-4, Boston, MA 02130 USA. NR 36 TC 3 Z9 3 U1 2 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD JUN PY 2003 VL 25 IS 2 BP 129 EP 138 DI 10.1023/A:1023399100404 PG 10 WC Psychology, Clinical SC Psychology GA 668QM UT WOS:000182304700006 ER PT J AU Nalbant, S Corominas, H Hsu, B Chen, LX Schumacher, HR Kitumnuaypong, T AF Nalbant, S Corominas, H Hsu, B Chen, LX Schumacher, HR Kitumnuaypong, T TI Ultrasonography for assessment of subcutaneous nodules SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE ultrasonography; subcutaneous nodules; tophi; rheumatoid nodules; musculoskeletal system ID RHEUMATOID-ARTHRITIS; BONE EROSIONS; ULTRASOUND; SONOGRAPHY; APPEARANCES AB Objective. To characterize a variety of subcutaneous lesions by their ultrasonographic (US) appearance, and establish these images as a starting point to measure changes with treatments. Methods. Twenty-six patients with 48 subcutaneous nodular swellings of various types were imaged using a portable US machine equipped with a 10 MHz linear transducer. All patients had a known diagnosis of a rheumatic disease. We used US to examine subcutaneous lesions and the underlying cortical surface of the bone or joint. Two measurements of some tophi and rheumatoid nodules were done on different dates to examine reproducibility of the measurements. Results. Nodular lesions included 20 tophi and 20 rheumatoid nodules, 2 sarcoid nodules, 2 lipomas, and 4 synovial cysts. Tophi most often appeared as heterogeneous masses; hypoechoic areas in 2 tophi were decreased after aspiration of chalky liquid tophaceous material. Occasionally tophi had calcifications appearing hyperechoic with acoustic shadowing. Cortical bone erosions could be seen adjacent to some tophi. The nodules in patients with rheumatoid arthritis were often attached closely to the bone surface and less erosive to bone, allowing the cortical bone to be seen easily. The nodules were more homogeneous. Some showed a central sharply demarcated hypoechoic area, possibly corresponding to necrosis inside the rheumatoid nodules. Nodules were easily measured. The repeated measurements of both tophi and rheumatoid nodules showed excellent reproducibility. Lipomas had different echogenic patterns depending on composition of the associated connective tissue and position of the mass. They could be hypoechogenic, hyperechogenic, or mixed, but were easily distinguished by oval shapes with well demarcated capsules. Synovial cysts seen in this study had a characteristic hypoechoic pattern. Conclusion. Subcutaneous nodules examined by sonography show characteristics and patterns that, although not diagnostic, can be used to help distinguish their etiology. Tophi and rheumatoid nodules can be easily measured and these measurements used to help follow disease progression or response to therapy. C1 Hosp Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Rheumatol Sect, Philadelphia, PA USA. RP Schumacher, HR (reprint author), Univ Penn, VA Med Ctr, Woodland Ave, Philadelphia, PA 19104 USA. NR 34 TC 39 Z9 41 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUN PY 2003 VL 30 IS 6 BP 1191 EP 1195 PG 5 WC Rheumatology SC Rheumatology GA 687BV UT WOS:000183356700011 PM 12784388 ER PT J AU Ang, DC Ibrahim, SA Burant, CJ Kwoh, CK AF Ang, DC Ibrahim, SA Burant, CJ Kwoh, CK TI Is there a difference in the perception of symptoms between African Americans and whites with osteoarthritis? SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE osteoarthritis; joint arthroplasty; ethnicity; health service ID NUTRITION EXAMINATION SURVEY; INDIVIDUAL RADIOGRAPHIC FEATURES; REPORTED FUNCTIONAL STATUS; TOTAL HIP-ARTHROPLASTY; 1ST NATIONAL-HEALTH; OSTEO-ARTHRITIS; RHEUMATOID-ARTHRITIS; KNEE OSTEOARTHRITIS; RACIAL-DIFFERENCES; ETHNIC-DIFFERENCES AB Objective. To determine if there is a difference in the perception of pain and functional disability between African Americans and Whites at any given radiographic severity of osteoarthritis (OA). Ethnic differences in utilization of joint replacement may reflect differences in the perception of symptoms of OA. Methods. A cross-sectional survey included 596 male veterans (44% African Americans and 56% Whites) with chronic moderate to severe knee and/or hip pain at the General Medicine Clinics. The average age of the total cohort was 65.63 +/- 9.5 years. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for pain and function were the primary outcome measures of interest. All knee and or hip radiographs were graded using the Kellgren-Lawrence (K/L) grading system. Results. African Americans and Whites were comparable with respect to age (65 +/- 9.5 vs 66 +/- 9, respectively); body mass index greater than or equal to 30 kg/m(2) (53.9% vs 58.8%); Lequesne severity score (11 +/- 4 vs 11 +/- 4); geriatric depression score (4.5 +/- 3.3 vs 5.0 +/- 3.8) and Charlson Comorbidity Index (2.3 +/- 2 vs 2.5 +/- 2). African Americans had lower socioeconomic status with fewer high school graduates (57% vs 71%, p = 0.001), lower employment rate (8.4% vs 14.7%, p = 0.017), and lower total household incomes (41.4% vs 20.4% reported income < $10,000, p = 0.000). African Americans and Whites were. not different in mean scores for WOMAC pain and WOMAC function when stratified by joint space narrowing, osteophyte and Kellgren Lawrence grades. After controlling for important covariates, ethnicity was not a significant predictor of WOMAC pain and function. Conclusion. In this sample of male veterans, African Americans and Whites perceived the same degree of pain and functional difficulties at any given radiographic severity of OA. Differences in the perception of symptoms cannot explain the observed ethnic disparity in utilization of joint replacement. C1 Indiana Univ, Dept Med, Div Rheumatol, Indianapolis, IN 46202 USA. Case Western Reserve Univ, Sch Med, Dept Bioeth, Cleveland, OH 44106 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Dept Med, Div Rheumatol & Clin Immunol, Pittsburgh, PA USA. RP Ang, DC (reprint author), Indiana Univ, Dept Med, Div Rheumatol, 1110 W Michigan St,Room 545, Indianapolis, IN 46202 USA. NR 47 TC 40 Z9 43 U1 2 U2 4 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 JUN PY 2003 VL 30 IS 6 BP 1305 EP 1310 PG 6 WC Rheumatology SC Rheumatology GA 687BV UT WOS:000183356700030 PM 12784407 ER PT J AU Petchkrua, W Little, JW Burns, SP Stiens, SA James, JJ AF Petchkrua, W Little, JW Burns, SP Stiens, SA James, JJ TI Vitamin B-12 deficiency in spinal cord injury: A retrospective study SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE spinal cord injuries; cyanocobalamin; vitamin B-12 deficiency; anemia; rehabilitation; weakness; paresthesias ID SERUM METHYLMALONIC ACID; COBALAMIN DEFICIENCY; TOTAL HOMOCYSTEINE; PREVALENCE; FOLATE; MACROCYTOSIS; OUTPATIENTS; DIAGNOSIS; SPECTRUM; ANEMIA AB Background/Objective: Vitamin B-12 (or cobalamin) deficiency is well known in geriatric patients, but not in those with spinal cord injury (SCI). This retrospective study describes vitamin B-12 deficiency in SCI. Methods: This study utilized a retrospective chart review of patients with SCI who had received serum vitamin B-12 testing over the last 10 years. Results: Probable vitamin B-12 deficiency was noted in 16 patients with SCI. Twelve patients had subnormal serum vitamin B-12 levels (<220 pg/mL), whereas 4 patients had low-normal vitamin B-12 levels (<300 pg/mL) with neurologic and/or psychiatric symptoms that improved following vitamin B-12 replacement. Classic findings of paresthesias and numbness often were not evident; such findings likely were masked by the pre-existing sensory impairment caused by SCI. Of the 16 SCI patients, 7 were ambulatory; 4 of the 7 presented with deterioration of gait. In addition, 3 of the 16 SCI patients presented with depression and fatigue, 2 had worsening pain, 2 had worsening upper limb weakness, and 2 had memory decline. Of the 12 patients with subnormal serum vitamin B-12 levels, 6 were asymptomatic. Classic laboratory findings of low serum vitamin B-12, macrocytic red blood cell indices, and megaloblastic anemia were not always present. Anemia was identified in 7 of the 16 patients and macrocytic red blood cells were found in 3 of the 16 patients. Only I of the 16 SCI patients had a clear pathophysiologic mechanism to explain the vitamin B-12 deficiency (ie, partial gastrectomy); none of the patients were vegetarian. Twelve of the SCI patients appeared to experience clinical benefits from cyanocobalamin replacement (some patients experienced more than I benefit), including reversal of anemia (5 patients), improved gait (4 patients), improved mood (3 patients), improved memory (2 patients), reduced pain (2 patients), strength gain (I patient), and reduced numbness (I patient). Conclusion: It is recommended that physicians consider vitamin B-12 deficiency in their patients with SCI, particularly in those with neurologic and/or psychiatric symptoms. These symptoms often are reversible if treatment is initiated early. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv S 128, Seattle, WA 98108 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Little, JW (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv S 128, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 29 TC 9 Z9 10 U1 1 U2 3 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD SUM PY 2003 VL 26 IS 2 BP 116 EP 121 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 739PH UT WOS:000186355300003 PM 12828286 ER PT J AU Barber, D Foster, D Rogers, S AF Barber, D Foster, D Rogers, S TI The importance of nutrition in the care of persons with spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Editorial Material ID VITAMIN-B-12 DEFICIENCY; METFORMIN C1 S Texas Vet Healthcare Syst, Spinal Cord Injury Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Rehabil Med, San Antonio, TX USA. RP Barber, D (reprint author), S Texas Vet Healthcare Syst, Spinal Cord Injury Ctr, San Antonio, TX USA. NR 5 TC 2 Z9 2 U1 0 U2 3 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD SUM PY 2003 VL 26 IS 2 BP 122 EP 123 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 739PH UT WOS:000186355300004 PM 12828287 ER PT J AU Guihan, M Goldstein, B Smith, BM Schwartz, A Manheim, LM AF Guihan, M Goldstein, B Smith, BM Schwartz, A Manheim, LM TI SCI health care provider attitudes about pressure ulcer management SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE spinal cord injuries; pressure ulcers; clinical practice variations; medical decision making; quality enhancement research initiative (QUERI) AB Background/Objective: To evaluate the variability in clinical decisions about pressure ulcer management for persons with spinal cord injury (SCI) and expand understanding of the various factors influencing variability. Methods: Eighty-one SCI physicians and nurses completed a survey on pressure ulcer management. Patient scenarios were used to assess the effect of patient characteristics on provider decisions regarding inpatient treatment of severe pressure ulcers, surgery vs medical management, and amount of healing before discharge. Results: The availability of social support to facilitate bed rest appears to be a more important factor in deciding whether the patient is managed at home vs in the hospital than is the level of injury. Medical condition does not appear to influence surgical vs medical management of severe pressure ulcers. For patients with poor social support, more healing was required before discharge, regardless of their medical condition. Providers were queried about other issues that influence management, including inpatient resource availability, patient preferences, the availability and quality of local home care, and the availability and use of formal care protocols. Respondents were virtually unanimous in their agreement that patients who are compliant with prevention measures can avoid ulcer development. Conclusion: Like many health care providers, those who provide care to people with SCI are struggling to provide quality care to improve their patients' lives in the absence of good evidence to guide their treatment decisions. The results of the present study indicate that in situations in which there is no strong empirical evidence, variation in care provided is extensive. C1 Edward Hines Jr Vet Adm Hosp, Midwest Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. VA Puget Sound Hlth Care Syst, Spinal Cord Injury & Disorders Strateg Healthcare, Seattle, WA USA. Edward Hines Jr Vet Adm Hosp, Spinal Cord Qual Enhancement Res Initiat, Dept Vet Affairs Hlth Serv Res & Dev Serv, Hines, IL USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Illinois, Coll Med, Dept Med Educ, Chicago, IL USA. Northwestern Univ, Inst Hlth Serv Res & Policy Studies, Evanston, IL USA. RP Guihan, M (reprint author), Edward Hines Jr Vet Adm Hosp, Midwest Ctr Hlth Serv & Policy Res, 151H,5th Ave & Roosevelt Rd, Hines, IL 60141 USA. RI Schwartz, Alan/G-2814-2010; OI Schwartz, Alan/0000-0003-3809-6637 NR 10 TC 2 Z9 2 U1 0 U2 1 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD SUM PY 2003 VL 26 IS 2 BP 129 EP 134 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 739PH UT WOS:000186355300006 PM 12828289 ER PT J AU Corfman, TA Cooper, RA Boninger, ML Koontz, AM Fitzgerald, SG AF Corfman, TA Cooper, RA Boninger, ML Koontz, AM Fitzgerald, SG TI Range of motion and stroke frequency differences between manual wheelchair propulsion and pushrim-activated power-assisted wheelchair propulsion SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE wheelchair propulsion; range of motion; upper limb; kinematics ID SPINAL-CORD INJURY; UPPER EXTREMITY; MECHANICAL EFFICIENCY; COORDINATE SYSTEM; BIOMECHANICS; KINEMATICS; SHOULDER; RESPONSES; POSITION; KINETICS AB Background/Objective: The objective of this study was to examine the use and efficacy of a pushrim-activated power-assist wheelchair (PAPAW) in the reduction of upper extremity range of motion (ROM) and stroke frequency in manual wheelchair users. Methods: Ten manual wheelchair users were evaluated using a repeated-measures design with and without the use of a PAPAW for maximum ROM of shoulder flexion/extension, abduction/adduction, internal/external rotation, and horizontal flexion/extension; elbow flexion/extension; wrist flexion/extension, supination/pronation, and ulnar/radial deviation; and stroke frequency. Participants propelled a Quickie 2 manual wheelchair configured as a PAPAW and their own wheelchair on a computer-controlled dynamometer at 3 different resistance levels and 2 different speeds. Results: The use of the PAPAW significantly (P < 0.05) decreased shoulder flexion/extension and horizontal flexion/extension, elbow flexion/extension, and wrist flexion/extension and ulnar/radial deviation for many speed and resistance combinations. Univariate analysis revealed that stroke frequency was unaltered in all cases. Conclusion: These findings provide the foundation for studying the utility of the PAPAW in reducing the risk of upper limb injury and neuropathy in the manual wheelchair user population. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Ctr Excellence Wheelchairs & Related Technol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Ctr Excellence Wheelchairs & Related Technol, 151 R1,7180 Highland Dr, Pittsburgh, PA 15261 USA. OI Boninger, Michael/0000-0001-6966-919X NR 31 TC 23 Z9 24 U1 1 U2 6 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD SUM PY 2003 VL 26 IS 2 BP 135 EP 140 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 739PH UT WOS:000186355300007 PM 12828290 ER PT J AU McRae, AL Budney, AJ Brady, KT AF McRae, AL Budney, AJ Brady, KT TI Treatment of marijuana dependence: a review of the literature SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Review DE marijuana; substance use disorders; psychotherapy; pharmacotherapy; cannabinoid receptors ID RANDOMIZED CONTROLLED TRIAL; ADULTS SEEKING TREATMENT; CANNABIS USE; AVERSION THERAPY; WITHDRAWAL; RECEPTOR; ALCOHOLICS; INCENTIVES; PLACEBO; HUMANS AB Until recently, relatively little research has focused on the treatment of marijuana abuse or dependence; however, marijuana use disorders are now receiving increased attention. This paper reviews the initial clinical trials evaluating the efficacy of outpatient treatments for adult marijuana dependence. Findings from five controlled trials of psychotherapeutic interventions suggest that this disorder appears responsive to the same types of treatment as other substance dependencies. Moreover, these initial studies suggest that many patients do not show a positive treatment response, indicating that marijuana dependence is not easily treated. Strengths and weaknesses of the data are presented. Preliminary data from less controlled studies relevant to the treatment of marijuana dependence are discussed to suggest future research areas. Although very few studies on treatment for marijuana abuse and dependence have been completed, the initial reports identify promising treatment approaches and demonstrate a need for more research on the development of effective interventions. (C) 2003 Elsevier Inc. All rights reserved. C1 Ralph H Johnson VAMC, MUSC CTN, Charleston, SC 29401 USA. Treatment Res Ctr, S Burlington, VT 05403 USA. RP McRae, AL (reprint author), Ralph H Johnson VAMC, MUSC CTN, 109 Bee St, Charleston, SC 29401 USA. RI McRae-Clark, Aimee/I-3341-2013 OI McRae-Clark, Aimee/0000-0002-9774-318X FU NIDA NIH HHS [DA00435, DA12157, DA15440] NR 44 TC 65 Z9 67 U1 4 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JUN PY 2003 VL 24 IS 4 BP 369 EP 376 DI 10.1016/S0740-5472(03)00041-2 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 705JX UT WOS:000184392900012 PM 12867212 ER PT J AU McCracken, JT Biederman, J Greenhill, LL Swanson, JM McGough, JJ Spencer, TJ Posner, K Wigal, S Pataki, C Zhang, YX Tulloch, S AF McCracken, JT Biederman, J Greenhill, LL Swanson, JM McGough, JJ Spencer, TJ Posner, K Wigal, S Pataki, C Zhang, YX Tulloch, S TI Analog classroom assessment of a once-daily mixed amphetamine formulation, SLI381 (ADDERALL XR), in children with ADHD SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; amphetamine; Adderall (R); ADDERALL XR (TM); stimulant; children ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; SUSTAINED-RELEASE; STANDARD METHYLPHENIDATE; STIMULANT MEDICATION; RESPONSE ANALYSIS; TIME-RESPONSE; DOUBLE-BLIND; BEHAVIOR; DEXTROAMPHETAMINE AB developed as a once-daily treatment for children with attention-deficit/hyperactivity disorder (ADHD). Secondary objectives included examination of the time course, pharmacokinetic, and pharmacodynamic properties of SLI381. Method: This was a randomized, double-blind, crossover study of three doses of SL1381 (10, 20, and 30 mg), placebo, and an active control (Adderall(R) 10 mg) given once daily to 51 children with ADHD. Weekly assessments in an analog classroom setting included blind ratings of attention and deportment and a performance measure (math test) obtained every 1.5 hours over a 12-hour period. Results: SL1381 was well tolerated. All active treatment conditions displayed significant time course effects and were superior to placebo in improving efficacy measures. Dose-dependent improvements were evident for SLI381. SLI381 20 and 30 mg and Adderall all showed rapid improvements by 1.5 hours, but only the SLI381 20 and 30-mg doses showed continued activity at 10.5 and 12 hours for classroom behavior and math test performance versus placebo. Conclusions: These data provide support for the benefit of this novel, once-daily amphetamine preparation in the treatment of ADHD. The longer duration of action of SL1381 has the potential to simplify psychostimulant dosing, thus reducing dose diversion and eliminating the need for in-school administration. SLI381 appears to be a useful treatment option for many children with ADHD. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Div Child & Adolescent Psychiat, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Columbia Univ, Dept Psychiat, New York, NY USA. Univ Calif Irvine, Child Dev Ctr, Irvine, CA 92717 USA. Shire Pharmaceut Dev Inc, Rockville, MD USA. RP McCracken, JT (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Div Child & Adolescent Psychiat, 760 Westwood Plaza, Los Angeles, CA 90024 USA. NR 33 TC 69 Z9 69 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2003 VL 42 IS 6 BP 673 EP 683 DI 10.1097/01.CH1.0000046863.56865.FE PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 681DQ UT WOS:000183022000013 PM 12921475 ER PT J AU McGough, JJ Biederman, J Greenhill, LL McCracken, JT Spencer, TJ Posner, K Wigal, S Gornbein, J Tulloch, S Swanson, JM AF McGough, JJ Biederman, J Greenhill, LL McCracken, JT Spencer, TJ Posner, K Wigal, S Gornbein, J Tulloch, S Swanson, JM TI Pharmacokinetics of SLI381 (ADDERALL XR), an extended-release formulation of Adderall SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention deficit; pharmacokinetics; amphetamine; ADDERALL XR ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; RESPONSE ANALYSIS; TIME-RESPONSE; CHILDREN; AMPHETAMINE; METHYLPHENIDATE; DEXTROAMPHETAMINE; LEVOAMPHETAMINE; BEHAVIOR AB To assess the pharmacokinetic (PK) properties of a single daily dose of Adderall@ (mixed amphetamine salts) and the extended-release formulation, SLI381 (ADDERALL XRTM), in pediatric attention-deficit/hyperactivity disorder (ADHD). Method: Fifty-one children (aged 6-12 years) with ADHD participated in a 6-week, seven-visit, PK and pharmacodynamic study. PK sampling occurred during visit 1 and again at visit 7. At visit 1, subjects received an initial oral dose of SLI381, 20 mg. At visit 7 subjects completed 1 week of medication treatment following random assignment to once-daily orally dosed SLI381 10 mg, 20 mg, or 30 mg; Adderall 10 mg; or placebo. Results: PK parameters evidenced substantial intersubject variability (coefficients of variation = 28-56%). Time to maximum concentration (T-max) for SLI381 versus Adderall showed average increases of 3.0 hours for dextroamphetamine (t= -2.35, p =.04, df = 8.6) and 3.2 hours for levoamphetamine (t= -2.39, p =.04, df = 9.2). The d- and I-isomer concentrations were highly correlated and approximated a 3:1 ratio. Conclusions: SLI381 showed extended T-max values compared with Adderall and appears suitable for once-daily dosing. Intersubject variability underscores the need for individual dose titration. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Div Child & Adolescent Psychiat, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Columbia Univ, Dept Psychiat, New York, NY 10027 USA. Univ Calif Irvine, Child Dev Ctr, Irvine, CA 92717 USA. Univ Calif Los Angeles, Sch Med, Dept Biomath, Los Angeles, CA 90024 USA. Shire Pharmaceut Dev Inc, Rockville, MD USA. RP McGough, JJ (reprint author), 300 UCLA Med Plaza,Suite 1414, Los Angeles, CA 90095 USA. FU NIMH NIH HHS [MH01966] NR 20 TC 46 Z9 46 U1 2 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2003 VL 42 IS 6 BP 684 EP 691 DI 10.1097/01.CH1.0000046850.56865.CB PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 681DQ UT WOS:000183022000014 PM 12921476 ER PT J AU Friedlander, AH Marder, SR Pisegna, JR Yagiela, JA AF Friedlander, AH Marder, SR Pisegna, JR Yagiela, JA TI Alcohol abuse and dependence - Psychopathology, medical management and dental implications SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID GASTROESOPHAGEAL REFLUX DISEASE; PLACEBO-CONTROLLED TRIAL; EPIDERMAL GROWTH-FACTOR; ORAL HYGIENE; MANDIBULAR FRACTURES; NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; SUBSTANCE-ABUSE; HEAVY DRINKERS; OPIOID SYSTEM AB Background. The authors review the clinical features, epidemiology, pathophysiology, medical management, dental findings and dental treatment of patients with alcoholism. Literature Reviewed. The authors conducted a MEDLINE search for 1995 through 2001 using the key terms of alcoholism, epidemiology, pathophysiology, treatment and dentistry. Reports selected for further review included those published in English in peer-reviewed journals. The authors gave preference to articles reporting randomized, controlled trials. Conclusions. Alcoholism is a chronic and progressive psychiatric illness that afflicts more than 14 million Americans. It is characterized by a loss of control over the use of alcohol, resulting in impaired social functioning, and the consequent development of medical illnesses. The disease arises in genetically vulnerable people when they are overwhelmed by their cravings for the alcohol-associated euphoria that results from the actions of several neurotransmitter systems in the brain's pleasure center. New medications to counteract alcohol-induced neurotransmission imbalance may assist patients in reducing their craving. Clinical Implications. The prevalence of dental disease usually is extensive because of a disinterest in performing appropriate oral hygiene techniques and diminished salivary flow. Concurrent abuse of tobacco products worsens dental disease and heightens the risk of developing oral cancer. Identification of the alcohol-abusing patient, a cancer-screening examination, preventive dental education, and use of saliva substitutes and anticaries agents are indicated. Special precautions must be taken when performing surgery and when prescribing or administering analgesics, antibiotics or sedative agents that are likely to have an adverse interaction with alcohol or psychiatric medications. C1 VA Greater Los Angeles Healthcare Syst, Chair Psychiat, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Med Ctr, Qual Assurance Hosp Dent Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Dept Vet Affairs, VISN 22, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, Los Angeles, CA 90073 USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, Chair Psychiat, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Reis, Aline/G-9573-2012 NR 96 TC 25 Z9 30 U1 4 U2 10 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUN PY 2003 VL 134 IS 6 BP 731 EP 740 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 693LK UT WOS:000183718900018 PM 12839410 ER PT J AU Saunders, MJ AF Saunders, MJ TI Still waiting for the revolution in aging SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. RP Saunders, MJ (reprint author), UTHSCSA, MC 7921,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 51 IS 6 BP 877 EP 878 DI 10.1046/j.1365-2389.2003.51274.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 681RM UT WOS:000183049200023 PM 12757580 ER PT J AU Drummond, I AF Drummond, I TI The skate weighs in on kidney regeneration SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID ACUTE-RENAL-FAILURE; BONE-MARROW; CELLS C1 Harvard Univ, Sch Med, Dept Med, Charlestown, MA USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA USA. RP Drummond, I (reprint author), Renal Unit, MGH 149-8000,149 13th St, Charlestown, MA 02129 USA. NR 15 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 2003 VL 14 IS 6 BP 1704 EP 1705 DI 10.1097/01.ASN.0000072725.30005.03 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 682MK UT WOS:000183095600033 PM 12761273 ER PT J AU Bonventre, JV AF Bonventre, JV TI Dedifferentiation and proliferation of surviving epithelial cells in acute renal failure SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT Meeting on Renal Epithelial Cells: Differentiation and Plasticity CY JUN 14-15, 2002 CL COUDRAY MONTCEAUX, FRANCE ID KIDNEY INJURY MOLECULE-1; HEPATOCYTE GROWTH-FACTOR; ACUTE TUBULAR-NECROSIS; ISCHEMIC-INJURY; RAT-KIDNEY; ADHESION MOLECULES; POLYSIALIC ACID; NEUROTROPHIC FACTOR; RGD PEPTIDES; IN-VITRO AB In contrast to the heart or brain, the kidney can completely recover from an ischemic or toxic insult that results in cell death. During recovery from ischemia/reperfusion injury, surviving tubular epithelial cells dedifferentiate and proliferate, eventually replacing the irreversibly injured tubular epithelial cells and restoring tubular integrity. Repair of the kidney parallels kidney organogenesis in the high rate of DNA synthesis and apoptosis and in patterns of gene expression. As has been shown by proliferating cell nuclear antigen and 5-bromo 2'-deoxyuridine labeling studies and, in unpublished studies, by counting mitotic spindles identified by labeling with antitubulin antibody, the proliferative response is rapid and extensive, involving many of the remaining cells of the proximal tubule. This extensive proliferative capacity is interpreted to reflect the intrinsic ability of the surviving epithelial cell to adapt to the loss of adjacent cells by dedifferentiating and proliferating. Adhesion molecules likely play important roles in the regulation of renal epithelial cell migration, proliferation, and differentiation, as do cytokines and chemokines. Better understanding of all of the characteristics resulting in dedifferentiation and proliferation of the proximal tubule epithelial cell and cell-cell and cell-matrix interactions important for this repair function will lead to novel approaches to therapies designed to facilitate the processes of recovery in humans. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Masachusetts Inst Technol, Div Hlth Sci & Technol, Charlestown, MA USA. RP Bonventre, JV (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK 38452, DK 39773]; NINDS NIH HHS [NS 10828] NR 80 TC 302 Z9 310 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 2003 VL 14 IS 6 SU 1 BP S55 EP S61 DI 10.1097/01.ASN.0000067652.51441.21 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 683PJ UT WOS:000183157700011 PM 12761240 ER PT J AU Ripoll, J Ntziachristos, V AF Ripoll, J Ntziachristos, V TI Iterative boundary method for diffuse optical tomography SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID PHOTON DENSITY WAVES; LIGHT; SCATTERING; BREAST; APPROXIMATION; SPECTROSCOPY; MAMMOGRAPHY; EQUATIONS; SURFACES; JOINTS AB The recent application of tomographic methods to three-dimensional imaging through tissue by use of light often requires modeling of geometrically complex diffuse-nondiffuse boundaries at the tissue-air interface. We have recently investigated analytical methods to model complex boundaries by means of the Kirchhoff approximation. We generalize this approach using an analytical approximation, the N-order diffuse-reflection boundary method, which considers higher orders of interaction between surface elements in an iterative manner. We present the general performance of the method and demonstrate that it can improve the accuracy in modeling complex boundaries compared with the Kirchhoff approximation. in the cases of small diffuse volumes or low absorption. Our observations are also contrasted with exact solutions. We furthermore investigate optimal implementation parameters and show that a second-order approximation is appropriate for most in vivo investigations. (C) 2003 Optical Society of America. C1 Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion 71110, Greece. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Ripoll, J (reprint author), Fdn Res & Technol Hellas, Inst Elect Struct & Laser, POB 1527, Iraklion 71110, Greece. RI Ripoll, Jorge/J-8134-2012 OI Ripoll, Jorge/0000-0001-8856-7738 FU NCI NIH HHS [R21-CA91807]; NIBIB NIH HHS [1 R01 EB000750-1] NR 39 TC 24 Z9 26 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0740-3232 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD JUN PY 2003 VL 20 IS 6 BP 1103 EP 1110 DI 10.1364/JOSAA.20.001103 PG 8 WC Optics SC Optics GA 683DE UT WOS:000183131500015 PM 12801178 ER PT J AU Italiano, JE Shivdasani, RA AF Italiano, JE Shivdasani, RA TI Megakaryocytes and beyond: the birth of platelets SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Review DE megakaryocyte; platelet assembly; platelet biogenesis; proplatelet; thrombopoiesis ID TRANSCRIPTION FACTOR NF-E2; BERNARD-SOULIER-SYNDROME; DEMARCATION MEMBRANE SYSTEM; HERMANSKY-PUDLAK-SYNDROME; ZINC-FINGER PROTEIN; BONE-MARROW; CIRCULATING MEGAKARYOCYTES; BLOOD-PLATELET; MPL LIGAND; IN-VITRO AB Megakaryocytes are highly specialized precursor cells that differentiate to produce blood platelets via intermediate cytoplasmic extensions known as proplatelets. Recent advances in the understanding of megakaryocyte differentiation and platelet formation rely on a combination of genetic and cell biological studies with detailed structural analysis of cultured cells. Visualization of sequential steps in endomitosis has expanded our views on how megakaryocytes acquire polyploid DNA content, whereas studies in mouse models of platelet disorders provide clues into transcriptional pathways and those leading to the assembly of platelet-specific secretory granules. The experimental findings forge stronger links between cellular processes and molecular mechanisms, while observation of the underlying morphologic events in beginning to yield insights into the cytoskeletal mechanics of proplatelet formation. Here we review salient aspects of the emerging appreciation of the cellular and molecular basis of thrombopoiesis. 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, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL 63143, HL 68130] NR 120 TC 91 Z9 98 U1 0 U2 11 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 JUN PY 2003 VL 1 IS 6 BP 1174 EP 1182 DI 10.1046/j.1538-7836.2003.00290.x PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 695GV UT WOS:000183823500012 PM 12871316 ER PT J AU Carew, JA Jackson, AA Bauer, KA AF Carew, JA Jackson, AA Bauer, KA TI ARP1 interacts with the 5 ' flanking region of the coagulation factor VII gene SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE coagulation; factor VII; transcription ID PROMOTER-TRANSCRIPTION FACTOR; RETINOID-X-RECEPTOR; BINDING-SITE; COUP-TF; HORMONE; SUPERFAMILY; MUTATION; HNF-4; DNA; EXPRESSION AB Factor (F)VII plays a critical role in initiation of coagulation. Several segments within the 5' flanking region of the FVII gene were previously demonstrated to recognize hepatic nuclear proteins, but few have been identified. To identify a regulatory protein binding the nuclear hormone response region (-237 to -200) of the FVII 5' flanking region and demonstrate that the interaction is functional. Electrophoretic mobility shift assays and mutation analysis showed that ARP1, an orphan nuclear hormone receptor, interacted with two regions of the FVII 5' flanking region, the hepatic nuclear factor 4 binding region (-77 to -47) and the nuclear hormone response region (-237 to -200). Transfection experiments demonstrated that reporter gene expression was decreased from vectors including the nuclear hormone response segment compared with that containing only the minimal promoter between positions -109 and +1, and that ARP1 also repressed expression through an interaction with the minimal promoter. These data indicate a role for ARPI in transcriptional modulation of the FVII gene. C1 VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Carew, JA (reprint author), VA Boston Healthcare Syst, Bldg 3,Room 2A106 151,1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 28 TC 5 Z9 5 U1 0 U2 1 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 JUN PY 2003 VL 1 IS 6 BP 1220 EP 1227 DI 10.1046/j.1538-7836.2003.00227.x PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 695GV UT WOS:000183823500019 PM 12871323 ER PT J AU Borthakur, G Cruz, MA Dong, JF McIntire, L Li, F Lopez, JA Thiagarajan, P AF Borthakur, G Cruz, MA Dong, JF McIntire, L Li, F Lopez, JA Thiagarajan, P TI Sulfatides inhibit platelet adhesion to von Willebrand factor in flowing blood SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE glycoprotein Ib; sulfatides; von Willebrand factor ID FACTOR A1 DOMAIN; GLYCOPROTEIN IB-ALPHA; HUMAN VONWILLEBRAND-FACTOR; VIII-RELATED PROTEIN; CRYSTAL-STRUCTURE; TERMINAL DOMAIN; BINDING DOMAIN; HUMAN-PLASMA; COLLAGEN; SEQUENCE AB Sulfatides are sulfated glycosphingolipids present on cell surfaces that bind to adhesive proteins such as von Willebrand factor (VWF), P-selectin, laminin and thrombospondin. Previous Studies have localized the sulfatide-binding site of VWF to amino acid residues Gln626-Val646 in the At domain. The A1 domain also contains the binding site for platelet glycoprotein Ib (GP Ib), a site that has been reported to be distinct from the sulfatide-binding site. In this study, we analyzed the interaction of sulfatides with VWF and its effect on GP Ib-mediated platelet adhesion under flow conditions. Recombinant VWF A I domain (rVWF-A1) bound specifically and saturably to sulfatides (half-maximal concentration of similar to 12.5 mug mL(-1)), binding that was blocked by dextran sulfate (IC50 approximate to 100 mug mL(-1)) but not by heparin at concentrations up to 100 U mL(-1). Furthermore, sulfatides (125 mug mL(-1)) prevented the adhesion of platelets or glycocalicin-coupled polystyrene beads to a rVWF-A1-coated surface under high shear stress. In addition, plasma VWF prebound to a sulfatide-coated surface failed to support subsequent platelet adhesion. These results provide firm evidence that sulfatides bind the VWFA1 domain at a site overlapping the GP Ib-binding site. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Hematol, Houston, TX USA. Baylor Coll Med, Thrombosis Res Sect, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Rice Univ, Cox Lab Biomed Engn, Houston, TX 77251 USA. RP Thiagarajan, P (reprint author), VA Med Ctr, Mail 113,2002 Holcombe Blvd, Houston, TX 77030 USA. FU NHLBI NIH HHS [HL 65096, P50 HL 65967] NR 34 TC 26 Z9 26 U1 1 U2 4 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 JUN PY 2003 VL 1 IS 6 BP 1288 EP 1295 DI 10.1046/j.1538-7836.2003.00156.x PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 695GV UT WOS:000183823500028 PM 12871332 ER PT J AU Gibson, CM Kirtane, AJ Murphy, SA Karha, J Cannon, CP Giugliano, RP Roe, MT Harrington, RA Ohman, EM Antman, EM AF Gibson, CM Kirtane, AJ Murphy, SA Karha, J Cannon, CP Giugliano, RP Roe, MT Harrington, RA Ohman, EM Antman, EM TI Distance from the coronary ostium to the culprit lesion in acute ST-elevation myocardial infarction and its implications regarding the potential prevention of proximal plaque rupture SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE acute myocardial infarction; percutaneous coronary intervention; drug-eluting stents ID COMBINATION REPERFUSION THERAPY; ANGIOGRAPHIC FOLLOW-UP; ARTERY DISEASE; TIMI 14; ANGIOPLASTY; TRIAL; STENT; SITE; THROMBOLYSIS; RESTENOSIS AB Background: Shorter distances from the coronary ostia to culprit lesions have been associated with a higher incidence of adverse outcomes in ST elevation acute myocardial infarction (STEMI). As drug-eluting stents are associated with low rates of restenosis and formation of a stable intima, we sought to develop a mathematical model to estimate how far down the coronary artery a drug-eluting stent would have to be placed to theoretically mitigate the risk of proximal plaque rupture. Objectives and Methods: Distances from the ostia to the end of the culprit lesions were planimetered in 1,914 patients from the TIMI 14, INTEGRITI, FASTER and ENTIRE/ TIMI 23 trials. Results: The first 60 mm of the coronary artery contained 75% of STEMI culprit lesions. The median distance from the vessel ostium to the end of the culprit lesion was 43 mm ( mean 50 +/- 34) and the relative distance from the vessel ostium to the end of the lesion was 29% ( mean 33 +/- 17%) of the total culprit artery length. Diabetes was the only baseline clinical characteristic associated with a longer absolute distance to the end of the culprit lesion ( 46 mm vs. 43 mm, p = 0.03) as well as relative to total artery length (31% vs. 29%, p = 0.04). Median distances from the artery ostium to the end of the culprit lesion were shortest among the left anterior descending culprits ( 40 mm), followed by circumflex lesions ( 43 mm) and then right coronary artery lesions ( 47 mm, 3-way p< 0.0001). Conclusion: The majority of culprit lesions in STEMI are contained within the proximal 30% of the major epicardial coronary arteries, but the distance varies depending upon which epicardial artery is involved. Cumulative distribution functions are presented to allow estimation of the percent of culprit lesions lying proximal to any given distance from the ostium to model the feasibility of prophylactic drug-eluting stenting to minimize the risk of subsequent proximal plaque rupture. C1 Brigham & Womens Hosp, Dept Med, TIMI Data Coordinating Ctr, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA USA. Duke Clin Res Inst, Durham, NC USA. Univ N Carolina, Chapel Hill, NC 27515 USA. RP Gibson, CM (reprint author), Brigham & Womens Hosp, Dept Med, TIMI Data Coordinating Ctr, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@perfuse.org NR 35 TC 31 Z9 32 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD JUN PY 2003 VL 15 IS 3 BP 189 EP 196 DI 10.1023/B:THRO.0000011374.60110.bc PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 761XJ UT WOS:000187940500007 PM 14739628 ER PT J AU Piontek, FA Coscia, R Marselle, CS Korn, RL Zarling, EJ AF Piontek, FA Coscia, R Marselle, CS Korn, RL Zarling, EJ TI Impact of American College of Surgeons verification on trauma outcomes SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE trauma system; outcomes; mortality; cost; American College of Surgeons verification ID LEVEL-I; SEVERITY SCORE; CARE; MORTALITY; CENTERS; SYSTEM; VOLUME; STATE; REGIONALIZATION; COMPLICATIONS AB Objective: The purpose of this study was to compare the impact of trauma patient outcomes before and after Level 11 American College of Surgeons (ACS) verification was received in a not-for-profit community hospital. Methods: This was a retrospective analysis of hospital discharge data for timeframes before and after Level II ACS verification was conducted. Originally, 8,674 patients were identified using the International Classification of Diseases, 9th Revision codes for trauma. These data were parsed to 7,811 patients by using International Classification of Diseases, 9th Revision codes 800xx through 959.9x, which signify an admitting diagnosis of trauma; 3,835 of the patients were admitted after the July 28, 1998, verification date. Blunt injuries constituted the vast majority of the patients (n = 7,488). Outcome measures studied included changes in length of stay (LOS), mortality, and total cost. Internal control was coronary artery bypass graft patients at the same hospital, and external control was trauma patients at a non-ACS hospital over the same time period. Data are presented with p values and SE and the ratio of observed/expected values on the basis of the all-payer severity-adjusted diagnosis-related group severity model. Results: The two timeframes exhibited statistically different outcomes in several variables. Adjusting for severity postverification, LOS was 10% less (p < 0.000). Similarly, severity-adjusted mortality observed/expected ratios were significantly different: 0.81 before versus 0.59 after (p < 0.000). The severity-adjusted ratio of costs found that the postverification era was 5% lower (p < 0.000). The contribution margin of the trauma patient population to the hospital well exceeded any postverification costs. Both control groups exhibited no significant changes in their severity-adjusted outcomes, which could have invalidated these results. Conclusion: This study suggests that the efforts and resources consumed achieving ACS Level II trauma center verification appear to result in desired outcomes as evidenced by decreased LOS, reduced in-hospital mortality rates, reduced cost, and improved contribution margins. C1 Trin Hlth Informat Syst, South Bend, IN 46628 USA. St Alphonsus Reg Med Ctr, Boise, ID USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. US Dept Vet Affairs, Hines, IL USA. RP Piontek, FA (reprint author), Trin Hlth Informat Syst, 3575 Moreau Court, South Bend, IN 46628 USA. OI Luchette, Fred/0000-0002-8857-9111 NR 27 TC 31 Z9 32 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD JUN PY 2003 VL 54 IS 6 BP 1041 EP 1046 DI 10.1097/01.TA.0000061107.55798.31 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 693PR UT WOS:000183727400001 PM 12813321 ER PT J AU Bolton, EE Glenn, DM Orsillo, S Roemer, L Litz, BT AF Bolton, EE Glenn, DM Orsillo, S Roemer, L Litz, BT TI The relationship between self-disclosure and symptoms of posttraumatic stress disorder in peacekeepers deployed to Somalia SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE self-disclosure; peacekeeping ID VIETNAM VETERANS; PSYCHIATRIC SYMPTOMATOLOGY; RISK-FACTORS; PTSD; SAMPLE; WAR; PREDICTORS; EXPOSURE; SUPPORT; VICTIMS AB The challenges of peacekeeping place individuals at risk for the development of significant psychological distress (e.g., B. T. Litz, S. Orsillo, M. Freidman, P. Ehlich, & A. Batres, 1997). Self-disclosure has been shown to ameliorate psychological distress following exposure to potentially traumatic events (J. W. Pennebaker & K. D. Harber, 1993). Sharing, or self-disclosure of deployment-related experiences, was the focus of this study and was hypothesized to be associated with adaptation. As part of a larger investigation, 426 U. S. military personnel who served as peacekeepers in Somalia were administered a comprehensive psychosocial questionnaire that included measures of exposure to negative and potentially traumatic experiences, reception at homecoming, self-disclosure, and PTSD symptom severity. The results indicate that adjustment to peacekeeping is significantly related to self-disclosure, especially to supportive significant others. C1 Boston Univ, Sch Med, Boston Dept Vet Affairs Med Ctr, Psychol Serv 116B2,Behav Sci Div,Natl Ctr Posttra, Boston, MA 02130 USA. Univ N Carolina, Chapel Hill, NC USA. DVAMC, Womens Hlth Sci Div, Boston, MA USA. Univ Massachusetts, Boston, MA 02125 USA. RP Bolton, EE (reprint author), Boston Univ, Sch Med, Boston Dept Vet Affairs Med Ctr, Psychol Serv 116B2,Behav Sci Div,Natl Ctr Posttra, 150 S Huntington Ave, Boston, MA 02130 USA. OI Roemer, Lizabeth/0000-0002-2453-5435 NR 23 TC 44 Z9 45 U1 0 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2003 VL 16 IS 3 BP 203 EP 210 DI 10.1023/A:1023754820991 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 678DL UT WOS:000182849700001 PM 12816331 ER PT J AU Smith, MR Eastham, J Gleason, DM Shasha, D Tchekmedyian, S Zinner, N AF Smith, MR Eastham, J Gleason, DM Shasha, D Tchekmedyian, S Zinner, N TI Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE diphosphonates; prostatic neoplasms; bone density; osteoporosis ID MINERAL DENSITY; PAMIDRONATE; CARCINOMA; WOMEN AB Purpose: A multicenter double-blind, randomized, placebo controlled clinical trial was performed to assess the effect of zoledronic acid, a potent new bisphosphonate, on bone mineral density during androgen deprivation therapy for non-metastatic prostate cancer. Materials and Methods: Men with MO (no distant metastases) prostate cancer beginning androgen deprivation therapy were randomly assigned to receive 4 mg. zoledronic acid or placebo intravenously every 3 months for I year. The primary efficacy variable was the percent change from baseline to I year in bone mineral density of the lumbar spine as measured by dual energy x-ray absorptiometry. Results: A total of 106 men were enrolled in the trial. Mean bone mineral density in the lumbar spine increased by 5.6% in men receiving zoledronic acid and decreased by 2.2% in those given placebo (mean difference 7.8%, 95% confidence interval 5.6%-10.0%, p < 0.001). Mean bone mineral density of the femoral neck, trochanter and total hip also increased in the zoledronic acid group and decreased in the placebo group. Zoledronic acid was well tolerated. Conclusions: Zoledronic acid increases bone mineral density in the hip and spine during androgen deprivation therapy for nonmetastatic prostate cancer. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Overtone Brooks Vet Adm Med Ctr, Shreveport, LA USA. Adv Clin Therapeut, Tucson, AZ USA. Beth Israel Med Ctr, New York, NY 10003 USA. Pacific Shores Med Grp, Long Beach, CA USA. Western Clin Res, Torrance, CA USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Shasha, Daniel/0000-0003-4798-1064 NR 10 TC 377 Z9 389 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2003 VL 169 IS 6 BP 2008 EP 2012 DI 10.1097/01.ju.0000063820.94994.95 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 679NU UT WOS:000182929500005 PM 12771706 ER PT J AU Freedland, SJ Presti, JC Terris, MK Kane, CJ Aronson, WJ Dorey, F Amling, CL AF Freedland, SJ Presti, JC Terris, MK Kane, CJ Aronson, WJ Dorey, F Amling, CL CA Search Database Study Grp TI Improved clinical staging system combining biopsy laterality and TNM stage for men with T1C and T2 prostate cancer: Results from the search database SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; neoplasm staging; biopsy; recurrence ID PROGRESSION-FREE SURVIVAL; AMERICAN JOINT COMMITTEE; RADICAL PROSTATECTOMY; BIOCHEMICAL FAILURE; RECURRENCE; ANTIGEN; DISEASE; ABILITY AB Purpose: A number of studies have failed to show significant differences in outcome following radical prostatectomy between men with palpable, clinically localized prostate cancer (cT2) and those whose tumors are not palpable (cT1c). We determined whether we could improve the prognostic value of the TNM staging system in men with cT1c and cT2 cancers by including information on whether prostate needle biopsy was unilaterally or bilaterally positive. Materials and Methods: A retrospective survey of 992 patients from the SEARCH (Shared Equal Access Regional Cancer Hospital) Database treated with radical prostatectomy at 4 equal access medical centers between 1988 and 2002 was done. TNM 1992 clinical stage was T1c in 421 patients, T2a in 287, T2b in 202 and T2c in 82. Multivariate analysis was used to examine whether biopsy laterality and clinical stage were significant predictors of surgical margin status, nonorgan confined disease, seminal vesicle invasion, and time to prostate specific antigen (PSA) recurrence following radical prostatectomy. Results: Patients with clinical stages T2b and T2c cancers had similar rates of PSA recurrence, which were significantly higher than in patients with T1c and T2a disease, who also had similar rates of PSA recurrence. Bilateral positive biopsy further stratified patients with T1c and T2a disease (p = 0.01) but not those with T2b and T2c cancers (p = 0.207). Grouping these 1992 clinical stages with biopsy laterality resulted in a new clinical staging system, which was a significant predictor of PSA recurrence following radical prostatectomy (p <0.001). On multivariate analysis whether TNM clinical stage was evaluated as a categorical or continuous variable only PSA, biopsy Gleason score and the new clinical staging system (1992 TNM stage groupings combined with biopsy laterality) were significant independent predictors of time to biochemical recurrence following radical prostatectomy. Conclusions: Combining low (T1c and T2a) and high (T2b and T2c) risk 1992 clinical stages with biopsy laterality (unilateral versus bilateral positive) resulted in a new clinical staging system that was a stronger predictor of PSA recurrence following radical prostatectomy than the 1992 or 1997 TNM clinical staging system. If confirmed at other centers and in men who undergo with other treatment modalities, consideration should be given to revising the current TNM staging system to reflect these findings. C1 Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Biostat, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. Stanford Univ, Dept Urol, Sch Med, Urol Sect, San Francisco, CA USA. Vet Adm Med Ctr, Dept Surg, San Francisco, CA 94121 USA. USN, Ctr Med, Dept Urol, San Diego, CA 92152 USA. Med Coll Georgia, Div Urol, Augusta, GA 30912 USA. RP Freedland, SJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Urol, Box 951738, Los Angeles, CA 90095 USA. OI Terris, Martha/0000-0002-3843-7270 NR 24 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2003 VL 169 IS 6 BP 2129 EP 2135 DI 10.1097/01.ju.0000065763.21602.14 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 679NU UT WOS:000182929500033 PM 12771734 ER PT J AU Freedland, SJ Aronson, WJ Terris, MK Kane, CJ Amling, CL Dorey, F Presti, JC AF Freedland, SJ Aronson, WJ Terris, MK Kane, CJ Amling, CL Dorey, F Presti, JC CA Search Database Study Grp TI Percent of prostate needle biopsy cores with cancer is a significant independent predictor of prostate specific antigen recurrence following radical prostatectomy: Results from the search database SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms, prostatectomy; biopsy, needle; prostate-specific antigen, recurrence ID BEAM RADIATION-THERAPY; SEXTANT BIOPSIES; EXTRACAPSULAR EXTENSION; DISEASE RECURRENCE; CLINICAL UTILITY; GLEASON SCORE; RISK; INTERMEDIATE; RELAPSE; RACE AB Purpose: Recent studies have suggested that the percent of positive cores in the prostate needle biopsy is a significant predictor of outcome among men undergoing radical prostatectomy or radiation therapy for prostate cancer. We evaluate whether either percent of cores with cancer or percent of cores positive from the most and least involved side of the prostate needle biopsy was associated with a worse outcome among men treated with radical prostatectomy. Materials and Methods: A retrospective survey of 1,094 patients from the SEARCH Database treated with radical prostatectomy at 4 different equal access medical centers in California between 1988 and 2002 was undertaken. We used multivariate analysis to examine whether total percent of prostate needle biopsy cores with cancer, percent of cores positive from each side of the prostate and other clinical variables were significant predictors of adverse pathology and time to prostate specific antigen (PSA) recurrence following radical prostatectomy. Results: On multivariate analysis serum PSA and percent of positive cores were significant predictors of positive surgical margins, nonorgan confined disease and seminal vesicle invasion. Percent of positive cores (p <0.001), serum PSA (p = 0.008) and biopsy Gleason score (p = 0.014) were significant independent predictors of time to biochemical recurrence. On a separate multivariate analysis that included the variables of total percent of positive cores, percent of positive cores from the most involved side of the biopsy, percent of positive cores from the least involved side of the biopsy and whether the biopsy was positive unilaterally or bilaterally, only the percent of positive cores from the most involved side of the biopsy was a significant independent predictor of PSA failure following radical prostatectomy. Percent of positive cores was used to separate patients into a low risk (less than 34%), intermediate risk (34% to 50%) and high risk (greater than 50%) groups, which provided significant preoperative risk stratification for PSA recurrence following radical prostatectomy (p <0.001). Percent of positive cores cut points were able to further risk stratify men who were at low (p = 0.001) or intermediate (p = 0.036) but not high (p = 0.674) risk for biochemical failure based on serum PSA and biopsy Gleason score. Conclusions: Percent of positive cores in the prostate needle biopsy was a significant predictor of adverse pathology and biochemical failure following radical prostatectomy, and the cut points of less than 34%, 34% to 50% and greater than 50% can be used to risk stratify patients preoperatively. The finding that percent of positive cores from the most involved side of the biopsy was a stronger predictor of PSA failure than the total percent of cores involved suggests that multiple positive biopsies from a single side might be a better predictor of a larger total cancer volume and thus correlate with clinical outcome. C1 Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Dept Surg, Los Angeles, CA USA. Stanford Univ, Med Ctr, Urol Sect,Sch Med, Vet Affairs Palo Alto Hlth Care Syst,Dept Urol, Palo Alto, CA 94304 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. USN, Ctr Med, San Diego, CA 92152 USA. RP Freedland, SJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Urol, Box 951738, Los Angeles, CA 90095 USA. NR 20 TC 61 Z9 65 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2003 VL 169 IS 6 BP 2136 EP 2141 DI 10.1097/01.ju.0000065588.82511.06 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 679NU UT WOS:000182929500034 PM 12771735 ER PT J AU Freedland, SJ Aronson, WJ Presti, JC Kane, CJ Terris, MK Elashoff, D Amling, CL AF Freedland, SJ Aronson, WJ Presti, JC Kane, CJ Terris, MK Elashoff, D Amling, CL CA Search Database Study Grp TI Should a positive surgical margin following radical prostatectomy be pathological stage T2 or T3? Results from the search database SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prostatectomy; prostate-specific antigen; neoplasm staging ID RETROPUBIC PROSTATECTOMY; SEXTANT BIOPSIES; BIOCHEMICAL RECURRENCE; CANCER; IMPACT; CARCINOMA; SPECIMENS; SITE; PROGRESSION; EXTENSION AB Purpose: The finding of a positive surgical margin associated with extracapsular extension at radical prostatectomy is a poor prognostic factor. However, whether a positive surgical margin with no documented extracapsular extension portends a similarly poor prognosis is unclear. We examined the significance of the pathological features of positive surgical margin and extracapsular extension for predicting biochemical failure following radical prostatectomy. Materials and Methods: We examined data on 1,621 men from the SEARCH Database of patients treated with radical prostatectomy without lymph node metastasis. Patients were separated into 5 groups based on the pathological findings of positive surgical margin, extracapsular extension, and/or seminal vesicle invasion. Preoperative clinical variables were compared across the groups and the groups were compared for time to biochemical recurrence using Cox proportional hazards analysis. Results: Men with seminal vesicle invasion had the highest prostate specific antigen (PSA) recurrence rates, while men with a negative surgical margin and no extracapsular extension had the lowest PSA recurrence rates. There were no differences in PSA failure rates between men with a positive surgical margin and no extracapsular extension versus men with a negative surgical margin and extracapsular extension versus men with extracapsular extension and a positive surgical margin. In this subset of patients with a positive surgical margin and/or extracapsular extension but no seminal vesicle invasion only serum PSA was a significant independent predictor of biochemical recurrence. Conclusions: Men with a positive surgical margin but no extracapsular extension had PSA recurrence rates similar to those in men with extracapsular extension with or without positive margins. Men with extracapsular extension had similar biochemical recurrence rates whether the surgical margin was positive or negative. If confirmed at other institutions, consideration should be given to modifying the current TNM staging system to reflect these findings. C1 Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Dept Surg, Los Angeles, CA USA. Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. USN, Ctr Med, Dept Urol, San Diego, CA 92152 USA. Med Coll Georgia, Div Urol, Augusta, GA 30912 USA. RP Freedland, SJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Urol, Box 951738, Los Angeles, CA 90095 USA. OI Terris, Martha/0000-0002-3843-7270 NR 20 TC 51 Z9 52 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2003 VL 169 IS 6 BP 2142 EP 2146 DI 10.1097/01.ju.0000061760.23169.be PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 679NU UT WOS:000182929500035 PM 12771736 ER PT J AU Clouse, WD Brewster, DC Marone, LK Cambria, RP LaMuraglia, GM Watkins, MT Kwolek, CJ Fan, CM Geller, SC Abbott, WM AF Clouse, WD Brewster, DC Marone, LK Cambria, RP LaMuraglia, GM Watkins, MT Kwolek, CJ Fan, CM Geller, SC Abbott, WM CA EVT Guidant Invest TI Durability of aortouniiliac endografting with femorofemoral crossover: 4-year experience in the EVT/Guidant trials SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY OCT 04-06, 2002 CL ROCKPORT, MAINE SP New England Soc Vasc Surg ID ABDOMINAL AORTIC-ANEURYSMS; ENDOVASCULAR REPAIR; EUROSTAR EXPERIENCE; GRAFT; BYPASS; ENDOLEAKS; INTERVENTIONS; MANAGEMENT AB Objectives. We evaluated mid-term results of the multicenter EVT/Guidant aortouniiliac endograft (AI) trial and ascertained the durability of this endovascular technique in patients unable to undergo standard bifurcated endografting. Methods. From November 1996 to December 1998, 121 patients were enrolled to receive the AI device on the basis of complex iliac artery anatomy contraindicating bifurcated endografting. Clinical data were centrally collected, and radiographic data were evaluated by core facility. Results: AI placement was technically successful in 113 of 121 patients. At operation, patients who underwent AI had significantly more arrhythmias, congestive heart failure, and peripheral occlusive disease (P < .05) compared with patients who underwent open aneurysmorrhaphy in the EVT/Guidant trials, indicating comorbid features in this anatomic cohort. Distal AI attachment was performed to the external iliac artery in 40 (36%) patients. Median follow-up was 38 months. In the AI group, overall aneurysm diameter decreased over the duration of study. from 54.4 +/- 9.6 mm to 44.4 +/- 16.4 mm (P = .004). At 24 and 36 months after repair, reduction in aneurysm size was associated with absence of endoleak (P = .003 and P = .008, respectively). Aneurysms shrunk or remained stable in 109 (96.5%) patients. Endoleak was identified in 52.3% of patients at discharge, and at follow-up in 30.9% at 1 year, 34.8% at 2 years, 28.6% at 3 years, and 30.4% at 4 years. Type II endoleak predominated. Leak from failure to completely occlude contralateral iliac flow accounted for 8 of 58 endoleaks (13.8%) at discharge. Sixteen patients (14.2%) underwent postoperative endoleak treatment; in one of these patients open conversion was necessary at 20 months. Post-procedure thigh or buttock claudication developed in 16 patients (14.2%). Thirteen patients (81.3%) had either distal attachment in the external iliac artery or contralateral type IIA occlusion. Fifteen patients (13.3%) required intervention because of reduced limb flow; one of these patients underwent open conversion at 27 months, and another underwent axillofemoral grafting at 28 months. Device migration was confirmed in 2 (1.8%) patients, without current clinical sequelae. Whereas no femoro-femoral graft thromboses occurred, graft infection developed in 3 patients (2.6%). During follow-up, aneurysm in 2 patients ruptured. Late death occurred in 41 patients (36.3%). Twenty-four patients (58.5%) died of cardiopulmonary disease; one death was endograft-related after aneurysm rupture; and one death was related to femorofemoral bypass infection. Actuarial survival was 78.4% (95% confidence interval [CI], 71%-86%) at 2 years and 63.4% (95% CI, 54%-73%) at 4 years. Conclusions. In patients with significant comorbid conditions and complex iliac anatomy unfavorable for bifurcated endografting, AI with femorofemoral bypass grafting is safe and effective. In most patients this endovascular option provides satisfactory mid-term results. C1 Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Sect Vasc Radiol, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Sect Vasc Radiol, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Brewster, DC (reprint author), Massachusetts Gen Hosp, Div Vasc Surg, 1 Hawthorne Pl,Ste 111, Boston, MA 02114 USA. NR 23 TC 29 Z9 29 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 JUN PY 2003 VL 37 IS 6 BP 1142 EP 1149 DI 10.1016/S0741-5214(03)00327-6 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 687CY UT WOS:000183359400002 PM 12764256 ER PT J AU LaBonte, JA Madani, N Sodroski, J AF LaBonte, JA Madani, N Sodroski, J TI Cytolysis by CCR5-using human immunodeficiency virus type 1 envelope glycoproteins is dependent on membrane fusion and can be inhibited by high levels of CD4 expression SO JOURNAL OF VIROLOGY LA English DT Review ID HUMAN LYMPHOID-TISSUE; T-CELL DEPLETION; MULTINUCLEATED GIANT-CELLS; IMMUNE-DEFICIENCY-SYNDROME; HTLV-III/LAV ENVELOPE; VPR INDUCES APOPTOSIS; HIV-1 NEF PROTEIN; AIDS-LIKE DISEASE; CHEMOKINE RECEPTORS; VIRAL REPLICATION AB T-tropic (X4) and dualtropic (R5X4) human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins kill primary and immortalized CD4(+) CXCR4(+) T cells by mechanisms involving membrane fusion. However, because much of HIV-1 infection in vivo is mediated by M-tropic (R5) viruses whose envelope glycoproteins use CCR5 as a coreceptor, we tested a panel of R5 and R5X4 envelope glycoproteins for their ability to lyse CCR5(+) target cells. As is the case for CXCR4(+) target cells, HIV-1 envelope glycoproteins expressed by single-round HIV-1 vectors killed transduced CD4(+) CCR5(+) cells in a membrane fusion-dependent manner. Furthermore, a CD4-independent R5 HIV-1 envelope glycoprotein was able to kill CD4-negative target cells expressing CCR5, demonstrating that CD4 is not intrinsically required for the induction of death. Interestingly, high levels of CD4 expression protected cells from lysis and syncytium formation mediated by the HIV-1 envelope glycoproteins. Immunoprecipitation experiments showed that high levels of CD4 coexpression inhibited proteolytic processing of the HIV-1 envelope glycoprotein precursor gp160. This inhibition could be overcome by decreasing the CD4 binding ability of gp120. Studies were also undertaken to investigate the ability of virion-bound HIV-1 envelope glycoproteins to kill primary CD4(+) T cells. However, neither X4 nor R5X4 envelope glycoproteins on noninfectious virions caused death in primary CD4(+) T cells. These results demonstrate that the interaction of CCR5 with R5 HIV-1 envelope glycoproteins capable of inducing membrane fusion leads to cell lysis; overexpression of CD4 can inhibit cell killing by limiting envelope glycoprotein processing. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, DIV AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NIAID NIH HHS [R37 AI024755, AI24755] NR 121 TC 27 Z9 28 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2003 VL 77 IS 12 BP 6645 EP 6659 DI 10.1128/JVI.77.12.6645-6659.2003 PG 15 WC Virology SC Virology GA 684LT UT WOS:000183209400006 PM 12767984 ER PT J AU Coburn, JW Maung, HM AF Coburn, JW Maung, HM TI Use of active vitamin D sterols in patients with chronic kidney disease, stages 3 and 4 SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 4th Symposium on Advances in Renal Osteodystrophy CY JUN 06-07, 2002 CL OVIEDO, SPAIN SP Plan Reg Invest Principado Asturias, FICYT, Consejeria Salud Serv Sanitar Principado Asturias, Cajastur, Abbott Labs, Genzyme, Amgen, Fresenius, Agua Mineral Bezoya DE secondary hyperparathyroidism; calcitriol; alfacalcidol; doxercalciferol; mild to moderate renal insufficiency; treatment; guidelines; bone density; hypercalcemia ID CHRONIC-RENAL-FAILURE; LOW-DOSE CALCITRIOL; BONE-DISEASE; SECONDARY HYPERPARATHYROIDISM; 1,25-DIHYDROXYVITAMIN D-3; THERAPY; 1,25(OH)2D3; CALCIUM; PLACEBO; TRIAL AB This paper reviews randomized controlled trials and other reported data on the use of the active vitamin D sterols, such as calcitriol, alfacalcidol, and doxercalciferol, in the management of secondary hyperparathyroidism in patients with mild-to-moderate renal insufficiency (stage 3 or 4 chronic kidney disease). Data on potential benefits, including improved histologic abnormalities of bone from secondary hyperparathyroidism, increased bone mineral density, and a reduction of elevated parathyroid hormone levels, are documented. Consideration is given to the risks of such therapy, which include the production of hypercalcemia, more rapid progression of renal insufficiency, the induction of adynamic bone "disease," and accelerated vascular and soft tissue calcification. The low therapeutic index, or "benefit/risk ratio" of calcitriol and alfacalcidol, the sterols currently licensed for such treatment, is recognized. It is recommended that phosphate-restricted diets, phosphate-binding agents, and oral calcium supplements be given adequate trials before starting calcitriol or alfacalcidol. If PTH levels cannot be controlled by these measures, initial doses of these sterols and the proper surveillance during treatment are given. It is emphasized that the risks of hypercalcemia are likely to increase as the degree of kidney failure worsens. Further research using the "less calcemic" vitamin D sterols is clearly needed. C1 W Los Angeles VA Healthcare Ctr, Nephrol Sect 111L, Med Serv, Los Angeles, CA 90073 USA. W Los Angeles VA Healthcare Ctr, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Coburn, JW (reprint author), W Los Angeles VA Healthcare Ctr, Nephrol Sect 111L, Med Serv, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jcoburn@ucla.edu NR 22 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2003 VL 63 SU 85 BP S49 EP S53 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 680TG UT WOS:000182994200012 ER PT J AU Hartnick, CJ Dailey, S Franco, R Zeitels, SM AF Hartnick, CJ Dailey, S Franco, R Zeitels, SM TI Office-based pulsed dye laser treatment for hemorrhagic telangiectasias and epistaxis SO LARYNGOSCOPE LA English DT Article DE pulsed dye laser; epistaxis ID ND-YAG LASER; PHOTOCOAGULATION; COAGULATION; ENDOGLIN; TYPE-1; GENE C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Surg, Div Otolaryngol, Boston, MA 02115 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 23 TC 6 Z9 7 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 JUN PY 2003 VL 113 IS 6 BP 1085 EP 1087 DI 10.1097/00005537-200306000-00033 PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 687RZ UT WOS:000183391900033 PM 12782829 ER PT J AU Baden, LR AF Baden, LR TI Prevention and therapy of fungal infections in bone marrow transplantation SO LEUKEMIA LA English DT Article ID INVASIVE PULMONARY ASPERGILLOSIS; EMPIRICAL ANTIFUNGAL THERAPY; STEM-CELL TRANSPLANTATION; BLOOD-STREAM INFECTIONS; AMPHOTERICIN-B; FLUCONAZOLE PROPHYLAXIS; NEUTROPENIC PATIENTS; CONTROLLED TRIAL; ORAL ITRACONAZOLE; PERSISTENT FEVER C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Baden, LR (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, PBB-A4,15 Francis St, Boston, MA 02115 USA. NR 33 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUN PY 2003 VL 17 IS 6 BP 1038 EP 1041 DI 10.1038/sj.leu.2402949 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 686BJ UT WOS:000183300400005 PM 12764365 ER PT J AU Sanhes, L Tang, R Delmer, A DeCaprio, JA Ajchenbaum-Cymbalista, F AF Sanhes, L Tang, R Delmer, A DeCaprio, JA Ajchenbaum-Cymbalista, F TI Fludarabine-induced apoptosis of B chronic lymphocytic leukemia cells includes early cleavage of p27kip1 by caspases SO LEUKEMIA LA English DT Article DE chronic lymphocytic leukemia; apoptosis; cyclin; caspase; p27kip1 ID DEPENDENT KINASE INHIBITOR; RETINOBLASTOMA PROTEIN; EXPRESSING P27(KIP1); CYCLE ARREST; CANCER CELLS; DEATH; P27; FIBROBLASTS; ACTIVATION; INDUCTION AB B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of growth arrested clonal B lymphocytes that undergo apoptosis when treated with fludarabine. To further explore the mechanism for the cell cycle arrest, we examined the expression and activity of cyclin-dependent kinases and inhibitors in primary B-CLL cells. We observed high levels of p27kip1, cyclin D2, cyclin E, cdk2, and cdk4 expression in freshly isolated B-CLL cells. Despite high levels of cyclins and cdks, little cdk2 or cdk4 activity was observed with p27kip1 in complex with cyclinD2/ cdk4 and cyclin E/cdk2. Remarkably, when B-CLL cells were treated in vitro with fludarabine, p27kip1 underwent caspase-specific degradation accompanied by an increase in cdk4 activity. We conclude that the G0/G1 arrest of B-CLL cells may protect against apoptosis and that the decrease in p27kip1 expression by caspase cleavage may be a key step in chemotherapy-induced apoptosis in B-CLL. C1 Hop Hotel Dieu, APHP, Dept Hematol, INSERM 9912,EA 1517, F-75004 Paris, France. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ajchenbaum-Cymbalista, F (reprint author), Hop Hotel Dieu, APHP, Dept Hematol, INSERM 9912,EA 1517, 1 Pl Parvis Notre Dame, F-75004 Paris, France. NR 39 TC 21 Z9 24 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUN PY 2003 VL 17 IS 6 BP 1104 EP 1111 DI 10.1038/sj.leu.2402895 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 686BJ UT WOS:000183300400016 PM 12764376 ER PT J AU Gray, RJ AF Gray, RJ TI Weighted estimating equations for linear regression analysis of clustered failure time data SO LIFETIME DATA ANALYSIS LA English DT Article DE exchangeable working model; asymptotic relative efficiency; stable model; Clayton's model ID CENSORED-DATA; RANK-TESTS; MODEL; PARAMETERS AB Estimation of regression parameters in linear survival models is considered in the clustered data setting. One step updates from an initial consistent estimator are proposed. The updates are based on scores that are functions of ranks of the residuals, and that incorporate weight matrices to improve efficiency. Optimal weights are approximated as the solution to a quadratic programming problem, and asymptotic relative efficiencies to various other weights computed. Except under strong dependence, simpler methods are found to be nearly as efficient as the optimal weights. The performance of several practical estimators based on exchangeable and independence working models is explored in simulations. C1 Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Gray, RJ (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. EM gray@jimmy.harvard.edu FU NCI NIH HHS [CA57253] NR 19 TC 5 Z9 5 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD JUN PY 2003 VL 9 IS 2 BP 123 EP 138 DI 10.1023/A:1022932117951 PG 16 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 659AK UT WOS:000181754000001 PM 12735492 ER PT J AU Yoganathan, S Nicolosi, R Wilson, T Handelman, G Scollin, P Tao, R Binford, P Orthoefer, F AF Yoganathan, S Nicolosi, R Wilson, T Handelman, G Scollin, P Tao, R Binford, P Orthoefer, F TI Antagonism of croton oil inflammation by topical Emu oil in CD-1 mice SO LIPIDS LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; MOUSE SKIN; PLASMA-LIPOPROTEINS; BONE DESTRUCTION; PROMOTION; ARTHRITIS; CELLS AB Emu oil is derived from the emu (Dromaius novaehollandiae), which originated in Australia, and has been reported to have anti-inflammatory properties. Inflammation was induced in anesthetized CD-1 mice by applying 50 muL of 2% croton oil to the inner surface of the left ear. After 2 h, the area was treated with 5 muL of emu, fish, flaxseed, olive, or liquified chicken fat, or left untreated. Animals were euthanized at 6 h postapplication of different oils, and earplugs (EP) and plasma samples were collected. Inflammation was evaluated by change in earlobe thickness, increase in weight of EP tissue (compared to the untreated ear), and induction in cytokines interleukin (IL)-1alpha and tumor necrosis factor-alpha (TNF-alpha) in EP homogenates. Although reductions relative to control (croton oil) were noted for all treatments, auricular thickness and EP weights were significantly reduced (-72 and -71%, respectively) only in the emu oil-treated group. IL-1alpha levels in homogenates of auricular tissue were significantly reduced in the fish oil (-57%) and emu oil (-70%) groups relative to the control group. The cytokine TNF-alpha from auricular homogenates was significantly reduced in the olive oil (-52%) and emu oil (-60%) treatment groups relative to the control group. Plasma cytokine levels were not changed by croton oil treatment. Although auricular thickness and weight were significantly correlated with each other (r = 0.780, P < 0.003), auricular thickness but not weight was significantly correlated with cytokine IL-1alpha (r = 0.750, P < 0.006) and TNF-alpha (r = 0.690, P < 0.02). These studies indicate that topical emu oil has anti-inflammatory properties in the CD-1 mouse that are associated with decreased auricular thickness and weight, and with the cytokines IL-1alpha and TNF-alpha. C1 Univ Massachusetts, Ctr Hlth & Dis Res, Lowell, MA 01854 USA. Forsyth Inst Boston, Boston, MA 02115 USA. Biomed Res Inst, Rockville, MD 20825 USA. LB Processors, Chapmansboro, TN 37035 USA. Arkansas State Univ, Jonesboro, AR 72467 USA. RP Nicolosi, R (reprint author), Univ Massachusetts, Ctr Hlth & Dis Res, 3 Solomont Way,Suite 4, Lowell, MA 01854 USA. OI Wilson, Thomas/0000-0001-8363-4356 NR 30 TC 37 Z9 42 U1 1 U2 8 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD JUN PY 2003 VL 38 IS 6 BP 603 EP 607 DI 10.1007/s11745-003-1104-y PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 709JP UT WOS:000184622300002 PM 12934669 ER PT J AU Mandell, MS Seem, DL D'Alesandro, A Niemann, CU Delmonico, F AF Mandell, MS Seem, DL D'Alesandro, A Niemann, CU Delmonico, F TI Attitudes of health care providers to controlled Donation after Cardiac Death in the United States SO LIVER TRANSPLANTATION LA English DT Meeting Abstract CT 9th Meeting of the International-Liver-Transplantation-Society/13th Meeting of the Liver-Intensive-Care-Group-of-Europe CY JUN 18-21, 2003 CL BARCELONA, SPAIN SP Int Liver Transplantat Soc, Liver Intensive Care Grp Europe C1 Univ Colorado, Hlth Sci Ctr, Dept Anesthesiol, Denver, CO USA. United Network Organ Sharing, Profess Serv Dept, Richmond, VA USA. Univ Wisconsin, Dept Surg, Madison, WI 53706 USA. Univ Calif San Francisco, Dept Anesthesia& Perioperat Care, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUN PY 2003 VL 9 IS 6 MA 80 BP C20 EP C20 PG 1 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 685GB UT WOS:000183252300101 ER PT J AU Su, L Sai, Y Fan, R Thurston, SW Miller, DP Zhou, W Wain, JC Lynch, TJ Liu, G Christiani, DC AF Su, L Sai, Y Fan, R Thurston, SW Miller, DP Zhou, W Wain, JC Lynch, TJ Liu, G Christiani, DC TI P53 (codon 72) and P21 (codon 31) polymorphisms alter in vivo mRNA expression of p21 SO LUNG CANCER LA English DT Article DE p53; p21; polymorphism; RNA; expression; lung cancer ID KINASE INHIBITOR GENE; HUMAN LUNG-CANCER; HUMAN-PAPILLOMAVIRUS; CERVICAL-CANCER; ESOPHAGEAL CANCER; BLADDER-CANCER; ASSOCIATION; TUMOR; WAF1; RISK AB p21 (Waf1/Cip 1) is a downstream target of p53. We evaluated the association between p21 polymorphism (codon 31), p53 polymorphism (codon 72) and their corresponding in vivo mRNA expression. In this study, p21 and p53 genetic polymorphisms (using standard PCR-RFLP techniques) and p21 and p53 gene expressions (using a radiolabelled ribonuclease protection assay (RPA) technique) were evaluated in the peripheral leukocytes of 84 individuals (63 with lung cancer). Log-transformed values of mRNA expression by RPA, which approximated a normal distribution, were analyzed. p53 genotypes did not correlate with p53 mRNA log-expression (P > 0.05 for all comparisons), but the Pro allele variants of p53 were associated with a significant decrease in mRNA log-expression of its downstream target, p21. The variant Arg allele of p21 was also associated with a significant decrease in p21 mRNA log-expression. When individuals with at least one variant allele of both p53 and p21 (double-variants) were compared with all other genotype groups, these double-variants had significantly lower log-expression of p21 (P < 0.005 by both t-tests (crude) and linear regression analyses (adjusted)). This is translated into an approximate 48% reduction in the geometric mean of the mRNA expression of the double-variants, when compared with all other groups. Results were consistent in both patients with lung cancer (n = 63) and in normal controls (n = 21). In conclusion, the presence of a p53 Pro allele and/or p21 Arg allele is associated with lower downstream target gene expression of p21. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Thorac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Hematol Oncol Canc Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA 74386]; NIEHS NIH HHS [ES 00002] NR 36 TC 25 Z9 26 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUN PY 2003 VL 40 IS 3 BP 259 EP 266 DI 10.1016/S0169-5002(03)00081-3 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 687RY UT WOS:000183391800004 PM 12781424 ER PT J AU Sales, AE Liu, CF Sloan, KL Malkin, J Fishman, PA Rosen, AK Loveland, S Nichol, WP Suzuki, NT Perrin, E Sharp, ND Todd-Stenberg, J AF Sales, AE Liu, CF Sloan, KL Malkin, J Fishman, PA Rosen, AK Loveland, S Nichol, WP Suzuki, NT Perrin, E Sharp, ND Todd-Stenberg, J TI Predicting costs of care using a pharmacy-based measure risk adjustment in a veteran population SO MEDICAL CARE LA English DT Article DE case-mix; pharmacy; veterans; risk adjustment ID CHRONIC DISEASE SCORE; MEDICARE CAPITATION PAYMENTS; CASE-MIX; DIAGNOSES AB BACKGROUND. Although most widely used risk adjustment systems use diagnosis data to classify patients, there is growing interest in risk adjustment based on computerized pharmacy data. The Veterans Health Administration (VHA) is an ideal environment in which to test the efficacy of a pharmacy-based approach. OBJECTIVE. To examine the ability of RxRisk-V to predict concurrent and prospective costs of care in VHA and compare the performance of RxRisk-V to a simple age/gender model, the original RxRisk, and two leading diagnosis-based risk adjustment approaches: Adjusted Clinical Groups and Diagnostic Cost Groups/Hierarchical Condition Categories. METHODS. The study population consisted of 161,202 users of VHA services in Washington, Oregon, Idaho, and Alaska during fiscal years (FY) 1996 to 1998. We examined both concurrent and predictive model fit for two sequential 12-month periods (FY 98 and FY 99) with the patient-year as the unit of analysis, using split-half validation. RESULTS. Our results show that the Diagnostic Cost Group/Hierarchical Condition Categories model performs best (R-2 = 0.45) among concurrent cost models, followed by ADG (0.31), RxRisk-V (0.20), and age/sex model (0.01). However, prospective cost models other than age/sex showed comparable R-2: Diagnostic Cost Group/Hierarchical Condition Categories R-2 = 0.15, followed by ADG (0.12), RxRisk-V (0.12), and age/sex (0.01). CONCLUSIONS. RxRisk-V is a clinically relevant, open source risk adjustment system that is easily tailored to fit specific questions, populations, or needs. Although it does not perform better than diagnosis-based measures available on the market, it may provide a reasonable alternative to proprietary systems where accurate computerized pharmacy data are available. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Pharm, Seattle, WA 98195 USA. RAND Corp, Arlington, VA USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ, Bedford, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Sales, AE (reprint author), VA Puget Sound Hlth Care Syst, 152 HSRD,1660 S Columbian Way, Seattle, WA 98108 USA. OI Sales, Anne/0000-0001-9360-3334 NR 23 TC 61 Z9 61 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 2003 VL 41 IS 6 BP 753 EP 760 DI 10.1097/00005650-200306000-00008 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 685XC UT WOS:000183288800008 PM 12773841 ER PT J AU Sloan, KL Sales, AE Liu, CF Fishman, P Nichol, P Suzuki, NT Sharp, ND AF Sloan, KL Sales, AE Liu, CF Fishman, P Nichol, P Suzuki, NT Sharp, ND TI Construction and characteristics of the RxRisk-V - A VA-adapted pharmacy-based case-mix instrument SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Annual Meeting of the Academy-for-Health-Services-Research-and-Health-Policy CY JUN 10-11, 2001 CL ATLANTA, GEORGIA SP Acad Hlth Serv Res & Hlth Policy DE case-mix; pharmacy; veterans; risk adjustment ID CHRONIC DISEASE SCORE; OF-VETERANS-AFFAIRS; HEALTH-STATUS; CARE AB BACKGROUND. Assessment of disease burden is the key to many aspects of health care management. Patient diagnoses are commonly used for case-mix assessment. However, issues pertaining to diagnostic data availability and reliability make pharmacy-based strategies attractive. Our goal was to provide a reliable and valid pharmacy-based case-mix classification system for chronic diseases found in the Veterans Health Administration (VHA) population. OBJECTIVE. To detail the development and category definitions of a VA-adapted version of the RxRisk (formerly the Chronic Disease Score); to describe category prevalence and reliability; to check category criterion validity against ICD-9 diagnoses; and to assess category-specific regression coefficients in concurrent and prospective cost models. RESEARCH DESIGN. Clinical and pharmacological review followed by cohort analysis of diagnostic, pharmacy, and utilization databases. SUBJECTS. 126,075 veteran users of VHA services in Washington, Oregon, Idaho, and Alaska. METHODS. We used Kappa statistics to evaluate RxRisk category reliability and criterion validity, and multivariate regression to estimate concurrent and prospective cost models. RESULTS. The RxRisk-V classified 70.5% of the VHA Northwest Network 1998 users into an average of 2.61 categories. Of the 45 classes, 33 classes had good-excellent 1-year reliability and 25 classes had good-excellent criterion validity against ICD-9 diagnoses. The RxRisk-V accounts for a distinct proportion of the variance in concurrent (R-2 = 0.18) and prospective cost (R-2 = 0.10) models. CONCLUSIONS. The RxRisk-V provides a reliable and valid method for administrators to describe and understand better chronic disease burden of their treated populations. Tailoring to the VHA permits assessment of disease burden specific to this population. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Pharm, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. RP Sloan, KL (reprint author), VA Puget Sound Hlth Care Syst, 116-DDTP,1660 S Columbian Way, Seattle, WA 98108 USA. OI Sales, Anne/0000-0001-9360-3334 NR 41 TC 102 Z9 104 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 2003 VL 41 IS 6 BP 761 EP 774 DI 10.1097/00005650-200306000-00009 PG 14 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 685XC UT WOS:000183288800009 PM 12773842 ER PT J AU Iftimia, I Devlin, PM Chin, LM Baron, JM Cormack, RA AF Iftimia, I Devlin, PM Chin, LM Baron, JM Cormack, RA TI GAF film dosimetry of a tandem positioned beta-emitting intravascular brachytherapy source train SO MEDICAL PHYSICS LA English DT Article DE coronary artery radiation therapy (CART); brachytherapy; Sr-90/Y-90; dosimetry measurements ID INTRACORONARY RADIATION-THERAPY; RADIOCHROMIC FILM; BALLOON ANGIOPLASTY; RESTENOSIS; STENT; TRIAL; IMPLANTATION; WIRE AB Coronary artery brachytherapy may require treatment of lesions longer than a single source length. A treatment option is tandem positioning of the single source. This study presents relative dosimetric measurements of a cardiovascular brachytherapy source and the dosimetric characteristics in the junction region of tandem treatments. Measurements were carried out using a Novoste Beta Cath(TM) Sr-90/Y-90 40 mm beta source in a plastic water phantom. Radiochromic MD-55-2 film, calibrated using both 6 MV photon and 6 MeV electron beams from a linear accelerator, was used as the dosimeter. Dose distributions around a single source and in the junction region of tandem irradiation were measured. Measurements of the near field dose as close as 1.2 mm from the source are presented. Significant over- or underdoses in the junction region of tandem irradiation were quantified. At a radial distance of 2 mm from the longitudinal axis of the source, the dose value in the middle of the junction region, normalized to the dose at 2 mm midline single source, was about 182% for a 2-seed overlap and 16% for a 2-seed gap, respectively. Dose distributions in the junction region as a function of source overlap and radial distance have fairly high gradients and exhibit characteristic patterns. The fraction of prescription dose was found to have a sigmoidal dependence on overlap size, for radial distances ranging between 1.2 and 3 mm. The parameters of these sigmoids, quantified as functions of radial distance, could be used to provide quick and reasonable over/underdose estimates, given any potential overlap or gap in the junction area, with an uncertainty within 10%. (C) 2003 American Association of Physicists in Medicine. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol,Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM iiftimia@lifespan.org RI Grams, Michael/G-5197-2011 NR 29 TC 4 Z9 4 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1004 EP 1012 DI 10.1118/1.1573206 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500003 PM 12852522 ER PT J AU Kung, JH Zygmanski, P Choi, N Chen, GTY AF Kung, JH Zygmanski, P Choi, N Chen, GTY TI A method of calculating a lung clinical target volume DVH for IMRT with intrafractional motion SO MEDICAL PHYSICS LA English DT Article DE intrafractional; organ motion; intensity modulated; dose error ID INTENSITY-MODULATED RADIOTHERAPY; MULTILEAF COLLIMATION; IRRADIATION; DELIVERY; TUMOR; ERROR AB The motion of lung tumors from respiration has been reported in the literature to be as large as 1-2 cm. This motion requires an additional margin between the Clinical Target Volume (CTV) and the Planning Target Volume (PTV). In Intensity Modulated Radiotherapy (IMRT), while such a margin is necessary, the margin may not be sufficient to avoid unintended high and low dose regions to the interior on moving CTV. Gated treatment has been proposed to improve normal tissues sparing as well as to ensure accurate dose coverage of the tumor volume. The following questions have not been addressed in the literature: (a) what is the dose error to a target volume without a gated IMRT treatment? (b) What is an acceptable gating window for such a treatment. In this study, we address these questions by proposing a novel technique for calculating the three-dimensional (3-D) dose error that would result if a lung IMRT plan were delivered without a gated linac beam. The method is also generalized for gated treatment with an arbitrary triggering window. IMRT plans for three patients with lung tumors were studied. The treatment plans were generated with HELIOS for delivery with 6 MV on a CL2100 Varian linear accelerator with a 26 pair MLC. A CTV to PTV margin of 1 cm was used. An IMRT planning system searches for an optimized fluence map Phi(x,y) for each port, which is then converted into a dynamic MLC file (DMLC). The DMLC file contains information about MLC subfield shapes and the fractional Monitor Units (MUs) to be delivered for each subfield. With a lung tumor, a CTV that executes a quasiperiodic motion z(t) does not receive Phi(x,y), but rather an Effective Incident Fluence EIF(x,y). We numerically evaluate the EIF(x,y) from a given DMLC file by a coordinate transformation to the Target's Eye View (TEV). In the TEV coordinate system, the CTV itself is stationary, and the MLC is seen to execute a motion -z(t) that is superimposed on the DMLC motion. The resulting EIF(x,y) is input back into the dose calculation engine to estimate the 3-D dose to a moving CTV. In this study, we model respiratory motion as a sinusoidal function with an amplitude of 10 mm in the superior- inferior direction. a period of 5 s, and an initial phase of zero. (C) 2003 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kung, JH (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 19 TC 21 Z9 21 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 JUN PY 2003 VL 30 IS 6 BP 1103 EP 1109 DI 10.1118/1.1576233 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500015 PM 12852534 ER PT J AU Wu, T Moore, R Rafferty, E Kopans, D Stewart, A Phillips, W Stanton, M Eberhard, J Opsahl-Ong, B Niklason, L Williams, M AF Wu, T Moore, R Rafferty, E Kopans, D Stewart, A Phillips, W Stanton, M Eberhard, J Opsahl-Ong, B Niklason, L Williams, M TI Tomosynthesis mammography reconstruction using a Maximum Likelihood method SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02254 USA. Archemix Corp, Cambridge, MA USA. Gen Elect Corp Res & Dev, Niskayuna, NY USA. Univ Virginia, Charlottesville, VA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1332 EP 1332 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500056 ER PT J AU Rosenthal, SJ Wolfgang, J AF Rosenthal, SJ Wolfgang, J TI Targeting the prostate using on line imaging for proton therapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1337 EP 1337 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500080 ER PT J AU Trofimov, A Bortfeld, T Jiang, S Rietzel, E Chen, GTY AF Trofimov, A Bortfeld, T Jiang, S Rietzel, E Chen, GTY TI Accounting for target motion in inverse treatment planning SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1339 EP 1339 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500092 ER PT J AU Gierga, D Chen, G Kung, J Betke, M Lombardi, J Willett, C AF Gierga, D Chen, G Kung, J Betke, M Lombardi, J Willett, C TI Quantitative fluoroscopy of respiration-induced abdominal tumor motion and the impact of motion on IMRT dose distributions SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1340 EP 1340 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500095 ER PT J AU Sharp, G Jiang, SB Ruan, D Castanon, D Shirato, H AF Sharp, G Jiang, SB Ruan, D Castanon, D Shirato, H TI Evaluation of prediction methods for real-time tumor tracking during treatment SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Boston, MA 02215 USA. Hokkaido Univ, Sapporo, Hokkaido, Japan. RI Shirato, Hiroki/A-7068-2010 NR 1 TC 1 Z9 1 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1346 EP 1346 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500123 ER PT J AU Doppke, K AF Doppke, K TI Treatment planning system verification SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1355 EP 1355 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500165 ER PT J AU Rietzel, E Doppke, K Pan, T Choi, N Willett, C Chen, G AF Rietzel, E Doppke, K Pan, T Choi, N Willett, C Chen, G TI 4D computer tomography for radiation therapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Gen Elect Co, Brookfield, WI USA. NR 0 TC 4 Z9 4 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1365 EP 1366 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500206 ER PT J AU Berbeco, R Jiang, SB Sharp, G Mostafavi, H Kollipara, S Chen, GTY AF Berbeco, R Jiang, SB Sharp, G Mostafavi, H Kollipara, S Chen, GTY TI Patient setup with respiratory gated electronic portal imaging SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Varian Med Syst Inc, Mt View, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1383 EP 1384 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500275 ER PT J AU Jiang, SB Bortfeld, T Trofimov, A Rietzel, E Sharp, G Choi, N Chen, GTY AF Jiang, SB Bortfeld, T Trofimov, A Rietzel, E Sharp, G Choi, N Chen, GTY TI Synchronized moving aperture radiation therapy (SMART): Plan optimization and MLC leaf sequencing based on 4D CT data SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 JUN PY 2003 VL 30 IS 6 BP 1384 EP 1384 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500276 ER PT J AU Lee, SY Niemierko, A AF Lee, SY Niemierko, A TI Monte Carlo simulation of cell survival phenomena SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 JUN PY 2003 VL 30 IS 6 BP 1393 EP 1394 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500320 ER PT J AU Paganetti, H AF Paganetti, H TI Combining the concepts of lethal potentially lethal lesions and cellular dose deposition pattern to predict proton RBE values SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1394 EP 1394 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500323 ER PT J AU Jiang, SB Neicu, T Zygmanski, P AF Jiang, SB Neicu, T Zygmanski, P TI Synchronized moving aperture radiation therapy (SMART): Superimposing tumor motion on IMRT MLC leaf sequences under realistic delivery limitations SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 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 JUN PY 2003 VL 30 IS 6 BP 1399 EP 1399 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500346 ER PT J AU Neicu, T Papiez, L Jiang, SB AF Neicu, T Papiez, L Jiang, SB TI Synchronized Moving Aperture Radiation Therapy (SMART): Dynamic MLC leaf sequencing with tumor motion SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. NR 1 TC 0 Z9 0 U1 1 U2 1 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 JUN PY 2003 VL 30 IS 6 BP 1405 EP 1405 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500371 ER PT J AU Berbeco, R Jiang, SB Sharp, G Mostafavi, H Chen, GTY AF Berbeco, R Jiang, SB Sharp, G Mostafavi, H Chen, GTY TI Integrated radiotherapy imaging system (IRIS): Considerations of tumor tracking with gantry-mounted kilovoltage x-ray systems SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Varian Med Syst Inc, Mt View, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1416 EP 1416 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500410 ER PT J AU Pope, CJ Berbeco, RI Jiang, SB AF Pope, CJ Berbeco, RI Jiang, SB TI Dosimetric analysis of the effect of respiration-induced lung tumor motion on dynamic IMRT treatments using EDR2 film SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1418 EP 1418 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500421 ER PT J AU Rietzel, E Jackson, J Adams, J Harris, T Chen, G AF Rietzel, E Jackson, J Adams, J Harris, T Chen, G TI The impact of organ motion on dose distributions SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. N Shore Canc Ctr, Peabody, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1428 EP 1428 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500469 ER PT J AU Biggs, P Gierga, D AF Biggs, P Gierga, D TI A Monte Carlo investigation of photoneutron shielding for medical linear accelerators SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1437 EP 1437 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500511 ER PT J AU Trofimov, A Bortfeld, T Jennekens, W AF Trofimov, A Bortfeld, T Jennekens, W TI Considering the constraints of delivery method in treatment planning for proton pencil beam scanning SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Tech Univ Eindhoven, NL-5600 MB Eindhoven, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1447 EP 1448 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500551 ER PT J AU Wolfgang, J Bortfeld, T AF Wolfgang, J Bortfeld, T TI Reducing sensitivity of intensity modulated proton therapy plans to uncertainties in the distal dose fall-off SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUN PY 2003 VL 30 IS 6 BP 1448 EP 1448 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500552 ER PT J AU Paganetti, H Rietzel, E Can, A Singh, H Chen, GTY AF Paganetti, H Rietzel, E Can, A Singh, H Chen, GTY TI Real four-dimensional Monte Carlo dose calculation for double-dynamic systems (time-dependent delivery under organ motion) SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUN PY 2003 VL 30 IS 6 BP 1451 EP 1451 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500568 ER PT J AU Kung, J Gierga, D Zygmanski, P Leong, J Cail, D Masganas, G Chu, K Rietzel, E Biggs, P Chen, G AF Kung, J Gierga, D Zygmanski, P Leong, J Cail, D Masganas, G Chu, K Rietzel, E Biggs, P Chen, G TI Linac beam Gating for tumors in the abdominal site based on ultrasound imaging (WIP) SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU 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 JUN PY 2003 VL 30 IS 6 BP 1471 EP 1471 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500666 ER PT J AU Sharp, G Jiang, SB Kollipara, S Rosenthal, S AF Sharp, G Jiang, SB Kollipara, S Rosenthal, S TI Toward an automatic method of anatomical landmark localization for daily patient positioning SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 JUN PY 2003 VL 30 IS 6 BP 1472 EP 1472 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500667 ER PT J AU Gierga, D Kung, J Jackson, J Schneider, R Chen, G AF Gierga, D Kung, J Jackson, J Schneider, R Chen, G TI Intercomparison of IMRT treatment planning systems using a standard head and neck dataset SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. N Shore Canc Ctr, Peabody, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1486 EP 1486 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500739 ER PT J AU Niemierko, A AF Niemierko, A TI Can IMRT affect cancer mortality? SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med ID MODULATED RADIATION-THERAPY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1488 EP 1488 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500750 ER PT J AU Zygmanski, P Que, W Chen, G Kung, J AF Zygmanski, P Que, W Chen, G Kung, J TI DMLC sequence that are least sensitive to intrafractional organ motion SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY AUG 10-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Physicists Med C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Ryerson Polytech Univ, Toronto, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 30 IS 6 BP 1493 EP 1493 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692JT UT WOS:000183658500775 ER PT J AU Durand, RJ Castracane, VD Hollander, DB Tryniecki, JL Bamman, MM O'Neal, S Hebert, EP Kraemer, RR AF Durand, RJ Castracane, VD Hollander, DB Tryniecki, JL Bamman, MM O'Neal, S Hebert, EP Kraemer, RR TI Hormonal responses from concentric and eccentric muscle contractions SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE testosterone; growth hormone; lactate; eccentric contractions ID HEAVY-RESISTANCE EXERCISE; BIOASSAYABLE GROWTH-HORMONE; TESTOSTERONE; PROTOCOLS; MEN; YOUNG AB Intense resistance exercise can acutely increase testosterone (T), free testosterone (FT), and growth hormone (GH) concentrations. but there are few investigations concerning acute endocrine responses to concentric (CON) and eccentric (ECC) contractile actions. Purpose: The purpose of the study was to compare acute anabolic hormonal responses to bouts of dynamic CON and ECC contractions from multiple exercises at the same absolute load. Methods: Ten young men (age: 24.7+/-1.2 yr, weight: 85.45+/-24.2 kg, and height: 178+/-0.2 cm) completed two trials in counterbalanced fashion consisting of only CON or FCC contractions at the same absolute workload. Subjects performed four sets of 12 repetitions of bench press, leg extension, military press, and leg curl at 80% of a 10-repetition maximum with 90-s rest periods. Blood samples were collected pre-, post-, and 15-min postexercise. Results: There were significant increases in GH, T, and FT and lactate for both trials, but only GH and lactate were greater for the CON trial. Conclusion: CON exercise increases GH concentrations to a much greater extent than ECC exercise at the same absolute load, and it is likely that greater GH responses were related to intensity rather than mode of contraction. Also, CON and ECC dynamic contraction trials at the same absolute workload elicited similar small but significant increases in T and FT, indicating that the greater metabolic stress produced by during the CON trial did not affect these hormone responses. C1 SE Louisiana Univ, Dept Kinesiol & Hlth Studies, Hammond, LA 70402 USA. Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, GRECC Muscle Res Lab, Birmingham, AL USA. Texas Tech Univ, Hlth Sci Ctr, Dept Obstet & Gynecol, Amarillo, TX USA. RP Durand, RJ (reprint author), Pennington Biomed Res Ctr, Hlth & Fitness Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. RI Hollander, Daniel/A-8725-2009 NR 31 TC 49 Z9 53 U1 0 U2 4 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 JUN PY 2003 VL 35 IS 6 BP 937 EP 943 DI 10.1249/01.MSS.0000069522.38141.0B PG 7 WC Sport Sciences SC Sport Sciences GA 687PK UT WOS:000183385500008 PM 12783041 ER PT J AU Xu, B Bhattacharjee, A Roy, B Xu, HM Anthony, D Frank, DA Feldman, GM Cathcart, MK AF Xu, B Bhattacharjee, A Roy, B Xu, HM Anthony, D Frank, DA Feldman, GM Cathcart, MK TI Interleukin-13 induction of 15-lipoxygenase gene expression requires p38 mitogen-activated protein kinase-mediated serine 727 phosphorylation of Stat1 and Stat3 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN ATHEROSCLEROTIC PLAQUES; POLAR STEROL ESTERS; MAP KINASE; TRANSCRIPTIONAL ACTIVATION; JANUS KINASE; TYROSINE PHOSPHORYLATION; HUMAN MONOCYTES; GROWTH-HORMONE; C-DELTA; SER-727 PHOSPHORYLATION AB Interleukin-13 (IL-13) is a cytokine secreted by Th2 lymphocytes that is capable of inducing expression of 15-lipoxygenase (15-LO) in primary human monocytes. We recently demonstrated that induction of 15-LO requires the activation of Jak2 and Tyk2 kinases and Stats 1, 3, 5, and 6. Since IL-13-induced 15-LO expression was inhibited by H7 (a serine-threonine kinase inhibitor), we predicted that Stat serine phosphorylation may also be crucial for 15-LO expression. In this study, we present evidence indicating that IL-13-induced 15-LO mRNA expression was detectable as early as I h by real-time reverse transcription-PCR. We found that IL-13 induced a time-dependent serine phosphorylation of both Stat1 and Stat3, detectable at 15 min after IL-13 treatment. In addition, the activation of p38 mitogen-activated protein kinase (MAPK) was detected in a time-dependent fashion, with peak phosphorylation at 15 min after IL-13 treatment. SB202190, a p38 MAPK-specific inhibitor, markedly inhibited IL-13-induced Stat1 and Stat3 serine phosphorylation as well as DNA binding. Furthermore, treatment of cells with Stat1 or Stat3 decoys significantly impaired IL-13-induced 15-LO expression. Taken together, our results provide the first evidence that IL-13 induces p38 MAPK phosphorylation/activation, which regulates Stat1 and Stat3 serine 727 phosphorylation. Both of these events are important steps in IL-13-induced 15-LO expression in human monocytes. C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44195 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. US FDA, Ctr Biolog Evaluat & Res, Off Therapeut Res & Review, Bethesda, MD 20892 USA. RP Cathcart, MK (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Cell Biol, 9500 Euclid Ave, Cleveland, OH 44195 USA. FU NHLBI NIH HHS [HL51068] NR 64 TC 61 Z9 62 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2003 VL 23 IS 11 BP 3918 EP 3928 DI 10.1128/MCB.23.11.3918-3928.2003 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 681HZ UT WOS:000183031900018 PM 12748293 ER PT J AU Tohyama, Y Katagiri, K Pardi, R Lu, C Springer, TA Kinashi, T AF Tohyama, Y Katagiri, K Pardi, R Lu, C Springer, TA Kinashi, T TI The critical cytoplasmic regions, of the alpha L/beta 2 integrin in Rap1-induced adhesion and migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; FUNCTION-ASSOCIATED MOLECULE-1; CELL-ADHESION; T-CELL; LEUKOCYTE ADHESION; PHORBOL ESTER; BETA-SUBUNIT; ALPHA-SUBUNITS; SMALL GTPASE; LFA-1 AB Rap1 is a potent inside-out signal that increases LFA-1 adhesive activity. In this study, we have defined the cytoplasmic region of the alphaL, and beta2 integrin that are required for Rap1-stimulated adhesion and subsequent migration on ICAM-1. Human LFA-1 bearing truncated and point-mutated alphaL and beta2 cytoplasmic regions were reconstituted in mouse IL-3-dependent proB cells, BAF/3. Truncation of the aL, but not beta2 subunit cytoplasmic region, abolished Rap1V12-dependent adhesion to, ICAM-1. The alanine substitution of two lysine residues (K1097/K1099) in the alphaL subunit was found to be critical in adhesion induced by Rap1V12, but not PMA. This mutation suppressed Rap1V12-induced LFA-1 conformation changes and ligand-binding affinity. The K1097/K10991 mutation also impaired binding, to ICAM-1 induced by TCR cross-linking or SDF-1. In contrast, the alanine substitution for tyrosine in the beta2 subunit endocytosis motif inhibited internalization of LFA-1, and severely impaired detachment at the cell rearm which resulted in long-elongated cell shapes. This result demonstrates that internalization of LFA-1 is a critical step in the deadhesion process. Our study revealed novel requirements of amino add residues of the LFA-1 cytoplasmic region in the response to the inside-out signaling and the subsequent deadhesion process. C1 Kyoto Univ, Grad Sch Med, Bayer Chair Dept Mol Immunol & Allergy, Kyoto 6068501, Japan. San Raffaele Sci Inst, DIBIT, I-20132 Milan, Italy. Univ Milan, Sch Med, Human Immunol Unit, I-20132 Milan, Italy. Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kinashi, T (reprint author), Kyoto Univ, Grad Sch Med, Bayer Chair Dept Mol Immunol & Allergy, Kyoto 6068501, Japan. NR 58 TC 71 Z9 73 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUN PY 2003 VL 14 IS 6 BP 2570 EP 2582 DI 10.1091/mbc.E02-09-0615 PG 13 WC Cell Biology SC Cell Biology GA 690AA UT WOS:000183524100032 PM 12808052 ER PT J AU Shi, YJ Gera, J Hsu, JH Van Ness, B Lichtenstein, A AF Shi, YJ Gera, J Hsu, JH Van Ness, B Lichtenstein, A TI Cytoreductive effects of farnesyl transferase inhibitors on multiple myeloma tumor cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID GERANYLGERANYLTRANSFERASE-I INHIBITORS; K-RAS ONCOGENES; NF-KAPPA-B; FARNESYLTRANSFERASE INHIBITORS; ACTIVATING MUTATIONS; PROTEIN-KINASES; CANCER-THERAPY; LINE ANBL6; AKT KINASE; GROWTH AB Farnesyl transferase inhibitors (FTIs) are anticancer agents designed to target ras processing and ras-dependent signal pathways. Because oncogenic ras mutations are found in up to 50% of multiple myeloma (MM) specimens, these agents may be effective in this disease. However, some preclinical studies suggest that FTI antitumor responses are unrelated to effects on ras. To address this issue in myeloma, we used the ANBL-6 myeloma cell line where interleukin (IL)-6-dependent cells are stably transfected with mutated N-ras or K-ras genes. Because expression of mutated ras allows for IL-6-independent growth, this is a good model to test whether FTIs specifically target growth-promoting ras-activated pathways in myeloma. Although they had little effect in 10% serum, two separate FTIs induced apoptosis of myeloma cells when cultured in low serum, and mutated ras-expressing cells were more sensitive than wild-type (WT) ras-expressing cells. However, induction of apoptosis did not correlate with inhibition of ras processing. Although they had no effect on AKT activity, under low serum conditions FTIs inhibited constitutive activation of the p70S6kinase and nuclear factor kappaB signal proteins in both mutated ras-expressing MM lines and extracellular signal-regulated kinase (ERK) activity in mutated N-ras-expressing cells. However, in studies where p70, nuclear factor kappaB, and ERK were comparably inhibited by other inhibitors or by gene transfer, we could not identify effects on these pathways as participating in the apoptotic response. FTIs were also able to abrogate the IL-6 proliferative response of WT ras-expressing MM cells, and this was associated with inhibition of IL-6-induced activation of ERK, AKT, and p70. The induction of apoptosis and prevention of the IL-6 response in MM cells containing mutated or WT ras provide support for the therapeutic potential of FTIs in this disease. C1 Univ Calif Los Angeles, W Los Angeles VA Med Ctr, Hematol Oncol Div W111H, Los Angeles, CA 90073 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. RP Lichtenstein, A (reprint author), Univ Calif Los Angeles, W Los Angeles VA Med Ctr, Hematol Oncol Div W111H, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [CA 62242, CA 96920] NR 47 TC 13 Z9 14 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUN PY 2003 VL 2 IS 6 BP 563 EP 572 PG 10 WC Oncology SC Oncology GA 691LC UT WOS:000183606900008 PM 12813136 ER PT J AU Shang, YF Myers, M Brown, M AF Shang, YF Myers, M Brown, M TI Formation of the androgen receptor transcription complex (vol 9, pg 601, 2002) SO MOLECULAR CELL LA English DT Correction C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 1 TC 3 Z9 3 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUN PY 2003 VL 11 IS 6 BP 1697 EP 1697 DI 10.1016/S1097-2765(03)00237-5 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 693LU UT WOS:000183719700028 ER PT J AU Chakravarty, G Hadsell, D Buitrago, W Settleman, J Rosen, JM AF Chakravarty, G Hadsell, D Buitrago, W Settleman, J Rosen, JM TI p190-B RhoGAP regulates mammary ductal morphogenesis SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID TERMINAL END BUDS; GLAND DEVELOPMENT; IGF-I; BREAST-CANCER; CELL; INVASION; GTPASES; GROWTH; GENE; PROLIFERATION AB Previous studies from our laboratory have demonstrated that p190-B RhoGAP (p190-B) is differentially expressed in the Cap cells of terminal end buds (TEBs) and poorly differentiated rodent mammary tumors. Based on these observations we hypothesized that p190-B might play an essential role in invasion of the TEBs into the surrounding fat pad during ductal morphogenesis. To test this hypothesis, mammary development was studied in p190B- deficient mice. A haploinsufficiency phenotype was observed in p190-B heterozygous mice as indicated by decreased number and rate of ductal outgrowth(s) at 3, 4, and 5 wk of age when compared with their wild-type littermates. This appeared to result from decreased proliferation in the Cap cells of the TEBs, a phenotype remarkably similar to that observed previously in IGF-I receptor null mammary epithelium. Furthermore, decreased expression of insulin receptor substrates 1 and 2 were observed in TEBs of p190-B heterozygous mice. These findings are consistent with decreased IGF signaling observed previously in p190B(-/-) mouse embryo fibroblasts. To further assess if this defect was cell autonomous or due to systemic endocrine effects, the mammary anlagen from p190-B+/+, p190-B+/-, and p190-B-/- mice was rescued by transplantation into the cleared fat pad of recipient Rag1(-/-) mice. Surprisingly, as opposed to 75-80% outgrowths observed using wildtype donor epithelium, only 40% of the heterozygous and none of the p190-B-/- epithelial transplants displayed any outgrowths. Together, these results suggest that p190-B regulates ductal morphogenesis, at least in part, by modulating the IGF signaling axis. C1 Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Childrens Nutr Res Ctr, Dept Pediat, Houston, TX USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. RP Rosen, JM (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. OI Buitrago, William/0000-0002-7075-2203 FU NCI NIH HHS [R01-CA-64255]; NIDDK NIH HHS [R01-DK-052197-06A1] NR 32 TC 36 Z9 37 U1 1 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 2003 VL 17 IS 6 BP 1054 EP 1065 DI 10.1210/me.2002-0428 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683LY UT WOS:000183152000007 PM 12637587 ER PT J AU Wang, S Petravicz, J Breakefield, XO AF Wang, S Petravicz, J Breakefield, XO TI Single HSV-amplicon vector mediates drug-induced gene expression via dimerizer system SO MOLECULAR THERAPY LA English DT Article DE HSV; amplicon; rapamycin; dimerizer; regulation; vector ID HERPES-SIMPLEX VIRUS; BACTERIAL ARTIFICIAL CHROMOSOME; FLUORESCENT PROTEIN; ESCHERICHIA-COLI; PACKAGING SYSTEM; MAMMALIAN-CELLS; LONG-TERM; MICE; DNA; TRANSDUCTION AB A variety of viral vectors have been used to deliver genes into various tissues. Most have typically relied on either viral or cell-specific mammalian promoters to express transgenes. More recently, regulated promoter systems have been developed to fine-tune gene expression. Due to limited transgene capacity in most viral vectors, regulatory elements are typically subcloned into two separate vectors, which must be delivered simultaneously to a target cell. Here, we have cloned all the components of the rapamycin-based "dimerizer" system into the pantropic HSV-amplicon vector and used it to deliver and regulate red fluorescent protein (RFP) expression in cultured cells in a drug-dose-dependent manner. 293T/17 cells infected at an m.o.i. of 1 transducing unit/cell and induced with 20 nM rapamycin resulted in a 25-fold increase in RFP mRNA levels after 24 h as assessed by quantitative RT-PCR. However, due to a reduced ability to detect RFP optically, only a 5-fold induction in the number of RFP-expressing cells was noted by FACS analysis 48 h after infection. Further, there was at least 100-fold variation in the levels of RFP in individual, infected cells in the induced state. Gene induction in several neuronal models, including primary cell culture and organotypic cultures, as well as in rodent brain, was observed. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Neurosci Program, Charlestown, MA 02129 USA. RP Wang, S (reprint author), Massachusetts Gen Hosp E, Mol Neurogenet Unit, 13th St,Bldg 149,6th Floor, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA86355]; NINDS NIH HHS [NS24279] NR 46 TC 19 Z9 20 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 1525-0016 J9 MOL THER JI Mol. Ther. PD JUN PY 2003 VL 7 IS 6 BP 790 EP 800 DI 10.1016/S1525-0016(03)00094-7 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 687PF UT WOS:000183385100012 PM 12788653 ER PT J AU Weisskopf, MG Chen, HL Schwarzschild, MA Kawachi, I Ascherio, A AF Weisskopf, MG Chen, HL Schwarzschild, MA Kawachi, I Ascherio, A TI Prospective study of phobic anxiety and risk of Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; anxiety; prospective studies; epidemiology; risk factors ID PANIC ATTACKS; HEART-DISEASE; BINDING-SITES; DEPRESSION; DISORDERS; MECHANISMS; MEN; CONSUMPTION; COMORBIDITY; DEMENTIA AB Anxiety disorders are common in Parkinson's disease (PD). However, the risk of PD among people with anxiety has not been examined in a prospective cohort study. We examined this relation prospectively within the Health Professionals Follow-Up Study, a cohort of US male health professionals. In 1988, anxiety was assessed using the Crown-Crisp phobic anxiety index in 35,815 men without PD, stroke, or cancer at baseline. There were 189 incident cases of PD during 12 years of follow-up. After adjusting for age, smoking, and caffeine intake, the relative risk of PD among men with the highest level of anxiety (Crown-Crisp index scores of 4 and above) was 1.5 (95% Cl = 1.0-2.1; P-trend = 0.01) compared to men with the lowest level of anxiety. This positive association persisted after excluding cases of PD with onset in the first 2 years of follow-up. Use of anxiolytic medication was also associated with an elevated risk of PD (RR = 1.6; 95% Cl = 0.9-3.1), but adjusting for this potential confounder did not materially affect the association between anxiety and risk of PD. Our results suggest that anxiety is a risk factor for PD. Whether this association is causal or the result of shared underlying biology remains a question. (C) 2003 Movement Disorder Society. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Weisskopf, MG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 666 Huntington Ave,Bldg 2, Boston, MA 02115 USA. OI Chen, Honglei/0000-0003-3446-7779 FU NINDS NIH HHS [NS35624] NR 39 TC 74 Z9 76 U1 3 U2 4 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 JUN PY 2003 VL 18 IS 6 BP 646 EP 651 DI 10.1002/mds.10425 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 687ZR UT WOS:000183407800005 PM 12784267 ER PT J AU Jain, RK AF Jain, RK TI Molecular regulation of vessel maturation SO NATURE MEDICINE LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; EMBRYONIC STEM-CELLS; BLOOD-VESSELS; BONE-MARROW; IN-VIVO; HIF-1-ALPHA/VP16 HYBRID; VASCULAR DEVELOPMENT; SIGNALING PATHWAYS; PROGENITOR CELLS; TUMOR-GROWTH AB The maturation of nascent vasculature, formed by vasculogenesis or angiogenesis, requires recruitment of mural cells, generation of an extracellular matrix and specialization of the vessel wall for structural support and regulation of vessel function. In addition, the vascular network must be organized so that all the parenchymal cells receive adequate nutrients. All of these processes are orchestrated by physical forces as well as by a constellation of ligands and receptors whose spatio-temporal patterns of expression and concentration are tightly regulated. Inappropriate levels of these physical forces or molecules produce an abnormal vasculature- a hallmark of various pathologies. Normalization of the abnormal vasculature can facilitate drug delivery to tumors and formation of a mature vasculature can help realize the promise of therapeutic angiogenesis and tissue engineering. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab, 100 Blossom St, Boston, MA 02114 USA. NR 100 TC 1395 Z9 1467 U1 18 U2 181 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 JUN PY 2003 VL 9 IS 6 BP 685 EP 693 DI 10.1038/nm0603-685 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 688PH UT WOS:000183444100023 PM 12778167 ER PT J AU Ishida, S Yamashiro, K Usui, T Kaji, Y Ogura, Y Hida, T Honda, Y Oguchi, Y Adamis, AP AF Ishida, S Yamashiro, K Usui, T Kaji, Y Ogura, Y Hida, T Honda, Y Oguchi, Y Adamis, AP TI Leukocytes mediate retinal vascular remodeling during development and vaso-obliteration in disease SO NATURE MEDICINE LA English DT Article ID ENDOTHELIAL-CELL APOPTOSIS; OXIDIZED LDL; IN-VIVO; GROWTH; NEOVASCULARIZATION; EXPRESSION; VEGF; INHIBITOR; SYSTEM; DEATH AB Retinal ischemia can cause vision-threatening pathological neovascularization. The mechanisms of retinal ischemia are not fully understood, however. Here we have shown that leukocytes prune the retinal vasculature during normal development and obliterate it in disease. Beginning at postnatal day 5 (P5) in the normal rat, vascular pruning began centrally and extended peripherally, leaving behind a less dense, smaller-caliber vasculature. The pruning was correlated with retinal vascular expression of intercellular adhesion molecule-1 (ICAM-1) and coincided with an outward-moving wave of adherent leukocytes composed in part of cytotoxic T lymphocytes. The leukocytes adhered to the vasculature through CD18 and remodeled it through Fas ligand (FasL)-mediated endothelial cell apoptosis. In a model of oxygen-induced ischemic retinopathy, this process was exaggerated. Leukocytes used CD18 and FasL to obliterate the retinal vasculature, leaving behind large areas of ischemic retina. In vitro, T lymphocytes isolated from oxygen-exposed neonates induced a FasL-mediated apoptosis of hyperoxygenated endothelial cells. Targeting these pathways may prove useful in the treatment of retinal ischemia, a leading cause of vision loss and blindness. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Angiogenesis Retina Res Lab, Boston, MA 02114 USA. Keio Univ, Sch Med, Dept Ophthalmol, Shinjuku Ku, Tokyo 1608582, Japan. Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Sakyo Ku, Kyoto 6068507, Japan. Univ Tokyo, Fac Med, Dept Ophthalmol, Bunkyo Ku, Tokyo 1138655, Japan. Nagoya City Univ, Med Univ, Dept Ophthalmol, Mizuho Ku, Aichi 4678601, Japan. Kyorin Eye Ctr, Tokyo 1818611, Japan. Eyetech Res Ctr, Woburn, MA 01801 USA. RP Adamis, AP (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Angiogenesis Retina Res Lab, 325 Cambridge St, Boston, MA 02114 USA. RI ISHIDA, SUSUMU/D-7067-2012 FU NEI NIH HHS [EY12611, EY11627] NR 25 TC 145 Z9 148 U1 0 U2 9 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 JUN PY 2003 VL 9 IS 6 BP 781 EP 788 DI 10.1038/nm877 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 688PH UT WOS:000183444100036 PM 12730690 ER PT J AU Brown, E McKee, T diTomaso, E Pluen, A Seed, B Boucher, Y Jain, RK AF Brown, E McKee, T diTomaso, E Pluen, A Seed, B Boucher, Y Jain, RK TI Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation SO NATURE MEDICINE LA English DT Article ID 2ND-HARMONIC GENERATION; MICROSCOPY; RELAXIN; TRANSPORT; DIFFUSION; TISSUE AB The content and structure of collagen is essential in governing the delivery of therapeutic molecules in tumors. Thus, simple histological staining of tumor tissue biopsies for collagen could be used to assess the accessibility of molecular therapeutics in tumors. Here we show that it is possible to optically image fibrillar collagen in tumors growing in mice using second-harmonic generation (SHG). Using this noninvasive technique, we estimated relative diffusive hindrance, quantified the dynamics of collagen modification after pharmacologic intervention and provided mechanistic insight into improved diffusive transport induced by the hormone relaxin. This technology could offer basic scientists and clinicians an enhanced ability to estimate the relative penetrabilities of molecular therapeutics. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester M13 9PL, Lancs, England. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RI Pluen, Alain/F-5300-2015; OI Pluen, Alain/0000-0002-5953-8011; McKee, Trevor/0000-0002-2195-6146 FU NCI NIH HHS [P01CA80124]; NIGMS NIH HHS [T32GM08334] NR 20 TC 516 Z9 523 U1 9 U2 82 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 JUN PY 2003 VL 9 IS 6 BP 796 EP 800 DI 10.1038/nm879 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 688PH UT WOS:000183444100038 PM 12754503 ER PT J AU Williams, ZM Elfar, JC Eskandar, EN Toth, LJ Assad, JA AF Williams, ZM Elfar, JC Eskandar, EN Toth, LJ Assad, JA TI Parietal activity and the perceived direction of ambiguous apparent motion SO NATURE NEUROSCIENCE LA English DT Article ID PERCEPTUAL DECISION; VISUAL GUIDANCE; MACAQUE MONKEY; CORTICAL AREAS; MT; CORTEX; ATTENTION; SIGNALS; PERFORMANCE; MODULATION AB We recorded from parietal neurons in monkeys (Macacca mulatta) trained to report the direction of an apparent motion stimulus consisting of regularly spaced columns of dots surrounded by an aperture. Displacing the dots by half their inter-column spacing produced vivid apparent motion that could be perceived in either the preferred or anti-preferred direction for each neuron. Many neurons in the lateral intraparietal area (LIP) responded more strongly on trials in which the animals reported perceiving the neurons' preferred direction, independent of the hand movement used to report their percept. This selectivity was less common in the medial superior temporal area (MST) and virtually absent in the middle temporal area (MT). Variations in activity of LIP and MST neurons just before motion onset were also predictive of the animals' subsequent perceived direction. These data suggest a hierarchy of representation in parietal cortex, whereby neuronal responses become more aligned with subjective perception in higher parietal areas. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Assad, JA (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA. FU NEI NIH HHS [EY12106] NR 30 TC 105 Z9 105 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JUN PY 2003 VL 6 IS 6 BP 616 EP 623 DI 10.1038/nn1055 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 683GQ UT WOS:000183140400019 PM 12730699 ER PT J AU Kuchroo, VK Umetsu, DT DeKruyff, RH Freeman, GJ AF Kuchroo, VK Umetsu, DT DeKruyff, RH Freeman, GJ TI The TIM gene family: Emerging roles in immunity and disease SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID GENOME-WIDE SEARCH; HEPATITIS-A VIRUS; KIDNEY INJURY MOLECULE-1; AUTOIMMUNE-DISEASE; CELLULAR RECEPTOR; CUTTING EDGE; ASTHMA; CELLS; SUSCEPTIBILITY; IDENTIFICATION AB The search for cell-surface markers that can distinguish T helper 1 (T(H)1) cells from T(H)2 cells has led to the identification of a new gene family, encoding the T-cell immunoglobulin mucin (TIM) proteins, some of which are differentially expressed by T(H)1 and T(H)2 cells. The role of the TIM-family proteins in immune regulation is just beginning to emerge. Here, we describe the various TIM-family members in mice and humans, and discuss the genetic and functional evidence for their role in regulating autoimmune and allergic diseases. C1 Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Stanford Univ, Dept Pediat, Sch Med, Div Immunol & Allergy, Stanford, CA 94305 USA. RP Kuchroo, VK (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. NR 44 TC 251 Z9 287 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD JUN PY 2003 VL 3 IS 6 BP 454 EP 462 DI 10.1038/nri1111 PG 9 WC Immunology SC Immunology GA 688FJ UT WOS:000183423300011 PM 12776205 ER PT J AU Autran, B Debre, P Walker, B Katlama, C AF Autran, B Debre, P Walker, B Katlama, C TI Opinion - Therapeutic vaccines against HIV need international partnerships SO NATURE REVIEWS IMMUNOLOGY LA English DT Editorial Material ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS-INFECTION; CELLULAR IMMUNE-RESPONSES; CYTOTOXIC T-LYMPHOCYTES; LOW VIRAL LOAD; REVERSE-TRANSCRIPTASE; TYPE-1 INFECTION; VIREMIA; CD8(+); CELLS C1 CHU Pitie Salpetriere, Lab Immunol Cellulaire, Serv Malad Infect, F-75651 Paris, France. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Howard Hughes Med Inst, Boston, MA 02129 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02129 USA. RP Autran, B (reprint author), CHU Pitie Salpetriere, Lab Immunol Cellulaire, Serv Malad Infect, F-75651 Paris, France. NR 39 TC 29 Z9 30 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD JUN PY 2003 VL 3 IS 6 BP 503 EP 508 DI 10.1038/nri1107 PG 6 WC Immunology SC Immunology GA 688FJ UT WOS:000183423300016 PM 12776210 ER PT J AU Estepa, JC Lopez, I Felsenfeld, AJ Gao, P Cantor, T Rodriguez, M Aguilera-Tejero, E AF Estepa, JC Lopez, I Felsenfeld, AJ Gao, P Cantor, T Rodriguez, M Aguilera-Tejero, E TI Dynamics of secretion and metabolism of PTH during hypo- and hypercalcaemia in the dog as determined by the 'intact' and 'whole' PTH assays SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE calcium; hypercalcaemia; hypocalcaemia; intact PTH; parathyroid hormone; whole PTH ID PARATHYROID-HORMONE SECRETION; IONIZED CALCIUM-CONCENTRATION; CARBOXYL-TERMINAL FRAGMENTS; RENAL-FAILURE; IMPROVEMENT; STIMULATION; PHOSPHATE; DECREASE; RECEPTOR; DIET AB Background. Recent evidence has shown that the assay for 'intact' parathyroid hormone (I-PTH) not only reacts with 1-84 PTH but also with large non-1-84 PTH fragments, most of which is probably 7-84 PTH. As a result, an assay specific for 1-84 PTH named whole' PTH (W-PTH) has been developed. The present study was designed: (i) to determine whether the W-PTH assay reliably measures PTH values in the dog; (ii) to evaluate differences between the W-PTH and I-PTH assays during hypo- and hypercalcaemia; and (iii) to assess the peripheral metabolism of W-PTH and I-PTH. Methods. In normal dogs, hypocalcaemia was induced by EDTA infusion and was followed with a 90 min hypocalcaemic clamp. Hypercalcaemia was induced with a calcium infusion. Results. I-PTH and W-PTH values increased from 36 +/- 8 and 13 +/- 3 pg/ml (P = 0.01) at baseline to a maximum of 158 40 and 62 15 pg/ml (P = 0.02 vs I-PTH) during hypocalcaemia. The W-PTH/I-PTH ratio, 38 +/- 4% at baseline, did not change during the induction of hypocalcaemia, but sustained hypocalcaemia increased (P < 0.05) this ratio. During hypercalcaemia, maximal suppression for I-PTH was 2.0 +/- 0.5 and only 5.7 +/- 0.6 pg/ml for W-PTH, due to a decreased sensitivity of the W-PTH assay at values < 5 pg/ml. The disappearance rate of PTH was determined in five additional dogs which underwent a parathyroidectomy (PTX). At 2.5 min after PTX1 W-PTH was metabolized more rapidly, with a value of 25 +/- 2% of the pre-PTX value vs 30 +/- 3% for I-PTH (P < 0.05). Conclusions. (i) The W-PTH/I-PTH ratio is less in the normal dog than in the normal human, suggesting that the percentage of non-1-84 PTH measured with the I-PTH assay is greater in normal dogs than in normal humans; (ii) the lack of change in the W-PTH/I-PTH ratio during acute hypocalcaemia is different from the situation observed in humans; and (iii) the dog appears to be a good model to study I-PTH and W-PTH assays during hypocalcaemia. C1 Univ Cordoba, Dept Med & Cirugia Anim, Cordoba 14014, Spain. Hosp Univ Reina Sofia, Dept Nefrol, Cordoba 14004, Spain. Hosp Univ Reina Sofia, Unidad Invest, Cordoba 14004, Spain. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Scantibodies Lab Inc, Dept R&D & Diagnost, Santee, CA USA. RP Aguilera-Tejero, E (reprint author), Univ Cordoba, Dept Med & Cirugia Anim, Campus Univ Rabanales,Ctra Madrid Cadiz km 396, Cordoba 14014, Spain. RI Rodriguez, teresa/H-5452-2011 NR 25 TC 6 Z9 6 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD JUN PY 2003 VL 18 IS 6 BP 1101 EP 1107 DI 10.1093/ndt/gfg104 PG 7 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 689VF UT WOS:000183513100012 PM 12748341 ER PT J AU Reid, SJ Rees, MI van Roon-Mom, WMC Jones, AL MacDonald, ME Sutherland, G During, MJ Faull, RLM Owen, MJ Dragunow, M Snell, RG AF Reid, SJ Rees, MI van Roon-Mom, WMC Jones, AL MacDonald, ME Sutherland, G During, MJ Faull, RLM Owen, MJ Dragunow, M Snell, RG TI Molecular investigation of TBP allele length: a SCA17 cellular model and population study SO NEUROBIOLOGY OF DISEASE LA English DT Article ID TATA-BINDING PROTEIN; DOMINANT CEREBELLAR-ATAXIA; NEURONAL INTRANUCLEAR INCLUSIONS; EXPANDED POLYGLUTAMINE; CAG REPEAT; NEURODEGENERATIVE DISEASES; TRINUCLEOTIDE REPEAT; EXPANSION; GENE; HUNTINGTIN AB Recently, an inherited spinocerebellar ataxia (SCA17) has been attributed to polyglutamine coding expansions within the gene coding for human TATA-box binding protein (TBP). The normal repeat range is 25-42 units with patients having as few as 46 repeats. We undertook a TBP repeat length population study showing its relative stability, skewed distribution, and substantial population specific differences. To investigate the mechanism of neurodegeneration in SCA17 we have developed a cellular model expressing full-length TBP with a range of polyQ expansions. As has been found with other polyQ cellular models, insoluble intracellular inclusions form in a repeat-length-dependent manner. In addition, we have shown that the expanded TBP polyQ tract is able to interact with other overexpressed polyQ-containing proteins. Importantly, overexpression of expanded TBP results in increased Cre-dependent transcriptional activity. As TBP is required for transcription by all RNA polymerases, this may indicate a mechanism for aberrant polyQ gain of function. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Univ Auckland, Dept Mol Med, Auckland 1, New Zealand. Univ Auckland, Dept Anat Radiol, Auckland 1, New Zealand. Univ Wales Coll Med, Dept Med Genet, Cardiff CF4 4XN, S Glam, Wales. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Univ Wales Coll Med, Dept Psychol Med, Cardiff CF4 4XN, S Glam, Wales. Univ Auckland, Dept Pharmacol, Auckland 1, New Zealand. RP Snell, RG (reprint author), Univ Auckland, Dept Mol Med, Private Bag 92019, Auckland 1, New Zealand. RI turton, miranda/F-4682-2011; Reid, Suzanne/H-7082-2012; Rees, Mark/J-3129-2012; Sutherland, Greg/C-8674-2015; OI Sutherland, Greg/0000-0003-2493-9736; Reid, Suzanne/0000-0002-8068-6529 FU Medical Research Council [G9810900] NR 35 TC 16 Z9 18 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JUN PY 2003 VL 13 IS 1 BP 37 EP 45 DI 10.1016/S0969-9961(03)00014-7 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 681TJ UT WOS:000183051200004 PM 12758065 ER PT J AU Nahas, Z George, MS Horner, MD Markowitz, JS Li, XB Lorberbaum, JP Owens, SD McGurk, S DeVane, L Risch, SC AF Nahas, Z George, MS Horner, MD Markowitz, JS Li, XB Lorberbaum, JP Owens, SD McGurk, S DeVane, L Risch, SC TI Augmenting atypical Antipsychotics with a cognitive enhancer (donepezil) improves regional brain activity in schizophrenia patients: A pilot double-blind placebo controlled BOLD fMRI study SO NEUROCASE LA English DT Article DE donepezil; schizophrenia; prefrontal; cingulate; fMRI; cognition; verbal fluency ID POSITRON-EMISSION-TOMOGRAPHY; ATTENUATED FRONTAL ACTIVATION; VERBAL FLUENCY TASK; PREFRONTAL CORTEX; FUNCTIONAL-ANATOMY; ALZHEIMERS-DISEASE; WORKING-MEMORY; FIRST-EPISODE; GENETIC RISK; WORD LISTS AB Cognitive impairments are cardinal features of schizophrenia and predictors of poor vocational and social outcome. Imaging studies with verbal fluency tasks (VFT) lead some to suggest that in schizophrenia, the combination of a failure to deactivate the left temporal lobe and a hypoactive frontal lobe reflects a functional disconnectivity between the left prefrontal cortex and temporal lobe. Others have theorized that an abnormal cingulate gyrus modulates such fronto-temporal connectivity. Thus addition of a cognitive enhancing medication to current antipsychotic therapy might improve functionality of networks necessary in working memory and internal concept generation. To test this hypothesis, we serially measured brain activity in 6 subjects on stable atypical antipsychotics performing a VFT, using BOLD fMRI. Measurements were made at baseline and again after groups were randomized to receive 12 weeks of donepezil (an acetylcholinesterase inhibitor) and placebo in a blind cross-over design. Donepezil addition provided a functional normalization with an increase in left frontal lobe and cingulate activity when compared to placebo and from baseline scans. This pilot study supports the cingulate's role in modulating cognition and neuronal connectivity in schizophrenia. C1 Med Univ S Carolina, Inst Psychiat & Behav Sci, Ctr Adv Imaging Res, Dept Psychiat,Brain Stimulat Lab, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. Mt Sinai Med Ctr, Northport, NY USA. RP Nahas, Z (reprint author), Med Univ S Carolina, Inst Psychiat & Behav Sci, Ctr Adv Imaging Res, Dept Psychiat,Brain Stimulat Lab, POB 25086167,President St,Room 502 N, Charleston, SC 29425 USA. NR 52 TC 38 Z9 40 U1 2 U2 2 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1355-4794 J9 NEUROCASE JI Neurocase PD JUN PY 2003 VL 9 IS 3 BP 274 EP 282 PG 9 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 707YR UT WOS:000184538000009 PM 12925933 ER PT J AU Berman, SM Mandelkern, MA Phan, H Zaidel, E AF Berman, SM Mandelkern, MA Phan, H Zaidel, E TI Complementary hemispheric specialization for word and accent detection SO NEUROIMAGE LA English DT Article DE hemispheric laterality; dichotic listening; language; prosodic processing; brain imaging ID CORPUS-CALLOSUM MORPHOMETRY; AUDITORY-VERBAL MEMORY; BASE-LINE CONDITIONS; IMAGING COGNITION; PREFRONTAL CORTEX; EPISODIC MEMORY; FUNCTIONAL MRI; BRAIN SYSTEMS; PET; RETRIEVAL AB When we hear a familiar word pronounced in a foreign accent, which parts of the brain identify the word and which identify the accent? Here we present converging evidence from PET blood flow, event-related scalp potentials, and behavioral responses during dichotic listening, showing homologous and complementary hemispheric specialization for word and accent detection. Accuracy of detecting target words was greater when stimuli were presented to the right ear, indicating left hemisphere specialization, with no ear advantage for detecting target accents. Detection of words also produced increased blood flow in a left frontal area associated with motor and phonetic processing, and a left temporal area associated with semantic memory. Homologous areas of the right hemisphere, together with right prefrontal and precuneus regions, showed increased blood flow during detection of accents. Separate analyses for each detection task indicated that voxels whose activity maximally correlated with accuracy were in the left hemisphere for word detection, but in the right hemisphere for accent detection. Voxels whose activity maximally correlated with inaccuracy were in the opposite hemisphere for both tasks, strengthening the interpretation that between-task differences in brain activation are related to lateralized specializations for task performance. ERP waveforms and reaction times suggested that greater left hemisphere activation during word detection preceded greater right hemisphere activation during accent detection. The results are interpreted as supporting left hemisphere specialization for extraction of the linguistic, phonetic, and semantic information contained in speech, and right hemisphere specialization for pragmatics, the social context of linguistic communication. (C) 2003 Elsevier Science (USA). All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, Nucl Med Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA. Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90024 USA. RP Berman, SM (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Box 11,760 Westwood Plaza, Los Angeles, CA 90024 USA. FU NINDS NIH HHS [NS20187] NR 60 TC 13 Z9 13 U1 3 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 JUN PY 2003 VL 19 IS 2 BP 319 EP 331 DI 10.1016/S1053-8119(03)00120-4 PN 1 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 690UP UT WOS:000183568900011 PM 12814582 ER PT J AU Wiegell, MR Tuch, DS Larsson, HBW Wedeen, VJ AF Wiegell, MR Tuch, DS Larsson, HBW Wedeen, VJ TI Automatic segmentation of thalamic nuclei from diffusion tensor magnetic resonance imaging SO NEUROIMAGE LA English DT Article ID HUMAN BRAIN; IN-VIVO; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; ANISOTROPY; ATLAS; MRI; SCHIZOPHRENIA; THALAMOTOMY; CORTEX AB The nuclei of the thalamus have traditionally been delineated by their distinct cyto/myeloarchitectural appearance on histology. Here, we show that diffusion tensor magnetic resonance imaging (DTI) can noninvasively resolve the major thalamic nuclei based on the characteristic fiber orientation of the corticothalamic/thalamocortical striations within each nucleus. Using an automatic clustering algorithm, we extracted the Talairach coordinates for the individual thalamic nuclei. The center-of-mass coordinates for the segmented nuclei were found to agree strongly with those obtained from a histological atlas. The ability to resolve thalamic nuclei with DTI will allow for morphometric analysis of specific nuclei and improved anatomical localization of functional activation in the thalamus. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Hvidovre Univ Hosp, Danish Res Ctr Magnet Resonance, DK-2650 Hvidovre, Denmark. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Wiegell, MR (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA. FU NIMH NIH HHS [1R01 MH 64044 A 01]; NINDS NIH HHS [5R01 NS 38477-02] NR 61 TC 162 Z9 169 U1 1 U2 14 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 JUN PY 2003 VL 19 IS 2 BP 391 EP 401 DI 10.1016/S1053-8119(03)00044-2 PN 1 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 690UP UT WOS:000183568900017 PM 12814588 ER PT J AU Chen, JF Moratalla, R Yu, LQ Martin, AB Xu, K Bastia, E Hackett, E Alberti, I Schwarzschild, MA AF Chen, JF Moratalla, R Yu, LQ Martin, AB Xu, K Bastia, E Hackett, E Alberti, I Schwarzschild, MA TI Inactivation of adenosine A(2A) receptors selectively attenuates amphetamine-induced behavioral sensitization SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE adenosine A(2A)receptor; dopamine receptor; amphetamine; psychostimulant; behavioral sensitization; drug addiction ID STRIATAL DOPAMINE RELEASE; AGONIST-INDUCED ROTATION; RAT NEOSTRIATAL NEURONS; MUTANT MICE; 6-HYDROXYDOPAMINE-LESIONED RATS; MEDIATED MODULATION; C-FOS; STRIATOPALLIDAL NEURONS; CELLULAR-RESPONSES; NUCLEUS-ACCUMBENS AB Repeated treatment with the psychostimulant amphetamine produces behavioral sensitization that may represent the neural adaptations underlying some features of psychosis and addiction in humans. In the present study we investigated the role of adenosine A(2A) receptors in psychostimulant-induced locomotor sensitization using an A(2A) receptor knockout (A(2A) KO) model. Daily treatment with amphetamine for 1 week resulted in an enhanced motor response on day 8 (by two-fold compared to that on day 1), and remained enhanced at day 24 upon rechallenge with amphetamine. By contrast, locomotor sensitization to daily amphetamine did not develop in A(2A) KO mice on day 8 or 24, and this absence was not the result of a nonspecific threshold effect. The absence of behavioral sensitization was selective for amphetamine since daily treatment with the D-1 agonist SKF81297 (2.5 mg/kg) or the D-2 agonist quinpirole (1.0mg/kg) produced similar behavioral sensitization in both WT and A(2A) KO mice. Furthermore, coinjection of SKF81297 and quinpirole also resulted in indistinguishable locomotor sensitization in A(2A) KO and WT mice, suggesting normal D-1 and D-2 receptor responsiveness. Finally, at the cellular level A(2A) receptor inactivation abolished the increase in striatal dynorphin mRNA induced by repeated amphetamine administration. The selective absence of amphetamine-induced behavioral sensitization in A(2A) KO mice suggests a critical role of the A(2A) receptor in the development of psychostimulant-induced behavioral sensitization, and supports the pharmacological potential of A(2A) adenosinergic agents to modulate adaptive responses to repeated psychostimulant exposure. C1 Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Mol Neurobiol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. CSIC, Inst Cajal, E-28002 Madrid, Spain. RP Schwarzschild, MA (reprint author), Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Mol Neurobiol Lab, 114 St, Charlestown, MA 02129 USA. OI Moratalla, Rosario/0000-0002-7623-8010 FU NIDA NIH HHS [DA13508, DA07496]; NINDS NIH HHS [NS37403] NR 62 TC 41 Z9 43 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 2003 VL 28 IS 6 BP 1086 EP 1095 DI 10.1038/sj.npp.1300152 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 686HT UT WOS:000183316100008 PM 12700712 ER PT J AU Kalkanis, SN Eskandar, EN Carter, BS Barker, FG AF Kalkanis, SN Eskandar, EN Carter, BS Barker, FG TI Microvascular decompression surgery in the United States, 1996 to 2000: Mortality rates, morbidity rates, and the effects of hospital and surgeon volumes SO NEUROSURGERY LA English DT Article DE microvascular decompression; mortality rate; volume-outcome relationship ID PARTIAL SENSORY RHIZOTOMY; TRIGEMINAL NEURALGIA; HEMIFACIAL SPASM; GLOSSOPHARYNGEAL NEURALGIA; RADIOFREQUENCY RHIZOTOMY; SURGICAL TREATMENTS; OUTCOMES; REEVALUATION; SERIES; EVENTS AB Objective: Microvascular decompression (MVD) is associated with low mortality and morbidity rates at specialized centers, but many MVD procedures are performed outside such centers. We studied short-term end points MVD in a national hospital discharge database sample. METHODS: A retrospective cohoert study was performed by using a nationwide Inpatient sample, 1996 to 2000. RESULTS: The sample included 1326 MVD procedures for treatment neuralgia, 237 for treatment of hemifacial spasm, and 27 for treatment of glossopharyngeal neuralgia, performed at 305 hospitals by 277 identified surgeons. The mortality rate was 0.3%, and the rate of discharge other than to home was 3.8%. Neurological complications were coded in 1.7% of cases, hematomas in 0.5%, and facial palsies on 0.6%, with 0.4% of patients requiring ventriculostomies and 0.7% postoperative ventilation. Trigeminal nerve section was also coded for 3.4% of patients with trigeminal neuralgia, more commonly among older pateients (P = 0.08), among female patients (P = 0.03), and at teaching hospitals (P = 0.02). The median annual caseloads were 5 cases per hospital (range, 1-195 cases) and 3 cases per surgeon (range, 1-107 cases). With adjustment for age, sex, race, primary insurance, diagnosis (trigeminal neuralgia versus hemifacial spasm versus glossopharyngeal neuralgia), geographic region, admission type and source, and medical comorbidities, outcomes at discharg were superior at higher-volume hospitals (P = 0.006) and with higher-volume surgeons (P = 0.02). Complications were less frequent after surgery performed at high volume hospitals (P = 0.04) or by high-volume surgeons (P = 0.01). The rate of discharge other than to home was 5.1% for the lowest-volume-quartile hospitals, compared with 1.6% for the highest-volume-quartile hospitals, compared with 1.6% for the highest-volume-quartile hospitals. Volume and mortality rate were not significantly related, but three of the four deaths in the in the serier followed procedures performed by surgeons who had performed only one MVD procedure that year. Length of stay (median, 3d) and hospital volume were not significantly related. Hospital charges were slightly higher at higher-volume hospitals (P = 0.07). CONCLUSION: Although most MVD procedures in the United States are performed at low-volume centers, mortality rates remain low. Mortality rates are significantly lower at high-volume hospitals and with high-volume surgeons. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Cox 315,32 Fruit St, Boston, MA 02114 USA. NR 43 TC 131 Z9 150 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUN PY 2003 VL 52 IS 6 BP 1251 EP 1261 DI 10.1227/01.NEU.0000065129.25359 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 687FW UT WOS:000183366600015 PM 12762870 ER PT J AU Carpentieri, SC Waber, DP Pomeroy, SL Scott, RM Goumnerova, LC Kieran, MW Billett, AL Tarbell, NJ AF Carpentieri, SC Waber, DP Pomeroy, SL Scott, RM Goumnerova, LC Kieran, MW Billett, AL Tarbell, NJ TI Neuropsychological functioning after surgery in children treated for brain tumor SO NEUROSURGERY LA English DT Article DE brain tumor; neuropsychological functioning; pediatric ID LONG-TERM SURVIVORS; SERIAL-ORDER MEMORY; WHITE-MATTER LOSS; NEUROCOGNITIVE DEFICITS; COGNITIVE DYSFUNCTION; GENERAL-ANESTHESIA; IONIZING-RADIATION; VOLUME DIFFERENCES; MEDULLOBLASTOMA; RADIOTHERAPY AB OBJECTIVE: To describe the neuropsychological functioning of children treated with surgery only for localized brain tumors in Dana-Farber Cancer Institute Protocol 92-077. Subsequent reports will describe the neuropsychological functioning of children treated with surgery and stereotactic radiation therapy on Dana-Farber Cancer Institute 92-077. METHODS: The intellectual functioning of 106 patients was evaluated within 3 months after surgery. An in-depth assessment of the neuropsychological functioning, including an impairment index, was conducted for a subset of 77 school-age children (6-16 yr old) across six functional domains. Descriptive statistics were generated; binomial distribution analyses were performed to assess whether the proportion of individuals with impaired performance on each measure exceeded normative expectations. The impairment index assessed whether poor performance was attributable to a few children or reflected the performance of the cohort as a whole. RESULTS: Although the Full-Scale IQ was within normative expectations, the Verbal IQ was higher than the Performance IQ with 45% of individuals showing a significant discrepancy (P < 0.01) between these scales. There was an increased prevalence of poor performance for measures of motor output, verbal memory, and visuospatial organization. The distribution of the impairment index indicated moderate impairment across the school-age cohort rather than severe impairment in a few patients. CONCLUSION: The results document a moderate level of neuropsychological morbidity among children with brain tumors before stereotactic radiation therapy, presumably referable to the tumor itself and the surgery. The extent to which stereotactic radiation therapy may increase this burden will be assessed in follow-up studies evaluating the longitudinal neuropsychological data. C1 Childrens Hosp, Dept Psychiat, Div Psychol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. RP Carpentieri, SC (reprint author), POB 57580, Webster, TX 77598 USA. OI Kieran, Mark/0000-0003-2184-7692 NR 52 TC 33 Z9 34 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUN PY 2003 VL 52 IS 6 BP 1348 EP 1356 DI 10.1227/01.NEU.0000064804.00766.62 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 687FW UT WOS:000183366600035 PM 12762880 ER PT J AU Loeffler, JS Niemierko, A Chapman, PH AF Loeffler, JS Niemierko, A Chapman, PH TI Second tumors after radiosurgery: Tip of the iceberg or a bump in the road? SO NEUROSURGERY LA English DT Review DE glioma; oncogenesis; radiation; radiosurgery; second tumors ID BREAST-CANCER; BRAIN-TUMOR; RADIOTHERAPY; CHILDHOOD; MENINGIOMA; SURGERY; SYSTEM; RISK AB OBJECTIVE: Radiosurgery-associated second tumors have been reported in four isolated patients during the past 2 years., In our own experience, we are aware of two additional patients. The purpose of this report is to call attention to this potentially emerging problem. METHODS: A review of the English-language literature concerning patients with radiosurgery-associated second tumors was performed. In addition, we report on two patients, in our own practice who were treated in the past year. RESULTS: Four patients were found in the literature, and two additional patients were seen by the authors. Malignant tumors occurred as early as 6 years after radiosurgery. The pathological findings in three of these four malignant tumors were glioblastoma multiforme. Benign tumors developed between 16 and 19 years later. Tumors developed both within the full-dose prescription volume and in the lower-dose periphery. Of interest three of the six patients experienced complications of the radiosurgery treatment before developing second, tumors. CONCLUSION Although patients will increasingly be reported with second tumors after,radiosurgery in the future, the overall incidence seems quite low and should not alter current radiosurgical practice. However, continual surveillance of treated patients should-be considered. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Radiat Oncol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Massachusetts Gen Hosp, Dept Radiat Oncol, Radiat Oncol Serv, Cox 301,100 Blossom St, Boston, MA 02114 USA. EM jloeffler@partners.org OI Kaye, Andrew Henry/0000-0001-5049-8861; Flickinger, John/0000-0001-6900-1384 FU NCI NIH HHS [CA 21239, CA 50628] NR 21 TC 111 Z9 113 U1 0 U2 2 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 JUN PY 2003 VL 52 IS 6 BP 1436 EP 1440 DI 10.1227/01.NEU.0000064809.59806.E8 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 687FW UT WOS:000183366600051 PM 12762888 ER PT J AU Hess, C Schifferli, JA AF Hess, C Schifferli, JA TI Immune adherence revisited: Novel players in an old game SO NEWS IN PHYSIOLOGICAL SCIENCES LA English DT Article ID ERYTHROCYTE-MEMBRANE; COMPLEMENT RECEPTORS; BINDING LECTIN; T-CELLS; TYPE-1; CR-1; ANTIBODIES; CLEARANCE; PROTEIN; INNATE AB Erythrocytes bind immune complexes (IC) composed of antibodies binding their respective antigen (e.g., bacteria, parasites, viruses, or autoantigen) plus complement proteins via complement receptors [immune adherence (IA)]. In vivo studies have shown that erythrocytes act as an inert shuttle, targeting ICs to fixed macrophages in liver and spleen. Here we outline established and emerging implications of IA in health and disease. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Dept Med, Charlestown, MA 02129 USA. Univ Basel Hosp, CH-4031 Basel, Switzerland. RP Hess, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Dept Med, Charlestown, MA 02129 USA. NR 20 TC 27 Z9 30 U1 0 U2 1 PU NEWS IN PHYSIOLOGICAL SCIENCES PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0886-1714 J9 NEWS PHYSIOL SCI JI News Physiol. Sci. PD JUN PY 2003 VL 18 BP 104 EP 108 DI 10.1152/nips.01425.2002 PG 5 WC Physiology SC Physiology GA 687JT UT WOS:000183373700004 PM 12750445 ER PT J AU Moran, S Thorndike, AN Armstrong, K Rigotti, NA AF Moran, S Thorndike, AN Armstrong, K Rigotti, NA TI Physicians' missed opportunities to address tobacco use during prenatal care SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID PREGNANCY; SMOKERS; WOMEN AB Smoking cessation during pregnancy reduces the risk of adverse perinatal outcomes and leads to long-term cessation for at least some women smokers. Prenatal care offers repeated opportunities for smoking status identification and smoking cessation counseling. Using cross-sectional data from the 1991-1996 National Ambulatory Medical Care Survey, we assessed how frequently physicians caring for pregnant women identified pregnant women's smoking status and provided counseling to pregnant smokers. Data were available from 793 physicians reporting on 5,622 office visits by pregnant patients from 1991 through 1996. Physicians identified pregnant women's smoking status at 81% of visits but provided smoking counseling at only 23% of visits by pregnant smokers. Physicians were less likely to identify smoking status of non-White pregnant women but no less likely to counsel non-White smokers. These results indicate a clear need to improve quality of care provided to pregnant women who use tobacco. C1 Harvard Univ, Tobacco Res & Treatment Ctr, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Hosp Univ Penn, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Moran, S (reprint author), Harvard Univ, Tobacco Res & Treatment Ctr, Sch Med, Massachusetts Gen Hosp, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL 04440]; PHS HHS [T32HP10026-07] NR 22 TC 21 Z9 21 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JUN PY 2003 VL 5 IS 3 BP 363 EP 368 DI 10.1080/1462220031000094150 PG 6 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 716HE UT WOS:000185022100010 PM 12791532 ER PT J AU Sami, S Liu, G Mithoefer, K Suri, M Mankin, HJ AF Sami, S Liu, G Mithoefer, K Suri, M Mankin, HJ TI Pigmented villonodular synovitis of the anserine bursa SO ORTHOPEDICS LA English DT Article ID DIAGNOSIS C1 Massachusetts Gen Hosp, Orthoped Oncol Serv, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Orthoped Oncol Serv, Gray 6 Orthopaed, Boston, MA 02114 USA. RI Suri, Misty/E-7739-2011 NR 16 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD JUN PY 2003 VL 26 IS 6 BP 651 EP 652 PG 2 WC Orthopedics SC Orthopedics GA 688UX UT WOS:000183456200011 PM 12817733 ER PT J AU Jimenez-Chillaron, JC Reamer, CJ Przybyla, R Oge, A AF Jimenez-Chillaron, JC Reamer, CJ Przybyla, R Oge, A TI Altered glucose-stimulated insulin secretion causes primary hyperinsulinemia in a mouse model of low birth weight associated type 2 diabetes: Role of the glucokinase/hexokinase glucose sensing machinery SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT 2nd World Congress on Dietal Origins of Adult Disease CY JUN 07-10, 2003 CL BRIGHTON, ENGLAND C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 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 JUN PY 2003 VL 53 IS 6 SU S BP 7A EP 7A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 686RB UT WOS:000183333800048 ER PT J AU Buisine, MP Aubert, JP Walker, WA Savidge, TC AF Buisine, MP Aubert, JP Walker, WA Savidge, TC TI Developmental patterns of mucin gene expression in human fetal small intestinal xenografts maintained in severe-combined immunodeficient mice SO PEDIATRIC RESEARCH LA English DT Article ID ESCHERICHIA-COLI RDEC-1; EPITHELIAL-CELLS; IN-VITRO; YERSINIA-ENTEROCOLITICA; ABERRANT EXPRESSION; INVASIVE BACTERIA; INFECTION; ADHESION; TRACT; RABBIT AB The lack of a suitable animal model that expresses human intestinal mucin genes limits the study of mucin function. The aim of this study was to examine whether human fetal intestinal xenografts, known to model host-restricted interactions with human-specific pathogens, express mucin genes in an appropriate developmental pattern when transplanted into severe-combined immunodeficient (scid) mice. Expression profiles for eight mucin genes were examined in human fetal ileal xenografts transplanted ectopically into scid mice for 10 wk. In situ hybridization was performed on fetal, xenograft, and adult intestinal tissue sections with 35 S-labeled oligonucleotides specific to human tandem repeat sequences for MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, and MUC7 Hybridization patterns observed with the MUC2, MUC3, MUC4, and MUC5AC probes demonstrated that mucin gene expression in xenografted fetal intestine was comparable to third trimester fetal and/or adult tissues. MUC2 and MUC5AC were expressed in a developmental-specific fashion. MUC5AC, expressed in first and early second trimester fetal bowel, was never detected in intestinal xenografts. MUC2 expression displayed a late fetal and/or adult-type hybridization pattern. MUC3 and MUC4 were not developmentally expressed. Appropriate developmental regulation of known intestinal mucin genes was recorded in ectopically grafted human fetal intestinal xenografts. Adult-like patterns of mucin gene expression in this model system will permit future studies aimed at characterizing cis/trans-acting factors that regulate mucin gene expression and function during development, disease, and wound healing and also in mucin-pathogen interactions during host defense. C1 Massachusetts Gen Hosp, Dev Gastroenterol Lab, Combined Program Pediat Gastroenterol & Nutr, Combined Dept Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. INSERM, U560, F-59045 Lille, France. Hop Huriez, Lab Biochim & Biol Mol, Lille, France. Harvard Univ, Sch Med, Lab Dev Gastroenterol, Combined Dept Pediat Gastroenterol & Nutr, Charlestown, MA USA. RP Savidge, TC (reprint author), Massachusetts Gen Hosp, Dev Gastroenterol Lab, Combined Program Pediat Gastroenterol & Nutr, Combined Dept Pediat Gastroenterol & Nutr, 114 16th St, Charlestown, MA 02129 USA. EM savidge@helix.mgh.harvard.edu FU NICHD NIH HHS [R01-HD31852, R37-HD12437]; NIDDK NIH HHS [P01-DK33506, P30-DK40561] NR 42 TC 3 Z9 3 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD JUN PY 2003 VL 53 IS 6 BP 898 EP 904 DI 10.1203/01.PDR.0000064582.30004.62 PG 7 WC Pediatrics SC Pediatrics GA 685XB UT WOS:000183288600007 PM 12646731 ER PT J AU Pbert, L Moolchan, ET Muramoto, M Winickoff, JP Curry, S Lando, H Ossip-Klein, D Prokhorov, AV DiFranza, J Klein, JD AF Pbert, L Moolchan, ET Muramoto, M Winickoff, JP Curry, S Lando, H Ossip-Klein, D Prokhorov, AV DiFranza, J Klein, JD CA Ctr Child Hlth Res Am Acad Pediat TI The state of office-based interventions for youth tobacco use SO PEDIATRICS LA English DT Review DE tobacco; youth; treatment; primary care providers ID PRIMARY-CARE PHYSICIANS; COMMUNITY-HEALTH CENTERS; CIGARETTE-SMOKING; NICOTINE DEPENDENCE; ADOLESCENT SMOKERS; PREVENTIVE SERVICES; CONTROLLED TRIAL; SUBSTANCE USE; CESSATION INTERVENTION; COUNSELING ADOLESCENTS AB Tobacco use is a serious pediatric health issue as dependence begins during childhood or adolescence in the majority of tobacco users. Primary care settings provide tremendous opportunities for delivering tobacco treatment to young tobacco users. Although evidence-based practice guidelines for treating nicotine dependence in youths are not yet available, professional organizations and the current clinical practice guideline for adults provide recommendations based on expert opinion. This article reports on the current tobacco treatment practices of pediatric and family practice clinicians, discusses similarities and differences between adolescent and adult tobacco use, summarizes research efforts to date and current cutting-edge research that may ultimately help to inform and guide clinicians, and presents existing recommendations regarding treating tobacco use in youths. Finally, recommendations are made for the primary care clinician, professional organizations, and health care systems and policies. Pediatricians and other clinicians can and should play an important role in treating tobacco dependence in youths. C1 Univ Massachusetts, Sch Med, Div Prevent & Behav Med, Worcester, MA 01655 USA. NIDA, Teen Tobacco Addict Treatment Res Ctr, NIH, Baltimore, MD USA. Univ Arizona, Arizona Hlth Sci Ctr, Tucson, AZ USA. MassGen Hosp Children, Div Gen Pediat, MGH Ctr Child & Adolescent Hlth Policy, Boston, MA USA. Tobacco Res & Treatment Ctr, Boston, MA USA. Univ Illinois, Hlth Res Ctr, Chicago, IL USA. Univ Illinois, Policy Ctr, Chicago, IL USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. RP Pbert, L (reprint author), Univ Massachusetts, Sch Med, Div Prevent & Behav Med, 55 Lake Ave N, Worcester, MA 01655 USA. NR 127 TC 25 Z9 25 U1 4 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 2003 VL 111 IS 6 BP E650 EP E660 DI 10.1542/peds.111.6.e650 PG 11 WC Pediatrics SC Pediatrics GA 693CA UT WOS:000183696000003 PM 12777581 ER PT J AU Ledgerwood, LG Ewald, PW Cochran, GM AF Ledgerwood, LG Ewald, PW Cochran, GM TI Genes, germs, and schizophrenia - an evolutionory perspective SO PERSPECTIVES IN BIOLOGY AND MEDICINE LA English DT Review ID TOXOPLASMA-GONDII INFECTION; CHRONIC OCULAR TOXOPLASMOSIS; FIRST-EPISODE SCHIZOPHRENIA; CONGENITAL TOXOPLASMOSIS; NITRIC-OXIDE; RISK-FACTORS; ADULT SCHIZOPHRENIA; FOLLOW-UP; REPRODUCTIVE FAILURE; SPONTANEOUS-ABORTION AB Literature on schizophrenia and other mental illnesses has emphasized the compatibility of evidence with genetic causation without adequately considering alternative hypotheses of disease causation. Although some studies from the mid-20th century reported associations between certain pathogens and schizophrenia, only recently has the possibility of infectious causation of schizophrenia again become an active focus of research. Infectious causation of schizophrenia is still, however, generally regarded as less well demonstrated than genetic causation. This article evaluates the evidence that has been used to support genetic and infectious causation. Our consideration of infectious causation focuses on the protozoan Toxoplasma gondii but also assesses other pathogens that may contribute to the development of some of the illnesses currently categorized as schizophrenia. Although evidence generally accepted as demonstrating genetic causation can be readily explained by hypotheses of infectious causation, some of the evidence implicating infectious causation cannot be similarly explained by genetic causation. This asymmetry indicates that a scientific approach to the causation of schizophrenia needs to put a greater emphasis on tests that distinguish hypotheses of genetic causation from those of infectious causation. C1 Univ Louisville, Dept Biol, Louisville, KY 40292 USA. Amherst Coll, Dept Biol, Amherst, MA 01002 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Univ Utah, Dept Anthropol, Salt Lake City, UT 84112 USA. RP Ewald, PW (reprint author), Univ Louisville, Dept Biol, Louisville, KY 40292 USA. NR 211 TC 18 Z9 20 U1 3 U2 9 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 0031-5982 J9 PERSPECT BIOL MED JI Perspect. Biol. Med. PD SUM PY 2003 VL 46 IS 3 BP 317 EP 348 DI 10.1353/pbm.2003.0038 PG 32 WC History & Philosophy Of Science; Medicine, Research & Experimental SC History & Philosophy of Science; Research & Experimental Medicine GA 705NP UT WOS:000184401400001 PM 12878806 ER PT J AU Lin, TYD McAuliffe, DJ Michaud, N Zhang, H Lee, S Doukas, AG Flotte, TJ AF Lin, TYD McAuliffe, DJ Michaud, N Zhang, H Lee, S Doukas, AG Flotte, TJ TI Nuclear transport by laser-induced pressure transients SO PHARMACEUTICAL RESEARCH LA English DT Article DE drug delivery; nuclear envelope; ablation; shock waves; electroporation ID INDUCED PHOTOACOUSTIC INJURY; SHOCK-WAVE PERMEABILIZATION; FLUORESCENCE MICROPHOTOLYSIS; NUCLEOCYTOPLASMIC FLUX; GENE-TRANSFER; STRESS WAVES; IN-VITRO; MEMBRANE; CELLS; ELECTROPORATION AB Purpose. Control of the transport of molecules into the nucleus represents a key regulatory mechanism for differentiation, transformation, and signal transduction. Permeabilization of the nuclear envelope by physical methods can have applications in gene therapy. Laser-induced pressure transients can produce temporary aqueous pores analogous to those produced by electroporation and that the cells can survive this procedure. In this study, we examine the role of the pressure transients in creating similar pores in the nuclear envelope. Methods. The target human peripheral blood mononuclear cells in a 62 muM 72 kDa fluoresceinated dextran solution were exposed to the pressure transients generated by laser ablation. An in vitro fluorescence confocal microscope was used to visualize and quantify the fluoresceinated dextran in the cytoplasmic and nuclear compartments. Results. In contrast to electroporation, the pressure transients could deliver 72 kDa fluoresceinated dextrans, which are normally excluded by the nucleus, across the nuclear envelope into the nucleus. In addition to creating pores in the plasma membrane, temporary pores were also created in the nuclear envelope following exposure to pressure transients. Conclusion. The production of temporary nuclear pores could provide a unique resource for drug-delivery and gene therapy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Photopathol & Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Flotte, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Photopathol & Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. NR 30 TC 15 Z9 15 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JUN PY 2003 VL 20 IS 6 BP 879 EP 883 DI 10.1023/A:1023835219041 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 681PN UT WOS:000183044700006 PM 12817891 ER PT J AU Leaf, A Xiao, YF Kang, JX Billman, GE AF Leaf, A Xiao, YF Kang, JX Billman, GE TI Prevention of sudden cardiac death by n-3 polyunsaturated fatty acids SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE omega-3-fatty acids; fatal arrhythmias; fish oils; ionic membrane currents; sodium currents; calcium currents; ventricular fibrillation ID RAT VENTRICULAR MYOCYTES; CHANNEL ALPHA-SUBUNIT; NA+ CHANNELS; SODIUM-CHANNEL; MYOCARDIAL-INFARCTION; LOCAL-ANESTHETICS; GRAMICIDIN CHANNELS; LONG-CHAIN; SARCOPLASMIC-RETICULUM; ANTIARRHYTHMIC-DRUGS AB This is a review of our present understanding of the mechanism by which the n - 3 polyunsaturated fatty acids (PUFA) in fish oils prevent fatal ventricular arrhythmias in animals and cultured heart cells. A brief review of three clinical trials that suggest that these PUFAs prevent sudden cardiac death is also included in order to emphasize the potential importance of these fatty acids in human nutrition. The PUFAs act by stabilizing electrically every cardiac myocyte by modulating conductance of ion channels in the sarcolemma, particularly the fast, voltage-dependent sodium current and the L-type calcium currents, though other ion currents are also affected. Work in progress suggests that the primary site of action of the PUFAs may be on the phospholipid bilayer of the heart cells in the microdomains through which the ion channels penetrate the membrane bilayer in juxtaposition with the ion channels rather than directly on the channel protein itself These PUFAs then allosterically alter the conformation and conductance of the channels. Both potential benefits and possible adverse effects of the PUFAs in man will be discussed. Knowing that the ion channels have been structurally conserved among all excitable tissues, we tested their effects on the electrophysiology of rat hippocampal CA1 neurons and found that the sodium and calcium ion channels in these neurons were also affected by PUFAs. An attempt to show the place of the PUFAs in human nutrition during the 2-4 million years of our evolution will conclude the review. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, 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), Massachusetts Gen Hosp E, 149 13th St, Charlestown, MA 02129 USA. EM aleaf@partners.org RI Billman, George/E-2758-2011 FU NHLBI NIH HHS [HL38165]; NIDDK NIH HHS [DK62284] NR 76 TC 111 Z9 117 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD JUN PY 2003 VL 98 IS 3 BP 355 EP 377 DI 10.1016/S0163-7258(03)00039-1 PG 23 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 691CZ UT WOS:000183588400005 PM 12782244 ER PT J AU Bates, AL Zadai, CC AF Bates, AL Zadai, CC TI Acute care physical therapist evaluation and intervention for an adult after right hemispherectomy SO PHYSICAL THERAPY LA English DT Article DE hemispherectomy; physical therapy; rehabilitation ID LUMBOSACRAL SPINAL-CORD; FUNCTIONAL HEMISPHERECTOMY; INTRACTABLE SEIZURES; MOTOR FUNCTION; UNDERGONE HEMISPHERECTOMY; CHILDREN; BRAIN; CATS; HEMIPLEGIA; LOCOMOTION AB Background and Purpose. Hemispherectomy is performed to help control intractable seizures, yet little research quantifies and projects the clinical course of the impairments, functional limitations, and disabilities of patients who have undergone the procedure. This case report describes the physical therapist preoperative and postoperative examination, evaluation, and intervention during the acute hospitalization of an adult who underwent a right hemispherectomy. Case Description. The patient was a 27-year-old man who had intractable seizures despite having tried multiple drug regimens and undergoing several surgical interventions after a brain injury at age 5 years. He underwent a right functional hemispherectomy and then had 9 postoperative physical therapy sessions during his acute hospitalization. Outcomes. The patient made rapid gains, surpassing all initial goals. At discharge, the patient had distal left-sided sensorimotor impairments, but he was able to ambulate 121.9 in (400 ft) with assistance to maintain his balance. Discussion. The patient's posthemispherectomy recovery was rapid. His brain injury at a young age may have triggered preoperative transfer of function to the unaffected left hemisphere. The prognosis for this patient's improvements of impairments and functional limitations was better than initially expected, perhaps because of the redundant features and plasticity of the central nervous system. C1 Massachusetts Gen Hosp, Phys Therapy Serv, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Rehabil Serv, Boston, MA 02215 USA. MGH, Inst Hlth Profess, Boston, MA USA. RP Bates, AL (reprint author), Massachusetts Gen Hosp, Phys Therapy Serv, WACC 128,15 Parkman St, Boston, MA 02114 USA. NR 55 TC 2 Z9 2 U1 0 U2 1 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD JUN PY 2003 VL 83 IS 6 BP 567 EP 580 PG 14 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 685JX UT WOS:000183260600006 PM 12775202 ER PT J AU Cooppan, R AF Cooppan, R TI The changing model of insulin use in type 2 diabetes - Techniques, tactics for getting to goal SO POSTGRADUATE MEDICINE LA English DT Article ID BLOOD-GLUCOSE CONTROL; NOCTURNAL HYPOGLYCEMIA; GLYCEMIC CONTROL; MELLITUS; THERAPY; LISPRO; NIDDM; RISK; CELL AB Type 2 diabetes is by far the predominant type of diabetes in. the United States. Lifestyle changes can be effective in controlling blood glucose levels in many patients with early type 2 diabetes. However, as the disease evolves and slowly progresses, its successful treatment can move beyond diet and exercise to oral antidiabetic agents and later to the addition of insulin to oral therapy. Both physicians and patients may be hesitant to start insulin treatment, which can be complex and need ongoing adjustment. Here, Dr Coop, pan describes the indications for insulin use in type 2 diabetes, outlines the insulin analogue therapies available, and explains the latest in best management strategies for using insulin and getting to goal. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RP Cooppan, R (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM chan.cooppan@joslin.harvard.edu NR 15 TC 2 Z9 2 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 JUN PY 2003 VL 113 IS 6 BP 59 EP 64 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 835UB UT WOS:000222509900007 PM 12838804 ER PT J AU Shapiro, EL Ginzberg, R AF Shapiro, EL Ginzberg, R TI To accept or not to accept: Referrals and the maintenance of boundaries SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article ID EXPLOITATION INDEX; GROUP-THERAPY; PSYCHOTHERAPY; VIOLATIONS AB Psychotherapists of all disciplines are confronted with many dilemmas in accepting or declining referrals from colleagues and patients, as well as referrals that may entail contact outside the office. The authors explore countertransference, confidentiality, boundaries, and ethics related to referral sources. Case material illustrates clinical dilemmas. Some suggestions are offered to help therapists critically examine the conscious and unconscious influences affecting their decisions about whether to accept a referral. C1 Massachusetts Gen Hosp, Ctr Psychoanalyt Studies, Dept Psychiat, Boston, MA 02114 USA. RP Shapiro, EL (reprint author), Massachusetts Gen Hosp, Ctr Psychoanalyt Studies, Dept Psychiat, WACC 805,15 Parkman St, Boston, MA 02114 USA. NR 15 TC 0 Z9 0 U1 0 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD JUN PY 2003 VL 34 IS 3 BP 258 EP 263 DI 10.1037/0735-7028.34.3.258 PG 6 WC Psychology, Multidisciplinary SC Psychology GA 682DD UT WOS:000183075300006 ER PT J AU Corey, E Quinn, JE Buhler, KR Nelson, PS Macoska, JA True, LD Vessella, RL AF Corey, E Quinn, JE Buhler, KR Nelson, PS Macoska, JA True, LD Vessella, RL TI LuCaP 35: A new model of prostate cancer progression to androgen independence SO PROSTATE LA English DT Article DE prostate cancer; prostate specific antigen; xenografts; metastasis ID XENOGRAFT MODEL; RECEPTOR GENE; CHROMOSOME 8P; CARCINOMA; ESTABLISHMENT; DELETION; CELLS; CWR22 AB BACKGROUND. Generation of suitable in vivo models is critical for understanding of processes associated with development and progression of prostate cancer (CaP). METHODS. Lymph nodes containing metastatic androgen-independent CaP were implanted into athymic mice. A xenograft designated LuCaP 35 and its hormone-independent variant LuCaP 35V were established and characterized. RESULTS. LuCaP 35 is an androgen-sensitive, prostate-specific antigen (PSA)-producing xenograft. It expresses the wild-type androgen receptor and exhibits deletions in chromosome 8p, but not in chromosome 10. The response of LuCaP 35 to androgen ablation is similar to that observed in man. Using recurring LuCaP 35 tumors we have also established an androgen-insensitive variant of LuCaP 35. CONCLUSIONS. The availability of hormone-dependent and -independent variants of LuCaP 35, which exhibit many properties analogous to those of CaP in man, provides an excellent model system to study the processes associated with development of androgen independence and to evaluate new treatment modalities. Prostate 55: 239-246, 2003. (C) 2003 Wiley-Liss, Inc. C1 Univ Washington, Dept Urol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Michigan, Ctr Comprehens Canc, Dept Urol, Ann Arbor, MI 48109 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Corey, E (reprint author), Univ Washington, Dept Urol, Mail Stop 356510,1959 NE Pacific St, Seattle, WA 98195 USA. FU NCI NIH HHS [5 R01 CA60948-08]; NIDDK NIH HHS [2 P50 DK47656-07] NR 27 TC 92 Z9 95 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 0270-4137 J9 PROSTATE JI Prostate PD JUN 1 PY 2003 VL 55 IS 4 BP 239 EP 246 DI 10.1002/pros.10198 PG 8 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 681PX UT WOS:000183045500001 PM 12712403 ER PT J AU Straits-Troster, KA Sloan, KL Dominitz, JA AF Straits-Troster, KA Sloan, KL Dominitz, JA TI Psychiatric and substance use disorders comorbidity with hepatitis C SO PSYCHIATRIC ANNALS LA English DT Article; Proceedings Paper CT Annual Meeting on VA Health Services Research and Development CY 2001 CL WASHINGTON, D.C. ID METHADONE-MAINTENANCE PATIENTS; VIRUS-INFECTION; INTERFERON-ALPHA; DRUG-USERS; PREVALENCE; VETERANS; RIBAVIRIN; DISEASE; ILLNESS; HIV C1 VA Puget Sound Hlth Care Syst, NW Hepatitis C Resource Ctr, VA Ctr Excellence Substance Abuse Treatment & Edu, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, NW Hepatitis, Seattle, WA 98195 USA. RP Straits-Troster, KA (reprint author), VA Puget Sound Hlth Care Syst, NW Hepatitis C Resource Ctr, VA Ctr Excellence Substance Abuse Treatment & Edu, 116-ATC,1660 S Columbian Way, Seattle, WA 98108 USA. NR 30 TC 4 Z9 4 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JUN PY 2003 VL 33 IS 6 BP 362 EP 366 PG 5 WC Psychiatry SC Psychiatry GA 687PM UT WOS:000183385800003 ER PT J AU Loftis, JM Hauser, P AF Loftis, JM Hauser, P TI Comanagement of depression and HCV treatment SO PSYCHIATRIC ANNALS LA English DT Article ID CHRONIC HEPATITIS-C; INTERFERON-ALPHA TREATMENT; CHRONIC VIRAL-HEPATITIS; INITIAL TREATMENT; PLUS RIBAVIRIN; THERAPY; INFECTION; DISORDER; RETINOPATHY; PAROXETINE C1 Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, NW Hepatitis C Resource Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR USA. RP Loftis, JM (reprint author), Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, NW Hepatitis C Resource Ctr, P3MHAdm,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. NR 42 TC 11 Z9 15 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JUN PY 2003 VL 33 IS 6 BP 385 EP 391 PG 7 WC Psychiatry SC Psychiatry GA 687PM UT WOS:000183385800006 ER PT J AU Fireman, M AF Fireman, M TI Hepatitis C treatment and substance use disorders SO PSYCHIATRIC ANNALS LA English DT Article ID INTERFERON THERAPY; LIVER-DISEASE; DRUG USERS; ALCOHOL-CONSUMPTION; VIRUS-INFECTION; NATURAL-HISTORY; PROGRESSION; DRINKING; DRINKERS; LESIONS C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. RP Fireman, M (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, P-3-MHDC,3710 SW Vet Hosp Rd, Portland, OR 97239 USA. NR 31 TC 3 Z9 3 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JUN PY 2003 VL 33 IS 6 BP 402 EP 408 PG 7 WC Psychiatry SC Psychiatry GA 687PM UT WOS:000183385800008 ER PT J AU Rosenbaum, JF Dunner, DL AF Rosenbaum, JF Dunner, DL TI Drug therapy: predictors of response - Preface SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Washington, Ctr Anxiety & Depress, Dept Psychiat & Behav Sci, Seattle, WA 98105 USA. RP Rosenbaum, JF (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WAC 815, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD JUN PY 2003 VL 26 IS 2 BP XIII EP XIV DI 10.1016/S0193-953X(03)00026-1 PG 2 WC Psychiatry SC Psychiatry GA 679NR UT WOS:000182929300001 ER PT J AU Perlis, RH Iosifescu, DV Renshaw, PF AF Perlis, RH Iosifescu, DV Renshaw, PF TI Biological predictors of treatment response in affective illness SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID MAGNETIC-RESONANCE SPECTROSCOPY; MAJOR DEPRESSIVE DISORDER; OBSESSIVE-COMPULSIVE DISORDER; AUDITORY-EVOKED-POTENTIALS; TREATMENT-RESISTANT DEPRESSION; POSITRON-EMISSION-TOMOGRAPHY; BRAIN GLUCOSE-METABOLISM; EVENT-RELATED POTENTIALS; WHITE-MATTER LESIONS; LATE-LIFE DEPRESSION AB Clinicians and investigators have sought better means of matching patients to treatments since the advent of modern psychopharmacology. Attempts to use clinical features to predict which patients will respond to specific medications have met with limited success (see article by Nierenberg in this issue). Researchers also have sought biological tests that might discriminate between likely treatment responders and nonresponders or identify those at greater risk for relapse. Investigating techniques have ranged from urine neurotransmitter metabolites to electroencephalogram (EEG). Most recently, the widespread availability of neuroimaging technology has led to new efforts to apply these techniques to predict treatment response in psychiatry. The search for response predictors is driven by two related goals. The first is identifying the underlying pathophysiology associated with a given disease. Just as the utility of selective serotonin reuptake inhibitors in major depression provided evidence for serotonergic dysregulation in some affective illnesses, the discovery that changes in the metabolism of certain brain regions predict treatment response would implicate those structures in the process of disease development or recovery. These findings could guide future drug development. A second goal is to allow more targeted and focused clinical interventions. For example, while first-line antidepressant treatments have response rates of 50% or more, many patients still fail to respond to multiple interventions [1,2]. As each new pharmacotherapy is tried, patients are exposed to additional cost, adverse effect burden, and the potential for loss of function and suicide. Importantly, these two goals imply different criteria for what makes a response predictor useful. From a research perspective, identifying any association would be valuable in guiding future studies. From a clinical perspective, however, the requirements are more stringent and rarely have been achieved. Such factors as positive and negative predictive value and cost and availability of technology become critical in determining the utility of a predictive test (see article by Nierenberg in this issue). Attempts to identify biological response predictors generally have met with limited success, particularly where the goal is to develop clinically useful indices. This article reviews the biological approaches to predicting treatment response, beginning with neuroendocrine studies and EEG analysis and concludes with structural and functional neuroimaging. Where relevant, the authors identify studies correlating change in a measure during treatment; though these studies identify correlates of response rather than true predictors, they also may point the way to useful predictive measures. The article describes the designs of typical studies to aid in interpreting their results and concludes by addressing some of the problems and limitations associated with these approaches and suggesting future directions for this research. Original reports or reviews included in this article were identified by conducting a MEDLINE search with the terms "response," "predictor," and "treatment," combined with "depression," "bipolar disorder," or "affective illness." References in the publications identified were reviewed manually to locate additional relevant publications. Of note, pharmacogenomics, which shows great promise for response prediction in psychiatry, is discussed elsewhere (see article by Pickar in this issue). C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. McLean Hosp Brain Imaging Ctr, Belmont, MA 02478 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. RI Granados, Lily Magally/B-4827-2012 NR 125 TC 6 Z9 6 U1 8 U2 12 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD JUN PY 2003 VL 26 IS 2 BP 323 EP + DI 10.1016/S0193-953X(02)00112-0 PG 23 WC Psychiatry SC Psychiatry GA 679NR UT WOS:000182929300003 PM 12778836 ER PT J AU Nierenberg, AA AF Nierenberg, AA TI Predictors of response to antidepressants - General principles and clinical implications SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID MAJOR DEPRESSIVE DISORDER; TRUE DRUG RESPONSE; PATTERN-ANALYSIS; CLASSIFICATION; DEFINITIONS; FLUOXETINE; RELAPSE AB What variables predict who should be treated with antidepressants and who should not? if someone should be treated, what variables predict which treatment is most likely to work? If patients are treated, what predicts who will respond and who will not? Clinicians have asked these questions ever since researchers established that antidepressants were superior to placebo in the treatment of depression. Innumerable reports claim either biologic or psychosocial predictor variables of response, and every few years yet another review of predictors is published in the literature [1-4]. Although a few predictors have stood the test of time, most have been only of academic interest. Why has the enterprise of finding clinically useful predictors been minimally successful despite such intense effort? This article reviews methodologic issues that have been neglected in the pursuit of predictors to antidepressant response and proposes improved requirements for predictor research that impact clinical practice. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, WACC 812,15 Parkman St, Boston, MA 02114 USA. NR 25 TC 62 Z9 63 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD JUN PY 2003 VL 26 IS 2 BP 345 EP + DI 10.1016/S0193-953X(02)00105-3 PG 9 WC Psychiatry SC Psychiatry GA 679NR UT WOS:000182929300004 PM 12778837 ER PT J AU Fava, M Rush, AJ Trivedi, MH Nierenberg, AA Thase, ME Sackeim, HA Quitkin, FM Wisniewski, S Lavori, PW Rosenbaum, JF Kupfer, DJ AF Fava, M Rush, AJ Trivedi, MH Nierenberg, AA Thase, ME Sackeim, HA Quitkin, FM Wisniewski, S Lavori, PW Rosenbaum, JF Kupfer, DJ CA STAR D Invest Grp TI Background and rationale for the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID TREATMENT-RESISTANT DEPRESSION; SEROTONIN REUPTAKE INHIBITORS; TREATMENT-REFRACTORY DEPRESSION; CONTINUING MEDICAL-EDUCATION; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND CROSSOVER; FORM HEALTH SURVEY; OPEN-LABEL TRIAL; MAJOR DEPRESSION; PHYSICIAN PERFORMANCE AB Sequenced Treatment Alternatives to Relieve Depression (STAR*D) attempts to fill in major clinical information gaps and to evaluate the theoretical principles and clinical beliefs that currently guide pharmacotherapy of major depressive disorder. The study is conducted in representative participant groups and settings using clinical management tools that easily can be applied in daily practice. Outcomes include clinical outcomes and health care utilization and cost estimates. Research findings should be immediately applicable to, and easily implemented in, the daily primary and specialty care practices. This article provides the overall rationale for STAR*D and details the rationale for key design, measurement, and analytic features of the study. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Pittsburgh, Ctr Med, Grad Sch Publ Hlth, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Med, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA USA. Dept Vet Affairs Cooperat Studies Program, Palo Alto, CA USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY USA. Columbia Univ Coll Phys & Surg, Dept Radiol, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY USA. RP Rush, AJ (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01-MH-90003] NR 156 TC 315 Z9 319 U1 3 U2 15 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD JUN PY 2003 VL 26 IS 2 BP 457 EP + DI 10.1016/S0193-953X(02)00107-7 PG 39 WC Psychiatry SC Psychiatry GA 679NR UT WOS:000182929300010 PM 12778843 ER PT J AU Thase, ME Bhargava, M Sachs, GS AF Thase, ME Bhargava, M Sachs, GS TI Treatment of bipolar depression: current status, continued challenges, and the STEP-BD approach SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID DOUBLE-BLIND; LITHIUM-CARBONATE; ADJUNCTIVE THERAPY; AFFECTIVE-ILLNESS; MOOD STABILIZERS; CONTROLLED TRIAL; CLINICAL-TRIAL; DISORDER; LAMOTRIGINE; IMIPRAMINE AB This article takes an evidence-based medicinal approach to the treatment of bipolar depression. Mood stabilizers are strongly recommended as the first line of treatment for milder bipolar depressive episodes, primarily because subsequent preventive therapy will be necessary. In addition to lithium, recent research has established the antidepressant effects of lamotrigine and olanzapine. There is agreement that three presentations of bipolar I depression warrant combined antidepressant/ mood stabilizer strategies: episodes not responsive to mood stabilizers, episodes that "break through" despite prophylaxis, and markedly severe or psychotic episodes. Bupropion and selective serotonin reuptake inhibitors (of which fluoxetine and paroxetine have received the most extensive study) are uniformly considered the antidepressants of choice; venlafaxine and monoamine oxidase inhibitors rank highly for treatment-resistant cases. With concomitant mood stabilizer therapy, the risk of antidepressant-induced mania therapy is low (5%-10% during acute phase therapy with a selective serotonin reuptake inhibitor or bupropion). The optimal duration of antidepressant therapy is not known, and experts tend to recommend relatively short or indefinite courses of therapy based on factors such chronicity and past history of recurrence. The goals of the Systematic Treatment Enhancement Program for Bipolar Disorder (www.stepbd.org), which was sponsored by the National Institute of Mental Health are described in terms of filling several large gaps in knowledge that preclude a truly evidence-based approach to treatment of bipolar depression. C1 Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Thase, ME (reprint author), Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, 3811 O Hara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [MH-80001, MH-30915] NR 76 TC 10 Z9 11 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD JUN PY 2003 VL 26 IS 2 BP 495 EP + DI 10.1016/S0193-953X(03)00029-7 PG 26 WC Psychiatry SC Psychiatry GA 679NR UT WOS:000182929300011 PM 12778844 ER PT J AU Butterfield, MI Bosworth, HB Meador, KQ Stechuchak, KM Essock, SM Osher, FC Goodman, SA Swanson, JW Bastian, LA Horner, RD AF Butterfield, MI Bosworth, HB Meador, KQ Stechuchak, KM Essock, SM Osher, FC Goodman, SA Swanson, JW Bastian, LA Horner, RD CA Five-Site Hlth Risk Study Res Comm TI Gender differences in hepatitis C infection and risks among persons with severe mental illness SO PSYCHIATRIC SERVICES LA English DT Article ID INTRAVENOUS-DRUG-USERS; SUBSTANCE USE DISORDER; SEXUAL TRANSMISSION; VIRUS-INFECTION; HIV RISK; PREVALENCE; COMORBIDITY; WOMEN; EPIDEMIOLOGY; ALCOHOL AB Objectives: The authors assessed gender differences in hepatitis C infection and associated risk behaviors among persons with severe mental illness. Methods: The, sample consisted of 777 patients (251 women and 526 men) from four sites. Results: Across sites, the rate of hepatitis C infection among men was nearly twice that among women. Clear differences were noted in hepatitis C risk behaviors. Men had higher rates of lifetime drug-related risk behaviors: needle use (23.1 percent compared with 12.5 percent), needle sharing (17.6 percent compared with, 7.7 percent), and crack cocaine use (45.2 percent compared with 30.8 percent). Women had significantly higher rates of lifetime sexual risk behaviors: unprotected sex in exchange for drugs (17.8 percent compared with 11.2 percent), unprotected sex in exchange for money or gifts (30.6 percent compared with 17 percent), unprotected vaginal sex (94 percent compared with 89.7 percent), and anal sex (33.7 percent compared with 22.6 percent). Gender appeared to modify some sex risks. Unprotected sex in exchange for drugs 'increased the risk of hepatitis C seropositivity for both men and women. In the multivariate model, gender was not significantly associated with hepatitis C seropositivity after adjustment for otherrisk factors. Conclusions: Gender differences in the lifetime rates of drug risks explain the higher rates of hepatitis C infection among men with severe mental illness. C1 Dept Vet Affairs Med Ctr, Hlth Serv Res & Dev Serv, Durham, NC 27705 USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, New York, NY USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. Boston Coll, Dept Counseling Dev & Educ Psychol, Chestnut Hill, MA 02167 USA. Duke Univ, Med Ctr, Dept Psychiat, Durham, NC USA. RP Butterfield, MI (reprint author), Dept Vet Affairs Med Ctr, Hlth Serv Res & Dev Serv, 508 Fulton St, Durham, NC 27705 USA. EM mimi@acpub.duke.edu NR 31 TC 21 Z9 22 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JUN PY 2003 VL 54 IS 6 BP 848 EP 853 DI 10.1176/appi.ps.54.6.848 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 839BM UT WOS:000222758300011 PM 12773599 ER PT J AU Agretelis, J Picard, C DeMarco, R AF Agretelis, J Picard, C DeMarco, R TI Clinical insights shared by nurse cancer survivors SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 JUN PY 2003 VL 12 IS 4 SU S MA 176 BP S121 EP S121 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 684UR UT WOS:000183225400143 ER PT J AU Muriel, AC Rauch, PK AF Muriel, AC Rauch, PK TI A pilot parent guidance program for parents with cancer SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 JUN PY 2003 VL 12 IS 4 SU S MA 284 BP S151 EP S151 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 684UR UT WOS:000183225400228 ER PT J AU Patenaude, AF Orozco, S AF Patenaude, AF Orozco, S TI Interviews with women about prophylactic mastectomy: implications for psychological and peer consultation SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 12 IS 4 SU S MA 232 BP S136 EP S137 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 684UR UT WOS:000183225400188 ER PT J AU Pirl, W Liverant, G Goode, M Isaacowitz, D Smith, MR AF Pirl, W Liverant, G Goode, M Isaacowitz, D Smith, MR TI Pessimism and attributional styles in prostate cancer SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 12 IS 4 SU S MA 179 BP S122 EP S122 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 684UR UT WOS:000183225400145 ER PT J AU Pirl, W Baker-Niendorf, K Mahoney-Shannon, K Chan-Smutko, G AF Pirl, W Baker-Niendorf, K Mahoney-Shannon, K Chan-Smutko, G TI A model of psychosocial care in genetic testing for cancer susceptibility SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 12 IS 4 SU S MA 109 BP S102 EP S103 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 684UR UT WOS:000183225400085 ER PT J AU Pirl, WF AF Pirl, WF TI Screening for depression in men with prostate cancer SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2003 VL 12 IS 4 SU S MA 186 BP S124 EP S124 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 684UR UT WOS:000183225400151 ER PT J AU Smith, JJ Sorensen, AG Thrall, JH AF Smith, JJ Sorensen, AG Thrall, JH TI Biomarkers in imaging: Realizing radiology's future SO RADIOLOGY LA English DT Editorial Material DE Opinions; radiology and radiologists, research; radiology and radiologists, socioeconomic issues ID CLINICAL-TRIALS; SURROGATE AB Modern pharmaceuticals and medical devices have provided substantial benefits to patients throughout the world. These benefits come at a high and increasing cost, with development of the typical pharmaceutical requiring 12 years and hundreds of millions of dollars before gaining U.S. Food and Drug Administration marketing approval. Appropriate use of imaging biomarkers-defined as anatomic, physiologic, biochemical, or molecular parameters detectable with imaging methods used to establish the presence or severity of disease-offer the prospect of smaller, less expensive, and more efficient preclinical studies and clinical trials. Scientists, government regulators, and industry have all recognized the potential of biomarkers in imaging. Although real, this promise can only be realized with the rigorous application of science to their use. Success is most likely when (a) the presence of an imaging marker is closely linked with the presence of a target disease; (b) detection and/or measurement of the biomarker is accurate, reproducible, and feasible over time; and (c) measured changes are closely linked to success or failure of the therapeutic effect of the product being evaluated. By applying this paradigm to the array of imaging modalities, the radiology community is poised to become a major force in preclinical and clinical evaluations of new medical treatments. (C) RSNA 2003. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biomarkers Imaging, Boston, MA 02114 USA. RP Smith, JJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 15 Parkman St,WACC 515, Boston, MA 02114 USA. NR 16 TC 73 Z9 75 U1 0 U2 6 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 JUN PY 2003 VL 227 IS 3 BP 633 EP 638 DI 10.1148/ PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 679LW UT WOS:000182924800006 PM 12663828 ER PT J AU Visser, K Kock, MCJM Kuntz, KM Donaldson, MC Gazelle, GS Hunink, MGM AF Visser, K Kock, MCJM Kuntz, KM Donaldson, MC Gazelle, GS Hunink, MGM TI Cost-effectiveness targets for multi-detector row CT angiography in the work-up of patients with intermittent claudication SO RADIOLOGY LA English DT Article DE arteries, stenosis or obstruction; computed tomography (CT), angiography; cost-effectiveness; radiology and radiologists, socioeconomic issues ID MAGNETIC-RESONANCE ANGIOGRAPHY; PERIPHERAL ARTERIAL-DISEASE; AORTOILIAC OCCLUSIVE DISEASE; ENHANCED MR-ANGIOGRAPHY; LOWER-EXTREMITY; CONTRAST ARTERIOGRAPHY; DIAGNOSTIC PERFORMANCE; CARBON-DIOXIDE; METAANALYSIS; REVASCULARIZATION AB PURPOSE: To determine the costs, sensitivity for detection of significant stenoses, and proportion of equivocal multi-detector row computed tomographic (CT) angiography results in the work-up of patients with intermittent claudication that would make this imaging examination cost-effective compared with gadolinium-enhanced magnetic resonance (MR) angiography. MATERIALS AND METHODS: A decision model was used to compare the societal cost-effectiveness of a new imaging modality with that of gadolinium-enhanced MR angiography. Main outcome measures were quality-adjusted life years (QALYs) and lifetime costs. By using threshold analysis of a given willingness to pay per QALY, target values for costs, sensitivity for detection of significant stenoses, and proportion of cases requiring additional work-up with intraarterial digital subtraction angiography owing to equivocal results of the new modality were determined. The base case evaluated was that of 60-year-old men with severe intermittent claudication and assumed an incremental cost-effectiveness threshold of $100,000 per QALY. RESULTS: If treatment were limited to angioplasty, a new imaging modality would be cost-effective if the costs were $300 and the sensitivity was 85%, even if up to 35% of patients needed additional work-up. When both angioplasty and bypass surgery were considered as treatment options, a new imaging modality was cost-effective if the costs were $300, the sensitivity was higher than 94%, and 20% of patients required additional work-up. CONCLUSION: Multi-detector row CT angiography, as compared with currently used imaging modalities such as MR angiography, has the potential to be cost-effective in the evaluation of patients with intermittent claudication. (C) RSNA, 2003. C1 Univ Rotterdam, Med Ctr, Eramus MC, ART Program,Dept Epidemiol & Biostat, NL-3015 GE Rotterdam, Netherlands. Univ Rotterdam, Med Ctr, Eramus MC, Dept Radiol, NL-3015 GE Rotterdam, Netherlands. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Vasc Surg, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol, Decis Anal & Technol Assessment Grp, Boston, MA 02115 USA. RP Visser, K (reprint author), Univ Rotterdam, Med Ctr, Eramus MC, ART Program,Dept Epidemiol & Biostat, Dr Molewaterplein 50,Rm Ee21040B, NL-3015 GE Rotterdam, Netherlands. NR 50 TC 17 Z9 18 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 JUN PY 2003 VL 227 IS 3 BP 647 EP 656 DI 10.1148/ PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 679LW UT WOS:000182924800008 PM 12773672 ER PT J AU Hunter, GJ Silvennoinen, HM Hamberg, LM Koroshetz, WJ Buonanno, FS Schwamm, LH Rordorf, GA Gonzalez, RG AF Hunter, GJ Silvennoinen, HM Hamberg, LM Koroshetz, WJ Buonanno, FS Schwamm, LH Rordorf, GA Gonzalez, RG TI Whole-brain CT perfusion measurement of perfused cerebral blood volume in acute ischemic stroke: Probability curve for regional infarction SO RADIOLOGY LA English DT Article DE brain, blood flow; brain, infarction; brain, perfusion; computed tomography (CT), perfusion study; thrombolysis ID 3-DIMENSIONAL FUNCTIONAL CT; PROUROKINASE; THROMBOLYSIS; PROACT; TRIAL AB PURPOSE: To determine the probability curve for regional cerebral infarction as a function of percentage normalized perfused cerebral blood volume (pCBV) in patients with acute ischemic stroke. MATERIALS AND METHODS: The authors retrospectively analyzed whole-brain computed tomographic (CT) perfusion scans from 28 patients with acute stroke (<6 hours) due to major arterial occlusion, without intracranial hemorrhage. Each patient had a positive follow-up CT scan 1-4 days later, without interval thrombolysis. Normalized pCBV, expressed as a percentage of contralateral normal brain pCBV, was determined in the core infarction and in regions just inside and outside the boundary between infarcted and noninfarcted brain. These regions were dichotomized into infarcted (core and inner band) and noninfarcted (outer band) categories. Logistic regression analysis was then used to create a reference curve of probability of infarction as a function of percentage normalized pCBV. RESULTS: Normalized pCBV values in the core, inner band, and outer band were 24.5% +/- 2.3, 36.3% +/- 2.4, and 72.1% +/- 2.4, with corresponding probabilities of infarction of .99, .96, and .11. The normalized pCBV at which the probability of survival reached .5 was 58.0% +/- 0.5. Sensitivity, specificity, and accuracy of the reference probability curve were 90.5% (209 of 231), 89.5% (212 of 237), and 90.0% (421 of 468), respectively. Negative and positive predictive values were 90.6% (212 of 234) and 89.3% (209 of 234), respectively. R 2 was 0.73, and differences in perfusion between core and inner and outer bands were highly significant (P <.0001). CONCLUSION: A probability of infarction curve can help predict the likelihood of infarction as a function of percentage normalized pCBV. (C) RSNA, 2003. C1 Massachusetts Gen Hosp, MGH Perfus & Physiol Anal Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Hunter, GJ (reprint author), Massachusetts Gen Hosp, MGH Perfus & Physiol Anal Lab, Gray Bldg,Rm 285,55 Fruit St, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 NR 15 TC 36 Z9 39 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 JUN PY 2003 VL 227 IS 3 BP 725 EP 730 DI 10.1148/ PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 679LW UT WOS:000182924800018 PM 12728181 ER PT J AU Jaramillo, D Connolly, SA Vajapeyam, S Robertson, RL Dunning, PS Mulkern, RV Hayward, A Maier, SE Shapiro, F AF Jaramillo, D Connolly, SA Vajapeyam, S Robertson, RL Dunning, PS Mulkern, RV Hayward, A Maier, SE Shapiro, F TI Normal and ischemic epiphysis of the femur: Diffusion MR imaging - Study in piglets SO RADIOLOGY LA English DT Article DE animals; bones, epiphyses; bones, growth and development; bones, infarction; femur, MR; magnetic resonance (MR), diffusion study ID DEVELOPING APPENDICULAR SKELETON; CALVE-PERTHES DISEASE; FEMORAL-HEAD; CARTILAGINOUS EPIPHYSIS; CONGENITAL DISLOCATION; VERTEBRAL METASTASES; AVASCULAR NECROSIS; BONE-MARROW; HIP; IMAGES AB PURPOSE: To evaluate normal diffusion characteristics in the femur in piglets and changes in diffusion with increasing duration of femoral head ischemia. MATERIALS AND METHODS: Normal epiphyses, physes, and metaphyses of piglets were evaluated with line-scan diffusion imaging (n = 12) and diffusion-tensor imaging (n = 4). Apparent diffusion coefficient (ADC) differences between normal proximal and distal femoral structures, epiphyseal and physeal cartilage, and epiphyseal and metaphyseal marrow were compared (Mann-Whitney test). Shortterm femoral ischemia was investigated after maximal abduction of the hips for 3 hours (n = 6); ADCs before and after abduction were compared (Wilcoxon signed rank test). Prolonged ischemia was investigated with placement of a ligature around the neck of a femur (n = 7); the ADC of the femur in this condition was compared (Wilcoxon signed rank test) with that of the normal contralateral femur. Changes in ADC ratios at three durations of ischemia (Kruskal-Wallis test) were compared. RESULTS: ADC was greater in epiphyseal cartilage (mean +/- 1 SD, 1.62 x 10(-3) 28 x 10(-3) mm(2)/sec +/- 0.38) than it was in physeal cartilage (1.28 x 10(-3) mm(2)/sec +/- 0.31) (P < .007) and greater in epiphyseal marrow (1.26 x 10(-3) mm(2)/sec +/- 0.38) than it was in metaphyseal marrow (0.91 x 10(-3) mm(2)/sec +/- 0.35) (P < .001). There was columnar arrangement of tensors in the physis. ADC decreased 26% after 3 hours of maximal abduction. After femoral neck ligature, ADC increased a mean of 27% after 6 hours and a mean of 75% after 96 hours. CONCLUSION: Normal line-scan diffusion imaging findings indicate relative restriction of diffusion in the metaphysis and parallel orientation of tensors in the physis. Diffusion is initially restricted with decreased blood flow but increases if ischemia lasts longer. (C) RSNA, 2003. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Jaramillo, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. OI Robertson, Richard/0000-0001-8811-4405 FU NIAMS NIH HHS [AR42396-05] NR 35 TC 37 Z9 48 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 JUN PY 2003 VL 227 IS 3 BP 825 EP 832 DI 10.1148/radiol.2273011673 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 679LW UT WOS:000182924800031 PM 12773684 ER PT J AU Stone, ME AF Stone, ME TI Guide to top doctors. SO REFERENCE & USER SERVICES QUARTERLY LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, Reference Serv, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Treadwell Lib, Reference Serv, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER LIBRARY ASSOC PI CHICAGO PA 50 E HURON ST, CHICAGO, IL 60611 USA SN 1094-9054 J9 REF USER SERV Q JI Ref. User Serv. Q. PD SUM PY 2003 VL 42 IS 4 BP 354 EP 355 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA 683RJ UT WOS:000183163000011 ER PT J AU Stone, ME AF Stone, ME TI Guide to hospitals. SO REFERENCE & USER SERVICES QUARTERLY LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, Reference Serv, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Treadwell Lib, Reference Serv, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER LIBRARY ASSOC PI CHICAGO PA 50 E HURON ST, CHICAGO, IL 60611 USA SN 1094-9054 J9 REF USER SERV Q JI Ref. User Serv. Q. PD SUM PY 2003 VL 42 IS 4 BP 354 EP 355 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA 683RJ UT WOS:000183163000010 ER PT J AU Meyerhardt, JA Mayer, RJ AF Meyerhardt, JA Mayer, RJ TI Follow-up strategies after curative resection of colorectal cancer SO SEMINARS IN ONCOLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; SERUM CARCINOEMBRYONIC ANTIGEN; OF-CLINICAL-ONCOLOGY; COLON-CANCER; RANDOMIZED TRIAL; RADICAL SURGERY; LARGE BOWEL; POSTOPERATIVE SURVEILLANCE; COLONOSCOPIC SURVEILLANCE; F-18 FLUORODEOXYGLUCOSE C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [T32 CA 090001-27] NR 91 TC 37 Z9 38 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD JUN PY 2003 VL 30 IS 3 BP 349 EP 360 DI 10.1016/S0093-7754(03)00095-2 PG 12 WC Oncology SC Oncology GA 690GP UT WOS:000183539800003 PM 12870136 ER PT J AU Cohen, SP Larkin, T Abdi, S Chang, A Stojanovic, M AF Cohen, SP Larkin, T Abdi, S Chang, A Stojanovic, M TI Risk factors for failure and complications of intradiscal electrothermal therapy: A pilot study SO SPINE LA English DT Article DE back pain; discogenic pain; discography; internal disc disruption; intradiscal electrothermal therapy ID LOW-BACK-PAIN; FOLLOW-UP; DISC AB Study Design. A bi-institutional, retrospective clinical data analysis. Objectives. To determine risk factors for failure and complications of intradiscal electrothermal therapy, a treatment for discogenic back pain. Summary of the Background Data. Intradiscal electrothermal therapy is a relatively new treatment for discogenic back pain. Though previous studies have shown it to be an effective treatment, there are few published studies examining complications and none examining risk factors for failure. Methods. The authors treated 79 patients with discogenic back pain using intradiscal electrothermal therapy. Complications were assessed by patient report and, when indicated, further diagnostic testing. Success or failure was determined by visual analogue pain scores at 6-month follow-up. Variables examined for their relationship to failure and complications were age, sex, duration of pain, number of levels heated, smoking history, diabetes, obesity, leg pain, and previous back surgery. Results. Forty-eight percent of patients reported more than 50% pain relief at their 6-month follow-up. There were eight complications (10%), most of which were self-limited and transient. The only risk factor associated with intradiscal electrothermal therapy failure was obesity (P = 0.01). Whereas 54% of nonobese patients reported good pain relief at 6 months, only one out of 10 obese patients had successful intradiscal electrothermal therapy. The obese patients in our study were more likely to have a complication from intradiscal electrothermal therapy than they were to obtain pain relief. Conclusion. The only risk factor found to be associated with IDET outcome was obesity, which was a strong predictor of failure. Obesity should be considered a relative contraindication to performing IDET. C1 Walter Reed Army Med Ctr, Dept Anesthesia, Pain Management Ctr, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Dept Clin Invest, Washington, DC 20307 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,MGH Pain Ctr, Dept Anesthesia & Crit Care, Boston, MA USA. RP Cohen, SP (reprint author), NYU, Sch Med, Dept Anesthesiol, 550 1st Ave, New York, NY 10016 USA. NR 17 TC 53 Z9 53 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD JUN 1 PY 2003 VL 28 IS 11 BP 1142 EP 1147 DI 10.1097/00007632-200306010-00011 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 685GT UT WOS:000183254600010 PM 12782982 ER PT J AU Ellsworth, JL Garcia, R Yu, J Kindy, MS AF Ellsworth, JL Garcia, R Yu, J Kindy, MS TI Fibroblast growth factor-18 reduced infarct volumes and behavioral deficits after transient occlusion of the middle cerebral artery in rats SO STROKE LA English DT Article DE animal models; growth factors; neuroprotection; rats ID BRAIN INJURY; EXPRESSION; ISCHEMIA; STROKE; FGF18 AB Background and Purpose-Fibroblast growth factor 18 (FGF18) is expressed in rodent brain and is a trophic factor for neuron-derived cells in culture. The purpose of the present study was to evaluate whether FGF18 was neuroprotective in a rat model of cerebral ischemia and to compare the results with those obtained with FGF2. Methods-Cerebral ischemia was produced in rats by a transient 2-hour occlusion of the middle cerebral artery (MCAo) with an intraluminal filament followed by 22-hour reperfusion. Starting 15 minutes after MCAo, FGF18 or FGF2 was administered by a 3-hour intravenous infusion. Infarct volumes and behavioral deficits were measured 24 hours after MCAo. Results-Infusion of FGF18 produced dose-dependent reductions in infarct volumes and improvements in tests of reference and working memory, motor ability, and exploratory behavior. FGF18 was more efficacious than FGF2 on virtually all measures examined. The reductions in infarct volume and behavioral deficit were associated with FGF-mediated increases in regional cerebral blood flow. Conclusions-These results demonstrate that FGF18 is an effective neuroprotective agent in a rat model of transient MCAo. C1 Zymogenet Inc, Seattle, WA 98102 USA. Med Univ S Carolina, Dept Physiol & Neurosci, Stroke Program, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. Mol Therapeut Inc, Mt Pleasant, SC USA. RP Ellsworth, JL (reprint author), Zymogenet Inc, 1201 Eastlake Ave E, Seattle, WA 98102 USA. NR 29 TC 25 Z9 27 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 JUN PY 2003 VL 34 IS 6 BP 1507 EP 1512 DI 10.1161/01.STR.0000071760.66720.5F PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 686YJ UT WOS:000183348300033 PM 12738892 ER PT J AU Kelly, PJ Shih, VE Kistler, JP Barron, M Lee, H Mandell, R Furie, KL AF Kelly, PJ Shih, VE Kistler, JP Barron, M Lee, H Mandell, R Furie, KL TI Low vitamin B6 but not homocyst(e)ine is associated with increased risk of stroke and transient ischemic attack in the era of folic acid grain fortification SO STROKE LA English DT Article DE cerebrovascular disorders; homocyst(e)ine; pyridoxine; risk factors ID HOMOCYSTEINE CONCENTRATIONS; DISEASE; FOLATE; INFLAMMATION AB Background and Purpose-The introduction of cereal grain folic acid fortification in 1998 has reduced homocyst(e)ine (tHcy) concentrations in the US population. We performed a case-control study to determine the risk of stroke and transient ischemic attack (TIA) associated with tHcy and low vitamin status in a postfortification US sample. Methods-Consecutive cases with new ischemic stroke/TIA were compared with matched controls. Fasting tHcy, folate, pyridoxal 5'-phosphate (PLP), B12, and MTHFR 677C-->T genotype were measured. Results-Mean PLP was significantly lower in cases than controls (39.97 versus 84.1 nmol/L, P<0.0001). After stroke risk factors were controlled for, a strong independent association was present between stroke/TIA and low PLP (adjusted odds ratio [OR], 4.6; 95% CI, 1.4 to 15.1; P<0.001) but not elevated tHcy (OR, 0.92; 95% CI, 0.4 to 2.1). Conclusions-Low B6 but not tHcy was strongly associated with cerebrovascular disease in this postfortification, folate-replete sample. C1 Massachusetts Gen Hosp, Dept Neurol, VBK 802, Stroke Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Amino Acid Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kelly, PJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 802, Stroke Serv, Fruit St, Boston, MA 02114 USA. NR 11 TC 50 Z9 50 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 JUN PY 2003 VL 34 IS 6 BP E51 EP E54 DI 10.1161/01.STR.0000071109.23410.AB PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 686YJ UT WOS:000183348300061 PM 12738890 ER PT J AU Reed, GL AF Reed, GL TI Good breeding matters: in-bred rodents provide genetic insights into platelet secretion SO THROMBOSIS AND HAEMOSTASIS LA English DT Editorial Material C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reed, GL (reprint author), Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, HSPH 2-127,677 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL58496] NR 14 TC 0 Z9 0 U1 1 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 2003 VL 89 IS 6 BP 951 EP 952 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 710MB UT WOS:000184683000001 PM 12783105 ER PT J AU Blasco, MA Hahn, WC AF Blasco, MA Hahn, WC TI Evolving views of telomerase and cancer SO TRENDS IN CELL BIOLOGY LA English DT Editorial Material ID NORMAL HUMAN-CELLS; HUMAN-DIPLOID FIBROBLASTS; HUMAN TUMOR-CELLS; LARGE T-ANTIGEN; INDUCED SENESCENCE; EPITHELIAL-CELLS; IMMORTAL CELLS; MOUSE CELLS; LIFE-SPAN; MICE AB The maintenance of telomeres, nucleoprotein structures that constitute the ends of eukaryotic chromosomes, regulates many crucial cellular functions and might, in multicellular organisms, participate in the control of complex phenotypes such as aging and cancer. Stabilization of telomere length is strongly associated with cellular immortalization, and constitutive telomerase activation occurs in most human cancers. Such observations form the basis for the prevailing model that postulates that alterations in telomere biology both suppress and facilitate malignant transformation by regulating genomic stability and cell life span. However, recent findings suggest that telomere maintenance might not be an obligate requirement for initial tumor formation in some settings and that telomerase activation contributes to tumorigenesis independently of its role in maintaining telomere length. These recent developments indicate that our understanding of telomere biology remains incomplete and implicate additional complexity in the relationships among telomeres, telomerase and cancer. C1 CSIC, Natl Biotechnol Ctr, Dept Immunol & Oncol, E-28049 Madrid, Spain. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Hahn, WC (reprint author), CSIC, Natl Biotechnol Ctr, Dept Immunol & Oncol, Campus Cantoblanco, E-28049 Madrid, Spain. RI Blasco , Maria A./M-1694-2014 OI Blasco , Maria A./0000-0002-4211-233X FU NCI NIH HHS [K01 CA94223] NR 59 TC 90 Z9 92 U1 0 U2 5 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 JUN PY 2003 VL 13 IS 6 BP 289 EP 294 DI 10.1016/S0962-8924(03)00085-0 PG 6 WC Cell Biology SC Cell Biology GA 690VA UT WOS:000183570100005 PM 12791294 ER PT J AU Cantiello, HF AF Cantiello, HF TI A tale of two tails: ciliary mechanotransduction in ADPKD SO TRENDS IN MOLECULAR MEDICINE LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; PRIMARY CILIUM; C-ELEGANS; CATION CHANNEL; GENE HOMOLOG; CELL-CYCLE; PROTEIN; MICE; MUTATIONS; POLARIS AB Autosomal dominant polycystic kidney disease (ADPKD) is a common lethal genetic disorder, characterized by the progressive development of fluid-filled cysts in the kidney, pancreas and liver, and anomalies of the cardiovascular system. Mutations in PKD1 and PKD2, which encode the transmembrane proteins polycystin-1 (PC1) and polycystin-2 (PC2) respectively, account for almost all cases of ADPKD. However, the mechanisms by which abnormalities in PKD1 and PKD2 lead to aberrant kidney development remain unknown. Recent progress in the understanding of ADPKD has focused on primary cilia, which act as sensory transducers in renal epithelial cells. New evidence shows that a mechanosensitive signal, cilia bending, activates the PC1-PC2 channel complex. When working properly, this functional complex elicits a transient Ca2+ influx, which is coupled to the release of Ca2+ from intracellular stores. C1 Massachusetts Gen Hosp East, Renal Unit, Charlestown, MA 02129 USA. RP Cantiello, HF (reprint author), Massachusetts Gen Hosp East, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. NR 37 TC 12 Z9 13 U1 0 U2 0 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 JUN PY 2003 VL 9 IS 6 BP 234 EP 236 DI 10.1016/S1471-4914(03)00073-X PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 700TD UT WOS:000184126500003 PM 12829010 ER PT J AU Settleman, J AF Settleman, J TI A memory GAP SO TRENDS IN NEUROSCIENCES LA English DT Article ID P190 RHOGAP; ACTIN CYTOSKELETON; KINASE; CELL; EXPRESSION; PLASTICITY; STABILITY; AMYGDALA; GTPASES; BRAIN AB Pavlovian conditioning of the response to fear has provided an important model for memory formation in mammals. Several studies have begun to identify the key signal-transduction components that provide the molecular basis for this complex neural process. A recent report has revealed that the Rho GTPase and its regulator p190 Rho-GTPase-activating protein (p190 RhoGAP) also play an important regulatory role in fear memory formation. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. NR 26 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUN PY 2003 VL 26 IS 6 BP 285 EP 287 DI 10.1016/S0166-2236(03)00103-6 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 691TN UT WOS:000183621700002 PM 12798594 ER PT J AU Koenen, KC Lyons, MJ Goldberg, J Simpson, J Williams, WM Toomey, R Eisen, SA True, WR Cloitre, M Wolfe, J Tsuang, MT AF Koenen, KC Lyons, MJ Goldberg, J Simpson, J Williams, WM Toomey, R Eisen, SA True, WR Cloitre, M Wolfe, J Tsuang, MT TI A high risk twin study of cornbat-related PTSD comorbidity SO TWIN RESEARCH LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; PSYCHIATRIC-DISORDERS; URBAN-POPULATION; TRAUMATIC EVENTS; YOUNG-ADULTS; COMMUNITY; REGISTRY; FAMILY; VALIDITY AB Combat-related posttraumatic stress disorder (PTSD) is highly comorbid with other mental disorders. However, the nature of the relationship between PTSD and other mental disorders remains unclear. A discordant high-risk twin design was used on data from a sub-sample of the male-male twin pair members of the Vietnam Era Twin Registry to examine whether patterns of comorbidity are consistent with a psychopathological response to combat exposure or reflect familial vulnerability to psychopathology. Mental disorders were assessed via the Mental Health Diagnostic Interview Schedule Version III - Revised. Discordant monozygotic within-pair comparisons revealed that PTSD probands had higher symptom counts and diagnostic prevalences of mood and anxiety disorders than their non-combat exposed co-twins. Monozygotic co-twins of PTSD probands had significantly more mood disorder symptoms than monozygotic co-twins of combat controls or dizygotic co-twins of veterans with PTSD. These findings suggest that a) major depression, generalized anxiety disorder and panic disorder are part of a post-combat response syndrome; b) a shared familial vulnerability also contributes to the association between PTSD and major depression, PTSD and dysthymia, and c) this shared vulnerability is mediated by genetic factors. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02150 USA. Boston Univ, Sch Med, Boston med Ctr, Dept Child & Adolescent Psychiat, Boston, MA 02118 USA. Boston Univ, Dept Psychol, Boston, MA 02118 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Brockton, MA 02401 USA. Harvard Univ, Sch Med, Mental Hlth Ctr, Dept Psychiat, Boston, MA USA. Seattle VA ERIC Vietnam Era Twin Registry, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. St Louis Vet Affairs Med Ctr, Res Serv, St Louis, MO USA. St Louis Vet Affairs Med Ctr, Med Serv, St Louis, MO USA. Washington Univ, Dept Internal Med, Div Gen Med Sci, St Louis, MO USA. St Louis Univ, Med Ctr, Sch Publ Hlth, St Louis, MO USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NYU, Child Study Ctr, New York, NY USA. RP Koenen, KC (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div 116B3, 150 S Huntington Ave, Boston, MA 02150 USA. RI Lyons, Michael/B-6119-2011 FU NIAAA NIH HHS [AA10586]; NIDA NIH HHS [DA04604]; NIMH NIH HHS [F31 MH011954, F31 MH011954-01, MH11954-01] NR 41 TC 52 Z9 52 U1 1 U2 3 PU AUSTRALIAN ACAD PRESS PI BOWEN HILLS PA 32 JEAYS ST, BOWEN HILLS, QLD 4006, AUSTRALIA SN 1369-0523 J9 TWIN RES JI Twin Res. PD JUN PY 2003 VL 6 IS 3 BP 218 EP 226 DI 10.1375/136905203765693870 PG 9 WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology GA 693KW UT WOS:000183717600007 PM 12855071 ER PT J AU Raju, BI Swindells, KJ Gonzalez, S Srinivasan, MA AF Raju, BI Swindells, KJ Gonzalez, S Srinivasan, MA TI Quantitative ultrasonic methods for characterization of skin lesions in vivo SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE high-frequency ultrasound; skin; dermis; tissue characterization; diffraction compensation; attenuation; coefficient; echogenicity; echo statistics; dermatology; contact dermatitis ID PATCH TEST REACTIONS; RAYLEIGH STATISTICS; FOLD THICKNESS; HUMAN DERMIS; BACKSCATTER; ATTENUATION; SYSTEM; TISSUE; DIFFERENTIATION; QUANTIFICATION AB Quantitative ultrasonic methods were studied for characterizing skin lesions in vivo using contact dermatitis as an example. The parameters studied include skin thickness, echogenicity, attenuation coefficient slope and parameters related to echo statistics (signal-to-noise ratio and shape parameters of Weibull, K and generalized gamma distributions). Data were collected using a high-frequency ultrasound (US) system (center frequency = 33 MHz). To compensate for depth-dependent diffraction effects, correction curves as a function of the distance between the transducer and the tissue were first empirically obtained. Diffraction-corrected quantitative parameters were then compared between healthy and affected skin of volunteers, who underwent patch testing for allergic and irritant contact dermatitis. A significant increase in skin thickness, decrease in echogenicity of the upper dermis and decrease in attenuation coefficient slope were found at the affected sites compared to those of healthy skin. However, no differences in parameters related to the echo statistics of the mid-dermis were found. These results indicate that a combination of quantitative ultrasonic parameters have the potential for extracting information for characterizing skin conditions. (E-mail: raju@alum.mit.edu) (C) 2003 World Federation for Ultrasound in Medicine Biology. C1 MIT, Elect Res Lab, Lab Human & Machine Hapt, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Dept Dermatol, Boston, MA 02114 USA. RP Raju, BI (reprint author), Philips Res, 345 Scarborough Rd, Briarcliff Manor, NY 10510 USA. NR 38 TC 42 Z9 42 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD JUN PY 2003 VL 29 IS 6 BP 825 EP 838 DI 10.1016/S0301-5629(03)00009-7 PG 14 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 694FB UT WOS:000183762200005 PM 12837498 ER PT J AU Dretler, SP AF Dretler, SP TI Variability of renal stone fragility in shock wave lithotripsy - Editorial comment SO UROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Ctr Ambulatory Care, Boston, MA 02114 USA. RP Dretler, SP (reprint author), Massachusetts Gen Hosp, Ctr Ambulatory Care, Boston, MA 02114 USA. NR 2 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JUN PY 2003 VL 61 IS 6 BP 1097 EP 1097 DI 10.1016/S0090-4295(03)00350-9 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 690KD UT WOS:000183547000004 ER PT J AU Freedland, SJ DeGregorio, F Sacoolidge, JC Elshimali, YI Csathy, GS Elashoff, DA Reiter, RE Aronson, WJ AF Freedland, SJ DeGregorio, F Sacoolidge, JC Elshimali, YI Csathy, GS Elashoff, DA Reiter, RE Aronson, WJ TI Predicting biochemical recurrence after radical prostatectomy for patients with organ-confined disease using p27 expression SO UROLOGY LA English DT Article ID DEPENDENT KINASE INHIBITOR; INDEPENDENT PREDICTOR; CANCER-CELLS; P27(KIP1); SURVIVAL; MARKERS; STAGE; MIB-1; CD44S; RACE AB Objectives. It is unclear why men who undergo radical prostatectomy (RP) and are found to have pathologically organ-confined disease develop prostate-specific antigen (PSA) recurrences. We previously found that patients with less than 45% of cells in the prostate needle biopsy specimen (PNBx) staining positive for the cell cycle regulator p27 had a significantly increased risk of biochemical recurrence after RP. We sought to determine whether p27 staining in the PNBx specimen might serve as a molecular marker for PSA failure in the subset of patients who develop PSA recurrence despite organ-confined disease at RP. Methods. The PNBx specimens of 161 men treated with RP between 1991 and 2000 were examined for p27 expression using immunohistochemistry. The p27 cutpoint of less than 45% expression was used to define the high and low-risk categories. Patients were separated into two groups for analysis: organ-confined (pT2 and negative surgical margins) and non-organ-confined (pT2 with positive surgical margins, pT3, pT4, or lymph node involvement). The mean and median follow-up for patients with organ-confined and non-organ-confined disease was 47 and 43 months and 42 and 38 months, respectively. Multivariate Cox proportional hazards analysis was used to examine the preoperative clinical variables that were the strongest predictors of biochemical recurrence after RP among each group. Results. Among organ-confined patients, p27 expression was the only significant independent predictor of the time to biochemical recurrence after RP (hazard ratio 5.15, 95% confidence interval 1.41 to 18.83, P = 0.013). Among patients with non-organ-confined disease, the percentage of biopsy tissue with cancer, biopsy Gleason score, and PSA level were independent predictors of PSA recurrence. p27 expression was not a significant independent predictor of PSA recurrence among men with non-organ-confined disease. Conclusions. p27 expression in the PNBx was a significant independent predictor of PSA failure for patients with pathologically organ-confined disease, but not for those with non-organ-confined disease. Patients with organ-confined disease but low p27 expression had a greater than fivefold risk of developing PSA recurrence than were men with high p27 expression, suggesting that p27 may be a molecular marker associated with micrometastatic disease at the time of RP. (C) 2003 Elsevier Inc. C1 Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Biostat, Los Angeles, CA 90095 USA. Olive View UCLA Med Ctr, Dept Pathol, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP Aronson, WJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Urol, Box 951738,1359 Brinkley Ave, Los Angeles, CA 90095 USA. FU NCI NIH HHS [P50 CA92131-01A1] NR 23 TC 10 Z9 11 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 JUN PY 2003 VL 61 IS 6 BP 1187 EP 1192 DI 10.1016/S0090-4295(03)00034-7 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 690KD UT WOS:000183547000031 PM 12809895 ER PT J AU Demling, RH DeSanti, L AF Demling, RH DeSanti, L TI Topical doxepin significantly decreases itching and erythema in the chronically pruritic burn scar SO WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE LA English DT Article ID NEURAL PATHWAY; HISTAMINE; CREAM; DERMATITIS AB The chronically pruritic burn wound is an incapacitating problem. Itching, which can last months to years, is most common in a burn that required three to four weeks to heal. The incidence of chronic itch in burn scars has been reported to be up to 80 percent of patients. Chronic inflammation is likely present in a wound still itching beyond four months. Increased release of histamine from local wound most cells and/or increased sensitivity of sensory nerves to local histamine release is considered a major causative factor. The current standard approach for chronic itch, which consists of oral antihistamines, skin moisturizers, and sedatives, is often ineffective. Doxepin is a tricyclic compound found to have extremely potent antihistamine properties. A five-percent doxepin cream is used to control the histamine-induced itch of atopic dermatitis, urticaria, and other pruritic skin disorders, including more acute burn wounds. The authors' purpose was to test the efficacy of doxepin cream in controlling post-burn itch in outpatients with healed chronically itching burn wounds of four months to one year in duration. Patients were randomized into a standard of care group using oral antihistamines or the use of topical doxepin. The study was continued over a three-month period or until the itch ceased. A 0-to-10 itch scale, 10 being the worst and a 0-to-3 erythema scale, 3 being the worst, were used in this randomized prospective trial. The authors found that itch and erythema were 5 2 and 2 1, respectively, with standard care; values were significantly decreased to 2 1 and 1 1, respectively, with the doxepin cream compared to standard care, for the length of the study period. Itching ceased in 75 percent of patients using doxepin cream before the end of the three-month period compared to only 20 percent of patients using the oral antihistamines. Mild and transient somnolence was seen in 10 percent of patients using the doxepin cream, compared to 50 percent of patients using standard care. The authors concluded that the five-percent doxepin cream significantly decreases itching and erythema in the healed, chronically itching, burn wound compared to oral antihistamines. C1 Brigham & Womens Hosp, Burn & Wound Ctr, Boston, MA 02115 USA. RP Demling, RH (reprint author), Brigham & Womens Hosp, Burn & Wound Ctr, 75 Francis St,PBB-B4, Boston, MA 02115 USA. NR 26 TC 5 Z9 5 U1 0 U2 2 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1044-7946 J9 WOUNDS JI Wounds-Compend. Clin. Res. Pract. PD JUN PY 2003 VL 15 IS 6 BP 195 EP 200 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 689YW UT WOS:000183521400004 ER PT J AU Vielma, SA Krings, G Lopes-Virella, MF AF Vielma, SA Krings, G Lopes-Virella, MF TI Chlamydophila pneumoniae induces ICAM-1 expression in human aortic endothelial cells via protein kinase C-dependent activation of nuclear factor-kappa B SO CIRCULATION RESEARCH LA English DT Article DE Chlamydophila pneumoniae; intercellular adhesion molecule-1; nuclear factor-kappa B; protein kinase C; mitogen-activated protein kinase pathway ID ADHESION MOLECULE-1 ICAM-1; LOW-DENSITY-LIPOPROTEIN; CHLAMYDIA-PNEUMONIAE; GENE-EXPRESSION; MONOCYTE ADHESION; TYROSINE KINASE; SMOOTH-MUSCLE; OXIDIZED LDL; IN-VITRO; INFECTION AB Chlamydophila pneumoniae has an epidemiological link with atherosclerosis and acute cardiovascular events. One mechanism that may explain such a link is the increased expression of intracellular adhesion molecule-1 (ICAM-1) in C pneumoniae - infected endothelial cells. Upregulation of ICAM-1 by C pneumoniae is well recognized and has been extensively studied, but the signaling pathways involved are not yet defined. Because upregulation of ICAM-1 by cytokines and other stimuli has been shown to be mediated by either mitogen-activated protein kinase, protein kinase C (PKC), or nuclear factor-kappaB (NF-kappaB) pathways, we examined whether these pathways were involved in the ICAM-1 upregulation induced by C pneumoniae. Our data show a time-dependent phosphorylation of p44/p42 and SAPK/JNK pathways in C pneumoniae - infected cells. However, inhibition of the classic mitogen-activated protein kinase pathway using the PD98059 and U0126 inhibitors and inhibition of SAPK/JNK pathway did not suppress C pneumoniae - induced ICAM-1 expression. C pneumoniae also activates the NF-kappaB pathway at 30 minutes after infection. Treatment of human aortic endothelial cells (HAECs) with the NF-kappaB inhibitors BAY117085 and caffeic acid phenethyl ester led to a concentration-dependent inhibition of C pneumoniae - induced ICAM-1 upregulation. Finally, C pneumoniae - infected HAECs show membrane translocation of total PKC 30 minutes after cell infection. Calphostin C, a general PKC inhibitor, blocked both C pneumoniae - induced ICAM-1 expression and C pneumoniae - induced NF-kappaB translocation. In conclusion, we demonstrated that C pneumoniae - induced ICAM-1 expression in HAECs requires NF-kappaB and PKC activation and that NF-kappaB activation is PKC dependent. C1 Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Grad Program Mol & Cellular Biol & Pathobiol, Div Endocrinol Metab Nutr, Charleston, SC 29425 USA. RP Lopes-Virella, MF (reprint author), Ralph H Johnson VA Med Ctr, Strom Thurmon Res Bldg,114 Doughty St, Charleston, SC 29425 USA. FU NHLBI NIH HHS [HL-46815] NR 41 TC 18 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAY 30 PY 2003 VL 92 IS 10 BP 1130 EP 1137 DI 10.1161/01.RES.0000074001.46892.1C PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 684HV UT WOS:000183200100012 PM 12714566 ER PT J AU Houng, A Polgar, J Reed, GL AF Houng, A Polgar, J Reed, GL TI Munc18-syntaxin complexes and exocytosis in human platelets SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-GRANULE SECRETION; SYNAPTIC VESICLE FUSION; MOLECULAR MECHANISMS; GLUT4 TRANSLOCATION; NEGATIVE REGULATOR; 3T3-L1 ADIPOCYTES; VACUOLE FUSION; YEAST SEC1; SYNTAXIN; PROTEINS AB The Sec1-Munc18 (SM) proteins are required for cellular exocytosis, but their mechanistic function remains poorly understood. We examined SM-syntaxin complexes in human platelets, which are terminally differentiated, anuclear cells that secrete the contents of their intracellular granules through syntaxin 2- and syntaxin 4-dependent mechanisms. Munc18a, Munc18b, and Munc18c were detected in human platelets by immunoblotting and/or PCR. The SM proteins and syntaxin 2 were found in the membrane and cytosolic fractions of cells, whereas syntaxin 4 was detected only in the membrane. Platelet membranes contain Munc18c-syntaxin 4 complexes, but minimal if any Munc18c-syntaxin 2 complexes were found. No significant amounts of Munc18a or Munc18b complexes were seen with either syntaxin. Munc18c-syntaxin 4 complexes were dissociated when cells were activated to secrete. Two potential inhibitors of Munc18c-syntaxin 4 complexes were generated to examine whether complex dissociation may lead to exocytosis. Peptides that mimic the projected intermolecular contact sites of Munc18c with syntaxin enhanced Ca2+-triggered dense granule exocytosis in permeabilized cells. Similarly, an anti-Munc18c monoclonal antibody that inhibited the Munc18c-syntaxin complex potently amplified Ca2+-induced platelet granule secretion. In summary, Munc18 proteins bind to specific syntaxin isoforms in platelets despite the presence of other potential binding partners. Acute inhibition of the SM-syntaxin complex promotes Ca2+-induced exocytosis, suggesting that complex formation per se has a regulatory effect on triggered secretion. C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reed, GL (reprint author), Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, 665 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-64057] NR 54 TC 33 Z9 33 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 MAY 30 PY 2003 VL 278 IS 22 BP 19627 EP 19633 DI 10.1074/jbc.M212465200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 682EH UT WOS:000183078000010 PM 12649283 ER PT J AU Puglielli, L Ellis, BC Saunders, AJ Kovacs, DM AF Puglielli, L Ellis, BC Saunders, AJ Kovacs, DM TI Ceramide stabilizes beta-site amyloid precursor protein-cleaving enzyme 1 and promotes amyloid beta-peptide biogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NERVE GROWTH-FACTOR; CULTURED HIPPOCAMPAL-NEURONS; ALZHEIMERS-DISEASE; CELLULAR SENESCENCE; GAMMA-SECRETASE; DEATH; EXPRESSION; GENERATION; CHOLESTEROL; SURVIVAL AB The lipid second messenger ceramide regulates several biochemical events that occur during aging. In addition, its level is highly elevated in the amyloid-burdened brains of Alzheimer's disease patients. Here, we analyzed the impact of aberrant ceramide levels on amyloid beta- peptide (Abeta) generation by using a cell-permeable analog of ceramide, C6-ceramide, and several biochemical inhibitors of the sphingomyelin/glycosphingolipid biosynthetic pathway. We found that C6-ceramide increased the biogenesis of Abeta by affecting beta- but not gamma-cleavage of the amyloid precursor protein. Similarly to C6-ceramide, increased levels of endogenous ceramide induced by neutral sphingomyelinase treatment also promoted the biogenesis of Abeta. Conversely, fumonisin B1, which inhibits the biosynthesis of endogenous ceramide, reduced Abeta production. Exogenous C6-ceramide restored both intracellular ceramide levels and Abeta generation in fumonisin B1-treated cells. These events were specific for amyloid precursor protein and were not associated with apoptotic cell death. Pulse-chase and time-course degradation experiments showed that ceramide post-translationally stabilizes the beta-secretase BACE1. Taken together, these data indicate that the lipid second messenger ceramide, which is elevated in the brains of Alzheimer's disease patients, increases the half-life of BACE1 and thereby promotes Abeta biogenesis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurobiol Dis Lab,Genet & Aging Res Unit,CAGN, Charlestown, MA 02129 USA. RP Kovacs, DM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurobiol Dis Lab,Genet & Aging Res Unit,CAGN, 114 16th St, Charlestown, MA 02129 USA. NR 28 TC 142 Z9 145 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 30 PY 2003 VL 278 IS 22 BP 19777 EP 19783 DI 10.1074/jbc.M300466200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 682EH UT WOS:000183078000028 PM 12649271 ER PT J AU De Groef, B Geris, KL Manzano, J Bernal, J Millar, RP Abou-Samra, AB Porter, TE Iwasawa, A Kuhn, ER Darras, VM AF De Groef, B Geris, KL Manzano, J Bernal, J Millar, RP Abou-Samra, AB Porter, TE Iwasawa, A Kuhn, ER Darras, VM TI Involvement of thyrotropin-releasing hormone receptor, somatostatin receptor subtype 2 and corticotropin-releasing hormone receptor type 1 in the control of chicken thyrotropin secretion SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE chicken pituitary; CRH receptor; TRH receptor; SSTR2; TSH; thyrotropes ID RAT ANTERIOR-PITUITARY; FOWL GALLUS-DOMESTICUS; GROWTH-HORMONE; PROOPIOMELANOCORTIN POMC; MOLECULAR-CLONING; BRAIN; TRH; EXPRESSION; LOCALIZATION; SEQUENCE AB Thyrotropin or thyroid-stimulating hormone (TSH) secretion in the chicken is controlled by several hypothalamic hormones. It is stimulated by thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH), whereas somatostatin (SRIH) exerts an inhibitory effect. In order to determine the mechanism by which these hypothalamic hormones modulate chicken TSH release, we examined the cellular localization of TRH receptors (TRH-R), CRH receptors type I (CRH-R1) and somatostatin subtype 2 receptors (SSTR2) in the chicken pars distalis by in situ hybridization (ISH), combined with immunological staining of thyrotropes. We show that thyrotropes express TRH-Rs and SSTR2s, allowing a direct action of TRH and SRIH at the level of the thyrotropes. CRH-R1 expression is virtually confined to corticotropes, suggesting that CRH-induced adrenocorticotropin release is the result of a direct stimulation of corticotropes, whereas CRH-stimulated TSH release is not directly mediated by the known chicken CRH-R1. Possibly CRH-induced TSH secretion is mediated by a yet unknown type of CRH-R in the chicken. Alternatively, a pro-opiomelanocortin (POMC)-derived peptide, secreted by the corticotropes following CRH stimulation, could act as an activator of TSH secretion in a paracrine way. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Katholieke Univ Leuven, Lab Comparat Endocrinol, B-3000 Louvain, Belgium. CSIC, Inst Invest Biomed Alberto Sols, Madrid 28029, Spain. MRC, Human Reprod Sci Unit, Edinburgh EH16 4SB, Midlothian, Scotland. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. Gifu Univ, Fac Agr, Dept Anim Sci & Technol, Gifu 5011193, Japan. RP De Groef, B (reprint author), Katholieke Univ Leuven, Lab Comparat Endocrinol, Naamsestr 61, B-3000 Louvain, Belgium. RI Bernal, Juan/J-6086-2014; OI Bernal, Juan/0000-0002-5867-4951; Abou-Samra, Abdul/0000-0001-8735-1142 NR 43 TC 22 Z9 22 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 MAY 30 PY 2003 VL 203 IS 1-2 BP 33 EP 39 DI 10.1016/S0303-7207(03)00120-5 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 688JG UT WOS:000183430200004 PM 12782401 ER PT J AU Papakostas, GI Petersen, T Mischoulon, D Hughes, ME Alpert, JE Nierenberg, AA Rosenbaum, JE Fava, M AF Papakostas, GI Petersen, T Mischoulon, D Hughes, ME Alpert, JE Nierenberg, AA Rosenbaum, JE Fava, M TI Serum cholesterol and serotonergic function in major depressive disorder SO PSYCHIATRY RESEARCH LA English DT Article DE 5HT agonist; cholesterol; DL-fenfluramine; cortisol; prolactin; treatment response ID PLASMA-MEMBRANE FLUIDITY; META-CHLOROPHENYLPIPERAZINE; FENFLURAMINE CHALLENGE; HYPERCHOLESTEROLEMIC PATIENTS; HIPPOCAMPAL-NEURONS; CORONARY-ARTERIES; NITRIC-OXIDE; RECEPTOR; RESPONSES; VASODILATATION AB Studies have revealed a relationship between serum cholesterol levels and serotonergic (5HT) function in healthy young adults. Patients with major depressive disorder (MDD) may have significant differences in cholesterol levels compared with healthy adults, while MDD patients with elevated cholesterol have a poorer prognosis for treatment response. The goal of the present study is to examine (1) the relationship between serum cholesterol levels and central 5HT function by way of the cortisol and prolactin response to the 5HT-selective agonist DL-fenfluramine in MDD patients and (2) differences in 5HT-function between MDD patients who present with and without elevated cholesterol. Fasting serum cholesterol levels were measured in 21 outpatients with MDD. After oral administration of 60 mg of DL-fenfluramine in these patients, cortisol and prolactin responses were measured to test whether cholesterol levels predicted the degree of cortisol or prolactin response. Cortisol and prolactin responses were compared between patients with and without elevated cholesterol levels, defined as greater than or equal to 200 mg/dl. MDD patients with elevated cholesterol levels were more likely to demonstrate an attenuated cortisol response. There was no relationship between cholesterol levels and cortisol or prolactin response. Excess cholesterol may adversely affect the function of membrane-bound serotonergic structures, and this may explain why MDD patients with elevated cholesterol are more likely to exhibit attenuated neuroendocrine responses, less likely to respond to treatment and more likely to relapse. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Depress Clin & Res Program, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Depress Clin & Res Program, 15 Pkman St,WAC 812, Boston, MA 02114 USA. RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R01 MH4848305] NR 50 TC 24 Z9 26 U1 1 U2 1 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 MAY 30 PY 2003 VL 118 IS 2 BP 137 EP 145 DI 10.1016/S0165-1781(03)00066-0 PG 9 WC Psychiatry SC Psychiatry GA 691FQ UT WOS:000183595700004 PM 12798978 ER PT J AU Papakostas, GI Petersen, T Iosifescu, DV Roffi, PA Alpert, JE Rosenbaum, JE Fava, M Nierenberg, AA AF Papakostas, GI Petersen, T Iosifescu, DV Roffi, PA Alpert, JE Rosenbaum, JE Fava, M Nierenberg, AA TI Axis III disorders in treatment-resistant major depressive disorder SO PSYCHIATRY RESEARCH LA English DT Article DE depression; antidepressants; co-morbidity; treatment-resistant; open-label; nortriptyline ID PHYSICAL ILLNESS; MEDICAL ILLNESS; RATING-SCALE; NORTRIPTYLINE; ANTIDEPRESSANTS; POPULATION; COMMUNITY; RECOVERY; SYMPTOMS; TRIAL AB A number of naturalistic studies have found that medical co-morbidity conveys a worse long-term prognosis in the treatment of major depressive disorder (MDD). The purpose of this study was to test whether the presence of comorbid medical conditions can predict clinical response in patients with treatment-resistant MDD (TRD) treated with open-label nortriptyline (NT). Ninety-two patients with TRD entered a 6-week open trial of NT. The presence of comorbid medical disorders was assessed during the screen visit. The degree of medical co-morbidity during the screen visit was then quantified with the use of the Cumulative Illness Rating Scale-Geriatric Version (CIRS(G)). We tested whether CIRS(G) scores predicted clinical response or depression severity at endpoint. CIRS scores at baseline did not significantly predict treatment response. The results of this study fail to confirm the relationship between comorbid medical conditions and poor outcome in the treatment of MDD for patients with TRD. Patients with TRD and co-morbid medical conditions can be expected to respond to antidepressants as well as their counterparts without concurrent axis III co-morbidity. The CIRS(G) scores for this TRD sample were lower than those reported for,geriatric depression, or for depressed patients with severe medical illness, common in medical and surgical wards and in most specialty clinics of large academic centers. Thus, the present results cannot be generalized to such populations. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program,Dept Psychiat, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program,Dept Psychiat, 15 Pkman St,WAC 812, Boston, MA 02114 USA. RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R29 MH46952] NR 28 TC 13 Z9 13 U1 3 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 MAY 30 PY 2003 VL 118 IS 2 BP 183 EP 188 DI 10.1016/S0165-1781(03)00067-2 PG 6 WC Psychiatry SC Psychiatry GA 691FQ UT WOS:000183595700009 PM 12798983 ER PT J AU Li, DW Zhao, R Lilyestrom, W Gai, DH Zhang, RG DeCaprio, JA Fanning, E Jochimiak, A Szakonyi, G Chen, XJS AF Li, DW Zhao, R Lilyestrom, W Gai, DH Zhang, RG DeCaprio, JA Fanning, E Jochimiak, A Szakonyi, G Chen, XJS TI Structure of the replicative helicase of the oncoprotein SV40 large tumour antigen SO NATURE LA English DT Article ID LARGE T-ANTIGEN; SIMIAN-VIRUS-40 DNA-REPLICATION; TEMPERATURE-SENSITIVE MUTANTS; RAT EMBRYO FIBROBLASTS; SIMIAN VIRUS-40; CRYSTAL-STRUCTURE; DOUBLE HEXAMERS; STRAND SYNTHESIS; BINDING DOMAINS; VIRAL ORIGIN AB The oncoprotein large tumour antigen (LTag) is encoded by the DNA tumour virus simian virus 40. LTag transforms cells and induces tumours in animals by altering the functions of tumour suppressors (including pRB and p53) and other key cellular proteins. LTag is also a molecular machine that distorts/melts the replication origin of the viral genome and unwinds duplex DNA. LTag therefore seems to be a functional homologue of the eukaryotic minichromosome maintenance (MCM) complex. Here we present the X-ray structure of a hexameric LTag with DNA helicase activity. The structure identifies the p53-binding surface and reveals the structural basis of hexamerization. The hexamer contains a long, positively charged channel with an unusually large central chamber that binds both single-stranded and double-stranded DNA. The hexamer organizes into two tiers that can potentially rotate relative to each other through connecting alpha-helices to expand/constrict the channel, producing an 'iris' effect that could be used for distorting or melting the origin and unwinding DNA at the replication fork. C1 Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Biochem & Mol Genet, Denver, CO 80262 USA. Argonne Natl Lab, Adv Photon Source, SBC, Argonne, IL 60439 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Vanderbilt Univ, VU Stn B 1634, Nashville, TN 37235 USA. RP Chen, XJS (reprint author), Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Biochem & Mol Genet, Denver, CO 80262 USA. RI Li, Dawei /I-8751-2016 OI Li, Dawei /0000-0003-4133-1263 NR 50 TC 210 Z9 217 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 29 PY 2003 VL 423 IS 6939 BP 512 EP 518 DI 10.1038/nature01691 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 683RH UT WOS:000183162900036 PM 12774115 ER PT J AU Puigserver, P Rhee, J Donovan, J Walkey, CJ Yoon, JC Oriente, F Kitamura, Y Altomonte, J Dong, HJ Accili, D Spiegelman, BM AF Puigserver, P Rhee, J Donovan, J Walkey, CJ Yoon, JC Oriente, F Kitamura, Y Altomonte, J Dong, HJ Accili, D Spiegelman, BM TI Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1 alpha interaction SO NATURE LA English DT Article ID FORKHEAD TRANSCRIPTION FACTOR; CARBOXYKINASE GTP GENE; PROTEIN-KINASE-B; PHOSPHOENOLPYRUVATE CARBOXYKINASE; COACTIVATOR PGC-1; FACTOR FOXO1; FACTOR FKHR; EXPRESSION; BETA; PHOSPHORYLATION AB Hepatic gluconeogenesis is absolutely required for survival during prolonged fasting or starvation, but is inappropriately activated in diabetes mellitus. Glucocorticoids and glucagon have strong gluconeogenic actions on the liver. In contrast, insulin suppresses hepatic gluconeogenesis(1-3). Two components known to have important physiological roles in this process are the forkhead transcription factor FOXO1 (also known as FKHR) and peroxisome proliferative activated receptor-gamma co-activator 1 (PGC-1alpha; also known as PPARGC1), a transcriptional co-activator; whether and how these factors collaborate has not been clear. Using wild-type and mutant alleles of FOXO1, here we show that PGC-1alpha binds and co-activates FOXO1 in a manner inhibited by Akt-mediated phosphorylation. Furthermore, FOXO1 function is required for the robust activation of gluconeogenic gene expression in hepatic cells and in mouse liver by PGC-1alpha. Insulin suppresses gluconeogenesis stimulated by PGC-1alpha but co-expression of a mutant allele of FOXO1 insensitive to insulin completely reverses this suppression in hepatocytes or transgenic mice. We conclude that FOXO1 and PGC-1alpha interact in the execution of a programme of powerful, insulin-regulated gluconeogenesis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Columbia Univ, Coll Phys & Surg, Naomi Berrie Diabet Ctr, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Mt Sinai Sch Med, Inst Human Gene Therapy & Mol Med, New York, NY 10029 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. OI Dong, H. Henry/0000-0003-0279-5241 NR 22 TC 737 Z9 767 U1 9 U2 41 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 29 PY 2003 VL 423 IS 6939 BP 550 EP 555 DI 10.1038/nature01667 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 683RH UT WOS:000183162900046 PM 12754525 ER PT J AU Basa, NR Wang, LX Arteaga, JR Heber, D Livingston, EH Tache, Y AF Basa, NR Wang, LX Arteaga, JR Heber, D Livingston, EH Tache, Y TI Bacterial lipopolysaccharide shifts fasted plasma ghrelin to postprandial levels in rats SO NEUROSCIENCE LETTERS LA English DT Article DE lipopolysaccharide; circulating ghrelin; food intake; rat; rectal temperature ID INDUCED ANOREXIA; EXPRESSION; RODENTS; HUMANS AB Lipopolysaccharide (LPS) injected intraperitoneally (i.p.) is known to decrease food intake. Ghrelin is a peptide hormone produced by the stomach with a potent orexigenic effect and plasma levels that are inversely correlated with the fed state. We examined changes in plasma ghrelin levels 3 h after LPS (100 mug/kg, i.p.) in fasted rats with or without a 1 h re-feeding period. LPS injection decreased the fasting levels of ghrelin by 51 +/- 5% compared with preinjection values while i.p. vehicle did not modify ghrelin levels in fasted rats. LPS at this dose reduced fasting-induced food intake by 60% compared with the i.p. vehicle group. Re-feeding decreased plasma ghrelin levels by 58 +/- 3% compared with pre-feeding fasting values in i.p. vehicle group. These data provide the first evidence that LPS shifts fasting ghrelin levels to those observed postprandially. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, CURE, Dept Med,David Geffen Sch Med, Digest Dis Res Ctr,Digest Dis Div,VAGLAHS, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Human Nutr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA 90073 USA. RP Basa, NR (reprint author), Univ Calif Los Angeles, CURE, Dept Med,David Geffen Sch Med, Digest Dis Res Ctr,Digest Dis Div,VAGLAHS, Bldg 115,Room 117B,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK 41301, P50DK 64539] NR 21 TC 56 Z9 57 U1 1 U2 1 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 MAY 29 PY 2003 VL 343 IS 1 BP 25 EP 28 DI 10.1016/S0304-3940903)00312-4 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 683CE UT WOS:000183128900007 PM 12749989 ER PT J AU Jha, AK Perlin, JB Kizer, KW Dudley, RA AF Jha, AK Perlin, JB Kizer, KW Dudley, RA TI Effect of the transformation of the Veterans Affairs health care system on the quality of care. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MEDICARE BENEFICIARIES; FEE SCHEDULE; MANAGED CARE; VA; DISPARITIES AB BACKGROUND: In the mid-1990s, the Department of Veterans Affairs (VA) health care system initiated a systemwide reengineering to, among other things, improve its quality of care. We sought to determine the subsequent change in the quality of health care and to compare the quality with that of the Medicare fee-for-service program. METHODS: Using data from an ongoing performance-evaluation program in the VA, we evaluated the quality of preventive, acute, and chronic care. We assessed the change in quality-of-care indicators from 1994 (before reengineering) through 2000 and compared the quality of care with that afforded by the Medicare fee- for-service system, using the same indicators of quality. RESULTS: In fiscal year 2000, throughout the VA system, the percentage of patients receiving appropriate care was 90 percent or greater for 9 of 17 quality-of-care indicators and exceeded 70 percent for 13 of 17 indicators. There were statistically significant improvements in quality from 1994-1995 through 2000 for all nine indicators that were collected in all years. As compared with the Medicare fee-for-service program, the VA performed significantly better on all 11 similar quality indicators for the period from 1997 through 1999. In 2000, the VA outperformed Medicare on 12 of 13 indicators. CONCLUSIONS: The quality of care in the VA health care system substantially improved after the implementation of a systemwide reengineering and, during the period from 1997 through 2000, was significantly better than that in the Medicare fee-for-service program. These data suggest that the quality-improvement initiatives adopted by the VA in the mid-1990s were effective. C1 Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94118 USA. Vet Hlth Adm, Off Qual & Performance, Washington, DC USA. San Francisco Vet Affairs Med Ctr, Div Gen Internal Med, San Francisco, CA USA. Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. Natl Qual Forum, Washington, DC USA. RP Dudley, RA (reprint author), Univ Calif San Francisco, Inst Hlth Policy Studies, Box 0936,333 Calif St,Suite 265, San Francisco, CA 94118 USA. NR 35 TC 435 Z9 437 U1 0 U2 13 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 MAY 29 PY 2003 VL 348 IS 22 BP 2218 EP 2227 DI 10.1056/NEJMsa021899 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 683EK UT WOS:000183134700009 PM 12773650 ER PT J AU Hirsch, MS Harris, NL Davis, BT Werner, B Basgoz, N Calderon, HA AF Hirsch, MS Harris, NL Davis, BT Werner, B Basgoz, N Calderon, HA TI Case 17-2003: A 38-year-old woman with fever, headache, and confusion - West Nile virus meningoencephalitis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ENCEPHALITIS; ASSAY C1 Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. State Lab Inst, Jamaica Plain, MA USA. RP Hirsch, MS (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. NR 20 TC 2 Z9 3 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 MAY 29 PY 2003 VL 348 IS 22 BP 2239 EP 2247 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 683EK UT WOS:000183134700011 PM 12773652 ER PT J AU Harris, NL AF Harris, NL TI Case records of the Massachusetts General Hospital - Continuing to learn from the patient SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Harris, NL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 9 TC 5 Z9 6 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 MAY 29 PY 2003 VL 348 IS 22 BP 2252 EP 2254 DI 10.1056/NEJMe030079 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 683EK UT WOS:000183134700014 PM 12773655 ER PT J AU An, JB Sun, YP Sun, R Rettig, MB AF An, JB Sun, YP Sun, R Rettig, MB TI Kaposi's sarcoma-associated herpesvirus encoded vFLIP induces cellular IL-6 expression: the role of the NF-kappa B and JNK/AP1 pathways SO ONCOGENE LA English DT Article DE KSHV; vFLIP; interleukin-6; NF-kappa B; jun N-terminal kinase; AP1 ID MULTICENTRIC CASTLEMANS-DISEASE; FLICE-INHIBITORY PROTEIN; INTERLEUKIN-6 GENE-EXPRESSION; EFFUSION LYMPHOMA-CELLS; C-JUN; DNA-SEQUENCES; NUCLEAR ANTIGEN; TERMINAL KINASE; EFFECTOR DOMAIN; GROWTH-FACTOR AB The Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a FADD-like interferon converting enzyme or caspase 8 (FLICE) inhibitory protein (vFLIP) that prevents death receptor-mediated apoptosis by inhibiting the recruitment and activation of FLICE. Since vFLIP physically interacts with tumor necrosis factor receptor associated factor 2 (TRAF2) and TRAF2 mediates activation of the jun NH2-terminal kinase (JNK)/activation protein 1 (AP1) pathway, we hypothesized that vFLIP might also activate this pathway. To evaluate this hypothesis, we transiently and stably transfected a vFLIP expression construct and performed several complementary assays to document that vFLIP activates the JNK/AP1 pathway and does so in a TRAF-dependent fashion. As vFLIP also activates the nuclear factor kappaB (NF-kappaB) signaling pathway and the NF-kappaB and JNK/AP1 pathways both modulate cellular interleukin-6 (cIL-6) expression, we postulated that vFLIP induces expression of this cytokine. We show that vFLIP induces cIL-6 expression and activates the cIL-6 promoter, and maximal activation of the cIL-6 promoter by vFLIP requires NF-kappaB and AP1 activation. In addition, vFLIP and latency-associated nuclear antigen (LANA), another KSHV-encoded latent protein, potentiate each other's ability to activate the cIL-6 promoter. Gene silencing experiments by RNA interference demonstrate that vFLIP in BCBL-1 endogenously infected primary effusion lymphoma (PEL) cells mediates JNK/AP1 activation and cIL-6 expression. Thus, we conclude that vFLIP, in addition to its known effects on NF-kappaB activation, also modulates the JNK/AP1 pathway and induces gene expression from the cIL-6 promoter in a JNK/AP1-dependent fashion. C1 VA Greater Los Angeles Healthcare Syst W LA, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Rettig, MB (reprint author), VA Greater Los Angeles Healthcare Syst W LA, Dept Med, 11301 Wilshire Blvd,Bldg 304,Room E1-113, Los Angeles, CA 90073 USA. FU NCI NIH HHS [1R01CA80004-01A1] NR 46 TC 75 Z9 79 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 29 PY 2003 VL 22 IS 22 BP 3371 EP 3385 DI 10.1038/sj.onc.1206407 PG 15 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 683CB UT WOS:000183128500003 PM 12776188 ER PT J AU Yaffe, K AF Yaffe, K TI Hormone therapy and the brain - Deja vu all over again? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; ESTROGEN REPLACEMENT; COGNITIVE IMPAIRMENT; OLDER WOMEN; RISK; DEMENTIA; POLYMORPHISMS; ONSET C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94121 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA. NR 25 TC 54 Z9 55 U1 0 U2 0 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 MAY 28 PY 2003 VL 289 IS 20 BP 2717 EP 2719 DI 10.1001/jama.289.20.2717 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 682DG UT WOS:000183075600031 PM 12771119 ER PT J AU Rosas, HD Koroshetz, WJ Chen, YI Skeuse, C Vangel, M Cudkowicz, ME Caplan, K Marek, K Seidman, LJ Makris, N Jenkins, BG Goldstein, JM AF Rosas, HD Koroshetz, WJ Chen, YI Skeuse, C Vangel, M Cudkowicz, ME Caplan, K Marek, K Seidman, LJ Makris, N Jenkins, BG Goldstein, JM TI Evidence for more widespread cerebral pathology in early HD - An MRI-based morphometric analysis SO NEUROLOGY LA English DT Article ID ADULT HUMAN BRAIN; HUNTINGTONS-DISEASE; ABNORMALITIES; VOLUMES; ATROPHY; HIPPOCAMPUS; LESIONS AB Background: Most clinical symptoms of Huntington disease (HD) have been attributed to striatal degeneration, but extrastriatal degeneration may play an important role in the clinical symptoms because postmortem studies demonstrate that almost all brain structures atrophy. Objective: To fully characterize the morphometric changes that occur in vivo in HD. Methods: High-resolution 1.5 mm T1-weighted coronal scans were acquired from 18 individuals in early to mid-stages of HD and 18 healthy age-matched controls. Cortical and subcortical gray and white matter were segmented using a semiautomated intensity contour-mapping algorithm. General linear models for correlated data of the volumes of brain regions were used to compare groups, controlling for age, education, handedness, sex, and total brain volumes. Results: Subjects with HD had significant volume reductions in almost all brain structures, including total cerebrum, total white matter, cerebral cortex, caudate, putamen, globus pallidus, amygdala, hippocampus, brainstem, and cerebellum. Conclusions: Widespread degeneration occurs in early to mid-stages of HD, may explain some of the clinical heterogeneity, and may impact future clinical trials. C1 Massachusetts Gen Hosp, Ctr Genet Aging & Neurodegenerat, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Morphometr Analyses, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, MGH NMR Ctr, Dept Radiol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Inst Neurogenet Disorders, New Haven, CT USA. Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Psychiat Epidemiol & Genet, Boston, MA 02114 USA. RP Rosas, HD (reprint author), Massachusetts Gen Hosp, Ctr Genet Aging & Neurodegenerat, Dept Neurol, 114 16th St,Suite 2000, Boston, MA 02114 USA. FU NINDS NIH HHS [NS37102, NS02060, NS02069, NS35255] NR 42 TC 274 Z9 278 U1 4 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 27 PY 2003 VL 60 IS 10 BP 1615 EP 1620 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 682LD UT WOS:000183092400013 PM 12771251 ER PT J AU Rajab, A Mochida, GH Hill, A Ganesh, V Bodell, A Riaz, A Grant, PE Shugart, YY Walsh, CA AF Rajab, A Mochida, GH Hill, A Ganesh, V Bodell, A Riaz, A Grant, PE Shugart, YY Walsh, CA TI A novel form of pontocerebellar hypoplasia maps to chromosome 7q11-21 SO NEUROLOGY LA English DT Article ID ATROPHY PEHO-SYNDROME; OPTIC ATROPHY; PROGRESSIVE ENCEPHALOPATHY; PONTONEOCEREBELLAR HYPOPLASIA; INHERITED SYNDROME; LINKAGE ANALYSIS; EDEMA; HYPSARRHYTHMIA; ABNORMALITIES; DYSKINESIA AB Objective: To describe a novel form of pontocerebellar hypoplasia (PCH) and map its genetic locus. Background: PCH is a heterogeneous group of disorders that are characterized by abnormally small cerebellum and brainstem. Autosomal recessive inheritance has been implied in many cases, but no genetic loci have been mapped to date. Methods: The authors studied a consanguineous family from the Sultanate of Oman with three siblings with a novel form of PCH. The authors performed clinical studies and linkage analysis of this pedigree. Results: The clinical features of the affected children include developmental delay, progressive microcephaly with brachycephaly, seizures during the first year of life, hypotonia with hyperreflexia, short stature, and optic atrophy. Imaging studies showed a small pons and cerebellum, prominent sulci and lateral ventricles, and decreased cerebral white matter volume. A lack of dyskinesias distinguishes this pedigree from PCH type 2. Genetic studies of this family revealed evidence of significant linkage to chromosome 7q11-21 (maximum multipoint lod score 3.23). Conclusions: This pedigree represents a novel form of autosomal recessive PCH, which the authors propose to call cerebellar atrophy with progressive microcephaly (CLAM). This disorder maps to chromosome 7q11-21, and this locus was named CLAM. This report represents the first identification of a genetic locus for PCH. C1 Harvard Univ, Sch Med, Inst Med, BIDMC,Div Neurogenet, Boston, MA 02115 USA. Harvard Univ, Sch Med, BIDMC, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Sect, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Walsh, CA (reprint author), Harvard Univ, Sch Med, Inst Med, BIDMC,Div Neurogenet, Room 816,77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NINDS NIH HHS [P01NS39404, 2R37NS35129] NR 21 TC 42 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 27 PY 2003 VL 60 IS 10 BP 1664 EP 1667 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 682LD UT WOS:000183092400021 PM 12771259 ER PT J AU Lessell, S Collins, TE AF Lessell, S Collins, TE TI Ophthalmoplegia in Powassan encephalitis SO NEUROLOGY LA English DT Editorial Material ID LESIONS C1 Massachusetts Eye & Ear Infirm, Neuroophthalmol Unit, Boston, MA 02114 USA. RP Lessell, S (reprint author), 243 Charles St, Boston, MA 02114 USA. NR 7 TC 10 Z9 10 U1 1 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 MAY 27 PY 2003 VL 60 IS 10 BP 1726 EP 1727 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 682LD UT WOS:000183092400050 PM 12771287 ER PT J AU Feng, Y Yu, S Lasell, TKR Jadhav, AP Macia, E Chardin, P Melancon, P Roth, M Mitchison, T Kirchhausen, T AF Feng, Y Yu, S Lasell, TKR Jadhav, AP Macia, E Chardin, P Melancon, P Roth, M Mitchison, T Kirchhausen, T TI Exo1: A new chemical inhibitor of the exocytic pathway SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Golgi; ADP-ribosylation factor; endoplasmic reticulum (ER); imaging-based screen; Bars50 ID TO-GOLGI TRANSPORT; BREFELDIN-A; ENDOPLASMIC-RETICULUM; ORGANELLE STRUCTURE; GUANINE-NUCLEOTIDE; ADP-RIBOSYLATION; GTP HYDROLYSIS; LIVING CELLS; SEC7 DOMAIN; IN-VIVO AB A phenotypic screen was used to search for drug-like molecules that can interfere with specific steps in membrane traffic. 2-(4-Fluorobenzoylamino)-benzoic acid methyl ester (Exo1), identified in this screen, induces a rapid collapse of the Golgi to the endoplasmic reticulum, thus acutely inhibiting the traffic emanating from the endoplasmic reticulum. Like Brefeldin A (BFA), Exo1 induces the rapid release of ADP-ribosylation factor (ARIF) 1 from Golgi membranes but has less effect on the organization of the trans-Golgi network. Our data indicate that Exo1 acts by a different mechanism from BFA. Unlike BFA, Exo1 does not induce the ADP-ribosylation of CtBP/Bars50 and does not interfere with the activity of guanine nucleotide exchange factors specific for Golgi-based ARFs. Thus, Exo1 allows the fatty acid exchange activity of Bars50 to be distinguished from ARF1 activity in the control of Golgi tubulation. C1 Harvard Univ, Sch Med, Inst Chem & Cell Biol, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75235 USA. Univ Alberta, Dept Cell Biol, Edmonton, AB T6H 2H7, Canada. CNRS, Inst Pharmacol Mol & Cellulaire, UMR 6097, F-06560 Valbonne, France. RP Feng, Y (reprint author), Harvard Univ, Sch Med, Inst Chem & Cell Biol, Dept Cell Biol, Boston, MA 02115 USA. OI Roth, Michael/0000-0002-9056-332X; Melancon, Paul/0000-0002-8085-3032 FU NIGMS NIH HHS [P01 GM62566-02, R01 GM036548, P01 GM062566, R01 GM36548-17] NR 27 TC 80 Z9 82 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 27 PY 2003 VL 100 IS 11 BP 6469 EP 6474 DI 10.1073/pnas.0631766100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 684DT UT WOS:000183190700034 PM 12738886 ER PT J AU Kushner, N Zhang, D Touzjian, N Essex, M Lieberman, J Lu, YC AF Kushner, N Zhang, D Touzjian, N Essex, M Lieberman, J Lu, YC TI A fragment of anthrax lethal factor delivers proteins to the cytosol without requiring protective antigen SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TOXIN-MEDIATED DELIVERY; IN-VIVO; BACILLUS-ANTHRACIS; RESPONSES; HEPATITIS; RECEPTOR; EPITOPE; BINDING AB Anthrax protective antigen (PA) is a 735-aa polypeptide that facilitates the exit of anthrax lethal factor (LF) from the endosome to the cytosol where the toxin acts. We recently found, however, that a fusion protein of the detoxified N-terminal domain of lethal factor (LFn) with a foreign peptide could induce CD8 T cell immune responses in the absence of PA. Because CD8 T cells recognize peptides derived from proteins degraded in the cytosol, this result suggests that lethal factor may be capable of entering the cytosol independently of PA. To investigate this further, the intracellular trafficking of an LFn-enhanced green fluorescent protein fusion protein (LFn-GFP) in the presence or absence of PA was examined by using confocal microscopy. LFn-GFP is able to enter the cytosol without PA. Moreover, it efficiently colocalizes with the proteosome 20s subunit, which degrades proteins into peptides for presentation to CD8 T cells by the MHC class I pathway. We further demonstrate that in the presence of an immune adjuvant LFn fusion protein without PA is able to effectively elicit anti-HIV cytotoxic T lymphocyte in-inbred mice. These results indicate that LFn may be used without PA in a protein vaccine as a carrier to deliver antigens into the cytosol for efficient induction of T lymphocyte responses. Furthermore, these results enable us to propose a modified molecular mechanism of anthrax lethal toxin. C1 Harvard Univ, Sch Publ Hlth, Harvard AIDS Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Inst Int Vaccine Dev, Cambridge, MA 02138 USA. RP Lu, YC (reprint author), FXB Bldg 304,651 Huntington Ave, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI47539] NR 21 TC 19 Z9 22 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 MAY 27 PY 2003 VL 100 IS 11 BP 6652 EP 6657 DI 10.1073/pnas.1131930100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 684DT UT WOS:000183190700066 PM 12740437 ER PT J AU Barth, RN Yamamoto, S LaMattina, JC Kumagai, N Kitamura, H Vagefi, PA Awwad, M Colvin, RB Cooper, DKC Sykes, M Sachs, DH Yamada, K AF Barth, RN Yamamoto, S LaMattina, JC Kumagai, N Kitamura, H Vagefi, PA Awwad, M Colvin, RB Cooper, DKC Sykes, M Sachs, DH Yamada, K TI Xenogeneic thymokidney and thymic tissue transplantation in a pig-to-baboon model: I. Evidence for pig-specific T-cell unresponsiveness SO TRANSPLANTATION LA English DT Article ID HUMORAL XENOGRAFT REJECTION; MINIATURE SWINE; ANTI-GAL-ALPHA-1-3GAL ANTIBODY; KIDNEY TRANSPLANTATION; SELF-TOLERANCE; BONE-MARROW; BARRIER; GRAFTS; XENOTRANSPLANTATION; EXPRESSION AB Background. The potential of xenotransplantation for clinical application will require overcoming barriers of humoral and cellular rejection, through strategies using immune suppression or tolerance induction. This laboratory has previously reported the induction of tolerance in the discordant xenogeneic model of pig-to-rodent thymic transplantation. We also have described a miniature swine model of fully mismatched allogeneic composite vascularized thymokidney transplantation that induced transplantation tolerance. We tested a combination of these approaches in a clinically relevant pig-to-primate model of xenotransplantation. Methods. Composite thymokidney grafts were prepared 40 to 80 days before transplantation by the antologous implantation of thymic tissue under the renal capsule of human decay-accelerating factor transgenic swine. Baboons received xenotransplants of both human decay-accelerating factor composite thymokidneys and omental implants of thymic tissue. Recipients were treated with an immunosuppressive-conditioning regimen including thymectomy or thymic irradiation, extracorporeal immunoadsorption of anti-alphaGal antibodies and T-cell depletion. Recipients were followed for indicators of xenograft rejection, T-cell depletion and reconstitution, anti-alphaGal antibody levels, and mixed lymphocyte responses. Immunologic responses were studied in those animals that survived for more than 3 weeks. Results. Thymokidney xenografts survived for up to 30 days, with evidence of viable thymic epithelium and Hassall's corpuscles under the renal capsule and in the omental implants, and with evidence of few host lymphocytes. Three animals demonstrated donor-specific unresponsiveness, while maintaining normal alloresponses, in mixed-lymphocyte-response assays performed after immunosuppression had been stopped. Rejected grafts demonstrated humoral damage without evidence of cellular infiltrates. After graftectomy, one animal maintained donor-specific cellular unresponsiveness and stable anti-alphaGal antibody levels for more than 2 months. Conclusions. We concluded that composite thymokidney and thymic-tissue xenotransplantation from swine to baboons can induce donor-specific cellular unresponsiveness and stable anti-alphaGal antibody levels, suggesting avoidance of sensitization after xenotransplantation. The presence of viable donor-swine thymic epithelium could have a role in the development of donor-specific T-cell tolerance. Further strategies to address humoral rejection could prolong graft survival and result in long-term tolerance to xenografts. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. Immerge BioTherapeut, Charlestown, MA USA. RP Yamada, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH-E,Bldg,13th St, Boston, MA 02129 USA. RI Barth, Rolf/B-2542-2014; LaMattina, John/B-2976-2014 OI LaMattina, John/0000-0001-7016-0382 FU NIAID NIH HHS [1P01 AI45897, 5P01 AI39755] NR 44 TC 51 Z9 53 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 27 PY 2003 VL 75 IS 10 BP 1615 EP 1624 DI 10.1097/01.TP.0000064335.50622.20 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 684BA UT WOS:000183184500001 PM 12777846 ER PT J AU Spitzer, TR McAfee, SL Dey, BR Colby, C Hope, J Grossberg, H Preffer, F Shaffer, J Alexander, SI Sachs, DH Sykes, M AF Spitzer, TR McAfee, SL Dey, BR Colby, C Hope, J Grossberg, H Preffer, F Shaffer, J Alexander, SI Sachs, DH Sykes, M TI Nonmyeloablative haploidentical stem-cell transplantation using anti-CD2 monoclonal antibody (MEDI-507)-based conditioning for refractory hematologic malignancies SO TRANSPLANTATION LA English DT Article ID MIXED CHIMERISM; INDUCTION; TOLERANCE; MEDI-507 AB We initiated a clinical trial of nonmyeloablative haploidentical stem-cell transplantation (SCT). using MEDI-507, an immunoglobulin-G1 monoclonal anti-CD2 antibody. The trial was based on a preclinical major histocompatibility complex-mismatched bone marrow transplant model in which graft-versus-host disease (GVHD) was prevented and mixed chimerism as a platform for adoptive cellular immunotherapy was reliably induced. Twelve patients (three cohorts of four patients each) received cyclophosphamide, MEDI-507, and haploidentical unmanipulated bone marrow (n=8) or ex vivo T-cell-depleted peripheral blood stem cells (n=4) for chemorefractory hematologic malignancy. A two-dose regimen and schedule modifications of MEDI-507 were undertaken because of graft loss in the first cohort of four patients and GVHD in the second cohort. With ex vivo T-cell-depleted, peripheral blood SCT, mixed chimerism occurred in all four patients without GVHD. Two patients, however, subsequently lost their grafts. Nonmyeloablative preparative therapy with MEDI-507 and haploidentical SCT have led to the reliable induction of at least transient mixed, chimerism as a potential platform for adoptive cellular immunotherapy. C1 Massachusetts Gen Hosp, Dept Med, Bone Marrow Transplant Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. BioTransplant Inc, Charlestown, MA USA. RP Spitzer, TR (reprint author), Massachusetts Gen Hosp, Dept Med, Bone Marrow Transplant Program, COX 640,100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [R01 CA79986-02]; NHLBI NIH HHS [R01 HL63474] NR 10 TC 71 Z9 75 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 MAY 27 PY 2003 VL 75 IS 10 BP 1748 EP 1751 DI 10.1097/01.TP.0000064211.23536.AD PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 684BA UT WOS:000183184500027 PM 12777868 ER PT J AU Haidet, P Paterniti, DA AF Haidet, P Paterniti, DA TI "Building" a history rather than "Taking" one - A perspective on information sharing during the medical interview SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PHYSICIAN-PATIENT COMMUNICATION; NARRATIVE BASED MEDICINE; PRIMARY-CARE PHYSICIANS; EXPLANATORY MODELS; SATISFACTION; SKILLS; CONSULTATIONS; RETENTION; LANGUAGE; BEHAVIOR AB Patients and physicians enter the medical encounter with unique perspectives on the illness experience. These perspectives influence the way that information is shared during the initial phase of the interview. Previous research has demonstrated that patients who are able to fully share their perspective often achieve better outcomes. However, studies of patient-physician communication have shown that the patient's perspective is often lost. Researchers and educators have responded with calls for practitioners to adopt a "narrative-based medicine" approach to the medical interview. In this article, we review the literature on narrative-based medicine with an emphasis on information sharing during the medical interview. We suggest a framework of skills and attitudes that can act as a foundation for future work in educating practitioners and researching the medical interview. C1 Houston Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Dept Vet Affairs, Hlth Serv Res Ctr Excellence, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Univ Calif Davis, Ctr Hlth Serv Res, Dept Internal Med, Sacramento, CA 95817 USA. RP Haidet, P (reprint author), Houston Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Dept Vet Affairs, Hlth Serv Res Ctr Excellence, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. NR 68 TC 66 Z9 67 U1 4 U2 13 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 MAY 26 PY 2003 VL 163 IS 10 BP 1134 EP 1140 DI 10.1001/archinte.163.10.1134 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 684KQ UT WOS:000183206400002 PM 12767949 ER PT J AU Jackson, VA Sesso, HD Buring, JE Gaziano, M AF Jackson, VA Sesso, HD Buring, JE Gaziano, M TI Alcohol consumption and mortality in men with preexisting cerebrovascular disease SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID US MALE PHYSICIANS; CORONARY HEART-DISEASE; MYOCARDIAL-INFARCTION; DEPRESSIVE SYMPTOMS; ISCHEMIC STROKE; BETA-CAROTENE; RISK; HEALTH; LIGHT; QUESTIONNAIRE AB Background: In counseling patients with a history of stroke, clinicians have limited information regarding the risks and benefits of alcohol consumption. Objective: To examine the relationship between alcohol intake and risks of total and cardiovascular mortality in men with a history of stroke. Methods: The study population consisted of 112528 men from the enrollment cohort of the Physicians' Health Study, 1320 of whom reported a baseline history of stroke. Men provided Self-reported data on alcohol consumption, which was classified into 1 of 4 categories: rarely or never drink, very light (<1 drink per week), light (1-6 drinks per week), or moderate (&GE;1 drink per day). Cox proportional hazards models were used to assess the relative risks of mortality associated with alcohol consumption, after adjustment for major coronary risk factors. Results: During a mean follow-up of 41/2 years, 369 men died, 267 of whom died of cardiovascular disease. Compared with men with a history of stroke who drank rarely or never, those with a very light to moderate alcohol intake had multivariate relative risks for total mortality of 0.88 (95% confidence interval [CI], 0.60-1.28), 0.64 (95% CI, 0.48-0.85), and 0.71 (95% CI, 0.54-0.94), respectively (P = .03 for trend); and relative risks for cardiovascular mortality of 0.89 (95% CI, 0.58-1.36), 0.56 (95% CI, 0.40-0.79), and 0.64 (95% CI, 0.46-0.88) P = .008 for trend). Compared with age-adjusted models, adjustment for major coronary risk factors did not significantly change risk estimates for total or cardiovascular mortality. Conclusions: These data indicate a possible inverse association between light to moderate alcohol intake and risks of total and cardiovascular mortality in men with a history of stroke. More data are needed to confirm or refute these results. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. Harvard Med Sch, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Jackson, VA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA097193] NR 22 TC 21 Z9 21 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 MAY 26 PY 2003 VL 163 IS 10 BP 1189 EP 1193 DI 10.1001/archinte.163.10.1189 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 684KQ UT WOS:000183206400008 PM 12767955 ER PT J AU Brugarolas, J Clark, JW Chabner, B AF Brugarolas, J Clark, JW Chabner, B TI Using "rationally designed drugs" rationally SO LANCET LA English DT Editorial Material ID CHRONIC MYELOGENOUS LEUKEMIA; ABL TYROSINE KINASE; INHIBITOR; BCR/ABL; CELLS; MICE; INDUCTION C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Brugarolas, J (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 13 TC 4 Z9 4 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 24 PY 2003 VL 361 IS 9371 BP 1758 EP 1759 DI 10.1016/S0140-6736(03)13446-0 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 682CY UT WOS:000183074800004 PM 12781531 ER PT J AU Robbins, GK Addo, MM Troung, H Rathod, A Habeeb, K Davis, B Heller, H Basgoz, N Walker, BD Rosenberg, ES AF Robbins, GK Addo, MM Troung, H Rathod, A Habeeb, K Davis, B Heller, H Basgoz, N Walker, BD Rosenberg, ES TI Augmentation of HIV-1-specific T helper cell responses in chronic HIV-1 infection by therapeutic immunization SO AIDS LA English DT Article DE AIDS; HIV; immunology; lymphoproliferation; T helper cells; therapeutic vaccine ID VIRUS TYPE-1 HIV-1; INCOMPLETE FREUNDS-ADJUVANT; MEDIATED IMMUNE-RESPONSES; PROLIFERATIVE RESPONSES; HIV-1-INFECTED PATIENTS; ANTIRETROVIRAL THERAPY; TREATMENT INTERRUPTION; X 10(6)/L; CD4; INDIVIDUALS AB Objective: To determine whether therapeutic immunization with a whole inactivated HIV-1 immunogen augments HIV-1-specific T helper cell responses in chronically infected individuals receiving suppressive antiretroviral therapy (ART). Design: An investigator-initiated, single center, double-blind, placebo-controlled, randomized trial. Methods: Subjects selected for study were HIV-1-infected adults on ART with an HIV-1-RNA plasma viral load of less than 500 copies/ml for at least 6 months, and a CD4 cell count greater than 250 cells/mm(3) before starting ART. Study subjects were randomly assigned to receive either immunogen (inactivated envelope-depleted HIV-1 coupled with incomplete Freund's adjuvant; IFA), versus placebo (IFA alone). The primary outcome was significant CD4 cell lymphoproliferative responses to HIV-1 proteins. Secondary endpoints included HIV-1-specific CD8 T cell responses, CD4 cell count/percentage, HIV-1-RNA plasma viral load, and delayed-type hypersensitivity (DTH) responses. Results: The augmentation of HIV-1-specific T helper cell responses was achieved in five out of five vaccine recipients and none out of four controls (P=0.008, Fisher's exact test). There were no significant changes in the breadth or magnitude of cytotoxic T lymphocyte responses, CD4 cell count/percentages, or DTH test responses. Conclusion: HIV-1-specific T helper cell responses can be successfully increased by therapeutic immunization in individuals with chronic infection on suppressive ART. Further studies will be needed to determine whether the augmentation of these responses correlate with long-term clinical benefits. (C) 2003 Lippincoft Williams Wilkins. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr,Div AIDS, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Walker, BD (reprint author), Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. RI Robbins, Gregory/F-7988-2011 NR 29 TC 44 Z9 45 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 23 PY 2003 VL 17 IS 8 BP 1121 EP 1126 DI 10.1097/01.aids.0000060368.78202.2f PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 687ZT UT WOS:000183408000002 PM 12819512 ER PT J AU Salomone, S Yoshimura, S Reuter, U Foley, M Thomas, SS Moskowitz, MA Waeber, C AF Salomone, S Yoshimura, S Reuter, U Foley, M Thomas, SS Moskowitz, MA Waeber, C TI S1P(3) receptors mediate the potent constriction of cerebral arteries by sphingosine-1-phosphate SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE sphingosine-1-phosphate; SIP receptor; cerebral vessel; vasoconstriction; suramin ID PROTEIN-COUPLED RECEPTOR; CELL-SURFACE RECEPTOR; SPHINGOSINE 1-PHOSPHATE; LYSOPHOSPHATIDIC ACID; SIGNAL-TRANSDUCTION; NEURITE RETRACTION; ENDOTHELIAL-CELLS; IN-VITRO; PLATELETS; EDG-1 AB We characterized the effect of Sphingosine-1-phosphate (SIP) on vascular tone. SIP selectively constricted isolated cerebral, but not peripheral arteries, despite ubiquitous expression of S1P(1), S1P(2), S1P(3) and S1P(5) receptor mRNA. Clostridium B and C3 toxins and the rhokinase inhibitor Y27632 (trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexane carboxamide) reduced this vasoconstriction to S1P, indicating that the response was mediated through Rho. Pertussis toxin displayed only weak inhibition, suggesting minor involvement of G(i/o) protein. The S1P effect was specifically reduced by adenovirus bearing a slp(3) but not slp(2), antisense construct. Furthermore, suramin, which selectively blocks S1P(3) receptors, inhibited the vasoconstrictor effect of S1P, indicating that S1P(3) receptors account for at least part of S1P-mediated vasoconstriction in cerebral arteries. In vivo, intracarotid injection of S1P decreased cerebral blood flow, an effect prevented by suramin treatment. Because SIP constricts cerebral blood vessels and is released from platelets during clotting, the S1P/S1P3 System constitutes a novel potential target for cerebrovascular disease therapy. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Catania Univ, Sch Med, Dept Pharmacol, Catania, Italy. RP Waeber, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol, Stroke & Neurovasc Regulat Lab, CNY 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009; OI Waeber, Christian/0000-0001-6078-0027; Salomone, Salvatore/0000-0001-5307-6103 FU NINDS NIH HHS [NS043216, NS10828, NS35611] NR 41 TC 81 Z9 82 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAY 23 PY 2003 VL 469 IS 1-3 BP 125 EP 134 DI 10.1016/S0014-2999(03)017131-X PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 688HD UT WOS:000183427400016 PM 12782194 ER PT J AU Rauch, SL Shin, LM Segal, E Pitman, RK Carson, MA McMullin, K Whalen, PJ Makriss, N AF Rauch, SL Shin, LM Segal, E Pitman, RK Carson, MA McMullin, K Whalen, PJ Makriss, N TI Selectively reduced regional cortical volumes in post-traumatic stress disorder SO NEUROREPORT LA English DT Article DE anterior cingulate cortex; anxiety disorders; cortical parcellation; magnetic resonance imaging; orbitofrontal cortex ID CHILDHOOD SEXUAL ABUSE; ANTERIOR CINGULATE; COUNTING STROOP; MOOD DISORDERS; FUNCTIONAL MRI; HUMAN BRAIN; PTSD; CORTEX; VETERANS; NEURONS AB Different subterritories of anterior cingulate cortex (ACC) and adjacent ventromedial frontal cortex have been shown to serve distinct functions. This scheme has influenced contemporary pathophysiologic models of psychiatric disorders. Prevailing neurocircuitry models of post-traumatic stress disorder (PTSD) implicate dysfunction within pregenual ACC and subcallosal cortex (SC), as well as amygdala and hippocampus. In the current study, cortical parcellation of magnetic resonance imaging data was per-formed to test for volumetric differences in pregenual ACC and SC, between women with PTSD and trauma-exposed women without PTSD. The PTSD group exhibited selectively decreased pregenual ACC and SC volumes. These results are consistent with contemporary schemes regarding functional and structural dissection of frontal cortex, and suggest specific regional cortical pathology in PTSD. C1 Massachusetts Gen Hosp, Psychiat Neuroimaging Res Grp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. St Anselm Coll, Manchester, NH 03102 USA. VA Res Serv, Manchester, NH 03102 USA. Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Rauch, SL (reprint author), Massachusetts Gen Hosp, Psychiat Neuroimaging Res Grp, Dept Psychiat, 13th St,Bldg 149,CNY-9, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH-60219] NR 25 TC 179 Z9 188 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 23 PY 2003 VL 14 IS 7 BP 913 EP 916 DI 10.1097/01.wnr.0000071767.24455.10 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 699LE UT WOS:000184057700002 PM 12802174 ER PT J AU Masland, RH AF Masland, RH TI Vision: The retina's fancy tricks SO NATURE LA English DT Editorial Material ID AMACRINE CELLS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Masland, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. NR 9 TC 4 Z9 4 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 22 PY 2003 VL 423 IS 6938 BP 387 EP 388 DI 10.1038/423387a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 681AJ UT WOS:000183012000021 PM 12761527 ER PT J AU Samaha, FF Iqbal, N Seshadri, P Chicano, KL Daily, DA McGrory, J Williams, T Williams, M Gracely, EJ Stern, L AF Samaha, FF Iqbal, N Seshadri, P Chicano, KL Daily, DA McGrory, J Williams, T Williams, M Gracely, EJ Stern, L TI A low-carbohydrate as compared with a low-fat diet in severe obesity SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INSULIN-RESISTANCE ATHEROSCLEROSIS; DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY HEART-DISEASE; HYPERTRIGLYCERIDEMIA AB Background: The effects of a carbohydrate-restricted diet on weight loss and risk factors for atherosclerosis have been incompletely assessed. METHODS: We randomly assigned 132 severely obese subjects (including 77 blacks and 23 women) with a mean body-mass index of 43 and a high prevalence of diabetes (39 percent) or the metabolic syndrome (43 percent) to a carbohydrate-restricted (low-carbohydrate) diet or a calorie- and fat-restricted (low-fat) diet. RESULTS: Seventy-nine subjects completed the six-month study. An analysis including all subjects, with the last observation carried forward for those who dropped out, showed that subjects on the low-carbohydrate diet lost more weight than those on the low-fat diet (mean [+/-SD], -5.8+/-8.6 kg vs. -1.9+/-4.2 kg; P=0.002) and had greater decreases in triglyceride levels (mean, -20+/-43 percent vs. -4+/-31 percent; P=0.001), irrespective of the use or nonuse of hypoglycemic or lipid-lowering medications. Insulin sensitivity, measured only in subjects without diabetes, also improved more among subjects on the low-carbohydrate diet (6+/-9 percent vs. -3+/-8 percent, P=0.01). The amount of weight lost (P<0.001) and assignment to the low-carbohydrate diet (P=0.01) were independent predictors of improvement in triglyceride levels and insulin sensitivity. CONCLUSIONS: Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydrate-restricted diet than on a calorie- and fat-restricted diet, with a relative improvement in insulin sensitivity and triglyceride levels, even after adjustment for the amount of weight lost. This finding should be interpreted with caution, given the small magnitude of overall and between-group differences in weight loss in these markedly obese subjects and the short duration of the study. Future studies evaluating long-term cardiovascular outcomes are needed before a carbohydrate-restricted diet can be endorsed. C1 Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Med Ctr, Dept Med, Div Cardiol, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Dept Med, Div Endocrinol, Philadelphia, PA 19104 USA. Drexel Univ, Coll Med, Dept Family Community & Prevent Med, Philadelphia, PA 19104 USA. RP Samaha, FF (reprint author), Cardiol 8th Fl,MC 111C,Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 21 TC 612 Z9 631 U1 12 U2 84 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 MAY 22 PY 2003 VL 348 IS 21 BP 2074 EP 2081 DI 10.1056/NEJMoa022637 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 680YU UT WOS:000183008300004 PM 12761364 ER PT J AU Campagna, JA Miller, KW Forman, SA AF Campagna, JA Miller, KW Forman, SA TI Drug therapy: Mechanisms of actions of inhaled anesthetics SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID ACID TYPE-A; NICOTINIC ACETYLCHOLINE-RECEPTORS; INHIBITORY SYNAPTIC TRANSMISSION; MEDULLARY EXPIRATORY NEURONS; MEYER-OVERTON HYPOTHESIS; RAT HIPPOCAMPAL-NEURONS; CENTRAL-NERVOUS-SYSTEM; DECEREBRATE DOG-MODEL; GATED ION CHANNELS; IN-VITRO NETWORKS C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, CLN-3,10 Fruit St, Boston, MA 02114 USA. NR 136 TC 388 Z9 419 U1 3 U2 30 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 MAY 22 PY 2003 VL 348 IS 21 BP 2110 EP 2124 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 680YU UT WOS:000183008300009 PM 12761368 ER PT J AU Friedlander, RM Gonzalez, RG Harris, NL Medlock, MD Pfannl, R Beigel, JH Afridi, NA AF Friedlander, RM Gonzalez, RG Harris, NL Medlock, MD Pfannl, R Beigel, JH Afridi, NA TI A 58-year-old woman with left-sided weakness and a right frontal brain mass - Brain abscess due to infection with Streptococcus milleri and Haemophilus aphrophilus. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DIFFERENTIAL-DIAGNOSIS; TUMORS C1 Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Friedlander, RM (reprint author), Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA. RI Friedlander, Robert/A-2845-2016 OI Friedlander, Robert/0000-0003-4423-9219 NR 17 TC 18 Z9 18 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 MAY 22 PY 2003 VL 348 IS 21 BP 2125 EP 2132 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 680YU UT WOS:000183008300010 PM 12761369 ER PT J AU Saxon, AJ AF Saxon, AJ TI Transporting efficacious treatments from academia to community: barriers and opportunities SO DRUG AND ALCOHOL DEPENDENCE LA English DT Editorial Material DE treatments; barriers; opportunities ID VOUCHER-BASED REINFORCEMENT; SUBSTANCE USE DISORDERS; DEPENDENCE; ABSTINENCE; THERAPIES; ADDICTION; OUTCOMES; ALCOHOL; ABUSE C1 Univ Washington, VA Puget Sound Hlth Care Syst, Ctr Excellence Substance Abuse Treatment & Educ, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. RP Saxon, AJ (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Ctr Excellence Substance Abuse Treatment & Educ, Dept Psychiat & Behav Sci, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 13 TC 2 Z9 2 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 MAY 21 PY 2003 VL 70 IS 2 BP 127 EP 129 DI 10.1016/S0376-8716(03)00034-6 PG 3 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 686XM UT WOS:000183346300002 PM 12732404 ER PT J AU Gokce, N Keaney, JF Hunter, LM Watkins, MT Nedeljkovic, ZS Menzoian, JO Vita, JA AF Gokce, N Keaney, JF Hunter, LM Watkins, MT Nedeljkovic, ZS Menzoian, JO Vita, JA TI Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; FLOW-MEDIATED VASODILATION; VASOMOTOR DYSFUNCTION; PROGNOSTIC VALUE; BRACHIAL-ARTERY; HEART-DISEASE; RISK AB OBJECTIVES The goal of this study was to prospectively examine the long-term predictive value of brachial-artery endothelial dysfunction for future cardiovascular events. BACKGROUND Brachial-artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors. The prospective relation between endothelial function determined by brachial-artery ultrasound and long-term cardiovascular risk is unknown. METHODS We examined brachial-artery endothelial function using ultrasound in 199 patients with peripheral arterial disease before elective vascular surgery. Patients were prospectively followed with an average follow-up of 1.2 years after surgery. RESULTS Thirty-five patients had an event during follow-up, including cardiac death (5 patients), myocardial infarction (17 patients), unstable angina (10 patients), or stroke (3 patients). Preoperative endothelium-dependent flow-mediated dilation (FMD) was significantly lower in patients with an event (4.4 +/- 2.8%) compared with those without an event (7.0 +/- 4.9%, p < 0.001), whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups. In a Cox proportional-hazards model, independent predictors of events included age (p = 0.003), more invasive surgery (surgery other than carotid endarterectomy, p = 0.02), and impaired brachial-artery endothelial function (p = 0.002). Risk was approximately nine-fold higher in patients with FMD <8.1% (lower two tertiles) compared with those in the upper tertile (odds ratio 9.5; 95% confidence interval 2.3 to 40). CONCLUSIONS Impaired brachial-artery endothelial function independently predicts long-term cardiovascular events in patients with peripheral arterial disease. The findings suggest that noninvasive assessment of endothelial function using brachial-artery FMD may serve as a surrogate end point for cardiovascular risk. (C) 2003 by the American College of Cardiology Foundation. C1 Boston Univ, Med Ctr, Cardiol Sect, Sch Med,Evans Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Surg, Surg Serv, Boston, MA 02114 USA. RP Vita, JA (reprint author), Boston Univ, Med Ctr, Cardiol Sect, Sch Med,Evans Dept Med, 88 E Newton St, Boston, MA 02118 USA. OI Vita, Joseph/0000-0001-5607-1797 FU NHLBI NIH HHS [HL 48152, HL 52936, HL 55993, HL 60886, K23 HL 04425] NR 21 TC 471 Z9 478 U1 1 U2 15 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 MAY 21 PY 2003 VL 41 IS 10 BP 1769 EP 1775 DI 10.1016/S0735-1097(03)00333-4 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 680DK UT WOS:000182960900020 PM 12767663 ER PT J AU Hodgson, DC Zhang, W Zaslavsky, AM Fuchs, CS Wright, WE Ayanian, JZ AF Hodgson, DC Zhang, W Zaslavsky, AM Fuchs, CS Wright, WE Ayanian, JZ TI Relation of hospital volume to colostomy rates and survival for patients with rectal cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TOTAL MESORECTAL EXCISION; QUALITY-OF-LIFE; POSTOPERATIVE ADJUVANT CHEMOTHERAPY; COLORECTAL-CANCER; HEALTH-CARE; BREAST-CANCER; SURGERY; RESECTION; OUTCOMES; MORTALITY AB Background: Postoperative mortality after some types of cancer surgery is inversely related to the number of operations performed at a hospital (i.e., hospital volume). This study assessed the association of hospital volume with colostomy rates and survival for patients with rectal cancer in a large representative cohort identified from the California Cancer Registry. Methods: We identified 7257 patients diagnosed from January 1, 1994, through December 31, 1997, with stage I-III rectal cancer who underwent surgical resection. Registry data were linked to hospital discharge abstracts and ZIP-code-level data from the 1990 U.S. Census. Associations of hospital volume with permanent colostomy and 30-day mortality were assessed with the Mantel-Haenszel trend test and logistic regression. Overall survival was examined with the Kaplan-Meier method and a multivariable Cox proportional hazards model. Multivariable analyses adjusted for demographic and clinical variables and patient clustering within hospitals. All tests of statistical significance were two-sided. Results: In unadjusted analyses across decreasing quartiles of hospital volume, we observed statistically significant increases in colostomy rates (29.5%, 31.8%, 35.2%, and 36.6%; P<.001) and in 30-day postoperative mortality (1.6%, 1.6%, 2.9%, and 4.8%; P<.001) and a decrease in 2-year survival (83.7%, 83.2%, 80.9%, and 76.6%; P<.001). The adjusted risks of permanent colostomy (odds ratio [OR] = 1.37, 95% confidence interval [CI] = 1.10 to 1.70), 30-day mortality (OR = 2.64, 95% CI = 1.41 to 4.93), and 2-year mortality (hazard ratio = 1.28, 95% CI = 1.15 to 1.44) were greater for patients at hospitals in the lowest volume quartile than for patients at hospitals in the highest volume quartile. Stratification by tumor stage and comorbidity index did not appreciably affect the results. Adjusted colostomy rates varied statistically significantly (P<.001) among individual hospitals independent of volume. Conclusions: Rectal cancer patients who underwent surgery at high-volume hospitals were less likely to have a permanent colostomy and had better survival rates than those treated in low-volume hospitals. Identifying processes of care that contribute to these differences may improve patients' outcomes in all hospitals. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Gen Med, Boston, MA 02115 USA. Calif Dept Hlth Serv, Canc Surveillance Sect, Sacramento, CA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Univ Toronto, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada. Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M4X 1K9, Canada. RP Ayanian, JZ (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. FU AHRQ HHS [R01HS09869] NR 52 TC 137 Z9 141 U1 0 U2 6 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 MAY 21 PY 2003 VL 95 IS 10 BP 708 EP 716 PG 9 WC Oncology SC Oncology GA 681MT UT WOS:000183040500007 PM 12759388 ER PT J AU Trofimov, A Bortfeld, T AF Trofimov, A Bortfeld, T TI Beam delivery sequencing for intensity modulated proton therapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RADIOTHERAPY AB Methods of beam fluence sequencing for intensity modulated proton therapy (IMPT) using the beam scanning technique are presented. Proton beam weight maps optimized by the treatment planning system (TPS) for a discrete set of regularly spaced narrow pencil beams were interpolated, using convolution with various kernel functions, to simulate continuous beam scanning on a raster pattern. Expected dose distributions at the proton Bragg peak range were then calculated and compared to those planned by the TPS, to evaluate the discrepancy due to the differences between the treatment planning and delivery approaches. An iteratively optimized adjustment was applied to the simulated continuous beam fluence profiles to reduce such discrepancy. Calculation showed that by accounting for the specifics of the scanning method, the planned dose distribution on the target may be reproduced to within 0.5% of the maximum target dose, given the pencil beam spacing smaller or equal to the beam Q is used for treatment planning. For the beam weight maps generated using a spot spacing larger than Q, a substantial reduction in the calculated dose discrepancy may be attained by applying an iterative adjustment of fluence profiles obtained by interpolating over artificially expanded set of beam spots. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. RP Trofimov, A (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. FU NCI NIH HHS [CA21239] NR 12 TC 6 Z9 6 U1 0 U2 2 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 MAY 21 PY 2003 VL 48 IS 10 BP 1321 EP 1331 AR PII S0031-9155(03)53462-5 DI 10.1088/0031-9155/48/10/306 PG 11 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 693AF UT WOS:000183691900006 PM 12812449 ER PT J AU Siegel, AM Culver, JP Mandeville, JB Boas, DA AF Siegel, AM Culver, JP Mandeville, JB Boas, DA TI Temporal comparison of functional brain imaging with diffuse optical tomography and fMRI during rat forepaw stimulation SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID CEREBRAL BLOOD-FLOW; NEAR-INFRARED SPECTROSCOPY; SOMATOSENSORY STIMULATION; OXYGENATION; BOLD; MRI; ACTIVATION; HEMODYNAMICS; REFLECTANCE; HEMOGLOBIN AB The time courses of oxyhaemoglobin ([HbO(2)]), deoxyhaemoglobin ([HbR]) and total haemoglobin ([HbT]) concentration changes following cortical activation in rats by electrical forepaw stimulation were measured using diffuse optical tomography (DOT) and compared to similar measurements performed previously with fMRI at 2.0 T and 4.7 T. We also explored the qualitative effects of varying stimulus parameters on the temporal evolution of the hemodynamic response. DOT images were reconstructed at a depth of 1.5 mm over a 1 cm square area from 2 mm anterior to bregma to 8 mm posterior to bregma. The measurement set included 9 sources and 16 detectors with an imaging frame rate of 10 Hz. Both DOT [HbR] and [HbO(2)] time courses were compared to the fMRI BOLD time course during stimulation, and the DOT [HbT] time course was compared to the fMRI cerebral plasma volume (CPV) time course. We believe that DOT and fMRI can provide similar temporal information for both blood volume and deoxyhaemoglobin changes, which helps to cross-validate these two techniques and to demonstrate that DOT can be useful as a complementary modality to fMRI for investigating the hemodynamic response to neuronal activity. C1 Tufts Univ, Ctr Bioengn, Medford, MA 02155 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. RP Siegel, AM (reprint author), Tufts Univ, Ctr Bioengn, Medford, MA 02155 USA. FU NCRR NIH HHS [P41-RR14075]; NINDS NIH HHS [K25-NS44339, R29-NS38842] NR 43 TC 81 Z9 81 U1 0 U2 2 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 MAY 21 PY 2003 VL 48 IS 10 BP 1391 EP 1403 AR PII S0031-9155(03)57976-3 DI 10.1088/0031-9155/48/10/311 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 693AF UT WOS:000183691900011 PM 12812454 ER PT J AU Spiegel, BMR Targownik, L Dulai, GS Gralnek, IM AF Spiegel, BMR Targownik, L Dulai, GS Gralnek, IM TI The cost-effectiveness of cyclooxygenase-2 selective inhibitors in the management of chronic arthritis SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; HELICOBACTER-PYLORI INFECTION; RANDOMIZED CONTROLLED TRIAL; PEPTIC-ULCER DISEASE; RHEUMATOID-ARTHRITIS; UNITED-STATES; DOUBLE-BLIND; GASTROINTESTINAL ENDOSCOPY; MYOCARDIAL-INFARCTION; UNINVESTIGATED DYSPEPSIA AB Background: Rofecoxib and celecoxib (coxibs) effectively treat chronic arthritis pain and reduce ulcer complications by 50% compared with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). However, their absolute risk reduction is small and the cost-effectiveness of treatment is uncertain. Objective: To determine whether the degree of risk reduction in gastrointestinal complications by coxibs offsets their increased cost compared with a generic nonselective NSAID. Design: Cost-utility analysis. Data Sources: Systematic review of MEDLINE and published abstracts. Target Population: Patients with osteoarthritis or rheumatoid arthritis who are not taking aspirin and who require long-term NSAID therapy for moderate to severe arthritis pain. Perspective: Third-party payer. Interventions: Naproxen, 500 mg twice daily, and coxib, once daily. Patients intolerant of naproxen were switched to a coxib. Outcome Measures: Incremental cost per quality-adjusted life-year (QALY) gained. Results of Base-Case Analysis: Using a coxib instead of a nonselective NSAID in average-risk patients cost an incremental $275 809 per year to gain 1 additional QALY. Results of Sensitivity Analysis: The incremental cost per QALY gained decreased to $55 803 when the analysis was limited to the subset of patients with a history of bleeding ulcers. The coxib strategy became dominant when the cost of coxibs was reduced by 90% of the current average wholesale price. In probabilistic sensitivity analysis, if a third-party payer was willing to pay $150 000 per QALY gained, then 4.3% of average-risk patients would fall within the budget. Conclusions: The risk reduction seen with coxibs does not offset their increased costs compared with nonselective NSAIDs in the management of average-risk patients with chronic arthritis. However, coxibs may provide an acceptable incremental cost-effectiveness ratio in the subgroup of patients with a history of bleeding ulcers. C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr,David Geffen Sch Med, Ctr Study Digest Healthcare Qual & Outcomes, Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Gralnek, IM (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr,David Geffen Sch Med, Ctr Study Digest Healthcare Qual & Outcomes, Vet Adm Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 115,Room 215B, Los Angeles, CA 90073 USA. FU NCRR NIH HHS [K23 RR-16188]; NIDDK NIH HHS [DK-07180] NR 90 TC 81 Z9 81 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 MAY 20 PY 2003 VL 138 IS 10 BP 795 EP 806 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 679KH UT WOS:000182920700003 PM 12755551 ER PT J AU Ahmed, S Pilote, L King, ME Sijbom, M de Moor, M Liberthson, R Child, JS Foster, E Graham, T Hopkins, W Landzberg, M Rouah, F Marelli, AJ AF Ahmed, S Pilote, L King, ME Sijbom, M de Moor, M Liberthson, R Child, JS Foster, E Graham, T Hopkins, W Landzberg, M Rouah, F Marelli, AJ TI Gender differences and adult congenital heart disease: A population profile from the International Society for Adult Congenital Cardiac Disease SO CIRCULATION LA English DT Meeting Abstract CT Asia Pacific Scientific Forum on New Discoveries in Cardiovascular Disease and Stroke CY JUN 08-10, 2003 CL HONOLULU, HAWAII SP World Heart Federat, Asian Pacific Soc Cardiol, Hong Kong Coll Cardiol, Japanese Circulat Soc, Chinese Soc Cardiol, Korean Soc Circulat, Japan Heart Fdn, Natl Heart, Lung, & Blood Inst C1 McGill Univ, Ctr Hlth, Montreal, PQ, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif San Francisco, Sch Med, San Francisco, CA USA. Vanderbilt Univ, Nashville, TN USA. Univ Vermont, Burlington, VT USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 20 PY 2003 VL 107 IS 19 MA P68 BP E157 EP E158 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 681AU UT WOS:000183014500160 ER PT J AU Corvera-Tindel, T Doering, LV Machuca, K Dracup, K AF Corvera-Tindel, T Doering, LV Machuca, K Dracup, K TI Combined effects of physical training and beta blocker use on functional performance and depression in heart failure SO CIRCULATION LA English DT Meeting Abstract CT Asia Pacific Scientific Forum on New Discoveries in Cardiovascular Disease and Stroke CY JUN 08-10, 2003 CL HONOLULU, HAWAII SP World Heart Federat, Asian Pacific Soc Cardiol, Hong Kong Coll Cardiol, Japanese Circulat Soc, Chinese Soc Cardiol, Korean Soc Circulat, Japan Heart Fdn, Natl Heart, Lung, & Blood Inst C1 VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 20 PY 2003 VL 107 IS 19 MA P169 BP E174 EP E174 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 681AU UT WOS:000183014500249 ER PT J AU Wang, ZJ Corey, E Hass, GM Higano, CS True, LD Wallace, D Tisdale, MJ Vessella, RL AF Wang, ZJ Corey, E Hass, GM Higano, CS True, LD Wallace, D Tisdale, MJ Vessella, RL TI Expression of the human cachexia-associated protein (HCAP) in prostate cancer and in a prostate cancer animal model of cachexia SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE human cachexia-associated factor; cachexia; prostate cancer (CaP); metastasis ID PROTEOLYSIS-INDUCING FACTOR; LIPID-MOBILIZING FACTOR; CACHECTIC FACTOR; IN-VITRO; MICE; ANOREXIA; MANAGEMENT; MYOBLASTS; TUMORS; VIVO AB Prostate cancer (CaP) patients with disseminated disease often suffer from severe cachexia, which contributes to mortality in advanced cancer. Human cachexia-associated protein (HCAP) was recently identified from a breast cancer library based on the available 20-amino acid sequence of proteolysis-inducing factor (PIF), which is a highly active cachectic factor isolated from mouse colon adenocarcinoma MAC16. Herein, we investigated the expression of HCAP in Cap and its potential involvement in CaP-associated cachexia. HCAP mRNA was detected in CaP cell lines, in primary CaP tissues and in its osseous metastases. In situ hybridization showed HCAP mRNA to be localized only in the epithelial cells in Cap tissues, in the metastatic foci in bone, liver and lymph node, but not in the stromal cells or in normal prostate tissues. HCAP protein was detected in 9 of 14 Cap metastases but not in normal prostate tissues from cadaveric donors or patients with organ-confined tumors. Our Western blot analysis revealed that HCAP was present in 9 of 19 urine specimens from cachectic CaP patients but not in 19 urine samples of noncachectic patients. HCAP mRNA and protein were also detected in LuCaP 35 and PC-3M xenografts from our cachectic animal models. Our results demonstrated that human CaP cells express HCAP and the expression of HCAP is associated with the progression of CaP and the development of CaP cachexia. (C) 2003 Wiley-Liss, Inc. C1 Univ Washington, Dept Urol, GU Canc Res Lab, Seattle, WA 98195 USA. Matritech, Newton, MA USA. Univ Washington, Dept Med, Div Oncol, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Aston Univ, Inst Pharmaceut Sci, Birmingham B4 7ET, W Midlands, England. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Vessella, RL (reprint author), Univ Washington, Dept Urol, GU Canc Res Lab, Mail Stop 356510, Seattle, WA 98195 USA. NR 36 TC 31 Z9 31 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 20 PY 2003 VL 105 IS 1 BP 123 EP 129 DI 10.1002/ijc.11035 PG 7 WC Oncology SC Oncology GA 666EC UT WOS:000182163000021 PM 12672042 ER PT J AU Iwasaki-Arai, J Iwasaki, H Miyamoto, T Watanabe, S Akashi, K AF Iwasaki-Arai, J Iwasaki, H Miyamoto, T Watanabe, S Akashi, K TI Enforced granulocyte/macrophage colony-stimulating factor signals do not support lymphopoiesis, but instruct lymphoid to myelomonocytic lineage conversion SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE commitment; lineage conversion; cytokine; plasticity ID HEMATOPOIETIC STEM-CELLS; RECEPTOR-TRANSGENIC MICE; ACUTE MYELOGENOUS LEUKEMIA; COMMON MYELOID PROGENITOR; RESCUES T-LYMPHOPOIESIS; G-CSF RECEPTOR; DEFICIENT MICE; GAMMA-CHAIN; B-CELL; ERYTHROPOIETIN RECEPTOR AB We evaluated the effects of ectopic granulocyte/macrophage colony-stimulating factor (GM-CSF) signals on hematopoietic commitment and differentiation. Lineage-restricted progenitors purified from mice with the ubiquitous transgenic human GM-CSF receptor (hGM-CSFR) were used for the analysis. In cultures with hGM-CSF alone, hGM-CSFR-expressing (hGM-CSFR+) granulocyte/monocyte progenitors (GMPs) and megakaryocyte/erythrocyte progenitors (MEPs) exclusively gave rise to granulocyte/monocyte (GM) and megakaryocyte/erythroid (MegE) colonies, respectively, providing formal proof that GM-CSF signals support the GM and MegE lineage differentiation without affecting the physiological myeloid fate. hGM-CSFR transgenic mice were crossed with mice deficient in interleukin (IL)-7, an essential cytokine for T and B cell development. Administration of hGM-CSF in these mice could not restore T or B lymphopoiesis, indicating that enforced GM-CSF signals cannot substitute for IL-7 to promote lymphopoiesis. Strikingly, > 50% hGM-CSFR+ common lymphoid progenitors (CLPs) and > 20% hGM-CSFR+ pro-T cells gave rise to granulocyte, monocyte, and/or myeloid dendritic cells, but not MegE lineage cells in the presence of hGM-CSF. Injection of hGM-CSF into mice transplanted with hGM-CSFR+ CLPs blocked their lymphoid differentiation, but induced development of GM cells in vivo. Thus, hGM-CSF transduces permissive signals for myeloerythroid differentiation, whereas it transmits potent instructive signals for the GM differentiation to CLPs and early T cell progenitors. These data suggest that a majority of CLPs and a fraction of pro-T cells possess plasticity for myelomonocytic differentiation that can be activated by ectopic GM-CSF signals, supporting the hypothesis that the down-regulation of GM-CSFR is a critical event in producing cells with a lymphoid-restricted lineage potential. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Kyushu Univ, Grad Sch Med Sci, Dept Med & Biosyst Sci, Fukuoka 8120054, Japan. Univ Tokyo, Inst Med Sci, Dept Mol & Dev Biol, Tokyo 1088639, Japan. RP Akashi, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIDDK NIH HHS [2P01DK050654, P01 DK050654] NR 63 TC 74 Z9 77 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 19 PY 2003 VL 197 IS 10 BP 1311 EP 1322 DI 10.1084/jem.20021843 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 682KF UT WOS:000183090200010 PM 12756267 ER PT J AU Widlund, HR Fisher, DE AF Widlund, HR Fisher, DE TI Microphthalamia-associated transcription factor: a critical regulator of pigment cell development and survival SO ONCOGENE LA English DT Article DE MITF; melanoma; development; melanocyte; survival ID WAARDENBURG SYNDROME TYPE-2; CREST-DERIVED MELANOCYTES; WNT SIGNALING PATHWAY; NEURAL-CREST; TYROSINASE GENE; BETA-CATENIN; MITF GENE; HIRSCHSPRUNG-DISEASE; MALIGNANT-MELANOMA; POLYCYSTIC KIDNEY AB The microphthalamia-associated transcription factor (MITF) is an integral transcriptional regulator in melanocyte, the lineage from which melanoma cells originate. This basic-helix-loop-helix-leucine-zipper (bHLHzip) protein is critical for melanocyte cell-fate choice during commitment from pluripotent precursor cells in the neural crest. Its role in differentiation pathways has been highlighted by its potent transcriptional and lineage-specific regulation of the three major pigment enzymes: tyrosinase, Tyrp1, and Dell as well as other pigmentation factors. However, the cellular functions of MITF seem to be wider than differentiation and celt-fate pathways alone, since melanocytes and melanoma cells appear to require an expression of this factor. Here, we discuss the transcriptional networks in which MITF is thought to reside and describe signaling pathways in the cell which impinge on MITF. Accumulating evidence supports the notion that MITF is involved in survival pathways during normal development as well as during neoplastic growth of melanoma. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NIAMS NIH HHS [AR43369] NR 88 TC 203 Z9 210 U1 4 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 19 PY 2003 VL 22 IS 20 BP 3035 EP 3041 DI 10.1038/sj.onc.1206443 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 682MV UT WOS:000183096600003 PM 12789278 ER PT J AU Sharpless, NE Chin, L AF Sharpless, NE Chin, L TI The INK4a/ARF locus and melanoma SO ONCOGENE LA English DT Article DE p19(ARF); cell cycle; cdk4; cdk6; ultraviolet light ID TUMOR-SUPPRESSOR GENE; CELL-CYCLE PROGRESSION; C-MYC; ULTRAVIOLET-RADIATION; HUMAN SKIN; P53-DEPENDENT APOPTOSIS; MALIGNANT-MELANOMA; SPORADIC MELANOMA; FAMILIAL MELANOMA; G(1) ARREST AB Inactivation of the INK4a/ARF (or CDKN2a) locus is a common and critical genetic event in the development of human and mouse melanoma. This locus engages the Rb and p53 tumor suppressor pathways through its capacity to encode two distinct gene products, p16(INK4a) and p14(ARF). This review highlights the body of evidence supporting a role for both p16(INK4a) and p14(ARF) in the suppression of melanoma, and speculates as to why this locus is preferentially targeted in this tumor type. In addition, the potential importance of these two pathways in mediating UV-induced melanoma genesis will be addressed via genetic and molecular evidence in the mouse. C1 Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Chin, L (reprint author), Harvard Univ, Sch Med, Dept Dermatol, 44 Binney St M413, Boston, MA 02115 USA. NR 76 TC 19 Z9 21 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 19 PY 2003 VL 22 IS 20 BP 3092 EP 3098 DI 10.1038/sj.onc.1206461 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 682MV UT WOS:000183096600011 ER PT J AU Wu, H Goel, V Haluska, FG AF Wu, H Goel, V Haluska, FG TI PTEN signaling pathways in melanoma SO ONCOGENE LA English DT Article DE PTEN; melanoma; signaling ID CELL-CYCLE ARREST; TUMOR-SUPPRESSOR GENE; PRIMARY CUTANEOUS MELANOMA; ENDOMETRIAL CANCER-CELLS; MALIGNANT-MELANOMA; PTEN/MMAC1 GENE; PROSTATE-CANCER; PHOSPHATASE-ACTIVITY; COWDEN-DISEASE; ALLELIC LOSS AB Phosphatase and tensin homolog deleted in from chromosome ten (PTEN), initially also known as mutated in multiple advanced cancers or TGF-beta-regulated and epithelia cell-enriched phosphatase, is a tumor suppressor gene that is mutated in a large fraction of human melanomas. A broad variety of human cancers carry PTEN alterations, including glioblastomas, endometrial, breast, thyroid and prostate cancers. The PTEN protein has at least two biochemical functions: it has both lipid phosphatase and protein phosphatase activity. The lipid phosphatase activity of PTEN decreases intracellutar PtdIns(3,4,5)P-3 level and downstream Akt activity. Cell-cycle progression is arrested at G1/S, mediated at least partially through the upregutation of the cyclin-dependent kinase inhibitor p27. In addition, agonist-induced apoptosis is mediated by PTEN, through the upregulation of proapoptotic machinery involving caspases and BID, and the downregulation of antiapoptotic proteins such as Bcl2. The protein phosphatase activity of PTEN is apparently less central to its involvement in tumorigenesis. It is involved in the inhibition of focal adhesion formation, cell spreading and migration, as well as the inhibition of growth factor-stimulated MAPK signaling. Therefore, the combined effects of the loss of PTEN lipid and protein phosphatase activity may result in aberrant cell growth and escape from apoptosis, as well as abnormal cell spreading and migration. In melanoma, PTEN loss has been mostly observed as a late event, although a dose-dependent loss of PTEN protein and function has been implicated in early stages of tumorigenesis as well. In addition, loss of PTEN and oncogenic activation of RAS seem to occur in a reciprocal fashion, both of which could cooperate with CDKN2A loss in contribution to melanoma tumorigenesis. C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Haluska, FG (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, GRJ1021,55 Fruit St, Boston, MA 02114 USA. NR 85 TC 213 Z9 231 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 19 PY 2003 VL 22 IS 20 BP 3113 EP 3122 DI 10.1038/sj.onc.1206451 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 682MV UT WOS:000183096600013 PM 12789288 ER PT J AU Streit, M Detmar, M AF Streit, M Detmar, M TI Angiogenesis, lymphangiogenesis, and melanoma metastasis SO ONCOGENE LA English DT Review DE VEGF; FGF; LYVE-1; VEGF-C ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; HUMAN-MALIGNANT MELANOMA; ANTIANGIOGENIC GENE-THERAPY; PRIMARY CUTANEOUS MELANOMA; BREAST-CANCER METASTASIS; CC-CHEMOKINE RECEPTOR-7; INCREASES TUMOR-GROWTH; LYMPH-NODE METASTASIS; IN-SITU HYBRIDIZATION AB The induction of angiogenesis is a critical point in the development of most human tumors - including melanomas. Some of the earliest studies in the field of tumor angiogenesis showed that transplantation of human melanoma fragments into the hamster cheek pouch stimulated blood vessel growth. Since then, numerous studies have demonstrated that human melanomas also induce angiogenesis. The prognostic importance of the degree of melanoma vascularization, however, has remained controversial. Elevated expression of several angiogenic factors, including vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8, has been detected in primary cutaneous melanomas, and the importance of these mediators in promoting melanoma angiogenesis and metastasis has been confirmed in tumor xenotransplant models. Based upon these findings, several clinical trials of angiogenesis inhibitors have been initiated in human melanoma patients and are currently underway. Recent experimental evidence indicates that tumor-associated lymphangiogenesis also plays an important role in mediating tumor spread to regional lymph nodes. These observations have important implications for prognosis and treatment of human melanomas. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Dermatol, Charlestown, MA 02129 USA. Berlex Biosci, Richmond, CA 94804 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69184, CA86410, CA91861] NR 110 TC 137 Z9 144 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 19 PY 2003 VL 22 IS 20 BP 3172 EP 3179 DI 10.1038/sj.onc.1206457 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 682MV UT WOS:000183096600019 PM 12789293 ER PT J AU Dranoff, G AF Dranoff, G TI GM-CSF-secreting melanoma vaccines SO ONCOGENE LA English DT Article DE GM-CSF; melanoma; cancer vaccine; tumor antigen ID COLONY-STIMULATING FACTOR; T-CELL RESPONSES; TUMOR-INFILTRATING LYMPHOCYTES; MHC CLASS-I; DENDRITIC CELLS; ANTITUMOR IMMUNITY; ANTIGEN-4 CTLA-4; CANCER ANTIGENS; BONE-MARROW; NKT CELLS AB The development of biochemical and genetic schemes to characterize cancer antigens led to the recognition that malignant melanoma frequently evokes a host response. While the generation of brisk T-cell infiltrates in early stage disease is correlated with prolonged survival, host reactions in most cases are insufficient to impede tumor progression. One variable that may limit the potency of the host response against nascent melanoma is the mixture of cytokines present in the tumor microenvironment. In a murine melanoma model, we identified granulocyte-macrophage colony stimulating factor (GM-CSF) as the most potent molecule for augmenting tumor immunity following gene transfer into melanoma cells. Vaccination with irradiated melanoma cells engineered to secrete GMCSF enhances host responses through improved tumor antigen presentation by recruited dendritic cells and macrophages. Melanoma-specific CD4(+) and CD8(+) T-cells, CD1d-restricted NKT-cells, and antibodies mediate tumor rejection. Initial testing of this immunization strategy in patients with metastatic melanoma revealed the consistent induction of cellular and humoral antitumor responses that provoked the extensive necrosis of distant metastases without significant toxicity. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Dana 510E,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA39542, CA74886] NR 51 TC 110 Z9 117 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 19 PY 2003 VL 22 IS 20 BP 3188 EP 3192 DI 10.1038/sj.onc.1206459 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 682MV UT WOS:000183096600021 PM 12789295 ER PT J AU Yamaguchi, DT Ma, DF AF Yamaguchi, DT Ma, DF TI Mechanism of pH regulation of connexin 43 expression in MC3T3-E1 cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE gap junctions; pH; connexin 43; transcription rate; mRNA stability; protein half-life ID INTERCELLULAR COMMUNICATION; TRANSCRIPTION FACTOR; OSTEOBLASTIC CELLS; GENE-EXPRESSION; AMBIENT PH AB Gap junction (GJ) expression and function allowing cell-cell communication among osteoblasts may be important in new bone formation. An alkaline milieu stimulates mineralization, while extracellular acidification leads to demineralization of bone. It was previously demonstrated that alkaline pH increases, while acid pH decreases GJ intercellular communication by an increase in steady-state GJ connexin 43 (Cx43) mRNA and protein expression. At pH 7.6, transcription of new Cx43 mRNA was significantly higher than that at pH 6.9 but not significantly different at pH 7.2, as assessed by nuclear run-on assay. Transcription of new Cx43 mRNA was higher at pH 7.2 compared to that at pH 6.9. Although Cx43 mRNA half-life tended to be longer at pH 7.6, analysis of variance did not yield a significant difference of the Cx43 mRNA half-life at any of the pHs tested. Likewise, the half-life of Cx43 protein at pHs of 6.9, 7.2, and 7.6 was not significantly different. Plasma membrane and cytosolic Cx43 fractions were proportionately similar at pH 7.2 and 6.9. Thus, the decrease in Cx43 mRNA at low pH compared to high pH is due to a decrease in the transcription rate of Cx43 but not due to an alteration of message stability. The early uncoupling of gap junctions by low pH found previously does not appear to be due to changes in the half-life nor distribution of Cx43 protein between cytosolic and plasma membrane compartments. (C) 2003 Elsevier Science (USA). All rights reserved. C1 VA Greater Los Angeles, Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. VA Greater Los Angeles, Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90073 USA. RP Yamaguchi, DT (reprint author), VA Greater Los Angeles, Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. NR 14 TC 11 Z9 11 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 16 PY 2003 VL 304 IS 4 BP 736 EP 739 DI 10.1016/S0006-291X(03)00633-8 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 679GH UT WOS:000182912000024 PM 12727217 ER PT J AU Liu, CX Song, YL McTeague, M Vu, AW Wexler, H Finegold, SM AF Liu, CX Song, YL McTeague, M Vu, AW Wexler, H Finegold, SM TI Rapid identification of the species of the Bacteroides fragilis group by multiplex PCR assays using group- and species-specific primers SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE multiplex PCR; identification; Bacteroides fragilis group ID 23S RIBOSOMAL-RNA; CLINICAL SPECIMENS; GENE; INSERTION; BACTERIA; SYSTEM; HUMANS AB We report a rapid and reliable two-step multiplex polymerase chain reaction (PCR) assay to identify the 10 Bacteroides fragilis group species - Bacteroides caccae, B. distasonis, B. eggerthii, B. fragilis, B. merdae, B. ovatus, B. stercoris, B. thetaiotaomicron, B. uniformis and B. vulgatus. These 10 species were first divided into three subgroups by multiplex PCR-G, followed by three multiplex PCR assays with three species-specific primer mixtures for identification to the species level. The primers were designed from nucleotide sequences of the 16S rRNA, the 16S-23S rRNA intergenic spacer region and part of the 23S rRNA gene. The established two-step multiplex PCR identification scheme was applied to the identification of 155 clinical isolates of the B. fragilis group that were previously identified to the species level by phenotypic tests. The new scheme was more accurate than phenotypic identification, which was accurate only 84.5% of the time. The multiplex PCR scheme established in this study is a simple, rapid and reliable method for the identification of the B. fragilis group species. This will permit more accurate assessment of the role of various B. fragilis group members in infections and of the degree of antimicrobial resistance in each of the group members. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier Science B.V.. All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Clin Microbiol Lab, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Infect Dis Sect, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90024 USA. RP Liu, CX (reprint author), W Los Angeles Vet Affairs Med Ctr, Res Serv, 11301 Wilshire Blvd,Room E3-237,Bldg 304, Los Angeles, CA 90073 USA. NR 29 TC 60 Z9 60 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD MAY 16 PY 2003 VL 222 IS 1 BP 9 EP 16 DI 10.1016/S0378-1097(03)00296-9 PG 8 WC Microbiology SC Microbiology GA 682WR UT WOS:000183115800002 PM 12757940 ER PT J AU Chauhan, D Li, GL Hideshima, T Podar, K Mitsiades, C Mitsiades, N Munshi, N Kharbanda, S Anderson, KC AF Chauhan, D Li, GL Hideshima, T Podar, K Mitsiades, C Mitsiades, N Munshi, N Kharbanda, S Anderson, KC TI JNK-dependent release of mitochondrial protein, Smac, during apoptosis in multiple myeloma (MM) cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OVERCOMES DRUG-RESISTANCE; CYTOCHROME-C; INDEPENDENT ACTIVATION; KINASE; STRESS; DEATH; SMAC/DIABLO; REQUIREMENT; INHIBITOR; INDUCTION AB Smac, second mitochondria-derived activator of caspases, promotes apoptosis via activation of caspases. Previous studies have shown that c-Jun NH2-terminal kinase (JNK) is involved in regulating another mitochondrial protein, cytochrome c during apoptosis; however, the role of JNK in the release of mitochondrial Smac is unknown. Here we show that induction of apoptosis in multiple myeloma (MM) cells is associated with activation of JNK, translocation of JNK from cytosol to mitochondria, and release of Smac from mitochondria to cytosol. Blocking JNK either by dominant-negative mutant (DN-JNK) or cotreatment with a specific JNK inhibitor, SP600125, abrogates both stress-induced release of Smac and induction of apoptosis. These findings demonstrate that activation of JNK is an obligatory event for the release of Smac during stress-induced apoptosis in MM cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02215 USA. FU NCI NIH HHS [CA 78373]; PHS HHS [50947] NR 27 TC 147 Z9 150 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 16 PY 2003 VL 278 IS 20 BP 17593 EP 17596 DI 10.1074/jbc.C300076200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 677YX UT WOS:000182838300003 PM 12665525 ER PT J AU Shand, JH Beattie, J Song, H Phillips, K Kelly, SM Flint, DJ Allan, GJ AF Shand, JH Beattie, J Song, H Phillips, K Kelly, SM Flint, DJ Allan, GJ TI Specific amino acid substitutions determine the differential contribution of the N- and C-terminal domains of insulin-like growth factor (IGF)-binding protein-5 in binding IGF-I SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CIRCULAR-DICHROISM; EXTRACELLULAR-MATRIX; HEPARIN-BINDING; SECONDARY STRUCTURE; SITE; IGFBP-3; LOCALIZATION; FRAGMENTS; RECEPTOR; REGION AB We have previously reported that two highly conserved amino acids in the C-terminal domain of rat insulin-like growth factor-binding protein (IGFBP)-5, Gly(203) and Gln(209), are involved in binding to insulin-like growth factor (IGF)-1. Here we report that mutagenesis of both amino acids simultaneously (C-Term mutant) results in a cumulative effect and an even greater reduction in IGF-I binding: 30-fold measured by solution phase IGF binding assay and 10-fold by biosensor analysis. We compared these reductions in ligand binding to the effects of specific mutations of five amino acids in the N-terminal domain (N-Term mutant), which had previously been shown by others to cause a very large reduction in IGF-I binding (1). Our results confirm this as the major IGF-binding site. To prove that the mutations in either N- or C-Term were specific for IGF-I binding, we carried out CD spectroscopy and showed that these alterations did not lead to gross conformational changes in protein structure for either mutant. Combining these mutations in both domains (N+C-Term mutant) has a cumulative effect and leads to a 126-fold reduction in IGF-I binding as measured by biosensor. Furthermore, the equivalent mutations in the C terminus of rat IG-FBP2 (C-Term 2) also results in a significant reduction in IGF-I binding, suggesting that the highly conserved Gly and Gln residues have a conserved IGF-I binding function in all six IGFBPs. Finally, although these residues lie within a major heparin-binding site in IGFBP-5 and -3, we also show that the mutations in C-Term have no effect on heparin binding. C1 Hannah Res Inst, Ayr KA6 5HL, Scotland. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Glasgow, Inst Biomed & Life Sci, Glasgow G12 8QQ, Lanark, Scotland. RP Allan, GJ (reprint author), Hannah Res Inst, Ayr KA6 5HL, Scotland. RI Kelly, Sharon/K-4611-2013 NR 35 TC 44 Z9 44 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 MAY 16 PY 2003 VL 278 IS 20 BP 17859 EP 17866 DI 10.1074/jbc.M300526200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 677YX UT WOS:000182838300035 PM 12626499 ER PT J AU Clarke, P Meintzer, SM Moffitt, LA Tyler, KL AF Clarke, P Meintzer, SM Moffitt, LA Tyler, KL TI Two distinct phases of virus-induced nuclear factor kappa B regulation enhance tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in virus-infected cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REOVIRUS-INDUCED APOPTOSIS; TRAIL-INDUCED APOPTOSIS; TRANSCRIPTION FACTOR; CANCER-CELLS; FACTOR-ALPHA; TRANSFORMING PROTEIN; REQUIRES ACTIVATION; SENSITIZES CELLS; DEATH RECEPTORS; PATHWAY AB Cellular transcription factors are often utilized by infecting viruses to promote viral growth and influence cell fate. We have previously shown that nuclear factor kappaB (NF-kappaB) is activated after reovirus infection and that this activation is required for virus-induced apoptosis. In this report we identify a second phase of reovirus-induced NF-kappaB regulation. We show that at later times post-infection NF-kappaB activation is blocked in reovirus-infected cells. This results in the termination of virus-induced NF-kappaB activity and the inhibition of tumor necrosis factor alpha and etoposide-induced NF-kappaB activation in infected cells. Reovirus-induced inhibition of NF-kappaB activation occurs by a mechanism that prevents IkappaBalpha degradation and that is blocked in the presence of the viral RNA synthesis inhibitor, ribavirin. Reovirus-induced apoptosis is mediated by tumor necrosis factor-related apoptosis inducing ligand (TRAIL) in a variety of epithelial cell lines. Herein we show that ribavirin inhibits reovirus-induced apoptosis in TRAIL-resistant HEK293 cells and prevents the ability of reovirus infection to sensitize TRAIL-resistant cells to TRAIL-induced apoptosis. Furthermore, TRAIL-induced apoptosis is enhanced in HEK293 cells expressing IkappaBDeltaN2, which blocks NF-kappaB activation. These results indicate that the ability of reovirus to inhibit NF-kappaB activation sensitizes HEK293 cells to TRAIL and facilitates virus-induced apoptosis in TRAIL-resistant cells. Our findings demonstrate that two distinct phases of virus-induced NF-kappaB regulation are required to efficiently activate host cell apoptotic responses to reovirus infection. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med Microbiol & Immunol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol B 182, 4200 E 9th Ave, Denver, CO 80262 USA. OI Tyler, Kenneth/0000-0003-3294-5888 FU NIA NIH HHS [1R01AG14071] NR 62 TC 35 Z9 38 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 16 PY 2003 VL 278 IS 20 BP 18092 EP 18100 DI 10.1074/jbc.M300265200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 677YX UT WOS:000182838300066 PM 12637521 ER PT J AU Du, LN Zhang, XP Han, YY Burke, NA Kochanek, PM Watkins, SC Graham, SH Carcillo, JA Szabo, C Clark, RSB AF Du, LN Zhang, XP Han, YY Burke, NA Kochanek, PM Watkins, SC Graham, SH Carcillo, JA Szabo, C Clark, RSB TI Intra-mitochondrial poly(ADP-ribosylation) contributes to NAD(+) depletion and cell death induced by oxidative stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LONG-TERM POTENTIATION; NITRIC-OXIDE SYNTHASE; POLYMERASE INHIBITORS; DNA DAMAGE; RAT-BRAIN; APOPTOSIS; PEROXYNITRITE; SYNTHETASE; REPAIR; ACTIVATION AB Poly(ADP-ribosylation), primarily via poly(ADP-ribose) polymerase-1 (PARP-1), is a pluripotent cellular process important for maintenance of genomic integrity and RNA transcription in cells. However, during conditions of oxidative stress and energy depletion, poly(ADP-ribosylation) paradoxically contributes to mitochondrial failure and cell death. Although it has been presumed that poly(ADP-ribosylation) within the nucleus mediates this pathologic process, PARP-1 and other poly(ADP-ribosyltransferases) are also localized within mitochondria. To this end, the presence of PARP-1 and poly(ADP-ribosylation) were verified within mitochondrial fractions from primary cortical neurons and fibroblasts. Inhibition of poly(ADP-ribosylation) within the mitochondrial compartment preserved transmembrane potential (DeltaPsi(m)), NAD(+) content, and cellular respiration, prevented release of apoptosis-inducing factor, and reduced neuronal cell death triggered by oxidative stress. Treatment with liposomal NAD(+) also preserved DeltaPsi(m) and cellular respiration during oxidative stress. Furthermore, inhibition of poly(ADP-ribosylation) prevented intranuclear localization of apoptosis-inducing factor and protected neurons from excitotoxic injury; and PARP-1 null fibroblasts were protected from oxidative stress-induced cell death. Collectively these data suggest that poly(ADP-ribosylation) compartmentalized to the mitochondria can be converted from a homeostatic process to a mechanism of cell death when oxidative stress is accompanied by energy depletion. These data implicate intra-mitochondrial poly(ADP-ribosylation) as an important therapeutic target for central nervous system and other diseases associated with oxidative stress and energy failure. C1 Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Crit Care Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Cell Biol & Physiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Pediat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Neurol, Pittsburgh, PA 15260 USA. Vet Affairs Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15261 USA. Inotek Pharmaceut Corp, Beverly, MA 01915 USA. RP Clark, RSB (reprint author), Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Crit Care Med, 3434 5th Ave, Pittsburgh, PA 15260 USA. RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X FU NICHD NIH HHS [T32 HD 40686]; NINDS NIH HHS [P50 NS30318, R01 NS38620] NR 47 TC 213 Z9 220 U1 1 U2 8 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 MAY 16 PY 2003 VL 278 IS 20 BP 18426 EP 18433 DI 10.1074/jbc.M301295200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 677YX UT WOS:000182838300109 PM 12626504 ER PT J AU Cho, GY Wu, YT Ackerman, JL AF Cho, GY Wu, YT Ackerman, JL TI Detection of hydroxyl ions in bone mineral by solid-state NMR spectroscopy SO SCIENCE LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; CALCIUM PHOSPHATES; HYDROXYAPATITE; TEMPERATURE; CARBONATE; CRYSTALS; PHASES; ENAMEL AB Previous measurements of the hydroxyl (OH-) ion content of the calcium phosphate crystals of bone mineral have indicated a substantial depletion or near-absence of OH-, despite its presumed status as a constituent of the hydroxyapatite lattice. Analytical methods for determining bone crystal OH content have depended on procedures or assumptions that may have biased the results, such as chemical pretreatment to eliminate interference from the organic matrix. We demonstrate a two-dimensional solid-state nuclear magnetic resonance (NMR) spectroscopy technique that detects the proton spectrum of bone crystals while suppressing the interfering matrix signals, eliminating the need for specimen pretreatment other than cryogenic grinding. Results on fresh-frozen and ground whole bone of several mammalian species show that the bone crystal OH- is readily detectable; a rough estimate yields an OH- content of human cortical bone of about 20% of the amount expected in stoichiometric hydroxyapatite. This finding sheds light on the biochemical processes underlying normal and abnormal bone mineral metabolism. C1 Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Biomat Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Dept Orthopaed Surg, Lab Study Skeletal Disorders & Rehabil, Boston, MA 02115 USA. RP Ackerman, JL (reprint author), Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Biomat Lab, Room 2301,149 13th St, Charlestown, MA 02129 USA. RI Ackerman, Jerome/E-2646-2015 OI Ackerman, Jerome/0000-0001-5176-7496 FU NCRR NIH HHS [RR03264]; NIAMS NIH HHS [AR42258] NR 22 TC 166 Z9 171 U1 6 U2 38 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 MAY 16 PY 2003 VL 300 IS 5622 BP 1123 EP 1127 DI 10.1126/science.1078470 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 678VC UT WOS:000182886500038 PM 12750514 ER PT J AU Gorse, GJ O'Connor, TZ Young, SL Mendelman, PM Bradley, SF Nichol, KL Strickland, JH Paulson, DM Rice, KL Foster, RA Fulambarker, AM Shigeoka, JW Kuschner, WG Goodman, RP Neuzil, KM Wittes, J Boardman, KD Peduzzi, PN AF Gorse, GJ O'Connor, TZ Young, SL Mendelman, PM Bradley, SF Nichol, KL Strickland, JH Paulson, DM Rice, KL Foster, RA Fulambarker, AM Shigeoka, JW Kuschner, WG Goodman, RP Neuzil, KM Wittes, J Boardman, KD Peduzzi, PN TI Efficacy trial of live, cold-adapted and inactivated influenza virus vaccines in older adults with chronic obstructive pulmonary disease: a VA cooperative study SO VACCINE LA English DT Article DE influenza virus; influenza vaccine; efficacy ID CHRONIC LUNG-DISEASE; ELDERLY PERSONS; REASSORTANT VIRUS; ILL ADULTS; UNDERLYING CONDITIONS; ANTIBODY-RESPONSES; HEALTHY-ADULTS; SAMPLE-SIZE; WILD-TYPE; VACCINATION AB We assessed whether trivalent live, cold-adapted influenza virus (CAIV-T) vaccine provides added protection when co-administered with trivalent inactivated influenza virus vaccine (TVV) in patients with chronic obstructive pulmonary disease (COPD). Subjects (N = 2215) were randomly assigned to receive either TVV intramuscularly (IM) and CAIV-T intranasally (TC), or TVV and placebo (TP). The vaccines were well-tolerated. Efficacy of TC compared to TP was not statistically significant and was 0.16 for any influenza virus strain (95% confidence limit (CL): -0.22, 0.43), 0.26 for A (H3N2) virus (95% CL: -0.17, 0.53), and -0.05 for type B virus (95% CL: -1.13, 0.48). However, there was a possible advantage for TC over TP in reducing respiratory consequences of an influenza season measured by pulmonary function and symptoms at end of study. Published by Elsevier Science Ltd. C1 St Louis Univ, Med Ctr, Dept Vet Affairs, St Louis, MO 63110 USA. Dept Vet Affairs, Cooperat Studies Program, Albuquerque, NM USA. Dept Vet Affairs, Cooperat Studies Program, West Haven, CT USA. Med Ctr, Dept Vet Affairs, Durham, NC USA. MedImmune Vaccines Inc, Mountain View, CA USA. Med Ctr, Dept Vet Affairs, Ann Arbor, MI USA. Med Ctr, Dept Vet Affairs, Minneapolis, MN USA. Med Ctr, Dept Vet Affairs, Birmingham, AL USA. Med Ctr, Dept Vet Affairs, Richmond, VA USA. Med Ctr, Dept Vet Affairs, Gainesville, FL USA. Med Ctr, Dept Vet Affairs, Chicago, IL USA. Med Ctr, Dept Vet Affairs, Salt Lake City, UT USA. Dept Vet Affairs, Palo Alto, CA USA. Med Ctr, Dept Vet Affairs, Boston, MA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Stat Collaborat, Washington, DC USA. RP Gorse, GJ (reprint author), St Louis Univ, Hlth Sci Ctr, Div Infect Dis & Immunol, 3635 Vista Ave,FDT-8N, St Louis, MO 63110 USA. NR 59 TC 37 Z9 40 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 16 PY 2003 VL 21 IS 17-18 BP 2133 EP 2144 DI 10.1016/S0264-410X(02)00748-X PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 682PF UT WOS:000183100200042 PM 12706704 ER PT J AU Wong, GC Frisch, D Murphy, SA Sabatine, MS Pai, R James, D Kraimer, N Katsiyiannis, PT Marble, SJ DiBattiste, PM Demopoulos, LA Gourlay, SG Barron, HV Cannon, CP Gibson, CM AF Wong, GC Frisch, D Murphy, SA Sabatine, MS Pai, R James, D Kraimer, N Katsiyiannis, PT Marble, SJ DiBattiste, PM Demopoulos, LA Gourlay, SG Barron, HV Cannon, CP Gibson, CM CA LIMIT AMI Study Grp TACTICS-TIMI 18 Study Grp TI Time for contrast material to traverse the epicardial artery and the myocardium in ST-segment elevation acute myocardial infarction versus unstable angina pectoris/non-ST-elevation acute myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TISSUE-PLASMINOGEN ACTIVATOR; RANDOMIZED TRIAL; PERFUSION GRADE; THROMBOLYSIS; REPERFUSION; ISCHEMIA; ECHOCARDIOGRAPHY; MORPHOLOGY; INHIBITOR; MORTALITY AB Although the time for contrast material to fill the epicardial artery in the setting of acute coronary syndromes has been studied extensively, the time for contrast material to fill the myocardium has not been evaluated. We compared differences in myocardial contrast material transit. among patients with unstable angina pectoris/ non-ST-elevation acute myocardial infarction (UAP/ NSTEAMI) with patients with ST-elevation acute myocardial infarction (STEAMI). The time it took for contrast material to first appear and to arrive at peak intensity in the myocardium was compared in 224 patients with STEAMI enrolled in the LIMIT-AMI study versus 430 patients with UAP/NSTEAMI enrolled in the TACTICS-TIMI 18 trial. In patients with STEAMI, there was a delay in both the time for contrast material to first enter the myocardium (5,619 +/- 1,789 vs 4,663 +/- 1,626 ms, p <0.0001) and the time from entrance to peak blush intensity (2,387 +/- 1,359 vs 1,959 +/- 1,244 ms, p = 0.003) compared with patients with UAP/NSTEAMI. STEAMI remained significantly associated with impaired entrance of contrast material into the myocardium (p <0.0001) in a multivariate model controlling for known correlates of impaired epicardial flow (presence of thrombus, percent diameter stenosis, left anterior descending artery location, and contrast material inflow in the epicardial artery [corrected TIMI frame count]). The time for contrast material to enter the myocardium is impaired to a greater degree in STEAMI compared with UAP/NSTEAMI, even after adjusting for other variables known to delay flow in the epicardial artery. These data provide insight into potential mechanistic differences between these 2 clinical syndromes. (C) 2003 by Excerpta Medica, Inc. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Data Coordinating Ctr,TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Merck & Co Inc, Blue Bell, PA USA. Genentech Inc, San Francisco, CA 94080 USA. Harvard Univ, Clin Res Inst, Boston, MA 02115 USA. RP Gibson, CM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Data Coordinating Ctr,TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. RI bashzar, salman/R-5748-2016 NR 26 TC 5 Z9 7 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 15 PY 2003 VL 91 IS 10 BP 1163 EP 1167 DI 10.1016/S0002-9149(03)00260-1 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 679PC UT WOS:000182930300002 PM 12745096 ER PT J AU Weiner, M Burman, W Vernon, A Benator, D Peloquin, CA Khan, A Weis, S King, B Shah, N Hodge, T AF Weiner, M Burman, W Vernon, A Benator, D Peloquin, CA Khan, A Weis, S King, B Shah, N Hodge, T CA Tuberculosis Trials Consortium TI Low isoniazid concentrations and outcome of tuberculosis treatment with once-weekly isoniazid and rifapentine SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE tuberculosis; isoniazid; rifapentine; treatment; pharmacokinetics ID CONTINUATION PHASE; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; FASTING CONDITIONS; 6-MONTH REGIMEN; RIFAMPIN; PHARMACOKINETICS; PYRAZINAMIDE; ANTACIDS; MICE AB To understand why once-weekly isoniazid/rifapentine therapy for tuberculosis was less effective than twice-weekly isoniazid/rifampin, we studied human immunodeficiency virus-seronegative patients with either failure (n = 4), relapse (n = 35), or cure (n = 94), recruited from a comparative treatment trial. In multivariate analyses that were adjusted for severity of disease, low plasma concentrations of isoniazid were associated with failure/relapse with once-weekly isoniazid/rifapentine (median isoniazid area under the concentration-time curve for 12 hours after the dose [AUCO(0-12)] was 36 mug (.) hour/ml in failure/relapse versus 56 mug - hour/ml in control cases p = 0.005), but not with twice-weekly isoniazid/rifampin. Furthermore, two patients who relapsed with Mycobacterium tuberculosis monoresistant to rifamycin had very low concentrations of isoniazid. Finally, isoniazid acetylator status determined by N-acetyltransferase type 2 genotype was associated with outcome with once-weekly isoniazid/rifapentine (p = 0.03) but not twice-weekly isoniazid/rifampin. No rifamycin pharmacokinetic parameter was consistently and significantly associated with outcome (p > 0.10). Because low isoniazid concentrations were associated with failure/ relapse, a drug with consistently greater area under the concentration-time curve than isoniazid may be needed to achieve highly active once-weekly therapy with rifapentine. C1 S Texas Vet Hlth Care Syst, Dept Med 111F, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Univ Colorado, Denver Publ Hlth & Dept Med, Ctr Hlth Sci, Denver, CO 80202 USA. Univ Colorado, Sch Pharm, Natl Jewish Med & Res Ctr, Denver, CO 80202 USA. Univ Colorado, Sch Med, Natl Jewish Med & Res Ctr, Denver, CO 80202 USA. Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. VAMC, Washington, DC USA. Univ N Texas, Ctr Hlth Sci, Ft Worth, TX USA. RP Weiner, M (reprint author), S Texas Vet Hlth Care Syst, Dept Med 111F, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 FU NCRR NIH HHS [M01-RR-00827, M01-RR-01346] NR 27 TC 118 Z9 121 U1 0 U2 5 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 MAY 15 PY 2003 VL 167 IS 10 BP 1341 EP 1347 DI 10.1164/rccm.200208-951OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 678HV UT WOS:000182862100012 PM 12531776 ER PT J AU Stenlund, P Babcock, GJ Sodroski, J Myszka, DG AF Stenlund, P Babcock, GJ Sodroski, J Myszka, DG TI Capture and reconstitution of G protein-coupled receptors on a biosensor surface SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID PARAMAGNETIC PROTEOLIPOSOMES; LIGAND; HIV-1; IMMOBILIZATION; LESTR/FUSIN; EXPRESSION; SDF-1; CCR5 AB Surface plasmon resonance (SPR) biosensors offer a unique opportunity to study the binding activity of G protein-coupled receptors (GPCRs) in real time with minimal sample preparation. Using two chemokine receptors (CXCR4 and CCR5) as model systems, we captured the proteins from crude cell preparations onto the biosensor surface and reconstituted a lipid environment to maintain receptor activity. The conformational states of the receptors were probed using conformationally dependent antibodies, and by characterizing the binding properties of a native chemokine ligand (stromal cell-derived factor lot). The results suggest that the detergent-solubilized receptors are active for ligand binding in the presence and absence of a reconstituted bilayer. There are three advantages to using this receptor-capturing approach: (1) there is no need to purify the receptor prior to immobilization on the biosensor surface, (2) the receptors are homogeneously immobilized through the capturing step, and (3) the receptors can be captured at high enough densities to allow the study of relatively low-molecular-mass ligands (2000-4000 Da). We also demonstrated that the receptors are sensitive to the solubilizing conditions, which illustrates the potential for using SPR biosensors to rapidly screen solublization conditions for GPCRs. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Univ Utah, Ctr Biomol Interact Anal, Salt Lake City, UT 84132 USA. Harvard Univ, Sch Med, Div Aids, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc & Immunol & AIDS, Boston, MA 02115 USA. RP Myszka, DG (reprint author), Univ Utah, Ctr Biomol Interact Anal, Salt Lake City, UT 84132 USA. FU NIAID NIH HHS [AI41851] NR 11 TC 77 Z9 78 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAY 15 PY 2003 VL 316 IS 2 BP 243 EP 250 DI 10.1016/S0003-2697(03)00046-0 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 673XP UT WOS:000182606500013 PM 12711346 ER PT J AU Potter-Perigo, S Hull, RL Tsoi, C Braun, KR Andrikopoulos, S Teague, J Verchere, CB Kahn, SE Wight, TN AF Potter-Perigo, S Hull, RL Tsoi, C Braun, KR Andrikopoulos, S Teague, J Verchere, CB Kahn, SE Wight, TN TI Proteoglycans synthesized and secreted by pancreatic islet beta-cells bind amylin SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE proteoglycans; amylin; islet amyloid polypeptide; type 2 diabetes; islet amyloid; beta-cells; islet ID HEPARAN-SULFATE PROTEOGLYCAN; SMOOTH-MUSCLE CELLS; COLONY-STIMULATING FACTOR; LOW-DENSITY LIPOPROTEINS; ALZHEIMERS-DISEASE; AMYLOID POLYPEPTIDE; FIBRIL FORMATION; GROWTH-FACTOR; A-BETA; DIFFERENTIAL EXPRESSION C1 Hope Heart Inst, Seattle, WA 98104 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. RP Wight, TN (reprint author), Hope Heart Inst, Seattle, WA 98104 USA. FU NHLBI NIH HHS [HL30086-19]; NIDDK NIH HHS [DK02456-42, DK-50703, DK-17047] NR 49 TC 23 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY 15 PY 2003 VL 413 IS 2 BP 182 EP 190 DI 10.1016/S0003-9861(03)00116-4 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 679WC UT WOS:000182944100005 PM 12729615 ER PT J AU Murata, M Bonassar, LJ Wright, M Mankin, HJ Towle, CA AF Murata, M Bonassar, LJ Wright, M Mankin, HJ Towle, CA TI A role for the interleukin-1 receptor in the pathway linking static mechanical compression to decreased proteoglycan synthesis in surface articular cartilage SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE cartilage; static compression; interleukin-1; proteoglycan; cartilage biomechanics ID NITRIC-OXIDE PRODUCTION; GROWTH-FACTOR-I; FOCAL ADHESION; BIOSYNTHETIC RESPONSE; DYNAMIC COMPRESSION; GENE-EXPRESSION; IGF-I; CHONDROCYTE; DEGRADATION; ANTAGONIST AB Loading of articular cartilage during weight bearing is essential for the maintenance of cartilage function. Although certain cyclic loading protocols stimulate extracellular matrix synthesis, constant or static compression decreases proteoglycan and collagen synthesis in cartilage explants. The goal of this study was to determine whether the compression-induced decrease in proteoglycan synthesis involves an interleukin-1 (IL-1) signaling pathway. Cartilage explants were compressed 50% in the presence of IL-1 receptor antagonist (IL-1ra), and the incorporation of [S-35]sulfate into macromolecules was measured. IL-1ra increased sulfate incorporation in compressed cartilage but not in cartilage maintained at the in situ thickness (0% compression). IL-1alpha and IL-1beta mRNAs were detected in cartilage compressed 50% for at least 3 h, while nitric oxide synthase 11 mRNA was only detected in cartilage compressed 50% for 6 h. The data support a role for the IL-1 receptor in the pathway linking static compression to reduced proteoglycan synthesis. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Ctr Tissue Engn, Worcester, MA 01655 USA. Univ Massachusetts, Sch Med, Dept Anaesthesiol, Worcester, MA 01655 USA. RP Towle, CA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Res Labs, 55 Fruit St, Boston, MA 02114 USA. RI Bonassar, Lawrence/C-2103-2016 OI Bonassar, Lawrence/0000-0003-1094-6433 FU NIA NIH HHS [1 R03 AG16885-01] NR 52 TC 32 Z9 36 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY 15 PY 2003 VL 413 IS 2 BP 229 EP 235 DI 10.1016/S0003-9861(03)00129-2 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 679WC UT WOS:000182944100011 PM 12729621 ER PT J AU Schwartz, CE Wright, CI Shin, LM Kagan, J Whalen, PJ McMullin, KG Rauch, SL AF Schwartz, CE Wright, CI Shin, LM Kagan, J Whalen, PJ McMullin, KG Rauch, SL TI Differential amygdalar response to novel versus newly familiar neutral faces: A functional MRI probe developed for studying inhibited temperament SO BIOLOGICAL PSYCHIATRY LA English DT Article DE amygdala; cortex; novelty; familiar; faces; emotion ID POSTTRAUMATIC-STRESS-DISORDER; FACIAL EMOTION DISCRIMINATION; BEHAVIORAL-INHIBITION; SYMPTOM PROVOCATION; PREFRONTAL CORTEX; CONDITIONED FEAR; HUMAN BRAIN; ACTIVATION; EXPRESSIONS; HABITUATION AB Background: As a prelude to future studies of subjects with different temperaments, we sought to develop a probe to measure differential amygdalar responses to novel versus familiar stimuli. Prior neuroimaging studies of the amygdala in humans to date have focused principally on responses to emotional stimuli, primarily aversive, rather than to novelty per se. Methods: Eight normal subjects aged 22.4 +/- 1.3 years were scanned using functional magnetic resonance imaging (fMRI) during passive viewing of novel and familiar faces. Results: Using this newly developed paradigm, we found greater fMRI blood oxygenation level dependent (BOLD) signal response within the right amygdala to novel versus familiar faces-all with neutral expression. Furthermore, although a new facial identity was always presented in the novel condition, signal in the amygdala declined over time as it did for the familiar condition. Conclusions: These results suggest that at least one primary function of the amygdala is to detect and process unexpected or unfamiliar events that have potential biological import, of which stimuli symbolic of fear or threat are but one possible example. We propose that this experimental paradigm will be useful for examining brain responses to novelty in different temperamental groups, as well as various psychiatric disorders. (C) 2003 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Dev Psychopathol Res Grp, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Psychiat Neuroimaging Res Grp, 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. Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. RP Schwartz, CE (reprint author), Massachusetts Gen Hosp, Dev Psychopathol Res Grp, 13th St,Bldg 149,CNY-9102, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH64806] NR 66 TC 140 Z9 143 U1 2 U2 11 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 MAY 15 PY 2003 VL 53 IS 10 BP 854 EP 862 DI 10.1016/S0006-3223(02)01906-6 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 676BZ UT WOS:000182733200002 PM 12742672 ER PT J AU Shaughnessy, J Jacobson, J Sawyer, J McCoy, J Fassas, A Zhan, FH Bumm, K Epstein, J Anaissie, E Jagannath, S Vesole, D Siegel, D Desikan, R Munshi, N Badros, A Tian, EM Zangari, M Tricot, G Crowley, J Barlogie, B AF Shaughnessy, J Jacobson, J Sawyer, J McCoy, J Fassas, A Zhan, FH Bumm, K Epstein, J Anaissie, E Jagannath, S Vesole, D Siegel, D Desikan, R Munshi, N Badros, A Tian, EM Zangari, M Tricot, G Crowley, J Barlogie, B TI Continuous absence of metaphase-defined cytogenetic abnormalities, especially of chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma treated with total therapy I: interpretation in the context of global gene expression SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; HIGH-DOSE THERAPY; GROWTH-FACTOR-I; SITU HYBRIDIZATION; POOR-PROGNOSIS; 13Q14; DELETION; AUTOTRANSPLANTS; MUTATION; RISK AB Metaphase cytogenetic abnormalities (CAs), especially of chromosome 13 (CA 13), confer a grave prognosis in multiple myeloma even with tandem autotransplantations as applied in Total Therapy 1, which enrolled 231 patients between 1989 and 1994. With a median follow-up of almost 9 years, the prognostic implications of all individual CAs, detected prior to treatment and at relapse, were investigated. Among all CAs and standard prognostic factors examined prior to therapy, only hypodiploidy and CA 13 (hypo-13 CA), alone or in combination, were associated with shortest event-free survival and overall survival (OS). The shortest postrelapse OS was observed with hypo-13 CA, which was newly detected in 18 of all 28 patients presenting with this abnormality at relapse. Superior prognosis was associated with the absence of any CA at both diagnosis and relapse (10-year OS, 40%). The lack of independent prognostic implications of other CAs points to a uniquely aggressive behavior of hypo-13 CA (present in 16% of patients at diagnosis). With the use of microarray data in 146 patients enrolled in Total Therapy 11, over-expression of cell cycle genes distinguished CA from no CA, especially in cases of del(l 3) detected by interphase fluorescence in situ hybridization (FISH). FISH 13, resulting in a haploinsufficiency of RB1 and other genes mapping to chromosome 13, as well as activation of IGF1R, appears to have an amplifying effect on cell cycle gene expression, thus providing a molecular explanation for the dire outcome of patients with CA 13 compared with those with other CAs. (C) 2003 by The American Society of Hematology. C1 Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. CRAB, Seattle, WA USA. Univ HNO Klin, Erlangen, Germany. St Vincent Comprehens Canc Ctr, New York, NY USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Hackensack Univ, Ctr Med, Hackensack, NJ USA. Harvard Univ, Ctr Med, Dana Farber Canc Ctr, Boston, MA 02115 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. RP Barlogie, B (reprint author), Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, 4301 W Markham,Slot 816, Little Rock, AR 72205 USA. FU NCI NIH HHS [CA55819] NR 37 TC 86 Z9 93 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 MAY 15 PY 2003 VL 101 IS 10 BP 3849 EP 3856 DI 10.1182/blood-2002-09-2873 PG 8 WC Hematology SC Hematology GA 677EB UT WOS:000182793000021 PM 12531801 ER PT J AU Wang, H Jiang, XH Yang, F Gaubatz, JW Ma, L Magera, MJ Yang, XF Berger, PB Durante, W Pownall, HJ Schafer, AI AF Wang, H Jiang, XH Yang, F Gaubatz, JW Ma, L Magera, MJ Yang, XF Berger, PB Durante, W Pownall, HJ Schafer, AI TI Hyperhomocysteinemia accelerates atherosclerosis in cystathionine beta-synthase and apolipoprotein E double knock-out mice with and without dietary perturbation SO BLOOD LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; DEFICIENT MICE; ENDOTHELIAL DYSFUNCTION; FAMILIAL HYPERCHOLESTEROLEMIA; S-ADENOSYLHOMOCYSTEINE; TOTAL HOMOCYSTEINE; MURINE MODEL; CHOLESTEROL; PLASMA; MACROPHAGES AB Although hyperhomocysteinemia is an independent risk factor for cardiovascular disease, a direct role for homocysteine (Hcy) in this disease remains to be shown. Whereas diet-induced hyperhomocysteinemia promotes atherosclerosis in animal models, the effects of Hcy on atherogenesis in the absence of dietary perturbations is not known. We have generated double knock-out mice with targeted deletions of the genes for apollpoprotein E (apoE) and cystathionine p-synthase (CBS), which converts Hcy to cystathionine. ApoE(-/-)/CBS-/- mice developed aortic lesions even in the absence of dietary manipulation; lesion area and lesion cholesteryl ester (CE) and triglyceride (TG) contents increased with animal age and plasma Hcy levels. Plasma total cholesterol was significantly increased, whereas high density lipoprotein (HDL) cholesterol and TG concentrations of apoE(-/-)/CBS-/- mice were decreased. Cholesterol esterification and activities of enzymes catalyzing CE or TG formation in the vessel wall and in peritoneal macrophages were not changed by hyperhomocysteinemia. However, uptake of human acetyl-LDL, but not native low density lipoprotein (LDL), by mouse peritoneal macrophages was higher in the presence of hyperhomocysteinemia. These results suggest that isolated hyperhomocysteinemia is atherogenic and alters hepatic and macrophage lipoprotein metabolism, in part, by enhancing uptake of modified LDL. (C) 2003 by The American Society of Hematology. C1 Baylor Coll Med, VA Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, VA Med Ctr, Dept Pharmacol, Houston, TX 77030 USA. Baylor Coll Med, VA Med Ctr, Dept Pathol, Houston, TX 77030 USA. Mayo Clin, Rochester, MN USA. RP Wang, H (reprint author), Baylor Coll Med, VA Med Ctr, Dept Med, 2002 Holcombe Blvd 109-129, Houston, TX 77030 USA. FU NHLBI NIH HHS [HL-67033, HL-56865, HL-59976, HL-62467, HL30914] NR 41 TC 104 Z9 109 U1 2 U2 5 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 MAY 15 PY 2003 VL 101 IS 10 BP 3901 EP 3907 DI 10.1182/blood-2002-08-2606 PG 7 WC Hematology SC Hematology GA 677EB UT WOS:000182793000030 PM 12506016 ER PT J AU Nicolaou, F Teodoridis, JM Park, H Georgakis, A Farokhzad, OC Bottinger, EP Da Silva, N Rousselot, P Chomienne, C Ferenczi, K Arnaout, MA Shelley, CS AF Nicolaou, F Teodoridis, JM Park, H Georgakis, A Farokhzad, OC Bottinger, EP Da Silva, N Rousselot, P Chomienne, C Ferenczi, K Arnaout, MA Shelley, CS TI CD11c gene expression in hairy cell leukemia is dependent upon activation of the proto-oncogenes ras and junD SO BLOOD LA English DT Review ID DNA-BINDING ACTIVITY; COLONY-STIMULATING FACTOR; LEUKOCYTE INTEGRIN GENE; C-FOS; NUCLEAR FACTOR; PHORBOL ESTER; TRANSCRIPTIONAL ACTIVATION; INDUCED TRANSFORMATION; LYMPHOID MALIGNANCIES; PENTOSTATIN NIPENT AB Hairy cell leukemia (HCL) is a chronic lym-phoproliferative disease, the cause of which is unknown. Diagnostic of HCL is abnormal expression of the gene that encodes the 02 integrin CD11c. In order to determine the cause of CD11c gene expression in HCL the CD11c gene promoter was characterized. Transfection of the CD11c promoter linked to a luciferase reporter gene indicated that it is sufficient to direct expression in hairy cells. Mutation analysis demonstrated that of predominant importance to the activity of the CD11c promoter is its interaction with the activator protein-1 (AP-1) family of transcription factors. Comparison of nuclear extracts prepared from hairy cells with those prepared from other cell types indicated that hairy cells exhibit abnormal constitutive expression of an AP-1 complex containing JunD. Functional inhibition of AP-1 expressed by hairy calls reduced CD11c promoter activity by 80%. Inhibition of Ras, which represents an upstream activator of AP-1, also significantly inhibited the CD11c promoter. Furthermore, in the hairy cell line EH, inhibition of Ras signaling through mitogen-activated protein kinase/extracellular signal-regulated kinase kinases 1 and 2 (MEK1/2) reduced not only CD11c promoter activity but also reduced both CD11c surface expression and proliferation. Expression in nonhairy cells of a dominant-positive Ras mutant activated the CD11c promoter to levels equivalent to those In hairy cells. Together, these data indicate that the abnormal expression of the CD11c gene characteristic of HCL is dependent upon activation of the proto-oncogenes ras and junD. (C) 2003 by The American Society of Hematology. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Albert Einstein Coll Med, Div Nephrol, Bronx, NY 10467 USA. Hop St Louis, Inst Hematol, Paris, France. Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. RP Shelley, CS (reprint author), Massachusetts Gen Hosp, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK50779, DK50305, DK43351] NR 108 TC 21 Z9 21 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 2003 VL 101 IS 10 BP 4033 EP 4041 DI 10.1182/blood-2002-01-0324 PG 9 WC Hematology SC Hematology GA 677EB UT WOS:000182793000048 PM 12576324 ER PT J AU Mitsiades, N Mitsiades, CS Richardson, PG McMullan, C Poulaki, V Fanourakis, G Schlossman, R Chauhan, D Munshi, NC Hideshima, T Richon, VM Marks, PA Anderson, KC AF Mitsiades, N Mitsiades, CS Richardson, PG McMullan, C Poulaki, V Fanourakis, G Schlossman, R Chauhan, D Munshi, NC Hideshima, T Richon, VM Marks, PA Anderson, KC TI Molecular sequelae of histone deacetylase inhibition in human malignant B cells SO BLOOD LA English DT Article ID SUBEROYLANILIDE HYDROXAMIC ACID; ACUTE PROMYELOCYTIC LEUKEMIA; MULTIPLE-MYELOMA CELLS; MARROW STROMAL CELLS; HUMAN NEUROBLASTOMA; CANCER CELLS; IN-VIVO; APOPTOSIS; SAHA; EXPRESSION AB Histone acetylation modulates gene expression, cellular differentiation, and survival and is regulated by the opposing activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDAC inhibition results in accumulation of acetylated nucleosomal histones and induces differentiation and/or apoptosis in transformed cells. In this study, we characterized the effect of suberoylanilide hydroxamic acid (SAHA), the prototype of a series of hydroxamic acid-based HDAC inhibitors, in cell lines and patient cells from B-cell malignancies, including multiple myeloma (MM) and related disorders. SAHA induced apoptosis in all tumor cells tested, with increased p21 and p53 protein levels and dephosphorylation of Rb. We also detected cleavage of Bid, suggesting a role for Bcl-2 family members in regulation of SAHA-induced cell death. Transfection of Bcl-2 cDNA into MMAS cells completely abrogated SAHA-induced apoptosis, confirming its protective role. SAHA did not induce cleavage of caspase-8, -9, or -3 in MMAS cells during the early phase of apoptosis, and the pan-caspase inhibitor ZVAD-FMK did not protect against SAHA. Conversely, poly(ADP)ribose polymerase (PARP) was cleaved in a pattern indicative of calpain activation, and the calpain inhibitor calpeptin abrogated SAHA-induced cell death. Importantly, SAHA sensitized MMAS cells to death receptor-mediated apoptosis and inhibited the secretion of interleukin 6 (IL-6) induced in bone marrow stromal cells (BMSCs) by binding of MM cells, suggesting that it can overcome cell adhesion-mediated drug resistance. Our studies delineate the mechanisms whereby HDAC inhibitors mediate anti-MM activity and overcome drug resistance in the BM milieu and provide the framework for clinical evaluation of SAHA, which is bioavailable, well tolerated, and bioactive after oral administration, to improve patient outcome. (C) 2003 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Aton Pharma, Tarrytown, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Mayer Bldg,Rm M557,44 Binney St, Boston, MA 02115 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 49 TC 226 Z9 230 U1 0 U2 12 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 MAY 15 PY 2003 VL 101 IS 10 BP 4055 EP 4062 DI 10.1182/blood-2002-11-3514 PG 8 WC Hematology SC Hematology GA 677EB UT WOS:000182793000051 PM 12531799 ER PT J AU Masutomi, K Hahn, WC AF Masutomi, K Hahn, WC TI Telomerase and tumorigenesis SO CANCER LETTERS LA English DT Review DE telomerase; telomerase reverse transcriptase (TERT); telomere; immortalization; human telomerase reverse transcriptase (hTERT); senescence; tumorigenesis; malignant transformation; cancer; telomere capping; tumor suppression; replication; mouse telomeres; tumor promotion; genomic instability; retinoblastoma; simian virus 40 (SV40); human papillomavirus; senescence ID NORMAL HUMAN-CELLS; IMMORTAL HUMAN-CELLS; HUMAN CANCER-CELLS; HUMAN TUMOR-CELLS; EPITHELIAL-CELLS; REVERSE-TRANSCRIPTASE; RNA COMPONENT; LIFE-SPAN; IN-VITRO; CATALYTIC SUBUNIT AB The unique biology of telomeres and telomerase plays important roles in many aspects of mammalian cell physiology. Over the past decade, several lines of evidence have confirmed that the maintenance of telomeres and telomerase participate actively in the pathogenesis of human cancer. Specifically, activation of telomerase is strongly associated with cancer, and recent observations confirm that telomeres and telomerase perform important roles in both suppressing and facilitating malignant transformation by regulating genomic stability and cell lifespan, In addition, recent evidence suggests that telomerase activation contributes to tumorigenesis independently of its role in maintaining telomere length. Here we review recent developments in our understanding of the relationships among telomeres, telomerase, and cancer. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Dana 710C, Boston, MA 02115 USA. FU NCI NIH HHS [K01 CA94223] NR 111 TC 38 Z9 43 U1 1 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAY 15 PY 2003 VL 194 IS 2 BP 163 EP 172 DI 10.1016/S0304-3835(02)00703-6 PG 10 WC Oncology SC Oncology GA 687VT UT WOS:000183398200004 PM 12757974 ER PT J AU Orsini, E Bellucci, R Alyea, EP Schlossman, R Canning, C McLaughlin, S Ghia, P Anderson, KC Ritz, J AF Orsini, E Bellucci, R Alyea, EP Schlossman, R Canning, C McLaughlin, S Ghia, P Anderson, KC Ritz, J TI Expansion of tumor-specific CD8+T cell clones in patients with relapsed myeloma after donor lymphocyte infusion SO CANCER RESEARCH LA English DT Article ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; MINOR HISTOCOMPATIBILITY ANTIGEN; CHRONIC MYELOGENOUS LEUKEMIA; CYTOTOXIC T-LYMPHOCYTES; MULTIPLE-MYELOMA; RECEPTOR REPERTOIRE; MONOCLONAL GAMMOPATHIES; IMMUNE RECONSTITUTION; VIRAL-INFECTION AB Donor lymphocyte infusions (DLI) provide effective therapy for patients with multiple myeloma who have relapsed after allogeneic bone marrow transplantation. However, the immunological mechanisms of the graft-versus-myeloma (GVM) effect have not been defined, and the target antigens of this response have not been identified. Molecular analysis of CDR3 Vbeta repertoire after CD4+ DLI demonstrated previously that the development of GVM and graft-versus-host-disease (GVHD) were associated with the clonal expansion of distinct T-cell populations in patient peripheral blood. In the current study, we undertook a molecular and functional characterization of GVM- and GVHD-associated T-cell clones. T-cell clones associated with GVM were detectable by clone-specific PCR at a low level in peripheral blood before DLI and expanded similar to10-fold after DLI. In contrast, T-cell clones associated with GVHD were not detectable before DLI or before the development of clinical GVHD. Two T-cell clones associated with GVM were isolated and expanded in vitro, allowing their phenotypic and functional characterization. Both GVM clones were derived from donor cells and had a CD3+CD8+CD4- phenotype. One GVM clone specifically recognized patient myeloma cells in an HLA class I-restricted manner, but was not reactive with patient normal bone marrow cells or patient EBV transformed B cells. Taken together, these findings suggest that the GVM response is mediated by donor-derived CD8+ T-cell clones with antimyeloma specificity that may be present before DLI. In contrast, T-cell clones associated with GVHD are expanded de novo after DLI. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St-M530, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009; Ghia, Paolo/K-7138-2016 OI Ritz, Jerome/0000-0001-5526-4669; Ghia, Paolo/0000-0003-3750-7342 FU NCI NIH HHS [CA78378]; NIAID NIH HHS [AI29530] NR 54 TC 29 Z9 29 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2003 VL 63 IS 10 BP 2561 EP 2568 PG 8 WC Oncology SC Oncology GA 680MH UT WOS:000182981600033 PM 12750280 ER PT J AU Ikeda, H Matsushita, M Waisfisz, Q Kinoshita, A Oostra, AB Nieuwint, AWM de Winter, JP Hoatlin, ME Kawai, Y Sasaki, MS D'Andrea, AD Kawakami, Y Joenje, H AF Ikeda, H Matsushita, M Waisfisz, Q Kinoshita, A Oostra, AB Nieuwint, AWM de Winter, JP Hoatlin, ME Kawai, Y Sasaki, MS D'Andrea, AD Kawakami, Y Joenje, H TI Genetic reversion in an acute myelogenous leukemia cell line from a Fanconi anemia patient with biallelic mutations in BRCA2 SO CANCER RESEARCH LA English DT Article ID COMPLEMENTATION ANALYSIS; DIAGNOSIS; MOSAICISM; AGENTS AB A 2-year old boy was diagnosed with Fanconi anemia (FA) and acute myeloid leukemia (AML). A cell line (termed FA-AML1) was established from blast cells obtained after a second relapse after a successful bone marrow transplant. Histochemical and surface marker analysis confirmed that the cells were derived from the myeloid lineage. Cytogenetic analysis revealed multiple chromosomal aberrations, including a ring 7. Stable proliferation of the cultured cells was absolutely dependent on the presence of granulocyte macrophage colony-stimulating factor or interleukin 3. This is the first AML cell line successfully established from a FA patient. Remarkably, FA-AML1 cells appeared to lack the characteristic cellular FA phenotype, i.e., a hypersensitivity to growth inhibition and chromosomal breakage by the cross-linking agent mitomycin C. Genomic DNA from the patient showed biallelic mutations [84156>T (K2729N)and 8732C>A (S2835STOP)] in the breast cancer susceptibility gene FANCD1/BBRCA2 [N. Howlett et al., Science (Wash. DC), 297: 606609, 2002]. In the AML cells, however, the 8732C>A nonsense mutation was changed into a missense mutation by a secondary alteration, 8731T>G, resulting in 2835E, which restored the open-reading frame of the gene and could explain the reverted phenotype of these cells. Loss of the FA phenotype by genetic correction of a FA gene mutation during AML progression may be a common late event in the pathogenesis of AML in FA patients, which may be treatment related. This finding suggests a novel mechanistic principle of tumor progression based on the genetic correction of an early caretaker gene defect. C1 Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet & Human Genet, NL-1081 BT Amsterdam, Netherlands. Keio Univ, Sch Med, Inst Adv Med Res, Div Cellular Signaling, Tokyo 1608582, Japan. Shizuoka Red Cross Hosp, Dept Pediat, Shizuoka 4200853, Japan. Oregon Hlth Sci Univ, Div Mol Med, Portland, OR 97201 USA. Keio Univ, Sch Med, Dept Lab Med, Tokyo 1608582, Japan. Kyoto Univ, Ctr Radiat Biol, Kyoto 6068501, Japan. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Joenje, H (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet & Human Genet, Van der Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 27 TC 39 Z9 39 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2003 VL 63 IS 10 BP 2688 EP 2694 PG 7 WC Oncology SC Oncology GA 680MH UT WOS:000182981600051 PM 12750298 ER PT J AU Srinivasan, DG Fisk, RM Xu, HH van den Heuvel, S AF Srinivasan, DG Fisk, RM Xu, HH van den Heuvel, S TI A complex of LIN-5 and GPR proteins regulates G protein signaling and spindle function in C-elegans SO GENES & DEVELOPMENT LA English DT Article DE LIN-5; GoLoco motif; G protein; chromosome segregation; spindle position ID ASYMMETRIC CELL-DIVISION; NEMATODE CAENORHABDITIS-ELEGANS; CLEAVAGE PLANE SPECIFICATION; G-ALPHA SUBUNITS; GENETIC INTERFERENCE; ORIENTATION; DROSOPHILA; POLARITY; EMBRYOS; PARTNER AB The Caenorhabditis elegans coiled-coil protein LIN-5 mediates several processes in cell division that depend on spindle forces, including alignment and segregation of chromosomes and positioning of the spindle. Here, we describe two closely related proteins, GPR-1 and GPR-2 (G protein regulator), which associate with LIN-5 in vivo and in vitro and depend on LIN-5 for localization to the spindle and cell cortex. GPR-1/GPR-2 contain a GoLoco/GPR motif that mediates interaction with GDP-bound Galpha(i/o). Inactivation of lin-5, gpr-1/gpr-2, or the Galpha(i/o) genes goa-1 and gpa-16 all cause highly similar chromosome segregation and spindle positioning defects, indicating a positive role for the LIN-5 and GPR proteins in G protein signaling. The lin-5 and gpr-1/gpr-2 genes appear to act downstream of the par polarity genes in the one- and two-cell stages and downstream of the tyrosine kinase-related genes mes-1 and src-1 at the four-cell stage. Together, these results indicate that GPR-1/GPR-2 in association with LIN-5 activate G protein signaling to affect spindle force. Polarity determinants may regulate LIN-5/GPR/Galpha locally to create the asymmetric forces that drive spindle movement. Results in C. elegans and other species are consistent with a novel model for receptor-independent activation of Galpha(i/o). signaling. C1 Massachusetts Gen Hosp, Ctr Canc, Cambridge, MA 02129 USA. RP van den Heuvel, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Cambridge, MA 02129 USA. RI van den Heuvel, Sander/B-8892-2011 FU NIGMS NIH HHS [GM57990-05, R01 GM057990] NR 40 TC 146 Z9 177 U1 0 U2 2 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 MAY 15 PY 2003 VL 17 IS 10 BP 1225 EP 1239 DI 10.1101/gad.1081203 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 679UU UT WOS:000182941000006 PM 12730122 ER PT J AU Liu, XZ Ouyang, XM Xia, XJ Zheng, J Pandya, A Li, F Du, LL Welch, KO Petit, C Smith, RJH Webb, BT Yan, D Arnos, KS Corey, D Dallos, P Nance, WE Chen, ZY AF Liu, XZ Ouyang, XM Xia, XJ Zheng, J Pandya, A Li, F Du, LL Welch, KO Petit, C Smith, RJH Webb, BT Yan, D Arnos, KS Corey, D Dallos, P Nance, WE Chen, ZY TI Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss SO HUMAN MOLECULAR GENETICS LA English DT Article ID OUTER HAIR-CELLS; RECESSIVE DEAFNESS; GENE; MUTATION; IDENTIFICATION; ABSENCE; 7Q31; FORM AB Prestin, a membrane protein that is highly and almost exclusively expressed in the outer hair cells (OHCs) of the cochlea, is a motor protein which senses membrane potential and drives rapid length changes in OHCs. Surprisingly, prestin is a member of a gene family, solute carrier (SLC) family 26, that encodes anion transporters and related proteins. Of nine known human genes in this family, three (SLC26A2, SLC26A3 and SLC26A4) are associated with different human hereditary diseases. The restricted expression of prestin in OHCs, and its proposed function as a mechanical amplifier, make it a strong candidate gene for human deafness. Here we report the cloning and characterization of four splicing isoforms for the human prestin gene (SLC26A5a, b, c and d). SLC26A5a is the predominant form of prestin whereas the others showed limited distribution associated with certain developmental stages. Based on the functional importance of prestin we screened for possible mutations involving the prestin gene in a group of deaf probands. We have identified a 5'-UTR splice acceptor mutation (IVS2-2A>G) in exon 3 of the prestin gene, which is responsible for recessive non-syndromic deafness in two unrelated families. In addition, a high frequency of heterozygosity for the same mutation was observed in these subjects, suggesting the possibility of semi-dominant influence of the mutation in causing hearing loss. Finally, the observation of this mutation only in the Caucasian probands indicated an association with a specific ethnic background. This study thereby reveals an essential function of prestin in human auditory processing. C1 Univ Miami, Dept Otolaryngol, Miami, FL 33101 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Human Genet, Richmond, VA 23298 USA. Northwestern Univ, Hugh Knowles Ctr, Dept Commun Sci & Disorders, Auditory Physiol Lab, Evanston, IL USA. Gallaudet Univ, Dept Biol, Washington, DC 20002 USA. Inst Pasteur, CNRS, URA 1968, Unite Genet Deficits Sensoriels, Paris, France. Univ Iowa, Dept Otolaryngol, Iowa City, IA 52242 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Liu, XZ (reprint author), Univ Miami, Dept Otolaryngol D48, 1666 NW 12th Ave, Miami, FL 33136 USA. RI Webb, Bradley/B-1459-2009; Zheng, Jing/F-5273-2017 OI Webb, Bradley/0000-0002-0576-5366; FU NIDCD NIH HHS [DC 05575, DC00089, DC02281, DC02842, DC04546] NR 23 TC 97 Z9 105 U1 5 U2 25 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 15 PY 2003 VL 12 IS 10 BP 1155 EP 1162 DI 10.1093/hmg/ddg127 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 679YU UT WOS:000182950200008 PM 12719379 ER PT J AU Talcott, JA AF Talcott, JA TI Quality of care in prostate cancer: Important to start and too important to stop here SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID RADICAL PROSTATECTOMY; OUTCOMES C1 Massachusetts Gen Hosp, Ctr Outcomes Res, MGH Canc Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Talcott, JA (reprint author), Massachusetts Gen Hosp, Ctr Outcomes Res, MGH Canc Ctr, Boston, MA 02114 USA. NR 11 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 MAY 15 PY 2003 VL 21 IS 10 BP 1902 EP 1903 DI 10.1200/JCO.2003.03.038 PG 2 WC Oncology SC Oncology GA 679CL UT WOS:000182903400002 PM 12743141 ER PT J AU Roach, M DeSilvio, M Lawton, C Uhl, V Machtay, M Seider, MJ Rotman, M Jones, C Asbell, SO Valicenti, RK Han, S Thomas, CR Shipley, WS AF Roach, M DeSilvio, M Lawton, C Uhl, V Machtay, M Seider, MJ Rotman, M Jones, C Asbell, SO Valicenti, RK Han, S Thomas, CR Shipley, WS TI Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation therapy oncology group 9413 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LONG-TERM SURVIVAL; DEFINITIVE RADIOTHERAPY; RADICAL PROSTATECTOMY; PREMENOPAUSAL WOMEN; CLINICAL STAGE; BREAST-CANCER; LYMPH-NODES; GROUP RTOG; RISK; DEPRIVATION AB Purpose: This trial tested the hypothesis that combined androgen suppression (CAS) and whole-pelvic (WP) radiotherapy (RT) followed by a boost to the prostate improves progression-free survival (PFS) by 10% compared with CAS and prostate-only (PO) RT. This trial also tested the hypothesis that neoadjuvant and concurrent hormonal therapy (NCHT) improves PFS compared with adjuvant hormonal therapy (AHT) by 10%. Materials and Methods: Eligibility included localized prostate cancer with an elevated prostate-specific antigen (PSA) less than or equal to 100 ng/mL and an estimated risk of lymph node (LN) involvement of 15%. Between April 1, 1995, and June 1, 1999, 1,323 patients were accrued. Patients were randomly assigned to WP + NCHT, PO + NCHT, WP + AHT, or PO + AHT. Failure for PFS was defined as the first occurrence of local, regional, or distant disease; PSA failure, or death for any cause. Results: With a median follow-up of 59.5 months, WP RT was associated with a 4-year PFS of 54% compared with 47% in patients treated with PO RT (P = .022). Patients treated with NCHT experienced a 4 year PFS of 52% versus 49% for AHT (P = .56). When comparing all four arms, there was a progression-free difference among VIP RT + NCHT, PO P-T + NCHT, WP RT + AHT, and PO RT + AHT (60% v 44% v 49% v 50%, respectively, P = AM). No survival advantage has yet been seen. Conclusion: WP RT + NCHT improves PFS compared with PO RT and NCHT or PO RT and AHT, and compared with WP RT + AHT in patients with a risk of LN involvement of 15%. (C) 2003 by American Society of Clinical Oncology. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Radiol Associates Sacramento, Sacramento, CA USA. Univ Penn, Albert Einstein Med Ctr, Radiat Therapy Oncol Grp Stat Headquarters, Philadelphia, PA 19104 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Akron City Hosp, Akron, OH USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. Wayne State Univ, Detroit, MI USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Roach, M (reprint author), Univ Calif San Francisco, 1600 Divisadero St,Suite H1031, San Francisco, CA 94143 USA. FU NCI NIH HHS [RTOG U10 CA21661]; ODCDC CDC HHS [CCOP U10 CA37422]; OHS HRSA HHS [STAT U10 CA32115] NR 34 TC 389 Z9 399 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 MAY 15 PY 2003 VL 21 IS 10 BP 1904 EP 1911 DI 10.1200/JCO.2003.05.004 PG 8 WC Oncology SC Oncology GA 679CL UT WOS:000182903400003 PM 12743142 ER PT J AU Smith, RS Chen, G Hudson, MM Link, MP Kun, L Weinstein, H Billett, A Marcus, KJ Tarbell, NJ Donaldson, SS AF Smith, RS Chen, G Hudson, MM Link, MP Kun, L Weinstein, H Billett, A Marcus, KJ Tarbell, NJ Donaldson, SS TI Prognostic factors for children with Hodgkin's disease treated with combined-modality therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LOW-DOSE RADIATION; INVOLVED-FIELD RADIOTHERAPY; PEDIATRIC-ONCOLOGY-GROUP; FRENCH-SOCIETY; INTERLEUKIN-10 LEVELS; MULTIVARIATE-ANALYSIS; PRIMARY CHEMOTHERAPY; SINGLE INSTITUTION; STAGE-I; TOXICITY AB Purpose: Evaluation of pretreatment factors to identify children at high risk for relapse after combined-modality therapy for Hodgkin's disease. Patients and Methods: From 1990 to 2000, 328 pediatric patients with clinical stage I to IV Hodgkin's disease were treated with chemotherapy and low-dose involved-field radiotherapy on prospective, collaborative, risk-adapted protocols at three institutions. Pretreatment factors were analyzed by univariate and multivariate analysis for prognostic significance for 5-year disease-free survival (DFS) and overall survival (OS). Results: With a median follow-up of 59 months (range, 9 to 125 months), the 5-year DFS and OS for all patients were 83% and 93%, respectively. Several factors were associated with inferior DFS and OS by univariate analysis. By multivariate, analysis, male sex, stage IIB, IIIB, or IV disease; bulky mediastinal disease, WBC more than 13.5 x 10(3)/mm(3); and hemoglobin less than 11.0 g/dL were significant for inferior DFS. A prognostic index was developed incorporating the five significant factors from the multivariate analysis, assigning each a score of 1. The 5-year DFS and OS for children with a prognostic score of 0 to 1 were 94% and 99%; score 2, 85% and 96%; score 3, 71% and 92%, and score 4 or 5, 49% and 72%, respectively. There was a significant difference in DFS among each of these groups, with significantly worse OS in those with a score of 4 to 5. Conclusion. A prognostic index that was based an five pretreatment factors correlated with inferior DFS by multivariate analysis stratified patients by outcome; this may be useful in assigning children with Hodgkin's disease to risk-adapted therapy. (C) 2003 by American Society of Clinical Oncology. C1 Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA USA. St Jude Childrens Res Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Radiat Oncol, Memphis, TN 38105 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp,Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp,Div Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. RP Smith, RS (reprint author), Mayo Clin, Dept Radiat Oncol, Immanuel St Josephs Hosp, 1025 Marsh St PO Box 8673, Mankato, MN 56002 USA. EM smith.ron@mayo.edu NR 40 TC 57 Z9 64 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 15 PY 2003 VL 21 IS 10 BP 2026 EP 2033 DI 10.1200/JCO.2003.07.12.4 PG 8 WC Oncology SC Oncology GA 679CL UT WOS:000182903400018 PM 12743158 ER PT J AU Hahn, WC AF Hahn, WC TI Role of telomeres and telomerase in the pathogenesis of human cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID CYTOTOXIC T-LYMPHOCYTES; TUMOR-ASSOCIATED ANTIGEN; CATALYTIC SUBUNIT GENE; HUMAN EPITHELIAL-CELLS; IMMORTAL HUMAN-CELLS; G-QUARTET FORMATION; REVERSE-TRANSCRIPTASE; LIFE-SPAN; IN-VITRO; DYSKERATOSIS-CONGENITA AB Specialized nucleoprotein structures, termed telomeres, cap the ends of human chromosomes. These terminal structures, composed of repetitive arrays of quanine-rich hexameric DNA together with specific telomere-binding proteins, play essential roles in protecting the chromosome from damage and degradation. In addition, several lines of evidence implicate telomere maintenance as an important regulator of cell life span. Activation of telomerase, a dedicated reverse transcriptase that synthesizes telomeric sequences, is strongly associated with cancer, and recent observations confirm that telomeres and telomerase perform important roles in both suppressing and facilitating malignant transformation. These dual functions of telomere biology are evident in the clinical manifestations of the multisystem syndrome, dyskeratosis congenita, forms of which display defects in telomerase function. Recent advances in our understanding of telomere biology indicate that the manipulation of telomeres and telomerase wilt lead to clinically significant applications in the diagnosis, prevention, and treatment of neoplastic disease. (C) 2003 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [K01 CA94223] NR 170 TC 93 Z9 113 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 MAY 15 PY 2003 VL 21 IS 10 BP 2034 EP 2043 DI 10.1200/JCO.2003.06.018 PG 10 WC Oncology SC Oncology GA 679CL UT WOS:000182903400019 PM 12743159 ER PT J AU Bar, M AF Bar, M TI A cortical mechanism for triggering top-down facilitation in visual object recognition SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Review ID PRIMATE PREFRONTAL CORTEX; SPATIAL-FREQUENCY CHANNELS; ORBITOFRONTAL CORTEX; RHESUS-MONKEY; INFEROTEMPORAL CORTEX; MACACA-FASCICULARIS; MEMORY RETRIEVAL; TEMPORAL CORTEX; MACAQUE MONKEY; SINGLE NEURONS AB The majority of the research related to visual recognition has so far focused on bottom-up analysis, where the input is processed in a cascade of cortical regions that analyze increasingly complex information. Gradually more studies emphasize the role of top-down facilitation in cortical analysis, but it remains something of a mystery how such processing would be initiated. After all, top-down facilitation implies that high-level information is activated earlier than some relevant lower-level information. Building on previous studies, I propose a specific mechanism for the activation of top-down facilitation during visual object recognition. The gist of this hypothesis is that a partially analyzed version of the input image (i.e., a blurred image) is projected rapidly from early visual areas directly to the prefrontal cortex (PFC). This coarse representation activates in the PFC expectations about the most likely interpretations of the input image, which are then back-projected as an "initial guess" to the temporal cortex to be integrated with the bottom-up analysis. The top-down process facilitates recognition by substantially limiting the number of object representations that need to be considered. Furthermore, such a rapid mechanism may provide critical information when a quick response is necessary. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Boston, MA 02129 USA. RP Bar, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, 149 13th St, Boston, MA 02129 USA. FU NINDS NIH HHS [R01 NS44319-01] NR 112 TC 420 Z9 430 U1 10 U2 34 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD MAY 15 PY 2003 VL 15 IS 4 BP 600 EP 609 DI 10.1162/089892903321662976 PG 10 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 674YT UT WOS:000182665800009 PM 12803970 ER PT J AU Means, TK Hayashi, F Smith, KD Aderem, A Luster, AD AF Means, TK Hayashi, F Smith, KD Aderem, A Luster, AD TI The toll-like receptor 5 stimulus bacterial flagellin induces maturation and chemokine production in human dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GRAM-NEGATIVE FLAGELLIN; INNATE IMMUNE-RESPONSE; CLASS-II COMPLEXES; NF-KAPPA-B; GENE-EXPRESSION; CUTTING EDGE; BLOOD MONOCYTES; ACTIVATION; INDUCTION; MICE AB Toll-like receptors (TLRs) are pattern recognition receptors that serve an important function in detecting pathogens and initiating inflammatory responses. Upon encounter with foreign Ag, dendritic cells (DCs) go through a maturation process characterized by an increase in surface expression of MHC class II and costimulatory molecules, which leads to initiation of an effective immune response in naive T cells. The innate immune response to bacterial flagellin is mediated by TLR5, which is expressed on human DCs. Therefore, we sought to investigate whether flagellin could induce DC maturation. Immature DCs were cultured in the absence or presence of flagellin and monitored for expression of cell surface maturation markers. Stimulation with flagellin induced increased surface expression of CD83, CD80, CD86, MHC class II, and the lymph node-homing chemokine receptor CCR7. Flagellin stimulated the expression of chemokines active on neutrophils (IL-8/CXC chemokine ligand (CXCL)8, GRO-alpha/ CXCL1, GRO-beta/CXCL2, GRO-gamma/CXCL3), monocytes (monocyte chemoattractant protein-1/CC chemokine ligand (CCL)2), and immature DCs (macrophage-inflammatory protein-1alpha/CCL3, macrophage-inflammatory protein-1beta/CCL4), but not chemokines active on effector T cells (IFN-inducible protein-10 kDa/CXCLIO, monokine induced by IFN-gamma/CXCL9, IFN-inducible T cell alpha chemoattractant/CXCL11). However, stimulating DCs with both flagellin and IFN-inducible protein-10 kDa, monokine induced by IFN-gamma, and IFN-inducible T cell alpha chemoattractant expression, whereas stimulation with IFN-beta or flagellin alone failed to induce these chemokines. In functional assays, flagellin-matured DCs displayed enhanced T cell stimulatory activity with a concomitant decrease in endocytic activity. Finally, DCs isolated from mouse spleens or bone marrows were shown to not express TLR5 and were not responsive to flagellin stimulation. These results demonstrate that flagellin can directly stimulate human but not murine DC maturation, providing an additional mechanism by which motile bacteria can initiate an acquired immune response. C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA. FU NHLBI NIH HHS [T32-HL07874]; NIAID NIH HHS [K08-AI01751, R01-AI052286, R01-AI32972, R01-AI40618, R37-AI025032]; NIAMS NIH HHS [T32-AR07258]; NIDDK NIH HHS [P01-DK50305] NR 57 TC 249 Z9 263 U1 5 U2 14 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2003 VL 170 IS 10 BP 5165 EP 5175 PG 11 WC Immunology SC Immunology GA 676NJ UT WOS:000182758200036 PM 12734364 ER PT J AU Nau, GJ Schlesinger, A Richmond, JFL Young, RA AF Nau, GJ Schlesinger, A Richmond, JFL Young, RA TI Cumulative toll-like receptor activation in human macrophages treated with whole bacteria SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL WALL COMPONENTS; GENE-EXPRESSION; CUTTING EDGE; LIPOTEICHOIC ACID; INTERFERON-GAMMA; DENDRITIC CELLS; INNATE; TLR4; LIPOPOLYSACCHARIDE; INTERLEUKIN-12 AB Purified components from bacteria selectively activate Toll-like receptors (TLR), leading to shared and unique responses in innate immune cells. Whole bacteria contain agonists for multiple TLR and induce a common macrophage activation program of transcription. It is not known, however, whether the stimulation of specific TLR by whole bacteria results in differential activation of the innate immune system. We evaluated gene expression data from human macrophages and found a unique gene expression, profile induced by Gram-negative bacteria. In contrast, Gram-positive bacteria evoked few specific alterations in gene expression. LPS, a TLR4-specific ligand, was sufficient to elicit the distinct expression profile observed with Gram-negative bacteria. TLR4 activation regulated gene expression by both an IFN-dependent and an IFN-independent mechanism, illustrated by I-TAC and IL-12 p70, respectively. IL-12 p70 was produced by cells in whole blood exposed to Gram-negative bacteria, demonstrating faithful reproduction of the macrophage response in mixed populations of cells and identifying a potential diagnostic marker of infection. Our results show that the macrophage response to bacteria is dominated by the accumulated input from multiple TLR. For macrophages exposed to Gram-negative bacteria, gene expression changes encompass those induced by Gram-positive bacteria plus a distinct TLR4 response. This distinct TLR4 response may provide the basis to diagnose clinical Gram-negative infections. C1 Whitehead Inst, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Young, RA (reprint author), Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA. RI Young, Richard/F-6495-2012; OI Young, Richard/0000-0001-8855-8647; Nau, Gerard/0000-0001-7921-8317 NR 29 TC 71 Z9 75 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2003 VL 170 IS 10 BP 5203 EP 5209 PG 7 WC Immunology SC Immunology GA 676NJ UT WOS:000182758200040 PM 12734368 ER PT J AU Lee, JS Frevert, CW Wurfel, MM Peiper, SC Wong, VA Ballman, KK Ruzinski, JT Rhim, JS Martin, TR Goodman, RB AF Lee, JS Frevert, CW Wurfel, MM Peiper, SC Wong, VA Ballman, KK Ruzinski, JT Rhim, JS Martin, TR Goodman, RB TI Duffy antigen facilitates movement of chemokine across the endothelium in vitro and promotes neutrophil transmigration in vitro and in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BLOOD-GROUP ANTIGEN; RECEPTOR; CELLS; EXPRESSION; GENE; IDENTIFICATION; INDIVIDUALS; ENDOTOXIN; MIGRATION; SURFACE AB The Duffy Ag expressed on RBCs, capillaries, and postcapillary venular endothelial cells binds selective CXC and CC chemokines with high affinity. Cells transfected with the Duffy Ag internalize but do not degrade chemokine ligand. It has been proposed that Duffy Ag transports chemokines across the endothelium. We hypothesized that Duffy Ag participates in the movement of chemokines across the endothelium and, by doing so, modifies neutrophil transmigration. We found that the Duffy Ag transfected into human endothelial cells facilitates movement of the radiolabeled CXC chemokine, growth related oncogene-alpha/CXC chemokine ligand 1 (GRO-alpha/CXCL1), across an endothelial monolayer. In addition, neutrophil migration toward GRO-alpha/CXCL1 and IL-8 (IL-8/CXCL8) was enhanced across an endothelial monolayer expressing the Duffy Ag. Furthermore, GRO-alpha/CXCL1 stimulation of endothelial cells expressing the Duffy Ag did not affect gene expression by oligonucleotide microarray analysis. These in vitro observations are supported by the finding that IL-8/CXCL8-driven neutrophil recruitment into the lungs was markedly attenuated in transgenic mice lacking the Duffy Ag. We conclude that Duffy Ag has a role in enhancing leukocyte recruitment to sites of inflammation by facilitating movement of chemokines across the endothelium. C1 Vet Affairs Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Div Pulm & Crit Care Med, Dept Med, Seattle, WA 98108 USA. Med Coll Georgia, Dept Pathol, Augusta, GA 30912 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Bethesda, MD 20814 USA. RP Goodman, RB (reprint author), Seattle Vet Affairs Med Ctr, S-111 Pulm,1660 S Columbian Way, Seattle, WA 98108 USA. FU NHLBI NIH HHS [F32 HL010470, K08 HL070178, K08 HL070178-01, HL70178, F32 HL010470-02, R01 HL069955, HL30542, HL69955] NR 28 TC 90 Z9 96 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2003 VL 170 IS 10 BP 5244 EP 5251 PG 8 WC Immunology SC Immunology GA 676NJ UT WOS:000182758200045 PM 12734373 ER PT J AU Jin, SX Zhuang, ZY Woolf, CJ Ji, RR AF Jin, SX Zhuang, ZY Woolf, CJ Ji, RR TI P38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain SO JOURNAL OF NEUROSCIENCE LA English DT Article DE p38 MAPK; neuropathic pain; microglia; spinal cord; dorsal root ganglion; spinal nerve ligation ID SIGNAL-REGULATED KINASE; PRIMARY SENSORY NEURONS; GLIAL ACTIVATION; INFLAMMATORY PAIN; PATHOLOGICAL PAIN; UP-REGULATION; RAT; EXPRESSION; HYPERALGESIA; AXOTOMY AB The possible involvement of p38 mitogen-activated protein kinase activation in spinal cord and dorsal root ganglion (DRG) cells in the development of peripheral neuropathic pain has been explored. Ligation of the L5 spinal nerve ( SNL) on one side in adult rats produces an early onset and long-lasting mechanical allodynia. This lesion results in activation of p38 in the L5 segment of the spinal cord, most prominently in the ipsilateral dorsal horn, starting soon after the lesion (< 1 d) and persisting for >3 weeks. The activated p38 in the spinal cord is restricted entirely to microglia; phospho-p38 colocalizes only with the microglial marker OX-42 and not with either the neuronal marker neuronal-specific nuclear protein or the astrocyte marker GFAP. In contrast, SNL induces a delayed ( > 3 d) activation of p38 in the L5 DRG that occurs predominantly in neurons. Continuous injection of the p38 inhibitor 4-(4- fluorophenyl)-2-(4-methylsulfonylphenyl)- 5-(4-pyridyl)-1H-imidazole (SB203580) via the intrathecal route, starting before the SNL surgery, reduces SNL-induced mechanical allodynia from day 1 to day 10, with maximal effects at early time points. Post-treatment with SB203580 starting on day 1 or on day 10 after surgery also reduces established mechanical allodynia. Because the reduction in neuropathic pain by p38 inhibition occurs before the appearance of p38 activation in DRG neurons, p38 activation in spinal cord microglia is likely to have a substantial role in the earliest phase of neuropathic pain. Coactivation of p38 in DRG neurons and spinal microglia may contribute to later phases of neuropathic pain. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Ji, RR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Neural Plast Res Grp, 149 13th St,Room 4309, Charlestown, MA 02129 USA. OI Ji, Ru-Rong/0000-0002-9355-3688 FU NINDS NIH HHS [R01 NS040698, R01NS 40698] NR 32 TC 507 Z9 550 U1 4 U2 23 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 MAY 15 PY 2003 VL 23 IS 10 BP 4017 EP 4022 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 681AT UT WOS:000183014300009 PM 12764087 ER PT J AU Meyers, JR MacDonald, RB Duggan, A Lenzi, D Standaert, DG Corwin, JT Corey, DP AF Meyers, JR MacDonald, RB Duggan, A Lenzi, D Standaert, DG Corwin, JT Corey, DP TI Lighting up the senses: FM1-43 loading of sensory cells through nonselective ion channels SO JOURNAL OF NEUROSCIENCE LA English DT Article DE FM1-43; hair cell; vanilloid receptor; purinergic receptor; Merkel cells; DRG; nociceptors; TRP channels; sensory ganglia ID P2X RECEPTOR IMMUNOREACTIVITY; SACCULAR HAIR-CELLS; ADAPTING TYPE-I; VANILLOID RECEPTOR; MERKEL CELLS; MECHANOELECTRICAL-TRANSDUCTION; TASTE TRANSDUCTION; DYE FM1-43; INNER-EAR; RAT AB We describe a novel mechanism for vital fluorescent dye entry into sensory cells and neurons: permeation through ion channels. In addition to the slow conventional uptake of styryl dyes by endocytosis, small styryl dyes such as FM1-43 rapidly and specifically label hair cells in the inner ear by entering through open mechanotransduction channels. This labeling can be blocked by pharmacological or mechanical closing of the channels. This phenomenon is not limited to hair cell transduction channels, because human embryonic kidney 293T cells expressing the vanilloid receptor (TRPV1) or a purinergic receptor (P2X2) rapidly take up FM1-43 when those receptor channels are opened and not when they are pharmacologically blocked. This channel permeation mechanism can also be used to label many sensory cell types in vivo. A single subcutaneous injection of FM1-43 ( 3 mg/kg body weight) in mice brightly labels hair cells, Merkel cells, muscle spindles, taste buds, enteric neurons, and primary sensory neurons within the cranial and dorsal root ganglia, persisting for several weeks. The pattern of labeling is specific; nonsensory cells and neurons remain unlabeled. The labeling of the sensory neurons requires dye entry through the sensory terminal, consistent with permeation through the sensory channels. This suggests that organic cationic dyes are able to pass through a number of different sensory channels. The bright and specific labeling with styryl dyes provides a novel way to study sensory cells and neurons in vivo and in vitro, and it offers new opportunities for visually assaying sensory channel function. C1 Univ Virginia, Sch Med, Grad Program Neurosci, Charlottesville, VA 22908 USA. Univ Virginia, Sch Med, Dept Otolaryngol Head & Neck Surg, Charlottesville, VA 22908 USA. Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA. MIT, Hlth Sci & Technol Program, Program Speech & Hearing Sci, Boston, MA 02139 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Neurol Serv, Boston, MA 02114 USA. RP Meyers, JR (reprint author), Univ Virginia, Sch Med, Grad Program Neurosci, MR 4,Room 5148,HSC Box 801392, Charlottesville, VA 22908 USA. OI Corey, David/0000-0003-4497-6016; Standaert, David/0000-0003-2921-8348 FU NIDCD NIH HHS [R01-DC00200, R01-DC00304] NR 60 TC 273 Z9 281 U1 1 U2 15 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 MAY 15 PY 2003 VL 23 IS 10 BP 4054 EP 4065 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 681AT UT WOS:000183014300014 PM 12764092 ER PT J AU Trail, M Nelson, ND Van, JN Appel, SH Lai, EC AF Trail, M Nelson, ND Van, JN Appel, SH Lai, EC TI A study comparing patients with amyotrophic lateral sclerosis and their caregivers on measures of quality of life, depression, and their attitudes toward treatment options SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE amyotrophic lateral sclerosis; quality of life; caregiver; depression; palliative care; treatment choices ID OF-LIFE; PHYSICAL FUNCTION; ALS; SURVIVAL AB Objective: To compare amyotrophic lateral sclerosis (ALS) patients and their caregivers on measures of quality of life (QOL), depression, and their attitudes toward treatment options. Methods: Over a 14-month period, we analyzed responses from 27 ALS patients and 19 ALS caregivers as they arrived at the Department of Neurology, Baylor College of Medicine, Vicki Appel MDA, ALS Clinic, and those who completed the study measures. Patients were given the Appel ALS Rating Scale (AALS), the ALS Functional Rating Scale (ALSFRS), McGill Quality of Life Questionnaire Single-Item Scale (MQOL-SIS), and the Beck Depression Inventory-II (BDI-II). An internally generated scale of 1-7 was used to measure perception of emotional support, QOL for others (i.e., the patient's perception of the caregiver's QOL and the caregiver's perception of the patient's QOL), and experience of pain. Attitudes toward treatment options were assessed by yes/ no/uncertain responses. Caregivers were administered all of the above measures except the AALS, ALSFRS, and pain scale. Percentage, mean, and standard deviation values were determined. Significance levels were also calculated. Results: Twenty-seven patients with a mean age of 57.2 (range 34-81) years and nineteen caregivers with a mean age of 56:9 (range 28-82) years completed the study. The patients were of moderate disease severity with a mean AALS total score of 76.3 (range 39-134) and a mean ALSFRS score of 28.4 (range 12-40). The mean rating of QOL for patients was 5.9 and the mean rating of QOL for caregivers was 5.7 (range 1-7). The patients reported slightly less depression (9.8) than their caregivers (10.7) (range 0-63). There was, however, no significant difference between patients and caregivers on scores of QOL and depression. Patients tended to overestimate caregivers' QOL by a small degree, whereas caregivers tended to underestimate the patients' QOL by a greater degree. Over one-half of both groups would consider percutaneous esophageal gastrostomy (PEG) placement. Patient and caregiver responses to the use of BIPAP differed. Though over half of both groups endorsed the idea of future BIPAP use, more patients (41%) than caregivers (5%) were uncertain. Only 3% of patients responded negatively compared to 32% of caregivers. Both groups were only minimally interested in future invasive ventilation. Discussion: Factors contributing to quality of life, depression, and attitudes toward treatment options need to be periodically explored with patients and caregivers throughout the course of the illness. Health care professionals should recognize that the needs and goals of the two groups might differ. For both patients and caregivers, health care professionals should provide education and opportunities for discussion centered on the issues followed by referrals and interventions appropriate to the situation. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. VA Med Ctr, Neurol Care Line, Houston, TX USA. RP Lai, EC (reprint author), Baylor Coll Med, Dept Neurol, 6550 Fannin,Suite 1801, Houston, TX 77030 USA. NR 22 TC 83 Z9 85 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD MAY 15 PY 2003 VL 209 IS 1-2 BP 79 EP 85 DI 10.1016/S0022-510X(03)00003-0 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 672VN UT WOS:000182543800014 PM 12686407 ER PT J AU Kronenberg, HM AF Kronenberg, HM TI Developmental regulation of the growth plate SO NATURE LA English DT Review ID HORMONE-RELATED PEPTIDE; ENDOCHONDRAL BONE-DEVELOPMENT; PARATHYROID-HORMONE; INDIAN HEDGEHOG; CHONDROCYTE DIFFERENTIATION; CBFA1-DEFICIENT MICE; TARGETED DISRUPTION; FACTOR RECEPTOR-3; JOINT FORMATION; MOUSE LIMB AB Vertebrates do not look like jellyfish because the bones of their skeletons are levers that allow movement and protect vital organs. Bones come in an enormous variety of shapes and sizes to accomplish these goals, but, with few exceptions, use one process endochondral bone formation to generate the skeleton. The past few years have seen an enormous increase in understanding of the signalling pathways and the transcription factors that control endochondral bone development. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 38 TC 1245 Z9 1312 U1 9 U2 90 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 15 PY 2003 VL 423 IS 6937 BP 332 EP 336 DI 10.1038/nature01657 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 678EX UT WOS:000182853100053 PM 12748651 ER PT J AU Fleming, CM Shepard, JAO Mark, EJ Scully, RE Wright, CD AF Fleming, CM Shepard, JAO Mark, EJ Scully, RE Wright, CD TI Case 15-2003: A 47-year-old man with waxing and waning pulmonary nodules five years after treatment for testicular seminoma - Bronchiolitis obliterans with organizing pneumonia due to gastroesophageal reflux and occult aspiration SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID HIGH-RESOLUTION CT; LANGERHANS-CELL HISTIOCYTOSIS; HALO SIGN; LUNG; GRANULOMATOSIS; SARCOIDOSIS; FEATURES; RECIPIENTS; METASTASES; DISEASE C1 Massachusetts Gen Hosp, Div Pulm Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Thorac 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 Fleming, CM (reprint author), Massachusetts Gen Hosp, Div Pulm Med, Boston, MA 02114 USA. NR 35 TC 10 Z9 13 U1 0 U2 1 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 MAY 15 PY 2003 VL 348 IS 20 BP 2019 EP 2027 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 677TJ UT WOS:000182823400011 PM 12748318 ER PT J AU Garraway, LA Lin, D Signoretti, S Waltregny, D Dilks, J Bhattacharya, N Loda, M AF Garraway, LA Lin, D Signoretti, S Waltregny, D Dilks, J Bhattacharya, N Loda, M TI Intermediate basal cells of the prostate: In vitro and in vivo characterization SO PROSTATE LA English DT Article DE prostate; PrEC; stem cells; p63; differentiation; basal cells; involucrin ID ANDROGEN RECEPTOR EXPRESSION; HYPERPLASTIC HUMAN PROSTATE; EPITHELIAL-CELLS; VENTRAL PROSTATE; RETINOIC ACID; RAT PROSTATE; SQUAMOUS DIFFERENTIATION; GROWTH-FACTORS; LUMINAL CELLS; ORGAN-CULTURE AB BACKGROUND. Progenitor cells within the prostate basal layer may play important roles in differentiation and carcinogenesis; however, prostate stem cell populations remain uncharacterized. METHODS. Immunohistochemical and immunoblot analyses were used to characterize prostate epithelial cells (PrEC), a commercially available prostate basal cell isolate. RESULTS. Proliferating PrECs exhibited immunophenotypic characteristics most consistent with basal cells, but during senescence PrECs up-regulated androgen receptor (AR) mRNA, p27, and low-molecular-weight cytokeratin (LMWCK) expression, suggestive of partial differentiation. PrECs also stained strongly for involucrin, which marked a subset of intermediate prostate basal cells in vivo. Basal hyperplasia consisting of involucrin-positive cells was prevalent in prostate tissue from androgen-ablated patients, and formed epithelial clusters flanked by involucrin-negative basal and luminal monolayers. Cultivation of PrECs on matrigel together with androgen-treated stromal conditioned media resulted in dense aggregates, with a peripheral rim of basal-like cells expressing p63 and basal cytokeratins. CONCLUSIONS. PrEC represents an epithelial population whose basal characteristics are modified in response to matrigel, stromal factors, and senescence, consistent with a transient amplifying population. These cells may derive from a previously unrecognized, involucrin-positive subset present in vivo. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Liege, Univ Hosp, Metastasis Res Lab, Liege, Belgium. RP Loda, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D740, Boston, MA 02115 USA. FU NCI NIH HHS [R01-CA81755] NR 59 TC 73 Z9 76 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 MAY 15 PY 2003 VL 55 IS 3 BP 206 EP 218 DI 10.1002/pros.10244 PG 13 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 675DE UT WOS:000182677100007 PM 12692787 ER PT J AU Kaplan-Lefko, PJ Chen, TM Ittmann, MM Barrios, RJ Ayala, GE Huss, WJ Maddison, LA Foster, BA Greenberg, NM AF Kaplan-Lefko, PJ Chen, TM Ittmann, MM Barrios, RJ Ayala, GE Huss, WJ Maddison, LA Foster, BA Greenberg, NM TI Pathobiology of autochthonous prostate cancer in a pre-clinical transgenic mouse model SO PROSTATE LA English DT Article DE TRAMP; pathology; prostate cancer; pre-clinical trials ID E-CADHERIN EXPRESSION; TRAMP MODEL; NEUROENDOCRINE DIFFERENTIATION; TUMOR-CELLS; PROGRESSION; MICE; ADENOCARCINOMA; CARCINOGENESIS; CARCINOMA; CHEMOPREVENTION AB BACKGROUND. Animal models that closely mimic clinical disease can be exploited to hasten the pace of translational research. To this end, we have defined windows of opportunity in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model of prostate cancer as a paradigm for designing pre-clinical trials. METHODS. The incidence of cancer, metastasis, and distribution of pathology were examined as a function of time in TRAMP mice. The expression of various markers of differentiation were characterized. RESULTS. The TRAMP model develops progressive, multifocal, and heterogeneous disease. Each lobe of the prostate progressed at a different rate. Cytokeratin 8, E-cadherin, and androgen receptor (AR) were expressed during cancer progression but levels were reduced or absent in late stage disease. A distinct epithelial to neuroendocrine (ENT) shift was observed to be a stochastic event related to prostate cancer progression in TRAMP. CONCLUSIONS. This study will serve as the basis for the rational design of pre-clinical studies with genetically engineered mouse models. (C) 2003 Wiley-Liss, Inc. C1 Dept Mol & Cellular Biol, Houston, TX 77030 USA. Scott Dept Urol, Houston, TX USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Houston Dept Vet Affairs Med Ctr, Houston, TX USA. Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA. RP Greenberg, NM (reprint author), Dept Mol & Cellular Biol, 1 Baylor Plaza, Houston, TX 77030 USA. FU NCI NIH HHS [U01 CA84296] NR 48 TC 277 Z9 284 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 0270-4137 J9 PROSTATE JI Prostate PD MAY 15 PY 2003 VL 55 IS 3 BP 219 EP 237 DI 10.1002/pros.10215 PG 19 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 675DE UT WOS:000182677100008 PM 12692788 ER PT J AU Reeve, JR Keire, DA Coskun, T Green, GM Evans, C Ho, FJ Lee, TD Davis, MT Shively, JE Solomon, TE AF Reeve, JR Keire, DA Coskun, T Green, GM Evans, C Ho, FJ Lee, TD Davis, MT Shively, JE Solomon, TE TI Synthesis of biologically active canine CCK-58 SO REGULATORY PEPTIDES LA English DT Article DE cholecystokinin; pancreatic secretion; molecular forms; peptide synthesis; amylase secretion; pancreatic fluid secretion ID PANCREATIC DUCT CELLS; DIFFERENT CONFORMATIONS; HUMAN-PLASMA; CHOLECYSTOKININ; RATS; IMMUNOREACTIVITY; SECRETION; BINDING; ANALOGS; CALCIUM AB The carboxyl terminal octapeptide of cholecystokinin (CCK-8) has been hypothesized to account for the bioactivity of all the molecular forms of cholecystokinin. However, the physiological relevance of CCK-58 has not been rigorously examined because of the lack of sufficient amounts of the peptide and concerns about inactivation of natural peptides during their purification. Therefore, canine-sulfated CCK-58 was synthesized and conditions determined for its unblocking and purification that preserved the sulfated tyrosine. Synthetic CCK-58 was indistinguishable from natural CCK-58 by amino acid analysis and by mass spectrometry. Synthetic CCK-58 and CCK-8 have different patterns of pancreatic stimulation: both caused a dose-related increase in amylase release, while only CCK-58 stimulated bile-pancreatic output volume. Thus, CCK-58 and CCK-8 are biased agonists at the CCK-A receptor (they have distinct patterns of action mediated by the same receptor). Previous work has demonstrated that the identical carboxyl termini of CCK-8 and CCK-58 have different solution conformations. Taken together, the physiological and structural results support the hypothesis that different carboxyl terminal conformations of CCK-58 and CCK-8 alter the expression of their biological activity. (C) 2003 Elsevier Science B.V. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, Res Serv 151, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA 90024 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Univ Calif Los Angeles, NPI, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. City Hope Natl Med Ctr, Beckman Res Inst, Div Immunol, Duarte, CA 91010 USA. RP Reeve, JR (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv 151, CURE Digest Dis Res Ctr, Bldg 115,Rm 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [CA3572]; NCRR NIH HHS [R01-RR06217]; NIDDK NIH HHS [DK-41301, R01-DK38626, R01- DK33580, R01-DK37482] NR 33 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD MAY 15 PY 2003 VL 113 IS 1-3 BP 71 EP 77 DI 10.1016/S0167-0115(02)00301-4 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 674GD UT WOS:000182628300009 PM 12686463 ER PT J AU Keire, DA Wu, SV Diehl, DL Chew, P Ho, FJ Davis, MT Lee, TD Shively, JE Walsh, JH Reeve, JR AF Keire, DA Wu, SV Diehl, DL Chew, P Ho, FJ Davis, MT Lee, TD Shively, JE Walsh, JH Reeve, JR TI Rat progastrin processing yields peptides with altered potency at the CCK-B receptor SO REGULATORY PEPTIDES LA English DT Article DE gastrin-16; sulfated and nonsulfated gastrin; DPP IV; pyroglutamate ID GLYCINE-EXTENDED PROGASTRIN; GASTRIN PRECURSOR; GROWTH; CHOLECYSTOKININ; SULFATION; ACID; BRADYKININ; METABOLISM; MODULATION; RELEASE AB Details of prohormone processing patterns are revealed by purification and characterization of molecular forms stored in the tissues where the hormones are expressed. Molecular forms of rat gastrin were purified from antral extracts by gel permeation anion exchange, and reverse-phase HPLC. Amidated and glycine-extended gastrins were detected with specific antisera and their structures determined by mass spectrometry. In rats, the only form shorter than gastrin-.17 observed contained 16 amino acids. These data suggest that two enzymes process the amino terminus of gastrin-17. Pyrrolidone carboxylic acid peptidase removes the amino terminal pyrrolidone carboxylic acid (pyroGlu), forming gastrin-16. In mammals other than rat, gastrin-16 is then cleaved by dipeptidyl peptidase IV to form gastrin-14. In rat, this reaction does not take place because of proline residues PrO2-PrO3 - in gastrin-16. Gastrin-16 is found in sulfated and nonsulfated forms and comprises 28% of the total gastrin immunoreactivity. Glycine-extended forms of gastrin-16 and gastrin-17 comprises 45% of the total gastrin immunoreactivity. The sulfated forms of gastrin-16 and gastrin-17 bind to the CCK-B receptor transfected into CHO cells with 10-fold higher affinity than the nonsulfated forms of these peptides. Therefore, processing of rat progastrin may modulate the expression of gastrin biological activity. (C) 2003 Elsevier Science B.V. All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, CURE UCLA Digest Dis Res Ctr, Los Angeles, CA 90073 USA. City Hope Res Inst, Beckman Res Inst, Duarte, CA 91010 USA. RP Reeve, JR (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE UCLA Digest Dis Res Ctr, Bldg 115,Room 117B,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. OI Diehl, David/0000-0003-4128-3839 FU NIDDK NIH HHS [DK33850, DK41301, DK17294] NR 36 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD MAY 15 PY 2003 VL 113 IS 1-3 BP 115 EP 124 DI 10.1016/S0167-0115(03)00005-3 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 674GD UT WOS:000182628300016 PM 12686470 ER PT J AU Chen, CY Doong, ML Rivier, JE Tache, Y AF Chen, CY Doong, ML Rivier, JE Tache, Y TI Intravenous urocortin II decreases blood pressure through CRF2 receptor in rats SO REGULATORY PEPTIDES LA English DT Article DE blood pressure; CRF2 receptor; human urocortin II; hypotension; RX-77368; urocortin; astressin(2)-B; rats ID CORTICOTROPIN-RELEASING-FACTOR; HORMONE-RECEPTOR; PEPTIDE; MICE; MECHANISMS; ARTERIES; STRESS; TYPE-2; FAMILY; ANTAGONISTS AB Urocortin II (Ucn II) is a new member of the corticotropin-releasing factor (CRF) family that binds selectively to the CRF subtype 2 receptor (CRF2). CRF or urocortin injected intravenously (iv) induced hypotension. We investigated the influence of iv human Ucn II (hUcn II) on basal mean blood pressure (MAP) and on the sympathetic mediated hypertensive response to TRH analog, RX-77368 injected intracisternally (ic) 20 min after hUcn II in urethane-anesthetized rats. Ucn II (3, 10, and 30 mug/kg, iv) significantly decreased basal MAP from baseline by - 20.9 +/- 6.5, - 21.3 +/- 5.4 and - 46.8 +/- 6.5 min Hg, respectively, after 10 min. RX-77368 (30 ng, ic) elevated MAP for over 90 min with a maximal hypertensive response at 20 min. Ucn II (3, 10, and 30 mug/kg, iv) did not alter the 20 min net rise in MAP induced by RX-77368 (35.7 +/- 7.1, 32.6 +/- 3.3 and 24.6 +/- 6.9 min Hg, respectively) compared with vehicle (33.6 +/- 4.3 min Hg). The selective CRF, antagonist, astressin(2)-B (60 mug/kg, iv) abolished hUcn II hypotensive action while having no effect on basal MAP. These data show that iv hUcn II induces hypotension through peripheral CRF2 receptor while not altering the responsiveness to sympathetic nervous system-mediated rise in MAP. (C) 2003 Elsevier Science B.V All rights reserved. C1 Univ Calif Los Angeles, Dept Med, Div Digest Dis,CURE Digest Dis Res Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, San Diego, CA 92186 USA. RP Tache, Y (reprint author), Univ Calif Los Angeles, Dept Med, Div Digest Dis,CURE Digest Dis Res Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Bldg 115,Room No 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-41301, DK-57238] NR 34 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD MAY 15 PY 2003 VL 113 IS 1-3 BP 125 EP 130 DI 10.1016/S0167-0115(03)00003-X PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 674GD UT WOS:000182628300017 PM 12686471 ER PT J AU Alessi, CA Martin, JL Webber, AP AF Alessi, CA Martin, JL Webber, AP TI Randomized controlled trial of nonpharmacological interventions on sleep in nursing home residents SO SLEEP LA English DT Meeting Abstract CT 17th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 03-08, 2003 CL CHICAGO, ILLINOIS SP Assoc Prof Sleep Soc C1 GRECC, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 15 PY 2003 VL 26 BP A158 EP A158 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 677ZY UT WOS:000182841100394 ER PT J AU Atwood, CW Shalaby, A Hartley, J Stahmann, J Ni, Q Lee, K AF Atwood, CW Shalaby, A Hartley, J Stahmann, J Ni, Q Lee, K TI Detection of sleep disordered breathing using implanted cardiac pacemakers SO SLEEP LA English DT Meeting Abstract CT 17th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 03-08, 2003 CL CHICAGO, ILLINOIS SP Assoc Prof Sleep Soc C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 15 PY 2003 VL 26 BP A229 EP A230 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 677ZY UT WOS:000182841100573 ER PT J AU Davis, HC Lenconi, MA Maglioni, ML Marmar, CR Neylan, TC AF Davis, HC Lenconi, MA Maglioni, ML Marmar, CR Neylan, TC TI Mood and PTSD symptom correlates with polysomnography and actigraphy SO SLEEP LA English DT Meeting Abstract CT 17th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 03-08, 2003 CL CHICAGO, ILLINOIS SP Assoc Prof Sleep Soc C1 San Francisco State Univ, San Francisco, CA USA. San Francisco Vet Adm Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 15 PY 2003 VL 26 BP A381 EP A381 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 677ZY UT WOS:000182841100960 ER PT J AU Gong, H Angara, C Stewart, D McGinty, D Szymusiak, R AF Gong, H Angara, C Stewart, D McGinty, D Szymusiak, R TI Projections from sleep-regulatory regions of the preoptic area to the perifornical lateral hypothalamus SO SLEEP LA English DT Meeting Abstract CT 17th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 03-08, 2003 CL CHICAGO, ILLINOIS SP Assoc Prof Sleep Soc C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 15 PY 2003 VL 26 BP A18 EP A19 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 677ZY UT WOS:000182841100046 ER PT J AU Hirshkowitz, M Raj, R Sharafkhaneh, A AF Hirshkowitz, M Raj, R Sharafkhaneh, A TI Improved alertness in CPAP-treated patients not meeting new medicare criteria for CPAP SO SLEEP LA English DT Meeting Abstract CT 17th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 03-08, 2003 CL CHICAGO, ILLINOIS SP Assoc Prof Sleep Soc C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 15 PY 2003 VL 26 BP A215 EP A216 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 677ZY UT WOS:000182841100536 ER PT J AU Mileykovskiy, BY Kiyashchenko, LI Siegel, JM AF Mileykovskiy, BY Kiyashchenko, LI Siegel, JM TI Activity of somatosensory neurons of the inferior olive across sleep-wake (S-W) cycle SO SLEEP LA English DT Meeting Abstract CT 17th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 03-08, 2003 CL CHICAGO, ILLINOIS SP Assoc Prof Sleep Soc C1 Vet Adm Greater Los Angeles Healthcare Syst, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Sepulveda, CA 91343 USA. Russian Acad Sci, Inst Evolutionary Physiol & Biochem, St Petersburg 194223, Russia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 15 PY 2003 VL 26 BP A26 EP A27 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 677ZY UT WOS:000182841100065 ER PT J AU Riggs, RL Partridge, A Winer, E Arnedt, JT Aloia, MS AF Riggs, RL Partridge, A Winer, E Arnedt, JT Aloia, MS TI Sleep complaints among breast cancer survivors SO SLEEP LA English DT Meeting Abstract CT 17th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 03-08, 2003 CL CHICAGO, ILLINOIS SP Assoc Prof Sleep Soc C1 Brown Univ, Sch Med, Providence, RI 02912 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 15 PY 2003 VL 26 BP A360 EP A361 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 677ZY UT WOS:000182841100910 ER PT J AU Ross, RJ Morrison, AR Sanford, LD Jha, SK AF Ross, RJ Morrison, AR Sanford, LD Jha, SK TI Suppression of REM sleep in rats recorded in a fearful context SO SLEEP LA English DT Meeting Abstract CT 17th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 03-08, 2003 CL CHICAGO, ILLINOIS SP Assoc Prof Sleep Soc C1 Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 15 PY 2003 VL 26 BP A443 EP A443 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 677ZY UT WOS:000182841101116 ER PT J AU Sharafkhaneh, A Richardson, P Hirshkowitz, M AF Sharafkhaneh, A Richardson, P Hirshkowitz, M TI Sleep related breathing disorders in veteran beneficiaries SO SLEEP LA English DT Meeting Abstract CT 17th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 03-08, 2003 CL CHICAGO, ILLINOIS SP Assoc Prof Sleep Soc C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 15 PY 2003 VL 26 BP A236 EP A236 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 677ZY UT WOS:000182841100590 ER PT J AU Stickgold, R Cain, M Goff, DC Manoach, DS AF Stickgold, R Cain, M Goff, DC Manoach, DS TI Schizophrenic patients do not show sleep-dependent motor skill learning SO SLEEP LA English DT Meeting Abstract CT 17th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 03-08, 2003 CL CHICAGO, ILLINOIS SP Assoc Prof Sleep Soc C1 Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Athinoula A Maritinos Ctr Biomed Imaging, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 15 PY 2003 VL 26 BP A444 EP A445 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 677ZY UT WOS:000182841101120 ER PT J AU Strecker, RE Thakkar, MM McKenna, JT McGuire, M Mulkern, KJ Dauphin, LJ Stronge, AM Mello, E McCarley, LL AF Strecker, RE Thakkar, MM McKenna, JT McGuire, M Mulkern, KJ Dauphin, LJ Stronge, AM Mello, E McCarley, LL TI The use of rat models to investigate the behavioral and neurobiological consequences of sleep apnea SO SLEEP LA English DT Meeting Abstract CT 17th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 03-08, 2003 CL CHICAGO, ILLINOIS SP Assoc Prof Sleep Soc C1 Harvard Univ, Med Sch, Dept Psychiat, Brockton, MA 02301 USA. Harvard Univ, Med Sch, Dept Med, Brockton, MA 02301 USA. VA Boston Healthcare Syst, Brockton, MA 02301 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 15 PY 2003 VL 26 BP A12 EP A12 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 677ZY UT WOS:000182841100029 ER PT J AU Thomas, RJ Kwong, KK AF Thomas, RJ Kwong, KK TI Effects of modafinil on working memory load responses after overnight sleep deprivation: A functional magnetic resonance Imaging SO SLEEP LA English DT Meeting Abstract CT 17th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 03-08, 2003 CL CHICAGO, ILLINOIS SP Assoc Prof Sleep Soc C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 15 PY 2003 VL 26 BP A187 EP A188 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 677ZY UT WOS:000182841100466 ER PT J AU Willie, JT Sinton, CM Mieda, M Maratos-Flier, E Yanagisawa, M AF Willie, JT Sinton, CM Mieda, M Maratos-Flier, E Yanagisawa, M TI Orexin and melanin-concentrating hormone (MCH) double knockout mice: Compensatory role for MCH in narcolepsy-cataplexy SO SLEEP LA English DT Meeting Abstract CT 17th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 03-08, 2003 CL CHICAGO, ILLINOIS SP Assoc Prof Sleep Soc C1 Univ Texas, SW Med Ctr, Dallas, TX USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Howard Hughes Med Inst, Dallas, TX USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 15 PY 2003 VL 26 BP A50 EP A50 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 677ZY UT WOS:000182841100121 ER PT J AU Pascual, M Curtis, J Delmonico, FL Farrell, ML Williams, WW Kalil, R Jones, P Cosimi, AB Tolkoff-Rubin, N AF Pascual, M Curtis, J Delmonico, FL Farrell, ML Williams, WW Kalil, R Jones, P Cosimi, AB Tolkoff-Rubin, N TI A prospective, randomized clinical trial of cyclosporine reduction in stable patients greater than 12 months after renal transplantation SO TRANSPLANTATION LA English DT Article ID CHRONIC ALLOGRAFT NEPHROPATHY; LONG-TERM; MYCOPHENOLATE-MOFETIL; RECIPIENTS; WITHDRAWAL; MULTICENTER; STRATEGIES; REJECTION; THERAPY AB Background. For stable kidney-transplant recipients receiving triple drug therapy with cyclosporine (CsA), prednisone, and mycophenolate mofetil (MMF), it remains unclear what is the optimal dose of CsA beyond the first 6 to 12 months after transplantation. Complete CsA withdrawal has been associated with a significant incidence of acute rejection and, in some studies, chronic rejection as well. Methods. We performed an open, prospectively randomized, controlled clinical trial to determine whether CsA could be safely reduced by 50%. At 1 year or more posttransplant, 64 patients were randomized to either continue their stable-maintenance CsA dose (control group, n = 32) or to lower their CsA dose by 50% over a 2 month period (CsA reduction group, n = 32). All patients had stable renal-allograft function at the time of enrollment. Results. Within 6 months of randomization, no episode of acute rejection or graft loss occurred in either group. Patients in the CsA reduction group had a slight but significant increase in their glomerular filtration rate and a trend towards lower serum creatinine. There was also a significant decrease in mean systolic blood pressure, triglycerides, and serum uric acid levels in the CsA reduction group. No significant changes in any of these parameters were observed in the control group. Conclusions. This study suggests that a strategy consisting of a 50% CsA reduction is safe and is not associated with the increased risk of acute rejection observed in CsA withdrawal studies. It also has the potential to improve short-term allograft function and appears to reduce cardiovascular risk factors such as hypertension and hyperlipidemia. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Univ Alabama, Med Ctr, Div Nephrol, Birmingham, AL 35294 USA. RP Pascual, M (reprint author), CHU Vaudois, Transplantat Ctr, Rue Bugnon 46, CH-1011 Lausanne, Switzerland. NR 21 TC 55 Z9 58 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 MAY 15 PY 2003 VL 75 IS 9 BP 1501 EP 1505 DI 10.1097/01.TP.0000061606.64917.BE PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 681LV UT WOS:000183038400015 PM 12792504 ER PT J AU Kidwell, CS Shephard, T Tonn, S Lawyer, B Murdock, M Koroshetz, W Alberts, M Hademenos, GJ Saver, JL AF Kidwell, CS Shephard, T Tonn, S Lawyer, B Murdock, M Koroshetz, W Alberts, M Hademenos, GJ Saver, JL TI Establishment of primary stroke centers - A survey of physician attitudes and hospital resources SO NEUROLOGY LA English DT Article ID PLASMINOGEN-ACTIVATOR; ISCHEMIC STROKE AB Objectives: To survey US physicians involved in acute stroke care to determine the proportion of hospitals that currently meet the recommended Brain Attack Coalition (BAC) criteria for Primary Stroke Centers (PSC) and obtain opinions regarding the value of stroke centers. Methods: A survey regarding the BAC guidelines for the establishment of stroke centers was mailed to 3,245 US neurologists, neurosurgeons, and emergency physicians. Results: A total of 1,032 responses were received. Seventy-nine percent (range by specialty 58 to 98%) of respondents believed there was a need for stroke centers. If formal stroke center designation were established, 81% (range 72 to 90%) would like their hospital to become a PSC. Although 77% of respondents believed that their hospital currently met recommended criteria for a PSC, only 7% actually meet all recommended elements. However, 44% of hospitals already provide most acute stroke services. The BAC criteria most frequently lacking were continuing medical education for professional stroke center staff, stroke training for emergency department staff, formal establishment of a stroke unit, and designation of a stroke center director. Conclusions: The majority of emergency medicine and neuroscience physician respondents involved in acute stroke care support the designation of primary stroke centers. Although respondents globally overestimated the extent to which their facilities currently meet BAC recommended criteria for PSC, detailed responses suggested that over 40% of hospitals possess substantial existing acute stroke care resources and are poised to function as PSC with modest additional administrative and financial commitment. C1 Univ Calif Los Angeles, Med Ctr, UCLA Stroke Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Med Ctr, Dept Neurol, Los Angeles, CA 90095 USA. Brain Attack Coalit, Bethesda, MD USA. Amer Acad Neurol, St Paul, MN USA. Natl Stroke Assoc, Englewood, CO USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Northwestern Univ, Sch Med, Dept Neurol, Chicago, IL 60611 USA. Amer Heart Assoc Natl Ctr, Off Sci & Med, Dallas, TX USA. RP Kidwell, CS (reprint author), Univ Calif Los Angeles, Med Ctr, UCLA Stroke Ctr, 710 Westwood Plaza, Los Angeles, CA 90095 USA. OI Saver, Jeffrey/0000-0001-9141-2251 FU NINDS NIH HHS [K23 NS 02088, K24 NS 02092] NR 10 TC 34 Z9 35 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 13 PY 2003 VL 60 IS 9 BP 1452 EP 1456 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 676LT UT WOS:000182754100012 PM 12743230 ER PT J AU Howieson, DB Camicioli, R Quinn, J Silbert, LC Care, B Moore, MM Dame, A Sexton, G Kaye, JA AF Howieson, DB Camicioli, R Quinn, J Silbert, LC Care, B Moore, MM Dame, A Sexton, G Kaye, JA TI Natural history of cognitive decline in the old old SO NEUROLOGY LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the American-Academy-of-Neurology CY APR 29-MAY 06, 2000 CL SAN DIEGO, CALIFORNIA SP Amer Acad Neurol ID APOLIPOPROTEIN-E GENOTYPE; HEALTHY ELDERLY PERSONS; ALZHEIMERS-DISEASE; DEMENTIA; IMPAIRMENT; POPULATION; PROGRESSION; VALIDATION; MARKERS; SCALE AB Objective: To prospectively examine the occurrence and outcome of cognitive decline in healthy, community-dwelling elders. Methods: Ninety-five elders (mean age 84 years) who at entry had no cognitive impairment were followed for up to 13 years. Cognitive decline was defined as obtaining either a Clinical Dementia Rating (CDR) = 0.5 or Mini-Mental State Examination (MMSE) score < 24 on two examinations. Results: Three outcomes of aging were determined: intact cognition, persistent cognitive decline without progression to dementia, and dementia. Whereas 49% remained cognitively intact, 51% developed cognitive decline. Mean follow-up to first CDR 0.5 was 3.8 years and age at conversion was 90.0 years. Those who remained cognitively intact had better memory at entry and were less likely to have APOE4 than those who developed cognitive decline. Of the 48 participants with cognitive decline, 27 (56%) developed dementia (CDR &GE;1) a mean of 2.8 years later. Participants with cognitive decline who progressed to dementia had poorer confrontation naming at the time of their first CDR 0.5 than those with persistent cognitive decline who did not progress during follow-up. Conclusion: The old old are at high risk for developing cognitive decline but many will not progress to dementia in the next 2 to 3 years or even beyond. These findings are important for understanding the prognosis of cognitive decline and for the design of treatment trials for AD. APOE genotype is a risk factor for cognitive decline. C1 Oregon Hlth Sci Univ, Layton Aging & Alzheimers Dis Ctr CR131, Dept Neurol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Publ Hlth, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Univ Alberta, Dept Med Neurol, Edmonton, AB, Canada. RP Howieson, DB (reprint author), Oregon Hlth Sci Univ, Layton Aging & Alzheimers Dis Ctr CR131, Dept Neurol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. OI Kaye, Jeffrey/0000-0002-9971-3478; Camicioli, Richard/0000-0003-2977-8660 FU NCRR NIH HHS [M01 RR0034]; NIA NIH HHS [P30 AG08017] NR 48 TC 58 Z9 59 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 MAY 13 PY 2003 VL 60 IS 9 BP 1489 EP 1494 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 676LT UT WOS:000182754100019 PM 12743237 ER PT J AU Mitra, RD Butty, VL Shendure, J Williams, BR Housman, DE Church, GM AF Mitra, RD Butty, VL Shendure, J Williams, BR Housman, DE Church, GM TI Digital genotyping and haplotyping with polymerase colonies SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; DNA; EXPRESSION; PCR; AMPLIFICATION; BLOCKS; APART AB Polymerase colony (polony) technology amplifies multiple individual DNA molecules within a thin acrylamide gel attached to a microscope slide. Each DNA molecule included in the reaction produces an immobilized colony of double-stranded DNA. We genotype these polonies by performing single base extensions with dye-labeled nucleotides, and we demonstrate the accurate quantitation of two allelic variants. We also show that polony technology can determine the phase, or haplotype, of two single-nucleotide polymorphisms (SNPs) by coamplifying distally located targets on a single chromosomal fragment. We correctly determine the genotype and phase of three different pairs of SNPs. In one case, the distance between the two SNPs is 45 kb, the largest distance achieved to date without separating the chromosomes by cloning or somatic cell fusion. The results indicate that polony genotyping and haplotyping may play an important role in understanding the structure of genetic variation. C1 Harvard Univ, Sch Med, Lipper Ctr Computat Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Grad Program Immunol, Joslin Diabet Ctr, Boston, MA 02215 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Church, GM (reprint author), Harvard Univ, Sch Med, Lipper Ctr Computat Genet, 200 Longwood Ave, Boston, MA 02115 USA. OI Shendure, Jay/0000-0002-1516-1865 NR 34 TC 110 Z9 117 U1 0 U2 10 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 MAY 13 PY 2003 VL 100 IS 10 BP 5926 EP 5931 DI 10.1073/pnas.0936399100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 679UB UT WOS:000182939400066 PM 12730373 ER PT J AU Apostol, BL Kazantsev, A Raffioni, S Illes, K Pallos, J Bodai, L Slepko, N Bear, JE Gertler, FB Hersch, S Housman, DE Marsh, JL Thompson, LM AF Apostol, BL Kazantsev, A Raffioni, S Illes, K Pallos, J Bodai, L Slepko, N Bear, JE Gertler, FB Hersch, S Housman, DE Marsh, JL Thompson, LM TI A cell-based assay for aggregation inhibitors as therapeutics of polyglutamine-repeat disease and validation in Drosophila SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NEURONAL INTRANUCLEAR INCLUSIONS; HUNTINGTONS-DISEASE; PROTEIN AGGREGATION; CAENORHABDITIS-ELEGANS; MUTANT HUNTINGTIN; MOLECULAR CHAPERONES; TRANSGENIC MICE; GENE-EXPRESSION; NEURODEGENERATION; MODEL AB The formation of polyglutamine-containing aggregates and inclusions are hallmarks of pathogenesis in Huntington's disease that can be recapitulated in model systems. Although the contribution of inclusions to pathogenesis is unclear, cell-based assays can be used to screen for chemical compounds that affect aggregation and may provide therapeutic benefit. We have developed inducible PC12 cell-culture models to screen for loss of visible aggregates. To test the validity of this approach, compounds that inhibit aggregation in the PC12 cell-based screen were tested in a Drosophila model of polyglutamine-repeat disease. The disruption of aggregation in PC12 cells strongly correlates with suppression of neuronal degeneration in Drosophila. Thus, the engineered PC12 cells coupled with the Drosophila model provide a rapid and effective method to screen and validate compounds. C1 Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92697 USA. Univ Calif Irvine, Dept Dev & Cellular Biol, Irvine, CA 92697 USA. Massachusetts Gen Hosp, Ctr Aging & Neurodegenerat, Charlestown, MA 02129 USA. MIT, Dept Biol, Canc Res Ctr, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Thompson, LM (reprint author), Univ Calif Irvine, Dept Psychiat & Human Behav, Gillespie 2121, Irvine, CA 92697 USA. RI Bodai, Laszlo/A-9764-2012 OI Bodai, Laszlo/0000-0001-8411-626X FU NCCIH NIH HHS [U01 AT000613, AT00613, R01 AT000613]; NCI NIH HHS [CA-62203, P30 CA062203]; NHLBI NIH HHS [P01 HL066105, P01HL66105]; NICHD NIH HHS [HD36049, HD36081, R01 HD036081]; NINDS NIH HHS [NS35255] NR 53 TC 108 Z9 111 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 13 PY 2003 VL 100 IS 10 BP 5950 EP 5955 DI 10.1073/pnas.2628045100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 679UB UT WOS:000182939400070 PM 12730384 ER PT J AU Ma, XJ Salunga, R Tuggle, JT Gaudet, J Enright, E McQuary, P Payette, T Pistone, M Stecker, K Zhang, BM Zhou, YX Varnholt, H Smith, B Gadd, M Chatfield, E Kessler, J Baer, TM Erlander, MG Sgroi, DC AF Ma, XJ Salunga, R Tuggle, JT Gaudet, J Enright, E McQuary, P Payette, T Pistone, M Stecker, K Zhang, BM Zhou, YX Varnholt, H Smith, B Gadd, M Chatfield, E Kessler, J Baer, TM Erlander, MG Sgroi, DC TI Gene expression profiles of human breast cancer progression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CARCINOMA IN-SITU; REDUCTASE R2 COMPONENT; DUCTAL CARCINOMA; HETEROZYGOSITY; TRANSFORMATION; ONCOGENES; ADJACENT AB Although distinct pathological stages of breast cancer have been described, the molecular differences among these stages are largely unknown. Here, through the combined use of laser capture microdissection and DNA microarrays, we have generated in situ gene expression profiles of the premalignant, preinvasive, and invasive stages of human breast cancer. Our data reveal extensive similarities at the transcriptome level among the distinct stages of progression and suggest that gene expression alterations conferring the potential for invasive growth are already present in the preinvasive stages. In contrast to tumor stage, different tumor grades are associated with distinct gene expression signatures. Furthermore, a subset of genes associated with high tumor grade is quantitatively correlated with the transition from preinvasive to invasive growth. C1 Arcturus, Appl Genom Div, Carlsbad, CA 92008 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Mol Pathol Res Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02129 USA. RP Sgroi, DC (reprint author), Arcturus, Appl Genom Div, 2715 Loker Ave W, Carlsbad, CA 92008 USA. NR 23 TC 492 Z9 506 U1 2 U2 10 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 MAY 13 PY 2003 VL 100 IS 10 BP 5974 EP 5979 DI 10.1073/pnas.0931261100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 679UB UT WOS:000182939400074 PM 12714683 ER PT J AU Davis, IJ Hsi, BL Arroyo, JD Vargas, SO Yeh, YA Motyckova, G Valencia, P Perez-Atayde, AR Argani, P Ladanyi, M Fletcher, JA Fisher, DE AF Davis, IJ Hsi, BL Arroyo, JD Vargas, SO Yeh, YA Motyckova, G Valencia, P Perez-Atayde, AR Argani, P Ladanyi, M Fletcher, JA Fisher, DE TI Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LOOP-HELIX PROTEIN; TRANSCRIPTION FACTOR GENE; SOFT PART SARCOMA; C-MYC ONCOGENE; CELL CARCINOMAS; DIFFERENTIAL EXPRESSION; EUKARYOTIC RIBOSOMES; MESSENGER-RNA; MICROPHTHALMIA; MITF AB MITF, TFE3, TFEB, and TFEC comprise a transcription factor family (MiT) that regulates key developmental pathways in several cell lineages. Like MYC, MiT members are basic helix-loop-helix-leucine zipper transcription factors. MiT members share virtually perfect homology in their DNA binding domains and bind a common DNA motif. Translocations of TFE3 occur in specific subsets of human renal cell carcinomas and in alveolar soft part sarcomas. Although multiple translocation partners are fused to TFE3, each translocation product retains TFE3 's basic helix-loop-helix leucine zipper. We have identified the genes fused by the chromosomal translocation t(6;11)(p21.1;q13), characteristic of another subset of renal neoplasms. In two primary tumors we found that Alpha, an intronless gene, rearranges with the first intron of TFEB, just upstream of TFEB's initiation ATG, preserving the entire TFEB coding sequence. Fluorescence in situ hybridization confirmed the involvement of both TFEB and Alpha in this translocation. Although the Alpha promoter drives expression of this fusion gene, the Alpha gene does not contribute to the CIRF. Whereas TFE3 is typically fused to partner proteins in subsets of renal tumors, we found that wild-type, unfused TFE3 stimulates clonogenic growth in a cell-based assay, suggesting that dysregulated expression, rather than altered function of TFEB or TFE3 fusions, may confer neoplastic properties, a mechanism reminiscent of MYC activation by promoter substitution in Burkitt's lymphoma. Alpha-TFEB is thus identified as a fusion gene in a subset of pediatric renal neoplasms. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 46 TC 142 Z9 147 U1 0 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 MAY 13 PY 2003 VL 100 IS 10 BP 6051 EP 6056 DI 10.1073/pnas.0931430100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 679UB UT WOS:000182939400087 PM 12719541 ER PT J AU Pantilat, SZ Billings, JA AF Pantilat, SZ Billings, JA TI Prevalence and structure of palliative care services in california hospitals SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED TRIAL AB Background: Most Americans die in hospitals where shortcomings in end-of-life care are endemic. Hospital-based palliative cafe services can. improve the care of these patients, yet there are limited data regarding the availability of such services. We sought to determine the prevalence of palliative care services in California hospitals. Methods: We conducted a cross-sectional survey of a random sample of 25% of all California hospitals. We recorded the percentage of hospitals reporting current or planned palliative care consultation services or inpatient palliative care units. Results: We collected data from 107 (96%) of 112 hospitals. Only 17% of hospitals have a palliative care consult service, and 6% have an inpatient palliative care unit. Nearly all services are multidisciplinary. Twenty per cent of hospitals have a contract to provide inpatient hospice beds, 19% have an outpatient-based hospice service affiliated with the hospital, and 74% offer bereavement services. Half of all palliative care services are funded exclusively by the hospital. Thirty-eight hospitals (36%) reported an interest in developing palliative care services. Conclusions: Few California hospitals currently have palliative care services, though more express interest in developing them. Bereavement and hospice services are more common and offer opportunities for increasing the number of palliative care services in hospitals. Further studies are needed to characterize palliative care services more fully and to assess the quality of care provided by these services. C1 Univ Calif San Francisco, Sch Med, Program Med Eth, Div Gen Internal Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Dept Med, Hospitalist Sect, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. RP Pantilat, SZ (reprint author), Univ Calif San Francisco, Sch Med, Program Med Eth, Div Gen Internal Med, 521 Parnassus Ave,Suite C-126,Box 0903, San Francisco, CA 94143 USA. FU NIA NIH HHS [K23 AG 01018-01] NR 11 TC 30 Z9 30 U1 1 U2 2 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 MAY 12 PY 2003 VL 163 IS 9 BP 1084 EP 1088 DI 10.1001/archinte.163.9.1084 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 676YZ UT WOS:000182781300013 PM 12742807 ER PT J AU Mukherjee, S AF Mukherjee, S TI Oversight - What the WHO should have learned from the flu. SO NEW REPUBLIC LA English DT Article C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mukherjee, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NEW REPUBLIC INC PI WASHINGTON PA 1220 19TH ST NW SUITE 600, WASHINGTON, DC 20036 USA SN 0028-6583 J9 NEW REPUBLIC JI New Repub. PD MAY 12 PY 2003 VL 228 IS 18 BP 20 EP 23 PG 4 WC Political Science SC Government & Law GA 675CH UT WOS:000182675100014 ER PT J AU Pham, W Weissleder, R Tung, CH AF Pham, W Weissleder, R Tung, CH TI A practical approach for the preparation of monofunctional azulenyl squaraine dye SO TETRAHEDRON LETTERS LA English DT Article ID FLUORESCENT-PROBES; TUMORS; ANALOGS AB The synthesis of monofunctional azulenyl squaraine dye NIRQ(700) is described. The essential azulene intermediate 3, 1-(methoxycarbonyl)-2-methylazulene, was achieved via [8+2] cycloaddition between lactone 2, 2H-3-methoxycarbonyl-cyclohepta[b]furan-2-one, and the in situ generated vinyl ethers under high temperature and pressure conditions. Methylation on the cycloheptatriene ring of 2-methyl azulene 6 via Meisenheimer-type intermediate following Schrott's method formed the carboxylic acid intermediate 9, 3-(2-methyl-azulen-4-yl)-propionic acid. Condensation of 9 with squaric acid provided the title compound NIRQ(700) at moderate yields. The non-fluorescent squaraine dye NIRQ(700) absorbed in a 600-700 nm range and potentially can be used to quench a number of available NIR fluorochromes in order to extend the spectrum of biological quenching assays. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50 CA086355, R33 CA088365, R33 CA088365-03] NR 19 TC 15 Z9 17 U1 1 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD MAY 12 PY 2003 VL 44 IS 20 BP 3975 EP 3978 DI 10.1016/S0040-4039(03)00819-0 PG 4 WC Chemistry, Organic SC Chemistry GA 677AJ UT WOS:000182784500022 PM 20740053 ER PT J AU Miller, DP De Vivo, I Neuberg, D Wain, JC Lynch, TJ Su, L Christiani, DC AF Miller, DP De Vivo, I Neuberg, D Wain, JC Lynch, TJ Su, L Christiani, DC TI Association between self-reported environmental tobacco smoke exposure and lung cancer: Modification by GSTP1 polymorphism SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE ETS; lung cancer; GSTP1; genetic susceptibility ID GLUTATHIONE-S-TRANSFERASE; SAMPLE-SIZE CALCULATIONS; RISK; GSTM1; SUSCEPTIBILITY; NONSMOKING; MULTICENTER; FREQUENCY; GENOTYPES; DAMAGE AB Environmental Tobacco Smoke (ETS) exposure has been associated with lung cancer risk. ETS is composed of emissions from cigarette smoke and contains a higher concentration of tobacco smoke carcinogens than mainstream smoke. Polymorphisms in genes that metabolize tobacco smoke carcinogens have been studied as effect modifiers of the association between active smoking and lung cancer risk. GSTPI is a polymorphic gene that encodes for GST pi, a detoxification enzyme and has a high expression in the lung. We investigated the association between ETS and lung cancer risk and the modification of this association by the GSTPI polymorphism. Using a case-control design, individuals were genotyped for GSTPI using PCR-RFLP techniques. All analyses were carried out using multiple logistic regression. The association between ETS exposure and lung cancer risk was evaluated in different strata based on smoking habits to evaluate the consistency of results. The effect of the GSTPI polymorphisms on lung cancer risk was evaluated by considering the joint effect of having both an ETS exposure and the GSTPI GG genotype compared to the absence of ETS exposure and the GSTPI AA genotype as a reference group as well as doing stratified analysis by genotype. ETS exposure was associated consistently with higher lung cancer risk in all the strata considered. The adjusted odds ratios (AOR) evaluating the association between ETS and lung cancer risk for the different strata were: nonsmokers (Cases/Controls 66/413; AOR = 1.38; 95% CI = 0.78-2.43), ex-smokers (Cases/Controls 560/527; AOR = 1.66; 95% CI = 1.22-2.25), current smokers (Cases/Controls 415/219; AOR = 1.56; 95% CI = 1.00-2.41). The AORs for ex-smokers and light smoking subgroups were: ex-smokers who quit for 19 years or more (Cases/Controls 144/244; AOR = 2.64; 95% Cl = 1.55-4.50), ex-smokers who quit for 10-19 years (Cases/Controls 141/128; AOR = 1.16; 95% CI = 0.66-2.04), ex-smokers who quit for 10 years or less (Cases/Controls 247/122; AOR = 1.45; 95% CI = 0.83-2.55) and participants who had <15 packyears and nonsmokers combined (Cases/Controls 143/640; AOR = 1.52; 95% CI = 1.02-2.28). Among those with the GSTPI GG genotype the ETS-lung cancer risk association was greater than those with the GSTPI AA genotype: nonsmokers (GSTPI GG AOR = 7.84; 95% Cl = 0.80-76.68; GSTPI AA AOR = 1.15; 95% CI 0.46-2.90), ex-smokers (GSTPI GG AOR = 2.32; 95% CI 0.90-5.96; GSTPI AA AOR = 2.15; 95% CI = 1.34-3.44), current smokers (GSTPI GG AOR = 1.75; 95% CI = 0.42-7.32; GSTPI AA AOR = 1.32; 95% CI = 0.67-2.58) and participants who had < 15 packyears and nonsmokers (GSTPI GG AOR = 1.93; 95% CI = 034-6.97; GSTPI AA AOR = 1.58; 95% CI = 0.83-3.01). We found that ETS exposure is associated with higher lung cancer risk. Furthermore, the presence of the GSTPI GG genotype appears to enhance the magnitude of the association between ETS exposure and lung cancer. Larger studies will be needed to confirm these preliminary findings. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Sch Publ Hlth, Channing Labs,Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Thorac Surg Unit,Dept Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Hematol Oncol Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Pulm & Crit Care Unit, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,Room 1402, Boston, MA 02115 USA. FU NCI NIH HHS [CA 74386]; NIEHS NIH HHS [ES/CA 06409, ES00002] NR 31 TC 39 Z9 42 U1 2 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 10 PY 2003 VL 104 IS 6 BP 758 EP 763 DI 10.1002/ijc.10989 PG 6 WC Oncology SC Oncology GA 667DE UT WOS:000182214900014 PM 12640684 ER PT J AU Ramaswamy, S Perou, CM AF Ramaswamy, S Perou, CM TI DNA microarrays in breast cancer: the promise of personalised medicine SO LANCET LA English DT Editorial Material ID GENE-EXPRESSION; PREDICTION; CLASSIFICATION; DISCOVERY; SURVIVAL C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Whitehead MIT Ctr Genome Res, Cambridge, MA USA. Univ N Carolina, Lineberger Canc Res Ctr, Chapel Hill, NC 27599 USA. RP Ramaswamy, S (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. OI Perou, Charles/0000-0001-9827-2247 NR 14 TC 35 Z9 37 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 10 PY 2003 VL 361 IS 9369 BP 1576 EP 1577 DI 10.1016/S0140-6736(03)13322-3 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 676HY UT WOS:000182746300002 PM 12747872 ER PT J AU Nisbet-Brown, E Olivieri, NF Giardina, PJ Grady, RW Neufeld, EJ Sechaud, R Krebs-Brown, AJ Anderson, JR Alberti, D Sizer, KC Nathan, DG AF Nisbet-Brown, E Olivieri, NF Giardina, PJ Grady, RW Neufeld, EJ Sechaud, R Krebs-Brown, AJ Anderson, JR Alberti, D Sizer, KC Nathan, DG TI Effectiveness and safety of ICL670 in iron-loaded patients with thalassaemia: a randomised, double-blind, placebo-controlled, dose-escalation trial SO LANCET LA English DT Article ID THALASSEMIA MAJOR; CHELATION-THERAPY; BETA-THALASSEMIA; DEFERIPRONE; OVERLOAD; FIBROSIS; GREEKS AB Background Transfusional iron overload is a potentially fatal complication of the treatment of thalassaemia. We aimed to investigate short-term efficacy, pharmacokinetic/pharmacodynamic (PK/PD) relations, and safety of ICL670, a novel, tridentate, orally active iron chelator. Methods We enrolled 24 patients and divided them into three cohorts consisting of a minimum of seven individuals. Patients were admitted to a metabolic unit and consumed a diet with a defined content of iron. Two patients in each cohort were randomly allocated placebo. Five or more patients received one daily dose of ICL670 at 10, 20, or 40 mg kg(-1) day(-1), from day 1 to 12. Net iron excretion (NIE) was measured between days I and 12. Primary objectives included assessment of safety and tolerability (measured by adverse events and clinical laboratory monitoring), pharmacokinetics (measured as drug and drug-iron complex), and cumulative net iron excretion (measured by faecal and urine output minus food input). Analysis was for efficacy. Findings ICL670 was absorbed promptly and was detectable in the blood for 24 h. Exposure (area under the curve of plasma concentration) to ICL670 at pharmacokinetic steady state was proportional to dose. All three doses resulted in positive NIE. The NIE achieved at 20 mg kg-1 clays would prevent net iron accumulation in most patients transfused with 12-15 mL packed red-blood-cells kg(-1) month(-1), equivalent to 0.3-0.5 mg iron kg(-1) day(-1). A linear relation (PK/PD) was recorded between exposure to ICL670 and total iron excretion, by contrast with placebo (r(2)=0.54, p< 0.0001). Skin rashes were noted in four patients treated at 20 and 40 mg kg(-1) day(-1), and one patient also developed grade 2 transaminitis. Interpretation ICL670 given once daily at 20 mg/kg seems to be an effective orally active iron chelator and is reasonably well tolerated. Long-term studies are now necessary to establish the practical contribution of this drug. C1 Harvard Univ, Sch Med, Dept Paediat, Boston, MA USA. Weill Med Coll, Dept Paediat, New York, NY USA. Univ Toronto, Dept Med, Toronto, ON, Canada. Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Toronto Gen Hosp, Toronto, ON, Canada. New York Presbyterian Hosp, New York, NY USA. Novartis Pharma AG, Basel, Switzerland. RP Nathan, DG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Neufeld, Ellis/F-9331-2011 FU NCRR NIH HHS [5M01 RR02172, 5M01-RR00047]; NHLBI NIH HHS [HL99016, HL04184, P50 HL54785] NR 27 TC 212 Z9 218 U1 0 U2 7 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 10 PY 2003 VL 361 IS 9369 BP 1597 EP 1602 DI 10.1016/S0140-6736(03)13309-0 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 676HY UT WOS:000182746300009 PM 12747879 ER PT J AU Scorrano, L Korsmeyer, SJ AF Scorrano, L Korsmeyer, SJ TI Mechanisms of cytochrome c release by proapoptotic BCL-2 family members SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PERMEABILITY TRANSITION PORE; OUTER MITOCHONDRIAL-MEMBRANE; DEPENDENT ANION CHANNEL; BH3 DOMAIN; CELL-DEATH; INDUCED APOPTOSIS; X-L; INNER MEMBRANE; BAX; PROTEIN AB A crucial amplificatory event in several apoptotic cascades is the nearly complete release of cytochrome c from mitochondria. Proteins of the BCL-2 family which include both anti- and proapoptotic members control this step. Here, we review the proposed mechanisms by which proapoptotic BCL-2 family members induce cytochrome c release. Data support a model in which the apoptotic pathway bifurcates following activation of a "BH3 only" family member. BH3 only molecules induce the activation of the multidomain proapoptotics BAX and BAK, resulting in the permeabilization of the outer mitochondrial membrane and the efflux of cytochrome c. This is coordinated with the activation of a distinct pathway characterized by profound changes of the inner mitochondrial membrane morphology and organization. This mitochondrial remodelling insures complete release of cytochrome e and the onset of mitochondrial dysfunction that is a typical feature of many apoptotic deaths. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Scorrano, Luca/A-6652-2008 OI Scorrano, Luca/0000-0002-8515-8928 NR 88 TC 483 Z9 509 U1 1 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 9 PY 2003 VL 304 IS 3 BP 437 EP 444 DI 10.1016/S0006-291X(03)00615-6 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 679GB UT WOS:000182911400002 PM 12729577 ER PT J AU Garnovskaya, MN Mukhin, YV Vlasova, TM Raymond, JR AF Garnovskaya, MN Mukhin, YV Vlasova, TM Raymond, JR TI Hypertonicity activates Na+/H+ exchange through Janus kinase 2 and calmodulin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INSULIN-STIMULATED PHOSPHORYLATION; CELL-VOLUME REGULATION; ASCITES TUMOR-CELLS; PROTEIN-KINASE; TYROSINE PHOSPHORYLATION; 5-HT1A RECEPTOR; GROWTH-FACTOR; ISOFORM-1 NHE1; OSMOTIC SHOCK; H+ EXCHANGER AB The type 1 sodium-hydrogen exchanger (NHE-1) is a ubiquitous electroneutral membrane transporter that is activated by hypertonicity in many cells. NHE-1 may be an important pathway for Na+ entry during volume restoration, yet the molecular mechanisms underlying the osmotic regulation of NHE-1 are poorly understood. In the present study we conducted a screen for important signaling molecules that could be involved in hypertonicity-induced activation of NHE-1 in CHO-K1 cells. Hypertonicity rapidly activated NHE-1 in a concentration-dependent manner as assessed by proton microphysiometry and by measurements of intracellular pH on a FLIPR(TM) (fluorometric imaging plate reader). Inhibitors of Ca2+/calmodulin (CaM) and Janus kinase 2 (Jak2) attenuated this activation, whereas neither calcium chelation nor inhibitors of protein kinase C, the Ras-ERK1/2 pathway, Src kinase, and Ca2+/calmodulin-dependent enzymes had significant effects. Hypertonicity also resulted in the rapid tyrosine phosphorylation of Jak2 and STAT3 (the major substrate of Jak2) and CaM. Phosphorylation of Jak2 and CaM were blocked by AG490, an inhibitor of Jak2. Immunoprecipitation studies showed that hypertonicity stimulates the assembly of a signaling complex that includes CaM, Jak2, and NHE-1. Formation of the complex could be blocked by AG490. Thus, we propose that hypertonicity induces activation of NHE-1 in CHO-K1 cells in large part through the following pathway: hypertonicity 3 Jak2 phosphorylation and activation 3 tyrosine phosphorylation of CaM 3 association of CaM with NHE-1 --> NHE-1 activation. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Med Serv, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29425 USA. RP Garnovskaya, MN (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St,Rm 829 CSB,POB 250623, Charleston, SC 29425 USA. FU NIDDK NIH HHS [DK52448, KO1-DK02694] NR 45 TC 51 Z9 53 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 9 PY 2003 VL 278 IS 19 BP 16908 EP 16915 DI 10.1074/jbc.M209883200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 677QG UT WOS:000182818600063 PM 12626508 ER PT J AU Campanella, GSV Lee, EMJ Sun, J Luster, AD AF Campanella, GSV Lee, EMJ Sun, J Luster, AD TI CXCR3 and heparin binding sites of the chemokine IP-10 (CXCL10) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-ALPHA-CHEMOATTRACTANT; INTERFERON-INDUCIBLE PROTEIN-10; MONOCYTE CHEMOTACTIC PROTEIN-1; ACUTE ALLOGRAFT-REJECTION; X-C CHEMOKINE; T-CELLS; DIFFERENTIAL EXPRESSION; RECEPTOR-BINDING; SULFATE PROTEOGLYCANS; MULTIPLE-SCLEROSIS AB The chemokine IP-10 (interferon-inducible protein of 10 kDa, CXCL10) binds the G protein-coupled receptor CXCR3, which is found mainly on activated T cells and NK cells, and plays an important role in Th1-type inflammatory diseases. IP-10 also binds to glycosaminoglycans (GAGs), an interaction thought to be important for its sequestration on endothelial and other cells. In this study, we performed an extensive mutational analysis to identify the CXCR3 and heparin binding sites of murine IP-10. The mutants were characterized for heparin binding, CXCR3 binding, and the ability to induce chemotaxis, Ca2+ flux, and CXCR3 internalization. Double mutations neutralizing adjacent basic residues at the C terminus did not lead to a significant reduction in heparin binding, indicating that the main heparin binding site of IP-10 is not along the C-terminal alpha helix. Alanine exchange of Arg-22 had the largest effect on heparin binding, with residues Arg-20, Ile-24, Lys-26, Lys-46, and Lys-47 further contributing to heparin binding. A charge change mutation of Arg-22 resulted in further reduction in heparin binding. The N-terminal residue Arg-8, preceding the first cysteine, was critical for CXCR3 signaling. Mutations of charged and uncharged residues in the loop regions of residues 20-24 and 46-47, which caused reduced heparin binding, also resulted in reduced CXCR3 binding and signaling. CXCR3 expressing GAG-deficient Chinese hamster ovary cells revealed that GAG binding was not required for IP-10 binding and signaling through CXCR3, which suggests that the CXCR3 and heparin binding sites of IP-10 are partially overlapping. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01-CA69212]; NIDDK NIH HHS [R01-DK50305] NR 50 TC 68 Z9 69 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 9 PY 2003 VL 278 IS 19 BP 17066 EP 17074 DI 10.1074/jbc.M212077200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 677QG UT WOS:000182818600084 PM 12571234 ER PT J AU Huse, JT Byant, D Yang, YX Pijak, DS D'Souza, I Lah, JJ Lee, VMY Doms, RW Cook, DG AF Huse, JT Byant, D Yang, YX Pijak, DS D'Souza, I Lah, JJ Lee, VMY Doms, RW Cook, DG TI Endoproteolysis of beta-secretase (beta-site amyloid precursor protein-cleaving enzyme) within its catalytic domain - A potential mechanism for regulation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DISEASE-ASSOCIATED PRESENILIN-1; NECROSIS-FACTOR-ALPHA; TRANS-GOLGI NETWORK; ALZHEIMERS-DISEASE; TRANSMEMBRANE ASPARTATES; PROTEOLYTIC-ENZYMES; HUMAN BRAIN; IN-VIVO; CLEAVAGE; PEPTIDE AB Sequential proteolysis of the amyloid precursor protein (APP) by beta- and gamma-secretase activities yields the amyloid beta peptide that is widely deposited in the brains of individuals with Alzheimer's disease. The membrane-anchored aspartyl protease (β) under bar- site (A) under bar PP- cleaving (e) under bar nzyme (BACE) exhibits all of the characteristics of a beta-secretase and has been shown to cleave APP at its beta-site in vitro and in vivo. We found that BACE undergoes cleavage on a surface-exposed alpha-helix between amino acid residues Leu-228 and Ala-229, generating stable N- and C-terminal fragments that remain covalently associated via a disulfide bond. The efficiency of BACE endoproteolysis was observed to depend heavily on cell and tissue type. In contrast to brain where holoprotein was predominant, BACE was found primarily as endoproteolyzed fragments in pancreas, liver, and muscle. In addition, we observed a marked up-regulation of BACE endoproteolysis in C2 myoblasts upon differentiation into multinucleated myotubes, a well established model system of muscle tissue specification. As in liver, BACE exists as endoproteolyzed fragments in the hepatic cell line, HepG2. We found that HepG2 cells are capable of generating amyloid beta peptide, suggesting that endoproteolyzed BACE retains measurable beta-secretase activity. We also found that BACE endoproteolysis occurs only after export from the endoplasmic reticulum, is enhanced in the trans-Golgi network, and is sensitive to inhibitors of vesicular acidification. The membrane-bound proteases tumor necrosis factor alpha-converting enzyme and furin were not found to be responsible for this cleavage nor was BACE observed to mediate its own endoproteolysis by an autocatalytic mechanism. Thus, we characterize a specific processing event that may serve to regulate the enzymatic activity of BACE on a post-translational level. C1 Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr 182B, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98108 USA. Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP Cook, DG (reprint author), Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr 182B, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIA NIH HHS [AG05136, NIA-R01 AG11762, P01 AG11542] NR 60 TC 27 Z9 30 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 MAY 9 PY 2003 VL 278 IS 19 BP 17141 EP 17149 DI 10.1074/jbc.M213303200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 677QG UT WOS:000182818600093 PM 12551920 ER PT J AU Luo, BH Springer, TA Takagi, J AF Luo, BH Springer, TA Takagi, J TI High affinity ligand binding by Integrins does not involve head separation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IIB-IIIA COMPLEX; MURINE MONOCLONAL-ANTIBODY; BETA-PROPELLER DOMAIN; INSIDE-OUT ACTIVATION; ALPHA-IIB-BETA-3 INTEGRIN; EXTRACELLULAR SEGMENT; CRYSTAL-STRUCTURE; ALPHA-SUBUNIT; I-DOMAIN; FIBRINOGEN AB Conformational change in the integrin extracellular domain is required for high affinity ligand binding and is also involved in post-ligand binding cellular signaling. Although there is evidence to the contrary, electron microscopic studies showing that ligand binding triggers alpha- and beta-subunit dissociation in the integrin headpiece have gained popularity and support the hypothesis that head separation activates integrins. To test directly the head separation hypothesis, we enforced head association by introducing disulfide bonds across the interface between the alpha-subunit beta-propeller domain and the beta-subunit I-like domain. Basal and activation-dependent ligand binding by alpha(IIb)beta(3) and alpha(V)beta(3) was unaffected. The covalent linkage prevented dissociation of alpha(IIb)beta(3) into its subunits on EDTA-treated cells. Whereas EDTA dissociated wild type alpha(IIb)beta(3) on the cell surface, a ligand-mimetic Arg-Gly-Asp peptide did not, as judged by binding of complex-specific antibodies. Finally, a high affinity ligand-mimetic compound stabilized noncovalent association between alpha(IIb) and beta(3) headpiece fragments in the presence of SDS, indicating that ligand binding actually stabilized subunit association at the head, as opposed to the suggested subunit separation. The mechanisms of conformational regulation of integrin function should therefore be considered in the context of the associated alphabeta headpiece. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Takagi, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave,Rm 238, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL48675] NR 44 TC 12 Z9 12 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 MAY 9 PY 2003 VL 278 IS 19 BP 17185 EP 17189 DI 10.1074/jbc.M301516200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 677QG UT WOS:000182818600099 PM 12600996 ER PT J AU Yu, ASL Enck, AH Lencer, WI Schneeberger, EE AF Yu, ASL Enck, AH Lencer, WI Schneeberger, EE TI Claudin-8 expression in Madin-Darby canine kidney cells augments the paracellular barrier to cation permeation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TIGHT JUNCTION STRANDS; EPITHELIAL-CELLS; MDCK CELLS; RABBIT GALLBLADDER; SELECTIVE CHANNELS; ADHESION MOLECULE; PROTEIN; OCCLUDIN; PERMEABILITY; MECHANISM AB Claudins are a family of integral membrane proteins of the tight junction that are thought to participate in the permeation of solutes across epithelia via the paracellular pathway. Claudin-8 is expressed in the distal renal tubule, which has a characteristically low passive permeability to monovalent cations. To test the hypothesis that claudin-8 plays a role in forming a tight paracellular barrier to cations, stably transfected Madin-Darby canine kidney II cell lines with inducible expression of claudin-8 were generated. Induction of claudin-8 expression was associated with down-regulation of endogenous claudin-2 protein. Other tight junction proteins were expressed and targeted normally, and the number of junctional strands was minimally altered. By Ussing chamber and radiotracer flux studies, claudin-8 expression was found to reduce paracellular permeability to monovalent inorganic and organic cations and to divalent cations but not to anions or neutral solutes. The size selectivity, charge dependence, and activation energy of paracellular cation permeation were all unchanged. These observations are consistent with a model in which claudin-2 encodes a highly cation-permeable channel, whereas claudin-8 acts primarily as a cation barrier. When exogenous claudin-8 is expressed, it replaces endogenous claudin-2, inserting in its place into existing tight junction strands, thereby reducing the apparent number of functional cation pores. Our findings suggest that claudin-8 plays an important role in the paracellular cation barrier of the distal renal tubule. C1 Univ So Calif, Keck Sch Med, Div Nephrol, Dept Med, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Harvard Digest Dis Ctr, Boston, MA 02115 USA. RP Yu, ASL (reprint author), Univ So Calif, Keck Sch Med, Div Nephrol, Dept Med, 2025 Zonal Ave,RMR 406, Los Angeles, CA 90033 USA. EM alanyu@usc.edu OI Yu, Alan/0000-0002-1776-2533 FU NHLBI NIH HHS [HL25822]; NIDDK NIH HHS [DK34854] NR 42 TC 186 Z9 193 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 9 PY 2003 VL 278 IS 19 BP 17350 EP 17359 DI 10.1074/jbc.M213286200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 677QG UT WOS:000182818600121 PM 12615928 ER PT J AU Grady, D AF Grady, D TI Postmenopausal hormones - Therapy for symptoms only SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID QUALITY-OF-LIFE; ESTROGEN/PROGESTIN REPLACEMENT; HEART; TRIAL; WOMEN C1 Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Grady, D (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. NR 5 TC 59 Z9 62 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 MAY 8 PY 2003 VL 348 IS 19 BP 1835 EP 1837 DI 10.1056/NEJMp030038 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 675FY UT WOS:000182684100001 PM 12642636 ER PT J AU Waxman, AB Shepard, JO Mark, EJ AF Waxman, AB Shepard, JO Mark, EJ TI Case 14-2003: A 73-year-old woman with pneumonia and progressive respiratory failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID COMMUNITY-ACQUIRED PNEUMONIA; DIFFUSE ALVEOLAR DAMAGE; DISTRESS-SYNDROME; SURVEILLANCE; MANAGEMENT; TULAREMIA; PROGNOSIS; ETIOLOGY; DISEASE; LUNG C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Thorac 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 Waxman, AB (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 30 TC 7 Z9 7 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 MAY 8 PY 2003 VL 348 IS 19 BP 1902 EP 1912 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 675FY UT WOS:000182684100010 PM 12736284 ER PT J AU Lorenz, K Lynn, J AF Lorenz, K Lynn, J TI Moral and practical challenges of physician-assisted suicide SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID OREGON; EUTHANASIA; DEATH C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA. Washington Home Ctr Palliat Care Studies, Washington, DC USA. RP Lorenz, K (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. NR 17 TC 2 Z9 2 U1 0 U2 0 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 MAY 7 PY 2003 VL 289 IS 17 BP 2282 EP 2282 DI 10.1001/jama.289.17.2282 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 675ET UT WOS:000182680700034 PM 12734143 ER PT J AU Zile, MR AF Zile, MR TI Heart failure with preserved ejection fraction: Is this diastolic heart failure? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID VENTRICULAR SYSTOLIC FUNCTION; HYPERTROPHY; DYSFUNCTION; DIAGNOSIS C1 Med Univ S Carolina, Dept Med, Gazes Cardiac Res Inst, Div Cardiol, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Zile, MR (reprint author), Med Univ S Carolina, Dept Med, Gazes Cardiac Res Inst, Div Cardiol, 135 Rutledge Ave,Suite 1201,POB 250592, Charleston, SC 29425 USA. NR 15 TC 64 Z9 66 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 MAY 7 PY 2003 VL 41 IS 9 BP 1519 EP 1522 DI 10.1016/S0735-1097(03)00186-4 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 674HR UT WOS:000182631800016 PM 12742292 ER PT J AU Shekelle, PG Rich, MW Morton, SC Atkinson, SW Tu, WL Maglione, M Rhodes, S Barrett, M Fonarow, GC Greenberg, B Heidenreich, PA Knabel, T Konstam, MA Steimle, A Stevenson, LW AF Shekelle, PG Rich, MW Morton, SC Atkinson, SW Tu, WL Maglione, M Rhodes, S Barrett, M Fonarow, GC Greenberg, B Heidenreich, PA Knabel, T Konstam, MA Steimle, A Stevenson, LW TI Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status - A meta-analysis of major clinical trials SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CHRONIC HEART-FAILURE; RANDOMIZED INTERVENTION TRIAL; MYOCARDIAL-INFARCTION; MERIT-HF; METOPROLOL; CARVEDILOL; MORTALITY; MORBIDITY; CAPTOPRIL; BLOCKADE AB OBJECTIVES This study sought to assess the effect of angiotensin-converting enzyme (ACE) inhibitors and beta-blockers on all-cause mortality in patients with left ventricular (LV) systolic dysfunction according to gender, race, and the presence of diabetes. BACKGROUND Major randomized clinical trials have established that ACE inhibitors and beta-blockers have life-saving benefits in patients with LV systolic dysfunction. Most patients enrolled in these trials were Caucasian men. Whether an equal effect is achieved in women, non-Caucasians, and patients with major comorbidities has not been established. METHODS The authors performed a meta-analysis of published and individual patient data from the 12 largest randomized clinical trials of ACE inhibitors and beta-blockers to produce random effects estimates of mortality for subgroups. RESULTS Data support beneficial reductions in all-cause mortality for the use of beta-blockers in men and women, the use of ACE inhibitors and some beta-blockers in black and white patients, and the use of ACE inhibitors and beta-blockers in patients with or without diabetes. Women with symptomatic LV systolic dysfunction probably benefit from ACE inhibitors, but women with asymptomatic LV systolic dysfunction may not have reduced mortality when treated with ACE inhibitors (pooled relative risk = 0.96; 95% confidence interval: 0.75 to 1.22). The pooled estimate of three beta-blocker studies supports a beneficial effect in black patients with heart failure, but one study assessing bucindolol reported a nonsignificant increase in mortality. CONCLUSIONS Angiotensin-converting enzyme inhibitors and beta-blockers provide life-saving benefits in most of the subpopulations assessed. Women with asymptomatic LV systolic dysfunction may not achieve a mortality benefit when treated with ACE inhibitors. (C) 2003 by the American College of Cardiology Foundation. C1 RAND Hlth, So Calif Evidence Based Practice Ctr, Santa Monica, CA 90407 USA. Greater Los Angeles VA Med Ctr, Div Gen Internal Med, Los Angeles, CA USA. Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. RAND Corp, Arroyo Ctr, Santa Monica, CA USA. USA, Dept Med, SE Reg Med Command, Athens, GA USA. Drexel Univ, Coll Med, Dept Med, Philadelphia, PA 19104 USA. Ahmanson UCLA, Cariomyopathy Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. Univ Calif San Diego, Heart Failure Cardiac Transplantat Program, San Diego, CA 92103 USA. Stanford Univ, Dept Med, Stanford, CA 94305 USA. VA Palo Alto Healthcare Syst, Stanford, CA USA. Ingenix, Eden Prairie, MN USA. Tufts New England Med Ctr, Dept Med, Div Cardiol, Boston, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Kaiser Permanente No Calif, Heart Failure Program, Santa Clara, CA USA. Brigham & Womens Hosp, Cardiomyopathy & Heart Failure Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Shekelle, PG (reprint author), RAND Hlth, So Calif Evidence Based Practice Ctr, 1700 Main St,POB 2138, Santa Monica, CA 90407 USA. OI Heidenreich, Paul/0000-0001-7730-8490 FU PHS HHS [290-97-0000, 290-97-0001] NR 34 TC 226 Z9 234 U1 4 U2 7 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 MAY 7 PY 2003 VL 41 IS 9 BP 1529 EP 1538 DI 10.1016/S0735-1097(03)00262-6 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 674HR UT WOS:000182631800018 PM 12742294 ER PT J AU Steere, AC AF Steere, AC TI Duration of antibiotic therapy for Lyme disease SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID ERYTHEMA MIGRANS; CEFTRIAXONE; DOXYCYCLINE; BORRELIOSIS; ARTHRITIS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Steere, AC (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 8301, Charlestown, MA 02129 USA. NR 18 TC 7 Z9 7 U1 0 U2 0 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 MAY 6 PY 2003 VL 138 IS 9 BP 761 EP 762 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 674XA UT WOS:000182661400010 PM 12729432 ER PT J AU Oberdoerffer, P Novobrantseva, TI Rajewsky, K AF Oberdoerffer, P Novobrantseva, TI Rajewsky, K TI Expression of a targeted lambda 1 light chain gene is developmentally regulated and independent of Ig kappa rearrangements SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE gene rearrangement; B lymphocyte; light chain; receptor editing; development ID B-CELL DEVELOPMENT; V(D)J RECOMBINATION; MICE; RECEPTOR; SEQUENCES; LOCUS; TRANSCRIPTION; GENERATION; TOLERANCE; ENHANCER AB Immunoglobulin light chain (IgL) rearrangements occur more frequently at Igkappa than at Iglambda. Previous results suggested that the unrearranged Igkappa locus negatively regulates Iglambda transcription and/or rearrangement. Here, we demonstrate that expression of a VJlambda1-joint inserted into its physiological position in the Iglambda locus is independent of Igkappa rearrangements. Expression of the inserted VJlambda1 gene segment is developmentally controlled like that of a VJkappa-joint inserted into the Igkappa locus and furthermore coincides developmentally with the occurrence of Igkappa rearrangements in wild-type mice. We conclude that developmentally controlled transcription of a gene rearrangement in the Iglambda locus occurs in the presence of an unrearranged Igkappa locus and is therefore not negatively regulated by the latter. Our data also indicate light chain editing in similar to30% of lambda1 expressing B cell progenitors. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Cologne, Inst Genet, D-50932 Cologne, Germany. RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA092625, P01 CA92625-01] NR 42 TC 21 Z9 21 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 5 PY 2003 VL 197 IS 9 BP 1165 EP 1172 DI 10.1084/jem.20030402 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 676KW UT WOS:000182752000010 PM 12719477 ER PT J AU de Stahl, TD Dahlstrom, J Carroll, MC Heyman, B AF de Stahl, TD Dahlstrom, J Carroll, MC Heyman, B TI A role for complement in feedback enhancement of antibody responses by IgG3 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE rodents; Fc receptors; cellular activation; transgenic/knockout ID RII-DEFICIENT MICE; MEDIATED ENHANCEMENT; IMMUNE-RESPONSE; FC RECEPTOR; CAPSULAR POLYSACCHARIDE; CD23-DEFICIENT MICE; IMMUNOGLOBULIN-E; H-2A(B) MICE; IGM; ANTIGEN AB IgG1, IgG2a, and IgG2b, passively administered with soluble Ags, enhance specific Ab responses. The effect of IgG3 in this type of feedback regulation has not been studied previously. We immunized mice with trinitrophenyl (TNP)-coupled carrier proteins (bovine serum albumin [BSA] or ovalbumin [OVA]) alone or complexed to monoclonal TNP-specific IgG3. The carrier-specific Ab responses were enhanced by several hundred-fold by IgG3. Enhancement was significantly impaired in mice depleted of complement factor C3 and in mice lacking complement receptors 1 and 2 (Cr2(-/-)). In contrast, mice lacking the common Fc-receptor gamma chain (FcRgamma(-/-)), resulting in reduced expression of FcgammaRI and lack of FcgammaRIII, and mice lacking FcgammaRIIB (FcgammaRIIB(-/-)), responded equally well to immunization with IgG3-complexed Ag as wild-type controls. These findings demonstrate that IgG3 can induce feedback enhancement and that IgG3, in analogy with IgM, uses the complement system for this function. C1 Uppsala Univ, Dept Genet & Pathol, Rudbeck Lab, SE-75185 Uppsala, Sweden. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Heyman, B (reprint author), Uppsala Univ, Dept Genet & Pathol, Rudbeck Lab, SE-75185 Uppsala, Sweden. NR 58 TC 23 Z9 23 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 MAY 5 PY 2003 VL 197 IS 9 BP 1183 EP 1190 DI 10.1084/jem.20022232 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 676KW UT WOS:000182752000012 ER PT J AU Enzler, T Gillessen, S Manis, JP Ferguson, D Fleming, J Alt, FW Mihm, M Dranoff, G AF Enzler, T Gillessen, S Manis, JP Ferguson, D Fleming, J Alt, FW Mihm, M Dranoff, G TI Deficiencies of GM-CSF and interferon gamma link inflammation and cancer SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE GM-CSF; IFN-gamma; cancer; inflammation; SLE ID COLONY-STIMULATING FACTOR; CELL-DEATH; B-CELLS; MICE; AUTOIMMUNITY; HOMEOSTASIS; FAS; TUMORIGENESIS; IMMUNITY; LYMPHOMA AB Chronic inflammation contributes to carcinogenesis, but the underlying mechanisms are poorly understood. We report that aged granulocyte-macrophage colony stimulating factor (GM-CSF)-deficient mice develop a systemic lupus erythematosis (SLE)-like disorder associated with the impaired phagocytosis of apoptotic cells. Concurrent deficiency of interferon (IFN)-gamma attenuates the SLE, but promotes the formation of diverse hematologic and solid neoplasms within a background of persistent infection and inflammation. Whereas activated B cells show a resistance to fas-induced apoptosis, antimicrobial therapy prevents lymphomagenesis and solid tumor development. These findings demonstrate that the interplay of infectious agents with cytokine-mediated regulation of immune homeostasis is a critical determinant of cancer susceptibility. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 510E,44 Binney St, Boston, MA 02115 USA. NR 30 TC 104 Z9 105 U1 0 U2 5 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 MAY 5 PY 2003 VL 197 IS 9 BP 1213 EP 1219 DI 10.1084/jem.20021258 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 676KW UT WOS:000182752000016 PM 12732663 ER PT J AU Tremblay, CL Hicks, JL Sutton, L Giguel, F Flynn, T Johnston, M Sax, PE Walker, BD Hirsch, MS Rosenberg, ES D'Aquila, RT AF Tremblay, CL Hicks, JL Sutton, L Giguel, F Flynn, T Johnston, M Sax, PE Walker, BD Hirsch, MS Rosenberg, ES D'Aquila, RT TI Antiretroviral resistance associated with supervised treatment interruptions in treated acute HIV infection SO AIDS LA English DT Article ID SELECTION; THERAPY AB We studied 14 patients acutely infected with wild-type HIV, who underwent supervised treatment interruptions after initial antiretroviral treatment including lamivudine. Lamivudine resistance mutations emerged for the first time during supervised treatment interruptions in one patient. Resistance should be monitored in supervised treatment interruptions trials, because mutations may first be detected only after therapy is interrupted. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Vanderbilt Univ, Med Ctr, Div Infect Dis, Nashville, TN USA. RP Tremblay, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. FU NIAID NIH HHS [AI 40873, AI 49414-31, AI29193, AI30914] NR 9 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 2 PY 2003 VL 17 IS 7 BP 1086 EP 1089 DI 10.1097/01.aids.0000060339.12269.b0 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 677XP UT WOS:000182834600021 PM 12700462 ER PT J AU Sekhon, B Sekhon, C Khan, M Patel, SJ Singh, I Singh, AK AF Sekhon, B Sekhon, C Khan, M Patel, SJ Singh, I Singh, AK TI N-Acetyl cysteine protects against injury in a rat model of focal cerebral ischemia SO BRAIN RESEARCH LA English DT Article DE focal cerebral ischemia; tumor necrosis factor; N-acetyl cysteine; nitric oxide; infarct volume ID NITRIC-OXIDE SYNTHASE; ACUTE-RENAL-FAILURE; ARTERY OCCLUSION; REPERFUSION INJURY; BRAIN INJURY; STROKE INCIDENCE; MICE LACKING; DAMAGE; INHIBITION; NECROSIS AB Ischemic cerebrovascular disease (stroke) is one of the leading causes of death and long-time disability. Ischemia/reperfusion to any organ triggers a complex series of biochemical events, which affect the structure and function of every organelle and subcellular system of the affected cells. The purpose of this study was to investigate the therapeutic efficacy of N-acetyl cysteine (NAC), a precursor of glutathione and a potent antioxidant, to attenuate ischemia/reperfusion injury to brain tissue caused by a focal cerebral ischemia model in rats. A total of 27 male Sprague-Dawley rats weighing 250-300 g were used in this study. Focal cerebral ischemia (45 min) was induced in anesthetized rats by occluding the middle cerebral artery (MCA) with an intra-luminal suture through the internal carotid artery. The rats were scored post-reperfusion for neurological deficits. They were then sacrificed after 24 h of reperfusion and infarct volume in the brain was assessed by 2,3,5-triphenyl tetrazolium chloride (TTC). Brain sections were immunostained for tumor necrosis factor (TNF-alpha) and inducible nitric oxide synthase (NOS). Animals treated with NAC showed a 49.7% (S.E.M. = 1.25) reduction in brain infarct volume and 50% (S.E.M. = 0.48) reduction in the neurological evaluation score as compared to the untreated animals. NAC treatment also blocked the ischemia/reperfusion-induced expression of tumor necrosis factor and inducible nitric oxide synthase. The data suggest that pre-administration of NAC attenuates cerebral ischemia and reperfusion injury in this brain ischemia model. This protective effect may be as a result of suppression of TNF-alpha and NOS. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Div Dev Neurogenet, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol Surg, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29403 USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pathol & Lab Med, Rm 316 CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. FU NINDS NIH HHS [NS-40810, NS-22576, NS-34741, NS-37766, NS-40144] NR 39 TC 104 Z9 111 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 2 PY 2003 VL 971 IS 1 BP 1 EP 8 DI 10.1016/S0006-8993(03)002244-3 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 673NJ UT WOS:000182586800001 PM 12691831 ER PT J AU Groisman, R Polanowska, J Kuraoka, I Sawada, J Saijo, M Drapkin, R Kisselev, AF Tanaka, K Nakatani, Y AF Groisman, R Polanowska, J Kuraoka, I Sawada, J Saijo, M Drapkin, R Kisselev, AF Tanaka, K Nakatani, Y TI The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage SO CELL LA English DT Article ID RNA-POLYMERASE-II; TRANSCRIPTION-COUPLED REPAIR; COCKAYNE-SYNDROME; PROTEIN; DEGRADATION; PROTEASOME; CELLS; NEDD8; PATHWAY; DEUBIQUITINATION AB Nucleotide excision repair (NER) is a major cellular defense against the carcinogenic effects of ultraviolet light from the sun. Mutational inactivation of NER proteins, like DDB and CSA, leads to hereditary diseases such as xeroderma pigmentosum (XP) and Cockayne syndrome (CS). Here, we show that DDB2 and CSA are each integrated into nearly identical complexes via interaction with DDB1. Both complexes contain cullin 4A and Roc1 and display ubiquitin ligase activity. They also contain the COP9 signalosome (CSN), a known regulator of cullin-based ubiquitin ligases. Strikingly, CSN differentially regulates ubiquitin ligase activity of the DDB2 and CSA complexes in response to UV irradiation. Knockdown of CSN with RNA interference leads to defects in NER. These results suggest that the distinct UV response of the DDB2 and CSA complexes is involved in diverse mechanisms of NER. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Osaka Univ, Grad Sch Frontier Biosci, Osaka 5650871, Japan. Japan Sci & Technol Corp, CREST, Osaka 5650871, Japan. RP Nakatani, Y (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. RI Drapkin, Ronny/E-9944-2016; Polanowska, Jolanta/P-9117-2016 OI Drapkin, Ronny/0000-0002-6912-6977; Polanowska, Jolanta/0000-0001-7666-7010 NR 39 TC 464 Z9 495 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAY 2 PY 2003 VL 113 IS 3 BP 357 EP 367 DI 10.1016/S0092-8674(03)00316-7 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 674MP UT WOS:000182640800010 PM 12732143 ER PT J AU Nojima, H Tokunaga, C Eguchi, S Oshiro, N Hidayat, S Yoshino, K Hara, K Tanaka, N Avruch, J Yonezawa, K AF Nojima, H Tokunaga, C Eguchi, S Oshiro, N Hidayat, S Yoshino, K Hara, K Tanaka, N Avruch, J Yonezawa, K TI The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; CELL-GROWTH; AMINO-ACID; PHAS-I; EIF-4E BP1; PHOSPHORYLATION; PATHWAY; IDENTIFICATION; TRANSLATION; INSULIN AB The mammalian target of rapamycin (mTOR) controls multiple cellular functions in response to amino acids and growth factors, in part by regulating the phosphorylation of p70 S6 kinase (p70S6k) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). Raptor (regulatory associated protein of mTOR) is a recently identified mTOR binding partner that also binds p70S6k and 4E-BP1 and is essential for TOR signaling in vivo. Herein we demonstrate that raptor binds to p70S6k and 4E-BP1 through their respective TOS (conserved TOR signaling) motifs to be required for amino acid- and mTOR-dependent regulation of these mTOR substrates in vivo. A point mutation of the TOS motif also eliminates all in vitro mTOR-catalyzed 4E-BP1 phosphorylation and abolishes the raptor-dependent component of mTOR-catalyzed p70S6k phosphorylation in vitro. Raptor appears to serve as an mTOR scaffold protein, the binding of which to the TOS motif of mTOR substrates is necessary for effective mTOR-catalyzed phosphorylation in vivo and perhaps for conferring their sensitivity to rapamycin and amino acid sufficiency. C1 Kobe Univ, Biosignal Res Ctr, Nada Ku, Kobe, Hyogo 6578501, Japan. Japan Sci & Technol Corp, CREST, Okayama 7000914, Japan. Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol Surg Transplant & Surg Oncol, Okayama 7000914, Japan. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Yonezawa, K (reprint author), Kobe Univ, Biosignal Res Ctr, Nada Ku, 1-1 Rokkodai Cho, Kobe, Hyogo 6578501, Japan. FU NCI NIH HHS [CA 73818]; NIDDK NIH HHS [DK 17776] NR 28 TC 332 Z9 341 U1 3 U2 17 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 MAY 2 PY 2003 VL 278 IS 18 BP 15461 EP 15464 DI 10.1074/jbc.C200665200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 675EL UT WOS:000182680000002 PM 12604610 ER PT J AU Scherer, SW Cheung, J MacDonald, JR Osborne, LR Nakabayashi, K Herbrick, JA Carson, AR Parker-Katiraee, L Skaug, J Khaja, R Zhang, JJ Hudek, AK Li, M Haddad, M Duggan, GE Fernandez, BA Kanematsu, E Gentles, S Christopoulos, CC Choufani, S Kwasnicka, D Zheng, XQH Lai, ZW Nusskern, D Zhang, Q Gu, ZP Lu, F Zeesman, S Nowaczyk, MJ Teshima, I Chitayat, D Shuman, C Weksberg, R Zackai, EH Grebe, TA Cox, SR Kirkpatrick, SJ Rahman, N Friedman, JM Heng, HHQ Pelicci, PG Lo-Coco, F Belloni, E Shaffer, LG Pober, B Morton, CC Gusella, JF Bruns, GAP Korf, BR Quade, BJ Ligon, AH Ferguson, H Higgins, AW Leach, NT Herrick, SR Lemyre, E Farra, CG Kim, HG Summers, AM Gripp, KW Roberts, W Szatmari, P Winsor, EJT Grzeschik, KH Teebi, A Minassian, BA Kere, J Armengol, L Pujana, MA Estivill, X Wilson, MD Koop, BF Tosi, S Moore, GE Boright, AP Zlotorynski, E Kerem, B Kroisel, PM Petek, E Oscier, DG Mould, SJ Dohner, H Dohner, K Rommens, JM Vincent, JB Venter, JC Li, PW Mural, RJ Adams, MD Tsui, LC AF Scherer, SW Cheung, J MacDonald, JR Osborne, LR Nakabayashi, K Herbrick, JA Carson, AR Parker-Katiraee, L Skaug, J Khaja, R Zhang, JJ Hudek, AK Li, M Haddad, M Duggan, GE Fernandez, BA Kanematsu, E Gentles, S Christopoulos, CC Choufani, S Kwasnicka, D Zheng, XQH Lai, ZW Nusskern, D Zhang, Q Gu, ZP Lu, F Zeesman, S Nowaczyk, MJ Teshima, I Chitayat, D Shuman, C Weksberg, R Zackai, EH Grebe, TA Cox, SR Kirkpatrick, SJ Rahman, N Friedman, JM Heng, HHQ Pelicci, PG Lo-Coco, F Belloni, E Shaffer, LG Pober, B Morton, CC Gusella, JF Bruns, GAP Korf, BR Quade, BJ Ligon, AH Ferguson, H Higgins, AW Leach, NT Herrick, SR Lemyre, E Farra, CG Kim, HG Summers, AM Gripp, KW Roberts, W Szatmari, P Winsor, EJT Grzeschik, KH Teebi, A Minassian, BA Kere, J Armengol, L Pujana, MA Estivill, X Wilson, MD Koop, BF Tosi, S Moore, GE Boright, AP Zlotorynski, E Kerem, B Kroisel, PM Petek, E Oscier, DG Mould, SJ Dohner, H Dohner, K Rommens, JM Vincent, JB Venter, JC Li, PW Mural, RJ Adams, MD Tsui, LC TI Human chromosome 7: DNA sequence and biology SO SCIENCE LA English DT Article ID HUMAN GENOME; SEGMENTAL DUPLICATIONS; LANGUAGE DISORDER; REGION; MAP; LOCALIZATION; SPEECH; GENES; MODEL AB DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism. C1 Hosp Sick Children, Dept Genet & Genom Biol, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Child Dev Ctr, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Dept Paediat, Div Neurol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada. Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF A1B 3V6, Canada. Celera Genom, Rockville, MD 20850 USA. Hamilton Hlth Sci Ctr, Hamilton, ON L8N 3Z5, Canada. McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON L8N 3Z5, Canada. Univ Toronto, Dept Pediat, Toronto, ON M5G 1X8, Canada. Childrens Hosp Philadelphia, Div Human Genet & Mol Biol, Philadelphia, PA 19104 USA. Univ Phoenix Genet Program, Phoenix, AZ 85016 USA. Univ Wisconsin, Dept Med Genet, Madison, WI 53706 USA. Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England. Univ British Columbia, Dept Med Genet, Vancouver, BC V6H 3N1, Canada. Wayne State Univ, Sch Med, Detroit, MI 48202 USA. European Inst Oncol, Dept Expt Oncol, I-20141 Milan, Italy. Firc Inst Mol Oncol, Canc Genet Unit, I-20134 Milan, Italy. Univ Roma Tor Vergata, Dipartimento Biopatol & Diagnost Immagini, I-00133 Rome, Italy. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurogenet Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. N York Gen Hosp, Dept Genet, Toronto, ON M2K 1E1, Canada. Alfred I DuPont Hosp Children, Div Med Genet, Wilmington, DE 19899 USA. Univ Toronto, Univ Hlth Network, Prenatal Diag Program, Toronto, ON M5G 1X5, Canada. Univ Toronto, Univ Hlth Network, Dept Lab Med & Pathobiol, Toronto, ON M5G 1X5, Canada. Univ Marburg, Med Zentrum Humangenet, D-35037 Marburg, Germany. Karolinska Inst, Novum, Dept Biosci, S-14157 Stockholm, Sweden. Huddinge Univ Hosp, Clin Res Ctr, S-14157 Stockholm, Sweden. Ctr Genom Regulat, Program Genes & Dis, Barcelona 08003, Catalonia, Spain. Univ Victoria, Dept Biol, Victoria, BC V8W 3N5, Canada. John Radcliffe Hosp, Inst Mol Med, MRC, Mol Haematol Unit, Oxford OX3 9DS, England. Univ London Imperial Coll Sci Technol & Med, Fac Med, Inst Reprod & Dev Biol, Dept Fetal & Maternal Med, London W12 0NN, England. Univ Toronto, Univ Hlth Network, Dept Med, Div Endocrinol, Toronto, ON M5G 2C4, Canada. Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. Karl Franzens Univ Graz, Inst Med Biol & Human Genet, A-8010 Graz, Austria. Royal Bournemouth Hosp, Dept Haematol, Bournemouth BH7 7DW, Dorset, England. Univ Hosp Ulm, Dept Internal Med 3, D-89081 Ulm, Germany. Univ Toronto, Clark Inst, Ctr Addict & Mental Hlth, Toronto, ON M5T 1R8, Canada. Univ Toronto, Dept Psychiat, Toronto, ON M5T 1R8, Canada. RP Scherer, SW (reprint author), Hosp Sick Children, Dept Genet & Genom Biol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM steve@genet.sickkids.on.ca RI Koop, Ben/A-8151-2008; Kere, Juha/A-9179-2008; Tsui, Lap-chee/A-1081-2010; Estivill, Xavier/E-2957-2012; Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013; Rahman, Nazneen/B-8890-2012; Wilson, Michael/K-6294-2014; Estivill, Xavier/A-3125-2013; pujana, Miguel Angel/N-3127-2014; Moore, Gudrun/A-2092-2009; belloni, elena/H-9909-2013; Rahman, Nazneen/D-2802-2013; OI Koop, Ben/0000-0003-0045-5200; Kere, Juha/0000-0003-1974-0271; Scherer, Stephen /0000-0002-8326-1999; Wilson, Michael/0000-0002-4015-3066; Estivill, Xavier/0000-0002-0723-2256; pujana, Miguel Angel/0000-0003-3222-4044; Zheng Bradley, Xiangqun/0000-0002-9324-2708; Rahman, Nazneen/0000-0003-4376-0440; Belloni, Elena/0000-0003-3214-0780 FU Canadian Institutes of Health Research [38103]; NIGMS NIH HHS [P01 GM061354] NR 31 TC 127 Z9 497 U1 0 U2 16 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 MAY 2 PY 2003 VL 300 IS 5620 BP 767 EP 772 DI 10.1126/science.1083423 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673KH UT WOS:000182579800041 PM 12690205 ER PT J AU Prasad, SR Sahani, D Nasser, S Farrell, J Fernandez-Del Castillo, C Hahn, PF Mueller, PR AF Prasad, SR Sahani, D Nasser, S Farrell, J Fernandez-Del Castillo, C Hahn, PF Mueller, PR TI Intraductal papillary mucinous tumors of the pancreas SO ABDOMINAL IMAGING LA English DT Article DE endoscopic retrograde cholangiopancreatography; (ERCP); pancreas, CT; pancreas, cysts; pancreas, MR; pancreas, neoplasms; pancreas; pancreatic ducts ID DUCTAL ECTASIA; CYSTIC LESIONS; HELICAL CT; NEOPLASMS; DIFFERENTIATION AB Intraductal papillary mucinous tumor (IPMT) is an uncommon pancreatic neoplasm with characteristic histology and distinctive clinicobiologic behavior. It is characterized by proliferation of ductal epithelium associated with ductal dilatation and variable mucin production. Due to indolent nature of these tumors, IPMTs are frequently missed or misdiagnosed. Prompt recognition and differentiation from other tumors are essential because IPMT has a better prognosis than other pancreatic malignancies. The purpose of this article is to display the radiologic spectrum of IPMT. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Gastrointestinal Endoscopy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Sahani, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 25 TC 14 Z9 19 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD MAY-JUN PY 2003 VL 28 IS 3 BP 357 EP 365 DI 10.1007/s00261-002-0037-z PG 9 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 673ZB UT WOS:000182610300010 PM 12719906 ER PT J AU Sahani, DV Jhaveri, KS D'souza, RV Varghese, JC Halpern, E Harisinghani, MG Hahn, PF Saini, S AF Sahani, DV Jhaveri, KS D'souza, RV Varghese, JC Halpern, E Harisinghani, MG Hahn, PF Saini, S TI Evaluation of simethicone-coated cellulose as a negative oral contrast agent for abdominal CT SO ACADEMIC RADIOLOGY LA English DT Article DE abdomen, CT; computed tomography (CT), contrast enhancement; computed tomography (CT), contrast media; intestines, CT; simethicone ID HELICAL CT; ABDOMEN AB Rationale and Objectives. Because of the increased clinical use of computed tomography (CT) for imaging the abdominal vasculature and urinary tract, there is a need for negative contrast agents. The authors undertook this study to assess the suitability of simethicone-coated cellulose (SCC), which is approved for use as an oral contrast agent in sonography, for use as a negative oral contrast agent in abdominal CT. Materials and Methods. This prospective study involved 40 adult patients scheduled to undergo abdominal CT for the evaluation of hematuria. Prior to scanning, 20 subjects received 800 mL of SCC and 20 received 800 mL of water as an oral contrast agent. Imaging was performed with a multi-detector row helical scanner in two phases, according to the abdominal CT protocol used for hematuria evaluation at the authors' institution. The first, "early" phase began an average of 15 minutes after the ingestion of contrast material; the second, "late" phase began an average of 45 minutes after the ingestion of contrast material. Blinded analysis was performed by three abdominal radiologists separately, using a three-point scale (0 = poor, 1 = acceptable, 2 = excellent) to assess the effectiveness of SCC for marking the proximal, middle, and distal small bowel. Average scores for enhancement with SCC and with water were obtained and compared. Statistical analysis was performed with a Wilcoxon signed-rank test. Results. SCC was assigned higher mean scores than water for enhancement in each segment of the bowel, both on early-phase images (0.8-1.35 for SCC vs 0.6-1.1 for water) and on late-phase images (1.1-1.4 vs 0.81-0.96). Bowel marking with SCC, particularly in the jejunum and ileum, also was rated better than that with water in a high percentage of patients. The differences between the scores for water and for SCC, however, were not statistically significant (P >.05). Conclusion. SCC is effective as a negative oral contrast agent for small bowel marking at CT. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. NR 10 TC 9 Z9 9 U1 2 U2 3 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAY PY 2003 VL 10 IS 5 BP 491 EP 496 DI 10.1016/S1076-6332(03)80057-0 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 673EG UT WOS:000182566800004 PM 12755536 ER PT J AU Zhukareva, V Sundarraj, S Mann, D Sjogren, M Blenow, K Clark, CM McKeel, DW Goate, A Lippa, CF Vonsattel, JP Growdon, JH Trojanowski, JQ Lee, VMY AF Zhukareva, V Sundarraj, S Mann, D Sjogren, M Blenow, K Clark, CM McKeel, DW Goate, A Lippa, CF Vonsattel, JP Growdon, JH Trojanowski, JQ Lee, VMY TI Selective reduction of soluble Tau proteins in sporadic and familial frontotemporal dementias: an international follow-up study SO ACTA NEUROPATHOLOGICA LA English DT Article DE frontotemporal dementia; dementia lacking distinctive histopathology; Tau proteins; paired helical; filament tau ID ARGYROPHILIC GRAIN DISEASE; PICKS-DISEASE; ALPHA-SYNUCLEIN; CORTICOBASAL DEGENERATION; DIAGNOSTIC-CRITERIA; ALZHEIMERS-DISEASE; WHITE-MATTER; EXON 10; MUTATIONS; FTDP-17 AB Recently, biochemical criteria were proposed to complement histological criteria for the diagnosis of dementia lacking distinctive histopathology (DLDH), the most common pathological variant of frontotemporal dementias (FTDs), based on evidence of a selective reduction of soluble tau proteins in brains from a large cohort of sporadic DLDH and hereditary FTD (HDDD2 family) patients. To ensure that these findings are not unique to the populations included in the initial report, we extended the previous work by analyzing 22 additional DLDH brains from the United States and international centers. Our biochemical analyses here confirmed the previous findings by demonstrating substantial reductions in soluble brain tau in gray and white matter of 14 cases and moderate reductions in 6 cases of DLDH. We also analyzed brain samples from an additional affected HDDD2 family member, and remarkably, unlike other previously studied members of this kindred, this patient's brain contained substantial amounts of pathological or insoluble tau. These findings confirm and extend the definition of DLDH as a sporadic or familial "tau-less" tauopathy with reduced levels of soluble brain tau and no insoluble tau or fibrillary tau inclusions, and the data also underline the phenotypic heterogeneity of HDDD2, which parallels the phenotypic heterogeneity of other hereditary neurodegenerative FTD, tauopathies caused by tau gene mutations. C1 Univ Penn, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. Greater Manchester Neurosci Ctr, Manchester, Lancs, England. Sahlgrens Univ Hosp, Dept Psychiat, Inst Clin Neurosci, Molndal, Sweden. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Washington Univ, St Louis, MO USA. Drexel Univ, Sch Med, Philadelphia, PA USA. Columbia Univ, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn, Inst Aging, Philadelphia, PA USA. RP Lee, VMY (reprint author), Univ Penn, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Maloney 3 HUP,3600 Spruce St, Philadelphia, PA 19104 USA. EM vmylee@mail.med.upenn.edu OI Sjogren, Magnus/0000-0003-2060-1914 NR 37 TC 36 Z9 37 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD MAY PY 2003 VL 105 IS 5 BP 469 EP 476 DI 10.1007/s00401-002-0668-8 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 675NX UT WOS:000182702400008 PM 12677447 ER PT J AU Samet, JH Horton, NJ Traphagen, ET Lyon, SM Freedberg, KA AF Samet, JH Horton, NJ Traphagen, ET Lyon, SM Freedberg, KA TI Alcohol consumption and HIV disease progression: Are they related? SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE HIV; alcohol dependence; disease progression ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; PRIMARY-CARE; INFECTED PATIENTS; AIDS; PREVALENCE; ADHERENCE; HEPATOTOXICITY; MEDICATIONS; LYMPHOCYTES AB Background: The relationship between alcohol consumption and HIV disease progression has received limited attention in the era of highly active antiretroviral therapy (HAART). Methods: We assessed CD4 cell count, HIV RNA levels, and alcohol consumption in the past month, defined as none, moderate, and at risk, in 349 HIV-infected people with a history of alcohol problems. We investigated the relationship between alcohol consumption and HIV disease markers CD4 cell count and HIV RNA level, stratified by HAART use, using multivariable regression. Results: No significant differences in CD4 cell count or HIV RNA level were found across the categories of alcohol consumption for patients who were not receiving HAART. However, among patients who were receiving HAART, log HIV RNA levels were significantly higher in those with moderate (2.17 copies/ml) and at-risk (2.73 copies/ml) alcohol use compared with none (1.73 copies/ml; p=0.006). CD4 cell counts in those with moderate (368 cells/mul) and at-risk (360 cells/mul) alcohol use were lower than for subjects who reported none (426 cells/mul; p=0.07). Conclusion: Among patients who have a history of alcohol problems and are receiving antiretroviral treatment, alcohol consumption was associated with higher HIV RNA levels and lower CD4 counts. No comparable association was found for similar patients who were not receiving HAART. Addressing alcohol use in HIV-infected patients, especially those who are receiving HAART, may have a substantial impact on HIV disease progression. C1 Boston Univ, Boston Med Ctr,Sch Med, Dept Med,Gen Internal Med Sect, Clin Addict Res & Educ Unit, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Social & Behav Sci, Sect Gen Internal Med,Clin Addict Res & Educ Unit, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. RP Samet, JH (reprint author), Boston Univ, Boston Med Ctr,Sch Med, Dept Med,Gen Internal Med Sect, Clin Addict Res & Educ Unit, 91 E Concord St,Suite 200, Boston, MA 02118 USA. RI Horton, Nicholas/A-2493-2008; OI Samet, Jeffrey/0000-0002-0897-3400; Horton, Nicholas/0000-0003-3332-4311 FU NIAAA NIH HHS [R01 AA 13766, R01 AA 10870, R01 AA 11785, R01 AA010870, R01 AA011785] NR 41 TC 84 Z9 84 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2003 VL 27 IS 5 BP 862 EP 867 DI 10.1097/01.ALC.0000065438.80967.56 PG 6 WC Substance Abuse SC Substance Abuse GA 682GN UT WOS:000183083500016 PM 12766632 ER PT J AU Kemper, KJ Amata-Kynvi, A Dvorkin, L Whelan, JS Woolf, A Samuels, RC Hibberd, P AF Kemper, KJ Amata-Kynvi, A Dvorkin, L Whelan, JS Woolf, A Samuels, RC Hibberd, P TI Herbs and other dietary supplements: Healthcare professionals' knowledge, attitudes, and practices SO ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE LA English DT Article ID ALTERNATIVE MEDICINE USE; PEDIATRIC ONCOLOGY; CANCER-PATIENTS; FOLK REMEDIES; THERAPY USE; COMPLEMENTARY; CARE; PREVALENCE; POPULATION; EMERGENCY AB Context . Herbs and other dietary supplements (H/DS) are frequently used by the public. They have significant health implications, yet little is known about health professionals' knowledge, attitudes, or clinical practices related to H/DS. Design . Cross-sectional survey of clinicians prior to participation in an Internet-based educational program on herbs and dietary supplements. Participants . The 537 participants included 111 physicians (MM 30 advanced practice nurses (RN), 46 pharmacists (PharmD), and 350 dietitians (RD). In addition to demographic information, participants were asked about their knowledge, attitudes, and practices related to H/DS. Results . Most participants were involved in direct patient care (85%), in practice or on faculty (84%), and from outside our local institutions (76%); 66% reported receiving professional education about H/DS in the past year. There were statistically significant differences between professional groups, with RDs scoring better than others, but even their average scores were less than 60% of possible. The average score on knowledge questions was 10/20, the average confidence score was 4 out of 10 possible, and the average communication score was 1.4 out of 4 possible. Most respondents knew the most common clinical uses Of echinacea and St. John's wort, and felt confident that they knew more than their colleagues about H/DS. Key deficits were in knowledge about adverse effects, confidence in reporting side effects, routinely communicating with patients about H/DS, and recording H/DS information in the medical record. Conclusions . Despite significant interest and previous training in H/DS, these clinicians had substantial room for improvement in knowledge, attitudes, and clinical practices about H/DS. Educational interventions (end institutional policies are needed to improve the quality of patient care regarding H/DS, and such interventions should be rigorously evaluated to ensure that continuous improvements occur. C1 Brenner Childrens Hosp, Winston Salem, NC USA. Massachusetts Coll Pharm & Hlth Sci, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. RP Kemper, KJ (reprint author), InnoVis Commun, 169 Saxony Rd,Suite 104, Encinitas, CA 92024 USA. RI eshaghian, azam/Q-8826-2016 OI eshaghian, azam/0000-0001-7918-2895 FU NCCIH NIH HHS [1R21 AT00213] NR 69 TC 39 Z9 40 U1 1 U2 3 PU INNOVISION COMMUNICATIONS PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1078-6791 J9 ALTERN THER HEALTH M JI Altern. Ther. Health Med. PD MAY-JUN PY 2003 VL 9 IS 3 BP 42 EP 49 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 678MN UT WOS:000182871100005 PM 12776474 ER PT J AU Wood, MJ Stewart, RL Merry, H Johnstone, DE Cox, JL AF Wood, MJ Stewart, RL Merry, H Johnstone, DE Cox, JL TI Use of complementary and alternative medical therapies in patients with cardiovascular disease SO AMERICAN HEART JOURNAL LA English DT Article ID HERBAL MEDICINES; UNITED-STATES; HEALTH-CARE; SUPPLEMENTS; POPULATION; PATTERNS; MERCURY AB Background Complementary and alternative medical (CAM) therapies are becoming increasingly popular, yet little information is available about the prevalence and patterns of CAM therapy use by patients with cardiovascular disease (CVD). Methods interviewers administered telephone questionnaires to 107 patients randomly selected from a stratified cohort of 2487 eligible patients participating in a registry of patients with CVD. Results The current use of CAM therapies was reported by 64010 of the patients surveyed. Nutritional supplements (40%) and megadose vitamins (35%) were the most frequently used preparations. Most CAM therapy users (65%) cited their underlying cardiac condition as the reason for taking such therapy. The most common sources of information about CAM were a friend or relative (43%) or the respondent's usual physician. However, although 80% of respondents claimed that they had discussed their use of CAM therapies with their physician, 58% of respondents taking a potentially toxic cardiovascular medication (digoxin, warfarin, sotalol, or amiodarone) were simultaneously taking an oral supplement. Conclusion The use of CAM therapies was high in the cohort of patients surveyed. Physicians caring for patients with CVD need to inquire about CAM therapy use. Further scientific study should be performed to evaluate the potential benefits and risks of CAM therapies in this patient population. C1 Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Dalhousie Univ, Dept Med, Div Cardiol, Halifax, NS, Canada. Dalhousie Univ, Dept Epidemiol & Community Hlth, Halifax, NS, Canada. RP Wood, MJ (reprint author), Massachusetts Gen Hosp VBK 508, 55 Fruit St, Boston, MA 02114 USA. NR 31 TC 58 Z9 59 U1 4 U2 9 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 MAY PY 2003 VL 145 IS 5 BP 806 EP 812 DI 10.1016/S0002-8703(03)00084-X PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 685JC UT WOS:000183258300009 PM 12766736 ER PT J AU Mauri, L Reisman, M Buchbinder, M Popma, JJ Sharma, SK Cutlip, DE Ho, KKL Prpic, R Zimetbaum, PJ Kuntz, RE AF Mauri, L Reisman, M Buchbinder, M Popma, JJ Sharma, SK Cutlip, DE Ho, KKL Prpic, R Zimetbaum, PJ Kuntz, RE TI Comparison of rotational atherectomy with conventional balloon angioplasty in the prevention of restenosis of small coronary arteries: Results of the Dilatation vs Ablation Revascularization Trial Targeting Restenosis (DART) SO AMERICAN HEART JOURNAL LA English DT Article ID STENT PLACEMENT; DIRECTIONAL ATHERECTOMY; SMALL VESSELS; DISEASE; ANGIOGRAPHY; DIAMETER AB Background The optimum treatment of obstructive coronary disease in small (<3.0 mm diameter) arteries remains unknown. Rotational atherectomy is an approved treatment that might reduce the vascular injury during percutaneous coronary intervention compared with angioplasty. We report on a multicenter, randomized, blinded end point trial comparing rotational atherectomy with balloon angioplasty in the prevention of restenosis of obstructed small coronary arteries. Methods A total of 446 patients with myocardial ischemia associated with an angiographic stenosis in a native coronary artery 2 to 3 mm in diameter and &LE;20 mm in length without severe calcification were randomly assigned to receive rotational atherectomy (n = 227) or balloon angioplasty (n = 219). The primary end point was target vessel failure at 12 months (defined as the composite of death, Q-wave myocardial infarction, and clinically driven repeat revascularization of the target vessel). Results The mean reference vessel diameter was 2.46 &PLUSMN; 0.40 mm, the mean lesion length was 9.97 &PLUSMN; 5.59 mm, and the prevalence of diabetes mellitus was 32%. Acute procedural success (91.6% for rotational atherectomy, 94.1% for balloon angioplasty, P = .36) and target vessel failure at 12 months were not significantly different (30.5% vs 31.2%, P = .98). At 8 months, there were no significant differences in minimum lumen diameter (1.28 &PLUSMN; 0.63 mm vs 1.19 &PLUSMN; 0.54 mm, P = .26), percent diameter stenosis (28% &PLUSMN; 12% vs 29% 15%, P = .59), binary restenosis rate (50.5% vs 50.5%, P = 1.0), or late loss index (0.57 vs 0.62, P = .7). No Q-wave myocardial infarctions occurred in either arm of the study, and non-Q-wave myocardial infarctions (defined as creatine kinase level >2 times normal with an elevated creatine kinase-myocardial band isoenzyme level) occurred in 2.2% and 1.4% of the patients in the rotational atherectomy and balloon angioplasty groups, respectively (P = .72). Conclusion Rotational atherectomy was found to be safe in the treatment of obstructed small arteries, but lower rates of target vessel failure were not achieved compared with balloon angioplasty. Because the acute gain and loss index ratios of the 2 treatments were similar, there was no evident beneficial antirestenosis mechanism seen for rotational atherectomy. C1 Brigham & Womens Hosp, Div Clin Biometr, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Swedish Med Ctr, Seattle, WA USA. Mt Sinai Hosp, New York, NY 10029 USA. Scripps Mem Hosp, La Jolla, CA USA. Harvard Univ, Clin Res Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA 02215 USA. RP Kuntz, RE (reprint author), Brigham & Womens Hosp, Div Clin Biometr, 75 Francis St, Boston, MA 02115 USA. OI Sharma, Sanjeev Kumar/0000-0002-3273-0708 NR 26 TC 37 Z9 40 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 MAY PY 2003 VL 145 IS 5 BP 847 EP 854 DI 10.1016/S0002-8703(03)00080-2 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 685JC UT WOS:000183258300015 PM 12766743 ER PT J AU Miller, DP Alfredson, T Cook, SF Sands, BE Walker, AM AF Miller, DP Alfredson, T Cook, SF Sands, BE Walker, AM TI Incidence of colonic ischemia, hospitalized complications of constipation, and bowel surgery in relation to use of alosetron hydrochloride SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID COLITIS; WOMEN; DIARRHEA; TRIAL AB OBJECTIVE: Alosetron hydrochloride (Lotronex), a potent selective 5-hydroxytryptamine(3) receptor antagonist, was approved in February, 2000 in the United States for the treatment of diarrhea-predominant irritable bowel syndrome (IBS) in women. Marketing was suspended in November, 2000, after reports of colonic ischemia and serious complications of constipation. We sought to compare the incidence of colonic ischemia, hospitalized complications of constipation. and bowel surgery among alosetron users and a cohort of patients with IBS who did not use alosetron. METHODS: We sought outcomes of colonic ischemia, hospitalized complications of constipation, and bowel surgery in 3,631 Lotronex users and 2,480 comparison IBS subjects using diagnoses, procedures, and drugs recorded in the UnitedHealthcare insurance claims database, and validated these by chart review. The initial assessment was to last for 3 yr beginning with the start of alosetron treatment and was to include 10,000 Lotronex users; however, the observation period ended by December 31, 2000, after suspension of marketing M, RESULTS: There were 3631 alosetron users among members of UnitedHealthcare from March through December, 2000, and we identified 2480 comparison IBS-only patients; follow-up time averaged about 5 months in both groups. There were no instances of colonic ischemia in either cohort. Thirty instances of bowel surgery occurred, giving rates of 10.2/1000 person-yr in the alosetron cohort and 11.8/1000 person-yr in the IBS/no alosetron cohort. There were three cases of hospitalized complications of constipation. The incidence rates were essentially the same in alosetron users (1.24/1000 person-yr) and in IBS patients with no alosetron use (0.92/1000 person-yr). CONCLUSIONS: Alosetron users did not differ from IBS patients not using alosetron in the incidence of bowel surgery or hospitalized complications of constipation; there were no cases of colonic ischemia. The statistical upper limit of colonic ischemia rates in alosetron users was 2.28/1000 person-yr. Because of the market withdrawal, the size of the cohort and the duration of follow-up were smaller than originally planned; consequently, the statements about the safety of alosetron were necessarily limited. On June 7, 2002, the Food and Drug Administration approved alosetron for reintroduction in the U.S. market for women with severe diarrhea-related IBS. (C) 2003 by Am. Coll. of Gastroenterology. C1 GlaxoSmithKline, Res Triangle Pk, NC USA. Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Ingenix Epidemiol, Newton, MA 02466 USA. RP Miller, DP (reprint author), Ingenix Epidemiol, 275 Grove St,Suite 3-120, Newton, MA 02466 USA. FU NIDDK NIH HHS [5K23 DK02850-03] NR 16 TC 36 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2003 VL 98 IS 5 BP 1117 EP 1122 DI 10.1016/S0002-9270(03)00136-9 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 688RG UT WOS:000183449300027 PM 12809837 ER PT J AU Serby, M Brickman, AM Haroutunian, V Purohit, DP Marin, D Lantz, M Mobs, RC Davis, KL AF Serby, M Brickman, AM Haroutunian, V Purohit, DP Marin, D Lantz, M Mobs, RC Davis, KL TI Cognitive burden and excess Lewy-body pathology in the Lewy-body variant of Alzheimer disease SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID DEMENTIA AB Authors compared the degrees of cognitive deficit among individuals with Alzheimer disease (AD), the Lewy-body variant of AD (LBV), and "pure" dementia with Lewy bodies (DLB); and compared cortical Lewy body (LB) counts in LBV versus DLB and neuritic plaque and neurofibrillary tangle severity in LBV versus AD. Methods: Authors examined brain specimens from consecutive autopsies of elderly nursing home subjects. Numbers and densities of plaques, Lewy bodies, and tangle severity were determined in multiple cortical regions, and demographic and clinical variables were compared among the three groups. Results: The three groups did not differ in demographic or clinical variables. The LBV group was significantly more impaired than the other groups. Cortical LB counts were significantly higher in LBV than in DLB. There was no evidence of increased plaque or tangle severity in LBV than in AD. Conclusion. The co-occurrence of AD and LB pathology is associated with higher numbers of LBs and more severe dementia than when classical AD or LB lesions occur alone. C1 Beth Israel Med Ctr, Dept Psychiat, New York, NY 10003 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Mt Sinai Sch Med, Dept Pathol, New York, NY USA. Bronx Vet Affairs Med Ctr, Psychiat Serv, Bronx, NY USA. Jewish Home & Hosp, New York, NY USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Serby, M (reprint author), Beth Israel Med Ctr, Dept Psychiat, 1st Ave & 16th St, New York, NY 10003 USA. FU NIA NIH HHS [P01 AG 02219, P50 AG 05138] NR 10 TC 16 Z9 16 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAY-JUN PY 2003 VL 11 IS 3 BP 371 EP 374 DI 10.1176/appi.ajgp.11.3.371 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 673DQ UT WOS:000182565300016 PM 12724118 ER PT J AU Bakker, SC van der Meulen, EM Buitelaar, JK Sandkuijl, LA Pauls, DL Monsuur, AJ van't Slot, R Minderaa, RB Gunning, WB Pearson, PL Sinke, RJ AF Bakker, SC van der Meulen, EM Buitelaar, JK Sandkuijl, LA Pauls, DL Monsuur, AJ van't Slot, R Minderaa, RB Gunning, WB Pearson, PL Sinke, RJ TI A whole-genome scan in 164 Dutch sib pairs with attention-deficit/hyperactivity disorder: Suggestive evidence for linkage on chromosomes 7p and 15q SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DEFICIT-HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER GENE; AUTISTIC DISORDER; RECEPTOR GENE; SUSCEPTIBILITY LOCI; READING-DISABILITY; BETA-HYDROXYLASE; ASSOCIATION; CHILDREN; ADHD AB A genome scan was performed on 164 Dutch affected sib pairs (ASPs) with attention-deficit/hyperactivity disorder (ADHD). All subjects were white and of Dutch descent and were phenotyped according to criteria set out in the Diagnostic and Statistical Manual Of Mental Disorders, 4th edition. Initially, a narrow phenotype was defined, in which all the sib pairs met the full ADHD criteria (117 ASPs). In a broad phenotype, additional sib pairs were included, in which one child had an autistic-spectrum disorder but also met the full ADHD criteria (164 ASPs). A set of 402 polymorphic microsatellite markers with an average intermarker distance of 10 cM was genotyped and analyzed using the Mapmaker/sibs program. Regions with multipoint maximum likelihood scores (MLSs) >11.5 in both phenotypes were fine mapped with additional markers. This genome scan indicated several regions of interest, two of which showed suggestive evidence for linkage. The most promising chromosome region was located at 15q, with an MLS of 3.54 under the broad phenotype definition. This region was previously implicated in reading disability and autism. In addition, MLSs of 3.04 and 2.05 were found for chromosome regions 7p and 9q in the narrow phenotype. Except for a region on chromosome 5, no overlap was found with regions mentioned in the only other independent genome scan in ADHD reported to date. C1 Univ Med Ctr, Dept Med Genet, NL-3508 AB Utrecht, Netherlands. Univ Med Ctr, Dept Child & Adolescent Psychiat, NL-3508 AB Utrecht, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit, Boston, MA USA. Univ Groningen, Univ Med Ctr Groningen, Univ Ctr Child & Adolescent Psychiat, Groningen, Netherlands. Univ Amsterdam, Acad Med Ctr, Dept Child & Adolescent Psychiat, NL-1105 AZ Amsterdam, Netherlands. Leiden Univ, Dept Med Stat, Med Ctr, NL-2300 RA Leiden, Netherlands. Univ Med Ctr Nijmegen, Dept Psychiat, Nijmegen, Netherlands. RP Bakker, SC (reprint author), Univ Med Ctr, Dept Med Genet, KC 04-084-2,POB 85090, NL-3508 AB Utrecht, Netherlands. EM s.c.bakker@med.uu.nl RI Sinke, Richard/A-1462-2009; Buitelaar, Jan/E-4584-2012 OI Buitelaar, Jan/0000-0001-8288-7757 NR 68 TC 178 Z9 185 U1 15 U2 19 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 MAY PY 2003 VL 72 IS 5 BP 1251 EP 1260 DI 10.1086/375143 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 671PZ UT WOS:000182474400016 PM 12679898 ER PT J AU Feng, JA Perry, G Wang, DJ Oparil, S Chen, YF AF Feng, JA Perry, G Wang, DJ Oparil, S Chen, YF TI Pressure overload in the atrial natriuretic peptide deficient mouse: A novel model of heart failure SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the American-Society-of-Hypertension CY MAY 14-17, 2003 CL NEW YORK, NEW YORK SP Amer Soc Hypertens DE atrial natriuretic peptide; heart hypertrophy and failure; transgenic mouse C1 Univ Alabama, Vasc Biol & Hypertens Program, Birmingham, AL USA. Birmingham VA Med Ctr, Cardiol Sect, Birmingham, AL 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 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2003 VL 16 IS 5 MA OR57 BP 26A EP 26A DI 10.1016/S0895-7061(03)00140-7 PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 677LK UT WOS:000182809000057 ER PT J AU Eslami, P Nyby, MD Corry, DB Eggena, P Tuck, ML AF Eslami, P Nyby, MD Corry, DB Eggena, P Tuck, ML TI Insulin increases vascular smooth muscle cell cytosolic angiotensin II via an angiotensin type-1 receptor dependent mechanism SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the American-Society-of-Hypertension CY MAY 14-17, 2003 CL NEW YORK, NEW YORK SP Amer Soc Hypertens DE angiotensin II; insulin; vascular smooth muscle cells C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles HEalthcare Syst, Sepulveda, CA USA. Olive View UCLA Med Ctr, Sylmar, CA 91342 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 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2003 VL 16 IS 5 MA P348 BP 164A EP 164A DI 10.1016/S0895-7061(03)00513-2 PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 677LK UT WOS:000182809000430 ER PT J AU Stevanovic, RD Deborah, PA Cecilia, LM Lori, LM Norman, HK AF Stevanovic, RD Deborah, PA Cecilia, LM Lori, LM Norman, HK TI Renin release in response to renin system blockade: Further evidence for activation of the intrarenal renin system in type-1 diabetes mellitus SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the American-Society-of-Hypertension CY MAY 14-17, 2003 CL NEW YORK, NEW YORK SP Amer Soc Hypertens DE plasma renin activity; renal plasma flow; diabetic nephropathy C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Joslin Clin, Boston, MA 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 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2003 VL 16 IS 5 MA P360 BP 168A EP 168A DI 10.1016/S0895-7061(03)00525-9 PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 677LK UT WOS:000182809000442 ER PT J AU Lloyd-Jones, DM Leip, EP Larson, MG Vasan, RS Levy, D AF Lloyd-Jones, DM Leip, EP Larson, MG Vasan, RS Levy, D TI Competing risks for first cardiovascular events after hypertension onset: The Framingham Heart Study SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the American-Society-of-Hypertension CY MAY 14-17, 2003 CL NEW YORK, NEW YORK SP Amer Soc Hypertens DE hypertension; epidemiology; outcomes C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RI Lloyd-Jones, Donald/C-5899-2009 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 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2003 VL 16 IS 5 MA P484 BP 213A EP 214A DI 10.1016/S0895-7061(03)00656-3 PN 2 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 677LK UT WOS:000182809000566 ER PT J AU Basile, JN AF Basile, JN TI Optimizing antihypertensive treatment in clinical practice. SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the American-Society-of-Hypertension CY MAY 14-17, 2003 CL NEW YORK, NEW YORK SP Amer Soc Hypertens DE hypertension; beta blockers; add-on therapy C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 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 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2003 VL 16 IS 5 BP 268A EP 268A DI 10.1016/S0895-7061(03)00808-2 PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 677LK UT WOS:000182809000716 ER PT J AU Pohland, CJ Scavnicky, SA Lasky, SS Good, CB AF Pohland, CJ Scavnicky, SA Lasky, SS Good, CB TI Lansoprazole overutilization: Methods for step-down therapy SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID PROTON PUMP INHIBITORS; BARRETTS-ESOPHAGUS; DUODENAL-ULCER; OMEPRAZOLE; RANITIDINE; OVERUSE AB Objective: To identify the documented indications for long-term therapy with lansoprazole 30 mg twice daily at the Veterans Affairs Pittsburgh Healthcare System, assess compliance with appropriate use criteria, evaluate patients eligible for step-down therapy, and recommend appropriate step-down therapy in order to improve patient care, decrease over-prescribing, and reduce medication costs. Study Design: Prospective intervention. Methods: The records of all patients with prescriptions for lansoprazole 30 mg twice daily as of June 2000 were reviewed. Patients were interviewed to assess medication compliance and symptom control and to provide education on lifestyle modifications. Interventions with the providers were completed to encourage step-down therapy in appropriate patients. Results: Two hundred forty-eight patients with active prescriptions for twice-daily lansoprazole were reviewed. Of these patients, 66% (n = 163) did not have an indication compliant with the medical center's guidelines for use of lansoprazole 30 mg twice daily. Of these, 88% (n = 143) had no documented attempt at step-down therapy and 49% (n = 80) had no documented gastrointestinal workup. Interventions for step-down therapy were recommended for 48% (n = 120) of the 248 patients. Forty-six percent (n = 60) of recommendations were accepted, resulting in a cost savings of $85 000 per year. Conclusions: A high rate of clinician noncompliance with the guidelines for appropriate use of lansoprazole 30 mg twice daily was found. These prescribing patterns resulted in significant cost concerns. Our review and interventions led to step-down therapy for almost half of the patients receiving twice-daily lansoprazole. This review of patient records and intervention with primary care providers resulted in cost reduction and offered an opportunity to educate patients on beneficial lifestyle modifications. C1 Vet Affairs Pittsburgh Healthcare Syst, Pharm SErv 132M U, Pittsburgh, PA 15240 USA. RP Scavnicky, SA (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Pharm SErv 132M U, Univ Dr C, Pittsburgh, PA 15240 USA. NR 21 TC 10 Z9 12 U1 0 U2 3 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 MAY PY 2003 VL 9 IS 5 BP 353 EP 358 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 677LA UT WOS:000182807900001 PM 12744297 ER PT J AU Leyne, M Mull, J Gill, SP Cuajungco, MP Oddoux, C Blumenfeld, A Maayan, C Gusella, JF Axelrod, FB Slaugenhaupt, SA AF Leyne, M Mull, J Gill, SP Cuajungco, MP Oddoux, C Blumenfeld, A Maayan, C Gusella, JF Axelrod, FB Slaugenhaupt, SA TI Identification of the first non-Jewish mutation in familial dysautonomia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE familial dysautonomia; IKBKAP; Ashkenazi Jewish mutation; non-Jewish familial dysautonomia ID B KINASE COMPLEX; IKBKAP GENE; IKAP; ELONGATOR; COMPONENT; PROTEIN AB Familial Dysautonomia is an autosomal recessive disease with a remarkably high carrier frequency in the Ashkenazi Jewish population. It has recently been estimated that as many as 1 in 27 Ashkenazi Jews is a carrier of FD. The FD gene has been identified as IKBKAP, and two disease-causing mutations have been identified. The most common mutation, which is present on 99.5% of all FD chromosomes, is an intronic splice site mutation that results in tissue-specific skipping of exon 20. The second mutation, R696P, is a missense mutation that has been identified in 4 unrelated patients heterozygous for the major splice mutation. Interestingly, despite the fact that FD is a recessive disease, normal mRNA and protein are expressed in patient cells. To date, the diagnosis of FD has been limited to individuals of Ashkenazi Jewish descent and identification of the gene has led to widespread diagnostic and carrier testing in this population. In this report, we describe the first non-Jewish IKBKAP mutation, a proline to leucine missense mutation in exon 26, P914L. This mutation is of particular significance because it was identified in a patient who lacks one of the cardinal diagnostic criteria for the disease-pure Ashkenazi Jewish ancestry. In light of this fact, the diagnostic criteria for FD must be expanded. Furthermore, in order to ensure carrier identification in all ethnicities, this mutation must now be considered when screening for FD. (C) 2003 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Harvard Inst Human Genet, Boston, MA USA. NYU Med Ctr, Dept Pediat, Human Genet Program, New York, NY 10016 USA. Hadassah Univ Hosp, Dept Ophthalmol, IL-91120 Jerusalem, Israel. Hadassah Univ Hosp, Dept Pediat, IL-91120 Jerusalem, Israel. NYU, Sch Med, Dept Pediat, New York, NY USA. RP Slaugenhaupt, SA (reprint author), HIM Bldg,Room 422,4 Blackfan Circle, Boston, MA 02115 USA. RI Cuajungco, Math/B-2647-2008 OI Cuajungco, Math/0000-0003-0749-9564 FU NINDS NIH HHS [NS36323] NR 23 TC 44 Z9 44 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 0148-7299 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAY 1 PY 2003 VL 118A IS 4 BP 305 EP 308 DI 10.1002/ajmg.a.20052 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 672FY UT WOS:000182511600001 PM 12687659 ER PT J AU Villa, VM Harada, NB Washington, D Damron-Rodriguez, J AF Villa, VM Harada, NB Washington, D Damron-Rodriguez, J TI The health and functional status of US veterans aged 65+: Implications for VA health programs serving an elderly, diverse veteran population SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE health services; health status; long-term care; race/ethnicity; veterans ID ALAMEDA COUNTY; LIFE AB As the US population is aging, so too is the US veteran population. Chief among the challenges facing the Department of Veterans Affairs (VA) is developing health programs and services that mesh with the needs of an aging veteran population and therefore improve the health status of elderly veterans. Meeting this challenge requires an understanding of the health needs of the older veteran population, including health disparities that exist across racial ethnic populations. This study examines the selfrated health and functioning of a national sample of veterans aged 65+ participating in the National Survey of Veterans. The results show that over one half of elderly veterans report difficulty in functioning and rate their health status as fair or poor. Additionally, elderly African American and Hispanic veterans report worse health than non-Hispanic white veterans across the majority of health indicators. Given the health profile of older veterans found in this study, it would seem necessary that programs serving older veterans be adept at the ongoing medical management of chronic disease and the provision of long-term care services. C1 Univ Calif Los Angeles, Sch Publ Hlth, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Policy & Social Res, Los Angeles, CA USA. RP Villa, VM (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, VA Greater Los Angeles Hlth Care Syst, Bldg 115,Room 328,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 24 TC 11 Z9 11 U1 0 U2 2 PU AMER COLLEGE MEDICAL QUALITY PI BETHESDA PA 4334 MONTGOMERY AVE, 2ND FL, BETHESDA, MD 20814-4402 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD MAY-JUN PY 2003 VL 18 IS 3 BP 108 EP 116 DI 10.1177/106286060301800304 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 687DJ UT WOS:000183360500004 PM 12836900 ER PT J AU Grady, D AF Grady, D TI Myocardial infarction during menses: Lessons from trials and errors SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID ESTROGEN-REPLACEMENT THERAPY; CORONARY-ARTERY DISEASE; POSTMENOPAUSAL WOMEN; HEART-DISEASE; HORMONE-THERAPY C1 Univ Calif San Francisco, Womens Hlth Clin Res Ctr, San Francisco, CA 94115 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Grady, D (reprint author), Univ Calif San Francisco, Womens Hlth Clin Res Ctr, Box 0739,1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAY PY 2003 VL 114 IS 7 BP 611 EP 612 DI 10.1016/S0002-9343(03)00126-8 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 678WP UT WOS:000182889900014 PM 12753888 ER PT J AU Burns, SP Rivara, FP Johansen, JM Thompson, DC AF Burns, SP Rivara, FP Johansen, JM Thompson, DC TI Rehabilitation of traumatic injuries - Use of the Delphi method to identify topics for evidence-based review SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE rehabilitation; spinal cord injuries; brain injuries; Delphi technique; evidence-based medicine AB Evidence-based reviews of research literature are useful in determining the efficacy of specific clinical practices, but the review process is frequently time-consuming and costly. The purpose of this study was to identify important research questions in rehabilitation that are appropriate for evidence-based reviews. The focus of this study was rehabilitation after traumatic injuries. Topics were identified using the Delphi method, which utilized a panel of 24 researchers and clinicians with expertise in rehabilitation of traumatic injuries. The experts identified 71 topics, predominantly in the areas of spinal cord injury and traumatic brain injury rehabilitation. The most commonly suggested intervention topics involved assessment of, pharmacologic agents, the timing or intensity of interventions, or specific nonpharmacologic therapies and exercises. Topics were ranked by mean importance score. Ten of 24 questions in the top tertile were considered to have some or a substantial amount of available research and thus may be appropriate for structured evidence-based reviews. Similar methods could be used to identify appropriate topics in other areas of rehabilitation. C1 VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv 128, Seattle, WA 98108 USA. Univ Washington, Harborview Injury Prevent & Res Ctr, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Harborview Injury Prevent & Res Ctr, Dept Pediat, Seattle, WA 98195 USA. Univ Washington, Harborview Injury Prevent & Res Ctr, Dept Epidemiol, Seattle, WA 98195 USA. RP Burns, SP (reprint author), VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv 128, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 15 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD MAY PY 2003 VL 82 IS 5 BP 410 EP 414 DI 10.1097/01.PHM.0000064739.60860.A7 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 670AY UT WOS:000182385800014 PM 12704283 ER PT J AU Yeh, CK Hymer, TK Sousa, AL Zhang, BX Lifschitz, MD Katz, MS AF Yeh, CK Hymer, TK Sousa, AL Zhang, BX Lifschitz, MD Katz, MS TI Epidermal growth factor upregulates beta-adrenergic receptor signaling in a human salivary cell line SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE adenylyl cyclase; G protein-coupled receptor; signal transduction; mitogen-activated protein kinase; protein kinase C ID PROTEIN-KINASE-C; OSTEOBLAST-LIKE CELLS; PAROTID ACINAR-CELLS; ADENYLATE-CYCLASE; PARATHYROID-HORMONE; BETA-2-ADRENERGIC RECEPTOR; GENE-EXPRESSION; DOWN-REGULATION; EGF RECEPTOR; GLAND AB The effects of epidermal growth factor (EGF) on the beta-adrenergic receptor-coupled adenylyl cyclase system were studied in a human salivary cell line (HSY). The beta-adrenergic agonist isoproterenol (10(-5) M) stimulated adenylyl cyclase activity by similar to2-fold, and the isoproterenol response was increased 1.8-fold after prolonged ( 48 h) exposure to EGF (5 x 10(-10) M). In contrast, enzyme activation via stimulatory prostaglandin receptors and by agents acting on nonreceptor components of the adenylyl cyclase system was not enhanced by EGF. beta-Adrenergic receptor density, assessed by binding of the beta-adrenergic receptor antagonist (-)-[I-125] iodopindolol, was increased threefold after EGF treatment. Competition binding studies with unlabeled antagonists selective for beta(1)- and beta(2)-adrenergic receptor subtypes indicated that the increase in (-)[I-25] iodopindolol binding sites induced by EGF reflected an increased number of beta(2)-adrenergic receptors. Likewise, Northern blot analysis of RNA from EGF-treated cells revealed selective induction of beta(2)-adrenergic receptor mRNA, which was blocked by the RNA synthesis inhibitor actinomycin D. The increase in beta-adrenergic receptor density produced by EGF was unaltered after phorbol ester-induced downregulation of protein kinase C (PKC). Enhancement of isoproterenol-responsive adenylyl cyclase activity and phosphorylation of mitogen-activated protein kinase ( MAPK) by EGF were both blocked by the MAPK pathway inhibitor PD-98059. The results suggest that in HSY cells EGF enhances beta-adrenergic responsiveness by upregulating beta(2)-adrenergic receptor expression at the transcriptional level. Moreover, the stimulatory effect of EGF on beta(2)-adrenergic receptor signaling appears to be mediated by the MAPK pathway and independent of PKC activation. C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Res Serv, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. RP Katz, MS (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr 182, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. FU NIDCR NIH HHS [DE-10756, DE-12188] NR 60 TC 6 Z9 6 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 MAY PY 2003 VL 284 IS 5 BP C1164 EP C1175 DI 10.1152/ajpcell.00343.2002 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 663AK UT WOS:000181982400009 PM 12540376 ER PT J AU Vaughan, DJ Brogan, TV Kerr, ME Deem, S Luchtel, DL Swenson, ER AF Vaughan, DJ Brogan, TV Kerr, ME Deem, S Luchtel, DL Swenson, ER TI Contributions of nitric oxide synthase isozymes to exhaled nitric oxide and hypoxic pulmonary vasoconstriction in rabbit lungs SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE nitric oxide synthase inhibitors; isolated perfused lung; 1400W; 7-nitroindazole; nitro-L-arginine methyl ester ID ENDOTHELIAL-CELLS; IN-VIVO; INHIBITION; HUMANS; AIRWAYS; CIRCULATION; EPITHELIUM; ASTHMA; MOUSE; FLOW AB We investigated the source(s) for exhaled nitric oxide (NO) in isolated, perfused rabbits lungs by using isozyme-specific nitric oxide synthase (NOS) inhibitors and antibodies. Each inhibitor was studied under normoxia and hypoxia. Only nitro-L-arginine methyl ester (L-NAME, a nonselective NOS inhibitor) reduced exhaled NO and increased hypoxic pulmonary vasoconstriction (HPV), in contrast to 1400W, an inhibitor of inducible NOS (iNOS), and 7-nitroindazole, an inhibitor of neuronal NOS (nNOS). Acetylcholine-mediated stimulation of vascular endothelial NOS (eNOS) increased exhaled NO and could only be inhibited by L-NAME. Selective inhibition of airway and alveolar epithelial NO production by nebulized L-NAME decreased exhaled NO and increased hypoxic pulmonary artery pressure. Immunohistochemistry demonstrated extensive staining for eNOS in the epithelia, vasculature, and lymphatic tissue. There was no staining for iNOS but moderate staining for nNOS in the ciliated cells of the epithelia, lymphoid tissue, and cartilage cells. Our findings show virtually all exhaled NO in the rabbit lung is produced by eNOS, which is present throughout the airways, alveoli, and vessels. Both vascular and epithelial-derived NO modulate HPV. C1 Childrens Hosp & Med Ctr, Dept Pediat, Seattle, WA 98105 USA. Univ Washington, Dept Med, Seattle, WA 98108 USA. Univ Washington, Dept Anesthesiol, Seattle, WA 98108 USA. Univ Washington, Dept Environm Hlth, Seattle, WA 98108 USA. RP Swenson, ER (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NHLBI NIH HHS [HL-03796-01, HL-45591] NR 38 TC 32 Z9 34 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD MAY PY 2003 VL 284 IS 5 BP L834 EP L843 DI 10.1152/ajplung.00341.2002 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 662VB UT WOS:000181968600018 PM 12533440 ER PT J AU Brown, D AF Brown, D TI The ins and outs of aquaporin-2 trafficking SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Review ID KIDNEY COLLECTING DUCT; NEPHROGENIC DIABETES-INSIPIDUS; RENAL EPITHELIAL-CELLS; VASOPRESSIN-MEDIATED TRANSLOCATION; HETEROTRIMERIC G-PROTEIN; A ANCHORING PROTEINS; WATER CHANNEL; APICAL MEMBRANE; RAT-KIDNEY; PRINCIPAL CELLS AB This review outlines recent advances related to the molecular mechanisms and pathways of aquaporin- 2 ( AQP2) water channel trafficking. AQP2 is a fascinating protein, whose sorting signals can be interpreted by different cell types to achieve apical or basolateral membrane insertion, in both regulated and constitutive trafficking pathways. In addition to the well- known cAMP- mediated, stimulatory effect of vasopressin on AQP2 membrane insertion, other signaling and trafficking events can also lead to AQP2 membrane accumulation via cAMP-independent mechanisms. These include 1) elevation of cGMP, mediated by sodium nitroprusside ( a nitric oxide donor), atrial natriuretic factor, and L- arginine ( via nitric oxide synthase); 2) disruption of the actin cytoskeleton; and 3) inhibition of the clathrin- mediated endocytotic arm of the AQP2 recycling pathway by dominant- negative dynamin expression and by membrane cholesterol depletion. Recent data also indicate that AQP2 recycles constitutively in epithelial cells, it can be inserted into different membrane domains in different cell types both in vitro and in vivo, and these pathways can be modulated by factors including hypertonicity. The roles of accessory proteins, including small GTPases and soluble N- ethylmaleimide- sensitive factor attachment protein receptor proteins in AQP2 membrane insertion, are also being uncovered. Understanding cAMP- independent mechanisms for membrane insertion of AQP2 is especially relevant to the therapeutic bypassing of the mutated, dysfunctional vasopressin receptor in patients with X- linked nephrogenic diabetes insipidus. C1 Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Brown, D (reprint author), Massachusetts Gen Hosp E, Program Membrane Biol, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM brown@receptor.mgh.harvard.edu NR 78 TC 155 Z9 159 U1 2 U2 11 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 MAY PY 2003 VL 284 IS 5 BP F893 EP F901 DI 10.1152/ajprenal.00387.2002 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 663RF UT WOS:000182018200003 PM 12676734 ER PT J AU Janech, MG Fitzgibbon, WR Chen, RH Nowak, MW Miller, DH Paul, RV Ploth, DW AF Janech, MG Fitzgibbon, WR Chen, RH Nowak, MW Miller, DH Paul, RV Ploth, DW TI Molecular and functional characterization of a urea transporter from the kidney of the Atlantic stingray SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article; Proceedings Paper CT Experimental Biology 2000 Meeting CY APR 14-19, 2000 CL SAN DIEGO, CA DE euryhaline; 5 '/3 '-rapid amplification of cDNA ends; osmoregulation ID ST-JOHNS RIVER; RAT-KIDNEY; COLLECTING DUCTS; DASYATIS-SABINA; RAJA-ERINACEA; SLC14A2 GENE; CLONING; ELASMOBRANCH; OSMOREGULATION; EXPRESSION AB In general, marine elasmobranch fishes ( sharks, skates, and rays) maintain body fluid osmolality above seawater, principally by retaining large amounts of urea. Maintenance of the high urea concentration is due in large part to efficient renal urea reabsorption. Regulation of renal urea reabsorption also appears to play a role in maintenance of fluid homeostasis of elasmobranchs that move between habitats of different salinities. We identified and cloned a novel 2.7- kb cDNA from the kidney of the euryhaline Atlantic stingray Dasyatis sabina ( GenBank accession no. AF443781). This cDNA putatively encoded a 431- amino acid protein ( strUT- 1) that had a high degree of sequence identity ( 71%) to the shark kidney facilitated urea transporter ( UT). However, the predicted COOH- terminal region of strUT- 1 appears to contain an additional sequence that is unique among cloned renal UTs. Injection of strUT- 1 cRNA into Xenopus oocytes induced a 33- fold increase in [ (14)C] urea uptake that was inhibited by phloretin. Four mRNA bands were detected in kidney by Northern blot: a transcript at 2.8 kb corresponding to the expected size of strUT- 1 mRNA and bands at 3.8, 4.5, and 5.5 kb. Identification of a facilitated UT in the kidney of the Atlantic stingray provides further support for the proposal that passive mechanisms contribute to urea reabsorption by elasmobranch kidney. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Marine Biomed & Environm Sci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pharmacol & Expt Therapeut, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29525 USA. RP Fitzgibbon, WR (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St,POB 250623, Charleston, SC 29425 USA. EM fitzgiwr@musc.edu NR 49 TC 32 Z9 33 U1 2 U2 10 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 MAY PY 2003 VL 284 IS 5 BP F996 EP F1005 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 663RF UT WOS:000182018200014 PM 12388386 ER PT J AU Chang, VW Christakis, NA AF Chang, VW Christakis, NA TI Self-perception of weight appropriateness in the United States SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID BODY-MASS INDEX; REPORTED WEIGHT; MARITAL-STATUS; AFRICAN-AMERICAN; SIZE PERCEPTIONS; NATIONAL-HEALTH; LOSE WEIGHT; WHITE WOMEN; OBESITY; ADULTS AB Background: The self-perception of weight appropriateness is an important component of eating and weight-loss behaviors. Self-perceived weight status, however, is not fully explained by objective weight status. Objective: To examine the influence of sociodemographic factors on Americans' perceptions of their weight appropriateness, controlling for objective weight status. Design: In the Third National Health and Nutrition Examination Survey, respondents were asked, "Do you consider yourself now to be overweight, underweight, or about the right weight?" Responses to this question were compared with how respondents (n = 15,593) would be classified by medical standards given their body mass index (BMI). A proportional odds logistic regression model was used to assess the predictive effects of various sociodemographic factors on weight self-perception. Results: Overall, 27.5% of women and 29.8% of men misclassified their own weight status by medical standards. Of particular note, 38.3% of normal weight women thought they were "overweight," while 32.8% of overweight men thought they were "about the right weight" or "underweight." Multivariate regression analysis revealed that, controlling for BMI, numerous factors-including gender, age, marital status, race, income, and education-were independently associated with the self-evaluation of weight status. Conclusions: The self-perceived appropriateness of weight status varies in highly predictable ways among population-level subgroups, likely reflecting differences in the normative evaluation of bodily weight standards. Such evaluations may assist in the explanation of discrepancies between clinical recommendations based on weight status and actual weight control behaviors, discrepancies that are socially patterned along some of the same subgroupings. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Chicago, Dept Sociol, Chicago, IL 60637 USA. Harvard Med Sch, Dept Hlth Care Policy, Cambridge, MA USA. VAMC, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. RP Chang, VW (reprint author), Univ Penn, Sch Med, Dept Med, 1233 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. RI Christakis, Nicholas/B-6690-2008; Christakis, Nicholas/C-3205-2009 FU AHRQ HHS [T32 HS 00084-04] NR 46 TC 141 Z9 142 U1 6 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAY PY 2003 VL 24 IS 4 BP 332 EP 339 DI 10.1016/S0749-3797(03)00020-5 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 679MV UT WOS:000182927100006 PM 12726871 ER PT J AU Religa, D Laudon, H Styczynska, M Winblad, B Naslund, J Haroutunian, V AF Religa, D Laudon, H Styczynska, M Winblad, B Naslund, J Haroutunian, V TI Amyloid beta pathology in Alzheimer's disease and schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NORMAL HUMAN CORTEX; ELDERLY PATIENTS; COGNITIVE IMPAIRMENT; CYTOARCHITECTONIC DEFINITION; PREFRONTAL AREAS; SYMPTOMS; DEMENTIA; PROGRESSION; POSTMORTEM; MECHANISM AB Objective: Severe cognitive impairment is common in elderly patients with schizophrenia. Alzheimer's disease is the main cause of dementia among the elderly. Biochemical and genetic studies suggest that amyloid beta-peptide is central in Alzheimer's disease. The authors examined the possible involvement of amyloid beta-peptide in cognitive impairment in schizophrenia. Method: Specific antibodies against two major forms of amyloid beta-peptide, Abetax-40 and Abetax-42, were used in sandwich enzyme-linked immunosorbent assays to determine the levels of amyloid beta-peptide in postmortem brain samples from Alzheimer's disease patients (N=10), normal elderly comparison subjects (N=11), and schizophrenia patients with (N=7) or without (N=26) Alzheimer's disease. Results: The levels of amyloid beta-peptide were highest in the Alzheimer's disease patients, followed by the patients with schizophrenia and comparison subjects. The mean Abetax-42 level in the schizophrenia patients without Alzheimer's disease was similar to that in the comparison subjects, but the level in the schizophrenia patients with Alzheimer's disease was significantly higher than in those without Alzheimer's disease or the comparison subjects. The Abetax-42 level in the schizophrenia patients with Alzheimer's disease was significantly lower than the level in the Alzheimer's disease cohort. Conclusions: In contrast to elderly schizophrenia patients with Alzheimer's disease pathology, those without Alzheimer's disease had amyloid beta-peptide levels that were not significantly different from those of normal subjects; hence amyloid beta-peptide does not account for the cognitive deficits in this group. These results suggest that the causes of cognitive impairment in "pure" schizophrenia are different from those in Alzheimer's disease. C1 Karolinska Inst, Dept Clin Neurosci Occupat Therapy & Elderly Care, S-14186 Huddinge, Sweden. Polish Acad Sci, Med Res Ctr, Dept Neurodegenerat Disorders, Warsaw, Poland. Mt Sinai Sch Med, Dept Psychiat, Bronx, NY USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. RP Religa, D (reprint author), Karolinska Inst, Dept Clin Neurosci Occupat Therapy & Elderly Care, S-14186 Huddinge, Sweden. NR 44 TC 22 Z9 22 U1 0 U2 6 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 MAY PY 2003 VL 160 IS 5 BP 867 EP 872 DI 10.1176/appi.ajp.160.5.867 PG 6 WC Psychiatry SC Psychiatry GA 673ZC UT WOS:000182610400010 PM 12727689 ER PT J AU Balbach, ED Gasior, RJ Barbeau, EM AF Balbach, ED Gasior, RJ Barbeau, EM TI R.J. Reynolds' targeting of African Americans: 1988-2000 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID TOBACCO INDUSTRY DOCUMENTS; CIGARETTE ADVERTISEMENTS; MAGAZINES; RELIABILITY; PORTRAYALS; CAMPAIGNS; EXPOSURE; IMAGES; FOCUS; LIFE AB Objectives. The purpose of this study was to describe RJ Reynolds (RJR) Tobacco Company's strategy for targeting African Americans, as revealed in tobacco industry documents and magazine advertisements. Methods. The authors searched industry documents to determine RJR's strategies and analyzed magazine advertising during 2 periods: the time of the launch of the company's Uptown cigarette (1989-1990) and a decade later (1999-2000). Results. RJR's efforts to target the African American market segment existed before and after Uptown, and the company's strategy was largely implemented via other RJR brands. Advertisements featured mentholated cigarettes, fantasy/escape, expensive objects, and nightlife. Conclusions. To help all populations become tobacco-free, tobacco control practitioners must understand and counter tobacco industry strategies. C1 Tufts Univ, Community Hlth Program, Medford, MA 02155 USA. Brown Univ, Providence, RI 02912 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. RP Balbach, ED (reprint author), Tufts Univ, Community Hlth Program, 112 Packard Ave, Medford, MA 02155 USA. NR 64 TC 67 Z9 67 U1 0 U2 5 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 MAY PY 2003 VL 93 IS 5 BP 822 EP 827 DI 10.2105/AJPH.93.5.822 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 675GG UT WOS:000182685100038 PM 12721151 ER PT J AU Schnapp, LM Matosian, M Weisman, I Welsh, CH AF Schnapp, LM Matosian, M Weisman, I Welsh, CH TI A snapshot of pulmonary medicine at the turn of the century - The American Thoracic Society membership SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE career choice; medical faculty; pulmonary disease (specialty); questionnaires ID WOMEN PHYSICIANS; UNDERSERVED POPULATIONS; ACADEMIC MEDICINE; RESPONSE RATES; CAREER; PROFESSION; RADIOLOGY; MINORITY; STUDENTS; LIFE AB To describe the characteristics of the American Thoracic Society, the Membership Committee developed a survey to assess demographics, training, professional activities, and needs of a diverse membership with a growing international segment. It also provided an opportunity to determine how the Society reflects the current state of pulmonary medicine in the United States. A self-administered survey was mailed to active members. Of responding members, 80% reside in the United States or Canada; the remainder come from 90 different countries. The majority of North American respondents (79%) were white, non-Hispanic. Seventeen percent of respondents were female. Female respondents were younger, with a mean age of 42 years, compared with 47 years for males. Sixty-five percent of respondents identified clinical practice, 20% research, and 5% teaching as their major activity. More women (33%) than men (22%) identified themselves as researchers. The majority of respondents (69%) have a medical school faculty affiliation. The American Thoracic Society represents a global organization with diverse clinical expertise and scientific interests. The majority of respondents are clinicians; however, the membership has a strong academic bent with most reporting academic affiliation, and describing teaching as a secondary activity. C1 Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care Med, Seattle, WA 98104 USA. Amer Thorac Soc, Membership Serv & Mkt, New York, NY USA. William Beaumont Army Med Ctr, Dept Clin Invest, El Paso, TX 79920 USA. William Beaumont Army Med Ctr, Pulm Crit Care Serv, El Paso, TX 79920 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. Denver Vet Affairs Med Ctr, Div Pulm, Denver, CO 80202 USA. RP Schnapp, LM (reprint author), Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care Med, Box 359640,325 9Th Ave, Seattle, WA 98104 USA. NR 29 TC 6 Z9 6 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 MAY 1 PY 2003 VL 167 IS 9 BP 1176 EP 1180 DI 10.1164/rccm.200203-1860C PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 675NC UT WOS:000182700600006 PM 12522026 ER PT J AU Celedon, JC Wright, RJ Litonjua, AA Sredl, D Ryan, L Weiss, ST Gold, DR AF Celedon, JC Wright, RJ Litonjua, AA Sredl, D Ryan, L Weiss, ST Gold, DR TI Day care attendance in early life, maternal history of asthma, and asthma at the age of 6 years SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE day care; maternal history; asthma ID LOWER RESPIRATORY ILLNESS; HOUSE-DUST ENDOTOXIN; EARLY-CHILDHOOD; SCHOOL-AGE; RISK; EXPOSURE; CHILDREN; WHEEZE; SENSITIZATION; COCKROACH AB Among children not selected on the basis of a parental history of atopy, day care attendance in early life is inversely associated with asthma at school age. We examined the relation between day care in the first year of life and asthma, recurrent wheezing, and eczema at the age of 6 years and wheezing in the first 6 years of life among 453 children with parental history of atopy followed from birth. Among all study participants, day care in the first year of life was inversely associated with eczema (odds ratio [OR] = 0.3, 95% confidence interval [CI] = 0.1-0.8). Day care attendance in early life was associated with a decreased risk of asthma (OR = 0.3, 95% CI = 0.1-0.7) and recurrent wheezing (OR = 0.3, 95% CI = 0.1-0.9) at the age of 6 years and with a decreased risk of any wheezing after the age of 4 years only among children without maternal history of asthma. Among children with maternal history of asthma, day care in early life had no protective effect on asthma or recurrent wheezing at the age of 6 years but was instead associated with an increased risk of wheezing in the first 6 years of life. Our findings suggest that maternal history of asthma influences the relation between day care-related exposures and childhood asthma. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Celedon, JC (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NHLBI NIH HHS [KO1 HL04370-01A1]; NIAID NIH HHS [AIEHS35786] NR 24 TC 107 Z9 109 U1 0 U2 3 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 MAY 1 PY 2003 VL 167 IS 9 BP 1239 EP 1243 DI 10.1164/rccm.200209-1063OC PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 675NC UT WOS:000182700600015 PM 12446273 ER PT J AU Wang, C Gill, TJ Zarins, B Herndon, JH AF Wang, C Gill, TJ Zarins, B Herndon, JH TI Extensor carpi ulnaris tendon rupture in an ice hockey player - A case report SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article ID RECURRENT DISLOCATION C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wang, C (reprint author), Massachusetts Gen Hosp, 15 Parkman St,Suite 508, Boston, MA 02114 USA. NR 20 TC 7 Z9 7 U1 0 U2 1 PU AMER ORTHOPAEDIC SOC SPORT MED PI WALTHAM PA 230 CALVARY STREET, WALTHAM, MA 02154 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD MAY-JUN PY 2003 VL 31 IS 3 BP 459 EP 461 PG 3 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 684CG UT WOS:000183187400023 PM 12750144 ER PT J AU Varnholt, H Vauthey, JN Dal Cin, P Marsh, RD Bhathal, PS Hughes, NR Lauwers, GY AF Varnholt, H Vauthey, JN Dal Cin, P Marsh, RD Bhathal, PS Hughes, NR Lauwers, GY TI Biliary adenofibroma - A rare neoplasm of bile duct origin with an indolent behavior SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE adenofibroma; benign; biliary; fluorescence in situ hybridization; liver ID VON-MEYENBURG COMPLEX; CHOLANGIOCARCINOMA; HEMOCHROMATOSIS; TRANSFORMATION; HAMARTOMAS; CYSTS AB We report a case of biliary adenofibroma in a 47-year-old woman, who presented with right upper quadrant pain for several months. Abdominal imaging revealed a 16-cm solid and cystic mass in the left hepatic lobe. Histologically. the tumor showed two distinct components: 1) cystic and tubular structures lined by low columnar to cuboidal biliary-type epithelium, and 2) a dense fibrous stroma composed of spindle-shaped cells with only mild nuclear pleomorphism and inconspicuous nucleoli. Mitoses and stromal invasion were absent. The glandular epithelium stained positively for keratin AE.3/Cam 5.2, cytokeratin 7, cytokeratin 19, carcinoembryonic antigen, and epithelial membrane antigen and had a low Ki-67 proliferative index, In addition, the epithelium was positive for D10 but did not stain for 1F6 or acid mucin with alcian blue stain. This staining pattern, similar to bile duct hamartoma (von Meyenburg complex) with which this tumor shares morphologic similarity, suggests that biliary adenofibroma originates from interlobular or larger bile ducts. Three years after a subtotal resection no metastasis or significant tumor growth was noted. However. given the marked nuclear p53 immunoreactivity and tetraploidy status observed in this tumor. we cannot exclude that biliary adenofibroma may represent a premalignant process that warrants complete resection and thorough histopathologic examination. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Florida, Coll Med, Dept Med, Div Hematol & Oncol, Gainesville, FL USA. Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Warren 2,55 Fruit St, Boston, MA 02114 USA. NR 16 TC 16 Z9 19 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 MAY PY 2003 VL 27 IS 5 BP 693 EP 698 DI 10.1097/00000478-200305000-00014 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 672LE UT WOS:000182521400014 PM 12717255 ER PT J AU Rosenheck, R Leslie, D Woody, G AF Rosenheck, R Leslie, D Woody, G TI Fiscal strain and access to opiate substitution therapy at department of Veterans Affairs Medical Centers SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID MENTAL-HEALTH-SERVICES; LEAST WELL; COST; SYSTEM; CARE AB This study examines the relationship between institutional fiscal strain and the availability of opiate substitution therapy (eg, methadone maintenance), an effective but relatively expensive treatment for heroin addiction. An observational design was used to examine the association of changes in funding and changes in provision for treating opiate addiction at 29 VA Medical Centers (VAMCs). We hypothesized that VAMCs experiencing greater fiscal strain would show reduced availability of opiate substitution treatment. Administrative records from each of 29 VAMCs that provided opiate substitution therapy in both Fiscal Year (FY) 1995 and FY 1999 were used to measure changes in the availability of this service, ie, the percent change in total patients treated, annual visits per patient, and total services delivered. Institutional fiscal strain was measured by the percent decline in per capita funding at four levels at each VAMC: the entire medical center, all mental health programs, all substance abuse programs (inpatient and outpatient), and outpatient substance abuse programs alone. The total number of patients receiving opiate substitution increased from 5,549 in FY 1995 to 6,884 in FY 1999 (24%), annual visits per patient decreased by 16%, and the total number of units of services increased by 4%. There were no significant relationships between changes in the delivery of opiate substitution services and changes in per capita funding at any of the four institutional levels. No new programs were started during these years. Although no new programs were started, the availability of opiate substitution therapy at VA facilities with existing programs was maintained over a five-year period regardless of local funding changes, although at somewhat reduced intensity. C1 VISN, Mental Illness Res Educ & Clin Ctr, West Haven, CT USA. Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. Yale Univ, Dept Epidemiol, New Haven, CT 06520 USA. Yale Univ, Dept Publ Hlth, New Haven, CT 06520 USA. Univ Penn, Dept Psychiat, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Rosenheck, R (reprint author), 182 NE Program Evaluat Ctr, 950 Campbell Ave, West Haven, CT 06516 USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAY-JUN PY 2003 VL 12 IS 3 BP 220 EP 228 DI 10.1080/10550490390202659 PG 9 WC Substance Abuse SC Substance Abuse GA 694PD UT WOS:000183782200005 PM 12851018 ER PT J AU Campagna, JA Carter, C AF Campagna, JA Carter, C TI Clinical relevance of the Bezold-Jarisch reflex SO ANESTHESIOLOGY LA English DT Review ID LEFT-VENTRICULAR RECEPTORS; THORACIC EPIDURAL-ANESTHESIA; CARDIAC VAGAL AFFERENTS; HEAD-UP TILT; SPINAL-ANESTHESIA; VASOVAGAL SYNCOPE; FREE-RADICALS; MYOCARDIAL ISCHEMIA; INTERSCALENE BLOCK; SITTING POSITION C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neuroplast Res Grp, Boston, MA 02114 USA. RP Campagna, JA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neuroplast Res Grp, 55 Fruit St, Boston, MA 02114 USA. NR 120 TC 77 Z9 81 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2003 VL 98 IS 5 BP 1250 EP 1260 PG 11 WC Anesthesiology SC Anesthesiology GA 672LY UT WOS:000182523200029 PM 12717149 ER PT J AU Ali, HH AF Ali, HH TI Criteria of adequate clinical recovery from neuromuscular block SO ANESTHESIOLOGY LA English DT Editorial Material ID RESIDUAL ANTIDEPOLARIZING BLOCK; QUANTITATIVE ASSESSMENT; STIMULUS FREQUENCY; TRAIN-OF-4; STIMULATION; HUMANS; FADE C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Clin 337, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ali, HH (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Clin 337, 32 Fruit St, Boston, MA 02114 USA. NR 15 TC 5 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2003 VL 98 IS 5 BP 1278 EP 1280 PG 3 WC Anesthesiology SC Anesthesiology GA 672LY UT WOS:000182523200032 PM 12717152 ER PT J AU Chang, BS Piao, XH Bodell, A Basel-Vanagaite, L Straussberg, R Dobyns, WB Qasrawi, B Winter, RM Innes, AM Voit, T Grant, PE Barkovich, AJ Walsh, CA AF Chang, BS Piao, XH Bodell, A Basel-Vanagaite, L Straussberg, R Dobyns, WB Qasrawi, B Winter, RM Innes, AM Voit, T Grant, PE Barkovich, AJ Walsh, CA TI Bilateral frontoparietal polymicrogyria: Clinical and radiological features in 10 families with linkage to chromosome 16 SO ANNALS OF NEUROLOGY LA English DT Article ID PERISYLVIAN POLYMICROGYRIA; EPILEPSY; CHILDREN; MAPS AB Polymicrogyria is a common malformation of cortical development characterized by an excessive number of small gyri and abnormal cortical lamination. Multiple syndromes of region-specific bilateral symmetric polymicrogyria have been reported. We previously have described two families with bilateral frontoparietal polymicrogyria (BFPP), an autosomal recessive syndrome that we mapped to, a locus on chromosome 16q12-21. Here, we extend our observations to include 19 patients from 10 kindreds, all linked to the chromosome 16q locus, allowing us to define the clinical and radiological features of BFPP in detail. The syndrome is characterized by global developmental delay of at least moderate severity, seizures, dysconjugate gaze, and bilateral pyramidal and cerebellar signs. Magnetic resonance imaging demonstrated symmetric polymicrogyria affecting the frontoparietal regions most severely, as well as ventriculomegaly, bilateral white matter signal changes, and small brainstem and cerebellar structures. We have refined our genetic mapping and describe two apparent founder haplotypes, one of which is present in two families with BFPP and associated microcephaly. Because 11 of our patients initially were classified as having other malformations, the syndrome of BFPP appears to be more common than previously recognized and may be frequently misdiagnosed. C1 Harvard Inst Med, Div Neurogenet, Boston, MA 02115 USA. Harvard Inst Med, Comprehens Epilepsy Ctr, Boston, MA 02115 USA. Harvard Inst Med, Dept Neurol, Boston, MA 02115 USA. Harvard Inst Med, Howard Hughes Med Inst, Dept Neurol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Rabin Med Ctr, Dept Med Genet, Petah Tiqwa, Israel. Schneider Childrens Med Ctr Israel, Neurogenet Clin, Petah Tiqwa, Israel. Schneider Childrens Med Ctr Israel, Dept Child Neurol, Petah Tiqwa, Israel. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Minist Social Affairs & Labor, Social Welf Inst, Kuwait, Kuwait. Inst Child Hlth, Clin Genet Unit, London, England. Univ Calgary, Dept Med Genet, Alberta Childrens Hosp, SW Calgary, AB, Canada. Univ Essen Gesamthsch, Dept Pediat, Essen, Germany. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. RP Chang, BS (reprint author), Harvard Inst Med, Div Neurogenet, Room 817,4 Blackfan Circle, Boston, MA 02115 USA. RI innes, allan micheil/A-9955-2017; OI Innes, Micheil/0000-0001-9881-5467; Dobyns, William/0000-0002-7681-2844 FU NICHD NIH HHS [HD07466]; NINDS NIH HHS [R01 NS35129] NR 30 TC 74 Z9 78 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2003 VL 53 IS 5 BP 596 EP 606 DI 10.1002/ana.10520 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 673EC UT WOS:000182566400006 PM 12730993 ER PT J AU Kentala, E Vivas, J Wall, C AF Kentala, E Vivas, J Wall, C TI Reduction of postural sway by use of a vibrotactile balance prosthesis prototype in subjects with vestibular deficits SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE balance prosthesis; balance rehabilitation; postural control AB To evaluate the effectiveness of a prototype vibrotactile balance prosthesis in maintaining balance during dynamic posturography, we studied 6 subjects with unilateral or bilateral vestibular deficit by means of Equitest computerized dynamic posturography (CDP). Their anterior-posterior (AP) sway at the small of the back was measured with a micromechanical rate gyroscope and a linear accelerometer. The resulting tilt estimate was displayed by a vibrotactile array attached to the torso. The vibration served as tilt feedback to the subject. Subject performance was evaluated with the tilt performance index (TPI), which is the inverse of the root-mean-square of tilt. We found that the balance prosthesis reduced the subjects' AP sway. The subjects' results without the balance prosthesis on CDP sensory organization tests (SOTS) 5 and 6 were compared to results with the prosthesis. The average TPI increased significantly (p <.05) when vibrotactile feedback was used as compared to the unaided condition. This finding was true for both SOTs 5 and 6. We conclude that vibrotactile feedback of estimated AP body tilt improved the subjects' ability to perform selected CDP tests. Some of the subjects were able to stand throughout the test with the device turned on, whereas they otherwise constantly fell. C1 Harvard Univ, Dept Otol & Laryngol, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Jenks Vestibular Diagnost Lab, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Neural Prosthesis Res Ctr, Cambridge, MA 02139 USA. RP Wall, C (reprint author), Harvard Univ, Dept Otol & Laryngol, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 7 TC 55 Z9 55 U1 5 U2 5 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 MAY PY 2003 VL 112 IS 5 BP 404 EP 409 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 676PK UT WOS:000182760800003 PM 12784977 ER PT J AU Mathisen, DJ AF Mathisen, DJ TI Long-term evaluation of the replacement of the trachea with an autologous aortic graft - Invited commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Gen Thorac Surg Unit, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Gen Thorac Surg Unit, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2003 VL 75 IS 5 BP 1578 EP 1578 AR PII S0003-4975(03)00358-8 DI 10.1016/S0003-4975(03)00358-8 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 671YP UT WOS:000182493400042 ER PT J AU Laham, RJ Li, J Tofukuji, M Post, M Simons, M Sellke, FW AF Laham, RJ Li, J Tofukuji, M Post, M Simons, M Sellke, FW TI Spatial heterogeneity in VEGF-induced vasodilation: VEGF dilates microvessels but not epicardial and systemic arteries and veins SO ANNALS OF VASCULAR SURGERY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; THERAPEUTIC ANGIOGENESIS; BLOOD-FLOW; HYPOTENSION; ACTIVATION; ISCHEMIA; HEART; MODEL AB This study was designed to investigate the site of vascular endothelial growth factor (VEGF)induced vasodilation in the systemic and coronary vasculature. Intracoronary infusion of VEGF in Yorkshire pigs resulted in a significant drop in the mean arterial blood pressure, with a decline in the left ventricular left end-diastolic pressure, and no change in the heart rate. Coronary blood flow increase after intracoronary infusion of 10 mug VEGF (2.63 +/- 0.49x) was comparable to that seen after 40 mug of intracoronary adenosine (2.5 +/- 0.53x, p = 0.67) and was significantly higher then after 200 mug of intracoronary nitroglycerine (1.9 +/- 0.12x, p = 0.0005). At the same time, intracoronary VEGF did not result in a significant increase in coronary cross-sectional area determined using intravascular ultrasound. In vitro, VEGF produced dose-dependent relaxation of myocardial and systemic arterioles and venules (arterioles: 60-100 mum and venules: 120-200 mum in internal diameter) that was partially inhibited by L-NNA, but had no effect on epicardial coronary arteries, systemic arteries, or veins. Both VEGF receptors (flt-1 and flk-1) were identified on endothelial cells of epicardial arteries and veins. We conclude that this spatial heterogeneity of VEGF vasomotor effects cannot be explained by the absence VEGF receptors and suggests differential patterns of signal transduction in the vascular tree. C1 Harvard Univ, Sch Med, Dept Med & Surg, Angiogenesis Res Ctr,Intervent Cardiol Sect,BIDMC, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Laham, RJ (reprint author), Harvard Univ, Sch Med, Dept Med & Surg, Angiogenesis Res Ctr,Intervent Cardiol Sect,BIDMC, 330 Brookline Ave, Boston, MA 02215 USA. RI Simons, Michael/G-8553-2014 OI Simons, Michael/0000-0003-0348-7734 FU NCRR NIH HHS [M01-RR01032]; NHLBI NIH HHS [HL 46716, HL 63609] NR 27 TC 30 Z9 30 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD MAY PY 2003 VL 17 IS 3 BP 245 EP 252 DI 10.1007/s10016-001-0299-x PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 687GL UT WOS:000183368100004 PM 12704544 ER PT J AU Akkina, R Banerjea, A Bai, JR Anderson, J Li, MJ Rossi, J AF Akkina, R Banerjea, A Bai, JR Anderson, J Li, MJ Rossi, J TI siRNAs, ribozymes and RNA decoys in modeling stem cell-based gene therapy for HIV/AIDS SO ANTICANCER RESEARCH LA English DT Article; Proceedings Paper CT 4th International Confrence on Gene Regulation, Oncogenesis and AIDS CY SEP 22-26, 2002 CL ATHENS, GREECE DE HIV vene therapy; stem cells; ribozymes; siRNAs; lentiviral vectors ID HUMAN-IMMUNODEFICIENCY-VIRUS; SCID-HU MOUSE; HEMATOPOIETIC PROGENITOR CELLS; TYPE-1 REPLICATION; CD34(+) CELLS; HIV DISEASE; IN-VIVO; INTERFERENCE; INHIBITION; VECTOR AB Gene therapy strategies for HIV infection require gene transduction of hematopoietic stem cells with effective therapeutic constructs. Here we summarize our studies on anti-HIV ribozymes, RNA decoys and the newly described siRNAs. The therapeutic constructs consisted of an anti-CCR5 riboZyme to down-regulate the HIV-1 cell surface co-receptor and ribozynmes targeted to viral mRNAs coding for the tat, rev and env proteins. The RAA decoy targeted rev and the siRNA was directed against a sequence common to rev and tat mRNAs. CD34 hematopoietic progenitor cells were transduced with retroviral or lentiviral vectors containing these constructs. They were differentiated into macrophages in vitro and T cells in vivo in a SCID-hu mouse thymopoiesis model. The transgene-containing macrophages and T cells were found to be phenotypically normal. When challenged in vitro with HIV-1, they showed significant anti-viral resistance. These proof-of-concept studies demonstrated the utility of RNA-based (anti-HIV constructs for gene therapy. C1 Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Biol, Duarte, CA 91010 USA. RP Akkina, R (reprint author), Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. FU NIAID NIH HHS [AI 42552, AI 42551, AI 50492] NR 38 TC 46 Z9 48 U1 0 U2 4 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAY-JUN PY 2003 VL 23 IS 3A BP 1997 EP 2005 PG 9 WC Oncology SC Oncology GA 704UN UT WOS:000184359100003 PM 12894572 ER PT J AU Spyropoulos, DD Bartel, FO Higuchi, T Deguchi, T Ogawa, M Watson, DK AF Spyropoulos, DD Bartel, FO Higuchi, T Deguchi, T Ogawa, M Watson, DK TI Marker-assisted study of genetic background and gene-targeted locus modifiers in lymphopoietic phenotypes SO ANTICANCER RESEARCH LA English DT Article; Proceedings Paper CT 4th International Confrence on Gene Regulation, Oncogenesis and AIDS CY SEP 22-26, 2002 CL ATHENS, GREECE DE Ets; knockout; targeted disruption; genetic background; genetic modifiers; QTL; speed congenics ID QUANTITATIVE TRAIT LOCI; ETS-1 TRANSCRIPTION FACTOR; NK-T-CELLS; DNA-BINDING; MOUSE MUTAGENESIS; 129 SUBSTRAINS; PRACTICAL CONSEQUENCES; AUTO-INHIBITION; NATURAL-KILLER; COMPLEX TRAITS AB forward and reverse genetic approaches facilitate the molecular dissection of individual gene functions and the integration of individual gene functions into multi-gene processes in the context of the whole organism. Variations in mutant phenotypes due to genetic background differences have been well documented through the analysis of mouse mutants. Nevertheless, recommendations concerning the assessment of genetic background as it impacts on phenotype, and utilization of genetic background differences to identify and integrate gene functions have been largely, overlooked. Genetic background as it relates to immunological mutants will be discussed utilizing an Ets1-targeted allele to exemplify phenotypic variation due to background. Marker-assisted strategies for the identification of genetic modifiers', especially those linked to the targeted locus, will also be considered. C1 Med Univ S Carolina, Hollings Canc Ctr, Lab Canc Genom, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Cell Biol & Anat, Charleston, SC 29425 USA. RP Spyropoulos, DD (reprint author), Med Univ S Carolina, Hollings Canc Ctr, Lab Canc Genom, Room 338,86 Jonathan Lucas St, Charleston, SC 29425 USA. FU NCI NIH HHS [P01CA78582] NR 100 TC 4 Z9 4 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAY-JUN PY 2003 VL 23 IS 3A BP 2015 EP 2026 PG 12 WC Oncology SC Oncology GA 704UN UT WOS:000184359100005 PM 12894574 ER PT J AU Doyle, PJ AF Doyle, PJ TI Preface SO APHASIOLOGY LA English DT Editorial Material C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. RP Doyle, PJ (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD MAY PY 2003 VL 17 IS 5 BP 421 EP 421 DI 10.1080/02687030344000201 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 669DB UT WOS:000182335700001 ER PT J AU Hula, WD McNeil, MR Doyle, PJ Rubinsky, HJ Fossett, TRD AF Hula, WD McNeil, MR Doyle, PJ Rubinsky, HJ Fossett, TRD TI The inter-rater reliability of the story retell procedure SO APHASIOLOGY LA English DT Article; Proceedings Paper CT 32nd Annual Clinical Aphasiology Conference CY JUN, 2002 CL RIDGEDALE, MISSOURI ID CONNECTED SPEECH; APHASIA; ADULTS AB Background: McNeil, Doyle, Fossett, Park, and Goda (2001) have presented the story retell procedure (SRP) as an efficient means of assessing discourse in adults with aphasia, in part because it provides reliable, valid, and sensitive indices of performance without the need for time-consuming transcription of language samples. Aims: The purpose of this study was to demonstrate that the SRP, when scored without transcription by judges with minimal training, produces a reliable measure of information transfer. Methods & Procedures: Four judges who had not used the SRP previously scored audio-recorded language samples, produced by four subjects with aphasia and eleven normal subjects, for percent information units per minute (%IU/Min). Outcomes & Results: The results demonstrate that the SRP has high inter-rater reliability. Reliability coefficients ranged from .89 to .995, and the standard error of measurement associated with inter-rater scoring error ranged from .59 to 1.42 %IU/Min. Point-to-point reliability in scoring individual information units ranged from 85-95% and averaged 91% for both subject groups. Conclusions: The SRP is a potentially useful tool for quantifying connected language behaviour, and may be particularly valuable in clinical and research settings where economy of assessment procedures is essential. C1 VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Hula, WD (reprint author), VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 19 TC 10 Z9 10 U1 1 U2 1 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD MAY PY 2003 VL 17 IS 5 BP 523 EP 528 DI 10.1080/02687030344000139 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 669DB UT WOS:000182335700010 ER PT J AU Nilsen, T Nes, IF Holo, H AF Nilsen, T Nes, IF Holo, H TI Enterolysin A, a cell wall-degrading bacteriocin from Enterococcus faecalis LMG 2333 SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID STREPTOCOCCUS-MILLERI NMSCC-061; STAPHYLOCOCCUS-AUREUS; SEQUENCE-ANALYSIS; GLYCYLGLYCINE ENDOPEPTIDASE; PEDIOCOCCUS-ACIDILACTICI; PSEUDOMONAS-AERUGINOSA; NUCLEOTIDE-SEQUENCE; LACTOBACILLUS-SAKE; GROWTH-CONDITIONS; LYSOSTAPHIN GENE AB A novel antimicrobial protein, designated enterolysin A, was purified from an Enterococcus faecalis LMG 2333 culture. Enterolysin A inhibits growth of selected enterococci, pediococci, lactococci, and lactobacilli. Antimicrobial activity was initially detected only on solid media, but by growing the bacteria in a fermentor under optimized production conditions (MRS broth with 4% [wt/vol] glucose, pH 6.5, and a temperature between 25 and 35degreesC), the bacteriocin activity was increased to 5,120 bacteriocin units ml(-1). Enterolysin A production was regulated by pH, and activity was first detected in the transition between the logarithmic and stationary growth phases. Killing of sensitive bacteria by enterolysin A showed a dose-response behavior, and the bacteriocin has a bacteriolytic mode of action. Enterolysin A was purified, and the primary structure was determined by combined amino acid and DNA sequencing. This bacteriocin is translated as a 343-amino-acid preprotein with an sec-dependent signal peptide of 27 amino acids, which is followed by a sequence corresponding to the N-terminal part of the purified protein. Mature enterolysin A consists of 316 amino acids and has a calculated molecular weight of 34,501, and the theoretical pI is 9.24. The N terminus of enterolysin A is homologous to the catalytic domains of different cell wall-degrading proteins with modular structures. These include lysostaphin, ALE-1, zoocin A, and LytM, which are all endopeptidases belonging to the M37 protease family. The N-terminal part of enterolysin A is linked by a threonine-proline-rich region to a putative C-terminal recognition domain, which shows significant sequence identity to two bacteriophage lysins. C1 Agr Univ Norway, Lab Microbial Gene Technol, N-1432 As, Norway. RP Nilsen, T (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 65 Landsdowne St, Cambridge, MA 01239 USA. NR 52 TC 93 Z9 96 U1 1 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAY PY 2003 VL 69 IS 5 BP 2975 EP 2984 DI 10.1128/AEM.69.5.2975-2984.2003 PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 677LD UT WOS:000182808300069 PM 12732574 ER PT J AU Davis, KL Stewart, DG Friedman, JI Buchsbaum, M Harvey, PD Hof, PR Buxbaum, J Haroutunian, V AF Davis, KL Stewart, DG Friedman, JI Buchsbaum, M Harvey, PD Hof, PR Buxbaum, J Haroutunian, V TI White matter changes in schizophrenia - Evidence for myelin-related dysfunction SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Review ID 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE; CENTRAL-NERVOUS-SYSTEM; LATE-ONSET SCHIZOPHRENIA; OLIGODENDROCYTE PRECURSOR CELLS; MAGNETIC-RESONANCE SPECTROSCOPY; ASPARTATE RECEPTOR ANTAGONISTS; ADHESION MOLECULES L1; LOCAL CIRCUIT NEURONS; MULTIPLE-SCLEROSIS; PREFRONTAL CORTEX AB Numerous lines of inquiry implicate connectivity as a central abnormality in schizophrenia. Myelination and factors that affect myelination, such. as the function of oligodendroglia, are critical processes that could profoundly affect neuronal connectivity, especially given the diffuse distribution of oligodendrocytes and the widespread distribution of brain regions that have been implicated in schizophrenia. Multiple lines of evidence now converge to implicate oligodendroglia and myelin in schizophrenia. Imaging and neurocytochemical evidence, similarities with demyelinating diseases, age-related changes in white matter, myelin-related gene abnormalities, and morphologic abnormalities in the oligodendroglia demonstrated in schizophrenic brains are all examined in light of the hypothesis that oligodendroglial dysfunction and even death, with subsequent abnormalities in myelin maintenance and repair, contribute to the schizophrenic syndrome. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10021 USA. Mt Sinai Sch Med, Kastor Neurobiol Aging Labs, Fishberg Res Ctr Neurobiol, New York, NY 10021 USA. Mt Sinai Sch Med, Kastor Neurobiol Aging Labs, Dept Geriatr Adult Dev, New York, NY 10021 USA. Bronx Vet Adm Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. Pilgrim Psychiat Ctr, Brentwood, NY USA. RP Davis, KL (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustav Levy Pl, New York, NY 10021 USA. OI Buxbaum, Joseph/0000-0001-8898-8313 NR 275 TC 499 Z9 511 U1 8 U2 32 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 MAY PY 2003 VL 60 IS 5 BP 443 EP 456 DI 10.1001/archpsyc.60.5.443 PG 14 WC Psychiatry SC Psychiatry GA 676CU UT WOS:000182735000002 PM 12742865 ER PT J AU Schnurr, PP Friedman, MJ Foy, DW Shea, MT Hsieh, FY Lavori, PW Glynn, SM Wattenberg, M Bernardy, NC AF Schnurr, PP Friedman, MJ Foy, DW Shea, MT Hsieh, FY Lavori, PW Glynn, SM Wattenberg, M Bernardy, NC TI Randomized trial of trauma-focused group therapy for posttraumatic stress disorder - Results from a Department of Veterans Affairs Cooperative Study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Annual Meeting of the International-Society-for-Traumatic-Stress-Studies CY DEC 08, 2001 CL NEW ORLEANS, LOUISIANA SP Int Soc Traumat Stress Studies ID ADMINISTERED PTSD SCALE; ASSAULT VICTIMS; CLINICAL-TRIALS; EXPOSURE; PATIENT; DESIGN; WOMEN AB Background: Department of Veterans Affairs Cooperative Study 420 is a randomized clinical trial of 2 methods of group psychotherapy for treating post-traumatic stress disorder (PTSD) in male Vietnam veterans. Methods: Vietnam veterans (360 men) were randomly assigned to receive trauma-focused group psychotherapy or a present-centered comparison treatment that avoided trauma focus. Treatment was provided weekly to groups of 6 members for 30 weeks, followed by 5 monthly booster sessions. Severity of PTSD was, the primary outcome. Additional measures were other psychiatric symptoms, functional status, quality of life, physical health, and service utilization. Follow-up assessments were conducted at the end of treatment (7 months) and at the end of the booster sessions (12 months); 325 individuals participated in 1 or both assessments. Additional follow-up for PTSD severity was performed in a subset of participants at 18 and 24 months. Results: Although posttreatment assessments of PTSD severity and other measures were significantly improved from baseline, intention-to-treat analyses found no overall differences between therapy groups on Any outcome. Analyses of data from participants who received an adequate dose of treatment suggested that trauma-focused group therapy reduced avoidance and numbing and, possibly, PTSD symptoms. Dropout from treatment was higher in trauma-focused group treatment. Average improvement was modest in both treatments, although approximately 40% of participants showed clinically significant change. Conclusions: This study did not find a treatment effect for trauma-focused group therapy. The difference between the effectiveness and adequate dose findings suggests the possible value of methods to enhance the delivery of cognitive-behavioral treatments in clinical practice settings. C1 Natl Ctr Posttraumat Stres Disorder, Dept Vet Affairs, White River Jct, VT USA. Dartmouth Coll Sch Med, Dept Psychiat, Hanover, NH USA. Dartmouth Coll Sch Med, Dept Pharmacol, Hanover, NH USA. Pepperdine Univ, Dept Psychol, Culver City, CA USA. Providence VA Med Ctr, Mental Hlth & Behav Sci Serv, Providence, RI USA. Brown Univ, Dept Psychiat, Providence, RI 02912 USA. VA Cooperat Studies Program, Menlo Pk, CA USA. Stanford Univ, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA. W Los Angeles VA Med Ctr, Res Serv, Los Angeles, CA USA. VA Outpatient Clin, Boston, MA USA. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA USA. Tufts Univ, Sch Med, Dept Psychiat, Boston, MA 02111 USA. RP Schnurr, PP (reprint author), VA Med & Reg Off Ctr, VA Natl Ctr PTSD, Mail Stop 116D, White River Jct, VT 05009 USA. NR 36 TC 191 Z9 192 U1 1 U2 19 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 MAY PY 2003 VL 60 IS 5 BP 481 EP 489 DI 10.1001/archpsyc.60.5.481 PG 9 WC Psychiatry SC Psychiatry GA 676CU UT WOS:000182735000006 PM 12742869 ER PT J AU Kang, K Chu, K Kim, DE Jeong, SW Lee, JW Roh, JK AF Kang, K Chu, K Kim, DE Jeong, SW Lee, JW Roh, JK TI POEMS syndrome associated with ischemic stroke SO ARCHIVES OF NEUROLOGY LA English DT Article ID MYOCARDIAL-INFARCTION; FIBRINOGEN; PROTEIN AB Background: A syndrome variously combining peripheral neuropathy, visceromegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS syndrome) is a rare variant of plasma cell dyscrasia with multisystemic manifestations. Acute ischemic strokes in patients with POEMS syndrome have rarely been reported, and the pathophysiologic mechanism of this disease is unknown. Fibrinogen is reported to be an independent risk factor for cerebrovascular disease and is correlated with the interleukin 6 level in the plasma. The serum level of interleukin 6 is high in the active stage of POEMS syndrome. Objective: To describe the neuroimaging findings and fibrinogen levels in patients with POEMS syndrome. Design: Case series. Setting: The neurology department of a tertiary referral center. Methods: Three patients with an acute cerebral infarction associated with POEMS syndrome underwent magnetic resonance imaging, diffusion-weighted imaging, magnetic resonance angiography, transcranial Doppler ultrasonography, and serum fibrinogen level and serum C-reactive protein level analysis. The serum fibrinogen level before the stroke was collected retrospectively from the hospital medical records. Results:, There was an elevated fibrinogen level in all of the patients. In 2 patients, unilateral or bilateral end artery border-zone infarcts were observed on the brain magnetic resonance imaging scan. The serum fibrinogen level was high before the stroke in 2 patients. Conclusions: The POEMS syndrome can be associated with stroke, particularly end artery border-zone infarctions. We suggest that an elevated fibrinogen level might play a role in the pathogenesis of stroke. C1 Seoul Natl Univ Hosp, Dept Neurol, Chongro Gu, Seoul 110744, South Korea. Seoul Natl Univ Hosp, Clin Res Inst, Chongro Gu, Seoul 110744, South Korea. Seoul Natl Univ, Med Res Ctr, Neurosci Res Inst, Seoul, South Korea. Kwangdong Univ, Coll Med, Dept Neurol, Kangwon Do, South Korea. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02115 USA. RP Roh, JK (reprint author), Seoul Natl Univ Hosp, Dept Neurol, Chongro Gu, 28 Yongon Dong, Seoul 110744, South Korea. RI Roh, Jae Kyu/J-5459-2012 NR 11 TC 15 Z9 17 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2003 VL 60 IS 5 BP 745 EP 749 DI 10.1001/archneur.60.5.745 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 678LA UT WOS:000182867600012 PM 12756139 ER PT J AU Yin, A Margolis, HC Grogan, J Yao, Y Troxler, RF Oppenheim, FG AF Yin, A Margolis, HC Grogan, J Yao, Y Troxler, RF Oppenheim, FG TI Physical parameters of hydroxyapatite adsorption and effect on candidacidal activity of histatins SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE histatins; adsorption; hydroxyapatit; Langmuir model; candidacidal activity ID HUMAN SALIVARY PROTEINS; PROLINE-RICH PROTEINS; HUMAN-PAROTID SECRETION; STREPTOCOCCUS-MUTANS; ENAMEL PELLICLE; HELICAL CONFORMATION; CALCIUM-PHOSPHATE; ACIDIC PEPTIDE; HIGH AFFINITY; INHIBITOR AB Histatins 1, 3 and 5 are the major members of a histidine-rich protein family present in human salivary secretions. These proteins are distinct from many salivary proteins in their high positive charge density at neutral pH, and their antibacterial and antifungal properties. In this study, the hydroxyapatite adsorption characteristics of, histatin 1, containing a single phosphoserine residue, recombinantly expressed histatin 1, native histatin 3, synthetic histatin 5 and an internal 12-residue sequence of histatin 5 were investigated. A Langmuir-type model. was used to analyse the adsorption. A comparison of the affinities and binding sites of phosphorylated and recombinant histatin 1 provided an estimate of the positive influence of the single phosphoseryl. group on mineral adsorption. Furthermore, an apparent correlation was shown to exist between peptide chain length and the number of binding sites. The influence of histatin 5 adsorption on its anticandidal activity was also investigated by performing Candida albicans killing assays with histatin 5 and histatin 5/hydroxyapatite suspensions. A decrease in killing activity was observed with the increase of hydroxyapatite present. The results suggest that the anticandidal properties of histatin 5 could be impaired by the conformations resulting from mineral adsorption, or that putative cellular receptors necessary for candidacidal. activity are inaccessible when histatin 5 is adsorbed on hydroxyapatite. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Boston Univ, Goldman Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA 02118 USA. Boston Univ, Goldman Sch Dent Med, Dept Biochem, Boston, MA 02118 USA. Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. RP Oppenheim, FG (reprint author), Boston Univ, Goldman Sch Dent Med, Dept Periodontol & Oral Biol, Suite W201,700 Albany St, Boston, MA 02118 USA. FU NIDCR NIH HHS [DE 05672, DE 11691, DE 07652] NR 44 TC 15 Z9 16 U1 1 U2 6 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 MAY PY 2003 VL 48 IS 5 BP 361 EP 368 DI 10.1016/S0003-9969(03)00012-8 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 686TK UT WOS:000183336900005 PM 12711380 ER PT J AU Novis, DA Miller, KA Howanitz, PJ Renner, SW Walsh, MK AF Novis, DA Miller, KA Howanitz, PJ Renner, SW Walsh, MK TI Audit of transfusion procedures in 660 hospitals - A College of American Pathologists Q-Probes study of patient identification and vital sign monitoring frequencies in 16494 transfusions SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID QUALITY-CONTROL DOCUMENTATION; NEW-YORK-STATE; PROGRAM CHARACTERISTICS; ACCURACY PERFORMANCE; 1639 HOSPITALS; UNITS; INSTITUTIONS; INDICATORS; ERRORS; ISSUES AB Context.-Hemolytic transfusion reactions are often the result of failure to follow established identification and monitoring procedures. Objective.-To measure the frequencies with which health care workers completed specific transfusion procedures required for laboratory and blood bank accreditation. Design.-In 2 separate studies, participants in the College of American Pathologists Q-Probes laboratory quality improvement program audited nonemergent red blood cell transfusions prospectively and completed questionnaires profiling their institutions' transfusion policies. Setting and Participants.-A total of 660 institutions, predominantly in the United States, at which transfusion medicine services are provided. Main Outcome Measures.-The percentages of transfusions for which participants completed 4 specific components of patient and blood unit identifications, and for which participants monitored vital signs at 3 specific intervals during transfusions. Results.-In the first study, all components of patient identification procedures were performed in 62.3%, and all required patient vital sign monitoring was performed in 81.6% of 12448 transfusions audited. The median frequencies with which institutions participating in the first study performed all patient identification and monitoring procedures were 69.0% and 90.2%, respectively. In the second study, all components of patient identification were performed in 25.4% and all patient vital sign monitoring was performed in 88.3% of 4046 transfusions audited. The median frequencies with which institutions participating in the second study performed all patient identification and monitoring procedures were 10.0% and 95.0%, respectively. Individual practices and/or institutional policies associated with greater frequencies of patient identification and/or vital sign monitoring included transporting units of blood directly to patient bedsides, having no more than I individual handle blood units in route, checking unit labels against physicians' orders, having patients wear identification tags (wristbands), reading identification information aloud when 2 or more transfusionists participated, using written checklists to guide the administration of blood, instructing health care personnel in transfusion practices, and routinely auditing the administration of transfusions. Conclusions.-In many hospitals, the functions of identification and vital sign monitoring of patients receiving blood transfusions do not meet laboratory and blood bank accreditation standards. Differences in hospital transfusion policies influence how well health care workers comply with standard practices. We would expect that efforts designed to perfect transfusion policies might also improve performance in those hospitals in which practice compliance is substandard. C1 Wentworth Douglass Hosp, Dept Pathol, Dover, NH 03820 USA. Clin Path Associates, Tempe, AZ USA. SUNY Downstate Med Ctr, Brooklyn, NY 11203 USA. VA Greater Los Angeles Healthcare Syst, Dept Pathol, Los Angeles, CA USA. Coll Amer Pathologists, Northfield, IL USA. RP Novis, DA (reprint author), Wentworth Douglass Hosp, Dept Pathol, Dover, NH 03820 USA. NR 23 TC 36 Z9 38 U1 0 U2 2 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 2003 VL 127 IS 5 BP 541 EP 548 PG 8 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 674XH UT WOS:000182662200002 PM 12708895 ER PT J AU Abid, MR Spokes, KC Aird, WC AF Abid, MR Spokes, KC Aird, WC TI VEGF-mediated induction of MnSOD in human coronary artery endothelial cells is negatively regulated by PI3K and positively regulated by PKC signaling pathways SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 4th Annual Conference on Arteriosclerosis Thrombosisand Vascular Biology CY MAY 08-10, 2003 CL WASHINGTON, D.C. C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2003 VL 23 IS 5 MA P279 BP A49 EP A49 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 676GG UT WOS:000182742500297 ER PT J AU Khan, T Medeiros, LA Moore, KJ AF Khan, T Medeiros, LA Moore, KJ TI Native and modified LDL degradation by mononuclear phagocytes is inhibited by beta-amyloid SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 4th Annual Conference on Arteriosclerosis Thrombosisand Vascular Biology CY MAY 08-10, 2003 CL WASHINGTON, D.C. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2003 VL 23 IS 5 MA P418 BP A73 EP A73 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 676GG UT WOS:000182742500426 ER PT J AU Kolodgie, FD Burke, AP Farb, A Weber, DK Kutys, R Gold, HK Virmani, R AF Kolodgie, FD Burke, AP Farb, A Weber, DK Kutys, R Gold, HK Virmani, R TI Evidence that intraplaque hemorrhage may contribute to plaque vulnerability in human coronary lesions SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 4th Annual Conference on Arteriosclerosis Thrombosisand Vascular Biology CY MAY 08-10, 2003 CL WASHINGTON, D.C. C1 Armed Forces Inst Pathol, Washington, DC 20306 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2003 VL 23 IS 5 MA P375 BP A65 EP A66 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 676GG UT WOS:000182742500386 ER PT J AU Medeiros, LA Khan, T Moore, KJ AF Medeiros, LA Khan, T Moore, KJ TI The CD36 C-terminal tail modulates OxLDL degradation - But is not required for signal transduction SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 4th Annual Conference on Arteriosclerosis Thrombosisand Vascular Biology CY MAY 08-10, 2003 CL WASHINGTON, D.C. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2003 VL 23 IS 5 MA P444 BP A77 EP A77 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 676GG UT WOS:000182742500451 ER PT J AU Morris, AL Fitzgerald, ML Freeman, MW AF Morris, AL Fitzgerald, ML Freeman, MW TI Exchangeable apolipoproteins that mediate ABCA1 efflux directly interact with the transporter SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 4th Annual Conference on Arteriosclerosis Thrombosisand Vascular Biology CY MAY 08-10, 2003 CL WASHINGTON, D.C. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2003 VL 23 IS 5 MA P269 BP A47 EP A47 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 676GG UT WOS:000182742500287 ER PT J AU Nishikawa, K Kolodgie, FD Yasuda, T Kodama, S Virmani, R Finn, AV Faustman, D Gold, H AF Nishikawa, K Kolodgie, FD Yasuda, T Kodama, S Virmani, R Finn, AV Faustman, D Gold, H TI Defective immunoproteosome (LMP2) promotes intimal hyperplasia after arterial injury SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 4th Annual Conference on Arteriosclerosis Thrombosisand Vascular Biology CY MAY 08-10, 2003 CL WASHINGTON, D.C. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2003 VL 23 IS 5 MA P216 BP A38 EP A38 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 676GG UT WOS:000182742500239 ER PT J AU Vielma-Angarita, SA Krings, G Lopes-Virella, MF Johnson, RH AF Vielma-Angarita, SA Krings, G Lopes-Virella, MF Johnson, RH TI Protein kinase c and nuclear factor-kappa B signaling pathways mediate the upregulation of intracellular adhesion molecule-1 induced by Chlamydophila pneumoniae SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 4th Annual Conference on Arteriosclerosis Thrombosisand Vascular Biology CY MAY 08-10, 2003 CL WASHINGTON, D.C. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VAMC, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2003 VL 23 IS 5 MA P121 BP A22 EP A22 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 676GG UT WOS:000182742500149 ER PT J AU Steadman, JR Briggs, KK Rodrigo, JJ Kocher, MS Gill, TJ Rodkey, WG AF Steadman, JR Briggs, KK Rodrigo, JJ Kocher, MS Gill, TJ Rodkey, WG TI Outcomes of microfracture for traumatic chondral defects of the knee: Average 11-year follow-up SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE outcomes; chondral defects of the knee; cartilage ID ARTICULAR-CARTILAGE; TRANSPLANTATION; OSTEOARTHRITIS; LESIONS; BONE AB Purpose: In this study, we measured functional outcomes of patients treated arthroscopically with microftacture for full-thickness traumatic defects of the knee. Type of Study: A case series of patients with 7 to 17 years' follow-up. Methods: Between 1981 and 1991, a total of 72 patients (75 knees) met the following inclusion criteria: (1) traumatic full-thickness chondral defect, (2) no meniscus or ligament injury, and (3) age 45 years and younger (range, 13 to 45 years). Seventy-one knees (95%) were available for final follow-up (range, 7 to 17 years). All patients completed self-administered questionnaires preoperatively and postoperatively. Results: The following results were significant at the P < .05 level. Significant improvement was recorded for both Lysholm (scale 1 to 100; preoperative, 59; final follow-up, 89) and Tegner (1 to 10; preoperative, 3; final follow-up, 6) scores. At final follow-up, the SF-36 and WOMAC scores showed good to excellent results. At 7 years after surgery, 80% of the patients rated themselves as "improved." Multivariate analysis revealed that age was a predictor of functional improvement. Conclusions: Over the 7- to 17-year follow-up period (average, 11.3 years), patients 45 years and younger who underwent the microfracture procedure for full-thickness chondral defects, without associated meniscus or ligament pathology, showed statistically significant improvement in function and indicated that they had less pain. C1 Steadman Hawkins Sports Med Fdn, Clin Res, Vail, CO 81657 USA. Univ Calif Davis, Dept Orthopaed, Sacramento, CA 95817 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Steadman, JR (reprint author), Steadman Hawkins Sports Med Fdn, Clin Res, 181 W Meadow Dr,Suite 1000, Vail, CO 81657 USA. EM karen.briggs@shsmf.org NR 30 TC 546 Z9 566 U1 8 U2 54 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD MAY-JUN PY 2003 VL 19 IS 5 BP 477 EP 484 DI 10.1053/jars.2003.50112 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 679GN UT WOS:000182912500004 PM 12724676 ER PT J AU Wright, JE Yurasek, GK Chen, YN Rosowsky, A AF Wright, JE Yurasek, GK Chen, YN Rosowsky, A TI Further studies on the interaction of nonpolyglutamatable aminopterin analogs with dihydrofolate reductase and the reduced folate carrier as determinants of in vitro antitumor activity SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE N-alpha-(4-amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithine (PT523) and analogs; dihydrofolate reductase; reduced folate carrier ID ANTIFOLATE N-ALPHA-(4-AMINO-4-DEOXYPTEROYL)-N-DELTA-HEMIPHTHALOYL-L-ORNITHINE PT; SIDE-CHAIN; BIOLOGICAL-ACTIVITY; METHOTREXATE ANALOGS; DEAZA ANALOGS; PHASE-I; RESISTANCE; TRANSPORT; CYTOTOXICITY; INHIBITORS AB Thirteen structural analogs of the potent nonpolyglutamatable dihydrofolate reductase inhibitor N-alpha-(4-amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithine (PT523) with modifications in the side chain, the para-aminobenzoyl moiety, or the 9,10-bridge were evaluated for the ability to inhibit human recombinant dihydrofolate reductase (DHFR), to utilize the reduced folate carrier (RFC) for influx, and to inhibit the growth of CCRF-CEM human leukemia cells in culture. In spectrophotometric assays of the kinetics of the reduction of dihydrofolate by DHFR in the presence of NADPH, these compounds had K-i values ranging from 0.2 to 1.3 pM, and thus were not greatly different in potency from the parent drug PT523. By comparison, the K-i values of aminopterin (AMT), methotrexate (MTX), and 10-ethyl-10-deazaaminopterin (EDX) were 3.7,4.8, and 11 pM. In assays of competitive inhibition of [H-3]MTX influx into CCRF-CEM cells, the K-i values ranged from 0.21 to 7.3 muM, as compared with 0.71, 5.4, and 1.1 muM for PT523, AMT, and EDX. The K-i for MTX was also reanalyzed and found to be 4.7 muM, in better agreement with the literature than our previously reported value of 7.1 muM. The IC50 Values of these compounds as inhibitors of the growth of CCRF-CEM cells after 72 hr of drug exposure ranged from 0.53 to 55 nM, and were qualitatively consistent with the other results. (C) 2003 Published by Elsevier Science Inc. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Rosowsky, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01-CA25394, R01-CA 70349] NR 33 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAY 1 PY 2003 VL 65 IS 9 BP 1427 EP 1433 DI 10.1016/S0006-2952(03)00102-3 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 680UC UT WOS:000182996100004 PM 12732354 ER PT J AU Moon, WK Lin, YH O'Loughlin, T Tang, Y Kim, DE Weissleder, R Tung, CH AF Moon, WK Lin, YH O'Loughlin, T Tang, Y Kim, DE Weissleder, R Tung, CH TI Enhanced tumor detection using a folate receptor-targeted near-infrared fluorochrome conjugate SO BIOCONJUGATE CHEMISTRY LA English DT Article ID IN-VIVO; CONTRAST AGENTS; CELL-LINES; BINDING-PROTEIN; XENOGRAFTS; BREAST; DENDRIMER; DELIVERY; LIGANDS; CANCERS AB Fluorescence optical imaging technologies are currently being developed to image specific molecular targets in vivo. Detection technologies range from those providing microscopic detail to whole body imaging systems with potential clinical use. A number of target-specific near-infrared imaging probes have recently been developed to image receptors, antigens, and enzymes. The goal of the current study was to evaluate a new near-infrared (NIR) folate receptor (FR)-targeted imaging probe for its ability to improve detection of FR-positive cancers. We hypothesized that modification of folate would retain receptor affinity in vivo, despite the bulkier NIR fluorochrome, NIR2 (em = 682 nm). Cellular uptake of the NIR conjugates was significantly higher in FR-positive nasopharyngeal epidermoid carcinoma, KB cells, compared to FR-negative human fibrosarcoma, HT1080 cells. When tumors were implanted in vivo, equal-sized KB tumors showed a 2.4-fold higher signal intensity compared to HT1080 tumors (24 h). The maximum signal-to-background ratio (3-fold) was observed at 24 h in KB tumor. Injection of the unmodified NIR2 fluorochrome did not result in persistent contrast increases under similar conditions. Furthermore, tumor enhancement with the NIR2-folate probe persisted over 48 h and was inhibitable in vivo by administration of unlabeled folate. These results indicate that folate-modified NIR fluorochrome conjugate can be used for improved detection of FR-positive tumors. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, 149 13th St,Rm 5406, Charlestown, MA 02129 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50-CA86355, R33-CA88365]; PHS HHS [N01-C017014] NR 34 TC 93 Z9 99 U1 6 U2 47 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAY-JUN PY 2003 VL 14 IS 3 BP 539 EP 545 DI 10.1021/bc0340114 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 682BU UT WOS:000183071100006 PM 12757377 ER PT J AU Wang, XW Seed, B AF Wang, XW Seed, B TI Selection of oligonucleotide probes for protein coding sequences SO BIOINFORMATICS LA English DT Article ID HYBRIDIZATION; MICROARRAYS; LOCUSLINK; RESOURCES; DUPLEXES; ARRAYS; REFSEQ; NCBI AB Motivation: Large arrays of oligonucleotide probes have become popular tools for analyzing RNA expression. However to date most oligo collections contain poorly validated sequences or are biased toward untranslated regions (UTRs). Here we present a strategy for picking oligos for microarrays that focus on a design universe consisting exclusively of protein coding regions. We describe the constraints in oligo design that are imposed by this strategy, as well as a software tool that allows the strategy to be applied broadly. Results: In this work we sequentially apply a variety of simple filters to candidate sequences for oligo probes. The primary filter is a rejection of probes that contain contiguous identity with any other sequence in the sample universe that exceeds a pre-established threshold length. We find that rejection of oligos that contain 15 bases of perfect match with other sequences in the design universe is a feasible strategy for oligo selection for probe arrays designed to interrogate mammalian RNA populations. Filters to remove sequences with low complexity and predicted poor probe accessibility narrow the candidate probe space only slightly. Rejection based on global sequence alignment is performed as a secondary, rather than primary, test, leading to an algorithm that is computationally efficient. Splice isoforms pose unique challenges and we find that isoform prevalence will for the most part have to be determined by analysis of the patterns of hybridization of partially redundant oligonucleotides. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Seed, B (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 50 Blossom St, Boston, MA 02114 USA. FU NHLBI NIH HHS [U01 HL66678] NR 19 TC 105 Z9 112 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAY 1 PY 2003 VL 19 IS 7 BP 796 EP 802 DI 10.1093/bioinformatics/btg086 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 674JZ UT WOS:000182634800002 PM 12724288 ER PT J AU Dey, BR McAfee, S Colby, C Sackstein, R Saidman, S Tarbell, N Sachs, DH Sykes, M Spitzer, TR AF Dey, BR McAfee, S Colby, C Sackstein, R Saidman, S Tarbell, N Sachs, DH Sykes, M Spitzer, TR TI Impact of prophylactic donor leukocyte infusions on mixed chimerism, graft-versus-host disease, and antitumor response in patients with advanced hematologic malignancies treated with nonmyeloablative conditioning and allogeneic bone marrow transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE mixed chimerism; full donor chimerism; donor leukocyte infusion; graft versus host disease; graft versus tumor effect ID STEM-CELL TRANSPLANTATION; RELAPSED MULTIPLE-MYELOMA; ANTIGEN-PRESENTING CELLS; LYMPHOCYTE INFUSIONS; LEUKEMIA RESPONSES; INDUCTION; TOLERANCE; THERAPY; ENGRAFTMENT; REGIMEN AB In an attempt to capture graft-versus-tumor effects without graft-versus-host disease (GVHD), the authors initiated a trial of nomnyeloablative allogeneic bone marrow transplantation (BMT) in patients with advanced hematologic malignancies, with the majority of patients having chemotherapy-refractory disease. Forty-two patients received an HLA-matched related donor BMT after a cyclophosphamide and antithymocyte globulin-based conditioning that also included thymic irradiation for patients who had not received prior mediastinal radiotherapy. Prophylactic donor leukocyte infusion (pDLI) at a dose of 1 x 10(7) CD3(+) cells per kilogram were given beginning 5 weeks post-BMT to 16 patients with mixed chimerism (MC) but without GVHD, whereas 26 patients did not receive pDLI, either because of GVHD or early relapse. Twelve of 16 patients (75%) receiving pDLI had T cell chimerism. at the time of pDLI greater than or equal to40%. These patients, by day 100 post-BMT, either converted to full donor chimerism (FDC) (n = 10) or had an increase in or stable donor chimerism (n = 2) after pDLI. Four of 4 patients whose T cell chimerism was less than or equal to20% at the time of pDLI, lost the graft. In contrast, only 5 of 18 evaluable patients (28%) not receiving a pDLI converted to FDC by day 100 post-BMT, 7 maintained MC, and 10 of an evaluable 22 lost the graft. Patients who had undergone a previous autologous stem cell transplant had a higher rate of conversion to FDC (69% v 31%) and higher incidence of GVHD (69% v 34%) compared with those who did not have a previous autologous SCT. Eleven of 16 patients (69%) who received a pDLI achieved a remission with 50% 1-year progression-free survival rate and 44% 3-year overall survival rate. Nineteen of 42 patients (45%) had greater than or equal tograde II acute GVHD, including 12 after BMT and 7 after pDLI. Approximately one third of patients, after having initial MC, eventually lost their donor graft. The authors, conclude that (1) pDLI has the potential to convert MC to FDC; (2) sustained remissions can be achieved in patients with chemorefractory hematologic malignancies who receive a pDLI, albeit with a significant risk of acute GVHD; and (3) the degree of donor T cell chimerism at the time of pDLI is predictive of the fate of MC, ie, donor T cell chimerism greater than or equal to40% or less than or equal to20% at the time of pDLI correlates with conversion of MC or loss of the graft, respectively. (C) 2003 American Society for Blood and Marrow Transplantation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Unit,Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Spitzer, TR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Unit,Dept Med, 100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [R01 CA79986-A1] NR 38 TC 87 Z9 92 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 MAY PY 2003 VL 9 IS 5 BP 320 EP 329 DI 10.1016/S1083-8791(03)00077-6 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 686UE UT WOS:000183338700005 PM 12766882 ER PT J AU Bhowmick, S Zhu, L McGinnk, L Lawitts, J Nath, BD Toner, M Biggers, J AF Bhowmick, S Zhu, L McGinnk, L Lawitts, J Nath, BD Toner, M Biggers, J TI Desiccation tolerance of spermatozoa dried at ambient temperature: Production of fetal mice SO BIOLOGY OF REPRODUCTION LA English DT Article DE assisted reproductive technology ID IN-VITRO FERTILIZATION; MOUSE SPERMATOZOA; CRYOPRESERVED SPERMATOZOA; SPERM CELLS; OOCYTES; EMBRYOS; FROZEN; SURVIVAL; MUTAGENESIS; INTEGRITY AB Long-term preservation of mouse sperm by desiccation is economically and logistically attractive. The current investigation is a feasibility study of the preservation of mouse sperm by convective drying in an inert gas (nitrogen). Mouse sperm from the B6D2F1 strain isolated in an ECTA-supplemented Tris-HCI buffer were dried using three different drying rates and were stored for 18-24 h at 4degreesC. The mean final moisture content was <5% for all the protocols. After intracytoplasmic sperm injection (ICSI), the mean blastocyst formation rates were 64%, 58%, and 35% using the rapid-, moderate-, and slow-drying protocols, respectively. The slow-drying protocol resulted in a rate of development significantly lower than that observed using rapid- and moderate-drying protocols and indicated that a slower drying rate may be detrimental to the DNA integrity of mouse sperm. The transfer of 85 two- or four-cell embryos that were produced using rapidly desiccated sperm resulted in 11 fetuses (13%) on Day 15 compared with the production of 34 fetuses (40%) produced using the transfer of 86 two- or four-cell embryos that were produced using fresh sperm (P < 0.05). The results demonstrate the feasibility of using a convective drying protocol for the successful desiccation of mouse sperm and identifies some of the important parameters required for optimization of the procedure. C1 Harvard Univ, Massachusetts Gen Hosp, SHC,Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Toner, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, SHC,Sch Med, Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA. FU NICHD NIH HHS [5U01HD38227-03] NR 43 TC 45 Z9 48 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAY PY 2003 VL 68 IS 5 BP 1779 EP 1786 DI 10.1095/biolreprod.102.009407 PG 8 WC Reproductive Biology SC Reproductive Biology GA 673PQ UT WOS:000182589700039 PM 12606475 ER PT J AU Muratoglu, OK Delaney, J O'Connor, DO Harris, WH AF Muratoglu, OK Delaney, J O'Connor, DO Harris, WH TI The use of trans-vinylene formation in quantifying the spatial distribution of electron beam penetration in polyethylene. Single-sided, double-sided and shielded irradiation SO BIOMATERIALS LA English DT Article DE UHMWPE irradiation; trans-vinylene unsaturation; dose-depth distribution; double-sided irradiation ID MOLECULAR-WEIGHT POLYETHYLENE; WEAR; UHMWPE AB The use of the quantification of trans-vinylene unsaturations in irradiated ultrahigh molecular weight polyethylene (UHMWPE) in determining the spatial distribution of electron beam penetration was investigated. UHMWPE was irradiated with a 10MeV linear electron beam accelerator to 100 kGy at both room temperature and 125degreesC in an-. The irradiation was carried out in shielded and unshielded single-sided and unshielded double-sided irradiation modes. Dose-depth profiles were measured by quantifying the yields of trans-vinylene unsaturations as a function of depth away from the e-beam incidence surfaces using infrared spectroscopy. The extent of beam penetration increased with increasing irradiation temperature as was manifested by the increase in the iso-dose penetration with the unshielded single-sided irradiation and increased dose overlap with the unshielded double-sided irradiation. The optimum thickness with maximum uniformity in dose-depth distribution for double-sided irradiation was 85 and 90 mill for 25degreesC and 125degreesC irradiation temperatures, respectively. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, GRJ, Boston, MA 02114 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, GRJ, 1206 55 Fruit St, Boston, MA 02114 USA. EM orhun@alum.mit.edu NR 11 TC 14 Z9 14 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD MAY PY 2003 VL 24 IS 12 BP 2021 EP 2029 DI 10.1016/S0142-9612(02)00632-4 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 659BW UT WOS:000181758200003 PM 12628821 ER PT J AU Yoshimoto, H Shin, YM Terai, H Vacanti, JP AF Yoshimoto, H Shin, YM Terai, H Vacanti, JP TI A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering SO BIOMATERIALS LA English DT Article DE electrostatic fiber spinning; poly(epsilon-caprolactone); mesenchymal stem cells; biodegradable polymer scaffold; mineralization; bone tissue engineering ID MESENCHYMAL STEM-CELLS; BIOREACTOR; CULTURE AB Microporous, non-woven poly(epsilon-caprolactone) (PCL) scaffolds were made by electrostatic fiber spinning. In this process, polymer fibers with diameters down to the nanometer range, or nanofibers, are formed by subjecting a fluid jet to a high electric field. Mesenchymal stem cells (MSCs) derived from the bone marrow of neonatal rats were cultured, expanded and seeded oil electrospun PCL scaffolds. The cell-polymer constructs were cultured with osteogenic supplements under dynamic culture conditions for up to 4 weeks. The cell-polymer constructs maintained the size and shape of the original scaffolds. Scanning electron microscopy (SEM), histological and immunohistochemical examinations were performed. Penetration of cells and abundant extracellular matrix were observed in the cell-polymer constructs after 1 week. SEM showed that the surfaces of the cell-polymer constructs were covered with cell multilayers at 4 weeks. In addition, mineralization and type I collagen were observed at 4 weeks. This suggests that electrospun PCL is a potential candidate scaffold for bone tissue engineering. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Wellman 627,5 Fruit St, Boston, MA 02114 USA. EM jvacanti@partners.org NR 11 TC 1180 Z9 1227 U1 75 U2 657 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD MAY PY 2003 VL 24 IS 12 BP 2077 EP 2082 DI 10.1016/S0142-9612(02)00635-X PG 6 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 659BW UT WOS:000181758200010 PM 12628828 ER PT J AU Gazit, A Yee, K Uecker, A Bohmer, FD Sjoblom, T Ostman, A Waltenberger, J Golomb, G Banai, S Heinrich, MC Levitzki, A AF Gazit, A Yee, K Uecker, A Bohmer, FD Sjoblom, T Ostman, A Waltenberger, J Golomb, G Banai, S Heinrich, MC Levitzki, A TI Tricyclic quinoxalines as potent kinase inhibitors of PDGFR kinase, Flt3 and Kit SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID RECEPTOR TYROSINE-KINASE; FACTOR BETA-RECEPTOR; GROWTH-FACTOR; IN-VITRO; PHOSPHORYLATION; COMPLEX; DESIGN; CELLS AB Here we report on novel quinoxalines as highly potent and selective inhibitors of the type III receptor tyrosine kinases PDGFR, FLT3, and KIT. These compounds, tricyclic quinoxalines, were generated in order to improve bioavailability over the highly hydrophobic bicyclic quinoxalines. Four of the highly active compounds were characterized in detail and are shown to inhibit PDGFR kinase activity of the isolated receptor as well as in intact cells in the sub-micromolar concentration range. We show that the most active inhibitor (compound 13, AGL 2043) is similar to 15-20 times more potent than its isomer (compound 14, AGL 2044). We therefore compared the three dimensional structures of the two compounds by X-ray crystallography. These compounds are also highly effective in blocking the kinase activity of FLT3, KIT, and the oncogenic protein Tel-PDGFR in intact cells. These compounds are potent inhibitors of the proliferation of pig heart smooth muscle cells. They fully arrest the growth of these cells and the effect is fully reversible. The chemical, biochemical and cellular properties of these compounds as well as the solubility properties make them suitable for development as anti-restenosis and anti-cancer agents. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel. Oregon Hlth Sci Univ, Inst Canc, Dept Hematol & Med Oncol, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. Klinikum Univ Jena, Res Unit Mol Cell Biol, D-07747 Jena, Germany. Ludwig Inst Canc Res, S-75124 Uppsala, Sweden. Univ Ulm, Dept Internal Med 2, D-89081 Ulm, Germany. Hebrew Univ Jerusalem, Sch Pharm, IL-91904 Jerusalem, Israel. Bikur Holim Hosp, Dept Cardiol, IL-91004 Jerusalem, Israel. RP Levitzki, A (reprint author), Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel. RI Heinrich, Michael/C-3727-2013; OI Heinrich, Michael/0000-0003-2611-6303; Waltenberger, Johannes/0000-0002-2417-9880; Golomb, Gershon/0000-0002-7369-9831 NR 23 TC 48 Z9 49 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAY 1 PY 2003 VL 11 IS 9 BP 2007 EP 2018 DI 10.1016/S0968-1896(03)00048-8 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 665CA UT WOS:000182101000008 PM 12670652 ER PT J AU O'Farrell, AM Abrams, TJ Yuen, HA Ngai, TJ Louie, SG Yee, KWH Wong, LM Hong, W Lee, LB Town, A Smolich, BD Manning, WC Murray, LJ Heinrich, MC Cherrington, JM AF O'Farrell, AM Abrams, TJ Yuen, HA Ngai, TJ Louie, SG Yee, KWH Wong, LM Hong, W Lee, LB Town, A Smolich, BD Manning, WC Murray, LJ Heinrich, MC Cherrington, JM TI SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; ENDOTHELIAL GROWTH-FACTOR; ACUTE MYELOGENOUS LEUKEMIA; BONE-MARROW; CELL-GROWTH; RISK GROUP; RECEPTOR; MUTATIONS; GENE AB FLT3 (fms-related tyrosine kinase/Flk2/ Stk-2) is a receptor tyrosine kinase (RTK) primarily expressed on hematopoietic cells. In blasts from acute myelogenous leukemia (AML) patients, 2 'classes of FLT3 activating mutations have been identified: internal tandem duplication (ITD) mutations in the juxtamembrane domain (25%-30% of patients) and point mutations in the kinase domain activation loop (7%-8% of patients). FLT3-ITD mutations are the most common molecular defect identified in AML and have been shown to be an independent prognostic factor for decreased survival. FLT3-ITD is therefore an attractive molecular target for therapy. SU11248 is a recently described selective inhibitor with selectivity for split kinase domain RTKs, including platelet-derived growth factor receptors, vascular endothelial growth,factor receptors, and KIT. We show that SU11248 Aldo has potent activity against Wild-type FLT3 ( FLT3-WT), FLT3-ITD, And FLT3 activation loop FLT3-Asp835) mutants in phosphorylation Assays. SU11246 inhibits FLT3-driven phosphorylation and induces apoptosis in vitro. In addition, SU11248 inhibits FLT3-induced VEGF production. The in vivo efficacy of SU11248 was investigated in 2 FLT3-ITD models: a subcutaneous tumor xenograft model and a bone marrow engraftment model. We show that SU11248 (20 mg/kg/d) dramatically regresses FLT3-ITD tumors in the subcutaneous tumor xenograft model And prolongs survival in the bone - marrow engraftment model: Pharmacokinetic and pharmacodynamic analysis in subcutaneous tumors showed that a single administration of an efficacious drug dose potently inhibits FLT3-ITD phosphorylation for up, to 16 hours following A single dose. These results suggest that further exploration of SU11248 activity in AML patients is warranted. (C) 2003 by The American Society of Hematology. C1 SUGEN, Preclin Res & Exploratory Dev, San Francisco, CA 94080 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Inst Canc, Div Hematol & Med Oncol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP O'Farrell, AM (reprint author), SUGEN, Preclin Res & Exploratory Dev, 230 E Grand Ave, San Francisco, CA 94080 USA. NR 43 TC 590 Z9 606 U1 3 U2 27 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 MAY 1 PY 2003 VL 101 IS 9 BP 3597 EP 3605 DI 10.1182/blood-2002-07-2307 PG 9 WC Hematology SC Hematology GA 674EZ UT WOS:000182625600050 PM 12531805 ER PT J AU Chauhan, D Li, GL Auclair, D Hideshima, T Richardson, P Podar, K Mitsiades, N Mitsiades, C Li, C Kim, RS Munshi, N Chen, LB Wong, W Anderson, KHC AF Chauhan, D Li, GL Auclair, D Hideshima, T Richardson, P Podar, K Mitsiades, N Mitsiades, C Li, C Kim, RS Munshi, N Chen, LB Wong, W Anderson, KHC TI Identification of genes regulated by 2-methoxyestradiol (2ME2) in multiple myeloma cells using oligonucleotide arrays SO BLOOD LA English DT Article ID ENDOGENOUS MAMMALIAN METABOLITE; INHIBITS TUBULIN POLYMERIZATION; CANCER-CELLS; GROWTH-FACTOR; SUPEROXIDE-DISMUTASE; EXPRESSION PATTERNS; DRUG-RESISTANCE; BREAST-CANCER; PLASMA-CELLS; APOPTOSIS AB Our previous study demonstrated that 2-methoxyestradiol (2ME2), an estrogen derivative, induces apoptosis in multiple myeloma (MM) cells; however, the related transcriptional events are unclear. In the present study, We used oligonucleotide microarrays to identify genes altered during 2ME2-induced apoptosis in MM cells. 2ME2 triggers an early transient induction of genes known to trigger cell death and repression of growth/survival-related genes. Many genes regulating cell defense/repair machinery also were tran slently induced. Since 2ME2. also induces apoptosis in MM cells resistant to conventional therapies such as dexamethasone (Dex), we compared the gene profiles of 2ME2-treated and Dex-resistant MM cells. Out results suggest that 2ME2 overcomes Dex resistance by modulating genes that confer chemoresistance in MM cells. Microarray results were confirmed by Northern and Western blot analyses. A comparative analysis of selected genes from freshly isolated MM patient cells and 2ME2-treated MM.1S MM cells further provides an in vivo relevance of our in vitro studies. Collectively, these findings suggest genetic events mediating anti-MM activity of 2ME2, as well as mechanisms whereby 2ME2 overcomes Mix resistance in MM cells. These studies may therefore allow improved therapeutic use of 2ME2, based upon targeting genes that regulate MM cell growth and survival. (C) 2003 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston Vet Affairs Healthcare Syst, Boston, MA 02215 USA. RP Anderson, KHC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02215 USA. FU NCI NIH HHS [CA 78373]; PHS HHS [50947] NR 45 TC 56 Z9 59 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 MAY 1 PY 2003 VL 101 IS 9 BP 3606 EP 3614 DI 10.1182/blood-2002-10-3146 PG 9 WC Hematology SC Hematology GA 674EZ UT WOS:000182625600051 PM 12480690 ER PT J AU Koshiyama, H Kuwamura, N Nakamura, Y Minamikawa, J Tachibana, M Miyauchi, A Ishimura, E Imai, Y Jonsson, KB Juepnner, H AF Koshiyama, H Kuwamura, N Nakamura, Y Minamikawa, J Tachibana, M Miyauchi, A Ishimura, E Imai, Y Jonsson, KB Juepnner, H TI Analysis of expression and circulating level of FGF-23 in non-McCune-Albright syndrome fibrous dysplasia SO BONE LA English DT Meeting Abstract CT 1ST Joint meeting of the International-Bone-and-Mineral-Society/Japanese-Society-for-Bone-and-Min eral-Research CY JUN 03-07, 2003 CL OSAKA, JAPAN SP Int Bone & Mineral Soc, Japanese Soc bone & Mineral Res C1 Hyogo Kenritsu Amagasaki Hosp, Dept Endocrinol, Amagasaki, Hyogo, Japan. Hyogo Kenritsu Amagasaki Hosp, Dept Metab, Amagasaki, Hyogo, Japan. Hyogo Kenritsu Amagasaki Hosp, Dept Pathol, Amagasaki, Hyogo, Japan. Natl Sanatorium Hyogo Chuo Hosp, Sanda, Japan. Osaka City Univ, Grad Sch Med, Dept Metab Endocrinol & Mol Med, Osaka, Japan. Univ Uppsala, Dept Med, S-75105 Uppsala, Sweden. Massachusetts Gen Hosp, Boston, MA 02114 USA. MassGen Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, 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 8756-3282 J9 BONE JI Bone PD MAY PY 2003 VL 32 IS 5 SU S BP S119 EP S119 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683AB UT WOS:000183123300210 ER PT J AU Neer, R Finkelstein, J AF Neer, R Finkelstein, J TI PTH and the future of anabolic treatments for osteoporosis SO BONE LA English DT Meeting Abstract CT 1ST Joint meeting of the International-Bone-and-Mineral-Society/Japanese-Society-for-Bone-and-Min eral-Research CY JUN 03-07, 2003 CL OSAKA, JAPAN SP Int Bone & Mineral Soc, Japanese Soc bone & Mineral Res C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 MAY PY 2003 VL 32 IS 5 SU S BP S69 EP S69 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683AB UT WOS:000183123300005 ER PT J AU Schipani, E AF Schipani, E TI Hypoxia and HIF 1 alpha in endochondral bone development SO BONE LA English DT Meeting Abstract CT 1ST Joint meeting of the International-Bone-and-Mineral-Society/Japanese-Society-for-Bone-and-Min eral-Research CY JUN 03-07, 2003 CL OSAKA, JAPAN SP Int Bone & Mineral Soc, Japanese Soc bone & Mineral Res C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02129 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 8756-3282 J9 BONE JI Bone PD MAY PY 2003 VL 32 IS 5 SU S BP S70 EP S70 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683AB UT WOS:000183123300009 ER PT J AU Wu, Y Glimcher, M Graham, L Chesler, D Wang, Y Ackerman, J AF Wu, Y Glimcher, M Graham, L Chesler, D Wang, Y Ackerman, J TI Noninvasive measurement of degree of bone mineralization with solid state proton and phosphorus MRI SO BONE LA English DT Meeting Abstract CT 1ST Joint meeting of the International-Bone-and-Mineral-Society/Japanese-Society-for-Bone-and-Min eral-Research CY JUN 03-07, 2003 CL OSAKA, JAPAN SP Int Bone & Mineral Soc, Japanese Soc bone & Mineral Res C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 MAY PY 2003 VL 32 IS 5 SU S BP S177 EP S177 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683AB UT WOS:000183123300459 ER PT J AU Herbert, MR Ziegler, DA Deutsch, CK O'Brien, LM Lange, N Bakardjiev, A Hodgson, J Adrien, KT Steele, S Makris, N Kennedy, D Harris, GJ Caviness, VS AF Herbert, MR Ziegler, DA Deutsch, CK O'Brien, LM Lange, N Bakardjiev, A Hodgson, J Adrien, KT Steele, S Makris, N Kennedy, D Harris, GJ Caviness, VS TI Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys SO BRAIN LA English DT Article DE autistic disorder; brain/growth and development; MRI; cerebral white matter; morphometry ID POSITRON-EMISSION-TOMOGRAPHY; NERVOUS-SYSTEM MYELINATION; BRAIN-DEVELOPMENT; INFANTILE-AUTISM; HEAD CIRCUMFERENCE; NEURODEVELOPMENTAL DAMAGE; POSTERIOR-FOSSA; HUMAN INFANCY; MRI; CHILDREN AB High-functioning autistic and normal school-age boys were compared using a whole-brain morphometric profile that includes both total brain volume and volumes of all major brain regions. We performed MRI-based morphometric analysis on the brains of 17 autistic and 15 control subjects, all male with normal intelligence, aged 7-11 years. Clinical neuroradiologists judged the brains of all subjects to be clinically normal. The entire brain was segmented into cerebrum, cerebellum, brainstem and ventricles. The cerebrum was subdivided into cerebral cortex, cerebral white matter, hippocampus-amygdala, caudate nucleus, globus pallidus plus putamen, and diencephalon (thalamus plus ventral diencephalon). Volumes were derived for each region and compared between groups both before and after adjustment for variation in total brain volume. Factor analysis was then used to group brain regions based on their intercorrelations. Volumes were significantly different between groups overall; and diencephalon, cerebral white matter, cerebellum and globus pallidus-putamen were significantly larger in the autistic group. Brain volumes were not significantly different overall after adjustment for total brain size, but this analysis approached significance and effect sizes and univariate comparisons remained notable for three regions, although not all in the same direction: cerebral white matter showed a trend towards being disproportionately larger in autistic boys, while cerebral cortex and hippocampus-amygdala showed trends toward being disproportionately smaller. Factor analysis of all brain region volumes yielded three factors, with central white matter grouping alone, and with cerebral cortex and hippocampus-amygdala grouping separately from other grey matter regions. This morphometric profile of the autistic brain suggests that there is an overall increase in brain volumes compared with controls. Additionally, results suggest that there may be differential effects driving white matter to be larger and cerebral cortex and hippocampus-amygdala to be relatively smaller in the autistic than in the typically developing brain. The cause of this apparent dissociation of cerebral cortical regions from subcortical regions and of cortical white from grey matter is unknown, and merits further investigation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Eunice Kennedy Shriver Ctr Mental Retardat Inc, Waltham, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. Childrens Hosp Oakland, Dept Infect Dis, Oakland, CA 94609 USA. Pennington Sch, Pennington, NJ USA. Tufts Univ, Boston, MA 02111 USA. Univ Illinois, Chicago, IL USA. RP Herbert, MR (reprint author), Massachusetts Gen Hosp, Ctr Morphometr Anal Pediat Neurol, Dept Neurol, Room CNY149-6012, Boston, MA 02114 USA. RI Kennedy, David/H-3627-2012 FU NIDA NIH HHS [DA 09467]; NIDCD NIH HHS [P01-DC 03610]; NIMH NIH HHS [MH 57180]; NINDS NIH HHS [NS 02126, NS 20489, NS 27950, NS 34189, NS 37483] NR 72 TC 238 Z9 243 U1 3 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAY PY 2003 VL 126 BP 1182 EP 1192 DI 10.1093/brain/awg110 PN 5 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 668ZR UT WOS:000182327900017 PM 12690057 ER PT J AU Keating, NL Weeks, JC Borbas, C Guadagnoli, E AF Keating, NL Weeks, JC Borbas, C Guadagnoli, E TI Treatment of early stage breast cancer: do surgeons and patients agree regarding whether treatment alternatives were discussed? SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; communication; decision-making; informed consent ID COMPARING TOTAL MASTECTOMY; DECISION-MAKING; CARE AB Background. Informing patients of available treatment alternatives is an important element of informed consent. We examined and compared patients' and their surgeons' reports of discussing treatment alternatives for early stage breast cancer. Methods. We surveyed early stage breast cancer patients in two states (Minnesota and Massachusetts) about discussions of breast cancer treatments. We also surveyed their surgeons. We compared how often patients' and surgeons' reports about discussions of treatment alternatives agreed, and we used generalized estimating equations to identify factors related to patients' reports that alternatives were not discussed when their surgeons reported that they were discussed. Results. Among 1154 women eligible for both breast-conserving surgery and mastectomy, only 71% reported that their surgeon discussed both treatments. Surgeons of 730 women returned surveys and reported discussing both treatments with 82% of the patients. One-third of the time, patients and surgeons disagreed about whether both treatments were discussed; with patients more often reporting that both treatments were not discussed when surgeons reported they were. In adjusted analyses, compared to better-educated patients, less-educated patients more often reported that their surgeons did not discuss both treatments when their surgeons reported that they did (compared to non-high school graduates, odds ratio (OR) 0.44, 95% confidence interval (CI) 0.22-0.87 for high school graduates; OR 0.51; 95% CI 0.27-0.96 for women with at least some college education; and OR 0.50; 95% CI 0.20-1.24 for women with any post-graduate work). Conclusion. Patients' and surgeons' reports of treatments discussed often disagree. Interventions to assure that surgeons present and patients fully comprehend treatment options may help to improve the decision-making process, particularly for less well-educated women. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Healthcare Educ & Res Fdn Inc, St Paul, MN USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA59408, CA57755] NR 24 TC 38 Z9 38 U1 0 U2 0 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 MAY PY 2003 VL 79 IS 2 BP 225 EP 231 DI 10.1023/A:1023903701674 PG 7 WC Oncology SC Oncology GA 682VG UT WOS:000183112600009 PM 12825857 ER PT J AU Hayashi, T Treon, SP Hideshima, T Tai, YT Akiyama, M Richardson, P Chauhan, D Grewal, IS Anderson, KC AF Hayashi, T Treon, SP Hideshima, T Tai, YT Akiyama, M Richardson, P Chauhan, D Grewal, IS Anderson, KC TI Recombinant humanized anti-CD40 monoclonal antibody triggers autologous antibody-dependent cell-mediated cytotoxicity against multiple myeloma cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE ADCC; CD40; multiple myeloma ID IN-VIVO; CD40 STIMULATION; GROWTH; SECRETION; LYMPHOMA AB Multiple myeloma (MM) is currently incurable, and novel therapies are needed. In this study, we examined a novel recombinant humanized monoclonal antibody against CD40 (rhuCD40 mAb) and demonstrate for the first time that rhuCD40 mAb induces antibody-dependent cell-mediated cytotoxicity (ADCC) against CD40-positive MM cells. Importantly, we show that rhuCD40 mAb induces autologous ADCC against primary patient MM cells, without triggering ADCC against normal B cells. This study, therefore, both demonstrates that rhuCD40 mAb triggers autologous ADCC against patient MM cells and provides the framework for the clinical evaluation of rhuCD40 mAb immunotherapy to improve patient outcome in MM. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. FU PHS HHS [P0178378] NR 12 TC 38 Z9 42 U1 0 U2 0 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 MAY PY 2003 VL 121 IS 4 BP 592 EP 596 DI 10.1046/j.1365-2141.2003.04322.x PG 5 WC Hematology SC Hematology GA 679XE UT WOS:000182946600006 PM 12752100 ER PT J AU Chen, TC Chao, CW Sorkin, JA AF Chen, TC Chao, CW Sorkin, JA TI Topiramate induced myopic shift and angle closure glaucoma SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CILIARY C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Childrens Hosp, Dept Ophthalmol, Microsurg Consultants, Peabody, MA 01960 USA. RP Chen, TC (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 28 Z9 29 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD MAY PY 2003 VL 87 IS 5 BP 648 EP 649 DI 10.1136/bjo.87.5.648 PG 2 WC Ophthalmology SC Ophthalmology GA 671MT UT WOS:000182469100036 PM 12714417 ER PT J AU Beckett, JR Kotre, CJ Michaelson, JS AF Beckett, JR Kotre, CJ Michaelson, JS TI Analysis of benefit : risk ratio and mortality reduction for the UK Breast Screening Programme SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID RADIATION RISK; CANCER; MAMMOGRAPHY; SURVIVAL; BALANCE; MODEL; TRIAL AB A quantitative analysis has been performed to predict the benefit:risk ratio and associated mortality reduction for the UK National Health Service Breast Screening Programme. The analysis is based on the results of an established biological simulation method coupled with dosimetric information and population statistics applicable to the UK breast screening programme. As well as the general breast screening population, the benefit:risk ratios for specific subgroups of women thought to be at higher risk are estimated. The effects of alterations in screening strategy are also investigated. The results indicate favourable benefit:risk ratios and mortality reductions for all women in the programme, with a breast cancer mortality reduction of approximately 9% over the whole UK female population, equivalent to a breast cancer mortality reduction in the region of 25% for the age range 55-69 years. C1 Newcastle Gen Hosp, Dept Reg Med Phys, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Beckett, JR (reprint author), Newcastle Gen Hosp, Dept Reg Med Phys, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. NR 36 TC 12 Z9 12 U1 0 U2 1 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD MAY PY 2003 VL 76 IS 905 BP 309 EP 320 DI 10.1259/bjr/64009424 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 689GX UT WOS:000183484200005 PM 12763946 ER PT J AU Hettiaratchy, S Melendy, E Randolph, MA Butler, PEM Sachs, DH Huang, CA Lee, WPA AF Hettiaratchy, S Melendy, E Randolph, MA Butler, PEM Sachs, DH Huang, CA Lee, WPA TI A large animal model of allotransplantation without long-term immunosuppression SO BRITISH JOURNAL OF SURGERY LA English DT Meeting Abstract CT 3rd Meeting of the Society-of-Academic-and-Research-Surgery CY JAN, 2003 CL ROYAL ARMOURIES MUSEUM, LEEDS, ENGLAND SP Soc Acad & Res Surg HO ROYAL ARMOURIES MUSEUM C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD MAY PY 2003 VL 90 IS 5 BP 630 EP 631 PG 2 WC Surgery SC Surgery GA 695YR UT WOS:000183858400101 ER PT J AU Garber, JE AF Garber, JE TI Breast cancer screening: A final analysis? SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Editorial Material ID MAMMOGRAPHY C1 Dana Farber Canc Inst, Canc Risk & Prevent Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Garber, JE (reprint author), Dana Farber Canc Inst, Canc Risk & Prevent Program, Boston, MA 02115 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAY-JUN PY 2003 VL 53 IS 3 BP 138 EP 140 PG 3 WC Oncology SC Oncology GA 687YX UT WOS:000183405500001 PM 12809407 ER PT J AU Wu, Y Ackerman, JL Strawich, ES Rey, C Kim, HM Glimcher, MJ AF Wu, Y Ackerman, JL Strawich, ES Rey, C Kim, HM Glimcher, MJ TI Phosphate ions in bone: Identification of a calcium-organic phosphate complex by P-31 solid-state NMR spectroscopy at early stages of mineralization SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE phosphoproteins; bone; P-31 NMR; calcification; apatite ID NUCLEAR-MAGNETIC-RESONANCE; DENTIN MATRIX PROTEIN-1; HYDROXYAPATITE FORMATION; MAGIC ANGLE; CROSS-POLARIZATION; CRYSTAL-FORMATION; COLLAGEN FIBRILS; CHICKEN-BONE; IN-VITRO; PHOSPHOPROTEINS AB Previous P-31 cross-polarization and differential cross-polarization magic angle spinning (CP/MAS and DCP/MAS) solid-state NMR spectroscopy studies of native bone and of the isolated crystals of the calcified matrix synthesized by osteoblasts in cell culture identified and characterized the major PO4-3 phosphate components of the mineral phase. The isotropic and anisotropic chemical shift parameters of the minor HPO4-2 component in bone mineral and in mineral deposited in osteoblast cell cultures were found to differ significantly from those of brushite, octacalcium phosphate, and other synthetic calcium phosphates. However, because of in vivo and in vitro evidence that phosphoproteins may play a significant role in the nucleation of the solid mineral phase of calcium phosphate in bone and other vertebrate calcified tissues, the focus of the current solid-state P-31 NMR experiments was to detect the possible presence of and characterize the phosphoryl groups of phosphoproteins in bone at the very earliest stages of bone mineralization, as well as the possible presence of calcium-phosphoprotein complexes. The present study demonstrates that by far the major phosphate components identified by solid-state P-31 NMR in the very earliest stages of mineralization are protein phosphoryl groups which are not complexed with calcium. However, very small amounts of calcium-complexed protein phosphoryl groups as well as even smaller, trace amounts of apatite crystals were also present at the earliest phases of mineralization. These data support the hypothesis that phosphoproteins complexed with calcium play a significant role in the initiation of bone calcification. C1 Harvard Univ, Childrens Hosp, Sch Med,Dept Orthopaed Surg, Lab Study Skeletal Disorders & Rehabil, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,NMR Ctr, Dept Radiol,Biomat Lab, Charlestown, MA 02129 USA. ENSCT, Ctr Interuniv Rech & Ingn Mat, UMR CNRS 5083, INPT, F-31400 Toulouse, France. Seoul Natl Univ, Coll Dent, Dept Oral Anat, Lab Hard Tissue Engn, Seoul 110749, South Korea. RP Ackerman, JL (reprint author), Harvard Univ, Childrens Hosp, Sch Med,Dept Orthopaed Surg, Lab Study Skeletal Disorders & Rehabil, Boston, MA 02115 USA. RI Ackerman, Jerome/E-2646-2015 OI Ackerman, Jerome/0000-0001-5176-7496 FU NCRR NIH HHS [RR03264]; NIA NIH HHS [AG14701]; NIAMS NIH HHS [R01-AR42258, T32-AR07112] NR 67 TC 60 Z9 60 U1 5 U2 28 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD MAY PY 2003 VL 72 IS 5 BP 610 EP 626 DI 10.1007/s00223-002-1068-8 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 685ZG UT WOS:000183294500011 PM 12724829 ER PT J AU Oh, WK Tully, P Kantoff, PW Regan, MM AF Oh, WK Tully, P Kantoff, PW Regan, MM TI Physician attitudes toward cytotoxic chemotherapy use in patients with advanced prostate carcinoma SO CANCER LA English DT Article DE prostate carcinoma; hormone refractory; chemotherapy; survey; attitudes ID PHASE-II; CANCER; HYDROCORTISONE; MITOXANTRONE; ESTRAMUSTINE; MANAGEMENT; DOCETAXEL; TRIAL; MEN AB BACKGROUND. Attitudes toward the use of chemotherapy in patients with prostate carcinoma have changed as new therapeutics have demonstrated efficacy. This is important as randomized trials using chemotherapy are proposed. The authors used a questionnaire to investigate the attitudes of physicians in the New England area who care for patients with advanced prostate carcinoma. METHODS. A 15-question survey was developed and mailed in the year 2000. No monetary incentives were used to encourage return of surveys. Baseline demographic data were obtained, including type of practice and number of patients with prostate carcinoma seen. Urologists, radiation oncologists, and medical oncologists were asked whether they had recommended chemotherapy for patients with prostate carcinoma, what they perceived as the effectiveness of specific drugs, what concerns they had regarding chemotherapy, and the appropriateness of chemotherapy in three hypothetical patient scenarios. RESULTS. Of 1068 surveys that were delivered to practicing physicians, 232 surveys (22%) were returned and evaluable. Forty-six percent of respondents were urologists, 41% were medical oncologists, and 10% were radiation oncologists. Eighty-seven percent of respondents had recommended cytotoxic chemotherapy to their patients. Four agents were rated as moderately effective to very effective by 41-60% of respondents who rated effectiveness: estramustine, mitoxantrone, paclitaxel, and docetaxel. In three hypothetical patient scenarios of hormone-refractory prostate carcinoma, only one patient was judged as an appropriate candidate for chemotherapy. In a multivariate analysis, female physicians and physicians with practices comprised of > 25% patients with hormone-refractory prostate carcinoma were more likely to recommend chemotherapy. Concerns regarding severe toxicity and lack of benefit were among the most influential on respondent decisions to use chemotherapy. CONCLUSIONS. Most physicians who cared for patients with prostate carcinoma had recommended chemotherapy for patients with hormone-refractory disease. There were differences between specialties regarding the likelihood of recommending chemotherapy and clinical judgment regarding which patients were appropriate candidates for chemotherapy. Cancer 2003;97:2171-9. (C) 2003 American Cancer Society. C1 Harvard Univ, Ctr Canc, Dana Farber Canc Inst, Dept Adult Oncol,Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med,Ctr Canc, Dana Farber Canc Inst, Beth Israel Deaconess Med Ctr,Biometr Ctr, Boston, MA 02115 USA. RP Oh, WK (reprint author), Harvard Univ, Ctr Canc, 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 14 TC 5 Z9 5 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 MAY 1 PY 2003 VL 97 IS 9 BP 2171 EP 2179 DI 10.1002/cncr.11344 PG 9 WC Oncology SC Oncology GA 671BT UT WOS:000182445700008 PM 12712468 ER PT J AU Crowley, R Casarett, D AF Crowley, R Casarett, D TI Patients' willingness to participate in symptom-related and disease-modifying research - Results of a research screening initiative in a palliative care clinic SO CANCER LA English DT Article DE palliative care; symptom management; informed consent; cancer; terminal illness ID RANDOMIZED CONTROLLED TRIAL; CANCER PAIN MANAGEMENT; GUIDELINES; ENROLLMENT; FENTANYL; PROGRAM; PLACEBO AB BACKGROUND. The growth of cancer symptom management research has been limited by challenges of slow recruitment and underenrollment. One potential solution to this problem is the use of screening questions that identify patients who are interested in participating in research. The goal of this study was to evaluate this strategy in patients with cancer. METHODS. Two screening questions (for symptom management research and disease-modifying research) were integrated into the intake process of the palliative care clinic of an urban Veteran's Administration medical center. A chart review was conducted to extract patients' reported willingness to be recruited for research, explanations for their responses, demographic data, Memorial Symptom Assessment Scale Global Distress Index (GDI) subscale scores, and Eastern Cooperative Oncology Group performance score. RESULTS. Charts were reviewed for the first 100 patients seen for a palliative care clinic visit, 86 of whom had cancer. Patients were less likely to be interested in symptom-related research than in disease-modifying research (32 of 86 [37%] vs. 46 of 86 [54%]; sign test, P = 0.009). Patients' interest in each type of research was associated moderately (kappa = 0.41; P < 0.001). Independent predictors of interest in symptom management research included younger age, white race, and a lower GDI symptom distress score. Independent predictors of interest in disease-modifying research included only younger age and white race. CONCLUSIONS. Screening questions may be useful in identifying patients who are willing to be recruited for research. However, further study is needed to evaluate this process in other populations, as well as to determine whether screening questions introduce selection bias in the recruitment process. Published 2003 by the American Cancer Society.*. C1 Univ Penn, Inst Aging, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Casarett, D (reprint author), Univ Penn, Inst Aging, 3615 Chestnut St, Philadelphia, PA 19104 USA. NR 26 TC 14 Z9 14 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 MAY 1 PY 2003 VL 97 IS 9 BP 2327 EP 2333 DI 10.1002/cncr.11329 PG 7 WC Oncology SC Oncology GA 671BT UT WOS:000182445700030 PM 12712490 ER PT J AU Santillan, AA Camargo, CA Colditz, GA AF Santillan, AA Camargo, CA Colditz, GA TI A meta-analysis of asthma and risk of lung cancer (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE asthma; epidemiology; lung neoplasm; meta-analysis; smoking ID OBSTRUCTIVE PULMONARY-DISEASE; NONSMOKING WOMEN; RESPIRATORY-DISEASE; FAMILY HISTORY; GLUCOCORTICOID THERAPY; MUCOCILIARY CLEARANCE; BRONCHIAL-ASTHMA; SMOKING; MORTALITY; ADULTS AB Objective: To review epidemiologic evidence that asthma is a risk factor for lung cancer, with particular attention to the role of smoking on this association. Methods: Through MEDLINE computer searches (January 1966 to April 2002) and a review of references, we identified studies with quantitative data on the relation of asthma to lung cancer. Summary estimates of relative risks (RR) were calculated using the fixed-effects model or the random-effects model as appropriate. Results: The combined results from five case-control studies - that presented data limited to individuals who had never smoked - showed a 1.8-fold increase in lung cancer risk among asthmatics (95% confidence interval (CI) = 1.3-2.3). The results from six case - control and four cohort studies, which controlled for smoking history also were significant (RR = 1.7; 95% CI = 1.3-2.2). Finally, to illustrate the potential confounding by tobacco, we combined data from seven cohort studies that did not control for smoking history and found an overall RR of 1.4 (95% CI = 1.2-1.6). Conclusions: The increased risk of lung cancer among never smoking individuals with asthma supports a direct relation between asthma and lung cancer. There is biological evidence to support this association. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Colditz, GA (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 NHLBI NIH HHS [HL-63841] NR 67 TC 96 Z9 100 U1 2 U2 4 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 MAY PY 2003 VL 14 IS 4 BP 327 EP 334 DI 10.1023/A:1023982402137 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 684JC UT WOS:000183201000004 PM 12846363 ER PT J AU Cools, J Stover, EH Boulton, CL Gotlib, J Legare, RD Amaral, SM Curley, DP Duclos, N Rowan, R Kutok, JL Lee, BH Williams, IR Coutre, SE Stone, RM DeAngelo, DJ Marynen, P Manley, PW Meyer, T Fabbro, D Neuberg, D Weisberg, E Griffin, JD Gilliland, DG AF Cools, J Stover, EH Boulton, CL Gotlib, J Legare, RD Amaral, SM Curley, DP Duclos, N Rowan, R Kutok, JL Lee, BH Williams, IR Coutre, SE Stone, RM DeAngelo, DJ Marynen, P Manley, PW Meyer, T Fabbro, D Neuberg, D Weisberg, E Griffin, JD Gilliland, DG TI PKC412 overcomes resistance to imatinib in a murine model of FIP1L1-PDGFR alpha-induced myeloproliferative disease SO CANCER CELL LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; GASTROINTESTINAL STROMAL TUMORS; CHRONIC MYELOGENOUS LEUKEMIA; PROTEIN-KINASE INHIBITOR; FACTOR RECEPTOR-BETA; ABL TYROSINE KINASE; C-KIT; PHILADELPHIA-CHROMOSOME AB FIP1L1-PDGFRalpha causes hypereosinophilic syndrome (HES) and is inhibited by the tyrosine kinase inhibitor imatinib (Gleevec). Imatinib is a potent inhibitor of ABL, ARG, PDGFRalpha, PDGFRbeta, and KIT and induces durable hematologic responses in HES patients. However, we observed relapse with resistance to imatinib as consequence of a T6741 mutation in FIP1L1-PDGFRalpha, analogous to the imatinib-resistant T3151 mutation in BCR-ABL. We developed a murine bone marrow transplant model of FIP1L1-PDGFRalpha-induced myeloproliferative disease to evaluate the efficacy of PKC412, an alternative inhibitor of PDGFRalpha, for the treatment of HES. PKC412 is effective for treatment of FIP1L1-PDGFRalpha-induced disease and of imatinib-induced resistance due to the T6741 mutation. Our data establish PKC412 as molecularly targeted therapy for HES and other diseases expressing activated PDGFRalpha and demonstrate the potential of alternative kinase inhibitors to overcome resistance in target tyrosine kinases. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Ctr Human Genet, B-3000 Louvain, Belgium. Flanders Interuniv Inst Biotechnol VIB, B-3000 Louvain, Belgium. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Med, Div Hematol, Stanford, CA 94305 USA. Brown Univ, Women & Infants Hosp, Sch Med, Providence, RI 02905 USA. Westerly Hosp, Providence, RI 02905 USA. Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Novartis Pharmaceut, CH-4002 Basel, Switzerland. RP Gilliland, DG (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Hematol, Boston, MA 02115 USA. EM gilliland@calvin.bwh.harvard.edu RI Williams, Ifor/D-3648-2011 OI Williams, Ifor/0000-0002-8810-2911 FU NCI NIH HHS [CA66996]; NIDDK NIH HHS [DK50654]; NIGMS NIH HHS [T32 GM007753, T32GM07753-24] NR 43 TC 174 Z9 181 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAY PY 2003 VL 3 IS 5 BP 459 EP 469 DI 10.1016/S1535-6108(03)00108-9 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 682RB UT WOS:000183104800009 PM 12781364 ER PT J AU Zhao, JJ Gjoerup, OV Subramanian, RR Cheng, Y Chen, W Roberts, TM Hahn, WC AF Zhao, JJ Gjoerup, OV Subramanian, RR Cheng, Y Chen, W Roberts, TM Hahn, WC TI Human mammary epithelial cell transformation through the activation of phosphatidylinositol 3-kinase SO CANCER CELL LA English DT Article ID SMALL-T-ANTIGEN; PROTEIN PHOSPHATASE 2A; SV40 SMALL-T; ANCHORAGE-INDEPENDENT GROWTH; MYC-INDUCED APOPTOSIS; SMALL TUMOR-ANTIGEN; MAP KINASE KINASE; NF-KAPPA-B; C-MYC; BREAST CARCINOMAS AB Recent studies have demonstrated that introduction of hTERT in combination with SV40 large T antigen (LT), small t antigen (st), and H-rasV12 suffices to transform many primary human cells. In human mammary epithelial cells (HMECs) expressing elevated c-Myc, activated H-Ras is dispensable for anchorage-independent growth. Using this system, we show that st activates the PI3K pathway and that constitutive PI3K signaling substitutes for st in transformation. Moreover, using constitutively active versions of Akt1 and Rac1, we show that these downstream pathways of PI3K synergize to achieve anchorage-independent growth. At lower levels of c-myc expression, activated PI3K also replaces st to complement H-rasV12 and LT and confers both soft agar growth and tumorigenicity. However, elevated c-myc expression cannot replace H-rasV12 for tumorigenesis. These observations begin to define the pathways perturbed during the transformation of HMECs. 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, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Roberts, TM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. FU NCI NIH HHS [2T32CA09361-21A1, CA30002, CA89021, K01 CA94223, P01-CAS0661] NR 75 TC 187 Z9 194 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAY PY 2003 VL 3 IS 5 BP 483 EP 495 DI 10.1016/S1535-6108(03)00088-6 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 682RB UT WOS:000183104800011 PM 12781366 ER PT J AU Skinner, HG Michaud, DS Colditz, GA Giovannucci, EL Stampfer, MJ Willett, WC Fuchs, CS AF Skinner, HG Michaud, DS Colditz, GA Giovannucci, EL Stampfer, MJ Willett, WC Fuchs, CS TI Parity, reproductive factors, and the risk of pancreatic cancer in women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GROWTH-FACTOR-I; FACTOR-BINDING PROTEIN-3; HUMAN-PREGNANCY SERUM; NATIONAL DEATH INDEX; REPLACEMENT THERAPY; CIRCULATING LEVELS; DIABETES-MELLITUS; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; BREAST-CANCER AB Incidence rates for pancreatic cancer are consistently lower in women than in men. Previous studies suggest that reproductive factors, particularly parity, may reduce pancreatic cancer risk in women. We examined parity, breast feeding history, age at first birth, menstrual factors, and exogenous hormone use in relation to pancreatic cancer risk in a prospective cohort study of women. Information on parity and other reproductive factors was assessed by questionnaires in 1976 and updated biennially. Multivariate relative risks were adjusted for cigarette smoking, body mass index, diabetes, and height. During 22 years of. follow-up (1976 1998), 115,474 women contributed 2.4 million years of person time, and 243 cases of pancreatic cancer were identified. Compared with nulliparous women, the relative risk of pancreatic cancer was 0.86 [95% confidence interval (CI), 0.55-1.36] for women with 1-2 births, 0.75 (95% CI, 0.48-1.17) for 3-4 births, and 0.58 (95% CI, 0.34-0.98) for those with greater than or equal to5 births after adjusting for other factors. An analysis for linear trend indicates a 10% reduction in risk for each birth (P-trend = 0.008). Other reproductive factors and exogenous hormone use were not significantly related to pancreatic cancer risk. In this large prospective cohort of women, parity was associated significantly with a reduced risk of pancreatic cancer. Additional studies should examine the physiological or hormonal changes underlying pregnancy or childbirth that may explain this finding. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Skinner, HG (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. RI Skinner, Halcyon/A-1049-2009; Michaud, Dominique/I-5231-2014; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA55075, CA86102, CA87969, CA9001] NR 45 TC 49 Z9 50 U1 0 U2 0 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 MAY PY 2003 VL 12 IS 5 BP 433 EP 438 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 680CU UT WOS:000182959400007 PM 12750238 ER PT J AU Yip, S Aboody, KS Burns, M Imitola, J Boockvar, JA Allport, J Park, KI Teng, YD Lachyankar, M McIntosh, T O'Rourke, DM Khoury, S Weissleder, R Black, PM Weiss, W Snyder, EY AF Yip, S Aboody, KS Burns, M Imitola, J Boockvar, JA Allport, J Park, KI Teng, YD Lachyankar, M McIntosh, T O'Rourke, DM Khoury, S Weissleder, R Black, PM Weiss, W Snyder, EY TI Neural stem cell biology may be well suited for improving brain tumor therapies SO CANCER JOURNAL LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; APOPTOSIS-INDUCING LIGAND; GROWTH-FACTOR RECEPTOR; PROGENITOR CELLS; IN-VITRO; GENE-THERAPY; EXTRACELLULAR-MATRIX; MICROARRAY ANALYSIS/; GLIOBLASTOMA CELLS; CHEMOKINE SDF-1 AB Neural stem cells (NSCs) are capable of tremendous migratory potential to areas of pathology in the central nervous system. When implanted into a diseased or injured nervous system, NSCs can travel through great distances to and engraft within areas of discrete as well as diffuse abnormalities. Engraftment is often followed by integration into the local neural milieu, accompanied by stable gene expression from the NSCs. In addition, the pluripotency of NSCs endows them with the capability to replace diseased tissues in an appropriate manner. Recent evidence has also suggested that engrafted exogenous NSCs may have effects on the surrounding microenvironment, such as promoting protection and/or regeneration of host neural pathways. These characteristics of NSCs would seem to make them ideal agents for the treatment of various central nervous system pathologies, especially brain tumors. Brain tumors are generally difficult to treat because of the unique location of the lesions. In primary gliomas, the extensive infiltrative nature of the tumor cells presents a challenge for their effective and total eradication, hence the high rate of treatment failure and disease recurrence. In addition, normal brain structures are distorted and are often destroyed by the growing neoplasm. Even with effective therapy to surgically resect and destroy the neoplastic tissues, the brain is still injured, which often leaves the patient in a debilitated state. The unique ability of NSCs to "home in" on tumor cells followed by the delivery of a desired gene product makes the NSC a very promising agent in brain tumor therapy. Cytolytic viruses and genes coding for anti-tumor cytokines, pro-drug converting enzymes, and various neurotrophic factors have all been engineered into engraftable NSCs for delivery to tumors. When they are specially tagged, such injected NSCs can be visualized with the use of novel imaging techniques and tracked in vivo within living animals over real time. If the NSCs were also capable of participating in the subsequent repair and regeneration of the tumor-afflicted brain-at present a potential but as-yet-unproven aspect of this intervention then its role in abetting anti-tumor therapy would be complete. It is important to emphasize, however, that the use of NSCs is adjunctive and is not a replacement for other therapies that should be used in parallel. C1 Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Sch Med,Dept Neurol, Boston, MA USA. Univ British Columbia, Div Neurosurg, Dept Surg, Vancouver Gen Hosp, Vancouver, BC V5Z 1M9, Canada. Layton Biosci, Sunnyvale, CA USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Penn, Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. Yonsei Univ, Coll Med, Dept Pediat, Seoul, South Korea. Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. Burnham Inst, Program Dev & Regenerat Cell Biol, La Jolla, CA 92037 USA. RP Snyder, EY (reprint author), Burnham Inst, Program Dev & Regenerat, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. OI khoury, samia/0000-0003-3198-6063 NR 101 TC 47 Z9 59 U1 0 U2 6 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAY-JUN PY 2003 VL 9 IS 3 BP 189 EP 204 PG 16 WC Oncology SC Oncology GA 711PP UT WOS:000184750500006 PM 12952304 ER PT J AU Krop, I Maguire, P Lahti-Domenici, J Lodeiro, G Richardson, A Johannsdottir, HK Nevanlinna, H Borg, A Gelman, R Barkardottir, RB Lindblom, A Polyak, K AF Krop, I Maguire, P Lahti-Domenici, J Lodeiro, G Richardson, A Johannsdottir, HK Nevanlinna, H Borg, A Gelman, R Barkardottir, RB Lindblom, A Polyak, K TI Lack of HIN-1 methylation in BRCAl-linked and "BRCA1-like" breast tumors SO CANCER RESEARCH LA English DT Article ID SPORADIC BREAST; OVARIAN-CANCER; X-CHROMOSOME; GENE; DNA; HYPERMETHYLATION; TUMORIGENESIS; INACTIVATION; EXPRESSION; MUTATIONS AB We recently identified a candidate tumor suppressor gene, HIN-1, that is silenced due to methylation in the majority of sporadic breast carcinomas and is localized to 5q33-qter, an area frequently lost in BRCA1 tumors and thought to harbor a BRCA1 modifier gene. To establish whether germ-line mutations in HIN-1 may influence breast cancer risk, we sequenced the HIN-1 coding region in 10 familial breast cancer patients with positive logarithm of the odds scores of at least one of the markers flanking HIN-1. We also sequenced the HIN-1 coding region in 15 BRCA1 and 35 sporadic breast tumors to determine whether HIN-1 is the target of the frequent 5q loss in BRCA1 tumors. No sequence alterations were found in any of the cases analyzed. However, analysis of HIN-1 promoter methylation status revealed that in striking contrast to sporadic cases, there is a nearly complete lack of HIN-1 methylation in BRCA1 tumors (P < 0.0001). Sporadic breast tumors with a "BRCA1-like" histopathological phenotype also demonstrated significantly lower frequency of HIN-1 promoter methylation (P = 0.01) compared with other cancer types, and there was also a difference among tumors based on their estrogen receptor and HER2 status (P = 0.006), suggesting that HIN-1 methylation patterns are associated with specific breast cancer subtypes. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Karolinska Hosp, S-10401 Stockholm, Sweden. Univ Hosp Iceland, Dept Pathol, Cell Biol Lab, Reykjavik, Iceland. Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D740C, Boston, MA 02115 USA. FU NCI NIH HHS [CA89393, CA94787-01, R01 CA94074-01A1] NR 22 TC 24 Z9 24 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2003 VL 63 IS 9 BP 2024 EP 2027 PG 4 WC Oncology SC Oncology GA 674MK UT WOS:000182640400006 PM 12727813 ER PT J AU Lamendola, DE Duan, ZF Yusuf, RZ Seiden, MV AF Lamendola, DE Duan, ZF Yusuf, RZ Seiden, MV TI Molecular description of evolving paclitaxel resistance in the SKOV-3 human ovarian carcinoma cell line SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; SELF-ORGANIZING MAPS; GENE-EXPRESSION DATA; OLIGONUCLEOTIDE ARRAYS; MULTIDRUG-RESISTANCE; INTERLEUKIN-1 RECEPTOR; MICROARRAY ANALYSIS; INDUCED APOPTOSIS; DRUG-RESISTANCE; BREAST-CANCER AB Ovarian cancer is currently the most lethal gynecological malignancy in the United States. Although effective therapies exist, the acquisition of multidrug resistance within persisting tumor cells renders curative therapies elusive for the majority of women with ovarian cancer. In an attempt to better define the evolution of paclitaxel resistance, three SKOV-3 sublines were selected during successive rounds of exposure to increasing paclitaxel concentrations. The sublines were selected to represent early (0.003 muM), intermediate (0.03 muM), and late (0.3 muM) paclitaxel resistance. RNA from these cell lines, SKOV-3(0.003TR), SKOV-3(0.03TR), and SKOV30.3TR, as well as the parent cell line SKOV-3, was analyzed by cDNA array to evaluate transcript expression profiles. Arrays were performed using Affymetrix HG-U95Av2 arrays, which contain probes for similar to9600 known human genes. Signal intensities were calculated by Microarray Suite 5.0 (Affymetrix, Santa Clara, CA). Expression patterns were analyzed by Affymetrix Data Mining Tool 3.0 with filtering of expression patterns for fold change in expression (maximum divided by minimum expression value/gene) and for variation of expression (maximum minus minimum expression value/gene). This analysis dismissed similar to11,000 of similar to12,000 expression patterns. The remaining similar to1000 expression patterns were normalized and segregated into 20 partitions of a self-organizing map (SOM). The resulting SOM discriminates between genes, which are differentially expressed in early versus intermediate versus late paclitaxel resistance. For example, multidrug resistance I transcript expression is not elevated in SKOV-3(0.003TR) as compared with parental SKOV-3 but demonstrates elevated expression in SKOV-3(0.03TR) and SKOV-3(0.3TR). In contrast, SOM analysis demonstrates early (SKOV-3(0.003TR)) transcriptional changes in a wide variety of genes, including gene families involved in cell growth/maintenance, cell structure, signal transduction, and inflammatory response. The use of array analysis with SOMs in sublines with progressive paclitaxel resistance can successfully define an evolution of resistance. Such an analysis may be useful at defining candidate gene families involved in the early-drug resistance phenotype. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Dept Hematol Oncol, Boston, MA 02114 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Dept Hematol Oncol, Cox 640, Boston, MA 02114 USA. FU NCI NIH HHS [CA 89150] NR 62 TC 57 Z9 60 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2003 VL 63 IS 9 BP 2200 EP 2205 PG 6 WC Oncology SC Oncology GA 674MK UT WOS:000182640400033 PM 12727840 ER PT J AU Abe, T Terada, K Wakimoto, H Inoue, R Tyminski, E Bookstein, R Basilion, JP Chiocca, EA AF Abe, T Terada, K Wakimoto, H Inoue, R Tyminski, E Bookstein, R Basilion, JP Chiocca, EA TI PTEN decreases in vivo vascularization of experimental gliomas in spite of proangiogenic stimuli SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; HUMAN GLIOBLASTOMA CELLS; TUMOR-SUPPRESSOR; FACTOR RECEPTOR; FACTOR EXPRESSION; P53 EXPRESSION; INHIBITS ANGIOGENESIS; SURVIVAL PATHWAY; FACTOR SECRETION; PROSTATE-CANCER AB Approximately 30-40% of malignant glial tumors exhibit mutations in the tumor suppressor gene, PTEN/MMAC. Additionally, these tumors are associated with (a) mutations in epidermal growth factor receptor (EGFR), leading to a pro-oncogenic constitutive activation, as well as amplification of its gene, and/or (b) mutations in p53, disrupting normal cellular homeostatic processes. Whereas PTEN/MMAC has been shown to possess antiangiogenic action, constitutively active EGFR or p53 gene defects have been associated with proangiogenic action. In this article, we asked if PTEN/MMAC gene transfer into human glioma cells that possess inactivating mutations of the PTEN/MMAC gene but also express either constitutively active EGFR (U87DeltaEGFR cells) or possess an inactivating mutation of p53 (U251 cells) still display inhibited angiogenesis in orthotopic and ectopic models of gliomas. Human glioma xenografts treated with PTEN/MMAC gene transfer exhibited significantly decreased vascularity both in an orthotopic and in an ectopic model. Taken in combination, these results provide strong evidence of PTEN/MMAC's role in regulating glioma angiogenesis even in the presence of strong proangiogenic signals provided by constitutive EGFR activation or p53 inactivation. C1 Harvard Univ, Massachusetts Gen Hosp, Mol Neurooncol Labs, Neurosurg Serv,Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Natl Fdn Canc Res,Ctr Mol Anal & Imaging, Charlestown, MA 02129 USA. Canji Inc, San Diego, CA 92121 USA. RP Chiocca, EA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Mol Neurooncol Labs, Neurosurg Serv,Sch Med, CNY6,E Bldg, Charlestown, MA 02129 USA. FU PHS HHS [P01] NR 56 TC 40 Z9 49 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2003 VL 63 IS 9 BP 2300 EP 2305 PG 6 WC Oncology SC Oncology GA 674MK UT WOS:000182640400046 PM 12727853 ER PT J AU Cusack, JC AF Cusack, JC TI Rationale for the treatment of solid tumors with the proteasome inhibitor bortezomib SO CANCER TREATMENT REVIEWS LA English DT Article; Proceedings Paper CT Symposium on Proteasome Inhibition - A New Pathway in Cancer Therapy CY DEC 06, 2002 CL PHIALDELPHIA, PENNSYLVANIA DE bortezomib; resistance; NF-kappa B; multidrug resistance; combination chemotherapy; solid tumors; proteasome ID NF-KAPPA-B; MULTIPLE-MYELOMA CELLS; HUMAN PANCREATIC-CARCINOMA; CANCER-CELLS; TRANSCRIPTION FACTOR; INDUCED APOPTOSIS; DRUG-RESISTANCE; BREAST-CANCER; LUNG-CANCER; CONSTITUTIVE ACTIVATION AB Given its role in cellular metabolism, the proteasome could prove to be a critical target that can be exploited in treating cancer. In preclinical studies, several mechanisms for bortezomib's activity in multiple myeloma cells have been identified (e.g., NF-kappaB inhibition); antitumor activity with bortezomib has been seen in myeloma patients, thereby supporting the validity of the preclinical work. Similar mechanisms may be in play in solid tumors, and cell culture and xenogr-aft data suggest bortezomib may be active in a wide range of tumor types. One promising possibility is the use of bortezomib for the treatment of chemoresistant tumors. Chemoresistance can be caused by a number of cellular factors; NF-kappaB is a prominent instigator of chemoresistance, and proteasome inhibition was an effective means of preventing NF-kappaB activation in myeloma and several solid tumor laboratory studies. However, the inhibition of NF-kappaB may not be the only mechanism for antitumor activity. This review explores the use of proteasome inhibitors to subvert intrinsic resistance mechanisms, disrupt inducible chemoresistance, or augment the mechanisms of action of standard chemotherapeutics. Thus, in addition to providing another target for anticancer treatment, proteasome inhibition may also provide a means to treat refractory tumors. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Cusack, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 82 TC 99 Z9 104 U1 0 U2 1 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 MAY PY 2003 VL 29 SU 1 BP 21 EP 31 DI 10.1016/S0305-7372(03)00079-3 PG 11 WC Oncology SC Oncology GA 688RW UT WOS:000183450600004 PM 12738240 ER PT J AU Richardson, P AF Richardson, P TI Clinical update: proteasome inhibitors in hematologic malignancies SO CANCER TREATMENT REVIEWS LA English DT Article; Proceedings Paper CT Symposium on Proteasome Inhibition - A New Pathway in Cancer Therapy CY DEC 06, 2002 CL PHIALDELPHIA, PENNSYLVANIA DE proteasome inhibition; bortezomib; multiple myeloma; hematologic malignancies ID FACTOR-KAPPA-B; PHASE-I TRIAL; MULTIPLE-MYELOMA; PANCREATIC-CANCER; DRUG-RESISTANCE; 26S PROTEASOME; PS-341; APOPTOSIS; GROWTH; CELLS AB The proteasome inhibitor bortezomib (VELCADE; formerly PS-341, LDP-341, MLN341) is a novel dipeptide boronic acid. In cell culture and xenograft models, bortezomib showed potent activity, enhanced the sensitivity of cancer cells to traditional chemotherapeutics, and appeared to overcome drug resistance. In vitro, bortzomib downregulated the NF-kappaB pathway. NF-kappaB is a transcription factor that enhances the production of growth factors (e.g, IL-6), cell-adhesion molecules, and anti-apoptotic factors, all of which contribute to the growth of the tumor cell and/or protection from apoptosis. Phase 11 trials have been conducted in patients with relapsed and refractory multiple myeloma (SUMMIT trial, 202 patients) or relapsed myeloma (CREST trial, n = 54) using a 1.3 mg/m(2) dose given twice weekly for 2 weeks (days 1, 4, 8, 1 1; rest days 12-21). Both trials showed responses (including complete responses) with manageable toxicities, forming the basis for an ongoing phase III trial comparing response to bortezomilb versus high-dose dexamethasone. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol,Jerome Lipper Multiple Myeloma, Boston, MA 02115 USA. RP Richardson, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol,Jerome Lipper Multiple Myeloma, Boston, MA 02115 USA. NR 25 TC 63 Z9 67 U1 0 U2 2 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 MAY PY 2003 VL 29 SU 1 BP 33 EP 39 DI 10.1016/S0305-7372(03)00080-X PG 7 WC Oncology SC Oncology GA 688RW UT WOS:000183450600005 PM 12738241 ER PT J AU Mutai, H Heller, S AF Mutai, H Heller, S TI Vertebrate and invertebrate TRPV-like mechanoreceptors SO CELL CALCIUM LA English DT Article DE mechanoreceptor; transduction; osmotic pressure; inner ear ID ACTIVATED CALCIUM-CHANNEL; SENSITIVE CATION CHANNEL; EPITHELIAL CA2+ CHANNEL; HEAT-EVOKED ACTIVATION; RECEPTOR-LIKE PROTEIN; CAENORHABDITIS-ELEGANS; HAIR-CELLS; MECHANOSENSORY TRANSDUCTION; ION-CHANNEL; MECHANOELECTRICAL-TRANSDUCTION AB Our senses of touch, hearing, and balance are mediated by mechanosensitive ion channels. In vertebrates, little is known about the molecular composition of these mechanoreceptors, an example of which is the transduction channel of the inner ear's receptor cells, hair cells. Members of the TRP family of ion channels are considered candidates for the vertebrate hair cell's mechanosensitive transduction channel and here we review the evidence for this candidacy. We start by examining the results of genetic screens in invertebrates that identified members of the TRP gene family as core components of mechanoreceptors. In particular, we discuss the Caenorhabditis elegans OSM-9 channel, an invertebrate TRPV channel, and the Drosophila melanogaster TRP channel NOMPC. We then evaluate basic features of TRPV4, a vertebrate member of the TRPV subfamily, which is gated by a variety of physical and chemical stimuli including temperature, osmotic pressure, and ligands. Finally, we compare the characteristics of all discussed mechanoreceptive TRP channels with the biophysical characteristics of hair cell mechanotransduction, speculating about the possible make-up of the elusive inner ear mechanoreceptor. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Neurosci Program, Div Hlth Sci & Technol,MIT, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Heller, S (reprint author), Harvard Univ, MIT, Dept Otolaryngol, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC 04563] NR 71 TC 63 Z9 70 U1 0 U2 7 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD MAY-JUN PY 2003 VL 33 IS 5-6 BP 471 EP 478 DI 10.1016/S0143-4160(03)00062-9 PG 8 WC Cell Biology SC Cell Biology GA 692RH UT WOS:000183673700018 PM 12765692 ER PT J AU Tilly, JL Kolesnick, RN AF Tilly, JL Kolesnick, RN TI Realizing the promise of apoptosis-based therapies: separating the living from the clinically undead SO CELL DEATH AND DIFFERENTIATION LA English DT Editorial Material ID INDUCED OVARIAN FAILURE; PROGRAMMED CELL-DEATH; MICE DEFICIENT; INHIBITION; SPHINGOSINE-1-PHOSPHATE; CYCLOPHOSPHAMIDE; CHEMOTHERAPY; INJURY; ENZYME; NEUROPROTECTION C1 Massachusetts Gen Hosp, Harvard Med Sch, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Lab Signal Transduct, New York, NY 10021 USA. RP Tilly, JL (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 38 TC 10 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD MAY PY 2003 VL 10 IS 5 BP 493 EP 495 DI 10.1038/sj.cdd.4401217 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 681DY UT WOS:000183022700003 PM 12728247 ER PT J AU Silverman, RA Boudreaux, ED Woodruff, PG Clark, S Camargo, CA AF Silverman, RA Boudreaux, ED Woodruff, PG Clark, S Camargo, CA CA Multicenter Airway Res Collaborati TI Cigarette smoking among asthmatic adults presenting to 64 emergency departments SO CHEST LA English DT Article DE acute disease; asthma; emergency medicine; smoking ID LUNG-FUNCTION; ALLERGIC RHINITIS; PASSIVE SMOKING; BRONCHIAL HYPERRESPONSIVENESS; PULMONARY-FUNCTION; MATERNAL SMOKING; CHILDREN; SYMPTOMS; PREVALENCE; EXPOSURE AB Study objectives: The emergency department (ED) is an important focal point for asthmatic individuals with uncontrolled illness. Anecdotally, many adults presenting to the ED with acute asthma are active cigarette smokers. The present study determined the prevalence of cigarette smoking among adults presenting to the ED with acute asthma and identified the factors associated with current smoking status. Design: A prospective cohort study conducted as part of the Multicenter Airway Research Collaboration. Patients: A structured interview was performed in 1,847 patients, ages 18 to 54 years, who presented to the ED with acute asthma. Setting: Sixty-four EDs in 21 US states and 4 Canadian provinces. Results: Thirty-five percent of the enrolled asthmatic patients were current smokers with a median of 10 pack-years (interduartile range, 4 to 20 pack-years), while 23% were former smokers, and 42% were never-smokers. Current smokers comprised 33% of asthmatic patients aged 18 to 29 years, 40% for ages 30 to 39 years, and 33% for ages 40 to 54 (p < 0.001). In a multivariate analysis, the factors independently associated with current smoking status (p < 0.05) were as follows: age 30 to 39 years; white race/ethnicity; non-high school graduate; lower household income; lack of private insurance; no recent inhaled steroid usage; and no history of systemic steroid usage. Although 50% of current smokers admitted that smoking worsens their asthma symptoms, only 4% stated that smoking was responsible for their current exacerbation. Conclusions: Although cigarette smoke is generally recognized as a respiratory irritant, cigarette smoking is common among adults presenting to the ED with acute asthma. The ED visit may provide an opportunity for patients to be targeted for smoking cessation efforts. C1 Long Isl Jewish Med Ctr, Dept Emergency Med, New Hyde Pk, NY 11040 USA. Earl K Long Med Ctr, Dept Emergency Med, Baton Rouge, LA USA. Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. RP Silverman, RA (reprint author), Long Isl Jewish Med Ctr, Dept Emergency Med, 270-05 76th Ave, New Hyde Pk, NY 11040 USA. OI Boudreaux, Edwin/0000-0002-3223-6371 FU NHLBI NIH HHS [HL-03533, HL-63253] NR 59 TC 101 Z9 109 U1 1 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2003 VL 123 IS 5 BP 1472 EP 1479 DI 10.1378/chest.123.5.1472 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 676VJ UT WOS:000182773000027 PM 12740263 ER PT J AU Koelling, TM Dec, GW Ginns, LC Semigran, MJ AF Koelling, TM Dec, GW Ginns, LC Semigran, MJ TI Left ventricular diastolic function in patients with advanced cystic fibrosis SO CHEST LA English DT Article DE cystic fibrosis; diastolic dysfunction; radionuclide ventriculography ID PEAK FILLING RATE; DOPPLER ECHOCARDIOGRAPHY; MYOCARDIAL FIBROSIS; EJECTION FRACTION; HEART-FAILURE; RADIONUCLIDE ANGIOGRAPHY; CARDIAC-FUNCTION; EXERCISE; CARDIOMYOPATHY; ALDOSTERONE AB Objectives: To assess left ventricular systolic and diastolic function in adult patients with cystic fibrosis using radionuclide ventriculography. Background: Although myocardial fibrosis has been described in autopsy specimens of patients with cystic fibrosis, the possibility that myocardial dysfunction may occur during life in adult patients with cystic fibrosis has not been explored. Methods: To assess the possibility of cardiac dysfunction occurring in cystic fibrosis, we studied 40 patients with advanced cystic fibrosis with first-pass radionuclide ventriculography and compared them to 9 patients with advanced bronchiectasis and 18 normal control subjects. Results: Indexes of right ventricular systolic function were similarly impaired in patients with cystic fibrosis and patients with bronchiectasis. Left ventricular ejection fraction of patients with cystic fibrosis, patients with bronchiectasis, and normal control subjects did not differ. Fractional left ventricular filling at 50% of diastole, an index of diastolic function, was significantly lower in patients with cystic fibrosis (54+/-13%, mean +/-SD) in comparison to patients with bronchiectasis (66+/-4%, p = 0.009) or normal control subjects (69+/-14, p = 0.0002). The contribution of atrial systole to total diastolic left ventricular filling was greater in patients with cystic fibrosis (38+/-18%) than in patients with bronchiectasis (21+/-4%, p = 0.01) or normal control subjects (25+/-12%, p = 0.01). Conclusions: Patients with advanced cystic fibrosis demonstrate impaired left ventricular distensibility when compared to normal control subjects and patients with bronchiectasis. Patients with cystic fibrosis may be at risk of heart failure due to right ventricular dysfunction or left ventricular diastolic dysfunction. C1 Harvard Univ, Heart Failure & Cardiac Transplantat Ctr, Sch Med, Massachusetts Gen Hosp,Cardiol Div, Boston, MA 02114 USA. Harvard Univ, Pulm Unit, Sch Med, Massachusetts Gen Hosp,Dept Med, Boston, MA 02114 USA. RP Semigran, MJ (reprint author), Harvard Univ, Heart Failure & Cardiac Transplantat Ctr, Sch Med, Massachusetts Gen Hosp,Cardiol Div, Bigelow 645,55 Fruit St, Boston, MA 02114 USA. NR 31 TC 20 Z9 21 U1 0 U2 8 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2003 VL 123 IS 5 BP 1488 EP 1494 DI 10.1378/chest.123.5.1488 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 676VJ UT WOS:000182773000029 PM 12740265 ER PT J AU Khayat, RN Xie, AL Patel, AK Kaminski, A Skatrud, JB AF Khayat, RN Xie, AL Patel, AK Kaminski, A Skatrud, JB TI Cardiorespiratory effects of added dead space in patients with heart failure and central sleep apnea SO CHEST LA English DT Article DE dead space; heat failure; sleep apnea ID CHEYNE-STOKES RESPIRATION; BLOOD-PRESSURE; CARBON-DIOXIDE; HYPOXIA; CO2; HYPERVENTILATION; PATHOGENESIS; VENTILATION; OXYGEN; DOG AB Background: Inhaled CO2 has been shown to stabilize the breathing pattern of patients with central sleep apnea (CSA) with and without congestive heart failure (CHF). Added dead space (DS) as a form of supplemental CO2 was effective in eliminating idiopathic CSA. The efficacy and safety of DS has not yet been evaluated in patients with CHF and CSA. Methods: We examined the respiratory and cardiovascular effects of added DS in eight patients with CHF and CSA. The DS consisted of a facemask attached to a cylinder of adjustable volume. During wakefulness, the cardiorespiratory response to 200 to 600 mL of DS was tested. Cardiac output and stroke volume were measured using echocardiography with and without DS. During the nocturnal study, patients slept with and without DS, alternating at approximately 1-h intervals. Results: Values are expressed as the mean SE. The wakefulness study revealed a plateau in the partial pressure of end-tidal CO2 (PETCO2) and the partial pressure of end-tidal O-2 between DS amounts of 400 and 600 mL. The mean stroke volume index (33 +/- 7 vs 34 +/- 7 mL/m(2), respectively) and the mean cardiac index (1.9 +/- 0.3 vs 1.9 +/- 0.4 L/min/m(2), respectively) were not affected by DS. Neither heart rate nor BP showed a significant change in response to DS of 600 mL. During sleep, DS increased the PETCO2 (40.7 +/- 2.7 vs 38.9 +/- 2.6 mm Hg, respectively; p < 0.05), reduced apnea (1 1 vs 29 7 episodes per hour, respectively; p < 0.01) and arousal (21 +/- 8 vs 30 +/- 8 arousals per hour, respectively; p < 0.05), increased the mean arterial oxygen saturation (Sao(2)) (94.4 +/- 1.0% vs 93.5 +/- 1.1%, respectively; p < 0.01), and reduced Sao(2) oscillations (DeltaSao(2) from maximum to minimum, 1.8 +/- 0.4% vs 5.5 +/- 0.9%, respectively; p < 0.01). Conclusion: DS stabilized CSA and improved sleep quality in patients with CHIP without significant acute adverse effects on the cardiovascular function. C1 William S Middleton Mem Vet Adm Med Ctr, Pulm Physiol Lab, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. RP Xie, AL (reprint author), William S Middleton Mem Vet Adm Med Ctr, Pulm Physiol Lab, 2500 Overlook Terrace, Madison, WI 53705 USA. RI Khayat, Rami/E-3380-2011 NR 38 TC 43 Z9 45 U1 1 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2003 VL 123 IS 5 BP 1551 EP 1560 DI 10.1378/chest.123.5.1551 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 676VJ UT WOS:000182773000037 PM 12740273 ER PT J AU Anzueto, A Niederman, MS AF Anzueto, A Niederman, MS TI Diagnosis and treatment of rhinovirus respiratory infections SO CHEST LA English DT Review DE antiviral agents; asthma; COPD; otitis media; pleconaril; rhinoviruses; sinusitis; viral respiratory infection ID TRACT INFECTIONS; PICORNAVIRUS INFECTIONS; VIRAL-INFECTIONS; COMMON COLDS; COMMUNITY; ADULTS; CARE; EXACERBATIONS; COMPLICATIONS; PHYSICIANS AB Acute upper viral respiratory infection (VRI) is the number one cause of illness for which patients seek medical care in the United States. Rhinoviruses, members of the family Picornaviridae, are the causative pathogens in more than half of VRIs, and they are associated with acute exacerbations of respiratory disease, including asthma, sinusitis, otitis media, and COPD. Owing to the lack of commercial availability of rapid and cost-effective laboratory tests to confirm the presence of VRI, the diagnosis is most commonly made empirically, based on patient history and physical examination. Currently, no antiviral agents that are active against picornaviruses are available for clinical use. Antimicrobial agents, frequently prescribed for VRIs, are not active against viruses, and their inappropriate and widespread use has contributed to an increase in antimicrobial resistance among bacteria commonly involved in respiratory tract infections. Several newer antiviral agents are being evaluated for treatment of VRIs. Although a variety of mechanisms and agents have been tested, few have shown significant clinical benefit in human trials. The most advanced antiviral agent in clinical trials is pleconaril, a novel viral capsid-binding inhibitor with potent and highly specific in vitro activity against the majority of serotypes of rhinoviruses and enteroviruses. Clinical trials of pleconaril for the treatment of VRIs have been conducted, and the role of pleconaril in patients with chronic lung disease is being evaluated. C1 Audie L Murphy Mem Vet Adm Med Ctr, Pulm Div Sect 111E, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. SUNY Stony Brook, Winthrop Univ Hosp, Dept Med, Mineola, NY 11501 USA. RP Anzueto, A (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, Pulm Div Sect 111E, S Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 40 TC 28 Z9 31 U1 0 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 MAY PY 2003 VL 123 IS 5 BP 1664 EP 1672 DI 10.1378/chest.123.5.1664 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 676VJ UT WOS:000182773000052 PM 12740288 ER PT J AU Feng, JA Perry, G Mori, T Hayashi, T Oparil, S Chen, YF AF Feng, JA Perry, G Mori, T Hayashi, T Oparil, S Chen, YF TI Pressure-independent enhancement of cardiac hypertrophy in atrial natriuretic peptide-deficient mice SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY LA English DT Article DE atrial natriuretic peptide; cardiac function; cardiac hypertrophy; echocardiography; salt depletion; transgenic mice ID RECEPTOR GENE-EXPRESSION; HYPERTENSION; MYOCYTES; ANP; HYPOXIA; FIBROBLASTS; INHIBIT; STRESS; CELLS; RATS AB 1. Homozygous deletion of the pro-atrial natriuretic peptide (Nppa) gene (ANP-/-) has been associated with both cardiac hypertrophy and salt-sensitive hypertension in mice, suggesting that cardiac hypertrophy in ANP-/- mice may be related, at least in part, to increased afterload. 2. To test the hypothesis that cardiac hypertrophy in ANP-/-mice is independent of blood pressure, male ANP-/- and wild-type ANP+/+ mice were fed a low (0.05%) or basal (0.55%) NaCl diet. Five weeks later, mean arterial pressure (MAP) was measured in conscious mice; the whole heart, atria, left and right ventricles (LV and RV, respectively), brain, lung, kidney, liver and spleen were weighed and fixed for histological analysis. Separate groups of mice were subjected to echocardiographic examination under tribromoethanol anaesthesia. 3. Mean arterial pressure and atrial, LV and RV mass were greater in ANP-/- mice than in ANP+/+ mice fed the basal salt diet. Salt depletion equalized MAP in the two genotypes, but did not alter the relative cardiac hypertrophy in ANP-/- mice. The ANP-/- mice had significant LV cardiomyocyte hypertrophy when fed either basal or low-salt diets. 4. Left ventricle chamber dimensions did not differ between genotypes, but were significantly reduced in mice fed the low-salt diet; LV posterior wall and septal thickness were greater in ANP-/- than ANP+/+ mice and were not altered by diet, indicating a concentric pattern of LV hypertrophy in ANP-/- mice. Left ventricle function (cardiac output, stroke volume, ejection fraction, circumferential wall stress and velocity of circumferential wall shortening) did not differ between strains on either diet; circumferential wall stress was reduced in the low-salt groups; other functional parameters were not altered by diet. 5. These findings indicate that ANP deletion results in cardiomyocyte hypertrophy and biventricular hypertrophy independent of blood pressure, supporting the concept that ANP has direct antihypertrophic effects in the heart. C1 Univ Alabama, UAB Stn, Dept Med, Div Cardiovasc Dis,Vasc Biol & Hypertens Program, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Cardiol Sect, Birmingham, AL USA. Osaka Med Coll, Dept Internal Med 3, Osaka, Japan. RP Chen, YF (reprint author), Univ Alabama, UAB Stn, Dept Med, Div Cardiovasc Dis,Vasc Biol & Hypertens Program, 1008 Zeigler Res Bldg, Birmingham, AL 35294 USA. FU NHLBI NIH HHS [HL-50147, HL-45990, HL-07457, HL-44195, HL-56046] NR 31 TC 33 Z9 35 U1 0 U2 0 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0305-1870 J9 CLIN EXP PHARMACOL P JI Clin. Exp. Pharmacol. Physiol. PD MAY-JUN PY 2003 VL 30 IS 5-6 BP 343 EP 349 DI 10.1046/j.1440-1681.2003.03836.x PG 7 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA 691AE UT WOS:000183582000006 PM 12859424 ER PT J AU Wirth, LJ Lucca, J Ostler, P Fidias, P Lynch, C Janne, PA Herbst, RS Johnson, BE Sugarbaker, DJ Mathisen, DJ Lukanich, JM Choi, NC Berman, SM Skarin, AT AF Wirth, LJ Lucca, J Ostler, P Fidias, P Lynch, C Janne, PA Herbst, RS Johnson, BE Sugarbaker, DJ Mathisen, DJ Lukanich, JM Choi, NC Berman, SM Skarin, AT TI Induction docetaxel and carboplatin followed by weekly docetaxel and carboplatin with concurrent radiotherapy, then surgery in stage III non-small cell lung cancer: A phase I study SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 12-15, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Clin Oncol ID THORACIC RADIATION-THERAPY; COMPARING PERIOPERATIVE CHEMOTHERAPY; SOUTHWEST-ONCOLOGY-GROUP; TWICE-DAILY RADIATION; RANDOMIZED TRIAL; FAILURE PATTERNS; CARCINOMA; SURVIVAL; PACLITAXEL; CISPLATIN AB Purpose: To determine the maximum-tolerated dose of docetaxel (DOC) in combination with carboplatin (CAR) and thoracic radiotherapy (RT), in the setting of trimodality treatment of patients with stage III non-small cell lung cancer (NSCLC). Experimental Design: Thirty-two patients with biopsy-proven stage IIIA (n = 20) or IIIB (n = 12) NSCLC were given two initial cycles of CAR (area under the curve = 6) and DOC (75 mg/m(2)), subsequent RT (54 Gy) with concurrent weekly CAR (area under the curve = 2), and DOC at six dose levels from 10 to 40 mg/m(2), then surgery if the patient's disease was resectable. Results: Three patients did not complete induction computed tomography (CT). Twenty-nine patients received concurrent CT/RT. Fifteen patients were eligible for surgery. Dose-limiting toxicities occurred in 2 patients, at dose levels two (atrial fibrillation) and three (transaminitis). The maximum-tolerated dose, as defined by the protocol, was not reached, although grade 3 and 4 toxicities were encountered at all dose levels. The most common more than or equal to grades 3 toxicities were neutropenia, nausea, vomiting, and fatigue. Four patients (13.3%) responded to induction CT. Ten patients (38.5%) responded to CT/RT. Eight surgical patients (57.1%) were downstaged, including 3 pathologic complete responses. Median relapse free and overall survivals are 8.5 and 12 months. One-year and estimated 2-year survival rates are 56.3 and 34.3%. Conclusion: This new regimen for stage III NSCLC of induction CAR/DOC, then weekly CAR/DOC with concurrent RT followed by surgery, can be safely administered and offers encouraging results. DOC at 30 mg/m(2) in combination with CAR and RT is recommended for Phase II study. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Skarin, AT (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 54 TC 10 Z9 11 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 2003 VL 9 IS 5 BP 1698 EP 1704 PG 7 WC Oncology SC Oncology GA 677MY UT WOS:000182813200016 PM 12738723 ER PT J AU Huang, MX Edgar, JC Thoma, RJ Hanlon, FM Moses, SN Lee, RR Paulson, KM Weisend, MP Irwin, JG Bustillo, JR Adler, LE Miller, GA Canive, JM AF Huang, MX Edgar, JC Thoma, RJ Hanlon, FM Moses, SN Lee, RR Paulson, KM Weisend, MP Irwin, JG Bustillo, JR Adler, LE Miller, GA Canive, JM TI Predicting EEG responses using MEG sources in superior temporal gyrus reveals source asynchrony in patients with schizophrenia SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE schizophrenia; auditory; P50; M50; superior temporal gyrus ID EVOKED MAGNETIC-FIELDS; HUMAN AUDITORY-CORTEX; MIDDLE LATENCY COMPONENTS; PLANUM TEMPORALE; SOURCE LOCALIZATION; NEUROPHYSIOLOGICAL EVIDENCE; TONOTOPIC ORGANIZATION; 40-HZ OSCILLATIONS; NEURONAL-ACTIVITY; VOLUME REDUCTION AB Objective: An integrated analysis using Electroencephalography (EEG) and magnetoencephalography (MEG) is introduced to study abnormalities in early cortical responses to auditory stimuli in schizophrenia. Methods: Auditory responses were recorded simultaneously using EEG and MEG from 20 patients with schizophrenia and 19 control subjects. Bilateral superior temporal gyrus (STG) sources and their time courses were obtained using MEG for the 30-100 ms post-stimulus interval. The MEG STG source time courses were used to predict the EEG signal at electrode Cz. Results: In control subjects, the STG sources predicted the EEG Cz recording very well (97% variance explained). In schizophrenia patients, the STG sources accounted for substantially (86%) and significantly (P < 0.0002) less variance. After MEG-derived STG activity was removed from the EEG Cz signal, the residual signal was dominated by 40 Hz activity, an indication that the remaining variance in EEG is probably contributed by other brain generators, rather than by random noise. Conclusions: Integrated MEG and EEG analysis can differentiate patients and controls, and suggests a basis for a well established abnormality in the cortical auditory response in schizophrenia, implicating a disorder of functional connectivity in the relationship between STG sources and other brain generators. (C) 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Science Ireland Ltd. All rights reserved. C1 Ctr Funct Brain Imaging, New Mexico VA Hlth Care Syst, Albuquerque, NM 87108 USA. Univ New Mexico, Dept Radiol, Hlth Sci Ctr, Albuquerque, NM 87131 USA. Univ Illinois, Dept Psychol, Champaign, IL 61820 USA. Univ Illinois, Beckman Inst, Champaign, IL 61820 USA. New Mexico VA Hlth Care Syst, Psychiat Serv, Albuquerque, NM 87108 USA. Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. Univ New Mexico, Hlth Sci Ctr, Dept Psychiat, Albuquerque, NM 87131 USA. Univ Colorado, Ctr Canc, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Illinois, Biomed Imaging Ctr, Urbana, IL 61801 USA. Univ Illinois, Dept Psychiat, Urbana, IL 61801 USA. RP Huang, MX (reprint author), Ctr Funct Brain Imaging, New Mexico VA Hlth Care Syst, Bldg 49 114M,1501 San Pedro Dr, Albuquerque, NM 87108 USA. RI bustillo, juan/J-7067-2013 FU NIMH NIH HHS [R01-MH65304] NR 96 TC 54 Z9 54 U1 3 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD MAY PY 2003 VL 114 IS 5 BP 835 EP 850 DI 10.1016/S1388-2457(03)00041-5 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 683JY UT WOS:000183146000006 PM 12738429 ER PT J AU Glynn, SM AF Glynn, SM TI Psychiatric rehabilitation in schizophrenia: advances and challenges SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Review DE schizophrenia; psychiatric rehabilitation; psychosocial interventions; family intervention; vocational rehabilitation; social skills training; cognitive behavioural therapy ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; FOLLOW-UP; FAMILY INTERVENTION; PSYCHOSOCIAL TREATMENT; SUPPORTED EMPLOYMENT; VOCATIONAL-REHABILITATION; EDUCATIONAL INTERVENTION; PERSISTENT SYMPTOMS; NEGATIVE SYMPTOMS AB Psychiatric rehabilitation for schizophrenia involves utilizing psychosocial interventions to assist persons with the illness to attain their highest level of independent functioning, strongest level of symptom control, and greatest level of subjective life satisfaction. The advent of newer, more well-tolerated antipsychotic medications may mean that more patients then ever are suitable for participation in concurrent psychiatric rehabilitation programs. In this article, the determinants of poor symptom control and social adjustment in schizophrenia are first discussed. Brief overviews of the procedures for the four most-well validated psychiatric rehabilitation strategies (family interventions, cognitive-behavior therapy, social skills training, and vocational rehabilitation) are then presented, with supporting data. Issues of relevance to recent-onset and older patients are then discussed. Finally, the role of individual psychotherapy in rehabilitation and opportunities for research and clinical integration of pharmacologic and psychosocial interventions are described. (C) 2003 Elsevier Science B.V. All rights reserved. C1 VA Greater Los Angeles, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. RP Glynn, SM (reprint author), VA Greater Los Angeles, Los Angeles, CA USA. NR 101 TC 9 Z9 10 U1 6 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD MAY PY 2003 VL 3 IS 1-2 BP 23 EP 33 DI 10.1016/S1566-2772(03)00016-1 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 722GR UT WOS:000185367500004 ER PT J AU Haroutunian, V Dracheva, S Davis, KL AF Haroutunian, V Dracheva, S Davis, KL TI Neurobiology of glutamatergic abnormalities in schizophrenia SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Review DE glutamate; receptors; schizophrenia; postmortem; dorsolateral prefrontal cortex; mRNA ID METHYL-D-ASPARTATE; DORSOLATERAL PREFRONTAL CORTEX; NMDA RECEPTOR SUBUNITS; MESSENGER-RNA EXPRESSION; IN-SITU HYBRIDIZATION; DOMAIN-CONTAINING PROTEIN; PURKINJE-CELL SYNAPSES; LONG-TERM POTENTIATION; AMINO-ACID TRANSPORTER; CENTRAL-NERVOUS-SYSTEM AB A variety of studies have implicated abnormalities of the glutamatergic systems in schizophrenia. Some of this evidence is based on the similarities of some of the symptoms of schizophrenia and the behavioral effects of dissociative anesthetics such as ketamine. More direct evidence has come from biological studies defining abnormalities at multiple levels of the glutamate neurotransmission cascade. These have included abnormalities in the receptor binding properties of the various classes of ionotropic glutamate receptors (AMPA, kainate, NMDA); mRNA expression levels of different subunits of each of the members of the ionotropic class of glutamate receptors; mRNA expression of glutamate receptor-specific binding and membrane anchoring proteins such as PSD-95; and alterations in the activity of the principal enzyme responsible for the synthesis of the glutamate from glutamine, phosphate activated glutaminase. Preliminary evidence from proton magnetic resonance spectroscopy studies also supports a role for increased levels of glutamate, or glutamine and glutamate, in schizophrenia. The evidence reviewed in this article, when viewed as a whole, suggests that the disruption or disregulation of glutamatergic systems contribute significantly to the pathophysiology and potentially to some of the symptoms of schizophrenia and defines a necessary role for continued investigation of this pivotal neurotransmitter system in schizophrenia. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Bronx Vet Adm Med Ctr, New York, NY 10029 USA. RP Haroutunian, V (reprint author), Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. NR 171 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD MAY PY 2003 VL 3 IS 1-2 BP 67 EP 76 DI 10.1016/S1566-2772(03)00020-3 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 722GR UT WOS:000185367500008 ER PT J AU Most, E Zayontz, S Li, GA Otterberg, E Sabbag, K Rubash, HE AF Most, E Zayontz, S Li, GA Otterberg, E Sabbag, K Rubash, HE TI Femoral rollback after cruciate-retaining and stabilizing total knee arthroplasty SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID IN-SITU FORCES; KINEMATICS; LIGAMENT; MOTION; PROSTHESIS; DESIGN AB Limited data comparing the kinematics of posterior cruciate ligament-retaining or substituting total knee arthroplasty with its own intact knee under identical loadings is available. In the current study, posterior femoral translation of the lateral and medial femoral condyles under unloaded conditions was examined for intact, cruciate-retaining, cruciate ligament-deficient cruciate-retaining and posterior-substituting knee arthroplasties. Cruciate-retaining and substituting total knee arthroplasties behaved similarly to the cruciate-deficient cruciate-retaining total knee arthroplasty between 0degrees and 30degrees flexion. Beyond 30degrees, the posterior cruciate-retaining arthroplasty showed a significant increase in posterior translation of both femoral condyles. The posterior cruciate-substituting arthroplasty only showed a significant increase in posterior femoral translation after 90degrees. At 120degrees, both arthroplasties restored approximately 80% of that of the native knee. Posterior translation of the lateral femoral condyle was greater than that observed in the medial condyle for all knees, indicating the presence of internal tibial rotation during knee flexion. The data showed that the posterior cruciate ligament is an important structure in posterior cruciate-retaining total knee arthroplasty and proper balancing is imperative to the success of the implant. The camspine engagement is valuable in restoring posterior femoral translation in posterior cruciate-substituting total knee arthroplasty. C1 Massachusetts Gen Hosp, Orthoped Biomech Lab, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, GA (reprint author), Harvard Univ, Sch Med, MGH, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. NR 34 TC 33 Z9 36 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 MAY PY 2003 IS 410 BP 101 EP 113 DI 10.1097/01.blo.0000062380.79828.2e PG 13 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 674HB UT WOS:000182630400012 PM 12771821 ER PT J AU Muratoglu, OK Perinchief, RS Bragdon, CR O'Connor, DO Konrad, R Harris, WH AF Muratoglu, OK Perinchief, RS Bragdon, CR O'Connor, DO Konrad, R Harris, WH TI Metrology to quantify wear and creep of polyethylene tibial knee inserts SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID MOLECULAR-WEIGHT POLYETHYLENE; REPLACEMENTS AB Assessment of damage on articular surfaces of ultrahigh molecular weight polyethylene tibial knee inserts primarily has been limited to qualitative methods, such as visual observation and classification of features such as pitting, delamination, and subsurface cracking. Semiquantitative methods also have been proposed to determine the linear penetration and volume of the scar that forms on articular surfaces of tibial knee inserts. The current authors report a new metrologic method that uses a coordinate measuring machine to quantify the dimensions of this scar. The articular surface of the insert is digitized with the coordinate measuring machine before and after regular intervals of testing on a knee simulator. The volume and linear penetration of the scar are calculated by mathematically taking the difference between the digitized surface maps of the worn and unworn articular surfaces. Three conventional polyethylene tibial knee inserts of a posterior cruciate-sparing design were subjected to five million cycles of normal gait on a displacement-driven knee wear simulator in bovine serum. A metrologic method was used to calculate creep and wear contributions to the scar formation on each tibial plateau. Weight loss of the inserts was determined gravimetrically with the appropriate correction for fluid absorption. The total average wear volume was 43 +/- 9 and 41 +/- 4 mm(3) measured by the metrologic and gravimetric methods, respectively. The wear rate averaged 8.3 +/- 0.9 and 8.5 +/- 1.6 mm(3) per million cycles measured by the metrologic and gravimetric methods, respectively. These comparisons reflected strong agreement between the metrologic and gravimetric methods. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Centerpulse Inc, Winterthur, Switzerland. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, GRJ 1206, Boston, MA 02114 USA. NR 19 TC 25 Z9 25 U1 2 U2 5 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 MAY PY 2003 IS 410 BP 155 EP 164 DI 10.1097/01.blo.0000063604.67412.04 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 674HB UT WOS:000182630400017 PM 12771826 ER PT J AU Silverman, SL AF Silverman, SL TI Calcitonin SO CLINICS IN GERIATRIC MEDICINE LA English DT Article ID INTRANASAL SALMON-CALCITONIN; POSTMENOPAUSAL BONE LOSS; OSTEOPOROTIC VERTEBRAL FRACTURES; ESTABLISHED OSTEOPOROSIS; RANDOMIZED TRIAL; DOUBLE-BLIND; NASAL SPRAY; MINERAL DENSITY; DOSE-RESPONSE; THERAPY AB Calcitonin is approved by the US Food and Drug Administration for the treatment of postmenopausal osteoporosis, but not for prevention. The preferred delivery system is nasal. Nasal calcitonin is safe and well tolerated. The vertebral fracture efficacy of calcitonin in older women is similar to the two approved bisphosphonates using a post hoc stratification analysis. Calcitonin has not been demonstrated to reduce hip fracture risk, although a post hoc pooled analysis suggests potential effectiveness of nasal calcitonin. Calcitonin produces small increments in bone mass of the spine and mostly reduces bone turnover in women with osteoporosis. Calcitonin may have analgesic benefits for women with acutely painful vertebral fractures. Treatment with calcitonin should be considered for older women with osteoporosis with painful vertebral fractures, and for older women with vertebral osteoporosis that is greater than hip osteoporosis. Calcitonin also should be considered for older women who are unable to take bisphosphonates due to gastrointestinal intolerance or impaired renal function. C1 OMC Clin Res Ctr, Beverly Hills, CA 90211 USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, Greater Los Angeles VA Med Ctr, Los Angeles, CA 90048 USA. RP Silverman, SL (reprint author), OMC Clin Res Ctr, 8641 Wilshire Blvd,Suite 301, Beverly Hills, CA 90211 USA. NR 56 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD MAY PY 2003 VL 19 IS 2 BP 381 EP + AR PII S0749-0690(02)00070-8 DI 10.1016/S0749-0690(02)00070-8 PG 15 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 672EM UT WOS:000182508300011 ER PT J AU Rayburn, NR Otto, MW AF Rayburn, NR Otto, MW TI Cognitive-behavioral therapy for panic disorder: A review of treatment elements, strategies, and outcomes SO CNS SPECTRUMS LA English DT Review ID 2-YEAR FOLLOW-UP; ALPRAZOLAM DISCONTINUATION; BENZODIAZEPINE TREATMENT; APPLIED RELAXATION; CASE SERIES; AGORAPHOBIA; IMIPRAMINE; EXPOSURE; ANXIETY; MAINTENANCE AB This article provides an overview of cognitive-behavioral therapy (CBT) for panic disorder. CBT is currently considered a first-line treatment for panic disorder. It offers benefit after short-term intervention, typically consisting of 12-15 sessions conducted in either an individual or a group format. The treatment focuses on the elimination of the patterns that underlie and perpetuate the disorder. Through CBT, patients learn about the nature of the disorder and acquire a set of strategies that counter the fears of panic attacks themselves, and break the recurring cycle of anticipatory anxiety, panic, and agoraphobic avoidance. The collaborative format of treatment, and a focus on elimination of core fears may be factors in enhancing longer-term outcome. In this article, we review the efficacy of CBT as a first-line treatment, a strategy for medication nonresponders, a replacement strategy for patients who wish to discontinue pharmacotherapy, and a potential preventive strategy for at-risk individuals. We also discuss some of the complex issues involved with combination-treatment strategies. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Psychol, Cognit Behav Therapy Program, Boston, MA 02114 USA. NR 69 TC 11 Z9 11 U1 7 U2 23 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTR JI CNS Spectr. PD MAY PY 2003 VL 8 IS 5 BP 356 EP 362 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 710MK UT WOS:000184683800003 PM 12766691 ER PT J AU Kaazempur-Mofrad, MR Bathe, M Karcher, H Younis, HF Seong, HC Shim, EB Chan, RC Hinton, DP Isasi, AG Upadhyaya, A Powers, MJ Griffith, LG Kamm, RD AF Kaazempur-Mofrad, MR Bathe, M Karcher, H Younis, HF Seong, HC Shim, EB Chan, RC Hinton, DP Isasi, AG Upadhyaya, A Powers, MJ Griffith, LG Kamm, RD TI Role of simulation in understanding biological systems SO COMPUTERS & STRUCTURES LA English DT Article DE finite element method; simulation; biomechanics; biological systems ID HUMAN CAROTID BIFURCATION; PULMONARY CAPILLARIES; SHEAR-STRESS; ATHEROSCLEROSIS; FLOWS; NEUTROPHIL; MECHANICS; STRAIN; CELLS AB Recent advances in computer performance and affordability have accelerated their application to understanding biological phenomena. Computational models are now an integral part of biological and biomedical research. This paper presents a range of examples that illustrate the important role that computational simulation plays in research in the biological and biomedical sciences. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. MIT, Div Biol Engn, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Kamm, RD (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Bathe, Mark/B-3531-2008 NR 24 TC 22 Z9 22 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-7949 J9 COMPUT STRUCT JI Comput. Struct. PD MAY PY 2003 VL 81 IS 8-11 BP 715 EP 726 DI 10.1016/S0045-7949(02)00481-9 PG 12 WC Computer Science, Interdisciplinary Applications; Engineering, Civil SC Computer Science; Engineering GA 672VZ UT WOS:000182544900022 ER PT J AU Blank, RD Baldini, TH Kaufman, M Bailey, S Gupta, R Yershov, Y Boskey, AL Coppersmith, SN Demant, P Paschalis, EP AF Blank, RD Baldini, TH Kaufman, M Bailey, S Gupta, R Yershov, Y Boskey, AL Coppersmith, SN Demant, P Paschalis, EP TI Spectroscopically determined collagen Pyr/deH-DHLNL cross-link ratio and crystallinity indices differ markedly in recombinant congenic mice with divergent calculated bone tissue strength SO CONNECTIVE TISSUE RESEARCH LA English DT Article DE bone quality; collagen; crystallinity; FTIR; mouse ID FEMORAL-NECK GEOMETRY; HIP FRACTURE; OSTEOPOROTIC FRACTURES; BIOMECHANICAL PROPERTIES; MECHANICAL-PROPERTIES; TRABECULAR BONE; INFRARED-SPECTROSCOPY; MINERALIZING TISSUES; GENETIC COMPOSITION; VERTEBRAL FRACTURE AB Whole bone strength can be partitioned into structural and material components. In three-point bending tests of 6-month-old female humeri from the HcB/Dem recombinant congenic series, strains HcB/8 and HcB/23 differed markedly in calculated failure stress but not ash percentage. Fourier transform infrared spectroscopic imaging was used to determine whether differences in the ratio of pyridinoline (pyr; nonreducible) to dehydrodihydroxynorleucine (de-DHLNL; reducible) collagen cross-links (XLR), mineral crystallinity, or spatial ordering could account for the strains' differing biomechanical performance. HcB/8 had significantly higher XLR and significantly higher crystallinity than HcB/23. XLR and crystallinity were highly and similarly correlated in both strains. There were no significant differences between the strains' one-dimensional spatial correlation functions, suggesting no difference in short-range order between them. The strong correlation between XLR and crystallinity reflects the interdependence of the protein and mineral elements of bone. The data illustrate the importance of material properties in addition to mineral quantity to bone tissue strength. C1 Univ Wisconsin, Sch Med, Dept Med, Endocrinol Sect, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. Hosp Special Surg, Div Res, New York, NY 10021 USA. Univ Wisconsin, Dept Phys, Madison, WI 53706 USA. Univ Virginia, Dept Phys, Charlottesville, VA 22901 USA. Netherlands Canc Inst, Dept Mol Genet, Amsterdam, Netherlands. RP Blank, RD (reprint author), Univ Wisconsin, Sch Med, Dept Med, Endocrinol Sect, H4-556 CSC 5148,600 Highland Ave, Madison, WI 53792 USA. OI Blank, Robert Daniel/0000-0003-2950-1944 FU NIAMS NIH HHS [AR043125, AR46124, AR46505] NR 60 TC 36 Z9 38 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PD MAY-SEP PY 2003 VL 44 IS 3-4 BP 134 EP 142 DI 10.1080/03008200390223918 PG 9 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA 722PW UT WOS:000185386100003 PM 14504033 ER PT J AU Tawakol, A Sims, K MacRae, C Friedman, JR Alpert, NM Fischman, AJ Gewirtz, H AF Tawakol, A Sims, K MacRae, C Friedman, JR Alpert, NM Fischman, AJ Gewirtz, H TI Myocardial flow regulation in people with mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes/myoclonic epilepsy and ragged red fibers and other mitochondrial syndromes SO CORONARY ARTERY DISEASE LA English DT Article DE myocardial blood flow; mitochondria; metabolic flow regulation ID ISCHEMIC-HEART-DISEASE; POSITRON-EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; N-13 AMMONIA; CARDIAC INVOLVEMENT; FRIEDREICH ATAXIA; OXIDATIVE STRESS; NITRIC-OXIDE; OXYGEN; METABOLISM AB Objective This study tests the hypothesis that elevated levels of rest myocardial blood flow (MBF), indicative of inefficient aerobic metabolism, will be present in some patients with mitochondrial disorders but structurally normal hearts. Background Regulation of MBF is a complex process closely linked to myocardial energy production. Aerobic metabolism in turn depends on normal mitochondrial function and so investigation of patients with mitochondrial disorders may provide important information regarding heritable mechanisms involved in regulation of myocardial flow. Methods Rest and adenosine-stimulated MBF was measured by the positron emission tomography (PET) (NH3)-N-13 technique in nine patients with mitochondrial disorders and compared with 15 age-matched control participants. Results Basal heart rate (beats/min) and rate pressure product (mmHg/min) were elevated in patients (76 +/- 13 and 9302 +/- 1910, mean +/- SD, respectively) compared with control participants (63 +/- 9 and 7411 +/- 1531, P<0.01 and P<0.05, respectively). However, rest and adenosine-stimulated MBF (ml/min per g) did not differ significantly between groups (patients, 1.13 +/- 0.52 and 4.17 +/- 0.84, respectively; control participants, 0.85 +/- 0.30 and 3.56 +/- 0.63, respectively). Normalization of rest MBF to rate pressure product however, demonstrated three patients whose values exceeded that of all control participants (chi(2) =5.71, P<0.05, Fisher's exact test). Conclusions Elevated basal MBF, in some patients with mitochondrial disorders but structurally normal hearts, suggests the level of basal flow is responsive to efficiency of aerobic metabolism, which closely reflects mitochondrial function. Mitochondrial heteroplasmy with relative sparing of myocardial mitochondria may account for normal basal flow in others with these disorders. C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol & Nucl Med, Boston, MA 02114 USA. RP Gewirtz, H (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Vincent Burnham 3, Boston, MA 02114 USA. NR 35 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD MAY PY 2003 VL 14 IS 3 BP 197 EP 205 DI 10.1097/01.mca.0000065743.52558.51 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 680MJ UT WOS:000182981700002 PM 12702922 ER PT J AU Burns, JP Edwards, J Johnson, J Cassem, NH Truog, RD AF Burns, JP Edwards, J Johnson, J Cassem, NH Truog, RD TI Do-not-resuscitate order after 25 years SO CRITICAL CARE MEDICINE LA English DT Review DE cardiopulmonary resuscitation refusal; do-not-resuscitate order; futility; presumed consent ID SERIOUSLY ILL PATIENTS; CARDIOPULMONARY-RESUSCITATION; MEDICAL FUTILITY; LIFE; END; CARE; DNR; COMMUNICATION; PREFERENCES; PHYSICIANS AB Background: In 1976, the first hospital policies on orders not to resuscitate were published in the medical literature. Since that time, the concept has continued to evolve and evoke much debate. Indeed, few initials in medicine today evoke as much symbolism or controversy as the Do-Not-Resuscitate (DNR) order. Objective: To review the development, implementation, and present standing of the DNR order. Design: Review article. Main Results: The DNR order concept brought an open decision-making framework to the resuscitation decision and did much to put appropriate restraint on the universal application of cardiopulmonary resuscitation for the dying patient. Yet, even today, many of the early concerns remain. Conclusions: After 25 yrs of DNR orders, it remains reasonable to presume consent and attempt resuscitation for people who suffer an unexpected cardiopulmonary arrest or for whom resuscitation may have physiologic effect and for whom no information is available at the time as to their wishes (or those of their surrogate). However, it is not reasonable to continue to rely on such a presumption without promptly and actively seeking to clarify the patient's (or surrogate's) wishes. The DNR order, then, remains an inducement to seek the informed patient's directive. C1 Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Castle Soc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Childrens Hosp, Off Eth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Burns, JP (reprint author), Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. NR 83 TC 83 Z9 89 U1 0 U2 5 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 MAY PY 2003 VL 31 IS 5 BP 1543 EP 1550 DI 10.1097/01.CCM.0000064743.44696.49 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 680ME UT WOS:000182981300038 PM 12771631 ER PT J AU Duncan, MJ AF Duncan, MJ TI Genomics of oral bacteria SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Review DE genomics of oral bacteria ID BACTEROIDES CONJUGATIVE TRANSPOSON; LACTAMASE-PRODUCING STRAINS; STREPTOCOCCUS-MUTANS UA159; HORIZONTAL GENE-TRANSFER; MAJOR SURFACE PROTEIN; PORPHYROMONAS-GINGIVALIS; FUSOBACTERIUM-NUCLEATUM; TREPONEMA-DENTICOLA; PREVOTELLA-INTERMEDIA; VIRULENCE FACTORS AB Advances in bacterial genetics came with the discovery of the genetic code, followed by the development of recombinant DNA technologies. Now the field is undergoing a new revolution because of investigators' ability to sequence and assemble complete bacterial genomes. Over 200 genome projects have been completed or are in progress, and the oral microbiology research community has benefited through projects for oral bacteria and their non-oral-pathogen relatives. This review describes features of several oral bacterial genomes, and emphasizes the themes of species relationships, comparative genomics, and lateral gene transfer. Genomics is having a broad impact on basic research in microbial pathogenesis, and will lead to new approaches in clinical research and therapeutics. The oral microbiota is a unique community especially suited for new challenges to sequence the metagenomes of microbial consortia, and the genomes of uncultivable bacteria. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Duncan, MJ (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. EM mduncan@forsyth.org FU NIDCR NIH HHS [DE 10510, DE 12082] NR 109 TC 27 Z9 30 U1 0 U2 4 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PD MAY PY 2003 VL 14 IS 3 BP 175 EP 187 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 891QG UT WOS:000226595000002 PM 12799321 ER PT J AU Vallejo, J Mann, DL AF Vallejo, J Mann, DL TI Antiinflammatory therapy in myocarditis SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE viral myocarditis; inflammation; innate immunity; immune modulation; cytokine ID TUMOR-NECROSIS-FACTOR; ACUTE VIRAL MYOCARDITIS; DILATED CARDIOMYOPATHY; FACTOR-ALPHA; INNATE IMMUNITY; ENCEPHALOMYOCARDITIS VIRUS; CARDIAC MYOCYTES; TRANSGENIC MICE; MURINE MODEL; IMMUNOADSORPTION AB Acute viral myocarditis progresses through several stages, including acute viral infection, autoimmunity, and dilated cardiomyopathy. Recent studies have identified an important role for the myocardial inflammatory response during the initial phases of acute viral myocarditis. In this review, we discuss new insights into the innate host response to viral myocarditis and the various therapeutic strategies that have been attempted in managing the deleterious consequences of the myocardial inflammatory response in acute viral myocarditis. C1 Houston Vet Affairs Med Ctr, Winters Ctr Heart Failure Res, Cardiol Sect Med Care Line, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Mann, DL (reprint author), Houston Vet Affairs Med Ctr, Winters Ctr Heart Failure Res, Cardiol Sect Med Care Line, MS F524,6565 Fannin, Houston, TX 77030 USA. OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [HL_4225_10/10, R01 HL61543_01, R01 HL58081_01, P50 HL_O6H] NR 30 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD MAY PY 2003 VL 18 IS 3 BP 189 EP 193 DI 10.1097/00001573-200305000-00003 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 705EA UT WOS:000184381700003 PM 12826819 ER PT J AU Knight, EL Curhan, GC AF Knight, EL Curhan, GC TI Albuminuria: moving beyond traditional microalbuminuria cut-points SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Editorial Material ID ALBUMIN/CREATININE RATIO; CARDIOVASCULAR EVENTS; MORTALITY; RISK C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Boston, MA USA. RP Knight, EL (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. NR 8 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAY PY 2003 VL 12 IS 3 BP 283 EP 284 DI 10.1097/01.mnh.0000069862.94246.57 PG 2 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 680AU UT WOS:000182954800009 PM 12698066 ER PT J AU Myrick, H Brady, K AF Myrick, H Brady, K TI Current review of the comorbidity of affective, anxiety, and substance use disorders SO CURRENT OPINION IN PSYCHIATRY LA English DT Editorial Material DE co-occurring disorders; mood disorders; anxiety disorders; dual diagnosis ID POSTTRAUMATIC-STRESS-DISORDER; PLACEBO-CONTROLLED TRIAL; OBSESSIVE-COMPULSIVE DISORDER; COGNITIVE-BEHAVIORAL THERAPY; PANIC DISORDER; DOUBLE-BLIND; GENERALIZED ANXIETY; ALCOHOL DEPENDENCE; SOCIAL PHOBIA; PSYCHIATRIC-DISORDERS AB Purpose of review This review will provide an update on the diagnoses treatment of co-occurring mood/anxiety and substance use disorders. Interest in co-occurring disorders is growing because of the prevalence and negative impact of comorbidity on course, treatment outcomes and prognoses of both disorders. Recent findings There have been a number of recent studies exploring psychotherapeutic and pharmacotherapeutic treatment of co-occurring disorders. In particular, serotonin reuptake inhibitors and/or buspirone have demonstrated efficacy in decreasing consumption and improving psychiatric symptons in individuals with depression, social phobia and generalized anxiety disorder. There have been promising pilot studies exploring manual-guided psychotherapeutic interventions specifically targeting individuals with co-occurring substance use and post-traumatic stress disorder, depression and bipolar disorder. Summary The co-occurrence of substance abuse and mood and anxiety disorders is common and has important treatment implications. Recent investigations of pharmacotherapeutic and psychotherapeutic strategies specifically targeting individuals with comorbidity provide cause for optimism, but much work remains to be done. C1 Ralph H Johnson VAMC, Dept Psychiat, MUSC, CTN, Charleston, SC 29401 USA. RP Brady, K (reprint author), Ralph H Johnson VAMC, Dept Psychiat, MUSC, CTN, 109 Bee St, Charleston, SC 29401 USA. NR 84 TC 32 Z9 32 U1 5 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAY PY 2003 VL 16 IS 3 BP 261 EP 270 DI 10.1097/01.yco.0000069080.26384.d8 PG 10 WC Psychiatry SC Psychiatry GA 679DR UT WOS:000182906000001 ER PT J AU Taber, KH Hurley, RA AF Taber, KH Hurley, RA TI The role for diffusion tensor imaging in neuropsychiatry SO CURRENT OPINION IN PSYCHIATRY LA English DT Article DE diffusion tensor imaging; magnetic resonance imaging; neuropsychiatry ID WHITE-MATTER TRACTS; NORMAL-APPEARING WHITE; HUMAN BRAIN; MULTIPLE-SCLEROSIS; MAGNETIZATION-TRANSFER; FIBER TRACKING; GRAY-MATTER; CORTICAL DEVELOPMENT; CORPUS-CALLOSUM; MRI AB Purpose of review Those studies published primarily since October 2001 that are relevant to psychiatric applications of diffusion tensor imaging are reviewed here. Diffusion tensor imaging is a recently developed method of magnetic resonance imaging that is sensitive to the rate and direction of water diffusion. While diffusion in gray matter is similar in all directions (isotropic), diffusion in white matter is faster along axons than across them (anisotropic). As a result, diffusion tensor imaging is extremely sensitive to the microstructure of white matter. Recent findings Although there are many technical challenges still to be conquered, diffusion tensor imaging has great potential for the study of normal brain anatomy as well as for disease- or damage-related changes. This technique is able to visualize white-matter changes and differences not seen with conventional magnetic resonance imaging. Thus it may provide a means of predicting/understanding neurological deficits related to processes or events that affect the structural integrity of white matter. Summary Diffusion tensor imaging has the potential to expand our knowledge of the brain a great deal. Currently, reports exist in the literature that demonstrate its potential use in both the acute and the chronic patient for diagnosis, prognosis, and/or treatment planning. Potential clinical applications range from developmental abnormalities (schizophrenia, congenital malformations, developmental disabilities, epilepsy) to acquired brain injury (traumatic brain injury, stroke, toxins, poisons) and degenerative conditions (Alzheimer's disease, multiple sclerosis, cancer). C1 Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Herbert J Frensley Ctr Imaging Res, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Mental Hlth Care Line, Houston, TX USA. RP Taber, KH (reprint author), Baylor Coll Med, Dept Radiol, 1 Baylor Plaza, Houston, TX 77030 USA. NR 76 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAY PY 2003 VL 16 IS 3 BP 341 EP 347 DI 10.1097/01.yco.0000069092.26384.ff PG 7 WC Psychiatry SC Psychiatry GA 679DR UT WOS:000182906000012 ER PT J AU Hirsch, RJ Shalita, AR AF Hirsch, RJ Shalita, AR TI Lasers, light, and acne SO CUTIS LA English DT Editorial Material ID PHOTODYNAMIC THERAPY; ENDOGENOUS PROTOPORPHYRIN; VULGARIS; ACID C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. SUNY Downstate Med Ctr, Dept Dermatol, Brooklyn, NY USA. RP Hirsch, RJ (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Box 630,55 Fruit St, Boston, MA 02114 USA. NR 19 TC 16 Z9 22 U1 1 U2 1 PU QUADRANT HEALTHCOM INC PI CHATHAM PA 26 MAIN ST, STE A, CHATHAM, NJ 07928-2402 USA SN 0011-4162 J9 CUTIS JI Cutis PD MAY PY 2003 VL 71 IS 5 BP 353 EP 354 PG 2 WC Dermatology SC Dermatology GA 679EK UT WOS:000182907600004 PM 12769401 ER PT J AU Ligon, KL Echelard, Y Assimacopoulos, S Danielian, PS Kaing, S Grove, EA McMahon, AP Rowitch, DH AF Ligon, KL Echelard, Y Assimacopoulos, S Danielian, PS Kaing, S Grove, EA McMahon, AP Rowitch, DH TI Loss of Emx2 function leads to ectopic expression of Wnt1 in the developing telencephalon and cortical dysplasia SO DEVELOPMENT LA English DT Article DE Emx2; Wnt1; dysplasia; cerebral; cortex; telencephalon; marginal zone; subplate; preplate; cortical hem; organizer; transgenic; leptomeningeal; glioneuronal; heterotopia ID DEVELOPING CEREBRAL-CORTEX; LEPTOMENINGEAL GLIONEURONAL HETEROTOPIA; CENTRAL-NERVOUS-SYSTEM; CAJAL-RETZIUS CELLS; HOMEOBOX GENE EMX2; NEURONAL MIGRATION; DORSAL TELENCEPHALON; GANGLIONIC EMINENCE; GERMLINE MUTATIONS; MUTANT MICE AB Leptomeningeal glioneuronal heterotopias are a focal type of cortical dysplasia in which neural cells migrate aberrantly into superficial layers of the cerebral cortex and meninges. These heterotopias are frequently observed as microscopic abnormalities in the brains of individuals with central nervous system (CNS) malformations and epilepsy. Previous work has demonstrated that the function of Emx2, which encodes a homeodomain transcription factor, is essential for development of the cortical preplate, which gives rise to the marginal zone and subplate. However, transcriptional targets of EMX2 during CNS development are unknown. We report that leptomeningeal glioneuronal heterotopias form in Emx2(-/-) mice that are equivalent to human lesions. Additionally, we observed ectopic expression of Wnt1 in the embryonic roofplate organizer region and dorsal telencephalon. To determine the phenotypic consequences of such Wnt1 misexpression, we deleted a putative EMX2 DNA-binding site from the Wnt1 enhancer and used this to misexpress Wnt1 in the developing murine CNS. Heterotopias were detected in transgenic mice as early as 13.5 days postcoitum, consistent with a defect of preplate development during early phases of radial neuronal migration. Furthermore, we observed diffuse abnormalities of reelin- and calretinin-positive cell populations in the marginal zone and subplate similar to those observed in Emx2-null animals. Taken together, these findings indicate that EMX2 is a direct repressor of Wnt1 expression in the developing mammalian telencephalon. They further suggest that EMX2-Wnt1 interactions are essential for normal development of preplate derivatives in the mammalian cerebral cortex. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 0215 USA. Brigham & Womens Hosp, Dept Pathol, Div Neuropathol, Boston, MA 02115 USA. Childrens Hosp Boston, Div Neuropathol, Boston, MA 02115 USA. GTC Biotherapeut, Framingham, MA 01701 USA. Univ Chicago, Dept Neurobiol Pharmacol & Physiol, Chicago, IL 60637 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Childrens Hosp Boston, Div Newborn Med, Boston, MA 02115 USA. RP Rowitch, DH (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NICHD NIH HHS [R01HD030249, T32HD007466-08]; NIMH NIH HHS [R01MH059962]; NINDS NIH HHS [R01NS040511] NR 55 TC 34 Z9 35 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 2003 VL 130 IS 10 BP 2275 EP 2287 DI 10.1242/dev.00421 PG 13 WC Developmental Biology SC Developmental Biology GA 683HZ UT WOS:000183143800022 PM 12668639 ER PT J AU Lin, SY Johnson, SM Abraham, M Vella, MC Pasquinelli, A Gamberi, C Gottlieb, E Slack, FJ AF Lin, SY Johnson, SM Abraham, M Vella, MC Pasquinelli, A Gamberi, C Gottlieb, E Slack, FJ TI The C-elegans hunchback homolog, hbl-1, controls temporal patterning and is a probable microRNA target SO DEVELOPMENTAL CELL LA English DT Article ID DROSOPHILA BODY PATTERN; CAENORHABDITIS-ELEGANS; RNA INTERFERENCE; REGULATORY RNA; MESSENGER-RNA; LIN-4 RNA; GENE; PUMILIO; EXPRESSION; NANOS AB Hunchback regulates the temporal identity of neuroblasts in Drosophila. Here we show that hbl-1, the C. elegans hunchback ortholog, also controls temporal patterning. Furthermore, hbl-1 is a probable target of microRNA regulation through its 3'UTR. hbl-1 loss-of-function causes the precocious expression of adult seam cell fates. This phenotype is similar to loss-of-function of lin-41, a known target of the let-7 microRNA. Like lin-41 mutations, hbl-1 loss-of-function partially suppresses a let-7 mutation. The hbl-1 3'UTR is both necessary and sufficient to downregulate a reporter gene during development, and the let-7 and lin-4 microRNAs are both required for HBL-1/GFP downregulation. Multiple elements in the hbl-1 3'UTR show complementarity to regulatory microRNAs, suggesting that microRNAs directly control hbl-1. MicroRNAs may likewise function to regulate Drusophila hunchback during temporal patterning of the nervous system. C1 Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Univ Texas, Inst Cell & Mol Biol, Austin, TX 78712 USA. RP Slack, FJ (reprint author), Yale Univ, Dept Mol Cellular & Dev Biol, POB 208103, New Haven, CT 06520 USA. RI Johnson, Steven/B-3940-2013; OI Slack, Frank/0000-0001-8263-0409 FU NIGMS NIH HHS [R01 GM50800, R01 GM62594] NR 39 TC 242 Z9 262 U1 2 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAY PY 2003 VL 4 IS 5 BP 639 EP 650 DI 10.1016/S1534-5807(03)00124-2 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 729RF UT WOS:000185787200007 PM 12737800 ER PT J AU Xu, Y Lu, L Greyson, C Lee, J Gen, M Kinugawa, K Long, CS Schwartz, GG AF Xu, Y Lu, L Greyson, C Lee, J Gen, M Kinugawa, K Long, CS Schwartz, GG TI Deleterious effects of acute treatment with a peroxisome proliferator-activated receptor-gamma activator in myocardial ischemia and reperfusion in pigs SO DIABETES LA English DT Article ID ATP CHANNEL ACTIVITY; PPAR-GAMMA; ISCHEMIA/REPERFUSION INJURY; INSULIN-SENSITIZERS; CALCIUM CHANNELS; SMOOTH-MUSCLE; UP-REGULATION; TROGLITAZONE; ROSIGLITAZONE; DYSFUNCTION AB Thiazolidinediones exert electrophysiologic effects in noncardiac cells in vitro, but to date there have been no reports of effects on cardiac rhythm. We previously demonstrated that chronic pretreatment with a thiazolidinedione peroxisome proliferator-activated receptor (PPAR)-gamma activator, troglitazone, improves recovery of left ventricular (LV) function and substrate metabolism after ischemia and reperfusion, without causing arrhythmias. In this study, we determined whether similar salutary effects are achieved with acute treatment with troglitazone. Anesthetized pigs underwent 90 min of regional LV ischemia and 90 min of reperfusion. Fifteen pigs were treated with troglitazone (10 mg/kg load, 5 mg (.) kg(-1) (.) h(-1) infusion i.v.) beginning 1 h before ischemia. Seven pigs received corresponding vehicle. Plasma troglitazone concentration (mean 5 mug/ml) was similar to that achieved in clinical use of this agent. Before ischemia, acute troglitazone treatment had no effect on LV function, electrocardiogram, or substrate utilization. During ischemia or reperfusion, eight pigs in the troglitazone group died of ventricular fibrillation, compared with no pigs in the vehicle group (P < 0.05). Pigs that developed ventricular fibrillation had shorter QT intervals than survivors of either group. Among survivors, neither LV function nor substrate utilization differed between groups. Acute treatment with troglitazone increases susceptibility to ventricular fibrillation during myocardial ischemia and reperfusion. Whether thiazolidinediones have proarrhythmic potential in clinical use requires further investigation. C1 Denver VA Med Ctr, Cardiol Sect 111B, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Schwartz, GG (reprint author), Denver VA Med Ctr, Cardiol Sect 111B, 1055 Clermont St, Denver, CO 80220 USA. FU NHLBI NIH HHS [HL 49944, R01 HL049944, R01 HL049944-08, R56 HL049944] NR 32 TC 18 Z9 19 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 MAY PY 2003 VL 52 IS 5 BP 1187 EP 1194 DI 10.2337/diabetes.52.5.1187 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 674ED UT WOS:000182623500019 PM 12716751 ER PT J AU Jaffa, AA Durazo-Arvizu, R Zheng, DY Lackland, DT Srikanth, S Garvey, WT Schmaier, AH AF Jaffa, AA Durazo-Arvizu, R Zheng, DY Lackland, DT Srikanth, S Garvey, WT Schmaier, AH CA DCCT EDIC Study Grp TI Plasma prekallikrein - A risk marker for hypertension and nephropathy in type 1 diabetes SO DIABETES LA English DT Article ID VASCULAR SMOOTH-MUSCLE; CONVERTING-ENZYME-INHIBITION; C-FOS INDUCTION; ENDOTHELIAL-CELLS; NITRIC-OXIDE; BRADYKININ; MELLITUS; KALLIKREIN; KININ; ACTIVATION AB The relevance and significance of the plasma kallikrein/ kinin system as a risk factor for the development of vascular. complications in diabetic patients was explored in a cross-sectional study. We measured the circulating levels of plasma prekallikrein (PK) activity, factor XII, and high-molecular weight kininogen in the plasma of 636 type I diabetic patients from the Diabetes Control and Complications Trial/Epidemiology and Diabetes Intervention and Complications Study cohort. The findings demonstrated that type 1 diabetic patients with blood pressure greater than or equal to140/90 mmHg have increased PK levels compared with type I diabetic patients with blood pressure < 140/90 (1.53 +/- 0.07 vs. 1.27 +/- 0.02 units/ml; P < 0.0001). Regression analysis also determined that plasma PK levels positively and significantly correlated with diastolic (DBP) and systolic blood pressures (SBP) as continuous variables (r = 0.17 and 0.18, respectively; P < 0.0001). In multivariate regression analysis, the semipartial r(2) value for PK was 2.93% for SBP and 2.92% for DBP (P < 0.0001). A positive correlation between plasma PK levels and the urinary albumin excretion rate (AER) was also observed (r = 0.16, P < 0.0001). In categorical analysis, patients with macroalbuminuria had a significantly higher level of plasma PK than normoalbuminuric patients (1.45 +/- 0.08 vs. 1.27 +/- 0.02 units/ml; P < 0.01), whereas microalbuminuric patients had an intermediate PK value (1.38 +/- 0.05 units/ml; P = NS). Among patients in the microalbuminuric subgroup, we observed a positive and independent correlation between PK and AER in univariate and multivariate regression analysis (r = 0.27, P < 0.03; n = 63). We concluded that in type 1 diabetes, 1) PK levels are elevated in association with increased blood pressure; 2) PK levels are independently correlated with AER and are categorically elevated in patients with macroalbuminuria; and 3) although the positive correlation between PK and AER within the subgroups of patients with microalbuminuria suggest that PK could be a marker for progressive nephropathy, longitudinal studies will be necessary to address this issue. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. NDIC, EDIC, Bethesda, MD USA. RP Jaffa, AA (reprint author), Med Univ S Carolina, Dept Med, 114 Doughty St,POB 250776, Charleston, SC 29425 USA. EM jaffaa@musc.edu FU NHLBI NIH HHS [HL 52779, P01 HL 55782, HL 71255]; NIDDK NIH HHS [DK 46543] NR 46 TC 40 Z9 41 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD MAY PY 2003 VL 52 IS 5 BP 1215 EP 1221 DI 10.2337/diabetes.52.5.1215 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 674ED UT WOS:000182623500023 PM 12716755 ER PT J AU Grant, RW Devita, NG Singer, DE Meigs, JB AF Grant, RW Devita, NG Singer, DE Meigs, JB TI Polypharmacy and medication adherence in patients with type 2 diabetes SO DIABETES CARE LA English DT Article ID ANTIRETROVIRAL THERAPY ADHERENCE; INFECTED DRUG-USERS; TUBERCULOSIS TREATMENT; VIRAL SUPPRESSION; ELDERLY PATIENTS; STATIN THERAPY; NIDDM PATIENTS; NONADHERENCE; CONSEQUENCES; CARE AB OBJECTIVE - To determine medication adherence and predictors of suboptimal adherence in a community cohort of patients with diabetes and to test the hypothesis that adherence decreases with increased number of medicines prescribed. RESEARCH DESIGN AND METHODS - A total of 128 randomly selected patients with type 2 diabetes from a single community health center responded to a pharmacist-administered questionnaire regarding medication use. Survey data were linked to clinical data available from the electronic medical record. We assessed self-reported adherence rates for each diabetes-related medicine, barriers and attitudes regarding medication use, and HbA(1c), total cholesterol, and blood pressure levels. RESULTS - Patients were taking a mean of 4.1 (+/-1.9) diabetes-related medicines. The average 7-day adherence was 6.7 +/- 1.1 days. Total number of medicines prescribed was not correlated with medication adherence. Adherence was significantly lower for medicines not felt to be improving current or future health (6.1 vs. 6.9 days out of 7, P < 0.001). Among patients on three or more medicines, 71% (15 of 21 patients) with suboptimal adherence were perfectly adherent with all but one medicine. Side effects were the most commonly reported problem with medication use. Of 29 medicines causing side effects that interfered with adherence, 24 (83%) did so for >1 month, and only 7 (24%) were reported to the patient's primary care physician. CONCLUSIONS - In this sample, patients reported very high medication adherence rates regardless of number of medicines prescribed. Among patients on multiple medicines, most patients with suboptimal adherence were perfectly adherent to all but one medicine. Unreported side effects and a lack of confidence in immediate or future benefits were significant predictors of suboptimal adherence. Physicians should not feel deterred from prescribing multiple agents in order to achieve adequate control of hyperglycemia, hypertension, and hyperlipidemia. C1 Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Partners Commun Hlth Care Inc, Boston, MA USA. Massachusetts Gen Hosp, Clin Res Program, Boston, MA 02114 USA. RP Grant, RW (reprint author), Massachusetts Gen Hosp, Div Gen Med, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. OI Grant, Richard/0000-0002-6164-8025 FU PHS HHS [2-T3211001-14] NR 37 TC 154 Z9 162 U1 2 U2 16 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 MAY PY 2003 VL 26 IS 5 BP 1408 EP 1412 DI 10.2337/diacare.26.5.1408 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UQ UT WOS:000185505400014 PM 12716797 ER PT J AU Klein, RL Hunter, SJ Jenkins, AJ Zheng, D Semler, AJ Clore, J Garvey, WT AF Klein, RL Hunter, SJ Jenkins, AJ Zheng, D Semler, AJ Clore, J Garvey, WT CA DCCT EDIC Study Grp TI Fibrinogen is a marker for nephropathy and peripheral vascular disease in type 1 diabetes - Studies of plasma fibrinogen and fibrinogen gene polymorphism in the DCCT/EDIC cohort SO DIABETES CARE LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; URINARY ALBUMIN EXCRETION; CORONARY-ARTERY-DISEASE; EDINBURGH ARTERY; MYOCARDIAL-INFARCTION; HEMOSTATIC FACTORS; GLYCEMIC CONTROL; PROMOTER REGION; HEART-DISEASE; COMPLICATIONS AB We exannined whether plasma fibrinogen levels and the beta-fibrinogen gene G(-455)-->A polymorphism Were related to microvascular or macrovascular disease in patients (n = 909) with type 1 diabetes enrolled in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC). Univariate regression showed that fibrinogen levels were correlated with BMI (r = 0.15 P < 0.0001), HbA(1c) (r = 0.11; P = 0.0014), total Cholesterol (r- = 0.17; P < 0.0001),and LDL cholesterol (r = 0.16; P < 0.0001) in all patients. In men, but not women, waist-to-hip ratio (r = 0.20, P < 0.0001) and triglycerides (r = 0.13; P = 0.0047) also became powerful predictors of fibrinogen level, in women, but not men, fibrinogen was correlated with both diastolic (r = 0.16; P = 0.0011) and systolic (r = 0.11; P = 0.0241) blood pressure. Fibrinogen was correlated with urinary albumin excretion rates in men (r = 0.13, P = 0.0033), but not in women. In both sexes, however, the development of proteinuria (albumin excretion >300 mg/24 h) was accompanied by 1.5-fold increment in plasma fibrinogen compared with patients with normal excretion or microalbuminuria. In addition, high fibrinogen levels Were associated with a lower average ankle-brachial index in women (r = -0.13, P = 0.0075), but not men. Multiple regression analyses demonstrated that plasma fibrinogen was independently correlated with high albumin excretion rate in men, and with low average ankle-brachial index in women. Fibrinogen was not correlated wit it the severity of retinopathy. Carotid artery intima-medial thickness was not correlated with fibrinogen, and the G(-455)-->A polymorphism in the 5' promoter region of the beta-fibrinogen gene did not influence circulating fibrinogen levels. However, the presence of the more common G(-455) allele was associated With greater intima-medial thickness in the internal carotid artery (ANCOVA P = 0.045). Last, hyperfibrinogenemia in type 1 diabetes is associated with components of the insulin resistance syndrome tran Cluster, and the association is influenced by sex. C1 Med Univ S Carolina, Dept Med, Div Endocrinol Metab & Med Genet, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Res Serv, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Natl Daibet Informat Clearinghouse, Diabet Control & Complicat Trial, Bethesda, MD USA. RP Klein, RL (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Metab & Med Genet, 114 Doughty St,POB 250770, Charleston, SC 29425 USA. EM kleinrl@musc.edu FU NHLBI NIH HHS [P01-HL55782] NR 53 TC 35 Z9 37 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2003 VL 26 IS 5 BP 1439 EP 1448 DI 10.2337/diacare.26.5.1439 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UQ UT WOS:000185505400019 PM 12716802 ER PT J AU Abdi, R Means, TK Luster, AD AF Abdi, R Means, TK Luster, AD TI Chemokines in islet allograft rejection SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Review DE islet allograft rejection; chemokine receptor 5; Th2 response; organ specificity of chemokines ID RENAL-TRANSPLANT REJECTION; RECEPTOR CXCR3; EXPRESSION; CCR5; CELL; TH1; MIGRATION; CYTOKINES; RANTES; RISK AB Chemokines have emerged as important regulators in the development, differentiation, and anatomic distribution of leukocytes. Studies of renal and cardiac allograft biopsies have revealed that the expression of many chemokine receptors and their ligands was associated with acute allograft rejection. However, the importance of these chemokine receptor systems varies in the host response to a particular allograft. In this regard, CXCR3 appears to play a more important role in cardiac allograft rejection than CCR2 and CCR5. We have found that CCR2, CCR5, and CXCR3 and their ligands, as well as Th1 cytokines are induced to high levels in rejecting islet allografts. Interestingly, targeting CCR5 resulted in a significant prolongation of islet allograft survival. This prolongation was associated with a Th2 response. Our data indicate that in the process of acute rejection, the temporal expression and the ultimate function of a given chemokine vary among different organs or tissues. Hence, each organ or tissue may require a unique set of chemokines to generate acute rejection. Targeting the appropriate chemokine receptors may provide a clinically useful strategy to prevent islet allograft rejection. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Brigham & Womens Hosp, Div Renal, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA 02115 USA. RP Abdi, R (reprint author), Brigham & Womens Hosp, Div Renal, Lab Immunogenet & Transplantat, 75 Francis St, Boston, MA 02115 USA. NR 28 TC 34 Z9 36 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD MAY-JUN PY 2003 VL 19 IS 3 BP 186 EP 190 DI 10.1002/dmrr.362 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 686XT UT WOS:000183346800003 PM 12789651 ER PT J AU Kim, KA Kang, K Chi, YI Chang, I Lee, MK Kim, KW Shoelson, SE Lee, MS AF Kim, KA Kang, K Chi, YI Chang, I Lee, MK Kim, KW Shoelson, SE Lee, MS TI Identification and functional characterization of a novel mutation of hepatocyte nuclear factor-1 alpha gene in a Korean family with MODY3 SO DIABETOLOGIA LA English DT Article DE MODY; HNF-1 alpha; mutation; glucose transporter type 2; insulin; HNF-1 beta; p300 ID TRANSCRIPTION FACTOR; JAPANESE SUBJECTS; INSULIN GENE; ALPHA-GENE; HNF-1-ALPHA; COACTIVATOR; P300; CBP; MECHANISMS; PROTEINS AB Aims/hypothesis. After screening 16 Korean families with early onset Type 2 diabetes in search for hepatocyte nuclear factor (HNF)-1alpha gene mutation, we identified a novel missense mutation (R263L) associated with MODY phenotype. We studied the biological characteristics of the mutation and the potential functional consequences based on the crystallographic structure of HNF-1alpha in complex with DNA. Methods. DNA from subjects with a familial form of early onset diabetes was isolated and HNF-1alpha was sequenced. The R263L substitution was generated by PCR-based sited-directed mutagenesis. Functional and biochemical studies were conducted by reporter assay using glucose-transporter type 2 (GLUT2) or insulin promoters and electrophoretic mobility shift assay, respectively. Results. Transfection of wild-type HNF-1alpha increased the reporter activities of GLUT2 and insulin promoters in NIH3T3 and SK-Hep1 cells, while R263L mutant was defective in transactivation of those promoters. Both wild-type HNF-1alpha and R263L mutant could not transactivate GLUT2 and insulin promoters in MIN6N8 insulinoma cells. R263L mutant had a defective cooperation with its heterodimeric partner HNF-1beta or coactivator p300. R263L mutant protein displayed greatly reduced DNA binding ability, despite its comparable protein stability to the wild-type HNF-1alpha. Conclusion/interpretation. These results suggest that the mutation of HNF-1alpha at codon 263 from arginine to leucine leads to the development of MODY3 through decreased insulin production and defective glucose sensing. These findings are in good agreement with the crystal structure in which R263 makes hydrogen bonds with phosphorus atoms of DNA backbone to mediate the stable binding of HNF-1alpha homeodomain to the promoter. C1 Sungkyunkwan Univ Sch Med, Samsung Med Ctr, Dept Med, Seoul 135710, South Korea. MizMedi Hosp, Dept Med, Seoul, South Korea. Chungnam Natl Univ, Dept Biochem, Inst Biotechnol, Taejon, South Korea. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Lee, MS (reprint author), Sungkyunkwan Univ Sch Med, Samsung Med Ctr, Dept Med, Irwon Dong 50, Seoul 135710, South Korea. RI Lee, Myung Shik/C-9606-2011 FU NIDDK NIH HHS [R01 DK43123] NR 25 TC 10 Z9 12 U1 0 U2 6 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAY PY 2003 VL 46 IS 5 BP 721 EP 727 DI 10.1007/s00125-003-1079-7 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 690DL UT WOS:000183532100016 PM 12712243 ER PT J AU Dackis, CA Lynch, KG Yu, E Samaha, FF Kampman, KM Cornish, JW Rowan, A Poole, S White, L O'Brien, CP AF Dackis, CA Lynch, KG Yu, E Samaha, FF Kampman, KM Cornish, JW Rowan, A Poole, S White, L O'Brien, CP TI Modafinil and cocaine: a double-blind, placebo-controlled drug interaction study SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE modafinil; cocaine; safety; drug interaction; euphoria ID HEALTHY MALE-VOLUNTEERS; VENTRAL TEGMENTAL AREA; SINGLE-DOSE PHARMACOKINETICS; NUCLEUS-ACCUMBENS; D-AMPHETAMINE; ABSTINENCE SYMPTOMATOLOGY; EXTRACELLULAR DOPAMINE; RECREATIONAL COCAINE; WITHDRAWAL SYMPTOMS; TREATMENT ATTRITION AB Modafinil is a novel compound that is approved for the treatment of narcolepsy. It is now being studied as a potential treatment for cocaine dependence. Cocaine withdrawal symptoms are associated with poor clinical outcome and are likely to be reversed by modafinil. In addition, the neurotransmitter actions of modafinil are opposite to cocaine-induced neuroadaptations affecting dopamine and glutamate reward circuits. Since cocaine-dependent subjects might use cocaine during a clinical trial with modafinil, this study tested the safety of intravenous cocaine (30 mg) in combination with modafinil. Each of seven subjects received a baseline (open-label) cocaine infusion. Three subsequent cocaine infusions were administered after subjects received 4 days of low dose modafinil (200 mg/day), high dose modafinil (400 mg/day), or placebo in randomized double-blind sequences. One subject received placebo prior to all infusions. Our results indicate that co-administering modafinil and a single dose of intravenous cocaine is not associated with medical risk in terms of blood pressure, pulse, temperature, or electrocardiogram measures. Furthermore, pretreatment with modafinil did not intensify cocaine euphoria or cocaine-induced craving. In fact, cocaine euphoria was significantly blunted (P=0.02) in one of our subjective measures. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Dept Cardiol, Philadelphia, PA 19104 USA. RP Dackis, CA (reprint author), Univ Penn, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [DA P50-12756, DA P60-05186, DA30012-02] NR 80 TC 119 Z9 119 U1 3 U2 7 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 MAY 1 PY 2003 VL 70 IS 1 BP 29 EP 37 AR PII S0376-8716(02)00335-6 DI 10.1016/S0376-8716(02)00335-6 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 676VN UT WOS:000182773400004 PM 12681523 ER PT J AU Munn, LL AF Munn, LL TI Aberrant vascular architecture in tumors and its importance in drug-based therapies SO DRUG DISCOVERY TODAY LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; HUMAN COLON ADENOCARCINOMA; BLOOD-VESSEL FORMATION; HUMAN-MELANOMA CELLS; VASCULOGENIC MIMICRY; IN-VIVO; SOLID TUMORS; MOLECULAR MEDICINE; ANGIOGENESIS; PERMEABILITY AB The vasculature is not simply a collection of hollow tubes through which blood flows - it is an organ in its own right, consisting of several cell types organized in a specific manner, and it mediates many unique biological and physiological functions such as selective filtration and angiogenesis. In tumors, blood vessels have structural and functional abnormalities that, to date, have generally hindered conventional therapies: the malformed networks make it difficult to deliver drugs uniformly to all cancer cells. Furthermore, flow in these vessels is chaotic, with intermittent stagnation followed by high-flow or even flow reversal in isolated segments. Cancer cells in stagnated or low-flow regions will receive suboptimal drug levels during chemotherapy. However, as more is learned about the formation of tumor vasculature and how it differs from that in normal tissue, more effective and directed therapies to fight cancer might be developed. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Munn, LL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 74 TC 63 Z9 67 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD MAY 1 PY 2003 VL 8 IS 9 BP 396 EP 403 AR PII S1359-6446(03)02686-2 DI 10.1016/S1359-6446(03)02686-2 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 671BQ UT WOS:000182445500008 PM 12706657 ER PT J AU Schlozman, SC AF Schlozman, SC TI The pain of losing a parent SO EDUCATIONAL LEADERSHIP LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. RP Schlozman, SC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU ASSOC SUPERVISION CURRICULUM DEVELOPMENT PI ALEXANDRIA PA 1703 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0013-1784 J9 EDUC LEADERSHIP JI Educ. Leadership PD MAY PY 2003 VL 60 IS 8 BP 91 EP 92 PG 2 WC Education & Educational Research SC Education & Educational Research GA 676BK UT WOS:000182731900021 ER PT J AU Kaufmann, C Yoshida, T Perotti, EA Landhuis, E Wu, P Georgopoulos, K AF Kaufmann, C Yoshida, T Perotti, EA Landhuis, E Wu, P Georgopoulos, K TI A complex network of regulatory elements in Ikaros and their activity during hemo-lymphopoiesis SO EMBO JOURNAL LA English DT Article DE DHS; gene regulation; GFP; Ikaros; transgenic mice ID POSITION-EFFECT VARIEGATION; LYMPHOCYTE DEVELOPMENT; TRANSCRIPTION FACTOR; GENE; HETEROCHROMATIN; DIFFERENTIATION; PROGENITORS; COMMITMENT; CHROMATIN; MUTATION AB Regulated expression of Ikaros is critical for normal hemopoiesis and lymphocyte development. To elucidate the mechanisms underlying transcription of Ikaros, tissue-specific DNase I-hypersensitive sites (DHS) were mapped throughout the Ikaros locus, and several promoters were identified. The activity of these regulatory regions was elucidated using an enhanced green fluorescent protein (EGFP) reporter in transgenic mice. Two genomic fragments, each containing a distinct promoter and its associated DHS cluster, were found to be active in the myeloid (DHS-C2 and DHS-C3) and B-cell (DHS-C3) lineages. Although neither of these regulatory regions was active within the majority of differentiating thymocytes and mature T cells, the DHS-C3 region was active at the earliest stages (DN1-DN3) of T-cell differentiation. However, when the DHS-C3 region was combined with the downstream intronic DHS-C6 cluster, its activity was maintained and raised to higher levels at subsequent stages of T-cell differentiation. This combination of regulatory elements provided reporter expression that closely resembles that of endogenous Ikaros during hemo-lymphopoiesis, and it decreased (but did not alleviate) position effect variegation within the expressing cell types. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Georgopoulos, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. FU NIAID NIH HHS [5R37 R01 AI33062, R01 AI033062] NR 27 TC 22 Z9 23 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 1 PY 2003 VL 22 IS 9 BP 2211 EP 2223 DI 10.1093/emboj/cdg186 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 674HG UT WOS:000182630900027 PM 12727887 ER PT J AU Schnitzer, JJ Donahoe, PK Tash, J Poppas, DP AF Schnitzer, JJ Donahoe, PK Tash, J Poppas, DP TI Single-stage surgical reconstruction for infants with congenital adrenal hyperplasia SO ENDOCRINOLOGIST LA English DT Article ID VAGINAL AGENESIS; REPAIR; MOBILIZATION C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Cornell Univ, Weill Med Coll, Childrens Hosp New York, New York, NY 10021 USA. RP Schnitzer, JJ (reprint author), Massachusetts Gen Hosp, WRN 1159,55 Fruit 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 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD MAY-JUN PY 2003 VL 13 IS 3 BP 190 EP 194 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 691RQ UT WOS:000183619600008 ER PT J AU Schneyer, A Schoen, A Quigg, A Sidis, Y AF Schneyer, A Schoen, A Quigg, A Sidis, Y TI Differential binding and neutralization of activins A and B by follistatin and follistatin like-3 (FSTL-3/FSRP/FLRG) SO ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; PITUITARY FOLLISTATIN; PROTEINS; CELL; SECRETION; CULTURES; INHIBINS; FSH AB Modulation of activin and other TGFbeta superfamily signaling is the primary mechanism of action for both follistatin (FS) and FS-like 3 (FSTL-3). However, most studies of these ligands use activin A due to its wide availability. We have now tested the ability of FS288 and FSTL-3 to bind and neutralize activin B relative to activin A. Activin B bound to both FS and FSTL-3 at a potency approximately 10-fold lower than that of activin A. Moreover, whereas both activins had similar biological activity in 293 cell reporter assays, FS and FSTL-3 were approximately fold more effective in neutralizing activin A relative to activin B. These results suggest that neutralization of activins A and B by FS and FSTL-3 are not identical, so that the relative activity of each activin in tissues where both are produced, such as in the ovary, could be quite different. In addition, biological systems that use primarily activin B, but which have been examined in vitro using activin A, may need to be reevaluated to determine the actual physiologic roles of FS or FSTL-3. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Schneyer, A (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RI Quigg, Antonietta/A-9345-2010 FU NICHD NIH HHS [R01-HD-39777]; NIDDK NIH HHS [R01-DK-55838] NR 20 TC 44 Z9 48 U1 0 U2 0 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 MAY PY 2003 VL 144 IS 5 BP 1671 EP 1674 DI 10.1210/en.2002-0203 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 668BE UT WOS:000182269800004 PM 12697670 ER PT J AU Ahuja, SS Zhao, SJ Bellido, T Plotkin, LI Jimenez, F Bonewald, LF AF Ahuja, SS Zhao, SJ Bellido, T Plotkin, LI Jimenez, F Bonewald, LF TI CD40 ligand blocks apoptosis induced by tumor necrosis factor alpha, glucocorticoids, and etoposide in osteoblasts and the osteocyte-like cell line murine long bone osteocyte-Y4 SO ENDOCRINOLOGY LA English DT Article ID TNF RECEPTOR SUPERFAMILY; FACTOR FAMILY MEMBER; DENDRITIC CELLS; OSTEOPROTEGERIN LIGAND; B-LYMPHOCYTES; IFN-GAMMA; T-CELLS; DEATH; ESTROGEN; TRANCE AB During characterization of the osteocyte-like murine long bone osteocyte-Y4 (MLO-Y4) cell line, comparison was made with antigen-presenting cells of the immune system known as dendritic cells. It was observed that the MLO-Y4 osteocyte-like cells express CD40 antigen and MHC class I antigen, but they are negative for a series of other dendritic cells markers (DEC-205, CD11b, CD11c, CD86, and MHC class II) and immune cell markers [ CD45, CD3, CD4, B220, Gr-1, and CD40 ligand (CD40L)]. RT-PCR results showed expression of CD40 mRNA and lack of CD40L mRNA expression. Like MLO-Y4 osteocyte cells, both primary osteoblasts and the osteoblast-like cell lines MC3T3, OCT-1, and 2T3 were shown to express CD40 antigen by fluorescence-activated cell sorting. Because CD40L has been shown to function as an antiapoptotic factor in dendritic cells, it was reasoned that this molecule may have a similar function in bone cells. In three different assays for apoptosis, including trypan blue exclusion, changes in nuclear morphology, and fluorescence-activated cell sorting staining for annexin V/propidium iodide, CD40L significantly inhibited apoptosis of MLO-Y4 cells induced by dexamethasone, TNFalpha, or etoposide. CD40L also inhibited dexamethasone and TNFalpha-induced apoptosis in the osteoblast cell lines, OCT1 and MC3T3-E1. These data support the hypothesis that CD40L preserves viability of osteoblasts and osteocytes against a wide variety of apoptotic factors independent of signaling or transcriptional mechanisms. Because osteocyte cell death appears to result in bone loss, these studies have important implications for the treatment of bone loss due to glucocorticoid excess and/or to osteoporosis in general. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78284 USA. Univ Arkansas Med Sci, Div Endocrinol & Metab, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Ctr Osteoporosis & Metab Bone Dis, Little Rock, AR 72205 USA. RP Bonewald, LF (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. FU NIAID NIH HHS [AI-48644]; NIAMS NIH HHS [AR-46798, KO2-AR-02127] NR 54 TC 58 Z9 61 U1 2 U2 6 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 MAY PY 2003 VL 144 IS 5 BP 1761 EP 1769 DI 10.1210/en.2002-221136 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 668BE UT WOS:000182269800015 PM 12697681 ER PT J AU Morton, GJ Niswender, KD Rhodes, CJ Myers, MG Blevins, JE Baskin, DG Schwartz, MW AF Morton, GJ Niswender, KD Rhodes, CJ Myers, MG Blevins, JE Baskin, DG Schwartz, MW TI Arcuate nucleus-specific leptin receptor gene therapy attenuates the obesity phenotype of Koletsky (fa(k)/fa(k)) rats SO ENDOCRINOLOGY LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; PROOPIOMELANOCORTIN MESSENGER-RNA; DB/DB MICE; OB/OB MICE; FEEDING-BEHAVIOR; BODY-WEIGHT; OB PROTEIN; BRAIN-STEM; IN-VIVO; EXPRESSION AB Leptin signaling in the hypothalamic arcuate nucleus (ARC) is hypothesized to play an important role in energy homeostasis. To investigate whether leptin signaling limited to this brain area is sufficient to reduce food intake and body weight, we used adenoviral gene therapy to express the signaling isoform of the leptin receptor, lepr(b), in the ARC of leptin receptor-deficient Koletsky (fa(k)/fa(k)) rats. Successful expression of adenovirus containing lepr(b) (Ad-lepr(b)) selectively in the ARC was documented by in situ hybridization. Using real-time PCR, we further demonstrated that bilateral microinjection of Ad-lepr(b) into the ARC restored low hypothalamic levels of lepr(b) mRNA to values approximating those of wild-type (Fa(k)/Fa(k)) controls. Restored leptin receptor expression in the ARC reduced both mean daily food intake (by 13%) and body weight gain (by 33%) and increased hypothalamic proopiomelanocortin mRNA by 65% while decreasing neuropeptide Y mRNA levels by 30%, relative to fa(k)/fa(k) rats injected with a control adenovirus (Ad-lacZ) (P<0.05 for each comparison). In contrast, Ad-lepr(b) delivery to either the lateral hypothalamic area of fa(k)/fa(k) rats or to the ARC of wild-type Fa(k)/Fa(k) rats had no effect on any of these parameters. These findings collectively support the hypothesis that leptin receptor signaling in the ARC is sufficient to mediate major effects of leptin on long-term energy homeostasis. Adenoviral gene therapy is thus a viable strategy with which to study the physiological importance of specific molecules acting in discrete brain areas. C1 Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. Univ Washington, Pacific NW Res Inst, Seattle, WA 98112 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98112 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98104 USA. Univ Washington, Dept Biol Struct, Seattle, WA 98104 USA. RP Schwartz, MW (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, 325 9th Ave,Box 359757, Seattle, WA 98104 USA. RI Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK-17047, DK-12829, DK-52989, DK-55269, DK-56731]; NINDS NIH HHS [NS-32273] NR 45 TC 120 Z9 122 U1 0 U2 5 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 MAY PY 2003 VL 144 IS 5 BP 2016 EP 2024 DI 10.1210/en.2002-0115 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 668BE UT WOS:000182269800044 PM 12697710 ER PT J AU Kim, JY Wand, MP Hauser, R Mukherjee, S Herrick, RF Christiani, DC AF Kim, JY Wand, MP Hauser, R Mukherjee, S Herrick, RF Christiani, DC TI Association of expired nitric oxide with occupational particulate exposure SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID FUEL-OIL ASH; DIESEL EXHAUST PARTICLES; AIRWAY INFLAMMATION; SMOKE; POLLUTION; SYNTHASE; PATHWAY; MARKERS; MICE AB Particulate air pollution has been associated with adverse respiratory health effects. This study assessed the utility of expired nitric oxide to detect acute airway responses to metal-containing fine particulates. Using a repeated-measures study design, we investigated the association between the fractional concentration of expired nitric oxide (FENO) and exposure to particulate matter with an aerodynamic mass median diameter of less than or equal to 2.5 mum (PM2.5) in boilermakers exposed to residual oil fly ash and metal fumes. Subjects were monitored for 5 days during boiler repair overhauls in 1999 (n = 20) or 2000 (n = 14). The Wilcoxon median baseline FENO was 10.6 ppb [95% confidence interval (CI): 9.1, 12.7] in 1999 and 7.4 ppb (95% CI: 6.7, 8.0) in 2000. The Wilcoxon median PM2.5 8-hr time-weighted average was 0.56 mg/m(3) (95% CI: 0.37, 0.93) in 1999 and 0.86 mg/m(3) (95% CI: 0.65, 1.07) in 2000. FENO, levels during the work week were significantly lower than baseline FENO in 1999 (p < 0.001). A significant inverse exposure-response relationship between log-transformed FENO and the previous workday's PM2.5 concentration was found in 1999, after adjusting for smoking status, age, and sampling year. With each 1 mg/m(3) incremental increase in PM2.5 exposure, log FENO, decreased by 0.24 (95% CI: -0.38, -0.10) in 1999. The lack of an exposure-response relationship between PM2.5 exposure and FENO in 2000 could be attributable to exposure misclassification resulting from the use of respirators. In conclusion, occupational exposure to metal-containing fine particulates was associated with significant decreases in FENO in a survey of workers with limited respirator usage. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm Sci & Engn Program, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Bldg 1,Rm 1402,665 Huntington Ave, Boston, MA 02115 USA. RI Wand, Matt /F-9413-2012 OI Wand, Matt /0000-0003-2555-896X FU NIEHS NIH HHS [ES00002, ES09860]; NIOSH CDC HHS [OH00152]; PHS HHS [T42110421] NR 33 TC 10 Z9 10 U1 0 U2 7 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 MAY PY 2003 VL 111 IS 5 BP 676 EP 680 DI 10.1289/ehp.5880 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 677CB UT WOS:000182788400022 PM 12727593 ER PT J AU Duty, SM Silva, MJ Barr, DB Brock, JW Ryan, L Chen, ZY Herrick, RF Christiani, DC Hauser, R AF Duty, SM Silva, MJ Barr, DB Brock, JW Ryan, L Chen, ZY Herrick, RF Christiani, DC Hauser, R TI Phthalate exposure and human semen parameters SO EPIDEMIOLOGY LA English DT Article DE semen quality; phthalate; urine; environment; human; epidemiology ID BUTYL BENZYL PHTHALATE; SEXUAL-DIFFERENTIATION; MALE-RAT; DIETHYLHEXYL PHTHALATE; REPRODUCTIVE-TRACT; QUALITY; SPERM; ESTERS; MEN; METABOLITES AB Background. There is scientific and public concern about commonly used chemicals, including phthalates, that are associated with reproductive toxicity in laboratory animals and are hormonally active. People are exposed to phthalates through diet, consumer products and medical devices. The present study explored whether environmental levels of phthalates are associated with altered semen quality in humans. Methods. We recruited 168 men who were part of subfertile couples and who presented to the Massachusetts General Hospital andrology laboratory for semen analysis between January 2000 and April 2001. Semen parameters were dichotomized based on 1999 World Health Organization reference values for sperm concentration (<20 million/ml) and motility (<50% motile), as well as Tygerberg Strict criteria for morphology (<4% normal). The comparison group was men for whom these semen parameters were all above the reference values. In urine, eight phthalate metabolites were measured with high-performance liquid chromatography and tandem mass spectrometry. Specific gravity-adjusted phthalate metabolite levels were categorized into tertiles. Results. There was a dose-response relation between tertiles of mono-butyl phthalate and sperm motility (odds ratio per tertile = 1.0, 1.8, 3.0; P-value for trend 0.02) and sperm concentration (1.0, 1.4, 3.3; P-value for trend 0.07). In addition, there was a dose-response relation between tertiles of monobenzyl phthalate and sperm concentration (1.0, 1.4, 5.5; P-value for trend = 0.02). Conclusions. There were dose-response relations for monobutyl phthalate and monobenzyl phthalate with one or more semen parameters, and suggestive evidence for monomethyl phthalate with sperm morphology. The lack of a relation for other phthalates may indicate a difference in spermatotoxicity among phthalates. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv Androl Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009; Barr, Dana/E-6369-2011; Barr, Dana/E-2276-2013 OI Ryan, Louise/0000-0001-5957-2490; FU NIEHS NIH HHS [ES00002, ES09718, T32 ES07069] NR 43 TC 220 Z9 233 U1 7 U2 40 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2003 VL 14 IS 3 BP 269 EP 277 DI 10.1097/00001648-200305000-00005 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 687TM UT WOS:000183393100005 PM 12859026 ER PT J AU Morrell, MJ Isojarvi, J Taylor, AE Dam, M Ayala, R Gomez, G O'Neill, F Tennis, P Messenheimer, J AF Morrell, MJ Isojarvi, J Taylor, AE Dam, M Ayala, R Gomez, G O'Neill, F Tennis, P Messenheimer, J TI Higher androgens and weight gain with valproate compared with lamotrigine for epilepsy SO EPILEPSY RESEARCH LA English DT Article DE valproate monotherapy; epilepsy; hyperandrogenism; lamotrigine monotherapy; weight gain; menstrual disturbances ID REPRODUCTIVE ENDOCRINE DISORDERS; POLYCYSTIC-OVARY-SYNDROME; TEMPORAL-LOBE EPILEPSY; RISK-FACTORS; WOMEN; HYPERANDROGENISM; OBESITY; MONOTHERAPY; HORMONES; SEIZURES AB Background: Valproate is used widely for the treatment of epilepsy but has been associated with hyperandrogenism, hyperinsulinemia, and dyslipidemia. The mechanism for these associations is unknown, but they have been hypothesized to be secondary to valproate-associated weight gain. This study was conducted to test the hypothesis that the antiepileptic drug lamotrigine, which also has a broad spectrum of anti-seizure efficacy, would not be associated with endocrine abnormalities and would not cause weight gain. Objective and Methods: This open-label, cross-sectional study compared (1) endocrine and lipid measures during the early follicular phase of the menstrual cycle, (2) prevalence of menstrual disorders (from patient diaries recorded over three cycles); and (3) body weight of women with epilepsy on lamotrigine monotherapy (n = 119) with those on valproate monotherapy (n = 103) for <5 years. Results: Mean total serum testosterone and androstenedione levels were higher (P < 0.02) in the valproate group compared with the lamotrigine group. More lamotrigine patients (87%) than valproate patients (77%) reported regular menstrual cycles at the Screening Visit. The prevalence of anovulation did not differ between lamotrigine and valproate. Mean HDL cholesterol levels were higher (P < 0.01) with lamotrigine compared with valproate as were LDL and total cholesterol levels (P < 0.05). Mean total insulin levels did not significantly differ between the groups. Whereas mean body weight in lamotrigine patients did not differ between the time lamotrigine treatment was initiated and the Study Visit, mean weight in valproate patients increased by 3.7 kg, Conclusions: Compared with lamotrigine monotherapy, valproate monotherapy was associated with weight gain and higher androgen levels in women with epilepsy. These data suggest that the hyperandrogenism observed in some women using valproate for epilepsy may be secondary to drug therapy. Lamotrigine monotherapy may be more appropriate than valproate for women whom reproductive endocrine or metabolic abnormalities are potential concerns, i.e. women with concerns about weight gain, diabetes, hirsutism, polycystic ovary syndrome, menstrual dysfunction or infertility. (C) 2003 Elsevier Science B.V. All rights reserved. C1 GlaxoSmithKline, Res Triangle Pk, NC 27709 USA. Columbia Univ, New York, NY USA. Univ Oulu, Oulu, Finland. Massachusetts Gen Hosp, Boston, MA 02114 USA. Aarhus Kommune Hosp, DK-8000 Aarhus, Denmark. AMO Corp, Tallahassee, FL USA. GlaxoSmithKline R&D, Greenford, Middx, England. RP Gomez, G (reprint author), GlaxoSmithKline, 5 Moore Dr, Res Triangle Pk, NC 27709 USA. NR 27 TC 73 Z9 76 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD MAY PY 2003 VL 54 IS 2-3 BP 189 EP 199 DI 10.1016/S0920-1211(03)00085-8 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 702KR UT WOS:000184223500012 PM 12837570 ER PT J AU Bornak, A Wicky, S Ris, HB Probst, H Milesi, I Corpataux, JM AF Bornak, A Wicky, S Ris, HB Probst, H Milesi, I Corpataux, JM TI Endovascular treatment of stenoses in the superior vena cava syndrome caused by non-tumoral lesions SO EUROPEAN RADIOLOGY LA English DT Article DE superior vena cava syndrome; endovascular stent; angioplasty; hemodialysis ID CENTRAL VENOUS OBSTRUCTION; STENT PLACEMENT; HEMODIALYSIS; OCCLUSION; ACCESS; WALLSTENT; ANGIOPLASTY; EXPERIENCE AB We report our experience in percutaneous treatment of non-tumoral superior vena cava syndrome (SVCS) between December 1998 and July 2001. During a period of 2.5 years, 9 patients (age range 27-84 years, mean age 50 years) were treated percutaneously for significant non-tumoral SVCS. Symptomatic SVCS were due to dialysis catheters (7), central line (1) and radiation therapy (1). In thrombotic occlusions and severe stenosis, a preliminary in situ thrombolysis was achieved before angioplasty. Patients were followed by echo-Doppler, computed tomography angiography (CTA), magnetic resonance angiography (MRA), or phlebography. Complete recanalization of the veins and immediate resolution of symptomatic SVCS were obtained in all patients, with no procedure-related complication. Thirteen stents were placed in 9 patients with a mean clinical follow-up of 9.1 months (range 2-23 months). One hundred percent patency at 6 months was obtained. Two patients recurred twice and were treated with new stent placement. At 12 months the patency was 67% and assisted patency was 100%. Stent placement in benign symptomatic SVCS is a safe and minimally invasive procedure, with no technical and clinical complications in our experience. It allowed immediate relief of symptoms, and in dialysed patients could provide continued use of hemodialysis access. Close clinical surveillance is mandatory to assess stent patency. C1 CHU Vaudois, Dept Thorac & Vasc Surg, CH-1011 Lausanne, Switzerland. CHU Vaudois, Dept Angiol, CH-1011 Lausanne, Switzerland. CHU Vaudois, Dept Radiodiagnost & Intervent Radiol, CH-1011 Lausanne, Switzerland. RP Wicky, S (reprint author), Massachusetts Gen Hosp, CIMIT Div, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. NR 30 TC 29 Z9 32 U1 1 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD MAY PY 2003 VL 13 IS 5 BP 950 EP 956 DI 10.1007/s00330-002-1637-2 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 677DE UT WOS:000182791000005 PM 12695814 ER PT J AU Liu, XM Chapman, GB Peyton, KJ Schafer, AI Durante, W AF Liu, XM Chapman, GB Peyton, KJ Schafer, AI Durante, W TI Antiapoptotic action of carbon monoxide on cultured vascular smooth muscle cells SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE cell death; circulation; cell cycle ID HEME OXYGENASE; GUANYLYL CYCLASE; APOPTOSIS; EXPRESSION; ATHEROSCLEROSIS; INHIBITOR; GROWTH; ENZYME AB Vascular smooth muscle cells (SMCs) generate carbon monoxide (CO) from the degradation of heme by the enzyme heme oxygenase. Because recent studies indicate that CO influences the properties of vascular SMCs, we examined whether this diatomic gas regulates apoptosis in vascular SMCs. Treatment of cultured rat aortic SMCs with a cytokine cocktail consisting of interleukin-1beta (5 ng/ml), tumor necrosis factor-alpha (20 ng/ml), and interferon-gamma (200 U/mI) for 48 hr stimulated apoptosis, as demonstrated by DNA laddering, caspase-3 activation, and annexin V staining. However, the exogenous addition of CO (200 ppm) completely blocked cytokine-mediated apoptosis. The antiapoptotic action of CO was partially reversed by the soluble guanylate cyclase inhibitor, H-[1,2,4]oxadiazolo[4,3a]quinoxalin-1-one (10 muM). In contrast, the p38 mitogen-activated protein kinase inhibitor, SB203580 (10 muM), had no effect on SMC apoptosis. These findings indicate that CO is a potent inhibitor of vascular SMC apoptosis and that it blocks apoptosis, in part, by activating the cGMP signaling pathway. The ability of CO to inhibit vascular SMC apoptosis may play a critical role in attenuating lesion formation at sites of arterial damage. C1 Baylor Coll Med, Houston 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), VA Med Ctr Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM wdurante@bcm.tmc.edu FU NHLBI NIH HHS [HL62467, HL59976, HL36045] NR 26 TC 31 Z9 34 U1 0 U2 2 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD MAY PY 2003 VL 228 IS 5 BP 572 EP 575 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 833ER UT WOS:000222319700025 PM 12709589 ER PT J AU Magavi, SSP Mitchell, BD Szentirmai, O Chen, J Carter, BS Macklis, JD AF Magavi, SSP Mitchell, BD Szentirmai, O Chen, J Carter, BS Macklis, JD TI Experience-dependent modification of adult-born olfactory neurons. SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 10th Annual Conference of the American-Society-for-Neural-Transplantation-and-Repair CY MAY 01-04, 2003 CL CLEARWATER, FLORIDA SP Amer Soc Neural Transplantat & Repair C1 Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurosci, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH HMS Ctr Nervous Syst Repair, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2003 VL 181 IS 1 BP 98 EP 98 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 672NQ UT WOS:000182527400064 ER PT J AU Ourednik, J Van der Loos, H Mitchell, DE Schachner, M Snyder, EY Ourednik, V AF Ourednik, J Van der Loos, H Mitchell, DE Schachner, M Snyder, EY Ourednik, V TI Neuroprotection and rescue are essential features of the restorative capacity of transplanted neural progenitors. SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 10th Annual Conference of the American-Society-for-Neural-Transplantation-and-Repair CY MAY 01-04, 2003 CL CLEARWATER, FLORIDA SP Amer Soc Neural Transplantat & Repair C1 Iowa State Univ, Dept Biomed Sci, Ames, IA 50011 USA. Univ Lausanne, Inst Anat, CH-1008 Lausanne, Switzerland. Dalhousie Univ, Dept Psychol, Halifax, NS B3H 4J1, Canada. Univ Hamburg, Ctr Mol Biol, D-20246 Hamburg, Germany. Harvard Univ, Sch Med, BIDMC, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2003 VL 181 IS 1 BP 101 EP 102 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 672NQ UT WOS:000182527400077 ER PT J AU Ourednik, V Schachner, M Snyder, EY Lynch, WP Ourednik, J AF Ourednik, V Schachner, M Snyder, EY Lynch, WP Ourednik, J TI Rescue of impaired host dopaminergic neurons and the role of overexpressed neural cell adhesion molecule L1 in aged mice grafted with neural stem cells (NSCS). SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 10th Annual Conference of the American-Society-for-Neural-Transplantation-and-Repair CY MAY 01-04, 2003 CL CLEARWATER, FLORIDA SP Amer Soc Neural Transplantat & Repair C1 Iowa State Univ, Coll Vet Med, Dept Biomed Sci, Ames, IA 50011 USA. Harvard Univ, Sch Med, BIDMC, Boston, MA 02115 USA. NE Ohio Univ, Coll Med, Dept Microbiol & Immunol, Rootstown, OH 44272 USA. Univ Hamburg, Ctr Mol Neurobiol, D-20246 Hamburg, Germany. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2003 VL 181 IS 1 BP 101 EP 101 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 672NQ UT WOS:000182527400076 ER PT J AU Guerra, DR Karha, J Gibson, CM AF Guerra, DR Karha, J Gibson, CM TI Safety and efficacy of tenecteplase in acute myocardial infarction SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE acute myocardial infarction; tenecteplase ID TISSUE-PLASMINOGEN-ACTIVATOR; PRIMARY CORONARY ANGIOPLASTY; SINGLE-BOLUS TENECTEPLASE; FRONT-LOADED ALTEPLASE; THROMBOLYTIC THERAPY; RANDOMIZED TRIAL; FIBRINOLYTIC THERAPY; ARTERY PATENCY; FRAME COUNT; B-10 TRIAL AB The use of intravenous thrombolytic agents has revolutionised the treatment of acute myocardial infarction. However, the improved mortality achieved with these drugs is tempered by the risk of serious bleeding complications, especially intracranial haemorrhage (ICH). Tenecteplase (TNKase(TM), Genetech Inc.) is an engineered variant of alteplase (Activase(R), Genentech Inc.) designed to have increased fibrin specificity, greater efficacy and a longer half-life. The longer half-life of tenecteplase compared to alteplase allows for convenient single bolus administration of the drug. In addition, tenecteplase dosing is based on actual or estimated patient weight, which enhances both the safety and efficacy outcomes. Large clinical trials have demonstrated equivalence in mortality and ICH between tenecteplase and alteplase. Compared to alteplase, tenecteplase, use leads to lower rates of bleeding complications and a decreased risk of ICH among low weight, elderly women. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Gibson, CM (reprint author), TIMI Data Coordinating Ctr, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. NR 45 TC 13 Z9 15 U1 2 U2 3 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD MAY PY 2003 VL 4 IS 5 BP 791 EP 798 DI 10.1517/14656566.4.5.791 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 695ZU UT WOS:000183860900014 PM 12740001 ER PT J AU Carlson, JA Slominski, A Linette, GP Mihm, MC Ross, JS AF Carlson, JA Slominski, A Linette, GP Mihm, MC Ross, JS TI Biornarkers in melanoma: staging, prognosis and detection of early metastases SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE biomarkers; melanoma; metastases; prognosis; staging ID CUTANEOUS MALIGNANT-MELANOMA; POLYMERASE-CHAIN-REACTION; SENTINEL LYMPH-NODE; AMERICAN-JOINT-COMMITTEE; POSITRON-EMISSION-TOMOGRAPHY; TYROSINASE-MESSENGER-RNA; VERTICAL GROWTH-PHASE; IMMUNE-COMPLEX ASSAY; INTERCELLULAR-ADHESION MOLECULE-1; DESMOPLASTIC NEUROTROPIC MELANOMA AB Currently, melanoma remains a surgical disease since early detection and excision of thin melanomas offers the best chance of a cure. Despite intensive clinical investigation, no effective systemic therapies exist for metastatic melanoma. Sentinel lymph node biopsy has greatly aided the staging and prognostic evaluation of primary cutaneous melanoma, however, approximately a third of patients diagnosed with metastatic melanomas present without prior regional lymph node involvement. Additional prognostic biomarkers exist which help determine the risk of advanced melanoma but the accuracy for each current marker is less than 100%. A greater understanding of the biology of melanomas and the development of new methods to identify patients with early (subclinical) metastatic disease may allow for selective and more effective therapy for patients at-risk for advanced disease. In this paper, current and novel potentially more accurate biomarkers for the staging and prognostic evaluation of melanoma patients, and for the detection of subclinical metastases are reviewed. C1 Albany Med Coll MC81, Div Dermatopathol, Albany, NY 12208 USA. Millennium Pharmaceut Inc, Div Dermatopathol, Cambridge, MA USA. Washington Univ, Dept Med, St Louis, MO 63110 USA. Albany Med Coll MC81, Dept Pathol & Lab Med, Albany, NY 12208 USA. Univ Tennessee, Ctr Hlth Sci, Dept Pathol & Lab Med, Memphis, TN 38163 USA. Massachusetts Gen Hosp, Div Mol Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Carlson, JA (reprint author), Albany Med Coll MC81, Div Dermatopathol, Albany, NY 12208 USA. EM carlsoa@mail.amc.edu; aslominski@utmem.edu; linette@mpi.com; martin.mihm@mgh.harvard.edu; rossj@mail.amc.edu OI Carlson, John Andrew/0000-0002-6866-6314 NR 302 TC 17 Z9 17 U1 0 U2 3 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAY PY 2003 VL 3 IS 3 BP 303 EP 330 DI 10.1586/14737159.3.3.303 PG 28 WC Pathology SC Pathology GA 767KB UT WOS:000188437800004 PM 12779006 ER PT J AU Zhang, XP Graham, SH Kochanek, PM Marion, DW Nathaniel, PD Watkins, SC Clark, RSB AF Zhang, XP Graham, SH Kochanek, PM Marion, DW Nathaniel, PD Watkins, SC Clark, RSB TI Caspase-8 expression and proteolysis in human brain after severe head injury SO FASEB JOURNAL LA English DT Article DE apoptosis; cysteine protease; Fas; programmed cell death; traumatic brain injury ID TUMOR-NECROSIS-FACTOR; CEREBROSPINAL-FLUID; NEURONAL APOPTOSIS; FAS LIGAND; CELL-DEATH; SIGNALING COMPLEX; ACTIVATION; MICE; CONTUSIONS; INDUCTION AB Programmed cell death involves a complex and interrelated cascade of cysteine proteases termed caspases that are synthesized as inactive zymogens, which are proteolytically processed to active enzymes. Caspase-8 is an initiator caspase that becomes activated when Fas death receptor-Fas ligand (FasL) coupling on the cell surface leads to coalescence of a "death complex" perpetuating the programmed cell death cascade. In this study, brain tissue samples removed from adult patients during the surgical management of severe intracranial hypertension after traumatic brain injury (TBI; n=17) were compared with postmortem control brain tissue samples (n=6). Caspase-8 mRNA was measured by semiquantitative reverse transcription and polymerase chain reaction, and caspase-8 protein was examined by Western blot and immunocytochemistry. Fas and FasL were also examined using Western blot. Caspase-8 mRNA and protein were increased in TBI patients vs. controls, and caspase-8 protein was predominately expressed in neurons. Proteolysis of caspase-8 to 20-kDa fragments was seen only in TBI patients. Fas was also increased after TBI vs. control and was associated with relative levels of caspase-8, supporting formation of a death complex. These data identify additional steps in the programmed cell death cascade involving Fas death receptors and caspase-8 after TBI in humans. C1 Safar Ctr Resuscitat Res, Dept Crit Care Med, Pittsburgh, PA 15260 USA. Safar Ctr Resuscitat Res, Dept Neurol, Pittsburgh, PA USA. Safar Ctr Resuscitat Res, Dept Pediat, Pittsburgh, PA USA. Safar Ctr Resuscitat Res, Dept Neurol Surg, Pittsburgh, PA USA. Safar Ctr Resuscitat Res, Dept Cell Biol & Physiol, Pittsburgh, PA USA. Univ Pittsburgh, Brain Trauma Res Ctr, Pittsburgh, PA USA. VA Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Clark, RSB (reprint author), Safar Ctr Resuscitat Res, Dept Crit Care Med, 3434 5th Ave, Pittsburgh, PA 15260 USA. EM clarkrs@ccm.upmc.edu RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X NR 33 TC 33 Z9 37 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2003 VL 17 IS 8 BP 1367 EP + DI 10.1096/fj.02-1067fje PG 17 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 683TE UT WOS:000183165000027 PM 12738800 ER PT J AU Fulci, G Chiocca, EA AF Fulci, G Chiocca, EA TI Oncolytic viruses for the therapy of brain tumors and other solid malignancies: A review SO FRONTIERS IN BIOSCIENCE LA English DT Review DE gene therapy; treatment; tumors; cancer; virus; oncolytic virus; review ID HERPES-SIMPLEX VIRUS; REPLICATING HUMAN ADENOVIRUS; RECOMBINANT VACCINIA VIRUS; VESICULAR STOMATITIS-VIRUS; THYMIDINE KINASE GENE; PHASE-I TRIAL; ACTIVATED PROTEIN-KINASE; DIFFUSE LIVER METASTASES; MONOCLONAL-ANTIBODY DF3; NECROSIS-FACTOR-ALPHA AB In spite of significant advances in the understanding of molecular processes in tumor biology that have led to the development of oncologic therapeutic strategies, the prognosis for several types of tumors ( such as brain, pancreas, or hepatic malignancies) remains dismal. Without question, a strong need exists for continued investigations in new agents and new therapeutic regimens. The realization that several genes used by viruses in their lytic life cycle interact and/or complement the function of genes employed by cells in cellular events linked to cell cycle progression, apoptosis, and/or metabolism immediately suggests the development of treatment strategies wherein viral mutants could be employed as selective anticancer agents. Such viruses ( designated as oncolytic viruses) can selectively grow in tumor cells, produce viral progeny in those cells, lyse them and release this progeny that can then infect additional cells in the tumor mass. A theoretical advantage of oncolytic viruses (OV) is that their numbers should augment within the tumor mass, a property that is lacking with drugs or radiation treatments. Additionally, Ovs' mode of tumor killing differs from standard anticancer agents, providing the possibility for synergistic interactions in multimodal tumor therapies. In this review, we will describe the development of OVs and briefly review the life cycle of their wild-type (wt) counterparts. We will also summarize published results from OV clinical trials and attempt to provide a perspective on research in this area. C1 Massachusetts Gen Hosp, Mol Neurooncol Labs, Charlestown, MA 02129 USA. RP Fulci, G (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Labs, E Bldg,CNY6,13th St, Charlestown, MA 02129 USA. NR 154 TC 20 Z9 21 U1 0 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY PY 2003 VL 8 BP E346 EP E360 DI 10.2741/976 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 669LG UT WOS:000182352300058 PM 12700108 ER PT J AU Friedman, LS AF Friedman, LS TI Our new president - Daniel K. Podolsky, MD SO GASTROENTEROLOGY LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Friedman, LS (reprint author), Massachusetts Gen Hosp Blake 456D, Med Serv, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 MAY PY 2003 VL 124 IS 5 BP 1524 EP 1531 DI 10.1016/S0016-5085(03)00343-3 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 673GF UT WOS:000182571800037 PM 12730890 ER PT J AU Cummings, DE Foster, KE AF Cummings, DE Foster, KE TI Ghrelin-leptin tango in body-weight regulation SO GASTROENTEROLOGY LA English DT Editorial Material ID INSULIN-INDUCED HYPOGLYCEMIA; FOOD-INTAKE; SECRETION; STOMACH; ADIPOSITY; PEPTIDE; RODENTS; OBESITY C1 Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. RP Cummings, DE (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 1660 S Columbian Way,S-111-Endo, Seattle, WA 98108 USA. NR 26 TC 104 Z9 107 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2003 VL 124 IS 5 BP 1532 EP 1535 DI 10.1016/S0016-5085(03)00350-0 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 673GF UT WOS:000182571800038 PM 12730891 ER PT J AU Datto, CJ Thompson, R Horowitz, D Disbot, M Oslin, DW AF Datto, CJ Thompson, R Horowitz, D Disbot, M Oslin, DW TI The pilot study of a telephone disease management program for depression SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE depression; disease management; primary care; treatment algorithm; treatment adherence ID PRIMARY-CARE; PRACTICE GUIDELINES; RANDOMIZED TRIAL; HEALTH; DISORDERS; SYSTEM AB Most depressed patients are seen and treated exclusively by primary care clinicians. However, primary care patients with depression are often not adequately treated. The aims of this pilot study were to measure the impact of a telephone disease management program on patient outcome and clinician adherence to practice guidelines, measure the relationship of clinician adherence to patient outcome, and explore the measurement of patient adherence to clinician recommendations and its impact on patient outcomes. Thirty-five primary care practices in the University of Pennsylvania Health System were randomized to telephone disease management (TDM) or "usual care" (UC). All patients received a baseline and a 16-week follow-up clinical evaluation performed over the telephone. Those from TDM practices also received follow-up contact at least every 3 weeks, with formal evaluations at weeks 6 and 12. These interval contacts were designed to facilitate patient and clinician adherence to a treatment algorithm based on the Agency for Health Research and Quality (AHRQ) practice guidelines. Depressive symptoms evaluated with the Community Epidemiologic Survey of Depression (CES-D) scale as well as guideline adherence were the primary outcome measures. Sixty-one patients were enrolled in this pilot project. The overall effect for CES-D scores over time was significant, (P < .001), indicating that those participating in the trial (both TDM and UC groups) showed significant improvement. The interaction between intervention condition and time was also significant (P < .05), indicating that TDM patients improved significantly more over time than did UC patients. A greater proportion of TDM patients had CES-D scores <16 by Week 16 (66.7 versus 33.3%; chi(2), p < .05). The improvement in depression outcome for the TDM group was related to its impact on improving clinician adherence to depression treatment algorithms. The TDM pilot did not show a statistically significant effect on improving patient adherence to clinician recommendations, however. This preliminary data suggests that TDM for depression improves both clinician guideline adherence and patient outcomes in the acute phase of depression. The effect on patient outcome is at least partially explained by the effect of TDM on clinician adherence to depression treatment algorithms. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Penn, Hlth Syst, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Oslin, DW (reprint author), Univ Penn, Hlth Syst, Philadelphia, PA 19104 USA. RI Thompson, Richard/G-5408-2011 OI Thompson, Richard/0000-0003-0127-513X FU PHS HHS [P30 52129] NR 23 TC 31 Z9 32 U1 0 U2 0 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 MAY-JUN PY 2003 VL 25 IS 3 BP 169 EP 177 DI 10.1016/S0163-8343(03)00019-7 PG 9 WC Psychiatry SC Psychiatry GA 679YT UT WOS:000182950100004 PM 12748029 ER PT J AU Lasser, KE Zeytinoglu, H Miller, E Becker, AE Hermann, RC Bor, DH AF Lasser, KE Zeytinoglu, H Miller, E Becker, AE Hermann, RC Bor, DH TI Do women who screen positive for mental disorders in primary care have lower mammography rates? SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE prevention; internal medicine ID PREVENTIVE MEDICAL-SERVICES; BREAST-CANCER; PSYCHIATRIC-PATIENTS; RISK AB Disparities in mammography rates have been documented for underserved populations, yet no data are available for women with mental illness in primary care settings. We analyzed data on mammography rates for 526 women age 40-70 who were new patients and completed the Primary Care Evaluation of Mental Disorders (PRIME-MD). There were no significant differences in mammography rates among women who screened negative and positive for any mental illness (56% and 53%, respectively). Screening for mental disorders in primary care does not appear to identify women at risk for nonreceipt of mammography. (C) 2003 Elsevier Inc. All rights reserved. C1 Cambridge Hlth Alliance, Dept Med, Cambridge, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Cambridge Hlth Alliance, Dept Clin Informat, Cambridge, MA USA. Massachusetts Gen Hosp, Stoeckle Ctr Primary Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. McLean Hosp, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Belmont, MA 02178 USA. RP Lasser, KE (reprint author), Cambridge Hlth Alliance, Dept Med, Cambridge, MA USA. RI Miller, Elizabeth/E-7939-2012 NR 11 TC 25 Z9 25 U1 0 U2 3 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 MAY-JUN PY 2003 VL 25 IS 3 BP 214 EP 216 DI 10.1016/S0163-8343(02)00014-8 PG 3 WC Psychiatry SC Psychiatry GA 679YT UT WOS:000182950100010 PM 12748035 ER PT J AU Lallemand, D Curto, M Saotome, I Giovannini, M McClatchey, AI AF Lallemand, D Curto, M Saotome, I Giovannini, M McClatchey, AI TI NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions SO GENES & DEVELOPMENT LA English DT Article DE NF2; merlin; tumor suppressor; metastasis; cytoskeleton; adherens junction ID TUMOR-SUPPRESSOR GENE; CELL-CELL ADHESION; NEUROFIBROMATOSIS TYPE-2; ACTIN CYTOSKELETON; E-CADHERIN; EPITHELIAL-CELLS; MERLIN; PRODUCT; DYNAMICS; PROTEIN AB Mutation of the Neurofibromatosis 2 (NF2) tumor suppressor gene leads to cancer development in humans and mice. Recent studies suggest that Nf2 loss also contributes to tumor metastasis. The Nf2-encoded protein, merlin, is related to the ERM ((e) under bar zrin, (r) under bar adixin, and (m) under bar oesin) family of membrane:cytoskeleton-associated proteins. However, the cellular mechanism whereby merlin controls cell proliferation from this location is not known. Here we show that the major cellular consequence of Nf2 deficiency in primary cells is an inability to undergo contact-dependent growth arrest and to form stable cadherin-containing cell:cell junctions. Merlin colocalizes and interacts with adherens junction (AJ) components in confluent wild-type cells, suggesting that the lack of AJs and contact-dependent growth arrest in Nf2(-/-) cells directly results from the absence of merlin at sites of cell:cell contact. Our studies indicate that merlin functions as a tumor and metastasis suppressor by controlling cadherin-mediated cell:cell contact. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. Ctr Etud Polymorphisme Humain, INSERM 434, Fondat Jean Dausset, F-75010 Paris, France. RP McClatchey, AI (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. NR 41 TC 186 Z9 189 U1 1 U2 13 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 MAY 1 PY 2003 VL 17 IS 9 BP 1090 EP 1100 DI 10.1101/gad.1054603 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 675AU UT WOS:000182671500004 PM 12695331 ER PT J AU Witmer, PD Doheny, KF Adams, MK Boehm, CD Dizon, JS Goldstein, JL Templeton, TM Wheaton, AM Dong, PN Pugh, EW Nussbaum, RL Hunter, K Kelmenson, JA Rowe, LB Brownstein, MJ AF Witmer, PD Doheny, KF Adams, MK Boehm, CD Dizon, JS Goldstein, JL Templeton, TM Wheaton, AM Dong, PN Pugh, EW Nussbaum, RL Hunter, K Kelmenson, JA Rowe, LB Brownstein, MJ TI The development of a highly informative mouse simple sequence length polymorphism (SSLP) marker set and construction of a mouse family tree using parsimony analysis (vol 13, pg 485, 2003) SO GENOME RESEARCH LA English DT Correction C1 Microbia Inc, Cambridge, MA 02141 USA. GeneData USA Inc, Waltham, MA 02451 USA. Univ Maryland, Dept Biol, College Pk, MD 20742 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Genome Therapeut Corp, Waltham, MA 02453 USA. RP Witmer, PD (reprint author), Microbia Inc, Cambridge, MA 02141 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAY PY 2003 VL 13 IS 5 BP 1027 EP 1027 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 674PQ UT WOS:000182645500030 ER PT J AU DeVito, C Morgan, RO Duque, M Abdel-Moty, E Virnig, BA AF DeVito, C Morgan, RO Duque, M Abdel-Moty, E Virnig, BA TI Physical performance effects of low-intensity exercise among clinically defined high-risk elders SO GERONTOLOGY LA English DT Article DE high-risk elders; equilibrium; exercise; gait; muscle strength ID RANDOMIZED CONTROLLED TRIAL; OLDER ADULTS; MUSCLE STRENGTH; FALLS; BALANCE; WOMEN; GAIT; MOBILITY; MEN; FRAILTY AB Background: Falls are among the leading causes of injuries and deaths. Results from a number of studies have suggested that a community-based exercise program may be effective in improving lower body strength, although some have shown only limited improvements. However, the impact of these programs on gait and balance are equivocal. Further, studies that have specifically targeted deconditioned elderly individuals, rather than individuals drawn from the general community, either showed limited or no improvements in gait and balance. Objective: This study examined the effectiveness of a community-based, short-term, low-intensity exercise intervention strategy on measures of mobility skills, gait and balance, and muscle strength for a clinically targeted group of elderly individuals at high risk of falls. Methods: 245 men and women aged 60 years or older were randomized into either an intervention or control group and received a baseline (T1) assessment. Subjects in the intervention group received up to 24 sessions (45 min long) of low-intensity standard exercise modalities tailored to the individual patient over an 8- to 10-week period. At the conclusion of the program, the participants in the intervention group were instructed to continue performing the exercises at home until 1 year after T1. Measures of physical function and performance were collected for all subjects at three different points of study enrollment. Results: Of the subjects assessed at baseline, 138 (56%) also had a postintervention assessment (T2), 128 (52%) had a 6-month follow-up assessment (T3), and 105 subjects had assessments at all time points. Primary analyses were based on the 105 subjects who had assessments at all time points. Intervention and control subjects did not differ in any of the physical function or performance measures at baseline. Between T1 and T2, the intervention subjects showed significantly greater improvement than the control subjects on all outcomes, with improvements plateauing for most measures between T2 and T3. Gait and balance scores continued to improve throughout the study period for both groups of subjects. Conclusions: This easily implemented, low-intensity exercise program may lead to improvements in physical functioning that are retained over the long term and effectively targets a clinically defined population of deconditioned elders at high risk of falling and sustaining serious injury. Copyright (C) 2003 S. Karger AG, Basel. C1 Dept Vet Affairs Med Ctr, Res Serv 151, Hlth Serv Res & Dev Ctr, GRECC, Miami, FL 33125 USA. Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL USA. Houston VAMC, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Miami, Sch Educ, Dept Exercise & Sport Sci, Coral Gables, FL 33124 USA. Univ Miami, Coll Engn, Dept Ind Engn, Coral Gables, FL 33124 USA. Univ Miami, Sch Med, Miami Beach, FL USA. Univ Miami, S Shore Hosp & Med Ctr, Comprehens Pain & Rehabil Ctr, Miami Beach, FL USA. Univ Minnesota, Sch Publ Hlth, Div Hlth Serv Res & Policy, Minneapolis, MN 55455 USA. RP DeVito, C (reprint author), Dept Vet Affairs Med Ctr, Res Serv 151, Hlth Serv Res & Dev Ctr, GRECC, 1201 NW 16th St, Miami, FL 33125 USA. RI Morgan, Robert/A-8577-2009 NR 46 TC 24 Z9 26 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0304-324X J9 GERONTOLOGY JI Gerontology PD MAY-JUN PY 2003 VL 49 IS 3 BP 146 EP 154 DI 10.1159/000069168 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 671QD UT WOS:000182474800002 PM 12679604 ER PT J AU Holt, DJ Phillips, KA Shapiro, ER Becker, AE AF Holt, DJ Phillips, KA Shapiro, ER Becker, AE TI "My face is my fate": Biological and psychosocial approaches to the treatment of a woman with obsessions and delusions SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE biopsychosocial; bipolar disorder; body dysmorphic disorder; cross-cultural; delusion; obsession; phenomenology; psychopathology models; psychosis; psychotherapy ID BODY DYSMORPHIC DISORDER; AFFECTIVE SPECTRUM DISORDER; CONTROLLED TRIAL; MENTAL-HEALTH; FAMILY; CHINA C1 Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brown Med Sch, Dept Psychiat, Providence, RI USA. Butler Hosp, Providence, RI 02906 USA. Harvard Univ, Sch Med, Dept Social Med, Cambridge, MA 02138 USA. RP Holt, DJ (reprint author), Massachusetts Gen Hosp E, CNY-9,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIMH NIH HHS [K24 MH063975] NR 36 TC 1 Z9 1 U1 1 U2 2 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2003 VL 11 IS 3 BP 142 EP 154 DI 10.1080/10673220390217917 PG 13 WC Psychiatry SC Psychiatry GA 696GY UT WOS:000183880300003 PM 12893504 ER PT J AU Dickler, R Blumenthal, D Evans, C AF Dickler, R Blumenthal, D Evans, C TI Do teaching hospitals need sweeping changes? SO HOSPITALS & HEALTH NETWORKS LA English DT Editorial Material C1 Assoc Amer Med Coll, Div Hlth Care Affairs, Washington, DC 20037 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Assoc Amer Med Coll, Amer Network Hlth Promoting Univ, Washington, DC USA. RP Dickler, R (reprint author), Assoc Amer Med Coll, Div Hlth Care Affairs, Washington, DC 20037 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HEALTH FORUM INC PI CHICAGO PA ONE NORTH FRANKLIN ST, CHICAGO, IL 60606 USA SN 1068-8838 J9 HOSP HEALTH NETWORK JI Hosp. Health Netw. PD MAY PY 2003 VL 77 IS 5 BP 30 EP 30 PG 1 WC Health Policy & Services SC Health Care Sciences & Services GA 678AW UT WOS:000182843500012 PM 12809127 ER PT J AU Hampl, JA Camp, SM Mydlarz, WK Hampl, M Ichikawa, T Chiocca, EA Louis, DN Sena-Esteves, M Breakefield, XO AF Hampl, JA Camp, SM Mydlarz, WK Hampl, M Ichikawa, T Chiocca, EA Louis, DN Sena-Esteves, M Breakefield, XO TI Potentiated gene delivery to tumors using herpes simplex virus/Epstein-Barr virus/RV tribrid amplicon vectors SO HUMAN GENE THERAPY LA English DT Article ID MALIGNANT BRAIN-TUMORS; PACKAGING CELL-LINE; RECOMBINANT RETROVIRUSES; THYMIDINE KINASE; PRODUCER CELLS; GLIOMA-CELLS; THERAPY; REPLICATION; EXPRESSION; ADENOVIRUS AB The development and use of gene transfer techniques creates an opportunity to achieve better treatment modalities for numerous disease entities. Promising results for treatment in tumor cells in culture and in small animal models have been reported. Nevertheless, the lack of widespread vector distribution throughout tumor tissue is one of the current limitations for successful clinical application of gene therapy paradigms. The use of migratory tumor cells themselves as vector delivery vehicles may allow wider vector distribution in tumors. In addition, continuous release of retrovirus vectors on-site could generate a high local virion concentration over an extended time period with consequent increases in transduction efficiency. In this paper, we present in culture and in vivo data of a herpes simplex virus-Epstein-Barr virus hybrid amplicon vector containing retrovirus vector components (tribrid vector) that allows conversion of tumor cells into retroviral producer cells. With this method, we were able to achieve a local fourfold amplification of stable transgene expression in tumors. The application of this system, which can integrate a transgene cassette into tumors with therapeutic bystander effects, could increase the local amplification effect to a level of clinical relevance. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol & Radiol, Charlestown, MA 02129 USA. Univ Cologne, Dept Neurosurg, D-50924 Cologne, Germany. Univ Dusseldorf, Dept Obstet & Gynecol, D-40225 Dusseldorf, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. Childrens Hosp Philadelphia, Dept Surg, Philadelphia, PA 19104 USA. RP Hampl, JA (reprint author), Massachusetts Gen Hosp E, Dept Neurol, Neurogenet Unit, CNY 6205, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA-69246]; NINDS NIH HHS [NS-24279] NR 56 TC 18 Z9 19 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 MAY PY 2003 VL 14 IS 7 BP 611 EP 626 DI 10.1089/104303403321618137 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 681NU UT WOS:000183042900002 PM 12804144 ER PT J AU Nenguke, T Aladjem, MI Gusella, JF Wexler, NS Arnheim, N AF Nenguke, T Aladjem, MI Gusella, JF Wexler, NS Arnheim, N CA Venezuela HD Project TI Candidate DNA replication initiation regions at human trinucleotide repeat disease loci SO HUMAN MOLECULAR GENETICS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; CPG ISLANDS; CTG REPEAT; SOMATIC INSTABILITY; HUMAN-CELLS; ORIGIN; EXPANSION; ORIENTATION; SITES; YEAST AB The positions of DNA replication initiation regions (IRs) at three human trinucleotide repeat (TNR) disease loci were examined in order to characterize the role played by IRs in explaining the known locus-specific variation in TNR instability levels. Using three different normal cell lines, candidate IRs were identified at the HD, SCA-7 and SBMA loci. At each locus the IR is less than 3.6 kb from the CAG/CTG repeat tract. Preliminary studies with a cell line homozygous for an HD disease mutation indicated no change in the position of the candidate IR in spite of the mutation. Comparison with experimental results from model systems suggests that a complex relationship may exist between instability and the proximity and/or orientation of the repeats with respect to an IR. C1 Univ So Calif, Program Mol & Computat Biol, Los Angeles, CA 90089 USA. NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Psychiat, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Hereditary Dis Fdn, New York, NY 10032 USA. RP Arnheim, N (reprint author), Univ So Calif, Program Mol & Computat Biol, Los Angeles, CA 90089 USA. RI Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 NR 48 TC 26 Z9 26 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 1 PY 2003 VL 12 IS 9 BP 1021 EP 1028 DI 10.1093/hmg/ddg111 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 674WQ UT WOS:000182660500007 PM 12700170 ER PT J AU Teixeira, CA Espinola, J Huo, L Kohlschutter, J Sawin, DAP Minassian, B Bessa, CJP Guimaraes, A Stephan, DA Miranda, MCS MacDonald, ME Ribeiro, MG Boustany, RMN AF Teixeira, CA Espinola, J Huo, L Kohlschutter, J Sawin, DAP Minassian, B Bessa, CJP Guimaraes, A Stephan, DA Miranda, MCS MacDonald, ME Ribeiro, MG Boustany, RMN TI Novel mutations in the CLN6 gene causing a variant late infantile neuronal ceroid lipofuscinosis SO HUMAN MUTATION LA English DT Article DE CLN6; Batten disease; neuronal ceroid lipofuscinosis; NCL; vLINCL; LINCL; neurodegeneration ID MUTANT MICE; PROTEIN AB The neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of autosomal recessive neurodegenerative diseases comprising Batten and other related diseases plus numerous variants. They are characterized by progressive neuronal cell death. The CLN6 gene was recently identified, mutations in which cause one of the variant late infantile forms of NCL (vLINCL). We describe four novel mutations in the CLN6 gene. This brings the total number of CLN6 mutations known to 11 in 38 families. This suggests that the CLN6 gene may be highly mutable. An American patient of Irish/French/Native American origin was heterozygous for a 4-bp insertion (c.267_268insAACG) in exon 3. The other allele had a point mutation (c.898T>C) in exon 7 resulting in a W300R amino acid change. Two Trinidadian siblings of Indian origin were homozygous for a mutation at the 5' donor splice site of exon 4 (IVS4+1G > T), affecting the first base of the invariant GTat the beginning of intron 4. The fourth novel mutation, a double deletion of 4 bp and 1 bp in exon 7 (c.829_832delGTCG;c.837delG), was identified in a Portuguese patient heterozygous for the 1154del Portuguese CLN6 mutation. Four of the 11 mutations identified are in exon 4. Three Portuguese patients with clinical profiles similar to CLN6 patients without defects in CLN6 or other known NCL genes are described. We conclude the following: 1) the CLN6 gene may be a highly mutable gene; 2) exon 4 must code for a segment of the protein crucial for function; 3) vLINCL disease in Portugal is genetically heterogeneous; 4) the 1154del accounts for 81.25% of affected CLN6 Portuguese alleles; and 5) three vLINCL Portuguese patients may have defects in a new NCL gene. (C) 2003 Wiley-Liss, Inc. C1 Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. Univ Porto, Inst Biol Mol & Celular, Dept Neurobiol Genet, P-4100 Oporto, Portugal. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Hosp Geral Santo Antonio, Unidade Neuropatol, Oporto, Portugal. Univ Porto, Inst Ciencias Biomed Abel Salazar, Dept Patol & Imunol, P-4100 Oporto, Portugal. Inst Genet Med Porto, Unidade Enzimol, Oporto, Portugal. Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. Toronto Sick Childrens Hosp, Dept Neurol, Toronto, ON, Canada. RP Boustany, RMN (reprint author), Duke Univ, Med Ctr, Dept Pediat, MSRB Box 2604,Res Dr, Durham, NC 27710 USA. RI Bessa, Carlos/M-3289-2013; Ribeiro, Maria Gil/B-6467-2013; Sa Miranda, Maria Clara Pereira/K-3920-2013 OI Bessa, Carlos/0000-0002-7031-9696; Ribeiro, Maria Gil/0000-0001-9365-6057; Teixeira, Carla/0000-0001-6277-6400; Sa Miranda, Maria Clara Pereira/0000-0003-0123-5525 FU NINDS NIH HHS [NS33648] NR 24 TC 25 Z9 26 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 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD MAY PY 2003 VL 21 IS 5 BP 502 EP 508 DI 10.1002/humu.10207 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 673AX UT WOS:000182557500006 PM 12673792 ER PT J AU Liu, WH Kaur, M Makrigiorgos, GM AF Liu, WH Kaur, M Makrigiorgos, GM TI Detection of hotspot mutations and polymorphisms using an enhanced PCR-RFLP approach SO HUMAN MUTATION LA English DT Article DE SNP; mutation detection; PCR-RFLP; hotspot mutations; MSH2; TP53; p53 ID SINGLE NUCLEOTIDE POLYMORPHISMS; LINKAGE DISEQUILIBRIUM; GENOTYPIC SELECTION; POINT MUTATIONS; P53 MUTATIONS; RAS MUTATIONS; DNA POOLS; ASSAY; DIAGNOSIS; CANCER AB Ethidium gel,based PCR-RFLP is widely used, and is perhaps the simplest method for detection of known mutations in cancer related genes and for genotyping a wide range of other human diseases. However, its application is limited by the fact that it can only detect mutant alleles that are present in more than 5-10% of wild-type alleles. Here we present a method that allows a 1-2 order enhancement in the sensitivity of the widely used PCR-RFLP without substantially increasing the effort and cost associated with it. This method is a modification to our previously reported amplification via primer ligation at the mutation (APRIL-ATM) method, which utilizes ligation of a primer at a restriction site formed by a mutation, followed by a ligation-mediated PCR amplification which amplifies only the mutation-containing DNA molecules. By combining this method with the artificial introduction of restriction sites during PCR, we demonstrate that assays can be designed and validated for detecting hot-spot mutations in codons 273, 158, and 248 of the TP53 gene (p53) and potentially for most mutations of interest. This approach is validated by using samples where the mutation was artificially introduced at these p53 positions. The increased sensitivity offered by the method further allows us to rapidly screen for low frequency polymorphisms in pooled DNA samples. The frequency of an MSH2 missense polymorphism (965G>A) was quantified in pooled genomic DNA samples from 205 and 221 U.S. and Polish colorectal cancer patients, respectively, and an equal number of ethnicity-matched controls. The data revealed a 3-5% prevalence of this polymorphism in the patient and the control populations. Individual sequencing of all 852 patient samples demonstrated an excellent agreement among the two independent approaches. The present enhanced PCR,RFLP reduces the effort involved in high throughput polymorphism studies and promises to find applications in genotyping and association studies involving low frequency polymorphisms and mutations. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Brigham & Womens Hosp, Longwood Radiat Oncol Ctr, Level L2,Radiat Therapy,75 Francis St, Boston, MA 02215 USA. FU NCI NIH HHS [5 T32 CA09078] NR 35 TC 8 Z9 8 U1 2 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD MAY PY 2003 VL 21 IS 5 BP 535 EP 541 DI 10.1002/humu.10184 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 673AX UT WOS:000182557500010 PM 12673796 ER PT J AU Miyata, S Casey, M Frank, DW Ausubel, FM Drenkard, E AF Miyata, S Casey, M Frank, DW Ausubel, FM Drenkard, E TI Use of the Galleria mellonella caterpillar as a model host to study the role of the type III secretion system in Pseudomonas aeruginosa pathogenesis SO INFECTION AND IMMUNITY LA English DT Article ID EXOENZYME-S; CAENORHABDITIS-ELEGANS; EPITHELIAL-CELLS; VIRULENCE FACTORS; BACTERIAL PATHOGENESIS; MOLECULAR MECHANISMS; MEDIATED APOPTOSIS; EFFECTOR PROTEINS; EUKARYOTIC CELLS; V-ANTIGEN AB Nonvertebrate model hosts represent valuable tools for the study of host-pathogen interactions because they facilitate the identification of bacterial virulence factors and allow the discovery of novel components involved in host innate immune responses. In this report, we determined that the greater wax moth caterpillar Galleria mellonella is a convenient nonmammalian model host for study of the role of the type III secretion system (TTSS) in Pseudomonas aeruginosa pathogenesis. Based on the observation that a mutation in the TTSS pscD gene of P. aeruginosa strain PA14 resulted in a highly attenuated virulence phenotype in G. mellonella, we examined the roles of the four known effector proteins of P. aeruginosa (ExoS, ExoT, ExoU, and ExoY) in wax moth killing. We determined that in P. aeruginosa strain PA14, only ExoT and ExoU play a significant role in G. mellonella killing. Strain PA14 lacks the coding sequence for the ExoS effector protein and does not seem to express ExoY. Moreover, using DeltaexoU DeltaexoY, DeltaexoT DeltaexoY, and DeltaexoT DeltaexoU double mutants, we determined that individual translocation of either ExoT or ExoU is sufficient to obtain nearly wild-type levels of G. mellonella killing. On the other hand, data obtained with a DeltaexoT DeltaexoU DeltaexoY triple mutant and a DeltapscD mutant suggested that additional, as-yet-unidentified P. aeruginosa components of type III secretion are involved in virulence in G. mellonella. A high level of correlation between the results obtained in the G. mellonella model and the results of cytopathology assays performed with a mammalian tissue culture system validated the use of G. mellonella for the study of the P. aeruginosa TTSS. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA. RP Drenkard, E (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 10, Boston, MA 02114 USA. FU NHLBI NIH HHS [NHLBI 202618] NR 56 TC 151 Z9 160 U1 1 U2 11 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 MAY PY 2003 VL 71 IS 5 BP 2404 EP 2413 DI 10.1128/IAI.71.5.2404-2313.2003 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 672BT UT WOS:000182501500013 PM 12704110 ER PT J AU Cullen, PA Haake, DA Bulach, DM Zuerner, RL Adler, B AF Cullen, PA Haake, DA Bulach, DM Zuerner, RL Adler, B TI LipL21 is a novel surface-exposed lipoprotein of pathogenic Leptospira species SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; LPS BIOSYNTHETIC LOCI; TREPONEMA-PALLIDUM; SEROVAR HARDJO; BORRELIA-BURGDORFERI; SUBTYPE HARDJOBOVIS; MAMMALIAN INFECTION; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; ESCHERICHIA-COLI AB Leptospira is the etiologic agent of leptospirosis, a bacterial zoonosis distributed worldwide. Leptospiral lipopolysaccharide is a protective immunogen, but the extensive serological diversity of leptospires has inspired a search for conserved outer membrane proteins (OMPs) that may stimulate heterologous immunity. Previously, a global analysis of leptospiral OMPs (P. A. Cullen, S. J. Cordwell, D. M. Bulach, D. A. Haake, and B. Adler, Infect. Immun. 70:2311-2318, 2002) identified pL21, a novel 21-kDa protein that is the second most abundant constituent of the Leptospira interrogans serovar Lai outer membrane proteome. In this study, we identified the gene encoding pL21 and found it to encode a putative lipoprotein; accordingly, the protein was renamed LipL21. Southern hybridization analysis revealed the presence of lipL21 in all of the pathogenic species but in none of the saprophytic species examined. Alignment of the LipL21 sequence from six strains of Leptospira revealed 96 to 100% identity. When specific polyclonal antisera to recombinant LipL21 were used, LipL21 was isolated together with other known leptospiral OMPs by both Triton X-114 extraction and sucrose density. gradient membrane fractionation. All nine strains of pathogenic leptospires investigated by Western blotting, whether culture attenuated or virulent, were found to express LipL21. In contrast, the expression of LipL21 or an antigenically related protein could not be detected in nonpathogenic L. biflexa. Infected hamster sera and two of eight human leptospirosis sera tested were found to react with recombinant LipL21. Native LipL21 was found to incorporate tritiated palmitic acid, consistent with the prediction of a lipoprotein signal peptidase cleavage site. Biotinylation of the leptospiral surface resulted in selective labeling of LipL21 and the previously known OMPs LipL32 and LipL41. These findings show that LipL21 is a surface-exposed, abundant outer membrane lipoprotein that is expressed during infection and conserved among pathogenic Leptospira species. C1 Monash Univ, Dept Microbiol, Bacterial Pathogenesis Res Grp, Melbourne, Vic 3800, Australia. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. USDA ARS, Natl Anim Dis Ctr, Bacterial Dis Livestock Res Unit, Ames, IA 50010 USA. RP Adler, B (reprint author), Monash Univ, Dept Microbiol, Bacterial Pathogenesis Res Grp, Melbourne, Vic 3800, Australia. RI Bulach, Dieter/D-5793-2011 OI Bulach, Dieter/0000-0001-9823-6078 FU NIAID NIH HHS [R01 AI034431, AI-34431, R01 AI034431-06A2, R21 AI034431, R29 AI034431] NR 43 TC 62 Z9 81 U1 0 U2 1 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 MAY PY 2003 VL 71 IS 5 BP 2414 EP 2421 DI 10.1128/IAI.71.5.2414-2421.2003 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 672BT UT WOS:000182501500014 PM 12704111 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 SO INFECTION AND IMMUNITY LA English DT Article ID ENTEROINVASIVE ESCHERICHIA-COLI; LARGE VIRULENCE PLASMID; COMPLETE DNA-SEQUENCE; LEUCINE-RICH REPEAT; PATHOGENICITY ISLAND; ATTENUATED SHIGELLA; INSERTION SEQUENCES; EFFECTOR PROTEINS; HOST-SPECIFICITY; SALMONELLA-TYPHI AB We determined the complete genome sequence of Shigella flexneri serotype 2a strain 2457T (4,599,354 bp). Shigella species cause >1 million deaths per year from dysentery and diarrhea and have a lifestyle that is markedly different from those of closely related bacteria, including Escherichia coli. The genome exhibits the backbone and island mosaic structure of E. coli pathogens, albeit with much less horizontally transferred DNA and lacking 357 genes present in E. coli. The strain is distinctive in its large complement of insertion sequences, with several genomic rearrangements mediated by insertion sequences, 12 cryptic prophages, 372 pseudogenes, and 195 S. flexneri-specitic genes. The 2457T genome was also compared with that of a recently sequenced S. flexneri 2a strain, 301. Our data are consistent with Shigella being phylogenetically indistinguishable from E. coli. The S. flexneri-specific regions contain many genes that could encode proteins with roles in virulence. Analysis of these will reveal the genetic basis for aspects of this pathogenic organism's distinctive lifestyle that have yet to be explained. C1 Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. Univ Wisconsin, Genome Ctr, Madison, WI 53706 USA. Univ Wisconsin, Anim Hlth & Biol Sci & 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 Cell & Mol Biol, Austin, TX 78712 USA. RP Blattner, FR (reprint author), Univ Wisconsin, Genet Lab, 445 Henry Mall, Madison, WI 53706 USA. RI Zhou, Shiguo/B-3832-2011; Mayhew, George/B-4042-2016; Plunkett III, Guy/B-8058-2009; OI Zhou, Shiguo/0000-0001-7421-2506; Mayhew, George/0000-0003-0609-6018; Plunkett III, Guy/0000-0003-1422-469X; Darling, Aaron/0000-0003-2397-7925 FU NIAID NIH HHS [AI-44387, AI-43562] NR 73 TC 273 Z9 1888 U1 0 U2 15 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 MAY PY 2003 VL 71 IS 5 BP 2775 EP 2786 DI 10.1128/IAI.71.5.2775-2786.2003 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 672BT UT WOS:000182501500055 PM 12704152 ER PT J AU Kinrys, G Pollack, MH Simon, NM Worthington, JJ Nardi, AE Versiani, M AF Kinrys, G Pollack, MH Simon, NM Worthington, JJ Nardi, AE Versiani, M TI Valproic acid for the treatment of social anxiety disorder SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE anticonvulsants; anxiety disorders; social anxiety disorder; valproic acid ID PANIC DISORDER; DOUBLE-BLIND; PSYCHIATRIC-DISORDERS; PHOBIA; PLACEBO; COMORBIDITY; PAROXETINE; SODIUM; PHARMACOTHERAPY; DIVALPROEX AB The aim of the study was to examine the efficacy of valproic acid in participants with social anxiety disorder. Following a 2-week single-blind, placebo run-in period, 17 participants were enrolled in a 12-week open flexible-dose trial of valproic acid (500-2500 mg). The primary outcome measures were the mean change from baseline in the Liebowitz Social Anxiety Scale (LSAS) total score and responder status [defined as a Clinical Global Impression of Improvement score (CGI-1) less than or equal to 2]. Social anxiety symptoms as measured by the LSAS and CGI-I scores significantly improved with treatment. The mean reduction in the LSAS was 21.3 points in the last visit carried forward analysis and 19.1 points for the completer analysis, with 41.1% and 46.6% participants, respectively, achieving responder status. The results from this open-label trial suggest the potential efficacy of valproic acid for the treatment of social anxiety disorder. Placebo-controlled trials are indicated to confirm these findings. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kinrys, G (reprint author), Massachusetts Gen Hosp, 15 Parkman St WACC 815, Boston, MA 02114 USA. RI Nardi, Antonio/E-6719-2010 NR 30 TC 41 Z9 43 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD MAY PY 2003 VL 18 IS 3 BP 169 EP 172 DI 10.1097/01.yic.0000064261.66765.9f PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 680ET UT WOS:000182963900008 PM 12702897 ER PT J AU Schiavone, C Salvatore, L Primavera, A Cuccurullo, F Verna, N Di Stefano, F Thomson, E Tenaglia, R Di Gioacchino, M AF Schiavone, C Salvatore, L Primavera, A Cuccurullo, F Verna, N Di Stefano, F Thomson, E Tenaglia, R Di Gioacchino, M TI Simple renal cysts in hypertensive patients: Relation between cyst growing and anti-hypertensive therapy SO INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY LA English DT Article DE renal simple cyst; hypertension; Ca-antagonists ID ARTERIAL BLOOD-PRESSURE; EPITHELIAL-CELLS; DISEASE; CALCIUM; EXPANSION AB The study investigates relationship between simple renal cyst enlargement studied by ultrasonography and anti-hypertensive treatment. To this purpose we enrolled 42 patients with newly diagnosed hypertension affected by simple renal cysts. Fourteen were randomly assigned to treatment with ACE-Inhibitors (group 1), twelve to diuretics (group 2) and sixteen to Ca-Antagonists (group 3). Patient performed a basal ultrasonography to evaluate basal cyst dimension before starting anti-hypertensive treatment. Following 12 months of the anti-hypertensive regimen, a new echograph was performed to evaluate changes in cyst size. A control group consisting of 15 patients with normal blood pressure and simple renal cysts was enrolled (group 0). An enlargement of cysts was detected in all patients. However, the enlargement observed in patients treated by Ca-Antagonists was significantly greater than that observed in the other groups (p<0,05). Our study supports the hypothesis that Ca-Antagonists may favor cyst enlargement by enhancing cyclic AMP production. In-fact, cAMP and cAMP agonists stimulate fluid secretion by lining cells of the cyst wall, inducing cyst enlargement. C1 Univ G DAnnunzio, Echog Unit, Chieti, Italy. Univ G DAnnunzio, Dept Med & Sci Aging, Chieti, Italy. Brigham & Womens Hosp, Trauma Ctr Lab, Dept Surg, Boston, MA 02115 USA. Univ G DAnnunzio, Dept Urol, Chieti, Italy. Massachusetts Gen Hosp, Genet & Ageing Unit, Boston, MA 02114 USA. RP Schiavone, C (reprint author), Univ G DAnnunzio, Echog Unit, Chieti, Italy. NR 21 TC 1 Z9 1 U1 0 U2 2 PU BIOLIFE SAS PI SILVA MARINA (TE) PA VIA S STEFANO 39 BIS, 64029 SILVA MARINA (TE), ITALY SN 0394-6320 J9 INT J IMMUNOPATH PH JI Int. J. Immunopathol. Pharmacol. PD MAY-AUG PY 2003 VL 16 IS 2 BP 175 EP 180 PG 6 WC Immunology; Pathology; Pharmacology & Pharmacy SC Immunology; Pathology; Pharmacology & Pharmacy GA 698HD UT WOS:000183992200012 PM 12797909 ER PT J AU Razzaque, MS Foster, CS Ahmed, AR AF Razzaque, MS Foster, CS Ahmed, AR TI Role of connective tissue growth factor in the pathogenesis of conjunctival scarring in ocular cicatricial pemphigoid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID COLLAGEN-BINDING HEAT-SHOCK-PROTEIN-47; IDIOPATHIC PULMONARY FIBROSIS; HUMAN DIABETIC NEPHROPATHY; FACTOR-BETA; GENE-EXPRESSION; IN-SITU; PROTEIN; GLOMERULONEPHRITIS; LOCALIZATION; INHIBITION AB PURPOSE. Conjunctival fibrosis due to excessive accumulation of collagens is an important histologic feature in ocular cicatricial pemphigoid (OCP). Studies have suggested a role of transforming growth factor (TGF)-beta1 in conjunctival fibrosis in patients with OCP. Connective tissue growth factor (CTGF) is an important downstream mediator of TGF-beta1-induced collagen synthesis. CTGF usually acts synergistically with TGF-beta1 during the process of fibrosis in various organs. Hence, studying the mechanism by Which CTGF influences TGF-beta1-induced synthesis of Collagen in conjunctiva of patients with OCP would provide insight into the mechanism of conjunctival fibrosis in patients with OCP. METHODS. Biopsy specimens from conjunctiva of 10 patients with OCP and 5 normal subjects, were studied, with immunohistochemistry and real-time PCR, for the expression of CTGF and interstitial type I Collagen. Using fibroblasts cultured from conjunctival biopsies we determined the effects of TGF-beta1 on the induction of CTGF and type I Collagen by immunostaining, and quantitative real-time PCR. The effects of blocking the bioactivity of TGF-beta1 on the expression of CTGF and type I Collagen were determined in TGF-beta1 -stimulated fibroblasts, before and after treatment with type II receptor neutralizing antibody. RESULTS. An increased stromal accumulation of interstitial type I Collagen with an increased expression of CTGF was observed in biopsy sections of patients with OCP, compared with the control. By quantitative real-time PCR, a 3.2-fold increase in the expression of CTGF was detected in conjunctival tissues obtained from patients with OCP, compared with control conjunctiva. Fibroblasts isolated from conjunctiva of patients with OCP expressed 4.4-fold more CTGF, compared with control conjunctival fibroblasts, by real-time PCR. When these cultured fibroblasts Were immunostained, an increased expression of CTGF was detected in fibroblasts isolated from patients with OCP, compared with control. Furthermore, when conjunctival fibroblasts were treated with TGF-beta1, an approximately ninefold increase in the expression of CTGF and an approximately threefold increase in the expression of type I Collagen were detected by real-time PCR, compared with unstimulated fibroblasts. Finally, when antibody to TGF-beta type II receptor was added before TGF-beta1 treatment of these fibroblasts, the expression of type I Collagen and CTGF was significantly reduced. CONCLUSIONS. In the present study, an increased expression of CTGF was recorded in conjunctiva of patients with OCP. TGF-beta1 can induce production of CTGF and type I Collagen by fibroblasts obtained from conjunctiva in OCP. This induction of CTGF by TGF-beta1 can be blocked by antibody to TGF-beta type II receptors. The findings lead to the conclusion that CTGF is one of the molecules involved in the pathogenesis of conjunctival fibrosis in patients with OCP. C1 Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Immunol & Uveitis Serv, Boston, MA USA. RP Ahmed, AR (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. FU NEI NIH HHS [EY08379] NR 38 TC 34 Z9 39 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 MAY PY 2003 VL 44 IS 5 BP 1998 EP 2003 DI 10.1167/iovs.02-0967 PG 6 WC Ophthalmology SC Ophthalmology GA 672CQ UT WOS:000182503700030 PM 12714635 ER PT J AU Ishida, S Usui, T Yamashiro, K Kaji, Y Ahmed, E Carrasquillo, KG Amano, S Hida, T Oguchi, Y Adamis, AP AF Ishida, S Usui, T Yamashiro, K Kaji, Y Ahmed, E Carrasquillo, KG Amano, S Hida, T Oguchi, Y Adamis, AP TI VEGF(164) is proinflammatory in the diabetic retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; INTERCELLULAR-ADHESION MOLECULE-1; VASCULAR-PERMEABILITY FACTOR; EXON 7-ENCODED DOMAIN; BARRIER BREAKDOWN; IN-VIVO; LEUKOCYTE ADHESION; CELL PROLIFERATION; ICAM-1 EXPRESSION; FACTOR RECEPTOR AB PURPOSE. The objectives of this study were to characterize the differential potency of two major VEGF isoforms, VEGF(120) and VEGF(164), for inducing leukocyte stasis (leukostasis) within the retinal vasculature and blood-retinal barrier (BRB) breakdown and to determine whether endogenous VEGF(164) mediates retinal leukostasis and BRB breakdown in early and established diabetes. METHODS. Retinal leukostasis and BRB breakdown were simultaneously quantified by combining concanavalin A lectin (Conk) perfusion labeling with a fluorophotometric dextran leakage assay. CD45 immunohistochemistry was performed to confirm that ConA-stained cells within the vasculature were leukocytes. Retinal leukostasis and BRB breakdown were compared in nondiabetic rats receiving intravitreous injections of VEGF(120) or VEGF(164). Retinal intercellular adhesion molecule (ICAM)-1 and VEGF protein levels were studied by Western blot and ELISA, respectively. An anti-VEGF(164(165)) aptamer (EYE001) was administered by intravitreous injection to 2-week and 3-month diabetic rats, and the effect on retinal leukostasis and BRB breakdown was quantified. RESULTS. Compared with VEGF120, VEGF164 more potently increased retinal ICAM-1 levels (2.2-fold), leukostasis (1.9-fold), and BRB breakdown (2.1-fold, P < 0.01 for all), despite negligible differences in vitreoretinal VEGF levels at the time of evaluation (P > 0.05). Retinal leukostasis and leakage increased with the duration of diabetes (P < 0.01) and correlated closely (P < 0.01, r = 0.889). The isoform-specific blockade of endogenous VEGF(164) with EYE001 resulted in a significant suppression of retinal leukostasis and BRB breakdown in both early (72.4% and 82.6%, respectively) and established (48.5% and 55.0%, respectively) diabetes (P < 0.01). CONCLUSIONS. On an equimolar basis, VEGF164 is at least twice as potent as VEGF(120), at inducing ICAM-1-mediated retinal leukostasis and BRB breakdown in vivo. The inhibition of diabetic retinal leukostasis and BRB breakdown with EYE001 in early and established diabetes indicates that VEGF(164) is an important isoform in the pathogenesis of early diabetic retinopathy. C1 Eyetech Res Ctr, Woburn, MA 01801 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. Keio Univ, Sch Med, Dept Ophthalmol, Tokyo, Japan. Univ Tokyo, Fac Med, Dept Ophthalmol, Tokyo 113, Japan. Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kyoto, Japan. Kyorine Eye Ctr, Mitaka, Tokyo, Japan. RP Adamis, AP (reprint author), Eyetech Res Ctr, 42 Cummings Pk, Woburn, MA 01801 USA. RI ISHIDA, SUSUMU/D-7067-2012 NR 51 TC 219 Z9 240 U1 2 U2 13 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 MAY PY 2003 VL 44 IS 5 BP 2155 EP 2162 DI 10.1167/iovs.02-0807 PG 8 WC Ophthalmology SC Ophthalmology GA 672CQ UT WOS:000182503700051 PM 12714656 ER PT J AU Acharya, N Paton, B Colby, K AF Acharya, N Paton, B Colby, K TI Spectrum of fungal keratitis at Massachusetts Eye and Ear Infirmary SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Microbiol Lab, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1410 BP U335 EP U335 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801360 ER PT J AU Adams, SM Berson, EL Dryja, TP AF Adams, SM Berson, EL Dryja, TP TI A screen for mutations of the SLC6A6 gene in patients with retinitis pigmentosa and Leber congenital amaurosis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2320 BP U400 EP U400 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802246 ER PT J AU Allingham, RR Hauser, ER Wiggs, JL Hauser, MA Graham, FL Abramson, KR del Bono, EA Shi, JR Haines, JL Pericak-Vance, MA AF Allingham, RR Hauser, ER Wiggs, JL Hauser, MA Graham, FL Abramson, KR del Bono, EA Shi, JR Haines, JL Pericak-Vance, MA TI Ordered subset analysis in primary open-angle glaucoma (POAG): Evidence for linkage to chromosomes 14 and 15 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Duke Univ, Med Ctr, Durham, NC USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Vanderbilt Univ, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3170 BP U133 EP U133 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000636 ER PT J AU Ambati, J Anand, A Sakurai, E Kuziel, WA Rollins, BJ Ambati, BK AF Ambati, J Anand, A Sakurai, E Kuziel, WA Rollins, BJ Ambati, BK TI An animal model of age-related macular degeneration in senescent macrophage recruitment impaired mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Kentucky, Lexington, KY 40506 USA. Univ Texas, Inst Cellular & Mol Biol, Austin, TX 78712 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Med Coll Georgia, Augusta, GA 30912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1718 BP U402 EP U402 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801669 ER PT J AU Andreoli, CM Rizzo, JF AF Andreoli, CM Rizzo, JF TI Cognitive slowing isolated for reading SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1964 BP U319 EP U319 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801914 ER PT J AU Androudi, SN Meniconi, M Christen, W Iaccheri, B Fiore, T Papadaki, T Foster, C AF Androudi, SN Meniconi, M Christen, W Iaccheri, B Fiore, T Papadaki, T Foster, C TI Outcomes of early versus late immunomodulatory treatment in patients with HLA-B27-associated chronic uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2414 BP U419 EP U419 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802342 ER PT J AU Barouch, FC Benson, MD Mukai, S AF Barouch, FC Benson, MD Mukai, S TI Isolated vitreoretinal amyloidosis in the absence of transthyretin mutations SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4857 BP U662 EP U662 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002318 ER PT J AU Bernardino, CR Fay, AM Rubin, PAD AF Bernardino, CR Fay, AM Rubin, PAD TI A clinicopathological series of the spectrum of long-term complications from hydrogel scleral buckles - Orbital cellulitis mimicry, prosthesis intolerance, and orbital pseudotumor SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2234 BP U382 EP U382 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802161 ER PT J AU Bertera, JH Dohlman, CH Ma, JJK AF Bertera, JH Dohlman, CH Ma, JJK TI Programmable microdroplet dispenser functions as an artificial lacrimal gland SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Adapt Med Syst Inc, Milford, MA USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2451 BP U427 EP U427 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802379 ER PT J AU Bhatia, LS Walton, DS Chen, TC AF Bhatia, LS Walton, DS Chen, TC TI Aphakic glaucoma after congenital cataract surgery SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 94 BP U15 EP U15 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800071 ER PT J AU Bressler, S Bressler, NM Chandra, SR Chew, EY Clemons, TE Klein, R Seddon, JM AF Bressler, S Bressler, NM Chandra, SR Chew, EY Clemons, TE Klein, R Seddon, JM CA AREDS Res Grp TI Mortality in the Age-Related Eye Disease Study: Associations with age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04-09, 2003 CL FT LAUDERDALE, FL SP Assoc Res Vis & Ophthalmol C1 Wilmer Eye Inst, Baltimore, MD USA. Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA. NEI, NIH, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2056 BP U342 EP U342 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801999 ER PT J AU Carrasquillo, KG Ray, S Rigas, IK Calias, P Miller, JW Gragoudas, ES Adamis, AP AF Carrasquillo, KG Ray, S Rigas, IK Calias, P Miller, JW Gragoudas, ES Adamis, AP TI Transscleral delivery of an anti-VEGF aptamer in a rabbit model SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Angiogenesis Lab, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Eyetech Pharmaceut, Chem Drug Delivery, Woburn, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4442 BP U526 EP U526 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001901 ER PT J AU Cestari, DM Rizzo, JF AF Cestari, DM Rizzo, JF TI Visual field loss associated with optic nerve tilting or congenitally enlarged optic nerve cups - A variant of optic nerve hypoplasia? SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 617 BP U122 EP U122 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800595 ER PT J AU Chang, EL Bernardino, CR Rubin, PAD Ksander, BR AF Chang, EL Bernardino, CR Rubin, PAD Ksander, BR TI Primary tumor growth and metastatic spread of human conjunctival melanomas in an animal model SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Doheny Eye Inst, Los Angeles, CA 90033 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2429 BP U422 EP U422 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802357 ER PT J AU Chang, JH Javier, JAD Chang, YG Gabison, E Azar, DT AF Chang, JH Javier, JAD Chang, YG Gabison, E Azar, DT TI Functional characterization of the 28 kDa endostatin-spanning fragment of collagen XVIII in mouse cornea SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 832 BP U236 EP U236 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800809 ER PT J AU Charukamnoetkanok, P Mian, S Javier, J Oliveira, H Chang, JH Azar, DT AF Charukamnoetkanok, P Mian, S Javier, J Oliveira, H Chang, JH Azar, DT TI Proangiogenic role of matrix metalloproteinase (MMP) 14 in cornea SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 833 BP U236 EP U236 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800807 ER PT J AU Chiao, CC Masland, RH AF Chiao, CC Masland, RH TI Contextual effects on direction selective ganglion cells in the rabbit SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Natl Tsing Hua Univ, Dept Life Sci, Hsinchu, Taiwan. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3255 BP U210 EP U210 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000718 ER PT J AU Christoforidis, JB Lit, ES Fernandez-Suntay, JP D'Amico, DJ AF Christoforidis, JB Lit, ES Fernandez-Suntay, JP D'Amico, DJ TI Histopathology of the optic nerve three months following lamina puncture SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 2996 BP U93 EP U93 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000464 ER PT J AU Clermont, AC Abiko, T Horio, N Abiko, A King, GL Bursell, SE AF Clermont, AC Abiko, T Horio, N Abiko, A King, GL Bursell, SE TI Leukostasis and microcirculation in retina of insulin resistance models SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3292 BP U221 EP U221 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000757 ER PT J AU Cote, J Rosner, B Seddon, J AF Cote, J Rosner, B Seddon, J TI Obesity and AMD: Results from a prospective study of men and women SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1763 BP U411 EP U411 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801715 ER EF