FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Holmes, LB AF Holmes, LB TI 2001 Teratogen Update Workshop summaries: Introduction SO TERATOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. RP Holmes, LB (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Warren 801, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD MAY PY 2002 VL 65 IS 5 BP 199 EP 199 DI 10.1002/tera.10055 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 547YQ UT WOS:000175361000001 ER PT J AU Cooper, DKC Gollackner, B Knosalla, C Teranishi, K AF Cooper, DKC Gollackner, B Knosalla, C Teranishi, K TI Xenotransplantation - how far have we come? SO TRANSPLANT IMMUNOLOGY LA English DT Review DE acure humoral xenograft rejection; genetic engineering; microbiology; physiology; tolerance ID CELL TRANSPLANTATION; PRIMATES; ORGAN AB The immunologic barriers to xenotransplantation are summarized and approaches to overcome them briefly reviewed. Intensive investigation is being directed to the problem of acute humoral xenograft rejection, which is the major current barrier. Although the induced antibody response appears to be prevented by combination therapy with an anti-CD154 monoclonal antibody and mycophenolate mofetil, deposition of natural anti-Gal antibody on the graft endothelial cells appears to be sufficient to lead to rejection or a state of consumptive coagulopathy. Approaches towards the induction of tolerance are described. The potential microbiologic risks and physiologic incompatibilities of pig-to-human organ transplantation are also briefly discussed. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,MGH East, Boston, MA 02129 USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,MGH East, 13th St, Boston, MA 02129 USA. FU PHS HHS [1PO1 A145897] NR 10 TC 25 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0966-3274 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD MAY PY 2002 VL 9 IS 2-4 BP 251 EP 256 AR PII S0966-3274(02)00010-2 DI 10.1016/S0966-3274(02)00010-2 PG 6 WC Immunology; Transplantation SC Immunology; Transplantation GA 581WM UT WOS:000177317300030 PM 12180839 ER PT J AU Wekerle, T Nikolic, B Pearson, DA Swenson, KG Sykes, M AF Wekerle, T Nikolic, B Pearson, DA Swenson, KG Sykes, M TI Minimal conditioning required in a murine model of T cell depletion, thymic irradiation and high-dose bone marrow transplantation for the induction of mixed chimerism and tolerance SO TRANSPLANT INTERNATIONAL LA English DT Article DE tolerance; mixed chimerism; bone marrow transplantation; T cell depletion ID DONOR-SPECIFIC TOLERANCE; HEMATOPOIETIC CHIMERISM; MONOCLONAL-ANTIBODIES; CLONAL DELETION; ENGRAFTMENT; REGIMEN; MICE; MOLECULE; BLOCKADE; SURFACE AB In a recently developed murine model for the induction of mixed chimerism and tolerance, hosts are treated with T cell depleting monoclonal antibodies (TCD mAbs; days -5, -1 and +7), thymic irradiation (TI) (7 Gy), and a high dose of fully allogeneic bone marrow cells (BMC, 200x10(6)). To find the minimum amount of each treatment required for success with this approach, we treated groups with (1) a lower dose of TI (3.5 Gy), (2) fewer BMC (100x10(6)), (3) no TI, (4) no TI plus additional TCD mAbs on day + 14, or (5) fewer injections of TCD mAbs (day -5 only). Chimerism was followed by flow cytometry (FCM), and tolerance was assessed by skin grafting. Without TI, no long-term chimerism or tolerance could be induced, even when an additional dose of TCD mAbs was administered on day +14. A reduction in the dose of either BMC or TI led to substantially reduced effectiveness, as demonstrated by lower levels of chimerism and poorer donor skin graft survival. However, the dose of TCD mAbs and hence the duration of recipient T cell depletion could be safely reduced and thus the potential toxicity of the conditioning regimen lowered. C1 Vienna Gen Hosp, Div Transplantat, Dept Surg, A-1090 Vienna, Austria. Harvard Univ, Massachusetts Gen Hosp, Sch Med, BMT Sect,Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Wekerle, T (reprint author), Vienna Gen Hosp, Div Transplantat, Dept Surg, Wahringer Gurtel 18, A-1090 Vienna, Austria. OI Wekerle, Thomas/0000-0001-5159-2796 FU NHLBI NIH HHS [HL49915] NR 23 TC 25 Z9 25 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0934-0874 J9 TRANSPLANT INT JI Transpl. Int. PD MAY PY 2002 VL 15 IS 5 BP 248 EP 253 DI 10.1007/s00147-002-0411-3 PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 561WW UT WOS:000176166900007 PM 12012046 ER PT J AU Guenette, SY AF Guenette, SY TI A role for APP in motility and transcription? SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article ID AMYLOID PRECURSOR PROTEIN; CYTOPLASMIC DOMAIN; BINDING PROTEIN; WW DOMAIN; FE65; PHOSPHORYLATION; INTERACTS; NUCLEUS; NOTCH; CELLS AB Recent studies suggest two novel roles for the amyloid precursor protein (APP): APP accelerates wound healing in MDCK cells and acts in a notch-like manner to activate transcription. Both of these putative functions are dependent on the interaction of APP with the APP-binding protein FE65. Future studies are required to understand the full implications of these new findings and to determine whether therapeutic strategies for Alzheimer's disease should take these putative functions into account. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Guenette, SY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit, 114 16th St, Charlestown, MA 02129 USA. NR 21 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAY PY 2002 VL 23 IS 5 BP 203 EP 205 AR PII S0165-6147(02)02003-5 DI 10.1016/S0165-6147(02)02003-5 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 547YV UT WOS:000175361400003 PM 12007991 ER PT J AU Linson, PW Lee, AK Doytchinova, T Chen, MH Weinstein, MH Richie, JP D'Amico, AV AF Linson, PW Lee, AK Doytchinova, T Chen, MH Weinstein, MH Richie, JP D'Amico, AV TI Percentage of core lengths involved with prostate cancer: Does it add to the percentage of positive prostate biopsies in predicting postoperative prostate-specific antigen outcome for men with intermediate-risk prostate cancer? SO UROLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Clinical-Pathologists CY OCT 19-21, 2001 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Clin Pathol ID RADICAL PROSTATECTOMY; SYSTEMATIC BIOPSIES; RADIATION-THERAPY; RECURRENCE; RELAPSE AB Objectives. To evaluate whether the percentage of core lengths involved with prostate cancer added clinically significant information concerning the time to postoperative prostate-specific antigen (PSA) failure in the intermediate-risk patient beyond what is provided by the percentage of positive biopsies. Methods. Cox regression multivariable analysis was performed to compare the ability of the two measurements of biopsy cancer volume to predict the time to PSA failure from a series of 184 surgically treated intermediate-risk patients. PSA outcome was estimated using the actuarial method of Kaplan and Meier, and comparisons were made using the log-rank test. Results. Both the percentage of core lengths involved with prostate cancer (P = 0.01) and the percentage of positive biopsies (P = 0.002) were significant predictors of the time to PSA failure on univarlable analysis. The 4-year PSA outcome was 83% versus 47% (P = 0.0008) and 83% versus 53% (P = 0.007) for the percentage of positive biopsies stratified by 50% or less versus greater than 50% and the percentage of core lengths involved with prostate cancer stratified by 25% or less versus greater than 25%, respectively. However, only the percentage of positive biopsies remained significant (P = 0.03) on multivariable analysis. Conclusions. The percentage of core lengths involved with prostate cancer did not provide additional clinically relevant information to the percentage of positive biopsies for patients with intermediate-risk prostate cancer. Therefore, the routine measurement of core involvement may not be necessary in this patient population. (C) 2002, Elsevier Science Inc. C1 Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02215 USA. Worcester Polytech Inst, Dept Math Sci, Worcester, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA USA. Dana Farber Canc Inst, Boston, MA USA. RP Linson, PW (reprint author), Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, 375 Longwood Ave, Boston, MA 02215 USA. NR 15 TC 22 Z9 24 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 MAY PY 2002 VL 59 IS 5 BP 704 EP 708 AR PII S0090-4295(01)01665-X DI 10.1016/S0090-4295(01)01665-X PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 549QF UT WOS:000175455200013 PM 11992844 ER PT J AU Chawla, AK Thakral, HK Zietman, AL Shipley, WU AF Chawla, AK Thakral, HK Zietman, AL Shipley, WU TI Salvage radiotherapy after radical prostatectomy for prostate adenocarcinoma: Analysis of efficacy and prognostic factors SO UROLOGY LA English DT Article ID STAGING ERRORS; CANCER; IRRADIATION; ADJUVANT; ANTIGEN; RECURRENCE; SURVIVAL; PATTERNS AB Objectives. To determine the probability of biochemical control for patients treated with salvage irradiation and identify prognostic factors associated with successful salvage. The optimal management of prostate cancer in patients with an elevated prostate-specific antigen (PSA) level after radical prostatectomy remains unclear. Methods. We reviewed the records of 54 patients with node-negative prostate cancer treated with radiotherapy alone between 1991 and 1998 for isolated biochemical relapse after prostatectomy. The median preoperative PSA level was 15 ng/mL, and the median salvage PSA level was 1.3 ng/mL. Complete pathologic information was recorded, as was the interval to postoperative PSA failure. Radiotherapy was delivered to the prostatic fossa using appropriate techniques. The primary endpoint was biochemical failure, measured from radiotherapy initiation to the first detectable PSA level. Biochemical control rates were determined using Kaplan-Meier methods. The median follow-up was 45 months. Results. The initial complete response rate was 76%. Only seminal vesicle status demonstrated borderline significance for the rate of the initial complete response, The 5-year actuarial biochemical control rate was 35%. The presence of seminal vesicle invasion, Gleason score greater than 6, and an immediately detectable postoperative PSA level all predicted for decreased 5-year biochemical control. Gleason score and detectable postoperative PSA retained significance on multivariate analysis. Those with a salvage PSA level of 1.2 ng/mL or less had a trend toward a decreased 5-year biochemical control rate (P = 0.07). Conclusions. Salvage radiotherapy yields a 76% complete response rate, with 35% of treated patients free of a detectable PSA at 5 years. Those with favorable biochemical and pathologic tumor features are most likely to remain disease free. (C) 2002, Elsevier Science Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Chawla, AK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Blossom St Cox 302, Boston, MA 02114 USA. NR 19 TC 76 Z9 76 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 MAY PY 2002 VL 59 IS 5 BP 726 EP 731 AR PII S0090-4295(02)01540-6 DI 10.1016/S0090-4295(02)01540-6 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 549QF UT WOS:000175455200017 PM 11992848 ER PT J AU Thompson, CA Oesterle, SN AF Thompson, CA Oesterle, SN TI Biointerventional cardiology: the future interface of interventional cardiovascular medicine and bioengineering SO VASCULAR MEDICINE LA English DT Article DE bioengineering; cardiomyopathy; cardiomyoplasty; congestive heart failure; gene; percutaneous; tissue engineering ID MYOCARDIAL GENE-TRANSFER; SKELETAL MYOBLAST TRANSPLANTATION; REPLICATION-DEFECTIVE ADENOVIRUS; MARROW STROMAL CELLS; IN-VIVO; PHOTODYNAMIC THERAPY; MOTEXAFIN LUTETIUM; HEART FUNCTION; CELLULAR CARDIOMYOPLASTY; CARDIOMYOCYTE GRAFTS AB Major advances in cardiovascular intervention for chronic disease are underway. These innovations lie at the interface of minimally invasive catheter-based. technologies and biologic approaches for the management of complex cardiovascular diseases. This review highlights key areas where much 'biointerventional' cardiovascular therapies are envisioned to occur: cardiac cell transplantation; myocardial gene therapy, genetic and photodynamic endovascular interventions, and vascular tissue engineering. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Cardiovasc Div, Cardiac Catheterizat Labs, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Tissue Engn Lab, Boston, MA 02114 USA. RP Thompson, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Cardiovasc Div, Cardiac Catheterizat Labs, 55 Fruit St,Blake 950, Boston, MA 02114 USA. NR 69 TC 4 Z9 4 U1 2 U2 2 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PD MAY PY 2002 VL 7 IS 2 BP 135 EP 140 DI 10.1191/1358863x02vm417ra PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 604HY UT WOS:000178614300007 PM 12402993 ER PT J AU Larsen, G Hallstrom, A McAnulty, J Pinski, S Olarte, A Sullivan, S Brodsky, M Powell, J Marchant, C Jennings, C Akiyama, T AF Larsen, G Hallstrom, A McAnulty, J Pinski, S Olarte, A Sullivan, S Brodsky, M Powell, J Marchant, C Jennings, C Akiyama, T CA AVID Investigators TI Cost-effectiveness of the implantable cardioverter-defibrillator versus antiarrhythmic drugs in survivors of serious ventricular tachyarrhythmias - Results of the Antiarrhythmics Versus Implantable Defibrillators (AVID) economic analysis substudy SO CIRCULATION LA English DT Article DE cost-benefit analysis; heart arrest; antiarrhythmia agents; defibrillation; tachyarrhythmias ID PREVENTION; AMIODARONE; DISEASE; DEATH; CIDS AB Background-The implantable cardioverter-defibrillator (ICD) is an effective but expensive device. We used prospectively collected data from a large randomized clinical trial of secondary prevention of life-threatening ventricular arrhythmias to determine the cost-effectiveness of the ICD compared with antiarrhythmic drug (AAD) therapy, largely with amiodarone. Methods and Results-Charges for initial and repeat hospitalizations, emergency room, and day surgery stays and the costs of antiarrhythmic drugs were collected on 1008 patients. Detailed records of all other medical encounters and expenses were collected on a subgroup of 237 patients. Regression models were then created to attribute these expenses to the rest of the patients. Charges were converted to 1997 costs using standard methods. Costs and life years were discounted at 3% per year. Three-year survival data from the Antiarrhythmics Versus Implantable Defibrillators trail were used to calculate the base-case cost-effectiveness (C/E) ratio. Six-year, twenty-year, and lifetime C/E ratios were also estimated. At 3 years. total costs were $71 421 for a patient taking AADs and $85 522 for a patient using an ICD, and the ICD provided a 0.21-year survival benefit over AAD treatment. The base-case C/E ratio was thus $66 677 per year of life saved by the ICD compared with AAD therapy (95% Cl. $30 761 to $154 768). Six- and 20-year C/E ratios remained stable between $68 000 and $80 000 per year of life saved. Conclusions-The ICD is moderately cost-effective for secondary prevention of life-threatening ventricular arrhythmias, as judged from prospectively collected data in a randomized clinical trial. C1 Portland VA Med Ctr, Cardiol Sect, Portland, OR USA. AVID Clin Trial Ctr, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Oregon Hlth Sci Univ, Div Cardiol, Portland, OR 97201 USA. Rush Presbyterian St Lukes Med Ctr, Cardiol Sect, Rush Med Coll, Chicago, IL 60612 USA. Univ Washington, Dept Pharm, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Calif Irvine, Dept Cardiol, Irvine, CA USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Rochester, Dept Cardiol, Rochester, NY USA. RP Larsen, G (reprint author), Portland VA Med Ctr, Cardiol Sect, P-3-CARD,3710 SW US Vet Hosp Rd, Portland, OR USA. FU NHLBI NIH HHS [N01-HC-25117] NR 16 TC 77 Z9 78 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 30 PY 2002 VL 105 IS 17 BP 2049 EP 2057 DI 10.1161/01.CIR.0000015504.57641.D0 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 548YR UT WOS:000175418000018 PM 11980684 ER PT J AU Vijg, J Dolle, MET AF Vijg, J Dolle, MET TI Large genome rearrangements as a primary cause of aging SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE aging; genome rearrangements; LacZ reporter genes; nuclear architecture; mutations ID IN-VIVO MUTATIONS; TRANSGENIC MICE; WERNER-SYNDROME; REPAIR; AGE; INSTABILITY; ACCUMULATION; ABERRATIONS; EVOLUTION; FREQUENCY AB In his introductory chapter of the Mutation Research special issue on 'Genetic Instability and Aging', the late Bernard Strehler provided some historical perspectives on the long-standing hypothesis that aging is primarily caused by changes in the genome of somatic cells (Strehler, 1995, Mutat. Res. 338 (1995) 3). Based on his own findings of a loss of ribosomal RNA gene copies in postmitotic tissues of dogs as well as humans during aging, his main conclusion was that deletional mutations are more likely than point mutations to be a main causal factor in aging. To directly assess the levels of different types of spontaneous mutations in organs and tissues during aging, we have used a mouse model harboring a chromosomally integrated cluster of lacZ-containing plasmids that can be recovered and analyzed in Escherichia coli. Our results indicate the accumulation of mutations in some but not all organs of the mouse with significant differences in mutational spectra. In addition to point mutations, genome rearrangements involving up to 66 Mb of genomic DNA appeared to be a major component of the mutational spectra. Physical characterization of the breakpoints of such rearrangements indicated their possible origin by erroneous, non-homologous DNA double-strand break repair. Based on their increased occurrence during aging in some tissues and their often very large size, we have designed a model for an aging tissue in terms of a cellular mosaic with a gradual increase in genome rearrangements that leads to functional senescence, neoplastic transformation or death of individual cells by disrupting nuclear architecture and patterns of gene regulation. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 STCBM, Sam & Ann Barshop Ctr Aging & Longev Res, Dept Physiol, San Antonio, TX 78245 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Vijg, J (reprint author), STCBM, Sam & Ann Barshop Ctr Aging & Longev Res, Dept Physiol, Room 2-200,15355 Lambda Dr, San Antonio, TX 78245 USA. FU NIA NIH HHS [AG 13319, AG 17242]; NIEHS NIH HHS [ES 11044] NR 39 TC 89 Z9 93 U1 0 U2 12 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD APR 30 PY 2002 VL 123 IS 8 BP 907 EP 915 AR PII S0047-6374(02)00028-3 DI 10.1016/S0047-6374(02)00028-3 PG 9 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 580MN UT WOS:000177238500012 PM 12044939 ER PT J AU Uyemura, K Castle, SC Makinodan, T AF Uyemura, K Castle, SC Makinodan, T TI The frail elderly: role of dendritic cells in the susceptibility of infection SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE aging; dendritic cells; frail elderly; cytokines ID T-HELPER CELL; PERIPHERAL-BLOOD; IMMUNE-RESPONSE; INTERLEUKIN-2 PRODUCTION; SENIEUR PROTOCOL; IL-10; SYSTEM; PROLIFERATION; POPULATIONS; ACTIVATION AB The decline in immunity in the elderly has largely been attributed to impairment of T cell mechanisms. This seems reasonable since the thymus involutes with age, so that the number of naive cells to respond to new foreign antigens also declines. However, little is known about how aging affects antigen-presenting cells (APC) that are responsible for the initiation and outcome of effector T cell immune responses. This review focuses on the age-related alterations of a key APC, the dendritic cell (DC). Recent findings suggest that interleukin-10, a key cytokine that can suppress cell mediated immunity and maturation of DC subsets, is elevated in the very healthy elderly. However, production of IL-12, required for the initiation of T cell immune responses, declines in frail elderly along with DC antigen presenting function. These findings suggest that shifts in IL-10 and IL-12 may not only directly influence immune response but may also alter the balance and maturation of DC subsets. Finally, study of immunologic differences between the very healthy and frail elderly may reveal important changes in DC function and regulation influenced by age and/or environment (disease, nutrition, medications, etc.). (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. Vet Adm Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. RP Uyemura, K (reprint author), Univ Calif Los Angeles, Sch Med, Dept Med, 11301 Wilshisre Blvd,Bldg 113,Room 257, Los Angeles, CA 90073 USA. NR 42 TC 68 Z9 73 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD APR 30 PY 2002 VL 123 IS 8 BP 955 EP 962 AR PII S0047-6374(02)00033-7 DI 10.1016/S0047-6374(02)00033-7 PG 8 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 580MN UT WOS:000177238500017 PM 12044944 ER PT J AU Guo, ZM Mitchell-Raymundo, F Yang, H Ikeno, Y Nelson, J Diaz, V Richardson, A Reddick, R AF Guo, ZM Mitchell-Raymundo, F Yang, H Ikeno, Y Nelson, J Diaz, V Richardson, A Reddick, R TI Dietary restriction reduces atherosclerosis and oxidative stress in the aorta of apolipoprotein E-deficient mice SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article; Proceedings Paper CT 5th International NILS Workshop on Longevity Sciences CY NOV 30-DEC 01, 2000 CL AICHI, JAPAN SP Japan Fdn Aging & Hlth DE atherosclerosis; mouse; apolipoprotein E; dietary restriction ID HUMAN-ENDOTHELIAL-CELLS; AGE-RELATED-CHANGES; FOOD RESTRICTION; LIPID-PEROXIDATION; PLASMA TRIGLYCERIDE; CALORIE RESTRICTION; ANTIOXIDANT ENZYMES; PROTEIN OXIDATION; FISCHER-344 RATS; GENE-EXPRESSION AB Dietary restriction (DR) has been shown to inhibit almost all the age-related diseases, e.g. cardiomyopathy and cancers, in rodents. However, there is little information for the effect of DR on atherosclerosis. In the present study, we examined the effect of DR on the development of atherosclerosis in mice homozygous knockout for apolipoprotein E gene (ApoE(-/-)). The ApoE(-/-) mice were fed either ad libitum (AL) or 60% of the diet consumed by the mice fed AL. Atherosclerotic lesions in the proximal aorta of these mice were measured. Our results showed that ApoE(-/-) mice fed the calorie-restricted diet had smaller and relatively early stages of atherosclerotic lesions (e.g. foam cells and free lipids) when compared to ApoE(-/-) mice fed AL, who developed more advanced lesions (e.g. fibrous caps and acellular areas). In addition, ApoE(-/-) mice fed the calorie-restricted diet showed a significant decrease in the level of lipid hydroperoxides and the production of superoxide and hydrogen peroxide in the aorta as compared to ApoE(-/-) mice fed AL. These observations suggest that reduction of oxidative stress in the arterial wall may contribute to the anti-atherogenic effect of DR in ApoE(-/-) mice. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Audie L Murphy Div, San Antonio, TX 78284 USA. Sam & Ann Barshop Ctr Longev & Aging Studies, San Antonio, TX 78284 USA. RP Guo, ZM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Physiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIA NIH HHS [P01 AG13319, AG 16998] NR 56 TC 74 Z9 75 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD APR 30 PY 2002 VL 123 IS 8 BP 1121 EP 1131 AR PII S0047-6374(02)00008-8 DI 10.1016/S0047-6374(02)00008-8 PG 11 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 580MN UT WOS:000177238500035 PM 12044962 ER PT J AU Liu, TX Zhou, Y Kanki, JP Deng, M Rhodes, J Yang, HW Sheng, XM Zon, LI Look, AT AF Liu, TX Zhou, Y Kanki, JP Deng, M Rhodes, J Yang, HW Sheng, XM Zon, LI Look, AT TI Evolutionary conservation of zebrafish linkage group 14 with frequently deleted regions of human chromosome 5 in myeloid malignancies SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POLYMERASE CHAIN-REACTION; MYELODYSPLASTIC SYNDROME; MOLECULAR DELINEATION; POSITIONAL CLONING; GENE; LEUKEMIA; GENOME; 5Q-SYNDROME; MAP; IDENTIFICATION AB Recurring interstitial loss of all or part of the long arm of chromosome 5, del(5q), is a hallmark of myelodysplastic syndrome and acute myeloid leukemia. Although the genes affected by these changes have not been identified, two critically deleted regions (CDRs) are well established. We have identified 76 zebrafish cDNAs orthologous to genes located in these 5q CDRs. Radiation hybrid mapping revealed that 33 of the 76 zebrafish orthologs are clustered in a genomic region on linkage group 14 (LG14). Fifteen others are located on LG21, and two on LG10. Although there are large blocks of conserved syntenies, the gene order between human and zebrafish is extensively inverted and transposed. Thus, intrachromosomal rearrangements and inversions appear to have occurred more frequently than translocations during evolution from a common chordate ancestor. Interestingly, of the 33 orthologs located on LG14, three have duplicates on LG21, suggesting that the duplication event occurred early in the evolution of teleosts. Murine orthologs of human 5q CDR genes are distributed among three chromosomes, 18, 11, and 13. The order of genes within the three syntenic mouse chromosomes appears to be more colinear with the human order, suggesting that translocations occurred more frequently than inversions during mammalian evolution, Our comparative map should enhance understanding of the evolution of the del(5q) chromosomal region. Mutant fish harboring deletions affecting the 5q CDR syntenic region may provide useful animal models for investigating the pathogenesis of myelodysplastic syndrome and acute myeloid leukemia. C1 Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. RP Look, AT (reprint author), Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, 300 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA 93152, R01 CA093152] NR 47 TC 32 Z9 33 U1 1 U2 1 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 APR 30 PY 2002 VL 99 IS 9 BP 6136 EP 6141 DI 10.1073/pnas.072560099 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 548FK UT WOS:000175377800071 PM 11983906 ER PT J AU Okuno, Y Iwasaki, H Huettner, CS Radomska, HS Gonzalez, DA Tenen, DG Akashi, K AF Okuno, Y Iwasaki, H Huettner, CS Radomska, HS Gonzalez, DA Tenen, DG Akashi, K TI Differential regulation of the human and murine CD34 genes in hematopoietic stem cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BONE-MARROW; C-KIT; ARTIFICIAL CHROMOSOME; PERIPHERAL-BLOOD; IN-VIVO; EXPRESSION; TRANSPLANTATION; ENGRAFTMENT; PROGENITOR; RECONSTITUTION AB Human CD34 (hCD34)-positive cells are used currently as a source for hematopoietic transplantation in humans. However, in steady-state murine hematopoiesis, hematopoietic stem cells (HSCs) with long-term reconstitution activity are found almost exclusively in the murine CD34 (mCD34)-negative to low fraction. To evaluate the possible differences in hCD34 and mCD34 gene expression in hematopoiesis, we made transgenic mouse strains with human genomic Fill artificial chromosome clones spanning the entire hCD34 genomic locus. In all transgenic mouse strains, a vast majority of phenotypic and functional HSC populations including mCD34(-/lo) express the hCD34 transgene. These data strongly support the notion that hCD34(+) human bone marrow cells contain long-term HSCs that can maintain hematopoiesis throughout life. C1 Harvard Univ, Inst Med, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Tenen, DG (reprint author), Harvard Univ, Inst Med, Div Hematol Oncol, Room 954,77 Ave Louis Pasteur, Boston, MA 02115 USA. OI Tenen, Daniel/0000-0002-6423-3888 NR 29 TC 52 Z9 52 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 APR 30 PY 2002 VL 99 IS 9 BP 6246 EP 6251 DI 10.1073/pnas.092027799 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 548FK UT WOS:000175377800090 PM 11983914 ER PT J AU Communal, C Sumandea, M de Tombe, P Narula, J Solaro, RJ Hajjar, RJ AF Communal, C Sumandea, M de Tombe, P Narula, J Solaro, RJ Hajjar, RJ TI Functional consequences of caspase activation in cardiac myocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FAILING HUMAN HEART; DILATED CARDIOMYOPATHY; HUMAN MYOCARDIUM; SARCOPLASMIC-RETICULUM; APOPTOSIS; FAILURE; IDENTIFICATION; TROPONIN; RELEASE AB Cardiomyocyte apoptosis is present in many cardiac disease states, including heart failure and ischemic heart disease. Apoptosis is associated with the activation of caspases that mediate the cleavage of vital and structural proteins. However, the functional contribution of apoptosis to these conditions is not known. Furthermore, in cardiac myocytes, apoptosis may not be complete, allowing the cells to persist for a prolonged period within the myocardium. Therefore, we examined whether caspase-3 cleaved cardiac myofibrillar proteins and, if so, whether it affects contractile function. The effects of caspase-3 were studied in vitro on individual components of the cardiac myofilament including a-actin, a-actinin, myosin heavy chain, myosin light chain 1/2, tropomyosin, cardiac troponins (T, 1, Q, and the trimeric troponin complex. Exposure of the myofibrillar protein (listed above) to caspase-3 for 4 h resulted in the cleavage of a-actin and a-actinin, but not myosin heavy chain, myosin light chain 1/2, and tropomyosin, into three fragments (30, 20, and 15 kDa) and one major fragment (45 kDa), respectively. When cTnT, cTnI, and cTnC were incubated individually with caspase-3, there was no detectable cleavage. However, when the recombinant troponin complex was exposed to caspase-3, cTnT was cleaved, resulting in fragments of 25 kDa. Furthermore, rat cardiac myofilaments exposed to caspase-3 exhibited similar patterns of myofibrillar protein cleavage. Treatment with the caspase inhibitor DEVD-CHO or z-VAD-fmk abolished the cleavage. Myofilaments, isolated from adult rat ventricular myocytes after induction of apoptotic pathway by using beta-adrenergic stimulation, displayed a similar pattern of actin and TnT cleavage. Exposure of skinned fiber to caspase-3 decreased maximal Ca2+-activated force and myofibrillar ATPase activity. Our results indicate that caspase-3 cleaved myofibrillar proteins, resulting in an impaired force/Ca2+ relationship and myofibrillar ATPase activity. Induction of apoptosis in cardiac cells was associated with similar cleavage of myofilaments. Therefore, activation of apoptotic pathways may lead to contractile dysfunction before cell death. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Illinois, Dept Physiol & Biophys, Chicago, IL 60612 USA. Med Coll Penn & Hahnemann Univ, Div Cardiol, Philadelphia, PA 19102 USA. RP Hajjar, RJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St,CNY-4, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [R01 HL061557, F32 HL010409, F32HL10409-02, HL 57623, HL61557, P01 HL062426, P01-HL62426]; PHS HHS [R01-63704] NR 23 TC 240 Z9 261 U1 3 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 30 PY 2002 VL 99 IS 9 BP 6252 EP 6256 DI 10.1073/pnas.092022999 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 548FK UT WOS:000175377800091 PM 11972044 ER PT J AU Hirsch, E Barberis, L Brancaccio, M Azzolino, O Xu, DZ Kyriakis, JM Silengo, L Giancotti, FG Tarone, G Fassler, R Altruda, F AF Hirsch, E Barberis, L Brancaccio, M Azzolino, O Xu, DZ Kyriakis, JM Silengo, L Giancotti, FG Tarone, G Fassler, R Altruda, F TI Defective Rac-mediated proliferation and survival after targeted mutation of the beta(1) integrin cytodomain SO JOURNAL OF CELL BIOLOGY LA English DT Article DE integrin; cytodomain; RAC; MAPK; proliferation ID FOCAL ADHESION KINASE; CELL-CYCLE PROGRESSION; JUN NH2-TERMINAL KINASE; ADAPTER PROTEIN SHC; CYTOPLASMIC DOMAIN; C-JUN; DISTINCT ROLES; G(1) PHASE; ACTIVATION; BINDING AB Cell matrix adhesion is required for cell proliferation and survival. Here we report that mutation by gene targeting of the cytoplasmic tail of beta(1) integrin leads to defective proliferation and survival both in vivo and in vitro. Primary murine embryonic fibroblasts (MEFs) derived from mutant homozygotes display defective cell cycle coupled to impaired activation of the FAK-PI3K-Akt and Rac-JNK signaling pathways. Expression in homozygous MEFs of a constitutively active form of Rac is able to rescue proliferation, survival, and JNK activation. Moreover, although showing normal Erk phosphorylation, mutant cells fail to display Erk nuclear translocation upon fibronectin adhesion. However, expression of the constitutively activated form of Rac restores Erk nuclear localization, suggesting that adhesion-dependent Rac activation is necessary to integrate signals directed to promote MAPK activity. Altogether, our data provide the evidence for an epistatic interaction between the beta(1) integrin cytoplasmic domain and Rac, and indicate that this anchorage-dependent signaling pathway is crucial for cell growth control. C1 Univ Turin, Dipartimento Genet Biol & Biochim, I-10126 Turin, Italy. San Giovanni Battista Hosp, Expt Med Res Ctr, I-10126 Turin, Italy. Max Planck Inst Biochem, D-8285 Martinsried, Germany. Univ Lund Hosp, Dept Expt Pathol, S-22285 Lund, Sweden. Massachusetts Gen Hosp, Med Serv, Diabet Res Lab, Boston, MA 02129 USA. Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA. RP Hirsch, E (reprint author), Univ Turin, Dipartimento Genet Biol & Biochim, Via Santena 5, I-10126 Turin, Italy. EM emilio.hirsch@unito.it RI Hirsch, Emilio/F-4848-2013; OI Hirsch, Emilio/0000-0002-9073-6024; Tarone, Guido/0000-0003-4805-086X NR 47 TC 63 Z9 64 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD APR 29 PY 2002 VL 157 IS 3 BP 481 EP 492 DI 10.1083/jcb.200111065 PG 12 WC Cell Biology SC Cell Biology GA 566KH UT WOS:000176427000012 PM 11980921 ER PT J AU Peng, Z Hauer, B Mihalek, RM Homanics, GE Sieghart, W Olsen, RW Houser, CR AF Peng, Z Hauer, B Mihalek, RM Homanics, GE Sieghart, W Olsen, RW Houser, CR TI GABA(A) receptor changes in delta subunit-deficient mice: Altered expression of alpha 4 and gamma 2 subunits in the forebrain SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE GABA; immunohistochemistry; knockout mice; synaptic inhibition ID AMINOBUTYRIC ACID(A) RECEPTOR; TEMPORAL-LOBE EPILEPSY; RAT-BRAIN; MESSENGER-RNAS; IN-SITU; CEREBRAL-CORTEX; THALAMIC NUCLEI; TRANSGENIC MICE; GENE-EXPRESSION; HIPPOCAMPUS AB The 6 subunit is a novel subunit of the pentameric gamma-aminobutyric acid (GABA)A receptor that conveys special pharmacological and functional properties to recombinant receptors and may be particularly important in mediating tonic inhibition. Mice that lack the 8 subunit have been produced by gene-targeting technology, and these mice were studied with immunohistochemical and immunoblot methods to determine whether changes in GABA(A) receptors were limited to deletion of the 8 subunit or whether alterations in other GABA(A) receptor subunits were also present in the 8 subunit knockout (delta-/-) mice. Immunohistochemical studies of wild-type mice confirmed the restricted distribution of the 8 subunit in the forebrain. Regions with moderate to high levels of 6 subunit expression included thalamic relay nuclei, caudate-putamen, molecular layer of the dentate gyrus, and outer layers of the cerebral cortex. Virtually no 8 subunit labeling was evident in adjacent regions, such as the thalamic reticular nucleus, hypothalamus, and globus pallidus. Comparisons of the expression of other subunits in delta-/- and wild-type mice demonstrated substantial changes in the alpha4 and gamma2 subunits of the GABA(A) receptor in the delta-/- mice. gamma2 Subunit expression was increased, whereas alpha4 subunit expression was decreased in delta-/- mice. Importantly, alterations of both the a4 and the gamma2 subunits were confined primarily to brain regions that normally expressed the 8 subunit. This suggests that the additional subunit changes are directly linked to loss of the 8 subunit and could reflect local changes in subunit composition and function of GABAA receptors in delta-/- mice. (C) 2002 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. Univ Vienna, Brain Res Inst, Div Biochem & Mol Biol, A-1090 Vienna, Austria. Univ Vienna, Psychiat Clin, Sect Biochem Psychiat, A-1090 Vienna, Austria. Univ Pittsburgh, Sch Med, Dept Anesthesiol Crit Care Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. RP Houser, CR (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurobiol, CHS 73-235, Los Angeles, CA 90095 USA. RI Sieghart, Werner/A-4877-2013 OI Sieghart, Werner/0000-0002-0443-0302 FU BLRD VA [I01 BX000404]; NIAAA NIH HHS [AA 10422]; NIGMS NIH HHS [GM 47818, GM 52035]; NINDS NIH HHS [NS 35985] NR 58 TC 164 Z9 166 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 29 PY 2002 VL 446 IS 2 BP 179 EP 197 DI 10.1002/cne.10210 PG 19 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 537MA UT WOS:000174761000007 PM 11932935 ER PT J AU Appel, JZ Newman, D Awwad, M Gray, HSK Down, J Cooper, DKC Robson, SC AF Appel, JZ Newman, D Awwad, M Gray, HSK Down, J Cooper, DKC Robson, SC TI Activation of human endothelial cells by mobilized porcine leukocytes in vitro - Implications for mixed chimerism in xenotransplantation SO TRANSPLANTATION LA English DT Article ID LARGE-ANIMAL-MODEL; PLATELET-AGGREGATION; THROMBOTIC MICROANGIOPATHY; NONHUMAN-PRIMATES; PIG; BABOONS; TRANSPLANTATION; TOLERANCE; REGIMEN; MODULATION AB Background. The induction of immunologic tolerance to pig antigens in primates may facilitate the development of successful clinical xenotransplantation protocols. The infusion of mobilized porcine peripheral blood leukocytes (PBPC, consisting of approximately 2% peripheral blood progenitor cells) into preconditioned baboons, intended to induce mixed hematopoietic cell chimerism, however, results in a severe thrombotic microangiopathy (TM) that includes vascular injury, microvascular thrombosis, and pronounced thrombocytopenia. Because the mechanisms responsible for TM are unclear, we have explored the effects of PBPC on human umbilical vein endothelial cell (HUVEC) activation. Methods. Confluent HUVEC monolayers were established in 96-well cell culture clusters. PBPC were mobilized from miniature swine with porcine interleukin 3 (pIL-3), porcine stem cell factor (pSCF), and human granulocyte-colony stimulating factor (hG-CSF) and were collected by leukapheresis. PBPC were added to HUVEC (0-1X10(7) PBPC/well) for 3- to 24-hr periods and, with cell-based ELISA techniques, surface levels of E-selectin, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) were measured. In some cases, peripheral blood leukocytes (PBL) were collected from pigs that did not receive pIL-3, pSCF, or hG-CSF and were added to HUVEC. PBPC were also sorted into subsets of CD2- cells, CD2+ cells, and cellular debris, each of which were added separately to HUVEC. Transwell permeable membrane inserts were placed over HUVEC to prevent direct cell-cell contact with PBPC in some instances. Results. PBPC from different pigs (n=6) induced an increase in the expression of E-selectin, VCAM-1, and ICAM-1 to levels 5,4, and 2 times greater than baseline, respectively. ICAM-1 expression reached maximum levels after the addition of 6X10(5) PBPC/well. Expression of E-selectin and VCAM-l increased further with the addition of greater numbers of PBPC, reaching maximum levels after the addition of 1X10(7) PBPC/well. PBPC-induced up-regulation of E-selectin, VCAM-1, and ICAM-1 had a maximum effect after approximately 6 hr, 12 hr, and 6 to 9 hr, respectively (n=3). The effects of fresh and frozen PBPC on HUVEC were similar (n=2). Compared to PBPC, PBL induced higher levels of E-selectin, VCAM-1, and ICAM-1 on HUVEC (n=2). The addition of CD2- cells to HUVEC induced an increase in E-selectin and VCAM-1 to levels 4 times greater than baseline, whereas the addition of CD2+ cells or debris did not elicit a substantial effect (n=2). Transwell permeable membranes prevented PBPC-induced up-regulation of E-selectin, VCAM-1, and ICAM-1 on HUVEC (n=2), suggesting that the mechanism of activation requires direct cell-cell contact. Conclusions. Porcine PBPC activate HUVEC, as suggested by an increase in surface E-selectin, VCAM-1, and ICAM-1 levels, and have a maximum effect after 9 hr. Freezing of PBPC does not affect PBPC-induced activation of HUVEC. PBL induce greater activation of HUVEC than do PBPC. CD2- cells are primarily responsible for PBPC-induced activation of HUVEC and direct cell-cell contact is required. Removal of CD2- cells before the administration of PBPC or the use of agents that interrupt PBPC-endothelial cell interactions may prevent or treat TM in baboons. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Immunobiol,Dept Med, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. BioTransplant Inc, Charlestown, MA USA. Immerge Biotherapeut Inc, Charlestown, MA USA. RP Robson, SC (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Immunobiol,Dept Med, 99 Brookline Ave,Room 370, Boston, MA 02215 USA. FU NHLBI NIH HHS [HL57307]; NIAID NIH HHS [AI45897] NR 22 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2002 VL 73 IS 8 BP 1302 EP 1309 DI 10.1097/00007890-200204270-00020 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 548AF UT WOS:000175364900020 PM 11981426 ER PT J AU Arnold, R Bartlett, S Bernat, J Colonna, J Dafoe, D Dubler, N Gruber, S Kahn, J Luskin, R Nathan, H Orloff, S Prottas, J Shapiro, R Ricordi, C Youngner, S Delmonico, FL AF Arnold, R Bartlett, S Bernat, J Colonna, J Dafoe, D Dubler, N Gruber, S Kahn, J Luskin, R Nathan, H Orloff, S Prottas, J Shapiro, R Ricordi, C Youngner, S Delmonico, FL TI Financial incentives for cadaver organ donation: An ethical reappraisal SO TRANSPLANTATION LA English DT Article ID BODY AB A panel of ethicists, organ procurement organization executives, physicians, and surgeons was convened by the sponsorship of the American Society of Transplant Surgeons to determine whether an ethically acceptable pilot trial could be proposed to provide a financial incentive for a family to consent to the donation of organs from a deceased relative. An ethical methodology was developed that could be applied to any proposal for monetary compensation to elucidate its ethical acceptability. Am inverse relationship between financial incentives for increasing the families' consent for cadaver donation that clearly would be ethically acceptable (e.g., a contribution to a charity chosen by the family or a reimbursement for funeral expenses) and those approaches that would more likely increase the rate of donation (e.g., direct payment or tax incentive) was evident. The panel was unanimously opposed to the exchange of money for cadaver donor organs because either a direct payment or tax incentive would violate the ideal standard of altruism in organ donation and unacceptably commercialize the value of human life by commodifying donated organs. However, a majority of the panel members supported reimbursement for funeral expenses or a charitable contribution as an ethically permissible approach. The panel concluded that the concept of the organ as a gift could be sustained by a funeral reimbursement or charitable contribution that conveyed the appreciation of society to the family for their donation. Depending on the amount of reimbursement provided for funeral expenses, this approach could be ethically distinguished from a direct payment, by their intrusion into the realm of altruism and voluntariness. We suggest that a pilot project be conducted to determine whether this kind of a financial incentive would be acceptable to the public and successful in increasing organ donation. RP Delmonico, FL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. OI Ricordi, Camillo/0000-0001-8092-7153 NR 15 TC 46 Z9 46 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2002 VL 73 IS 8 BP 1361 EP 1367 DI 10.1097/00007890-200204270-00034 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 548AF UT WOS:000175364900034 PM 11981440 ER PT J AU Bulitta, CJ Fleming, JV Raychowdhury, R Taupin, D Rosenberg, I Wang, TC AF Bulitta, CJ Fleming, JV Raychowdhury, R Taupin, D Rosenberg, I Wang, TC TI Autoinduction of the trefoil factor 2 (TFF2) promoter requires an upstream cis-acting element SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE trefoil peptides; gene regulation; restitution; SPRE ID HUMAN SPASMOLYTIC POLYPEPTIDE; GAGA BOX; RECEPTOR GENE; PEPTIDES; EXPRESSION; TRANSCRIPTION; BINDING; RAT; FAMILY; REGION AB Trefoil factor 2 (TFF2)/spasmolytic polypeptide (SP) is a highly stable peptide which is abundantly expressed and secreted by mucous cells of the stomach and which functions in gastric cytoprotection. Previous studies from our group have shown that TFF2 is an immediate early gene capable of regulating its own expression through activation of the TFF2 promoter. We therefore aimed to investigate the cis-acting elements mediating this response in AGS cells transfected with TFF2 promoter-reporter gene constructs, using a TFF2-expression system resembling physiologic paracrine conditions. TFF2 peptide expression was achieved through stable transfection of AGS cells with a TFF2-expression construct. Stimulation of transiently transfected cells with this TFF2-containing conditioned media resulted in a significant increase in TFF2 promoter activity. Promoter stimulation was blocked by an anti-TFF2 antibody, indicating that it was mediated specifically by TFF2. Deletion analysis of the TFF2 promoter led to the identification of a specific response element located between - 191 and - 174 upstream of the transcriptional initiation site. This region of the promoter. which was designated SPRE (for spasmolytic polypeptide response element), was sufficient to confer responsiveness in a heterologous promoter system. Mutational analysis and electrophoretic mobility shift assays (EMSA) showed that a GAG motif was responsible for mediating promoter activation in response to TFF2 stimulation, Since auto- and cross-induction of TFF2 promoter is likely to be a means of rapid amplification of TFF2 expression in the critical first minutes following mucosal injury, these results should lead to insight into the molecular events initiating epithelial restitution and healing. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Univ Massachusetts, Sch Med, Div Gastroenterol, Worcester, MA 01655 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Canberra Hosp, Gastroenterol Unit, Garran, ACT 2605, Australia. RP Wang, TC (reprint author), Univ Massachusetts, Sch Med, Div Gastroenterol, 365 Plantat St, Worcester, MA 01655 USA. FU NIDDK NIH HHS [R01 DK52778, R01 DK 58889] NR 36 TC 14 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 26 PY 2002 VL 293 IS 1 BP 366 EP 374 AR PII S0006-291X(02)00199-7 DI 10.1016/S0006-291X(02)00199-7 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 550QX UT WOS:000175514700056 PM 12054609 ER PT J AU Qiu, ZH Strickland, DK Hyman, BT Rebeck, GW AF Qiu, ZH Strickland, DK Hyman, BT Rebeck, GW TI alpha 2-macroglobulin exposure reduces calcium responses to N-methyl-D-aspartate via low density lipoprotein receptor-related protein in cultured hippocampal neurons SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LONG-TERM POTENTIATION; TISSUE-PLASMINOGEN ACTIVATOR; APOLIPOPROTEIN-E RECEPTOR; BETA-AMYLOID PEPTIDE; RAT CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; ALPHA(2)-MACROGLOBULIN RECEPTOR; INTRACELLULAR CALCIUM; GLUTAMATE RECEPTORS; CORTICAL-NEURONS AB There is increasing evidence that the low-density lipoprotein receptor-related protein (LRP) can function as a signaling link in the central nervous system. To investigate the pathophysiological role of LRP in the central nervous system, we examined the effects of activated alpha(2)-macroglobulin (alpha2M*), a ligand of LRP, on intracellular calcium signaling in cultured rat hippocampal neurons. Neuronal effects of alpha2M* (50 nM) were assessed by a comparison of calcium signals produced in control and alpha2M*-pretreated neurons by N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid. alpha2M* pretreatment significantly decreased the calcium signals to NMDA, whereas little change was observed for the signals to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid. Native alpha2M, which is not a ligand for LRP, did not affect signals to NMDA. The receptor-associated protein prevented alpha2M*-induced decrease of calcium responses to NMDA, suggesting that alpha2M* exerted its effects through an LRP-mediated pathway. Experiments changing calcium sources demonstrated that alpha2M* pretreatment altered calcium responses to NMDA by primarily changing extracellular calcium influx and subsequently affecting calcium release from intracellular calcium stores. Immunoblot analysis demonstrated that alpha2M* caused a reduction in the levels of the NMDA receptor subunit, NMDAR1. These results suggest that alpha2M* can alter the neuronal response to excitatory neurotransmitters and that alpha2M* pretreatment selectively reduced the calcium responses to NMDA by down-regulating the NMDA receptor. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA. Amer Red Cross, Holland Lab, Rockville, MD 20855 USA. RP Qiu, ZH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 114 16th St, Boston, MA 02129 USA. FU NIA NIH HHS [AG14473, AG12406] NR 57 TC 56 Z9 57 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 APR 26 PY 2002 VL 277 IS 17 BP 14458 EP 14466 DI 10.1074/jbc.M112066200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 545EH UT WOS:000175203000016 PM 11839752 ER PT J AU Liao, YF Gotwals, PJ Koteliansky, VE Sheppard, D Van de Water, L AF Liao, YF Gotwals, PJ Koteliansky, VE Sheppard, D Van de Water, L TI The EIIIA segment of fibronectin is a ligand for integrins alpha(9)beta(1) and alpha(4)beta(1) providing a novel mechanism for regulating cell adhesion by alternative splicing SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXTRA DOMAIN-A; VON-WILLEBRAND-FACTOR; EMBRYONIC FIBRONECTINS; ISOFORM DISTRIBUTION; CRYSTAL-STRUCTURE; III REPEATS; EDA SEGMENT; V-SEGMENT; EXPRESSION; RAT AB Alternative splicing of the fibronectin gene transcript gives rise to forms that include the EIIIA (or ED-A) segment. EIIIA-containing fibronectins are prominently expressed during embryogenesis and wound healing and appear to mediate changes in cell adhesion and gene expression. Nonetheless, integrins that bind the EIIIA segment have not been identified. We previously mapped the epitope for two function-blocking monoclonal antibodies to the C-C' loop region of the EIIIA segment (Liao, Y.-F., Wieder, K. G., Classen, J. M., and Van De Water, L. (1999) J. Biol. Chem. 274, 17876-17884). The sequence of this epitope ((39)PEDGIHELFP(48)) resembles the sequence within tenascin-C to which the integrin alpha(9)beta(1) binds. We now report that either integrin alpha(9)beta(1) or alpha(4)beta(1) can mediate cell adhesion to the EIIIA segment. Moreover, this interaction is blocked both by epitope-mapped EIIIA antibodies as well as by the respective anti-integrins. Deletion mutants of the EIIIA segment that include the C-C' loop and flanking sequence bind cells expressing either alpha(9)beta(1) or alpha(4)beta11. Adhesion of alpha(4)beta(1)-containing MOLT-3 cells to the EIIIA segment stimulates phosphorylation of p44/42 MAP kinase. Our observation that two integrins bind the EIIIA segment establishes a novel mechanism by which cell adhesion to fibronectin is regulated by alternative splicing. C1 Albany Med Coll, Ctr Cell Biol & Canc Res, Albany, NY 12208 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Shriners Burns Hosp, Sch Med, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Med, Lung Biol Ctr, San Francisco, CA 94143 USA. Biogen Inc, Cambridge, MA 02142 USA. RP Van de Water, L (reprint author), Albany Med Coll, Ctr Cell Biol & Canc Res, Mail Code 165,47 New Scotland Ave, Albany, NY 12208 USA. RI Liao, Yung-Feng/A-9761-2011 FU NHLBI NIH HHS [HL47412, HL/AI33259, HL53949, HL56385]; NIGMS NIH HHS [GM56442] NR 61 TC 122 Z9 129 U1 0 U2 6 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 APR 26 PY 2002 VL 277 IS 17 BP 14467 EP 14474 DI 10.1074/jbc.M201100200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 545EH UT WOS:000175203000017 PM 11839764 ER PT J AU Asea, A Rehli, M Kabingu, E Boch, JA Bare, O Auron, PE Stevenson, MA Calderwood, SK AF Asea, A Rehli, M Kabingu, E Boch, JA Bare, O Auron, PE Stevenson, MA Calderwood, SK TI Novel signal transduction pathway utilized by extracellular HSP70 - Role of Toll-like receptor (TLR) 2 AND TLR4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INNATE IMMUNE-RESPONSE; HEAT-SHOCK PROTEINS; BINDING PROTEINS; DROSOPHILA TOLL; FAMILY; MYD88; CELLS; ENDOTOXIN; MICE; HEAT-SHOCK-PROTEIN-70 AB Recent studies have initiated a paradigm shift in the understanding of the function of heat shock proteins (HSP). It is now clear that HSP can and do exit mammalian cells, interact with cells of the immune system, and exert immunoregulatory effects. We recently demonstrated that exogenously added HSP70 possesses potent cytokine activity, with the ability to bind with high affinity to the plasma membrane, elicit a rapid intracellular Ca2+ flux, activate NF-kappaB, and up-regulate the expression of pro-inflammatory cytokines in human monocytes. Here for the first time, we report that HSP70-induced proinflammatory cytokine production is mediated via the MyD88/IRAK/NF-kappaB signal transduction pathway and that HSP70 utilizes both TLR2 (receptor for Gram-positive bacteria) and TLR4 (receptor for Gram-negative bacteria) to transduce its proinflammatory signal in a CD14-dependent fashion. These studies now pave the way for the development of highly effective pharmacological or molecular tools that will either up-regulate or suppress HSP70-induced functions in conditions where HSP70 effects are desirable (cancer) or disorders where HSP70 effects are undesirable (arthritis and arteriosclerosis). C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Univ Regensburg, Hosp Med, Dept Hematol & Oncol, D-93042 Regensburg, Germany. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, New England Baptist Bone & Joint Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St D810, Boston, MA 02115 USA. RI Rehli, Michael/E-9093-2011; Asea, Alexzander/I-4112-2013 OI Rehli, Michael/0000-0003-3992-932X; Asea, Alexzander/0000-0003-3592-3481 FU NCI NIH HHS [CA77465, CA31303, CA47404, CA50642, CA68544]; NIAID NIH HHS [AI44122] NR 44 TC 888 Z9 959 U1 8 U2 58 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 APR 26 PY 2002 VL 277 IS 17 BP 15028 EP 15034 DI 10.1074/jbc.M200497200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 545EH UT WOS:000175203000086 PM 11836257 ER PT J AU Brogi, E Tambouret, R Bell, DA AF Brogi, E Tambouret, R Bell, DA TI Classification of benign endometrial glandular cells in cervical smears from postmenopausal women SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 90th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 03-09, 2001 CL ATLANTA, GEORGIA SP US & Canadian Acad Pathol DE benign endometrial glandular cells; hormone replacement therapy; post-menopausal women; cytology; cervical smears ID HORMONE REPLACEMENT; CARCINOMA; ACETATE AB BACKGROUND. The Bethesda System recommends reporting benign endometrial cells in cervical smears from postmenopausal (PMP) women as a glandular cell abnormality. However, PMP women on hormone replacement therapy (HRT) sometimes may experience endometrial shedding. The significance of such a finding has not been investigated in detail. METHODS. The authors evaluated 85 PMP women with cervical smears that contained benign endometrial glandular cells. Clinical information, including vaginal bleeding and the use of HRT or tamoxifen, was recorded, and follow-up was obtained. RESULTS. Thirty-three PMP women were not on HRT, and 11 women were symptomatic. Twenty women underwent endometrial biopsy: Two symptomatic patients had endometrial adenocarcinoma, and 3 symptomatic patients and 1 asymptomatic patient had endometrial polyps. The frequency of abnormal findings was 18%. Forty-seven PMP women received HRT; 15 were symptomatic. Twenty-two patients underwent endometrial biopsy: 1 symptomatic patient had cystic hyperplasia, and 2 symptomatic patients and 1 asymptomatic patient had an endometrial polyp. The frequency of abnormal findings was 8.5%. No one type of HRT was correlated with specific findings. Five PMP women were on tamoxifen, and two of them were symptomatic. Four patients underwent endometrial sampling: Two of them had an endometrial polyp, which was symptomatic in one patient. CONCLUSIONS. These data confirm that benign endometrial glandular cells in cervical smears from PMP women may indicate endometrial pathology, especially if vaginal bleeding is present. Although atypical endometrial hyperplasia or carcinoma was not identified in the group of PMP women on HRT, endometrial abnormalities of a lesser degree were present in 8.5% of patients. Thus, the authors favor continued classification of benign endometrial glandular cells in cervical smears of PMP women, whether or not they are on HRT, as a glandular cell abnormality. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Cytol Lab, Boston, MA USA. RP Brogi, E (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. NR 20 TC 11 Z9 11 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR 25 PY 2002 VL 96 IS 2 BP 60 EP 66 DI 10.1002/cncr.10478 PG 7 WC Oncology; Pathology SC Oncology; Pathology GA 542YD UT WOS:000175072500002 PM 11954022 ER PT J AU Akiyama, M Yamada, O Kanda, N Akita, S Kawano, T Ohno, T Mizoguchi, H Eto, Y Anderson, KC Yamada, H AF Akiyama, M Yamada, O Kanda, N Akita, S Kawano, T Ohno, T Mizoguchi, H Eto, Y Anderson, KC Yamada, H TI Telomerase overexpression in K562 leukemia cells protects against apoptosis by serum deprivation and double-stranded DNA break inducing agents, but not against DNA synthesis inhibitors SO CANCER LETTERS LA English DT Article DE telomerase; telomeres; human telomerase reverse transcriptase; double-stranded DNA breaks; apoptosis ID REVERSE-TRANSCRIPTASE GENE; CATALYTIC SUBUNIT HTERT; C-MYC; IMMORTAL CELLS; CANCER-CELLS; PROMOTER; EXPRESSION; ACTIVATION; CLONING AB Telomeres are specialized DNA/protein structures that act as protective caps to prevent end fusions. The maintenance of telomeres is essential for chromosomal stability. Telomerase is regulated by human telomerase reverse transcriptase (hTERT). c-Myc oncoprotein is also implicated in the positive regulation of hTERT expression. We show here that two clones of hTERT-transfected K562 erythroleukemia cells have elongated telomeres (22.5 and 24.0 kb), whereas telomere length of both c-Mye-transfected K562 cells and parental K562 cells is 6.5 k-b. Telomerase activity and hTERT mRNA expression increased in hTERT-transfected K562 cells, while the expression levels of telomerase activity and hTERT in cMyc-transfected K562 cells were similar to that in parental K562 cells, despite an overexpression of c-Myc. Importantly, we found that hTERT-transfected K562 cells are protected against apoptosis induced by serum deprivation and double-stranded DNA break inducing agents (ionizing irradiation, and etoposide (VP-16)), but not against DNA synthesis inhibitors (1-0-Darabinofuranosylcytosine and hydroxyurea). These findings suggest that overexpression of telomerase by transfecting hTERT confers telomere - elongation and resistance to double-stranded DNA break inducing agents. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Jikei Univ, Sch Med, Dept Pediat, Minato Ku, Tokyo 1058461, Japan. Jikei Univ, Sch Med, Dept Mol Genet, Inst DNA Med,Minato Ku, Tokyo 1058461, Japan. Tokyo Womens Med Coll, Dept Hematol, Shinjuku Ku, Tokyo 1628666, Japan. Tokyo Univ Agr & Technol, Sch Vet Med, Dept Vet Anat, Fuchu, Tokyo 1838509, Japan. Jikei Univ, Sch Med, Dept Oncol, Minato Ku, Tokyo 1058461, Japan. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Akiyama, M (reprint author), Jikei Univ, Sch Med, Dept Pediat, Minato Ku, 3-25-8 Nishi Shinbashi, Tokyo 1058461, Japan. NR 29 TC 63 Z9 76 U1 0 U2 3 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 APR 25 PY 2002 VL 178 IS 2 BP 187 EP 197 AR PII S0304-3835(01)00838-2 DI 10.1016/S0304-3835(01)00838-2 PG 11 WC Oncology SC Oncology GA 551VG UT WOS:000175582600010 PM 11867204 ER PT J AU Guo, SS Arora, C Shimoide, AT Sawicki, MP AF Guo, SS Arora, C Shimoide, AT Sawicki, MP TI Frequent deletion of chromosome 3 in malignant sporadic pancreatic endocrine tumors SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE pancreatic endocrine tumors; loss of heterozygosity; chromosome 3; tumor suppressor ID NEOPLASIA TYPE-1; SUPPRESSOR GENE; CELL TUMORS; GASTRINOMAS; HETEROZYGOSITY; TUMORIGENESIS; P53; MODEL; LOCI AB Pancreatic endocrine tumors (PETs) arise from neuroendocrine cells in and around the pancreas. As loss of heterozygosity (LOH) of chromosome 3 has been reported in sporadic PETs, we examined 16 sporadic PETs for LOH of 10 polymorphic DNA markers spanning both arms of chromosome 3. LOH was demonstrated in 4 of 8 (50%) sporadic PETs with hepatic metastasis, but in none of 8 sporadic PETs without hepatic involvement. The smallest common-deleted region (SCDR) mapped to 3q27-qter. Analysis of this data with the status of markers on chromosomes 1, 11, and MEN1 mutations in these 16 sporadic PETs revealed that chromosome 3q loss may be a late event in sporadic PET tumorigenesis. These data, combined with reports from other investigators, indicate that chromosome 3q27-qter may contain a tumor suppressor gene that's important in the tumorigenesis of sporadic PETs. (C) 2002 Published by Elsevier Science Ireland Ltd. C1 Univ Calif Los Angeles, Sch Med, Div Gen Surg, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA 90073 USA. RP Sawicki, MP (reprint author), Univ Calif Los Angeles, Sch Med, Div Gen Surg, Room 72-215 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 26 TC 21 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 APR 25 PY 2002 VL 190 IS 1-2 BP 109 EP 114 AR PII S0303-7207(02)00002-3 DI 10.1016/S0303-7207(02)00002-3 PG 6 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 554GT UT WOS:000175728000012 PM 11997184 ER PT J AU Rajewsky, K AF Rajewsky, K TI Cesar Milstein (1927-2002) - Obituary SO NATURE LA English DT Biographical-Item C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 25 PY 2002 VL 416 IS 6883 BP 806 EP 806 DI 10.1038/416806a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 544MH UT WOS:000175163800037 PM 11976669 ER PT J AU Long, A AF Long, A TI The nuts and bolts of peanut allergy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Long, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 7 Z9 8 U1 1 U2 3 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 APR 25 PY 2002 VL 346 IS 17 BP 1320 EP 1322 DI 10.1056/NEJM200204253461712 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 544GX UT WOS:000175150800011 PM 11973369 ER PT J AU Hampton, MB Stamenkovic, I Winterbourn, CC AF Hampton, MB Stamenkovic, I Winterbourn, CC TI Interaction with substrate sensitises caspase-3 to inactivation by hydrogen peroxide SO FEBS LETTERS LA English DT Article DE thiol; cysteine; hydrogen peroxide; oxidation; caspase; apoptosis ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; NITRIC-OXIDE; CYSTEINE PROTEASE; REDOX REGULATION; APOPTOSIS; THIOREDOXIN; INHIBITION AB Caspases have an active site cysteine whose oxidation blocks catalytic activity. Caspase activity, measured in lysates of apoptotic cells, was inhibited by H2O2 with an IC50 of 7 muM. Recombinant caspase-3 was directly inhibited by H2O2, with an estimated second-order rate constant of 750 M-1 s(-1). These values were determined when H2O2 was added while the caspases were cleaving a peptide substrate. There was a 40-fold decrease in sensitivity to inactivation if the substrate was absent at the time of H2O2 addition. These results rationalise conflicting reports of the sensitivity of caspase-3 to H2O2, and identify a novel mechanism for sensitising a thiol enzyme to oxidative inactivation. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. C1 Christchurch Sch Med & Hlth Sci, Free Rad Res Grp, Christchurch, New Zealand. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Cambridge, MA USA. RP Hampton, MB (reprint author), Christchurch Sch Med & Hlth Sci, Free Rad Res Grp, POB 4345, Christchurch, New Zealand. RI Hampton, Mark/A-8490-2008; OI Hampton, Mark/0000-0002-7349-3729 FU NIGMS NIH HHS [GM48614, GM54176] NR 22 TC 54 Z9 55 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 24 PY 2002 VL 517 IS 1-3 BP 229 EP 232 AR PII S0014-5793(02)02629-7 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 545PE UT WOS:000175225600046 PM 12062443 ER PT J AU Yaffe, K Fox, P Newcomer, R Sands, L Lindquist, K Dane, K Covinsky, KE AF Yaffe, K Fox, P Newcomer, R Sands, L Lindquist, K Dane, K Covinsky, KE TI Patient and Caregiver characteristics and nursing home placement in patients with dementia SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ALZHEIMERS-DISEASE DEMONSTRATION; LONG-TERM-CARE; CONTROLLED TRIAL; INSTITUTIONALIZATION; PREDICTORS; BURDEN; TIME; INTERVENTION; EXPERIENCE; POPULATION AB Context The decision to institutionalize a patient with dementia is complex and is based on patient and caregiver characteristics and the sociocultural context of patients and caregivers. Most studies have determined predictors of nursing home placement primarily according to patient or caregiver characteristics alone. Objective To develop and validate a prognostic model to determine the comprehensive predictors of placement among an ethnically diverse population of patients with dementia. Design, Setting, and Participants The Medicare Alzheimer's Disease Demonstration and Evaluation study, a prospective study at 8 sites in the United States, with enrollment between December 1989 and December 1994 of 5788 community-living persons with advanced dementia. Main Outcome Measures Time to nursing home placement throughout a 36-month follow-up period, assessed by interview and review of Medicare records, and its association with patient and caregiver characteristics, obtained by interview at enrollment. Results Patients were divided into a development (n=3859) and validation (n=1929) cohort. In the development cohort, the Kaplan-Meier estimates of nursing home placement throughout 1, 2, and 3 years were 22%, 40%, and 52%, respectively. After multivariate adjustment, patient characteristics that were associated with nursing home placement were as follows: black ethnicity (hazard ratio, 0.60; 95% confidence interval [CI], 0.48-0.74), Hispanic ethnicity (HR, 0.40; 95% Cl, 0.28-0.56) (both ethnicities were inversely associated with placement), living alone (HR, 1.74; 95% Cl, 1.49-2.02), 1 or more dependencies in activities of daily living (HR, 1.38; 95% Cl, 1.20-1.60), high cognitive impairment (for Mini-Mental Status Examination score less than or equal to20: HR, 1.52; 95% Cl, 1.33-1.73), and 1 or more difficult behaviors (HR, 1.30; 95% Cl, 1.11-1.52). Caregiver characteristics associated with patient placement were age 65 to 74 years (HR, 1.17; 95% Cl, 1.01-1.37), age 75 years or older (HR, 1.55; 95% Cl, 1.31-1.84), and high Zarit Burden Scale score (for highest quartile: HR, 1.73; 95% Cl, 1.49-2.00). Patients were assigned to quartiles of risk based on this model. In the development cohort, patients in the first, second, third, and fourth quartile had a 25%, 42%, 64%, and 91% rate of nursing home placement at 3 years, respectively. In the validation cohort, the respective rates were 21%, 50%, 64%, and 89%. The C statistic for 3-year nursing home placement was 0.66 in the development cohort and 0.63 in the validation cohort. Conclusions Patient and caregiver characteristics are both important determinants of long-term care placement for patients with dementia. Interventions directed at delaying placement, such as reduction of caregiver burden or difficult patient behaviors, need to take into account the patient and caregiver as a unit. 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 & Biostat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. Univ Calif San Francisco, Inst Hlth & Aging, 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 111G,4150 Clement St, San Francisco, CA 94121 USA. RI Sands, Laura/E-8919-2015 OI Sands, Laura/0000-0003-2446-4486 FU NIA NIH HHS [K23-AG00888] NR 36 TC 406 Z9 419 U1 6 U2 25 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 APR 24 PY 2002 VL 287 IS 16 BP 2090 EP 2097 DI 10.1001/jama.287.16.2090 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 542ZK UT WOS:000175075700026 PM 11966383 ER PT J AU Solomon, D Davey, D Kurman, R Moriary, A O'Connor, D Prey, M Raab, S Sherman, M Wilbur, D Wright, T Young, N AF Solomon, D Davey, D Kurman, R Moriary, A O'Connor, D Prey, M Raab, S Sherman, M Wilbur, D Wright, T Young, N TI The 2001 Bethesda System - Terminology for reporting results of cervical cytology SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID INTERLABORATORY COMPARISON PROGRAM; CERVICOVAGINAL CYTOLOGY; ADENOCARCINOMA INSITU; SPECIMEN ADEQUACY; ENDOMETRIAL CELLS; UTERINE CERVIX; FOLLOW-UP; FEATURES; LESIONS AB Objectives The Bethesda 2001 Workshop was convened to evaluate and update the 1991 Bethesda System terminology for reporting the results of cervical cytology. A primary objective was to develop a new approach to broaden participation in the consensus process. Participants Forum groups composed of 6 to 10 individuals were responsible for developing recommendations for discussion at the workshop. Each forum group included at least 1 cytopathologist, cytotechnologist, clinician, and international representative to ensure a broad range of views and interests. More than 400 cytopathologists, cytotechnologists, histopathologists, family practitioners, gynecologists, public health physicians, epidemiologists, patient advocates, and attorneys participated in the workshop, which was convened by the National Cancer Institute and cosponsored by 44 professional societies. More than 20 countries were represented. Evidence Literature review, expert opinion, and input from an Internet bulletin board were all considered in developing recommendations. The strength of evidence of the scientific data was considered of paramount importance. Consensus Process Bethesda 2001 was a year-long iterative review process. An Internet bulletin board was used for discussion of issues and drafts of recommendations. More than 1000 comments were posted to the bulletin board over the course of 6 months. The Bethesda Workshop, held April 30-May 2, 2001, was open to the public. Postworkshop recommendations were posted on the bulletin board for a last round of critical review prior to finalizing the terminology. Conclusions Bethesda 2001 was developed with broad participation in the consensus process. The 2001 Bethesda System terminology reflects important advances in biological understanding of cervical neoplasia and cervical screening technology. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Univ Kentucky, Med Ctr, Dept Pathol & Lab Med, Lexington, KY USA. Johns Hopkins Univ Hosp, Dept Gynecol & Obstet, Baltimore, MD 21287 USA. Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. AmeriPath Indiana, Indianapolis, IN USA. Clin Pathol Associates, Louisville, KY USA. Quest Diagnost Inc, St Louis, MO USA. Allegheny Hosp, Dept Pathol, Pittsburgh, PA USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Columbia Univ, Dept Pathol, New York, NY USA. Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA. RP Solomon, D (reprint author), EPN Room 2130,6130 Execut Blvd, Bethesda, MD 20892 USA. RI Manzotti, Grazia/C-5985-2008 NR 28 TC 1589 Z9 1731 U1 6 U2 24 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 APR 24 PY 2002 VL 287 IS 16 BP 2114 EP 2119 DI 10.1001/jama.287.16.2114 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 542ZK UT WOS:000175075700029 PM 11966386 ER PT J AU Kiefe, CI AF Kiefe, CI TI Race/ethnicity and cancer survival - The elusive target of biological differences SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID RACE C1 Univ Alabama, Dept Med, Birmingham, AL 35205 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Kiefe, CI (reprint author), Univ Alabama, Dept Med, 1717 11th Ave S,MT 700, Birmingham, AL 35205 USA. NR 11 TC 13 Z9 13 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 APR 24 PY 2002 VL 287 IS 16 BP 2138 EP 2139 DI 10.1001/jama.287.16.2138 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 542ZK UT WOS:000175075700032 PM 11966389 ER PT J AU Lynch, S Yanagi, G DelBono, E Wiggs, JL AF Lynch, S Yanagi, G DelBono, E Wiggs, JL TI DNA sequence variants in the tyrosinase-related protein 1 (TYRP1) gene are not associated with human pigmentary glaucoma SO MOLECULAR VISION LA English DT Article ID OPEN-ANGLE GLAUCOMA; DISPERSION SYNDROME; MELANOCYTES; MUTATION; ALBINISM; TRP-1 AB Purpose: Pigmentary glaucoma is a common form of glaucoma affecting young adults. Previous studies have suggested that multiple factors, including multiple genetic factors, may be responsible for this condition. Recently, a form of glaucoma associated with pigment dispersion and iris atrophy was identified in the DBA/2J mouse. Abnormalities in the mouse Tyrp1 gene contribute to this condition. The purpose of this study was to determine if DNA sequence variants in the human TYRP1 gene are associated with pigmentary glaucoma in humans. Methods: The protein coding regions and intron/exon boundaries of the human TYRP1 gene were sequenced using genomic DNA samples from probands from pedigrees affected by pigment dispersion syndrome and pigmentary glaucoma. Results: Three novel synonymous single nucleotide polymorphisms (SNPs) were found in two affected individuals. However, these polymorphisms did not define a haplotype that segregated with the disease in the families. DNA sequence variants that altered the amino acid sequence of TYRP1 were not found. Conclusions: Despite the phenotypic similarity between the glaucoma in the DBA/2J mouse and human pigmentary glaucoma, the results of this study suggest that DNA sequence variants in the human TYRP1 gene are not associated with inherited pigmentary glaucoma in humans. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY009847] NR 14 TC 17 Z9 19 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD APR 24 PY 2002 VL 8 IS 16 BP 127 EP 129 PG 3 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 552RM UT WOS:000175633900001 PM 12011806 ER PT J AU Leaf, A AF Leaf, A TI On the reanalysis of the GISSI-Prevenzione SO CIRCULATION LA English DT Editorial Material DE fatty acid; diet; fibrillation; death, sudden ID POLYUNSATURATED FATTY-ACIDS; ADENOVIRAL GENE-TRANSFER; MYOCARDIAL-INFARCTION; PREVENTION; DESATURASE; TRIAL; DEATH; CELLS; DIET C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Leaf, A (reprint author), 149 13th St, Charlestown, MA 02129 USA. EM aleaf@partners.org NR 11 TC 17 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 23 PY 2002 VL 105 IS 16 BP 1874 EP + DI 10.1161/01.CIR.0000015344.46176.99 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 544UJ UT WOS:000175179800001 PM 11997268 ER PT J AU Gibson, CM Cannon, CP Murphy, SA Marble, SJ Barron, HV Braunwald, E AF Gibson, CM Cannon, CP Murphy, SA Marble, SJ Barron, HV Braunwald, E CA TIMI Study Grp TI Relationship of the TIMI myocardial perfusion grades, flow grades, frame count, and percutaneous coronary intervention to long-term outcomes after thrombolytic administration in acute myocardial infarction SO CIRCULATION LA English DT Article DE perfusion; blood flow; trials; myocardial infarction; thrombolysis ID TISSUE-PLASMINOGEN-ACTIVATOR; LEFT-VENTRICULAR FUNCTION; RESCUE ANGIOPLASTY; CONTRAST ECHOCARDIOGRAPHY; RANDOMIZED TRIAL; FOLLOW-UP; REPERFUSION; MORTALITY; IMMEDIATE; SURVIVAL AB Background-Although 90-minute TIMI flow grades (TFGs), corrected TIMI frame counts (CTFCs), and TIMI myocardial perfusion grades (TMPGs) have been associated with 30-day outcomes, we hypothesized that these indices would be related to long-term outcomes after thrombolytic administration. Methods and Results-As a substudy of the TIMI I OB trial (tissue plasminogen activator versus tenecteplase), 49 centers carried out 2-year follow-up. TIMI grade 2/3 flow (Cox hazard ratio [HR] 0.41, P=0.001), reduced CTFCs (faster flow, P=0.02), and an open microvasculature (TMPG 2/3) (HR 0.51, P=0.038) were all associated with improved 2-year survival. Rescue percutaneous coronary intervention (PCI) of closed arteries (TFG 0/1) at 90 minutes was associated with reduced mortality (P=0.03), and mortality trended lower with adjunctive PCI of open (TFG 2/3) arteries (P=0.11). In a multivariate model correcting for previously identified correlates of mortality (age, sex, pulse, left anterior descending coronary artery infarction, and any PCI during initial hospitalization), patency (TFG 2/3) (HR 0.32, P<0.001), CTFC (P=0.01), and TMPG 2/3 remained associated with reduced mortality (HR 0.46, P=0.02). Conclusions-Both improved epicardial flow (TFG 2/3 and low CTFCs) and tissue-level perfusion (TMPG 2/3) at 90 minutes after thrombolytic administration are independently associated with improved 2-year survival, suggesting complementary mechanisms of improved long-term survival. Although rescue PCI reduced long-term mortality, improved microvascular perfusion (TMPG 2/3) before PCI was also related to improved mortality independently of epicardial blood flow and the performance of rescue or adjunctive PCI. Further prospective trials are warranted to re-examine the benefit of early PCI with thrombolysis. C1 Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Boston, MA 02215 USA. Univ Calif San Francisco, Dept Med, Div Cardiovasc, San Francisco, CA USA. RP Gibson, CM (reprint author), Brigham & Womens Hosp, Dept Med, TIMI Study Grp, 930 Commonwealth Ave,3rd Floor, Boston, MA 02215 USA. NR 26 TC 214 Z9 241 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 23 PY 2002 VL 105 IS 16 BP 1909 EP 1913 DI 10.1161/01.CIR.0000014683.52177.B5 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 544UJ UT WOS:000175179800010 PM 11997276 ER PT J AU Rosenberger, PB Rottenberg, DA AF Rosenberger, PB Rottenberg, DA TI Does training change the brain? SO NEUROLOGY LA English DT Editorial Material ID DYSLEXIA C1 Massachusetts Gen Hosp, Learning Disorders Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Neurol Serv, Boston, MA 02114 USA. Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Radiol, Minneapolis, MN 55455 USA. RP Rosenberger, PB (reprint author), Massachusetts Gen Hosp, Learning Disorders Unit, Suite E002E, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 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 APR 23 PY 2002 VL 58 IS 8 BP 1139 EP 1140 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 543QR UT WOS:000175113100001 PM 11971075 ER PT J AU Schwarzschild, MA Chen, JF Ascherio, A AF Schwarzschild, MA Chen, JF Ascherio, A TI Caffeinated clues and the promise of adenosine A(2A) antagonists in PD SO NEUROLOGY LA English DT Review ID ENVIRONMENTAL RISK-FACTORS; MPTP-TREATED MONKEYS; PARKINSONS-DISEASE; RECEPTOR ANTAGONIST; BASAL GANGLIA; KNOCKOUT MICE; CIGARETTE-SMOKING; NERVOUS-SYSTEM; L-DOPA; TWINS AB Large prospective epidemiologic studies have linked the consumption of coffee and other caffeinated beverages to a reduced risk of subsequently developing PD. Caffeine as well as more specific antagonists of the adenosine A(2A) receptor have also now been found to attenuate neurotoxicity in a mouse model of PD. The convergence of these epidemiologic and laboratory data supports the possibility that caffeine may reduce the risk of developing PD. However, a neuroprotective effect of caffeine in PD remains unproven; current evidence does not provide a rational basis for recommending caffeine consumption to modify the risk or progression of PD. In addition to possessing neuroprotective potential, caffeine and other A(2A) antagonists have long been known to acutely reverse motor deficits in a variety of PD models. This symptomatic antiparkinsonian benefit of blocking A(2A) receptors, coupled with their remarkably restricted expression in the basal ganglia, have made A(2A) antagonists attractive targets for drug development. Now, with the prospect of a neuroprotective bonus, the novel therapeutic potential of A(2A) antagonists appears all the more promising just as they are entering clinical trials for PD. C1 Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Dept Neurol, Charlestown, MA 02129 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Schwarzschild, MA (reprint author), Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. FU NIEHS NIH HHS [ES10804] NR 69 TC 94 Z9 98 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 23 PY 2002 VL 58 IS 8 BP 1154 EP 1160 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 543QR UT WOS:000175113100005 PM 11971080 ER PT J AU Scarmeas, N Brandt, J Albert, M Devanand, DP Marder, K Bell, K Ciappa, A Tycko, B Stern, Y AF Scarmeas, N Brandt, J Albert, M Devanand, DP Marder, K Bell, K Ciappa, A Tycko, B Stern, Y TI Association between the APOE genotype and psychopathologic symptoms in Alzheimer's disease SO NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E GENOTYPE; E EPSILON-4 ALLELE; NON-COGNITIVE SYMPTOMS; PSYCHOTIC SYMPTOMS; NONCOGNITIVE SYMPTOMS; EXTRAPYRAMIDAL SIGNS; PSYCHIATRIC-SYMPTOMS; BEHAVIORAL SYMPTOMS; MAJOR DEPRESSION; PRIMARY DEMENTIA AB Background: Psychiatric symptoms occur frequently in the course of AD, are a frequent contributor to institutionalization, predict cognitive decline and death, and often require treatment with psychotropic medications. Previous studies investigating the association between APOE genotype and psychiatric symptomatology in AD have reported contradictory results. Objective: To determine whether APOE genotype predicts incident psychiatric symptomatology in patients with AD. Methods: Eighty-seven patients with AD at early stages and no psychiatric history were followed semiannually for up to 9.3 years (mean 5.5 years) for development of delusions, illusions, hallucinations, behavioral symptoms, and depression. Cox proportional hazards models were used to examine the relative risk for incident psychiatric symptomatology (outcome) in relation to APOE genotype (predictor). Results: The presence of one epsilon4 allele carried a 2.5-fold risk, whereas the presence of two epsilon4 alleles carried a 5.6-fold risk for development of delusions. The associations remained significant even when age, ethnicity, sex, education, duration of disease, and cognitive and functional performance were controlled for. The presence Of two epsilon4 alleles was associated with reduced risk for developing hallucinations in the adjusted analysis only. No significant associations were detected between APOE genotype and the incidence of illusions, behavioral symptoms, or depression. Conclusion: The presence of one or more epsilon4 alleles is a significant predictor for the incidence of delusions in the course of AD. C1 Columbia Univ Coll Phys & Surg, Gertrude H Sergievsky Ctr, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Cognit Neurosci Div, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Stern, Y (reprint author), Columbia Univ Coll Phys & Surg, Gertrude H Sergievsky Ctr, 630 W 168th St, New York, NY 10032 USA. OI Brandt, Jason/0000-0001-7381-6244 FU NCRR NIH HHS [RR00645, M01 RR000645]; NIA NIH HHS [R01 AG007370, R01 AG007370-07, Z01 AG007370] NR 62 TC 66 Z9 69 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 23 PY 2002 VL 58 IS 8 BP 1182 EP 1188 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 543QR UT WOS:000175113100009 PM 11971084 ER PT J AU Killiany, RJ Hyman, BT Gomez-Isla, T Moss, MB Kikinis, R Jolesz, F Tanzi, R Jones, K Albert, MS AF Killiany, RJ Hyman, BT Gomez-Isla, T Moss, MB Kikinis, R Jolesz, F Tanzi, R Jones, K Albert, MS TI MRI measures of entorhinal cortex vs hippocampus in preclinical AD SO NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; TEMPORAL-LOBE; DEMENTIA; ATROPHY; DIAGNOSIS; DEFICITS; SCANS AB Background: MRI measures of the entorhinal cortex and the hippocampus have been used to predict which nondemented individuals with memory problems will progress to meet criteria for AD on follow-up, but their relative accuracy remains controversial. Objectives: To compare MRI measures of the entorhinal cortex and the hippocampus for predicting who will develop AD. Methods: MRI volumes of the entorhinal cortex and the hippocampus were obtained in 137 individuals comprising four groups: 1) individuals with normal cognition both at baseline and after 3 years of follow-up (n = 28), 2) subjects with memory difficulty but not dementia both at baseline and after 3 years of follow-up (n = 73), 3) subjects with memory difficulty at baseline who were diagnosed with probable AD within 3 years of follow-up (n = 21), and 4) patients with mild AD at baseline (n = 16). Results: Measures of both the entorhinal cortex and the hippocampus were different for each of the pairwise comparisons between the groups (p < 0.001) and were correlated with tests of memory (p < 0.01). However, the volume of the entorhinal cortex differentiated the subjects from those destined to develop dementia with considerable accuracy (84%), whereas the measure of the hippocampus did not. Conclusion: These findings are consistent with neuropathologic data showing substantial involvement of the entorhinal cortex in the preclinical phase of AD and suggest that, as the disease spreads, atrophic change develops within the hippocampus, which is measurable on MRI. C1 Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Brandeis Univ, Heller Sch Social Policy, Waltham, MA 02254 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Albert, MS (reprint author), Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [P01-AG04953] NR 58 TC 314 Z9 325 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 23 PY 2002 VL 58 IS 8 BP 1188 EP 1196 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 543QR UT WOS:000175113100010 PM 11971085 ER PT J AU Smith, M Cros, D Sheen, V AF Smith, M Cros, D Sheen, V TI Hyperperfusion with vasogenic leakage by fMRI in migraine with prolonged aura SO NEUROLOGY LA English DT Editorial Material C1 Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Sheen, V (reprint author), Beth Israel Hosp, Harvard Inst Med, Dept Neurol, 8th Floor,77 Ave Louis Pasteur, Boston, MA 02114 USA. FU NIMH NIH HHS [K08 MH063886, IK08MH/NS63886-01] NR 7 TC 33 Z9 33 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 23 PY 2002 VL 58 IS 8 BP 1308 EP 1310 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 543QR UT WOS:000175113100036 PM 11971111 ER PT J AU Chamberlain, MC AF Chamberlain, MC TI Etoposide for recurrent spinal cord ependymoma SO NEUROLOGY LA English DT Editorial Material ID ORAL ETOPOSIDE; PHASE-II; CHILDREN; THERAPY C1 Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Chamberlain, MC (reprint author), Beth Israel Hosp, Harvard Inst Med, Dept Neurol, 8th Floor,77 Ave Louis Pasteur, Boston, MA 02114 USA. NR 7 TC 18 Z9 18 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 APR 23 PY 2002 VL 58 IS 8 BP 1310 EP 1311 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 543QR UT WOS:000175113100037 PM 11971113 ER PT J AU Walensky, RP Losina, E Steger-Craven, KA Freedberg, KA AF Walensky, RP Losina, E Steger-Craven, KA Freedberg, KA TI Identifying undiagnosed human immunodeficiency virus - The yield of routine, voluntary inpatient testing SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID COST-EFFECTIVENESS; VIRAL LOAD; ANTIRETROVIRAL THERAPY; HIV-INFECTION; MEDICAL-CARE; AIDS; INITIATION; DIAGNOSIS; DISEASE; ADULTS AB Background: Despite current recommendations for human immunodeficiency virus (HIV) counseling and testing among patients admitted to hospitals with at least a 1% prevalence of HIV infection, an estimated 300000 people in the United States remain unaware of their HIV infection. Methods: We implemented the Think HIV program, which offered voluntary HIV counseling and testing to patients admitted to the medical service of a Boston, Mass, teaching hospital. We compared the results of this effort with testing results from a 15-month historical control period. Results: Patients admitted during the program period were 3.4 times more likely to undergo testing for HIV than those admitted during the control period (95% confidence interval [CI], 2.8-4.1). The testing program detected approximately 2 new diagnoses of HIV infection per month, compared with 1 per month during the control period. Patients who underwent testing during the program, and who likely would not have done so without this initiative, had an estimated prevalence of HIV infection of 3.8% (95% CI, 1.8%-5.8%). Conclusions: Testing efforts for HIV targeted to only symptomatic patients are inadequate to identify the one third of HIV-seropositive people in the United States who are unaware of their infection. We have shown that in a single urban hospital, offering voluntary, routine inpatient HIV counseling and testing can be successful as a screening program by identifying a substantial number of patients with undiagnosed HIV. These patients then can be informed, counseled, and linked to care and treatment. Seventy-two hospitals nationwide have demographics similar to those of the study hospital, suggesting that these results are generalizable to many urban hospitals. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr,Dept Med, Boston, MA 02114 USA. Boston Med Ctr, Dept Med, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02118 USA. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU AHRQ HHS [5T32HS00020-15]; NIAID NIH HHS [R01 AI042006, R01AI42006]; ODCDC CDC HHS [U64/CCU119525] NR 30 TC 54 Z9 55 U1 0 U2 3 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 APR 22 PY 2002 VL 162 IS 8 BP 887 EP 892 DI 10.1001/archinte.162.8.887 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 542JH UT WOS:000175039400004 PM 11966339 ER PT J AU Goldie, SJ Kaplan, JE Losina, E Weinstein, MC Paltiel, AD Seage, GR Craven, DE Kimmel, AD Zhang, H Cohen, CJ Freedberg, KA AF Goldie, SJ Kaplan, JE Losina, E Weinstein, MC Paltiel, AD Seage, GR Craven, DE Kimmel, AD Zhang, H Cohen, CJ Freedberg, KA TI Prophylaxis for human immunodeficiency virus-related Pneumocystis carinii pneumonia - Using simulation Modeling to inform clinical guidelines SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED PATIENTS; MYCOBACTERIUM-AVIUM COMPLEX; TRIMETHOPRIM-SULFAMETHOXAZOLE; OPPORTUNISTIC INFECTIONS; COST-EFFECTIVENESS; CONTROLLED TRIAL; TOXOPLASMIC ENCEPHALITIS; AEROSOLIZED PENTAMIDINE; SECONDARY PROPHYLAXIS AB Background: Human immunodeficiency virus (HIV)infected patients receiving highly active antiretroviral therapy (HAART) have experienced a dramatic decrease in Pneumocystis carinii pneumonia (PCP), necessitating reassessment of clinical guidelines for prophylaxis. Methods: A simulation model of HIV infection was used to estimate the lifetime costs and quality-adjusted life expectancy (QALE) for alternative CD4 cell count criteria for stopping primary PCP prophylaxis in patients with CD4 cell count increases receiving HAART and alternative agents for second-line PCP prophylaxis in those intolerant of trimethoprim-sulfametlloxazole (TMP/SMX). The target population was a cohort of HIV-infected patients in the United States with initial CD4 cell counts of 350/muL who began PCP prophylaxis after their first measured CD4 lymphocyte count less than 200/muL. Data were from randomized controlled trials and other published literature. Results: For patients with CD4 cell count increases during HAART, waiting to stop prophylaxis until the first observed CD4 cell count was greater than 300/muL prevented 9 additional cases per 1000 patients and cost $9400 per quality-adjusted life year (QALY) gained compared with stopping prophylaxis at 200/muL. For patients intolerant of TMP/SMX, using dapsone increased QALE by 2.7 months and cost $4500 per QALY compared with no prophylaxis. Using atovaquone rather than dapsone provided only 3 days of additional QALE and cost more than $1.5 million per QALY. Conclusions: Delaying discontinuation of PCP prophylaxis until the first observed CD4 cell count greater than 300/uL is cost-effective and provides an explicit "PCP prophylaxis stopping criterion." In TMP/SMX-intolerant patients, dapsone is more cost-effective than atovaquone. C1 Harvard Sch Publ Hlth, Ctr Risk Anal, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Community Res Initiat New England, Brookline, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA. RP Goldie, SJ (reprint author), Harvard Sch Publ Hlth, Ctr Risk Anal, Dept Hlth Policy & Management, 718 Huntington Ave,2nd Floor, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI042006, R01-AI42006]; ODCDC CDC HHS [U64/CCU 114927, U64/CCU 119525-01] NR 78 TC 25 Z9 25 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 APR 22 PY 2002 VL 162 IS 8 BP 921 EP 928 DI 10.1001/archinte.162.8.921 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 542JH UT WOS:000175039400009 PM 11966344 ER PT J AU Nelson, K Norris, K Mangione, CM AF Nelson, K Norris, K Mangione, CM TI Disparities in the diagnosis and pharmacologic treatment of high serum cholesterol by race and ethnicity - Data from the third national health and nutrition examination survey SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; LIPID-LOWERING MEDICATIONS; HIGH BLOOD CHOLESTEROL; UNITED-STATES ADULTS; CARDIOVASCULAR-DISEASE; RISK-FACTORS; ARTERY DISEASE; MYOCARDIAL-INFARCTION; ESTROGEN/PROGESTIN REPLACEMENT; REVASCULARIZATION PROCEDURES AB Background: Serum cholesterol is one of the most important modifiable risk factors for coronary artery disease. There are conflicting data on racial and ethnic variation in the treatment of high cholesterol. Methods: We analyzed data from the Third National Health and Nutrition Examination Survey, a nationally representative cross-sectional survey conducted between 1988 and 1994. Participants included 7679 white, 4467 African American, and 4113 Mexican American adults older than 25 years who completed the household adult questionnaire. The adjusted odds of serum cholesterol screening and of taking a prescription medication to lower serum cholesterol among African Americans and Mexican Americans were compared with those of whites, controlling for differences in age, sex, income, educational level, insurance status, comorbid illness, and having a regular source of health care. Results: African Americans and Mexican Americans were significantly less likely than whites to report ever having had their blood cholesterol checked (odds ratio, 0.7 for both; P<.001). Among individuals with high cholesterol who were told to take a medication, African Americans (P<.001) and Mexican Americans (P=.05) were less likely than whites to be taking a cholesterol-lowering agent (odds ratios, 0.3 and 0.5, respectively). Individuals who reported being told they had high cholesterol had significantly higher serum cholesterol measurements (from the laboratory examination) than those who reported being told their cholesterol was not high (234 vs 198 mg/dL [6.05 vs 5.12 mmol/L]; P<.001). Conclusions: African Americans and Mexican Americans were less likely to report serum cholesterol screening than whites. Even when identified as having high cholesterol that required medication, African Americans and Mexican Americans were less likely than whites to be taking cholesterol-lowering agents. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. Univ Calif Los Angeles, Charles Drew Univ, Dept Internal Med, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Sch Med, Los Angeles, CA USA. RAND Hlth, Santa Monica, CA USA. RP Nelson, K (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, 1660 S Columbian Way,Mail Stop S-111-GIMC, Seattle, WA 98108 USA. FU NCRR NIH HHS [U54RR14616] NR 67 TC 61 Z9 61 U1 1 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 APR 22 PY 2002 VL 162 IS 8 BP 929 EP 935 DI 10.1001/archinte.162.8.929 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 542JH UT WOS:000175039400010 PM 11966345 ER PT J AU Newhauser, WD Myers, KD Rosenthal, SJ Smith, AR AF Newhauser, WD Myers, KD Rosenthal, SJ Smith, AR TI Proton beam dosimetry for radiosurgery: implementation of the ICRU Report 59 at the Harvard Cyclotron Laboratory SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID ELECTRON-BEAMS; RECOMMENDATIONS; THERAPY AB Recent proton dosimetry intercomparisons have demonstrated that the adoption of a common protocol, e.g. ICRU Report 59, can lead to improved consistency in absorbed dose determinations. We compared absorbed dose values, measured in the 160 MeV proton radiosurgery beamline at the Harvard Cyclotron Laboratory, based on ionization chamber methods with those from a Faraday cup technique. The Faraday cup method is based on a proton fluence determination that allows the estimation of absorbed dose with the CEMA approximation, under which the dose is equal to the fluence times the mean mass stopping power. The ionization chamber technique employs an air-kerma calibration coefficient for Co-60 radiation and a calculated correction in order to take into account the differences in response to Co-60 and proton beam radiations. The absorbed dose to water, based on a diode measurement calibrated with a Faraday cup technique, is approximately 2% higher than was obtained from an ionization chamber measurement. At the Bragg peak depth, the techniques agree to within their respective uncertainties, which are both approximately 4% (1 standard deviation). The ionization chamber technique exhibited superior reproducibility and was adopted in our standard clinical practice for radiosurgery. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Dept Radiat Oncol, Boston, MA 02114 USA. RP Newhauser, WD (reprint author), MD Anderson Canc Ctr, Dept Radiat Phys, 1515 Holcombe Blvd, Houston, TX 77030 USA. NR 56 TC 19 Z9 19 U1 0 U2 1 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 APR 21 PY 2002 VL 47 IS 8 BP 1369 EP 1389 AR PII S0031-9155(02)27303-0 DI 10.1088/0031-9155/47/8/310 PG 21 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 550MC UT WOS:000175506000011 PM 12030561 ER PT J AU Barak, O Goshen, I Ben-Hur, T Weidenfeld, J Taylor, AN Yirmiya, R AF Barak, O Goshen, I Ben-Hur, T Weidenfeld, J Taylor, AN Yirmiya, R TI Involvement of brain cytokines in the neurobehavioral disturbances induced by HIV-1 glycoprotein120 SO BRAIN RESEARCH LA English DT Article DE gp120; sickness behavior; IL-1; TNF alpha; IL-10; AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; PITUITARY-ADRENAL AXIS; ENVELOPE PROTEIN GP120; SEXUAL-BEHAVIOR; FACTOR-ALPHA; MYCOPLASMA-FERMENTANS; PSYCHIATRIC-SYMPTOMS; RECEPTOR ANTAGONIST; GLIAL-CELLS AB lntracerebroventricular (i.c.v.) administration of HIV-1 glycoprotein 120 (gp120), the envelope protein used by the virus to gain access into immune cells, induces neurobehavioral alterations in rats. To examine the role of proinflammatory cytokines in mediating these effects, we measured the effects of gp120 on brain proinflammatory cytokine expression and the effects of anti-inflammatory agents, including interleukin-1 receptor antagonist (IL-1ra), pentoxifylline (a TNFalpha synthesis blocker) and IL-10, on gp120-induced sickness behavior. I.c.v. administration of gp120 induced the expression of IL-1beta, but not TNFalpha, mRNA in the hypothalamus. 3 h after the injection. Pretreatment of rats with IL-Ira, but not with pentoxifylline, significantly attenuated gp120-induced anorexia and loss in body weight, whereas both agents had no effect on gp120-induced reduction in locomotor activity in the open field. Pretreatment with either IL-1ra and pentoxifylline simultaneously. or with IL-10, produced effects that were similar to the effects of IL-Ira alone. Together, these findings indicate that IL-1. but not TNFalpha, mediates some of the behavioral effects of acute gp120 administration, suggesting that brain IL-1 may be involved in some of the neurobehavioral abnormalities evident in AIDS patients. (C) 2002 Elsevier Science BV All rights reserved. C1 Hebrew Univ Jerusalem, Dept Psychol, IL-91905 Jerusalem, Israel. Hadassah Univ Hosp, Dept Neurol, IL-91120 Jerusalem, Israel. Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Los Angeles, CA 90095 USA. RP Yirmiya, R (reprint author), Hebrew Univ Jerusalem, Dept Psychol, IL-91905 Jerusalem, Israel. EM msrazy@mscc.huji.ac.il RI Yirmiya, Raz/D-1090-2014 NR 66 TC 34 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 19 PY 2002 VL 933 IS 2 BP 98 EP 108 AR PII S0006-8993(02)02280-1 DI 10.1016/S0006-8993(02)02280-1 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 547YW UT WOS:000175361500002 PM 11931854 ER PT J AU Hellman, J Roberts, JD Tehan, MM Allaire, JE Warren, HS AF Hellman, J Roberts, JD Tehan, MM Allaire, JE Warren, HS TI Bacterial peptidoglycan-associated lipoprotein is released into the bloodstream in gram-negative sepsis and causes inflammation and death in mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI K-12; TOLL-LIKE RECEPTOR-2; BORRELIA-BURGDORFERI LIPOPROTEINS; OUTER-MEMBRANE PROTEINS; MULTIPLE ORGAN FAILURE; NF-KAPPA-B; NITRIC-OXIDE; NUCLEOTIDE-SEQUENCE; LIPOTEICHOIC ACID; CELL ACTIVATION AB Gram-negative bacterial sepsis commonly causes organ dysfunction and death in humans. Although circulating bacterial toxins trigger inflammation in sepsis, little is known about the composition of bacterial products released into the blood during sepsis or the contribution of various bacterial components to the pathogenesis of sepsis. We have shown that diverse Gram-negative bacteria release bacterial peptidoglycan-associated lipoprotein (PAL) into serum. The present studies explored release of PAL into the blood during sepsis and tested the hypothesis that PAL contributes to bacterial virulence and inflammation in Gram-negative sepsis. Released PAL was detected in the blood of 94% of mice following cecal ligation and puncture. Picomolar to nanomolar levels of PAL stimulated macrophages and splenocytes from lipopolysaccharide-hyporesponsive (C3H/HeJ) mice. Injection of PAL into C3H/HeJ mice stimulated production of serum cytokines and increased pulmonary and myocardial expression of inflammatory markers. PAL caused death in sensitized C3H/HeJ mice. Mutant Escherichia coli bacteria with reduced levels of PAL or truncated PAL were less virulent than wild-type bacteria, as indicated by higher survival rates and lower circulating levels of interleukin 6 and bacteria in a model of peritonitis in lipopolysaccharide-responsive mice. The studies suggest that PAL may be an important bacterial mediator of Gram-negative sepsis. C1 Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. RP Hellman, J (reprint author), Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, 149 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL-04237, K08 HL004237, K08 HL004237-02]; NIAID NIH HHS [AI01722]; NIGMS NIH HHS [GM59694] NR 67 TC 56 Z9 58 U1 1 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 APR 19 PY 2002 VL 277 IS 16 BP 14274 EP 14280 DI 10.1074/jbc.M109696200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 543HR UT WOS:000175096000119 PM 11830585 ER PT J AU Drenkard, E Ausubel, FM AF Drenkard, E Ausubel, FM TI Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation SO NATURE LA English DT Article ID SMALL-COLONY VARIANTS; BROWN BLOTCH DISEASE; CYSTIC-FIBROSIS; ESCHERICHIA-COLI; SURFACE HYDROPHOBICITY; PERSISTENT INFECTIONS; BACTERIAL BIOFILMS; AERUGINOSA; STRAINS; MULTIPLE AB Colonization of the lungs of cystic fibrosis (CF) patients by the opportunistic bacterial pathogen Pseudomonas aeruginosa is the principal cause of mortality in CF populations(1,2). Pseudomonas aeruginosa infections generally persist despite the use of long-term antibiotic therapy(1,3). This has been explained by postulating that P. aeruginosa forms an antibiotic-resistant biofilm(4,5) consisting of bacterial communities embedded in an exopolysaccharide matrix. Alternatively, it has been proposed that resistant P. aeruginosa variants may be selected in the CF respiratory tract by antimicrobial therapy itself(1,6). Here we report that both explanations are correct, and are interrelated. We found that antibiotic-resistant phenotypic variants of P. aeruginosa with enhanced ability to form biofilms arise at high frequency both in vitro and in the lungs of CF patients. We also identified a regulatory protein (PvrR) that controls the conversion between antibiotic-resistant and antibiotic-susceptible forms. Compounds that affect PvrR function could have an important role in the treatment of CF infections. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. NR 28 TC 512 Z9 537 U1 14 U2 119 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 18 PY 2002 VL 416 IS 6882 BP 740 EP 743 DI 10.1038/416740a PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 542FU UT WOS:000175033500043 PM 11961556 ER PT J AU Rosen, FS AF Rosen, FS TI Successful gene therapy for severe combined immunodeficiency SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DEFICIENCY; MUTATION; PATIENT C1 Ctr Blood Res, Boston, MA 02115 USA. RP Rosen, FS (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. NR 9 TC 6 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 APR 18 PY 2002 VL 346 IS 16 BP 1241 EP 1243 DI 10.1056/NEJM200204183461612 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 542FT UT WOS:000175033400011 PM 11961154 ER PT J AU Tommasi, S Dammann, R Jin, SG Zhang, XF Avruch, J Pfeifer, GP AF Tommasi, S Dammann, R Jin, SG Zhang, XF Avruch, J Pfeifer, GP TI RASSF3 and NORE1: identification and cloning of two human homologues of the putative tumor suppressor gene RASSF1 SO ONCOGENE LA English DT Article DE RASSF1; tumor suppressor gene; Ras association domain; Nore1 ID COMPARATIVE GENOMIC HYBRIDIZATION; DNA METHYLATION; FAMILY; CANCER; EFFECTORS; PROTEIN; EPIGENETICS; MULTIPLE; DOMAINS; 3P21.3 AB RASSF1A, one of the two major isoforms of the putative tumor suppressor gene RASSF1, located at 3p21.3, is inactivated in a variety of human cancers including lung, breast, bladder and renal cell carcinomas. We have isolated and cloned two human homologues of this gene, RASSF3 and NORE1, located at 12q14.1 and 1q32.1, respectively. Both RASSF3 and NORE1 share almost 60% homology, at the amino acid level, with RASSF1. The RASSF3 gene contains five exons and encodes a 247 amino acid protein (MW of 28.6 kDa) with a highly conserved Ras association (RalGDS/AF-6) (RA) domain at the C-terminus. RASSF3 is ubiquitously expressed in all normal tissues and cancer cell tines analysed. NORE1, which is homologous to the previously described mouse Nore1 gene, exists in at least two spliced isoforms, A and B. Transcript A encodes a protein of 418 amino acids (MW or 47 kDa) while transcript B contains an ORF of 265 aa (MW of 30.5 kDa). Both share a RA domain, encoded by exons 3 through 6. NORE1A and NORE1B are expressed in most of the normal tissues analysed but they appear to be down-regulated in several cancer cell lines. However, contrary to RASSF1A, gene silencing by methylation of the CpG islands at which the two NORE1 transcripts initiate is not a common event in human primary tumors. RASSF3 and NORE1B are very similar, at the N-terminus, to the splice variant C of RASSF1 (RASSF1C), which does not seem to be involved in tumorigenesis. NORE1A is most closely related to RASSF1A, for sequence homology and genomic organization. However, aberrations in tumors have so far not been found. The presence of a Ras association domain common to NORE1, RASSF1, and RASSF3 suggests their possible involvement in Ras-like signaling pathways. C1 Beckman Res Inst, Dept Biol, Duarte, CA 91010 USA. Univ Halle Wittenberg, Inst Humangenet & Med Biol, D-06097 Halle Saale, Germany. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Tommasi, S (reprint author), Beckman Res Inst, Dept Biol, 1450 E Duarte Rd, Duarte, CA 91010 USA. FU NCI NIH HHS [CA88873] NR 41 TC 82 Z9 93 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 18 PY 2002 VL 21 IS 17 BP 2713 EP 2720 DI 10.1038/sj/onc/1205365 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 541RA UT WOS:000174996500011 PM 11965544 ER PT J AU Komatsuzawa, H Asakawa, R Kawai, T Ochiai, K Fujiwara, T Taubman, MA Ohara, M Kurihara, H Sugai, M AF Komatsuzawa, H Asakawa, R Kawai, T Ochiai, K Fujiwara, T Taubman, MA Ohara, M Kurihara, H Sugai, M TI Identification of six major outer membrane proteins from Actinobacillus actinomycetemcomitans SO GENE LA English DT Article DE periodontitis; serum; virulence; Omp29 ID LOCALIZED JUVENILE PERIODONTITIS; YERSINIA-ENTEROCOLITICA; PORPHYROMONAS-GINGIVALIS; SALMONELLA-TYPHIMURIUM; NUCLEOTIDE-SEQUENCE; AIL GENE; LIPOPOLYSACCHARIDE; LEUKOTOXIN; EXPRESSION; RECEPTOR AB We have identified six major sarcosyl-insoluble outer membrane proteins (Omp) of Actinobacillus actinomycetemcomitans Y4, and designated them as Omp100, Omp64, Omp39, Omp29, Omp18 and Omp16 according to the molecular mass. A similar N-terminal sequence was found in the first 15 amino acid residues of Omp16 and Omp18. The N-terminal sequence of Omp29 matched perfectly with the sequence previously identified. We cloned and determined the DNA sequences of three complete genes encoding Omp100, Omp64 and Omp18/16, and one incomplete gene encoding Omp39. Each Omp revealed homologies with some bacterial virulence factors responsible for adhesion, invasion, serum resistance, or protein antigenieity. Serum from patients with periodontitis suspected to be related to A. actinomycetemcomintans infection strongly reacted with Omp100, Omp29 and Omp16 as did serum from mice immunized with A. actinomycetemcomitans Y4 whole bacteria. These findings suggest that Omps of A. actinomycetemcomitans can be associated with periodontal disease. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Hiroshima Univ, Fac Dent, Dept Microbiol, Minami Ku, Hiroshima 7348553, Japan. Hiroshima Univ, Fac Dent, Dept Periodontol & Endodontol, Minami Ku, Hiroshima 7348553, Japan. Forsyth Inst, Dept Immunol, Boston, MA USA. RP Komatsuzawa, H (reprint author), Hiroshima Univ, Fac Dent, Dept Microbiol, Minami Ku, Kasumi 1-2-3, Hiroshima 7348553, Japan. FU NIDCR NIH HHS [DE-03420] NR 30 TC 38 Z9 40 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 17 PY 2002 VL 288 IS 1-2 BP 195 EP 201 AR PII S0378-1119(02)00500-0 DI 10.1016/S0378-1119(02)00500-0 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 565MG UT WOS:000176373600022 PM 12034509 ER PT J AU Perry, GJ Wei, CC Hankes, GH Dillon, SR Rynders, P Mukherjee, R Spinale, FG Dell'Italia, LJ AF Perry, GJ Wei, CC Hankes, GH Dillon, SR Rynders, P Mukherjee, R Spinale, FG Dell'Italia, LJ TI Angiotensin II receptor blockade does not improve left ventricular function and remodeling in subacute mitral regurgitation in the dog SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HEART-FAILURE; CONVERTING ENZYME; CAPTOPRIL; DYSFUNCTION; LOSARTAN; TISSUE; ELITE; TRIAL AB OBJECTIVES We hypothesized that angiotensin II type-1 (AT(1)) receptor blocker (AT(1) RB) would prevent adverse left ventricular (LV) remodeling and LV dysfunction when started at the outset of, mitral regurgitation (MR). BACKGROUND Little is known regarding the efficacy of AT(1)RB treatment of MR. METHODS Mitral regurgitation was induced by chordal disruption in adult mongrel dogs. Six normal dogs (NLs) were compared to six untreated MR dogs (MR and seven dogs treated with the receptor blocker irbesartan (MR+AT(1)RB) started 24 h after induction of MR (60 mg/Lg p.o.b.i.d.) and continued for three months. RESULTS Treatment with AT(1)RB decreased systemic vascular resistance but did not significantly improve cardiac output, LV end-diastolic dimension (LVEDD) or LVEDD/wall thickness, compared to untreated MR dogs. Resting isolated cardiomyocyte length increased in MR versus NLs and was further increased in AT(1)RB dogs. Left ventricular end-systolic dimension increased to a greater extent from baseline in AT,RB dogs versus untreated MR dogs (29 +/- 9% vs. 12 6%, p < 0.05), despite a significantly lower LV peak systolic pressure in AT,RB dogs. Plasma-angiotensin (ANG) II was elevated greater than threefold in both MR and MR+AT(1)RB versus NLs. In contrast, intracardiac ANG II was increased greater than twofold in MR dogs versus NLs, but was normalized by AT(1)RB. CONCLUSIONS The use of AT,RB decreased systemic vascular resistance and attenuated local expression of the renin-angiotensin system ut did not prevent adverse LV chamber and cardiomyocyte remodeling. These results suggest that blockade of the AT, receptor does not improve I.V remodeling and function in the early myocardial adaptive phase of MR. (J Am Coll Cardiol 2002;39:1374-9) (C) 2002 by the American College of Cardiology Foundation. C1 Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. Auburn Coll Vet Med, Auburn, AL USA. Univ Alabama, Dept Med, Div Cardiovasc Dis, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Dell'Italia, LJ (reprint author), Univ Alabama, Dept Med, Div Cardiol, 834 MCLM,1918 Univ Blvd, Birmingham, AL 35294 USA. FU NHLBI NIH HHS [HL57952, R01 HL 54816] NR 20 TC 58 Z9 59 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 17 PY 2002 VL 39 IS 8 BP 1374 EP 1379 AR PII S0935-1097(02)01763-1 DI 10.1016/S0735-1097(02)01763-1 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 541TP UT WOS:000175000800020 PM 11955858 ER PT J AU Ganz, PA Castellon, SA Silverman, DHS AF Ganz, PA Castellon, SA Silverman, DHS TI Estrogen, tamoxifen, and the brain SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID HORMONE REPLACEMENT THERAPY; BREAST-CANCER; ADJUVANT CHEMOTHERAPY; DENSITY; HEALTH; WOMEN; RISK C1 Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Greater Los Angeses Vet Adm Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ahmanson Biol Imaging Ctr, Los Angeles, CA 90024 USA. RP Ganz, PA (reprint author), Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, 650 Charles Young Dr S, Los Angeles, CA 90095 USA. NR 26 TC 7 Z9 7 U1 0 U2 1 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 APR 17 PY 2002 VL 94 IS 8 BP 547 EP 549 PG 3 WC Oncology SC Oncology GA 542AV UT WOS:000175022000002 PM 11959884 ER PT J AU Carabello, BA AF Carabello, BA TI Evaluation and management of patients with aortic stenosis SO CIRCULATION LA English DT Article DE valves; heart diseases; stenosis; aorta ID VALVE-REPLACEMENT; SYMPTOMATIC PATIENTS; NATURAL-HISTORY; ADULTS; DETERMINANTS; PROGNOSIS; GRADIENT; SEVERITY; EXERCISE; SURVIVAL C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX USA. RP Carabello, BA (reprint author), 2002 Holcombe Blvd,111 MCL, Houston, TX 77030 USA. NR 27 TC 50 Z9 57 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 16 PY 2002 VL 105 IS 15 BP 1746 EP 1750 DI 10.1161/01.CIR.0000015343.76143.13 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 543XK UT WOS:000175127700002 PM 11956110 ER PT J AU Sabatine, MS Morrow, DA de Lemos, JA Gibson, CM Murphy, SA Rifai, N McCabe, C Antman, EM Cannon, CP Braunwald, E AF Sabatine, MS Morrow, DA de Lemos, JA Gibson, CM Murphy, SA Rifai, N McCabe, C Antman, EM Cannon, CP Braunwald, E TI Multimarker approach to risk stratification in non-ST elevation acute coronary syndromes - Simultaneous assessment of troponin I, C-reactive protein, and B-type natriuretic peptide SO CIRCULATION LA English DT Article DE coronary disease; prognosis; myocardial infarction; inflammation; natriuretic peptides ID MORTALITY; DISEASE; INFLAMMATION; MECHANISMS AB Background-In patients with acute coronary syndromes (ACS), troponin I (TnI), C-reactive protein (CRP), and B-type natriuretic peptide (BNP) each predict adverse cardiac events. Little is known, however, about the utility of these biomarkers in combination. Methods and Results-Base line measurements of TnI, CRP, and BNP were performed in 450 patients, in OPUS-TIMI 16. Elevations in TnI, CRP, and BNP each were independent predictors of the composite of death, myocardial infarction (MI), or congestive heart failure (CHF). When patients were categorized on the basis of the number of elevated biomarkers at presentation, there was a near doubling of the mortality risk for each additional biomarker that was elevated (P=0.01). Similar relationships existed for the endpoints of MI, CHF, and the composite, both at 30 days and through 10 months. In a validation cohort of 1635 patients in TACTICS-TIMI 18, the number of elevated biomarkers remained a significant predictor of the composite endpoint after adjustment for known clinical predictors: patients with one, two, and three elevated biomarkers had a 2.1- (P=0.006), 3.1- (P<0.001), and 3.7- (P=0.001) fold increase in the risk of death, MI, or CHF by 6 months. Conclusions-Troponin, CRP, and BNP each provide unique prognostic information in patients with ACS. A simple multimarker strategy that categorizes patients based on the number of elevated biomarkers at presentation allows risk stratification over a broad range of short- and long-term major cardiac events. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Univ Texas, SW Med Sch, Dallas, TX 75230 USA. Harvard Univ, Clin Res Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [F32 HL68455-01] NR 14 TC 476 Z9 502 U1 3 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 16 PY 2002 VL 105 IS 15 BP 1760 EP 1763 DI 10.1161/01.CIR.0000015464.18023.0A PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 543XK UT WOS:000175127700006 PM 11956114 ER PT J AU Sabatine, MS Aretz, HT Fang, LST Dec, GW AF Sabatine, MS Aretz, HT Fang, LST Dec, GW TI Fibrillary/immunotactoid glomerulopathy with cardiac involvement SO CIRCULATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Associates, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sabatine, MS (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bulfinch B001,55 Fruit St, Boston, MA 02114 USA. NR 0 TC 16 Z9 16 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 APR 16 PY 2002 VL 105 IS 15 BP E120 EP E121 DI 10.1161/01.CIR.0000016155.44486.59 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 543XK UT WOS:000175127700001 PM 11956134 ER PT J AU Freedman, SJ Sun, ZYJ Poy, F Kung, AL Livingston, DM Wagner, G Eck, MJ AF Freedman, SJ Sun, ZYJ Poy, F Kung, AL Livingston, DM Wagner, G Eck, MJ TI Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CREB-BINDING PROTEIN; FACTOR 1-ALPHA; TRANSCRIPTIONAL ACTIVITY; TRANSACTIVATION DOMAIN; O-2 HOMEOSTASIS; DNA-BINDING; HIF-ALPHA; NMR DATA; HYDROXYLATION; PROGRAM AB Adaptation to hypoxia is mediated by transactivation of hypoxia-responsive genes by hypoxia-inducible factor-1 (HIF-1) in complex with the CBP and p300 transcriptional coactivators. We report the solution structure of the cysteine/histidine-rich 1 (CH1) domain of p300 bound to the C-terminal transactivation domain of HIF-1alpha. CH1 has a triangular geometry composed of four a-helices with three intervening Zn2+-coordinating centers. CH1 serves as a scaffold for folding of the HIF-1alpha C-terminal transactivation domain, which forms a vise-like clamp on the CH1 domain that is stabilized by extensive hydrophobic and polar interactions. The structure reveals the mechanism of specific recognition of p300 by HIF-1alpha, and shows how HIF-1alpha transactivation is regulated by asparagine hydroxylation. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Eck, MJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA. EM eck@red.dfci.harvard.edu FU NHLBI NIH HHS [K08 HL] NR 42 TC 268 Z9 276 U1 3 U2 12 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 APR 16 PY 2002 VL 99 IS 8 BP 5367 EP 5372 DI 10.1073/pnas.082117899 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 543DX UT WOS:000175087000116 PM 11959990 ER PT J AU Oh, H Mammucari, C Nenci, A Cabodi, S Cohen, SN Dotto, GP AF Oh, H Mammucari, C Nenci, A Cabodi, S Cohen, SN Dotto, GP TI Negative regulation of cell growth and differentiation by TSG101 through association with p21(Cip1/WAF1) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID KERATINOCYTE GROWTH; SKIN CARCINOGENESIS; CDK INHIBITORS; CYCLE CONTROL; PROTEIN; P21(WAF1/CIP1); P300; CANCER; TRANSACTIVATION; PROGRESSION AB TSG101 was discovered in a screen for tumor susceptibility genes and has since been shown to have a multiplicity of biological effects. However, the basis for TSG101's ability to regulate cell growth has not been elucidated. We report here that the TSG101 protein binds to the cyclin/cyclin-dependent kinase (CDK) inhibitor (CKI) p21(Cip1) (WAF1) and increases stability of the p21 protein in HEK293F cells and differentiating primary keratinocytes, suppressing differentiation in a p21-dependent manner. In proliferating keratinocytes where the p21 protein is relatively stable, TSG101 does not affect the stability or expression of p21 but shows p21-dependent recruitment to cyclin/CDK complexes, inhibits cyclin. CDK activity, and causes strong growth suppression to a much greater extent in p21 +/+ than in p21 -/- cells. Conversely, suppression of endogenous TSG101 expression by an antisense TSG101 cDNA causes doubling of the fraction of keratinocytes in the S phase of the cell cycle as occurs during p21 deficiency. Our results indicate that TSG101 has a direct role in the control of growth and differentiation in primary epithelial cells, and that p21 is an important mediator of these TSG101 functions. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. RP Dotto, GP (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,E 13th St, Charlestown, MA 02129 USA. OI Cabodi, Sara/0000-0003-1248-6549 FU NCI NIH HHS [CA16038, CA79796, R01 CA073796, P01 CA016038]; NIAMS NIH HHS [AR39190] NR 34 TC 41 Z9 45 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 APR 16 PY 2002 VL 99 IS 8 BP 5430 EP 5435 DI 10.1073/pnas.082123999 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 543DX UT WOS:000175087000127 PM 11943869 ER PT J AU Nekhaeva, E Bodyak, ND Kraytsberg, Y McGrath, SB Van Orsouw, NJ Pluzhnikov, A Wei, JY Vijg, J Khrapko, K AF Nekhaeva, E Bodyak, ND Kraytsberg, Y McGrath, SB Van Orsouw, NJ Pluzhnikov, A Wei, JY Vijg, J Khrapko, K TI Clonally expanded mtDNA point mutations are abundant in individual cells of human tissues SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE somatic mutation; clonal expansion; single cell; aging; cancer ID MITOCHONDRIAL-DNA MUTATIONS; D-LOOP REGION; SOMATIC MUTATIONS; MICROSATELLITE INSTABILITY; MUSCLE-FIBERS; NUCLEAR-DNA; GENOME; TUMORS; SEGREGATION; PSEUDOGENES AB Using single-cell sequence analysis, we discovered that a high proportion of cells in tissues as diverse as buccal epithelium and heart muscle contain high proportions of clonal mutant mtDNA expanded from single initial mutant mtDNA molecules. We demonstrate that intracellular clonal expansion of somatic point mutations is a common event in normal human tissues. This finding implies efficient homogenization of mitochondrial genomes within individual cells. Significant qualitative differences observed between the spectra of clonally expanded mutations in proliferating epithelial cells and postmitotic cardiomyocytes suggest, however, that either the processes generating these mutations or mechanisms driving them to homoplasmy are likely to be fundamentally different between the two tissues. Furthermore, the ability of somatic mtDNA mutations to expand (required for their phenotypic expression), as well as their apparently high incidence, reinforces the possibility that these mutations may be involved actively in various physiological processes such as aging and degenerative disease. The abundance of clonally expanded point mutations in individual cells of normal tissues also suggests that the recently discovered accumulation of mtDNA mutations in tumors may be explained by processes that are similar or identical to those operating in the normal tissue. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, Sam & Ann Bishop Ctr, San Antonio, TX 78245 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78245 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. RP Khrapko, K (reprint author), Harvard Univ, Sch Med, 77 Ave Louis Pasteur,Suite 921, Boston, MA 02115 USA. RI Khrapko, Konstantin/A-3244-2009 FU NIA NIH HHS [R01 AG019787, AG00251, AG08812, AG13314, AG13319, AG17242, AG18356, AG18388, AG19787, P01 AG017242, P30 AG013319, P60 AG008812, R01 AG018388, T32 AG000251]; NIEHS NIH HHS [ES11343, R01 ES011343] NR 48 TC 126 Z9 139 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 16 PY 2002 VL 99 IS 8 BP 5521 EP 5526 DI 10.1073/pnas.072670199 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 543DX UT WOS:000175087000143 PM 11943860 ER PT J AU Zhao, Q Kho, A Kenney, AM Yuk, DI Kohane, I Rowitch, DH AF Zhao, Q Kho, A Kenney, AM Yuk, DI Kohane, I Rowitch, DH TI Identification of genes expressed with temporal-spatial restriction to developing cerebellar neuron precursors by a functional genomic approach SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE sonic hedgehog; proliferation; expression profiling; oligonucleotide microarray; noise ID SONIC HEDGEHOG; NERVOUS-SYSTEM; CELL; DIFFERENTIATION; PROLIFERATION; PROGRESSION; MICROARRAYS; AMYGDALA; PATTERNS; CANCER AB Hedgehog pathway activation is required for proliferation of cerebellar granule cell neuron precursors during development and is etiologic in certain cerebellar tumors. To identify genes expressed specifically in granule cell neuron precursors, we used oligonucleotide microarrays to analyze regulation of 13,179 genes' expressed sequence tags in heterogeneous primary cultures of neonatal mouse cerebellum that respond to the mitogen Sonic hedgehog. In conjunction, we applied experiment-specific noise models to render a gene-by-gene robust indication of up-regulation in Sonic hedgehog-treated cultures. Twelve genes so identified were tested, and 10 (83%) showed appropriate expression in the external granular layer (EGL) of the postnatal day (PN)7 cerebellum and down-regulation by PN 15, as verified by in situ hybridization. Whole-organ profiling of the developing cerebellum was carried out from PN 1 to 30 to generate a database of temporal gene regulation profiles (TRIPS). From the database an algorithm was developed to capture the TRIP typical of EGL-specific genes. The ''TRP-EGL'' accurately predicted expression in vivo of an additional 18 genes/expressed sequence tags with a sensitivity of 80% and a specificity of 88%. We then compared the positive predictive value of our analytical procedure with other widely used methods, as verified by the TRP-EGL in silico. These findings suggest that replicate experiments and incorporation of noise models increase analytical specificity. They further show that genome-wide methods are an effective means to identify stage-specific gene expression in the developing granule cell lineage. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Informat Program, Boston, MA 02115 USA. RP Rowitch, DH (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. RI Kohane, Isaac Kohane/K-3716-2012 OI Kohane, Isaac Kohane/0000-0003-2192-5160 FU NINDS NIH HHS [R01 NS4051, R21 NS41764-01] NR 30 TC 53 Z9 54 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 APR 16 PY 2002 VL 99 IS 8 BP 5704 EP 5709 DI 10.1073/pnas.082092399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 543DX UT WOS:000175087000176 PM 11960025 ER PT J AU Cagliero, E Apruzzese, W Perlmutter, GS Nathan, DM AF Cagliero, E Apruzzese, W Perlmutter, GS Nathan, DM TI Musculoskeletal disorders of the hand and shoulder in patients with diabetes mellitus SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID JOINT MOBILITY; ADHESIVE CAPSULITIS; DUPUYTRENS DISEASE; COMPLICATIONS; ASSOCIATION; PRODUCTS; ABNORMALITIES; LIMITATION C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Cagliero, E (reprint author), Massachusetts Gen Hosp, Ctr Diabet, 50 Staniford St, Boston, MA 02114 USA. NR 28 TC 74 Z9 75 U1 3 U2 3 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 APR 15 PY 2002 VL 112 IS 6 BP 487 EP 490 DI 10.1016/S0002-9343(02)01045-8 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 543WZ UT WOS:000175126000008 PM 11959060 ER PT J AU Kramer, BJ Harker, JO Wong, AL AF Kramer, BJ Harker, JO Wong, AL TI Descriptions of joint pain by American Indians: Comparison of inflammatory and noninflammatory arthritis SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE American Indians; semeiology; pain; arthritis ID SYSTEMIC LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; HIGH PREVALENCE; DISEASE; ALCOHOL AB Objective. To improve assessment of arthritis joint pain in American Indians by describing how symptoms are communicated. Method. In-depth interviews were conducted with American Indians who experience chronic joint pain (n = 56), to elicit descriptions and self-reported ratings of pain, disability, and beliefs associated with the pain for affected joints (n = 326). Results. Discrete sets of specific verbal descriptions distinguished inflammatory arthritis (n = 20 terms) from noninflammatory arthritis (n = 22 terms), and indicated levels of pain intensity. An additional set of 14 vague but commonly used verbal descriptors did not distinguish the type of joint disease or pain intensity. Conclusions. Subtle pain complaints and vague verbal descriptions, such as "ache," "hurt," and "discomfort," may reflect severe pain symptoms, disability, and more serious joint disease in American Indian patients. In addition, certain specific sensory descriptions used by American Indians suggest inflammatory arthritis and may warrant further evaluation. C1 VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ Clin Ctr 11E, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Olive View UCLA Med Ctr, Sylmar, CA 91342 USA. RP Kramer, BJ (reprint author), VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ Clin Ctr 11E, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 30 TC 10 Z9 10 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 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD APR 15 PY 2002 VL 47 IS 2 BP 149 EP 154 DI 10.1002/art1.10325 PG 6 WC Rheumatology SC Rheumatology GA 540UN UT WOS:000174948100008 PM 11954008 ER PT J AU Moore, CM Demopulos, CM Henry, ME Breeze, JL Sachs, GS Cohen, BM Renshaw, PF AF Moore, CM Demopulos, CM Henry, ME Breeze, JL Sachs, GS Cohen, BM Renshaw, PF TI Brain-to-serum lithium ratio and age: An in vivo lithium magnetic resonance spectroscopy study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. Harvard Med Sch, Dept Psychiat, Boston, MA USA. Massachusetts Gen Hosp, Harvard Bipolar Res Program, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 39 BP 13S EP 13S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400036 ER PT J AU Harvey, PD Goodman, M Mitropoulou, V Barch, DM Koenigsberg, H Siever, LJ AF Harvey, PD Goodman, M Mitropoulou, V Barch, DM Koenigsberg, H Siever, LJ TI Cognitive enhancement in schizotypal personality disorder: A study of adrenergic and dopaminergic approaches SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Bronx Vet Adm Med Ctr, MIRECC, Bronx, NY USA. Washington Univ, Dept Psychol, St Louis, MO 63130 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 47 BP 16S EP 17S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400044 ER PT J AU DeWitt, I Weiss, AP Deckersbach, T Kunkel, L Goff, D Heckers, S AF DeWitt, I Weiss, AP Deckersbach, T Kunkel, L Goff, D Heckers, S TI Assessing hippocampal volume in schizophrenia using a standardized MRI protocol SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 61 BP 21S EP 22S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400058 ER PT J AU Schuepbach, D Sanders, RD Keshavan, MS AF Schuepbach, D Sanders, RD Keshavan, MS TI Cognitive impairments correlate with specific neurological soft signs in first-episode schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Zurich, Psychiat Univ Hosp, Zurich, Switzerland. Western Psychiat Inst & Clin, UPMC HS, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 77 BP 26S EP 26S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400073 ER PT J AU Yao, JK Leonard, S Reddy, RD Cheng, P Bland, BW AF Yao, JK Leonard, S Reddy, RD Cheng, P Bland, BW TI Abnormal glutathione redox coupling in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80202 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 84 BP 28S EP 29S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400080 ER PT J AU Deckersbach, T Reilly-Harrington, N Clark, L Goodwin, G Savage, CR Dougherty, DD Rauch, SL Sachs, G AF Deckersbach, T Reilly-Harrington, N Clark, L Goodwin, G Savage, CR Dougherty, DD Rauch, SL Sachs, G TI Characteristics and functional anatomy of episodic memory impairment in bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. Univ Cambridge, Dept Expt Psychol, Cambridge, England. Univ Oxford, Dept Psychiat, Oxford, England. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 88 BP 30S EP 30S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400084 ER PT J AU Koenigsberg, HW Teicher, MH Mitropoulou, V Navalta, C New, AS Goodman, M Trestman, R Siever, LJ AF Koenigsberg, HW Teicher, MH Mitropoulou, V Navalta, C New, AS Goodman, M Trestman, R Siever, LJ TI 24-hour patterns of cortisol, norepinephrine, MHPG, growth hormone, and prolactin secretion in depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Mt Sinai Sch Med, New York, NY USA. Bronx Vet Affairs Med Ctr, New York, NY USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06030 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 94 BP 32S EP 32S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400090 ER PT J AU Grossman, R Buchsbaum, MS Yehuda, R Naidich, T New, A Siever, L AF Grossman, R Buchsbaum, MS Yehuda, R Naidich, T New, A Siever, L TI Hippocampal volume in personality disordered subjects: Associations with posttraumatic stress disorer, hypothalamic-pituitary-adrenal axis measures, and other factors SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Mt Sinai Sch Med, Bronx, NY USA. Bronx Vet Adm Med Ctr, New York, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 105 BP 35S EP 36S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400101 ER PT J AU Frazier, JA Chiu, S Kennedy, D Garroway, J Stein, N Rauch, S Herbert, M Melrose, R Sohma, M Grant, E Makris, N Caviness, V Biederman, J AF Frazier, JA Chiu, S Kennedy, D Garroway, J Stein, N Rauch, S Herbert, M Melrose, R Sohma, M Grant, E Makris, N Caviness, V Biederman, J TI Anatomic brain magnetic resonance imaging in pediatric bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, McLean Hosp, Belmont, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RI Kennedy, David/H-3627-2012 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 111 BP 37S EP 37S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400107 ER PT J AU Yao, JK van Kammen, DP Reddy, RD Keshavan, MS Schmid, PC Berdyshev, EV Krebsbach, RJ Schmid, HHO AF Yao, JK van Kammen, DP Reddy, RD Keshavan, MS Schmid, PC Berdyshev, EV Krebsbach, RJ Schmid, HHO TI Elevated endocannabinoids in plasma from patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. Robert Wood Johnson Pharmaceut Res Inst, Raritan, NJ USA. Univ Minnesota, Hormel Inst, Austin, MN 55912 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 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 APR 15 PY 2002 VL 51 IS 8 SU S MA 190 BP 64S EP 65S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400184 ER PT J AU Gonzalez-Heydrich, J Fleisher, C Raches, D Bourgeois, BF Pandina, GJ Janssen, PC Biederman, J AF Gonzalez-Heydrich, J Fleisher, C Raches, D Bourgeois, BF Pandina, GJ Janssen, PC Biederman, J TI Risperidone in pediatric patients with Epilepsy SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Childrens Hosp, OutPatient Psychiat Programs, Boston, MA 02115 USA. Haverford Coll, Haverford, PA 19041 USA. Childrens Hosp, Div Epilepsy & Clin Neurophysiol, Boston, MA 02115 USA. Janssen Pharmaceut Inc, CNS Med Affairs, Titusville, NJ USA. Janssen Pharmaceut NV, Dept Res, Beerse, Belgium. Massachusetts Gen Hosp, Dept Psychiat, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 216 BP 73S EP 74S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400210 ER PT J AU Kozel, FA Revell, LJ Lorberbaum, JP Shastri, A Smith, A Nahas, Z Nadeau, B Bohning, DE George, MS AF Kozel, FA Revell, LJ Lorberbaum, JP Shastri, A Smith, A Nahas, Z Nadeau, B Bohning, DE George, MS TI Regional brain correlates of electrodermal activity: A pilot fMRI study in healthy young men SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Ctr Adv Imaging, Charleston, SC 29425 USA. Ralph H Johnson VA, Mental Hlth Serv, Charleston, SC 29425 USA. Life Cycle, Comp Engn, Charleston, SC USA. RI Kozel, Frank/I-5366-2012 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 255 BP 86S EP 87S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400249 ER PT J AU Najib, A Lorberbaum, JP Kose, S Nahas, Z Bohning, DE George, MS AF Najib, A Lorberbaum, JP Kose, S Nahas, Z Bohning, DE George, MS TI Regional brain activity in women grieving a romantic relationship breakup SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Tubingen, Fac Med, Tubingen, Germany. Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 254 BP 86S EP 86S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400248 ER PT J AU Lyoo, IK Demopulos, CM Moore, C Kong, SW Lee, S Cohen, BM Renshaw, PF AF Lyoo, IK Demopulos, CM Moore, C Kong, SW Lee, S Cohen, BM Renshaw, PF TI Brain purine level following oral choline administration in subjects with rapid cycling bipolar disorder: A double-blind trial using proton and lithium magnetic resonance spectroscopy SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Bipolar Treatment Ctr, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 258 BP 87S EP 88S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400252 ER PT J AU Pearlson, GD Calhoun, VD Rauch, SL Frederick, BDB Van Horn, JD Saykin, AJ AF Pearlson, GD Calhoun, VD Rauch, SL Frederick, BDB Van Horn, JD Saykin, AJ TI Novel means for designing, analyzing and interpreting functional MRI studies SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Belmont, MA 02178 USA. Dartmouth Coll, Hanover, NH 03755 USA. Dartmouth Coll Sch Med, Lebanon, NH USA. RI Frederick, Blaise/G-6098-2012; Calhoun, Vince/H-7146-2013; Saykin, Andrew/A-1318-2007 OI Frederick, Blaise/0000-0001-5832-5279; Calhoun, Vince/0000-0001-9058-0747; Saykin, Andrew/0000-0002-1376-8532 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 277 BP 94S EP 94S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400266 ER PT J AU Manoach, DS AF Manoach, DS TI Prefrontal cortex dysfunction during working memory performance in schizophrenia: Reconciling discrepant findings SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 306 BP 104S EP 104S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400294 ER PT J AU Dougherty, DD Cosgrove, GR Weiss, AP Alpert, NM Cassem, EH Nierenberg, AA Price, BH Mayberg, HS Fischman, A Rauch, SL AF Dougherty, DD Cosgrove, GR Weiss, AP Alpert, NM Cassem, EH Nierenberg, AA Price, BH Mayberg, HS Fischman, A Rauch, SL TI Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for major depressive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. McLean Hosp, Belmont, MA 02178 USA. Univ Toronto, Rotman Res Inst, Toronto, ON, Canada. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 313 BP 107S EP 107S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400301 ER PT J AU Iosifescu, DV Renshaw, PF Lyoo, IK Lee, HK Fava, M AF Iosifescu, DV Renshaw, PF Lyoo, IK Lee, HK Fava, M TI Brain MRI white matter hyperintensities correlate with improved treatment outcome in depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Sungkyunkwan Univ, Coll Med, Dept Radiol, Seoul, South Korea. McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Dept Psychiat, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 315 BP 108S EP 108S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400303 ER PT J AU Weiss, AP Schacter, DL Goff, D Rauch, SL Alpert, NM Heckers, S AF Weiss, AP Schacter, DL Goff, D Rauch, SL Alpert, NM Heckers, S TI Impaired hippocampal activation in schizophrenia during conscious recollection SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 354 BP 121S EP 121S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400342 ER PT J AU Yao, JK Cheng, P AF Yao, JK Cheng, P TI A simple and sensitive method for simultaneous monitoring of antioxidant defense system and monoamine metabolic pathways in biological samples SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 386 BP 131S EP 131S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400374 ER PT J AU Valera, EM Seidman, LJ Biederman, J Faraone, SV AF Valera, EM Seidman, LJ Biederman, J Faraone, SV TI An fMRI study of working memory in adults with ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Massachusetts Mental Hlth Ctr, Dept Pediat,Pediat Psychopharmacol Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Pediat Psychopharmacol Unit, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 417 BP 143S EP 143S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400405 ER PT J AU Koenigsberg, HW Goodman, M Teicher, M Hollander, E Siever, LJ AF Koenigsberg, HW Goodman, M Teicher, M Hollander, E Siever, LJ TI Affective instability in borderline personality disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Mt Sinai Sch Med, New York, NY USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. Harvard Univ, Sch Med, Cambridge, MA 02138 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 429 BP 147S EP 147S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400412 ER PT J AU Yao, JK Hibbeln, JR Thomas, EA Glen, L Mahadik, SP Peet, M AF Yao, JK Hibbeln, JR Thomas, EA Glen, L Mahadik, SP Peet, M TI Arachidonic acid signaling in schizophrenia: Pathophysiological and treament implications SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Dept Psychiat, Pittsburgh, PA USA. Western Psychiat Inst & Clin, Pittsburgh, PA USA. NIAAA, Lab Memb Biochem & Biophys, NIH, Rockville, MD USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Craig Dunain Hosp, Highland Psychiat Res Grp, Inverness, Scotland. Med Coll Georgia, Dept Psychiat & Hlth Behav, Augusta, GA 30912 USA. No Gen Hosp, Dept Psychiat, Sheffield S5 7AU, S Yorkshire, England. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 431 BP 147S EP 148S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400414 ER PT J AU Bush, G Shin, L Holmes, J Rosen, BR Vogt, BA AF Bush, G Shin, L Holmes, J Rosen, BR Vogt, BA TI The oddball stroop: A potential diagnostic neuroimaging task SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Athinoula A Martinos Ctr Funct & Struct Biomed Im, HMS, MIT, MGH, Charlestown, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. MIT, Cambridge, MA 02139 USA. Cingulum NeuroSci Inst, Syracuse, NY USA. RI Vogt, Brent/C-4038-2015 OI Vogt, Brent/0000-0003-1228-4410 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 461 BP 157S EP 157S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400444 ER PT J AU Childress, AR Listerud, J Franklin, T Langleben, D Kampman, K Monterosso, J Acton, P Gray, J Fornash, A O'Brien, CP AF Childress, AR Listerud, J Franklin, T Langleben, D Kampman, K Monterosso, J Acton, P Gray, J Fornash, A O'Brien, CP TI Imaging the substrates of cue-induced drug craving and its modulation by pharmacologic or behavioral interventions SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 460 BP 157S EP 157S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400443 ER PT J AU Dracheva, S Elhakem, SL Davis, KL Haroutunian, V AF Dracheva, S Elhakem, SL Davis, KL Haroutunian, V TI GAD65 and GAD67 protein expression in DLPFC of elderly schizophrenia patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Mt Sinai Sch Med, Bronx, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 484 BP 166S EP 166S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400467 ER PT J AU Kubicki, M Fitchorov, T Westin, C Frumin, M Ersner-Hershfield, H Jolesz, F McCarley, R Shenton, M AF Kubicki, M Fitchorov, T Westin, C Frumin, M Ersner-Hershfield, H Jolesz, F McCarley, R Shenton, M TI White matter abnormalities in schizophrenia: Evidence from diffusion tensor and myelin saturation techniques SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Hershfield, Hal/J-2919-2016 OI Hershfield, Hal/0000-0002-1507-7022 NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 494 BP 169S EP 170S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400477 ER PT J AU Kunkel, L Weiss, AP Goff, D Shin, L Wright, C Rauch, S Heckers, S AF Kunkel, L Weiss, AP Goff, D Shin, L Wright, C Rauch, S Heckers, S TI Impaired anterior cingulate cortex function during the processing of emotional facial expression in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 495 BP 170S EP 170S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400478 ER PT J AU Spencer, KM McCarley, RW AF Spencer, KM McCarley, RW TI Visual gamma responses and evoked potentials elicited by gestalt perception in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 505 BP 173S EP 174S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400488 ER PT J AU Giordano, LF Olincy, A Hall, MH Freedman, R AF Giordano, LF Olincy, A Hall, MH Freedman, R TI Failure to inhibit the P50 auditory evoked potential in manic psychosis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Denver Vet Affairs Med Ctr, Denver, CO 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 521 BP 179S EP 179S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400504 ER PT J AU Savage, CR Sherman, BJ Eddy, KT Connor, C Blais, MA Deckersbach, T Rauch, SL Herzog, DB AF Savage, CR Sherman, BJ Eddy, KT Connor, C Blais, MA Deckersbach, T Rauch, SL Herzog, DB TI Strategic memory in anorexia nervosa: Are there similarities to OCD? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 528 BP 181S EP 181S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400511 ER PT J AU Rohan, ML Parow, AM Stoll, AL Demopulos, C Friedman, S Dager, S Hennen, J Cohen, BM Renshaw, PF AF Rohan, ML Parow, AM Stoll, AL Demopulos, C Friedman, S Dager, S Hennen, J Cohen, BM Renshaw, PF TI Low field TMS treatment for bipolar depression using a MRI based stimulator SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Washington, Seattle, WA 98195 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 545 BP 187S EP 187S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400527 ER PT J AU Shihabuddin, L Brickman, AM Miozzo, R Prikryl, R Shaw, R Davis, KL Buchsbaum, MS AF Shihabuddin, L Brickman, AM Miozzo, R Prikryl, R Shaw, R Davis, KL Buchsbaum, MS TI Caudate and putamen volume in good and poor outcome schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Bronx Vet Adm Med Ctr, Off Mental Hlth, Bronx, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 562 BP 193S EP 194S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400544 ER PT J AU Shin, LM Shin, PS Heckers, S Rauch, SL Orr, SP Macklin, M Lasko, N Schacter, DL Krangel, TS Pitman, RK AF Shin, LM Shin, PS Heckers, S Rauch, SL Orr, SP Macklin, M Lasko, N Schacter, DL Krangel, TS Pitman, RK TI Explicit memory and hippocampal function in posttraumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Dept Philosophy, Cambridge, MA USA. VA Med Ctr, Res Serv, Manchester, NH USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 570 BP 196S EP 196S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400552 ER PT J AU Bartzokis, G Beckson, M Lu, PH Edwards, N Bridge, P Mintz, J AF Bartzokis, G Beckson, M Lu, PH Edwards, N Bridge, P Mintz, J TI Brain maturation may be arrested in chronic cocaine addicts SO BIOLOGICAL PSYCHIATRY LA English DT Article DE brain; aging; maturation; cocaine; addiction; white matter; myelin; gray matter; frontal lobe; temporal lobe ID CEREBRAL BLOOD-FLOW; MAGNETIC-RESONANCE; WHITE-MATTER; GRAY-MATTER; ALZHEIMERS-DISEASE; IN-VIVO; ABUSERS; MRI; AGE; CORTEX AB Background: Animal and human newborn studies suggest that exposure to cocaine in utero delays glial maturation and white matter myelination. Postmortem data show that in the frontal and temporal lobes, white matter myelination continues into middle age. Recent magnetic resonance imaging (MRI) data have confirmed continued white matter volume increase in these regions, reaching a maximum at age 47. Methods: Thirty-seven male cocaine dependent (CD) and 52 normal control subjects between ages 19 and 47 were evaluated with MRI. Coronal images focused on the frontal and temporal lobes were acquired using pulse sequences that maximized gray/white matter contrast. Results: Highly significant positive correlations between white matter volume and age were observed in both the frontal and temporal lobes of the control group (r = .52, p = .0001 and r = .54, p = .0001, respectively); however, CD subjects did not demonstrate any age-related increase in white matter volume of the frontal (r = -.001; p = .99) and temporal (r = -.07; p = .67) lobes in this age range. Conclusions: The age-related expansion in white matter volume occurring in normal control subjects was absent in CD subjects. The findings suggest that in adults, cocaine dependence may arrest normal white matter maturation in the frontal and temporal lobes of addicts who continue using cocaine. (C) 2002 Society of Biological Psychiatry. C1 Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. NIDA, Med Dev Div, Rockville, MD USA. RP Bartzokis, G (reprint author), 710 Westwood Plaza,Room 2-238, Los Angeles, CA 90095 USA. RI Bartzokis, George/K-2409-2013 FU NIDA NIH HHS [1Y01 DA 50038]; NIMH NIH HHS [MH 51928] NR 50 TC 56 Z9 56 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 BP 605 EP 611 AR PII S0006-3223(02)01315-X DI 10.1016/S0006-3223(02)01315-X PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 540XN UT WOS:000174956300001 PM 11955460 ER PT J AU Yaffe, K Lui, LY Grady, D Stone, K Morin, P AF Yaffe, K Lui, LY Grady, D Stone, K Morin, P TI Estrogen receptor 1 polymorphisms and risk of cognitive impairment in older women SO BIOLOGICAL PSYCHIATRY LA English DT Article DE estrogen; cognition; elderly women; dementia; polymorphisms ID ALPHA GENE POLYMORPHISMS; CENTRAL-NERVOUS-SYSTEM; BONE-MINERAL DENSITY; ALZHEIMERS-DISEASE; REPLACEMENT THERAPY; MESSENGER-RNA; ASSOCIATION; DECLINE; GENOTYPES; DEMENTIA AB Background: Several genes associated with sporadic Alzheimer's disease have been identified; however, approximately 50% of genetic factors remain unidentified. We investigated whether estrogen receptor I (ESR1) polymorphisms are associated with risk of developing cognitive impairment in older women. Methods: A total of 2625 women greater than or equal to 65 years of age completed a modified Mini-Mental Status Exam (mMMSE) at baseline and at 6-8 years of follow-up. We defined cognitive impairment as a mMMSE decline of greater than or equal to 3 points, follow-up score less than or equal to 20, or a history of physician-diagnosed dementia. The ESR1 polymorphisms, PvuII (P or p) and XbaI (X or x), were coded so that the capital letter signifies the absence of the restriction site. Results: Women with a p allele had a greater age, education, and baseline-score adjusted decline in mMMSE (for PP, Pp, and pp, respectively: .6 +/- .1, .8 +/- .1, and .9 +/- .1 points, p for trend = .01); women with at least one x allele also had greater score decline (XX, Xx, and xx: .7 +/- .1, .7 +/- .1, and .9 +/- .1 points, p for trend = .02). Six percent (n = 166) of the women developed cognitive impairment. Compared to those who did not develop impairment, more women who developed cognitive impairment had a p allele 62% vs. 56%, p = .03; adjusted odds ration (OR) = 1.33; 95% confidence interval [CI], 1.03-1.72) or an x allele (70% vs. 64%, p = .03; adjusted OR = 1.38; 95% CI, 1.06-1.81). There was no interaction with current estrogen use, or with serum estradiol level and ESR1 polymorphisms (p > .10). Conclusions: Estrogen receptor I polymorphisms are associated with risk of developing cognitive impairment. More research is needed to determine the mechanism whereby ESR1 polymorphisms or linked genes influence cognitive function in older women. (C) 2002 Society of Biological Psychiatry. 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 & Biostat, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Axys Pharmaceut Inc, La Jolla, CA USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 111G,4150 Clement St, San Francisco, CA 94121 USA. FU NIA NIH HHS [AG 05407, AG 05394, K23-AG 00888]; NIADDK NIH HHS [AM 35584]; NIAMS NIH HHS [AR 35582, AR 35583] NR 31 TC 77 Z9 77 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 BP 677 EP 682 AR PII S0006-3223(01)01289-6 DI 10.1016/S0006-3223(01)01289-6 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 540XN UT WOS:000174956300009 PM 11955468 ER PT J AU Wilson, WH Grossbard, ML Pittaluga, S Cole, D Pearson, D Drbohlav, N Steinberg, SM Little, RF Janik, J Gutierrez, M Raffeld, M Staudt, L Cheson, BD Longo, DL Harris, N Jaffe, ES Chabner, BA Wittes, R Balis, F AF Wilson, WH Grossbard, ML Pittaluga, S Cole, D Pearson, D Drbohlav, N Steinberg, SM Little, RF Janik, J Gutierrez, M Raffeld, M Staudt, L Cheson, BD Longo, DL Harris, N Jaffe, ES Chabner, BA Wittes, R Balis, F TI Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; PROGNOSTIC-SIGNIFICANCE; INTERMEDIATE-GRADE; PROMACE-CYTABOM; DRUG-RESISTANCE; DOXORUBICIN; THERAPY; TRIAL; VINCRISTINE; INTENSITY AB We hypothesized that incremental improvements in the cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) chemotherapy regimen through optimization of drug selection, schedule, and pharmacokinetics would improve outcome in patients with large B-cell lymphomas. A prospective multi-institutional study of administration of etoposide, vincristine, and doxorubicin for 96 hours with bolus doses of cyclophosphamide and oral prednisone (EPOCH therapy) was done in 50 patients with previously untreated large B-cell lymphomas. The doses of etoposide, doxorubicin, and cyclophosphamide were adjusted 20% each cycle to achieve a nadir absolute neutrophil count below 0.5 x 10(9)/L. The median age of the patients was 46 years (range, 20-88 years); 24% were older than 60 years; and 44% were at high-intermediate or high risk according to International Prognostic Index (IPI) criteria. There was a complete response in 92% of patients, and at the median follow-up time of 62 months, the progression-free survival (PFS) and overall survival (OS) rates were 70% and 73%, respectively. Neither IPI risk factors nor the index itself was associated with response, PFS, or OS. Doses were escalated in 58% of cycles, and toxicity levels were tolerable. Significant inverse correlations were observed between dose intensity and age for all adjusted agents, and drug clearance of doxorubicin and free etoposide was also inversely correlated with age (r = -0.54 and P-2 = .08 and r = -0.45 and P-2 = .034, respectively). Free-etoposide clearance increased significantly during successive cycles (P-2 = .015). Lymphomas with proliferation of at least 80% had somewhat lower progression and those expressing bcl-2 had significantly higher progression (P-2 = .04). Expression of bcl-2 may discriminate the recently described activated B-like from germinal-center B-like large-cell lymphomas and provide important pathobiologic and prognostic information. Dose-adjusted EPOCH may produce more cell kill than CHOP-based regimens. Dynamic dose adjustment may overcome inadequate drug concentrations, particularly in younger patients, and compensate for increased drug clearance overtime. (C) 2002 by The American Society of Hematology. C1 NCI, Canc Res Ctr, Med Branch, Bethesda, MD 20892 USA. Holy Cross Hosp, Ft Lauderdale, FL USA. St Lukes Roosevelt Hosp, New York, NY 10025 USA. Beth Israel Med Ctr, New York, NY 10003 USA. NIA, Baltimore, MD 21224 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wilson, WH (reprint author), NCI, Canc Res Ctr, Med Branch, Bldg 10,Room 12N-226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 45 TC 125 Z9 130 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2002 VL 99 IS 8 BP 2685 EP 2693 DI 10.1182/blood.V99.8.2685 PG 9 WC Hematology SC Hematology GA 539JJ UT WOS:000174866500007 PM 11929754 ER PT J AU Wang, ZY Miura, N Bonelli, A Mole, P Carlesso, N Olson, DP Scadden, DT AF Wang, ZY Miura, N Bonelli, A Mole, P Carlesso, N Olson, DP Scadden, DT TI Receptor tyrosine kinase, EphB4 (HTK), accelerates differentiation of select human hematopoietic cells SO BLOOD LA English DT Article ID STEM-CELLS; CARDIOVASCULAR DEVELOPMENT; LIGAND; FAMILY; BLOOD; ANGIOGENESIS; EXPRESSION; CLONING; GROWTH; LINES AB EphB4 (HTK) and its ligand, ephrinB2, are critical for angiogenesis and result in fatal abnormalities of capillary formation in null mice. EphB4 was originally identified in human bone marrow CD34(+) cells by us and has since been reported to be expressed in erythroid progenitors, whereas the ligand ephrinB2 is expressed in bone marrow stromal cells. Reasoning that the developmental relationship between angiogenesis and hematopoiesis implies common regulatory molecules, we assessed whether EphB4 signaling influences the function and phenotype of primitive human hematopoietic cells. Ectopically expressed EphB4 in cell lines of restricted differentiation potential promoted megakaryocytic differentiation, but not granulocytic or monocytic differentiation. Primary cord blood CD34+ cells transduced with EphB4 resulted in the elevated expression of megakaryocytic and erythroid specific markers, consistent with EphB4 selectively enhancing some lineage-committed progenitors. In less mature cells, EphB4 depleted primitive cells, as measured by long-term culture-initiating cells or CD34(+)CD38(-) cell numbers, and increased progenitor cells of multiple cell types. Effects of ectopic EphB4 expression could be abrogated by either targeted mutations of select tyrosine residues or by the tyrosine kinase inhibitor, genistein. These data Indicate that EphB4 accelerates the differentiation of primitive cells in a nonlineage-restricted manner but alters only select progenitor populations, Influencing lineages linked by common ancestry with endothelial cells. EphB4 enforces preferential megakaryocytic and erythroid differentiation and may be a molecular bridge between angiogenesis and hematopolesis. (C) 2002 by The American Society of Hematology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, Boston, MA 02129 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr, 149 13th St,Room 5212D, Boston, MA 02129 USA. NR 54 TC 23 Z9 27 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 APR 15 PY 2002 VL 99 IS 8 BP 2740 EP 2747 DI 10.1182/blood.V99.8.2740 PG 8 WC Hematology SC Hematology GA 539JJ UT WOS:000174866500014 PM 11929761 ER PT J AU Basak, SK Harui, A Stolina, M Sharma, S Mitani, K Dubinett, SM Roth, MD AF Basak, SK Harui, A Stolina, M Sharma, S Mitani, K Dubinett, SM Roth, MD TI Increased dendritic cell number and function following continuous in vivo infusion of granulocyte macrophage-colony-stimulating factor and interleukin-4 SO BLOOD LA English DT Article ID RECOMBINANT HUMAN INTERLEUKIN-4; HEMATOPOIETIC PROGENITOR CELLS; NECROSIS-FACTOR-ALPHA; LIGAND-TREATED MICE; MOUSE BONE-MARROW; IN-VIVO; GM-CSF; FLT3 LIGAND; BLOOD MONOCYTES; CARCINOMA CELLS AB Dendritic cells (DCs) are rare antigen-presenting cells that play a central role in stimulating immune responses. The combination of recombinant granulocyte macrophage-colony-stimulating factor (rGM-CSF) and recombinant interleukin-4 (rIL-4) provides an important stimulus for generating DCs from murine bone marrow precursors in vitro. Using miniature osmotic pumps, we now demonstrate that continuous infusion of these cytokines for 7 days had a similar effect in vivo, increasing the number and function of splenic DCs. Administration of rGM-CSF/rlL-4 (10 mug/d each) increased the concentration of CD11(+) DCs by 2.7-fold and the absolute number of splenic DCs by an average of 5.7-fold. DC number also increased in peripheral blood and lymph nodes. The resultant DCs exhibited a different phenotype and function than those in control mice or mice treated with rGM-CSF alone. rGM-CSF/IL-4 increased both the myeloid (CD11c(+)/CD11b(+)) and the lymphoid (CD11c(+)/CD8alpha(+)) subpopulations, whereas rGM-CSF increased only myeloid DCs. DCs were highly concentrated in the T-cell areas of white pulp after rGM-CSF/IL-4 administration, whereas they were diffusely distributed throughout white pulp, marginal zones, and red pulp in mice treated with rGM-CSF alone. rGM-CSF/rIL-4 also significantly increased the expression of major histocompatibility complex (MHC) class I and MHC class II on CD11c(+) cells and increased their capacity to take up antigens by macropinocytosis and receptor-mediated endocytosis. Splenic DCs generated in response to rGM-CSF/rIL-4 were functionally immature in terms of allostimulatory activity, but this activity increased after short-term in vitro culture. Systemic treatment with rGM-CSF/rIL-4 enhanced the response to an adenoviral-based vaccine and led to antigen-specific retardation in the growth of established tumor. We conclude that systemic therapy with the combination of rGM-CSF/rIL-4 provides a new approach for generating DCs in vivo. (C) 2002 by The American Society of Hematology. C1 Univ Calif Los Angeles, Sch Med, Dept Med, Div Pulm & Crit Care, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Basak, SK (reprint author), Univ Calif Los Angeles, Sch Med, Dept Med, Div Pulm & Crit Care, Los Angeles, CA 90095 USA. FU NCI NIH HHS [CA16042, CA85686, IP50 CA90388]; NIAID NIH HHS [AI28697] NR 50 TC 43 Z9 53 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2002 VL 99 IS 8 BP 2869 EP 2879 DI 10.1182/blood.V99.8.2869 PG 11 WC Hematology SC Hematology GA 539JJ UT WOS:000174866500030 PM 11929777 ER PT J AU Nahta, R Iglehart, JD Kempkes, B Schmidt, EV AF Nahta, R Iglehart, JD Kempkes, B Schmidt, EV TI Rate-limiting effects of cyclin D1 in transformation by ErbB2 predicts synergy between Herceptin and flavopiridol SO CANCER RESEARCH LA English DT Article ID TRANSMEMBRANE DOMAIN; RECEPTOR; NEU; DIMERIZATION; CARCINOMA; CELLS; DRUGS AB Cyclin D1 is downstream of erbB2 and is required for erbB2 transformation. Here we report that cyclin D1 functions are essential, rate limiting for erbB2 transformation, and reciprocally increase erbB2 levels. This interaction depends on three cyclin D1 activities: cycl in-de pendent kinase 4-dependent kinase activity, titration of p27, and an intrinsic transcriptional activity, of cyclin D1. Drugs active against erbB2 and cyclin D1 (Herceptin and flavopiridol) were synergistically cytotoxic against erbB2-positive breast cancer cell lines. Addition of flavopiridol to Herceptin synergistically lowered erbB2 levels in these cells. Our data suggest the potential use of combinations of cyclin-dependent kinase inhibitors and Herceptin in breast cancer. C1 Massachusetts Gen Hosp, Ctr Canc, Lab Tumor Biol, Charlestown, MA 02129 USA. Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. Haematologikum GSF, Inst Clin Mol Biol & Tumor Genet, Munich, Germany. Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. RP Schmidt, EV (reprint author), Massachusetts Gen Hosp, Ctr Canc, Lab Tumor Biol, 13th St,Bldg 149, Charlestown, MA 02129 USA. RI Kempkes, Bettina/B-3322-2013 FU NCI NIH HHS [P50 CA 89393, R01 CA 69069] NR 17 TC 44 Z9 46 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 APR 15 PY 2002 VL 62 IS 8 BP 2267 EP 2271 PG 5 WC Oncology SC Oncology GA 543ML UT WOS:000175105700014 PM 11956082 ER PT J AU Weber, GF Bronson, RT Ilagan, J Cantor, H Schmits, R Mak, TW AF Weber, GF Bronson, RT Ilagan, J Cantor, H Schmits, R Mak, TW TI Absence of the CD44 gene prevents sarcoma metastasis SO CANCER RESEARCH LA English DT Article ID HUMAN COLON CARCINOMAS; INFLUENCES GROWTH; CELL-SURFACE; APC GENE; MICE; SUSCEPTIBILITY; TUMORIGENESIS; EXPRESSION; MUTATION; BINDING AB To test the role of the CD44 gene in tumorigenesis, mice with the min mutation of the APC gene or with the tm1 mutation of the p53 gene were crossed with CD44 knockout mice. The absence of CD44 gene products did not affect tumor incidence or survival; however, mice with disruption of the CD44 gene showed virtually aborted metastasis formation of osteosarcomas. This is in agreement with the role attributed to CD44 variants in the spread of cancer. Therefore, CD44 gene products are not essential for tumor incidence and growth but are important in regulating metastasis formation. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Ontario Canc Inst, Dept Cellular & Mol Biol, Toronto, ON M56 2M9, Canada. RP Weber, GF (reprint author), Tufts Univ New England Med Ctr, Dept Radiat Oncol, NEMC 824,750 Washington St, Boston, MA 02111 USA. FU NCI NIH HHS [CA 76176]; NIAID NIH HHS [AI 12184] NR 22 TC 100 Z9 110 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 APR 15 PY 2002 VL 62 IS 8 BP 2281 EP 2286 PG 6 WC Oncology SC Oncology GA 543ML UT WOS:000175105700016 PM 11956084 ER PT J AU Lentzsch, S Rogers, MS LeBlanc, R Birsner, AE Shah, JH Treston, AM Anderson, KC D'Amato, RJ AF Lentzsch, S Rogers, MS LeBlanc, R Birsner, AE Shah, JH Treston, AM Anderson, KC D'Amato, RJ TI S-3-amino-phthalimido-glutarimide inhibits angiogenesis and growth of B-cell neoplasias in mice SO CANCER RESEARCH LA English DT Article ID HUMAN MULTIPLE-MYELOMA; BONE-MARROW ANGIOGENESIS; BREAST-CANCER; PERIPHERAL-BLOOD; THALIDOMIDE; MALIGNANCIES; PROGRESSION; EXPRESSION; CARCINOMA; ANALOGS AB Thalidomide has recently been shown to be useful in the treatment of multiple myeloma and may also be useful in the treatment of other hematological malignancies. We have identified a new derivative of thalidomide, S-3-[3-amino-phthalimido]-glutarimide (S-3APG) with dual activity against B-cell neoplasias. S-3APG was able to directly inhibit the proliferation of myeloma and Burkitt's lymphoma cell lines in vitro without showing toxicity to normal bone marrow stromal cells or hematopoietic progenitor cells. In vivo, S-3APG treatment of drug resistant myeloma cell tumors in mice was able to produce complete and sustained regressions without any observed toxicity. Additionally, S-3APG induced complete regressions of Burkitt's lymphoma cell tumors. Furthermore, S-3APG inhibited angiogenesis more potently than thalidomide in the murine corneal micropocket model. We conclude that S-3APG is a powerful anti-myeloma and anti-B-cell-lymphoma agent that has both antiproliferative and antiangiogenic effects. C1 Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dept Adult Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. EntreMed Inc, Rockville, MD 20850 USA. RP D'Amato, RJ (reprint author), Childrens Hosp, Dept Surg, 300 Longwood Ave, Boston, MA 02115 USA. RI Rogers, Michael/A-9814-2009 OI Rogers, Michael/0000-0002-5250-8434 FU PHS HHS [P01 78378, R01 50947] NR 31 TC 58 Z9 60 U1 0 U2 8 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 APR 15 PY 2002 VL 62 IS 8 BP 2300 EP 2305 PG 6 WC Oncology SC Oncology GA 543ML UT WOS:000175105700019 PM 11956087 ER PT J AU Breedveld, GJ van Dongen, JWF Danesino, C Guala, A Percy, AK Dure, LS Harper, P Lazarou, LP van der Linde, H Joosse, M Gruters, A MacDonald, ME de Vries, BBA Arts, WFM Oostra, BA Krude, H Heutink, P AF Breedveld, GJ van Dongen, JWF Danesino, C Guala, A Percy, AK Dure, LS Harper, P Lazarou, LP van der Linde, H Joosse, M Gruters, A MacDonald, ME de Vries, BBA Arts, WFM Oostra, BA Krude, H Heutink, P TI Mutations in TITF-1 are associated with benign hereditary chorea SO HUMAN MOLECULAR GENETICS LA English DT Article ID TRANSCRIPTION FACTOR-I; ENHANCER-BINDING PROTEIN; PROXIMAL CHROMOSOME 14Q; RESPIRATORY-FAILURE; NKX2.1 GENE; DNA; HOMEODOMAIN; DELETION; SPECIFICITY; DISEASE AB Benign hereditary chorea (BHC) (MIM 118700) is an autosomal dominant movement disorder. The early onset of symptoms (usually before the age of 5 years) and the observation that in some BHC families the symptoms tend to decrease in adulthood suggests that the disorder results from a developmental disturbance of the brain. In contrast to Huntington disease (MIM 143100), BHC is non-progressive and patients have normal or slightly below normal intelligence. There is considerable inter- and intrafamilial variability, including dysarthria, axial dystonia and gait disturbances. Previously, we identified a locus for BHC on chromosome 14 and subsequently identified additional independent families linked to the same locus. Recombination analysis of all chromosome 14-linked families resulted initially in a reduction of the critical interval for the BHC gene to 8.4 cM between markers D14S49 and D14S278. More detailed analysis of the critical region in a small BHC family revealed a de novo deletion of 1.2 Mb harboring the TITF-1 gene, a homeodomain-containing transcription factor essential for the organogenesis of the lung, thyroid and the basal ganglia. Here we report evidence that mutations in TITF-1 are associated with BHC. C1 Erasmus Univ, Erasmus Med Ctr Rotterdam, Dept Clin Genet, NL-3000 DR Rotterdam, Netherlands. Univ Pavia, Dept Med Genet, I-27100 Pavia, Italy. Hosp SS Pietro & Paolo, ASL 11, Pediat UAO, Borgosesia, Italy. Univ Alabama, Div Pediat Neurol, Birmingham, AL USA. Univ Wales Coll Cardiff, Dept Med, Cardiff CF1 3NS, S Glam, Wales. Humboldt Univ, Charite, Otto Heubner Ctr Pediat, Berlin, Germany. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Univ Med Ctr, Dept Human Genet, Nijmegen, Netherlands. Erasmus Univ, Med Ctr, Dept Pediat Neurol, NL-3000 DR Rotterdam, Netherlands. RP Heutink, P (reprint author), Erasmus Univ, Erasmus Med Ctr Rotterdam, Dept Clin Genet, POB 1738, NL-3000 DR Rotterdam, Netherlands. FU NINDS NIH HHS [NS16367] NR 38 TC 118 Z9 125 U1 0 U2 3 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 APR 15 PY 2002 VL 11 IS 8 BP 971 EP 979 DI 10.1093/hmg/11.8.971 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 546KU UT WOS:000175273900011 PM 11971878 ER PT J AU Rao, UNM Ibrahim, J Flaherty, LE Richards, J Kirkwood, JM AF Rao, UNM Ibrahim, J Flaherty, LE Richards, J Kirkwood, JM TI Implications of microscopic satellites of the primary and extracapsular lymph node spread in patients with high-risk melanoma: Pathologic corollary of eastern cooperative oncology group trial E1690 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; PROGNOSTIC FACTORS; LARYNGEAL-CANCER; NECK DISSECTION; METASTASES; SENTINEL; FEATURES; BIOPSY AB Purpose To correlate the presence of extracapsular spread (ECS) of regional nodal metastases, and micrometastasis near the primary tumor, with disease outcome in the intergroup study E1690 in relation to the impact of recombinant interferon-alfa (rIFNalpha)-2b. Patients and Methods: E1690 included 642 patients with American Joint Committee on Cancer stage IIB or III cutaneous melanoma. Patients were randomized into high- and low-dose rIFNalpha-2b treatment arms and an observation arm. Pathologic slides were reviewed for selected parameters from at least half of the subjects in all three arms. Evaluation of the primary tumor included notations regarding ulceration, mitotic activity, thickness, microscopic satellites (MS), and nodal ECS on a standardized pathology form. These data were collated in relation to relapse-free survival (RFS) and overall survival (OS) at 50 months' follow-up and studied using Cox regression analysis. Results: Ulceration, mitotic activity, thickness, and size of tumor-bearing lymph nodes did not show a statistically significant correlation with either OS or RFS across all treatment arms. The presence of MS was correlated with RFS (P = .0008) and OS (P = .05). ECS correlated with RFS (hazard ratio = 1.44, P = .032) but not OS (P = .11). Conclusion: The presence of MS (in 6% [18 of 308 patients]) had a significant adverse impact on both RFS (P = .0008) and OS (P = .053). Ulceration, mitotic activity, thickness, and number of positive lymph nodes had no significant effect on OS in this subset study (univariate or multivariate Cox analysis). The presence of ECS in lymph nodes had a significant adverse effect on RFS (P = .032) but not on OS. (C) 2002 by American Society of Clinical Oncology. C1 Univ Pittsburgh, Sch Med, Dept Pathol & Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Med Ctr, Melanoma Ctr, Dept Pathol & Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Wayne State Univ, Harper Grace Hosp, Detroit, MI USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. RP Rao, UNM (reprint author), Univ Pittsburgh, Presbyterian Univ Hosp, Sch Med, 200 Lothrop St, Pittsburgh, PA 15213 USA. FU NCI NIH HHS [CA14028, CA21115, CA66636, CA23318, CA32102, CA39229] NR 23 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 15 PY 2002 VL 20 IS 8 BP 2053 EP 2057 DI 10.1200/JCO.2002.08.024 PG 5 WC Oncology SC Oncology GA 544JR UT WOS:000175154900016 PM 11956265 ER PT J AU Diller, L Nancarrow, CM Shaffer, K Matulonis, U Mauch, P Neuberg, D Tarbell, NJ Litman, H Garber, J AF Diller, L Nancarrow, CM Shaffer, K Matulonis, U Mauch, P Neuberg, D Tarbell, NJ Litman, H Garber, J TI Breast cancer screening in women previously treated for Hodgkin's disease: A prospective cohort study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article AB Purpose Young women who are exposed to chest irradiation for Hodgkin's disease (HD) are at increased risk of breast cancer; this study investigated patient awareness of breast cancer risk and patient screening behavior and assessed the utility of mammographic screening in HD survivors. Patients and Methods: This is a prospective cohort study of 90 female long-term survivors of HD who had been treated greater than or equal to 8 years previously with mantle irradiation (current age, 24 to 51 years). Participants completed surveys of their perceptions of breast cancer risk and screening behaviors and received written recommendations for breast examinations and mammography. Annual follow-up was conducted through medical records, telephone, and/or mailed questionnaires. Results: At baseline, women were often unaware of their increased risk of breast cancer; 40% (35 of 87) reported themselves to be at equal or lower risk than women of the some age. Only 47% (41 of 87) reported having had a mammogram in the previous 24 months. Women who had received information from an oncologist were more likely to assess correctly their risk than women who received information from other sources (P < .001). Ten women developed 12 breast cancers (ductal carcinoma-in-situ [n = 2], invasive ductal carcinoma [n = 10]) during the study; two were diagnosed at study entry, and 10 during follow-up (median, 3.1 years). All cancers were evident on mammogram, and eight of 10 invasive cancers were node negative. Conclusion: Practitioners who care for women after HD therapy need to educate patients regarding their risks and begin early screening. Screening by mammography can detect small, node-negative breast cancers in these patients. © 2002 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Diller, L (reprint author), Dana Farber Canc Inst, Dept Pediat, 44 Binney St,Dana 367, Boston, MA 02115 USA. OI Shaffer, Kitt/0000-0001-6488-6988 NR 9 TC 68 Z9 69 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 15 PY 2002 VL 20 IS 8 BP 2085 EP 2091 DI 10.1200/JCO.2002.08.031 PG 7 WC Oncology SC Oncology GA 544JR UT WOS:000175154900020 PM 11956269 ER PT J AU Ng, AK Bernardo, MP Weller, E Backstrand, KH Silver, B Marcus, KC Tarbell, NJ Friedberg, J Canellos, GP Mauch, PM AF Ng, AK Bernardo, MP Weller, E Backstrand, KH Silver, B Marcus, KC Tarbell, NJ Friedberg, J Canellos, GP Mauch, PM TI Long-term survival and competing causes of death in patients with early-stage Hodgkin's disease treated at age 50 or younger SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CONTROLLED CLINICAL-TRIALS; PROGNOSTIC FACTORS; RANDOMIZED TRIALS; ELDERLY PATIENTS; CHEMOTHERAPY; RADIOTHERAPY; IRRADIATION; RADIATION; THERAPY; MOPP AB Purpose : To analyze the long-term survival and the pattern and timing of excess mortality in patients with early-stage Hodgkin's disease. Patients and Methods: Between 1969 and 1997, 1,080 patients age 50 or younger were treated for clinical stage IA to IIB Hodgkin's disease. Overall survival was determined, and prognostic factors were assessed. Relative risk and absolute excess risk (AR) of mortality were calculated for the entire cohort and by prognostic groups (on the basis of B symptoms, mediastinal status, and number of sites, modified from the European Organization for Research and Treatment of Cancer). Results: The median follow-up was 12 years. The 15- and 20-year Kaplan-Meier survival estimates were 84% and 78%, respectively. Cox proportional hazards models showed that number of involved sites (P = .006), mediastinal status (P = .02), and histology (P = .02) were independent predictors of death from all causes. The AR of mortality in patients with a favorable prognosis creased over time, whereas for those with an unfavorable prognosis, the AR peaked in the first 5 years, predominantly from Hodgkin's disease. The relative risk of mortality from all causes, causes other than Hodgkin's disease, second tumors, and cardiac disease remained significantly elevated more than 20 years after treatment. Conclusion: Patients treated for early-stage Hodgkin's disease have a sustained excess mortality risk despite good control of the disease. Treatment reduction efforts in patients with early-stage, favorable-prognosis disease should continue, but for patients with an unfavorable prognosis, modified treatment may not be advisable. The excess mortality noted beyond two decades underscores the importance of long-term follow-up care in patients treated for Hodgkin's disease. (C) 2002 by American Society of Clinical Oncology. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Biostat Sci, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Mauch, PM (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 30 TC 206 Z9 215 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 15 PY 2002 VL 20 IS 8 BP 2101 EP 2108 DI 10.1200/JCO.2002.08.021 PG 8 WC Oncology SC Oncology GA 544JR UT WOS:000175154900022 PM 11956271 ER PT J AU Loberiza, FR Rizzo, JD Bredeson, CN Antin, JH Horowitz, MM Weeks, JC Lee, SJ AF Loberiza, FR Rizzo, JD Bredeson, CN Antin, JH Horowitz, MM Weeks, JC Lee, SJ TI Association of depressive syndrome and early deaths among patients after stem-cell transplantation for malignant diseases SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; METASTATIC BREAST-CANCER; LONG-TERM SURVIVORS; HEART-TRANSPLANTATION; OLDER ADULTS; MORTALITY; PREDICTORS; SYMPTOMS; ANXIETY; DISORDERS AB Purpose : The association of depression and increased mortality in the general population, and also various medical conditions, is well documented. However, depression is not well studied in the setting of hematopoietic stem-cell transplantation (HSCT). We examined the association between depressive syndrome and survival after HSCT. Patients and Methods: A total of 193 patients who received autologous or allogeneic HSCT from Brigham and Women's Hospital or Dana-Farber Cancer Institute were evaluated prospectively. The self-rated Likert-scaled symptom checklist, the SF-36, and the Spitzer Quality of Life Index Scale were administered. Outcomes evaluated included survival and quality of life. Results: Sixty-seven patients (35%) satisfied the criteria for depressive syndrome. The 1-year probability of survival for the depressed and nondepressed patients was 85% (95% confidence interval [CI], 74% to 92%) and 94% (95% CI, 89% to 97%), respectively (P = .04). In multivariable modeling, depressed patients have a three-fold greater risk of dying than nondepressed patients (95% CI, 1.07 to 8.30; P = .04) between 6 and 12 months after HSCT after adjusting for other prognostic factors. Global inferiority in quality of life was observed in the depressed cohort when lost measured at 24 months after transplantation. Conclusion: Depressive syndrome after HSCT is associated with decreased survival, at least from 6 to 12 months after transplantation. Persistence of this association after controlling for possible confounding factors suggests that depression may be more than simply a marker for concurrent ill health. This study raises an interesting hypothesis as to whether psychological or pharmacologic intervention for depression after HSCT can improve survival and/or quality of life. (C) 2002 by American Society of Clinical Oncology. C1 Med Coll Wisconsin, Hlth Policy Inst, Int Bone Marrow Transplant Registry, Milwaukee, WI 53224 USA. Med Coll Wisconsin, Dept Med Hematol & Oncol, Bone Marrow Transplant Program, Milwaukee, WI 53224 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Loberiza, FR (reprint author), Med Coll Wisconsin, Hlth Policy Inst, Int Bone Marrow Transplant Registry, 8701 Watertown Plank Rd, Milwaukee, WI 53224 USA. FU NCI NIH HHS [CA75267-03] NR 42 TC 98 Z9 98 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 15 PY 2002 VL 20 IS 8 BP 2118 EP 2126 DI 10.1002/JCO.2002.08.757 PG 9 WC Oncology SC Oncology GA 544JR UT WOS:000175154900024 PM 11956273 ER PT J AU Maccioni, M Zeder-Lutz, G Huang, HC Ebel, C Gerber, P Hergueux, J Marchal, P Duchatelle, V Degott, C van Regenmortel, M Benoist, C Mathis, D AF Maccioni, M Zeder-Lutz, G Huang, HC Ebel, C Gerber, P Hergueux, J Marchal, P Duchatelle, V Degott, C van Regenmortel, M Benoist, C Mathis, D TI Arthritogenic monoclonal antibodies from K/BxN mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE autoimmunity; arthritis; autoantibodies; glucose-6-phosphate isomerase; mouse model ID COLLAGEN-INDUCED ARTHRITIS; T-CELL; RHEUMATOID-ARTHRITIS; COMPLEMENT; DISEASE; AUTOANTIBODIES; ENZYME; LOCI AB Arthritis in the K/BxN mouse model is provoked by pathogenic antibodies (Abs) directed against a ubiquitously expressed protein, glucose-6-phosphate isomerase (GPI). To begin dissecting the repertoire of arthritogenic immunoglobulins (Igs) in the K/BxN model, and to provide a basis for comparison with RA patients we have generated anti-GPI monoclonal Abs (mAbs) from spontaneously activated B cells in the lymphoid organs of arthritic mice. B cell clones with anti-GPI specificities were present at extra ordinarily high frequencies in the spleen, and less frequently in other lymphoid organs and in the synovial fluid. None of the anti-GPI mAbs induced arthritis when injected individually into healthy recipients, but most were effective when combined in pairs or larger pools. Arthritogenic combinations depended on mAbs of the IgG1 isotype, which bound to GPI with Kd in the 10(-9) M range, with no indication of cooperative binding between complementing pairs pathogenicity was not associated with recognition of a particular epitope, but the ability to form mAb/GPI multimers by simultaneous recognition of different epitopes was clearly required, consistent with the known role of complement and FcRs in this model. Sequence analysis revealed structural similarities amongst the mAbs, indicating that a particular subset of B cells may evade tolerance in K/BxN mice, and that affinity maturation by somatic mutation likely takes place. These results confirm that GPI itself, rather than a cross-reactive molecule, is the target of pathogenic Igs. C1 ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67000 Strasbourg, France. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Joslin Diabet Ctr,Sect Immunol & Immunog, Boston, MA 02215 USA. CNRS, Inst Biol Mol & Cellulaire, F-67084 Strasbourg, France. Hop Beaujon, Serv Anat Pathol, F-92110 Clichy, France. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NIAMS NIH HHS [1R01 AR/AI46580-01] NR 21 TC 132 Z9 135 U1 0 U2 4 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 APR 15 PY 2002 VL 195 IS 8 BP 1071 EP 1077 DI 10.1084/jem.20011941 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 560ZE UT WOS:000176110600013 PM 11956298 ER PT J AU Shelley, CS Teodoridis, JM Park, H Farokhzad, OC Bottinger, EP Arnaout, MA AF Shelley, CS Teodoridis, JM Park, H Farokhzad, OC Bottinger, EP Arnaout, MA TI During differentiation of the monocytic cell line U937, Pur alpha mediates induction of the CD11c beta(2) integrin gene promoter SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SINGLE-STRANDED-DNA; T-LYMPHOCYTE ADHESION; BASIC-PROTEIN GENE; BINDING-PROTEIN; TRANSCRIPTION FACTORS; LEUKOSIALIN CD43; SIALOPHORIN CD43; DOWN-REGULATION; NUCLEAR FACTOR; EXPRESSION AB CD11c is a member of the beta(2) integrin family of adhesion molecules that, together with CD18, forms a heterodimeric receptor on the surface of myeloid, NK, dendritic, and certain leukemic, lymphoma, and activated lymphoid cells. Monocytic differentiation is associated with an induction of both CD11c and CD18 gene expression. The resulting CD11c/CD18 receptor mediates firm adhesion to the vascular endothelium, transendothelial migration, chemotaxis, and phagocytosis. Monocytic differentiation can be mimicked in vitro by treatment of the promonocytic cell line U937 with PMA. Recently, we reported that in U937 cells, expression of the CD11c gene is controlled by an unidentified transcription factor that binds ssDNA. This finding suggested that DNA secondary structure plays an important role in controlling the CD11c gene and prompted us to search for additional ssDNA-binding activities with which this gene interacts. In this study, we report that in U937 cells, expression of the CD11c gene is mediated by the ssDNA-binding protein Puralpha. During PMA-induced differentiation, the ability of Pura to activate the CD11c promoter in U937 cells increases, as does that of Sp1. Together, these increases in the functional activity of both Pura and Sill combine to induce CD11c expression. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. RP Shelley, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM shelley@receptor.mgh.harvard.edu FU NIAID NIH HHS [AI28465]; NIDDK NIH HHS [DK43351, DK50779] NR 51 TC 36 Z9 37 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2002 VL 168 IS 8 BP 3887 EP 3893 PG 7 WC Immunology SC Immunology GA 540DJ UT WOS:000174913300028 PM 11937543 ER PT J AU Yang, OO Garcia-Zepeda, EA Walker, BD Luster, AD AF Yang, OO Garcia-Zepeda, EA Walker, BD Luster, AD TI Monocyte chemoattractant protein-2 (CC chemokine ligand 8) inhibits replication of human immunodeficiency virus type 1 via CC chemokine receptor 5 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CHEMOTACTIC PROTEIN-2; T-CELLS; HIV-1; MCP-2; IDENTIFICATION; INFLAMMATION; CYTOKINES; BINDING; CD4 AB CC chemokine receptor 5 (CCR5) is a coreceptor for cellular entry of monocyte-tropic (R5) strains of human immunodeficiency virus (HIV) type 1, which has been implicated as the predominant phenotype of HIV in early infection. The CCR5 agonists macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated on activation, normally T cell-expressed and -secreted) have been shown to block replication of R5 virus in vitro and have gained attention as potential antiviral factors. However, a few reports have suggested that other chemokines may also block R5 HIV-1, including monocyte chemoattractant protein (MCP)-2 (CC chemokine ligand 8). We demonstrate that MCP-2 specifically inhibits replication of R5 HIV-1 and that this activity is additive to that of RANTES. Furthermore, MCP-2 induces a robust, pertussis toxin-sensitive calcium flux in primary lymphocytes, and cross-desensitization studies indicate that MCP-2 acts via CCR5. These data confirm that MCP-2 is a ligand for CCR5 on CD4(+) lymphocytes and can specifically block R5 HIV-1. C1 Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Yang, OO (reprint author), Univ Calif Los Angeles, Med Ctr, Div Infect Dis, 10833 LeConte Ave,37-121 CHS, Los Angeles, CA 90095 USA. FU NIAID NIH HHS [R01 AI 43203, R01 AI 46999, K08 AI 01413] NR 14 TC 13 Z9 15 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 APR 15 PY 2002 VL 185 IS 8 BP 1174 EP 1178 DI 10.1086/339678 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 536XH UT WOS:000174726800023 PM 11930329 ER PT J AU Nolin, TD Colaizzi, IV Palevsky, PM Matzke, GR Frye, RF AF Nolin, TD Colaizzi, IV Palevsky, PM Matzke, GR Frye, RF TI Rapid microtiter plate assay for determination of inulin in human plasma and dialysate SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE microtiter plate; spectrophotometry; colorimetric assay; inulin; hemodialysis ID PERFORMANCE LIQUID-CHROMATOGRAPHY; WATER PERMEABILITY; ENZYMATIC ANALYSIS; HEMODIALYSIS; SOLUTE AB A rapid, sensitive, and reproducible microtiter plate assay for the determination of inulin in human plasma, dialysate, and phosphate-buffered saline (PBS) was developed. Plasma or PBS samples (100 mul aliquots) were prepared by the addition of indole-3-acetic acid (150 muI) and HCl (3 ml) and then briefly vortex-mixed. Samples were then incubated in a 60 degreesC water bath for 20 min, cooled in a room temperature water bath for 40 min, then diluted with deionized, distilled water (DDW; 3 ml) and again vortex-mixed. Finally, an aliquot (200 mul) of each sample was transferred to a 96-well microtiter plate and read spectrophotometrically at 490 nm. Dialysate samples were processed in a similar manner, but required an initial enzymatic step in order to remove dextrose and minimize assay interference. Samples (100 mul aliquots) were prepared by the addition of glucose oxidase/catalase solution (100 mul), briefly vortex mixed, and then incubated in a 37 degreesC water bath for 60 min, samples were then reacted with indole-3-acetic acid as before. Calibration curves were linear over the concentration range of 0.5-4 mg/ml or 0.025-0.4 mg/ml for plasma or PBS and dialysate, respectively; correlation coefficients (r(2)) were > 0.99. The intra and inter-day coefficients of variation in plasma, PBS, and dialysate were < 15%. This method is well suited for the rapid analysis of large numbers of samples and is currently being used for in vitro investigations of solute removal by hemodialysis. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Pittsburgh, Dept Pharmaceut Sci, Sch Pharm, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. RP Frye, RF (reprint author), Univ Pittsburgh, Dept Pharmaceut Sci, Sch Pharm, 807 Salk Hall, Pittsburgh, PA 15261 USA. OI Palevsky, Paul/0000-0002-7334-5400; Frye, Reginald/0000-0002-1841-1401 NR 18 TC 3 Z9 3 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD APR 15 PY 2002 VL 28 IS 2 BP 209 EP 215 AR PII S0731-7085(01)00643-4 DI 10.1016/S0731-7085(01)00643-4 PG 7 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 546DH UT WOS:000175256300003 PM 11929663 ER PT J AU Affonce, DA Fowler, AJ AF Affonce, DA Fowler, AJ TI The effect of thermal lensing during selective photothermolysis SO JOURNAL OF QUANTITATIVE SPECTROSCOPY & RADIATIVE TRANSFER LA English DT Article; Proceedings Paper CT 3rd International Symposium on Radiative Transfer CY JUN, 2001 CL ANTALYA, TURKEY SP TUBITAK, Meddle E Tech Univ, Univ Kentucky DE laser; tissue; modelling ID PORT-WINE STAINS; LASER TREATMENT; LIGHT DISTRIBUTIONS; SKIN TISSUE; IRRADIATION; MODEL; TELANGIECTASIA AB The results of an integrated Monte Carlo and finite difference simulation of laser light propagation and heat transfer in the skin are reported. The study was performed to examine the effects of the change in refractive index that results during laser irradiation of tissue. When skin is irradiated with laser light its surface temperature rises dramatically. This results in a change in the refractive index of the tissue which has been shown in model systems to result in thermal lensing of the laser light. This paper reports on the development of a model to study the effect of thermal lensing on laser light propagation through skin as a function of beam geometry and incident irradiance. It was found that for high irradiance thermal lensing can result in a significant decrease in the predicted epidermal fluence, although it has only a small effect on overall beam penetration. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Massachusetts, Dept Mech Engn, N Dartmouth, MA 02747 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. RP Affonce, DA (reprint author), Univ Massachusetts, Dept Mech Engn, N Dartmouth, MA 02747 USA. NR 22 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 0022-4073 J9 J QUANT SPECTROSC RA JI J. Quant. Spectrosc. Radiat. Transf. PD APR 15 PY 2002 VL 73 IS 2-5 SI SI BP 473 EP 479 AR PII S0022-4073(01)00210-2 DI 10.1016/S0022-4073(01)00210-2 PG 7 WC Optics; Spectroscopy SC Optics; Spectroscopy GA 537AE UT WOS:000174733400032 ER PT J AU Singhal, AB Topcuoglu, MA Koroshetz, WJ AF Singhal, AB Topcuoglu, MA Koroshetz, WJ TI Diffusion MRI in three types of anoxic encephalopathy SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE coma; anoxia; global cerebral ischemia; prognosis; diffusion-weighted imaging ID INJURY; HYPOXIA; DAMAGE AB We report the clinical and diffusion-weighted MRI (DWI) features of three patients with different types of anoxic brain injury: attempted hanging (hypoxic hypoxia). carbon monoxide poisoning (histotoxic hypoxia). and hanging with cardiac arrest (hypoxic-ischemic encephalopathy. HIE). The first two patients, but not the third, recovered substantial neurological function. The distribution of DWI abnormalities was different and correlated well with the distinct neuropathological features of these entities, The prognosis after anoxic encephalopathy depends on the underlying mechanism and its severity, which may be reflected by DWI abnormalities. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, VBK-802,55 Fruit St, Boston, MA 02114 USA. NR 13 TC 68 Z9 68 U1 0 U2 2 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 APR 15 PY 2002 VL 196 IS 1-2 BP 37 EP 40 AR PII S0022-510X(02)00019-9 DI 10.1016/S0022-510X(02)00019-9 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 547EE UT WOS:000175319400006 PM 11959154 ER PT J AU Hahesy, AL Wilens, TE Biederman, J Van Patten, SL Spencer, T AF Hahesy, AL Wilens, TE Biederman, J Van Patten, SL Spencer, T TI Temporal association between childhood psychopathology and substance use disorders: findings from a sample of adults with opioid or alcohol dependency SO PSYCHIATRY RESEARCH LA English DT Article DE childhood-onset; substance use disorder; adults; developmental sequence ID DEFICIT HYPERACTIVITY DISORDER; SELF-MEDICATION HYPOTHESIS; PSYCHIATRIC-DISORDERS; ANXIETY DISORDERS; CONDUCT DISORDER; BIPOLAR DISORDER; RISK-FACTORS; EARLY-ONSET; DRUG-ABUSE; COMORBIDITY AB Adults with substance use disorders (SUD; alcohol or drug abuse or dependence) were evaluated to determine if childhood-onset psychopathology preceded the onset of SUD. Using structured psychiatric interviews, we assessed 47 clinically referred adults with SUD (27 with opioid dependence and 20 with alcohol dependence), with attention to childhood-onset psychopathology. A sequence of psychopathology and SUD was reconstructed using mean diagnosis onset data. Sixty-two percent of the 47 SUD adults (mean age 39.3 +/- 6.6 years) had early-onset SUD (defined as less than or equal to 18 years) and 38% had late-onset SUD (greater than or equal to 19 years at onset). psychopathology preceded the onset of SUD in 56% of adults. Attention deficit/hyperactivity disorder, multiple anxiety, and disruptive disorders typically preceded the onset of SUD in contrast, mood disorders (specifically depressive and bipolar disorders) followed the onset of SUD. The majority of clinically referred adults with SUD had psychopathology that began in childhood, frequently preceding the onset of their SUD. These findings further highlight the importance of targeting antecedent disorders for preventive and early intervention programs aimed at reducing the risk for SUD. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Pediat & Adult Psychopharmacol Clin, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Pediat & Adult Psychopharmacol Clin, 15 Parkman St,ACC 725, Boston, MA 02114 USA. FU NIDA NIH HHS [DA-12945, DA-11929]; NIMH NIH HHS [MH-K2001175A] NR 59 TC 26 Z9 26 U1 1 U2 2 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 APR 15 PY 2002 VL 109 IS 3 BP 245 EP 253 AR PII S0165-1781(02)00015-X DI 10.1016/S0165-1781(02)00015-X PG 9 WC Psychiatry SC Psychiatry GA 552VA UT WOS:000175639700004 PM 11959361 ER PT J AU Giray, N Castriotta, RJ Hirshkowitz, M Allen, T Swann, A AF Giray, N Castriotta, RJ Hirshkowitz, M Allen, T Swann, A TI Distinction between depression and vital exhaustion in sleep-disordered breathing SO SLEEP LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Univ Texas, Sch Med, Houston, TX USA. RI Castriotta, Richard/B-1158-2009 NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2002 VL 25 SU S MA 546 BP A389 EP A390 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 540KB UT WOS:000174927200548 ER PT J AU Krystal, AD Perlis, ML McCall, WV Zammit, G Hirshkowitz, M AF Krystal, AD Perlis, ML McCall, WV Zammit, G Hirshkowitz, M TI Three-month non-nightly use of zolpidem for the treatment of primary insomnia SO SLEEP LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. Univ Rochester, Rochester, NY USA. Wake Forest Univ, Sch Med, Wake Forest, NC USA. St Lukes Roosevelt Hosp, New York, NY USA. VA Med Ctr, Houston, TX USA. RI Krystal, Andrew/J-7109-2013 OI Krystal, Andrew/0000-0002-6702-781X NR 2 TC 3 Z9 3 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2002 VL 25 SU S MA 092 BP A68 EP A68 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 540KB UT WOS:000174927200094 ER PT J AU Mitler, M Westbrook, P Levendowski, DJ Ensign, WY Olmstead, RE Berka, C Davis, G Lumicao, MN Cventovic, M Petrovic, MM AF Mitler, M Westbrook, P Levendowski, DJ Ensign, WY Olmstead, RE Berka, C Davis, G Lumicao, MN Cventovic, M Petrovic, MM TI Validation of automated EEG quantification of alertness: Methods for early identification of individuals most susceptible to sleep deprivation SO SLEEP LA English DT Meeting Abstract C1 Pacific Sleep Med Serv, La Jolla, CA USA. USN, Hlth Res Ctr, San Diego, CA 92152 USA. Vet Affairs Greater Los Angeles CA Healthcare Sys, Los Angeles, CA USA. NR 3 TC 8 Z9 8 U1 2 U2 2 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2002 VL 25 SU S MA 196 BP A147 EP A148 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 540KB UT WOS:000174927200198 ER PT J AU Regestein, QR Friebely, J Shifren, JL Scharf, MB Wiita, B Carver, J Schiff, I AF Regestein, QR Friebely, J Shifren, JL Scharf, MB Wiita, B Carver, J Schiff, I TI Self-reported sleep in menopausal women correlates with symptoms more than with objectively-recorded sleep SO SLEEP LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tristate Sleep Disorders Ctr, Cleveland, OH USA. Johnson & Johnson Consumer Prod Inc, Skillman, NJ 08558 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2002 VL 25 SU S MA 509 BP A367 EP A367 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 540KB UT WOS:000174927200511 ER PT J AU Regestein, QR Friebely, J Shifren, JL Schiff, I AF Regestein, QR Friebely, J Shifren, JL Schiff, I TI Menopausal methyltestosterone treatment induces changes in subjective sleep that correlate with changes in motor speed but not in vigilance SO SLEEP LA English DT Meeting Abstract ID DOPAMINE C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2002 VL 25 SU S MA 332 BP A245 EP A245 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 540KB UT WOS:000174927200334 ER PT J AU Schmidt-Nowara, WW Haynes, JB Hirshkowitz, M AF Schmidt-Nowara, WW Haynes, JB Hirshkowitz, M CA Modafinil OSA Study Grp TI Modafinil improves quality of life in obstructive sleep apnea SO SLEEP LA English DT Meeting Abstract C1 Sleep Med Inst, Dallas, TX USA. St Thomas Hosp, Nashville, TN USA. VA Med Ctr, Houston, TX USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2002 VL 25 SU S MA 653 BP A461 EP A461 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 540KB UT WOS:000174927200654 ER PT J AU Thomas, RJ Kwong, KK Scammell, TE AF Thomas, RJ Kwong, KK Scammell, TE TI Effect of modafinil on working memory after sleep deprivation: A functional magnetic resonance imaging study. SO SLEEP LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2002 VL 25 SU S MA 451 BP A327 EP A327 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 540KB UT WOS:000174927200453 ER PT J AU Westbrook, P Berka, C Levendowski, DJ Lumicao, MN Davis, G Olmstead, RE Cventovic, M Petrovic, MM Zavora, TM AF Westbrook, P Berka, C Levendowski, DJ Lumicao, MN Davis, G Olmstead, RE Cventovic, M Petrovic, MM Zavora, TM TI Biobehavioral quantification of alertness and memory in patients with sleep apnea SO SLEEP LA English DT Meeting Abstract C1 Vet Affairs Greater Los Angeles CA Healthcare Sys, Los Angeles, CA USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2002 VL 25 SU S MA 067 BP A49 EP A50 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 540KB UT WOS:000174927200069 ER PT J AU Xi, X McGinty, D Szymusiak, R AF Xi, X McGinty, D Szymusiak, R TI Activity of ventral periaqueductal gray neurons during warming of the preoptic/anterior hypothalamic area SO SLEEP LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2002 VL 25 SU S MA 176 BP A132 EP A133 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 540KB UT WOS:000174927200178 ER PT J AU Rasmussen, RA Hofmann-Lehmann, R Li, PL Vlasak, J Schmitz, JE Reimann, KA Kuroda, MJ Letvin, NL Montefiori, DC McClure, HM Ruprecht, RM AF Rasmussen, RA Hofmann-Lehmann, R Li, PL Vlasak, J Schmitz, JE Reimann, KA Kuroda, MJ Letvin, NL Montefiori, DC McClure, HM Ruprecht, RM TI Neutralizing antibodies as a potential secondary protective mechanism during chronic SHIV infection in CD8+T-cell-depleted macaques SO AIDS LA English DT Article DE primate; neutralization; antibodies; CD8+T cells; cellular immunity; viral infections ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG-TERM NONPROGRESSORS; CYTOTOXIC T-LYMPHOCYTES; RHESUS-MONKEYS; TYPE-1 INFECTION; CELL DEPLETION; VIREMIA; AIDS; RESPONSES; COMPLEX AB Objective To directly examine the role of CD8+ T cells in controlling viremia and disease during chronic, low-level primate immunodeficiency virus infection in DNA prime/protein boost-vaccinated macaques. Background A cohort of macaques, vaccinated with either a DNA prime/HIV-1 gp160 ;boost regimen or with gp160 alone was previously protected partially from sequential challenges with non-pathogenic and pathogenic strains of chimeric simian/human immunodeficiency virus (SHIV). In this study, the effect of temporary ablation of CD8+ T cells in these animals was examined. Methods Animals were treated with an anti-CD8 antibody and CD8+ T-cell levels in peripheral blood, plasma viral loads, peripheral blood mononuclear cell-associated virus levels, neutralizing antibody (nAb) titers and simian immunodeficiency virus Gag-specific CD8+ T-cell numbers were followed. Results Plasma viremia rose sharply in direct synchrony with a rapid but transient drop in CD8+ T cells. However, although levels of cell-associated virus also rose concomitantly, peak levels were much lower than those in virus-challenged, naive animals. In addition, despite a rise of pathogenic SHIV89.6P RNA levels in three animals, CD4+ T-cell counts remained unchanged. in each of these animals, neutralizing antibody titers against the pathogenic SHIV89.6P strain were high. Conclusions The results indicate that CD8+ T cells play a key role in suppressing viremia in a chronically infected host. In addition, the results suggest that in the absence of CD8+ T cells, nAb may act as an effective second line of defense by limiting both the spread of infectious virus to new target cells and CD4+ T-cell loss. (C) 2002 Lippincott Williams Wilkins. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Div Microbiol & Immunol, Atlanta, GA 30322 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Div Res Resources, Atlanta, GA 30322 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Viral Pathogenesis, Boston, MA 02215 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. RI Hofmann-Lehmann, Regina/C-6528-2009 FU NCRR NIH HHS [R24 RR016001, RR-00165, P51 RR000165, RR13150]; NIAID NIH HHS [R01 AI34266, P01 AI048240, P01 AI48240, AI85343, R21 AI46177, R21 AI046177, R01 AI034266] NR 24 TC 45 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 12 PY 2002 VL 16 IS 6 BP 829 EP 838 DI 10.1097/00002030-200204120-00002 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 544NZ UT WOS:000175167900002 PM 11919484 ER PT J AU Aboulafia, DM Meneses, M Ginsberg, S Siegel, MS Howard, WW Dezube, BJ AF Aboulafia, DM Meneses, M Ginsberg, S Siegel, MS Howard, WW Dezube, BJ TI Acute myeloid leukemia in patients infected with HIV-1 SO AIDS LA English DT Article DE HIV-1; AIDS; cancers; acute myeloid leukemia; chemotherapy; treatment ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACUTE MYELOBLASTIC-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; FIBROBLAST-GROWTH-FACTOR; ACUTE MONOCYTIC LEUKEMIA; ACUTE NONLYMPHOBLASTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; SEROPOSITIVE MAN; POSITIVE PATIENT; TAT PROTEIN AB Objectives: Myelodysplasia is a frequent consequence of HIV infection, but acute myeloid leukemia (AML) is rare. Clinical presentations and outcomes of patients with HIV and subsequent AML are reviewed. Methods: Five HIV-infected individuals who were subsequently diagnosed with AML were evaluated and treated. A further 42 cases of AML among patients with antecedent HIV infection were identified using MEDLINE, AIDSLINE, and CancerLit searches. Results: HIV infection was present for a median of 48 months (71-180) before AML was diagnosed and the median reported CD4 cell count was 210 X 10(6) cells/l. In five instances, a delay in diagnosis occurred when cytopenias were initially attributed to HIV or zidovudine-based therapy. In 45 patients, diagnosis was according to the French-American-British (FAB) leukemia classification schema and in two the FAB type was not specified. M2 (n = 15) and M4 (n = 14) subtypes represented 64% (29/ 45) of reported cases. Patients with a CD4 cell count < 200 X 10(6) cells/l (n = 11) had a median survival time of 7 weeks, while patients with a CD4 cell count greater than or equal to 200 x 10(6) cells/l (n = 7) had a median survival of 7 months (P = 0.005). Although long-lasting chemotherapy-induced responses were rare, the majority of treated patients did achieve complete hematologic remissions. Treatment-related morbidity did not appear to be excessive. Conclusion: in the absence of randomized and prospective clinical studies to guide decision making, this analysis indicates that induction chemotherapy may be a reasonable option for selected HIV-infected patients with AML and adequate immune function. (C) 2002 Lippincott Williams Wilkins. C1 Virginia Mason Clin, Div Hematol Oncol, Seattle, WA 98111 USA. Polyclin Seattle, Grp Hlth Cooperat, Seattle, WA USA. Polyclin Seattle, Infect Dis Sect, Seattle, WA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. RP Aboulafia, DM (reprint author), Virginia Mason Clin, Div Hematol Oncol, 1100 9th Ave H14-HEM, Seattle, WA 98111 USA. NR 53 TC 16 Z9 16 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 12 PY 2002 VL 16 IS 6 BP 865 EP 876 DI 10.1097/00002030-200204120-00006 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 544NZ UT WOS:000175167900006 PM 11919488 ER PT J AU Brisman, JL Cosgrove, GR Cole, AJ AF Brisman, JL Cosgrove, GR Cole, AJ TI Phosphorylation of P42/P44 MAP kinase and DNA fragmentation in the rat perforant pathway stimulation model of limbic epilepsy SO BRAIN RESEARCH LA English DT Article DE MAP kinase; perforant pathway stimulation; epilepsy; rat; DNA fragmentation ID ACTIVATED PROTEIN-KINASE; NERVE GROWTH-FACTOR; SUSTAINED ELECTRICAL-STIMULATION; GRANULE CELL NEUROGENESIS; TYROSINE PHOSPHORYLATION; HIPPOCAMPAL-NEURONS; DENTATE GYRUS; STATUS EPILEPTICUS; BRAIN-DAMAGE; APOPTOSIS AB The intracellular signaling pathways associated with neuronal injury after perforant pathway stimulation of the rodent hippocampus have not been examined. To determine whether activation of the p42/p44 (Erk1/2) MAP kinase (MAPK) phosphorylation cascade is linked to neuronal injury after perforant pathway stimulation (PPS), we stained for phosphorylated Erk1/2 (P-Erk1/2) and for DNA fragmentation, a marker of cell death after PPS. Eighteen Sprague-Dawley rats underwent PPS for 6 (n=6), 12 (n=6), or 24 (n=6) h and were sacrificed either immediately (n=9) or 48 h (n=9) after stimulation. Sham-operated non-stimulated control animals (n=2) and control animals receiving low frequency stimulation only (n=4) were also examined. Brain sections were stained for DNA fragmentation and P-Erk1/2. DNA fragmentation was evident only in granule cells and CA3 pyramidal cells of the stimulated side 48 h after 24 h of PPS. PPS resulted in robust phosphorylation of Erk1/2 that displayed a stereotyped timecourse, appearing first in hilar neurons on the ipsilateral side and later in hilar neurons, granule cells, hippocampal pyramidal and non-neuronal cell populations on both the stimulated and contralateral sides. Both Erk1/2 phosphorylation and DNA fragmentation show definite and reproducible staining patterns after PPS that vary based on duration of stimulation. Populations displaying Erk1/2 activation appeared to differ from those showing DNA fragmentation and neuronal injury. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Epilepsy Serv, VBK 830, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Epilepsy Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Cole, AJ (reprint author), Massachusetts Gen Hosp, Epilepsy Serv, VBK 830, 55 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS036224] NR 43 TC 10 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 12 PY 2002 VL 933 IS 1 BP 50 EP 59 AR PII S0006-8993(02)02304-1 DI 10.1016/S0006-8993(02)02304-1 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 547YT UT WOS:000175361200006 PM 11929635 ER PT J AU Chalfant, CE Rathman, K Pinkerman, RL Wood, RE Obeid, LM Ogretmen, B Hannun, YA AF Chalfant, CE Rathman, K Pinkerman, RL Wood, RE Obeid, LM Ogretmen, B Hannun, YA TI De novo ceramide regulates the alternative splicing of caspase 9 and Bcl-x in A549 lung adenocarcinoma cells - Dependence on protein phosphatase-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHEMOTHERAPY-INDUCED APOPTOSIS; INSULIN-INDUCIBLE CHANGES; RECEPTOR MESSENGER-RNA; KINASE C-BETA; SR PROTEINS; SPHINGOLIPID BIOSYNTHESIS; NEUTRAL SPHINGOMYELINASE; SIGNAL-TRANSDUCTION; CELLULAR SENESCENCE; PHOSPHATIDIC-ACID AB Previous studies have demonstrated that several splice variants are derived from both the caspase 9 and Bcl-x genes in which the Bcl-x splice variant, Bcl-x(L) and the caspase 9 splice variant, caspase 9b, inhibit apoptosis in contrast to the pro-apoptotic splice variants, Bel-x(s) and caspase 9. In a recent study, we showed that ceramide induces the dephosphorylation of SR proteins, a family of protein factors that regulate alternative splicing. In this study, the regulation of the alternative processing of pre-mRNA of both caspase 9 and Bel-x(L) was examined in response to ceramide. Treatment of A549 lung adenocarcinoma cells with cellpermeable ceramide, D-e-C, ceramide, down-regulated the levels of Bcl-x(L) and caspase 9b mRNA and immunoreactive protein with a concomitant increase in the mRNA and immunoreactive protein levels of Bcl-x(s) and caspase 9 in a dose- and time-dependent manner. Pretreatment with calyculin A (5 nm), an inhibitor of protein phosphatase-1 (PP1) and protein phosphatase 2A (PP2A) blocked ceramide-induced alternative splicing in contrast to okadaic acid (10 nm), a specific inhibitor of PP2A at this concentrations in cells, demonstrating a PP1-mediated mechanism. A role for endogenous ceramide in regulating the alternative splicing of caspase 9 and Bcl-x was demonstrated using the chemotherapeutic agent, gemcitabine. Treatment of A549 cells with gemcitabine (1 muM) increased ceramide levels 3-fold via the de novo sphingolipid pathway as determined by pulse labeling experiments and inhibition studies with myriocin (50 nm), a specific inhibitor of serine palmitoyltransferase (the first step in de novo synthesis of ceramide). Treatment of A549 cells with gemcitabine downregulated the levels of Bcl-x(L) and caspase 9b mRNA with a concomitant increase in the mRNA levels of Bcl-x(s) and caspase 9. Again, inhibitors of ceramide synthesis blocked this effect. We also demonstrate that the change in the alternative splicing of caspase 9 and Bcl-x occurred prior to apoptosis following treatment with gemcitabine. Furthermore, doses of D-e-C-6 ceramide that induce the alternative splicing of both caspase 9 and Bel-x-sensitized A549 cells to daunorubicin. These data demonstrate a role for protein phosphatases 1 (PP1) and endogenous ceramide generated via the de novo pathway in regulating this mechanism. This is the first report on the dynamic regulation of RNA splicing of members of the Bcl-2 and caspase families in response to regulators of apoptosis. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Hannun, YA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, 173 Ashley Ave,POB 250509,Rm 501,Basic Sci Bldg, Charleston, SC 29425 USA. OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [CA 87584]; NIGMS NIH HHS [GM 19953-02, GM 43825] NR 81 TC 219 Z9 234 U1 2 U2 14 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 APR 12 PY 2002 VL 277 IS 15 BP 12587 EP 12595 DI 10.1074/jbc.M112010200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 542GZ UT WOS:000175036300015 PM 11801602 ER PT J AU Ogretmen, B Pettus, BJ Rossi, MJ Wood, R Usta, J Szulc, Z Bielawska, A Obeid, LM Hannun, YA AF Ogretmen, B Pettus, BJ Rossi, MJ Wood, R Usta, J Szulc, Z Bielawska, A Obeid, LM Hannun, YA TI Biochemical mechanisms of the generation of endogenous long chain ceramide in response to exogenous short chain ceramide the A549 human lung adenocarcinoma cell line - Role for endogenous ceramide in mediating the action of exogenous ceramide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NECROSIS-FACTOR-ALPHA; INDUCED APOPTOSIS; GOLGI-APPARATUS; SPHINGOLIPID BIOSYNTHESIS; NEUTRAL SPHINGOMYELINASE; DOWNSTREAM TARGET; CYCLE ARREST; BREFELDIN-A; DEATH; SYNTHASE AB Treatment of A549 cells with C-6-ceramide resulted in a significant increase in the endogenous long chain ceramide levels, which was inhibited by fumonisin B1 (FB1), and not by myriocin (MYR). The biochemical mechanisms of generation of endogenous ceramide were investigated using A549 cells treated with selectively labeled C-6-ceramides, [sphingosine-3-H-3]D-erythro-, and N-[N-hexanoyl-1-C-14]D-erythro-C-6-ceramide. The results demonstrated that 311 label was incorporated into newly synthesized long chain ceramides, which was inhibited by FB1 and not by MYR. Interestingly, the C-14 label was not incorporated into long chain ceramides. Taken together, these results show that generation of endogenous ceramide in response to C-6-ceramide is due to recycling of the sphingosine backbone of C-6-ceramide via deacylation/reacylation and not due to the elongation of its fatty acid moiety. Moreover, the generation of endogenous long chain ceramide in response to C-6-ceramide was completely blocked by brefeldin A, which causes Golgi disassembly, suggesting a role for the Golgi in the metabolism of ceramide. In addition, the generation of endogenous ceramide in response to short chain exogenous ceramide was induced by D-erythro- but not L-erythro-C-6-ceramide, demonstrating the stereospecificity of this process. Interestingly, several key downstream biological activities of ceramide, such as growth inhibition, cell cycle arrest, and modulation of telomerase activity were induced by D-erythro-C-6-ceramide, and not L-erythro-C6-ceramide (and inhibited by FB1) in A549 cells, suggesting a role for endogenous long chain ceramide in the regulation of these responses. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. Amer Univ Beirut, Dept Biochem, Beirut, Lebanon. RP Ogretmen, B (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, POB 250779, Charleston, SC 29425 USA. FU NCI NIH HHS [CA 87584]; NIA NIH HHS [AG 12467, AG 16583]; NIGMS NIH HHS [GM 48325] NR 45 TC 133 Z9 136 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 APR 12 PY 2002 VL 277 IS 15 BP 12960 EP 12969 DI 10.1074/jbc.M110699200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 542GZ UT WOS:000175036300062 PM 11815611 ER PT J AU Kaneto, H Sharma, A Suzuma, K Laybutt, DR Xu, G Bonner-Weir, S Weir, GC AF Kaneto, H Sharma, A Suzuma, K Laybutt, DR Xu, G Bonner-Weir, S Weir, GC TI Induction of c-Myc expression suppresses insulin gene transcription by inhibiting NeuroD/BETA2-mediated transcriptional activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PANCREATIC BETA-CELLS; BINDING-PROTEIN-BETA; DIABETES-MELLITUS; CONTROL ELEMENT; GLUCOSE TOXICITY; HOMEOBOX FACTOR; HIT-T15 CELLS; RAT; PROMOTER; JUN AB Insulin biosynthesis and secretion are critical for pancreatic beta-cell function, but both are impaired under diabetic conditions. We have found that hyperglycemia induces the expression of the basic helix-loop-helix transcription factor c-Myc in islets in several different diabetic models. To examine the possible implication of c-Myc in beta-cell dysfunction, c-Myc was overexpressed in isolated rat islets using adenovirus. Adenovirus-mediated c-Myc overexpression suppressed both insulin gene transcription and glucose-stimulated insulin secretion. Insulin protein content, determined by immunostaining, was markedly decreased in c-Myc-overexpressing cells. In gel-shift assays c-Myc bound to the E-box in the insulin gene promoter region. Furthermore, in betaTC1, MIN6, and HIT-T15 cells and primary rat islets, wild type insulin gene promoter activity was dramatically decreased by c-Myc overexpression, whereas the activity of an E-box mutated insulin promoter was not affected. In HeLa and HepG2 cells c-Myc exerted a suppressive effect on the insulin promoter activity only in the presence of NeuroD/BETA2 but not PDX-1. Both c-Myc and NeuroD can bind the E-box element in the insulin promoter, but unlike NeuroD, the c-Myc transactivation domain lacked the ability to activate insulin gene expression. Additionally p300, a co-activator of NeuroD, did not function as a co-activator of c-Myc. In conclusion, increased expression of c-Myc in beta-cells suppresses the insulin gene transcription by inhibiting NeuroD-mediated transcriptional activation. This mechanism may explain some of the beta-cell dysfunction found in diabetes. C1 Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. RP Kaneto, H (reprint author), Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 35449] NR 56 TC 41 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 APR 12 PY 2002 VL 277 IS 15 BP 12998 EP 13006 DI 10.1074/jbc.M111148200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 542GZ UT WOS:000175036300066 PM 11799123 ER PT J AU Koipally, J Heller, EJ Seavitt, JR Georgopoulos, K AF Koipally, J Heller, EJ Seavitt, JR Georgopoulos, K TI Unconventional potentiation of gene expression by Ikaros SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR; DNA-BINDING; CENTROMERIC HETEROCHROMATIN; LYMPHOCYTE DEVELOPMENT; COMPLEXES; FAMILY; DIFFERENTIATION; ACTIVATION; REPRESSION; MECHANISM AB Ikaros is essential for the normal development and regulated proliferation of lymphoid cells. In lymphocytes, Ikaros exists as an integral component of chromatin-remodeling complexes, including the Mi-2beta/nucleosome remodeling and deacetylation complex (NuRD) complex. It is expected that Ikaros, together with these associated activities effects repression, but here we show that they may also potentiate gene expression in cycling cells. Ikaros cannot activate transcription by itself, instead, it enhances the activity of both weak and strong activators. For this role in potentiation, Ikaros requires its DNA binding and dimerization domains. The DNA binding and dimerization properties of Ikaros are also responsible for its targeting to pericentromeric heterochromatin (PC-HQ. Significantly, Ikaros mutants with altered specificity for DNA binding that are unable to localize to PC-HC are incapable of stimulating transcription from reporters bearing their cognate sites. Thus, potentiation of gene expression by Ikaros correlates strongly with its ability to localize to PC-HC in combination with the chromatin remodeler Mi-2beta. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Georgopoulos, K (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, E Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIAID NIH HHS [R01 AI 380342-08]; NIGMS NIH HHS [F32-GM-20724] NR 33 TC 53 Z9 55 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 APR 12 PY 2002 VL 277 IS 15 BP 13007 EP 13015 DI 10.1074/jbc.M111371200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 542GZ UT WOS:000175036300067 PM 11799125 ER PT J AU Vaidya, CM Wright, JE Rosowsky, A AF Vaidya, CM Wright, JE Rosowsky, A TI Synthesis and in vitro antitumor activity of new deaza analogues of the nonpolyglutamatable antifolate N-alpha-(4-amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithine (PT523) SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID REDUCED FOLATE CARRIER; SIDE-CHAIN; DIHYDROFOLATE-REDUCTASE; BIOLOGICAL EVALUATION; POTENT; 10-PROPARGYL-10-DEAZAAMINOPTERIN; METHOTREXATE; CYTOTOXICITY; AMINOPTERIN; INHIBITORS AB Details are disclosed for the synthesis of N-alpha-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-N-delta-hemiphthaloyl-L-ornithine (2) and N-alpha-[4-[5-(2,4-diaminoteridin-6-yl)pent-1-yn-4-yl]benzoyl]-N-alpha-hemiphthaloyl-L-ornithine (6) as analogues of Na-(4-amino-4-deoxypteroyl) N-delta-hemiphthaloyl-L-ornithine (1, PT523), a nonpolyglutamatable antifolate currently in advanced preclinical development. In a 72 h growth inhibition assay against cultures of CCRF-CEM human leukemic lamphoblasts, the IC50 of 2 and 6 was 0.69 +/- 0.044 nM and 1.3 +/- 0.35 nM, respectively, as compared with previously reported values 4.4 +/- 0.10 nM for aminopterin (AMT) and 1.5 +/- 0.39 nM for PT523. In a spectrophotometric assay of dihydrofolate reductase (DHFR) inhibition using dihydrofolate and NADPH as the cosubstrates, the previously unreported compounds 2 and the mixed 10R and 10S diastereomers of 6 had K-i values of 0.21 +/- 0.05 pM and 0.60 +/- 0.02 pM, respectively, as compared with previously reported values of 3.70 +/- 0.35 pM for AMT and 0.33 +/- 0.04 pM for PT523. Thus, while they were comparable to 1 and several of its previously studied analogues in their ability to bind to DHFR and inhibit the growth of CCRF-CEM cells, 2 and the mixed diastereomers of 6 were several times more active than AMT despite the fact that they cannot form gamma-polyglutamylated metabolites of the type formed in cells from AMT and other classical antifolates with a glutamate side chain. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [CA25394, CA70349] NR 23 TC 10 Z9 10 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 11 PY 2002 VL 45 IS 8 BP 1690 EP 1696 DI 10.1021/jm010518t PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 538ZH UT WOS:000174844600017 PM 11931624 ER PT J AU Ramet, M Manfruelli, P Pearson, A Mathey-Prevot, B Ezekowitz, RAB AF Ramet, M Manfruelli, P Pearson, A Mathey-Prevot, B Ezekowitz, RAB TI Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E-coli SO NATURE LA English DT Article ID PEPTIDOGLYCAN RECOGNITION PROTEIN; CELLS; GENE; HEMATOPOIESIS; MELANOGASTER; MECHANISMS; EXPRESSION; REGULATOR; CLONING AB The recognition and phagocytosis of microbes by macrophages is a principal aspect of innate immunity that is conserved from insects to humans. Drosophila melanogaster has circulating macrophages that phagocytose microbes similarly to mammalian macrophages(1,2), suggesting that insect macrophages can be used as a model to study cell-mediated innate immunity. We devised a double-stranded RNA interference-based screen in macrophage-like Drosophila S2 cells, and have defined 34 gene products involved in phagocytosis. These include proteins that participate in haemocyte development, vesicle transport, actin cytoskeleton regulation and a cell surface receptor. This receptor, Peptidoglycan recognition protein LC (PGRP-LC), is involved in phagocytosis of Gram-negative but not Gram-positive bacteria. Drosophila humoral immunity also distinguishes between Gram-negative and Gram-positive bacteria through the Imd and Toll pathways, respectively; however, a receptor for the Imd pathway has not been identified. Here we show that PGRP-LC is important for antibacterial peptide synthesis induced by Escherichia coli both in vitro and in vivo. Furthermore, totem mutants, which fail to express PGRP-LC, are susceptible to Gram-negative (E. coli), but not Gram-positive, bacterial infection. Our results demonstrate that PGRP-LC is an essential component for recognition and signalling of Gram-negative bacteria. Furthermore, this functional genomic approach is likely to have applications beyond phagocytosis. C1 Massachusetts Gen Hosp Children, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Dept Pediat, Dana Faber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP Ramet, M (reprint author), Massachusetts Gen Hosp Children, Lab Dev Immunol, 55 Fruit St, Boston, MA 02114 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 31 TC 465 Z9 481 U1 3 U2 38 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 11 PY 2002 VL 416 IS 6881 BP 644 EP 648 DI 10.1038/nature735 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 539YV UT WOS:000174901900046 PM 11912489 ER PT J AU Albert, CM Campos, H Stampfer, MJ Ridker, PM Manson, JE Willett, WC Ma, J AF Albert, CM Campos, H Stampfer, MJ Ridker, PM Manson, JE Willett, WC Ma, J TI Blood levels of long-chain n-3 fatty acids and the risk of sudden death. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID VENTRICULAR-FIBRILLATION; MYOCARDIAL-INFARCTION; FISH CONSUMPTION; DIETARY-INTAKE; CARDIAC DEATH; PREVENTION; MYOCYTES; CURRENTS; HUMANS AB Background: Experimental data suggest that long-chain n-3 polyunsaturated fatty acids found in fish have antiarrhythmic properties, and a randomized trial suggested that dietary supplements of n-3 fatty acids may reduce the risk of sudden death among survivors of myocardial infarction. Whether long-chain n-3 fatty acids are also associated with the risk of sudden death in those without a history of cardiovascular disease is unknown. Methods: We conducted a prospective, nested case-control analysis among apparently healthy men who were followed for up to 17 years in the Physicians' Health Study. The fatty-acid composition of previously collected blood was analyzed by gas-liquid chromatography for 94 men in whom sudden death occurred as the first manifestation of cardiovascular disease and for 184 controls matched with them for age and smoking status. Results: Base-line blood levels of long-chain n-3 fatty acids were inversely related to the risk of sudden death both before adjustment for potential confounders (P for trend = 0.004) and after such adjustment (P for trend = 0.007). As compared with men whose blood levels of long-chain n-3 fatty acids were in the lowest quartile, the relative risk of sudden death was significantly lower among men with levels in the third quartile (adjusted relative risk, 0.28; 95 percent confidence interval, 0.09 to 0.87) and the fourth quartile (adjusted relative risk, 0.19; 95 percent confidence interval, 0.05 to 0.71). Conclusions: The n-3 fatty acids found in fish are strongly associated with a reduced risk of sudden death among men without evidence of prior cardiovascular disease. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiovasc, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Albert, CM (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. FU NCI NIH HHS [CA-34944, CA-40360]; NHLBI NIH HHS [1-K08-HL-03783, HL-26490, HL-34595] NR 25 TC 719 Z9 737 U1 2 U2 35 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 APR 11 PY 2002 VL 346 IS 15 BP 1113 EP 1118 DI 10.1056/NEJMoa012918 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 539PX UT WOS:000174880600003 PM 11948270 ER PT J AU Mouria, M Gukovskaya, AS Jung, Y Buechler, P Hines, OJ Reber, HA Pandol, SJ AF Mouria, M Gukovskaya, AS Jung, Y Buechler, P Hines, OJ Reber, HA Pandol, SJ TI Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome c release and apoptosis SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE pancreatic carcinoma; apoptosis; quercetin; trans-resveratrol; genistein; rutin ID NF-KAPPA-B; LEUKEMIA HL-60 CELLS; PERMEABILITY TRANSITION; DOWN-REGULATION; PROTEIN-KINASE; RESVERATROL; INDUCTION; DEATH; ACTIVATION; QUERCETIN AB There is increasing evidence that food-derived polyphenols have a beneficial effect for cancers. Our purpose was to determine the effect and mechanism of action of these compounds on pancreatic cancer. We measured effects of quercetin on pancreatic cancer in a nude mouse model. We also investigated the effects of quercetin, rutin, trans-resveratrol and genistein on apoptosis and underlying signaling in pancreatic carcinoma cells in vitro. Quercetin decreased primary tumor growth, increased apoptosis and prevented metastasis in a model of pancreatic cancer. In vitro quercetin and trans-resveratrol, but not rutin, markedly enhanced apoptosis, causing mitochondrial depolarization and cytochrome c release followed by caspase-3 activation. In addition, the effect of a combination of quercetin and trans-resveratrol on mitochondrial cytochrome c release and caspase-3 activity was greater than the expected additive response. The inhibition of mitochondrial permeability transition prevented cytochrome c release, caspase-3 activation and apoptosis caused by polyphenols. Nuclear factor-kappaB activity was inhibited by quercetin and trans-resveratrol, but not genistein, indicating that this transcription factor is not the only mediator of the polyphenols' effects on apoptosis. The results suggest that food-derived polyphenols inhibit pancreatic cancer growth and prevent metastasis by inducing mitochondrial dysfunction, resulting in cytochrome c release, caspase activation and apoptosis. (C) 2002 Wiley-Liss, Inc. C1 VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. RP Gukovskaya, AS (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, Bldg 258,Room 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 55 TC 184 Z9 201 U1 1 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 10 PY 2002 VL 98 IS 5 BP 761 EP 769 DI 10.1002/ijc.10202 PG 9 WC Oncology SC Oncology GA 531KC UT WOS:000174413700018 PM 11920648 ER PT J AU Hu, FB Bronner, L Willett, WC Stampfer, MJ Rexrode, KM Albert, CM Hunter, D Manson, JE AF Hu, FB Bronner, L Willett, WC Stampfer, MJ Rexrode, KM Albert, CM Hunter, D Manson, JE TI Fish and omega-3 fatty acid intake and risk of coronary heart disease in women SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; ALPHA-LINOLENIC ACID; DIETARY-INTAKE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; CONSUMPTION; DEATH; REPRODUCIBILITY; PREVENTION; GREENLAND AB Context Higher consumption of fish and omega-3 fatty acids has been associated with a lower risk of coronary heart disease (CND) in men, but limited data are available regarding women. Objective To examine the association between fish and long-chain omega-3 fatty acid consumption and risk of CHD in women. Design, Setting, and Participants Dietary consumption and follow-up data from 84688 female nurses enrolled in the Nurses' Health Study, aged 34 to 59 years and free from cardiovascular disease and cancer at baseline in 1980, were compared from validated questionnaires completed in 1980, 1984, 1986, 1990, and 1994. Main Outcome Measures Incident nonfatal myocardial infarction and CHD deaths. Results During 16 years of follow-up, there were 1513 incident cases of CHID (484 CHD deaths and 1029 nonfatal myocardial infarctions). Compared with women who rarely ate fish (<1 per month), those with a higher intake of fish had a lower risk of CHD. After adjustment forage, smoking, and other cardiovascular risk factors, the multivariable relative risks (RRs) of CHD were 0.79 (95% confidence interval [CI], 0.64-0.97) for fish consumption 1 to 3 times per month, 0.71 (95% CI, 0.58-0.87) for once per week, 0.69 (95% CI, 0.55-0.88) for 2 to 4 times per week, and 0.66 (95% Cl, 0.50-0.89) for 5 or more times per week (P for trend =.001). Similarly, women with a higher intake of omega-3 fatty acids had a lower risk of CHD, with multivariable RRs of 1.0, 0.93, 0.78, 0.68, and 0.67 (P<.001 for trend) across quintiles of intake. For fish intake and omega-3 fatty acids, the inverse association appeared to be stronger for CHID deaths (multivariate RR for fish consumption 5 times per week, 0.55 [95% Cl, 0.33-0.90] for CHID deaths vs 0.73 [0.51-1.04]) than for nonfatal myocardial infarction. Conclusion Among women, higher consumption of fish and omega-3 fatty acids is associated with a lower risk of CHID, particularly CHID deaths. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. RP Hu, FB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. OI Rexrode, Kathryn/0000-0003-3387-8429 FU NCI NIH HHS [CA87969]; NHLBI NIH HHS [HL34594, HL24074] NR 40 TC 557 Z9 592 U1 4 U2 41 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 APR 10 PY 2002 VL 287 IS 14 BP 1815 EP 1821 DI 10.1001/jama.287.14.1815 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 539QJ UT WOS:000174881700034 PM 11939867 ER PT J AU Del Monte, F Butler, K Boecker, W Gwathmey, JK Hajjar, RJ AF Del Monte, F Butler, K Boecker, W Gwathmey, JK Hajjar, RJ TI Novel technique of aortic banding followed by gene transfer during hypertrophy and heart failure SO PHYSIOLOGICAL GENOMICS LA English DT Article DE cardiac; gene therapy; rats ID MYOCYTES; CARDIOMYOPATHIES; PATHOPHYSIOLOGY; ATPASE; CA2+ AB Aortic banding in the rat has become a popular method to induce left ventricular (LV) hypertrophy and heart failure. However, because of often extensive intrathoracic adhesions and inflammatory cell infiltrates resulting from the traditional surgical approach, an uncomplicated second thoracic incision for genetic manipulation is impeded. In this study, we describe a novel surgical technique of aortic banding which avoids opening the sternum and thereby avoids adhesions and surgery-related inflammation. Placing a clip on the ascending aorta using a suprasternal approach in Sprague-Dawley rats created proximal aortic constriction. The present study was initiated to determine whether a replication-deficient adenovirus would enable efficient gene transfer to adult cardiac myocytes undergoing hypertrophy and transitioning to heart failure. Echocardiography performed at week 24 revealed significant concentric hypertrophy and increased fractional shortening followed by LV dilatation with decreased fractional shortening after 27 wk of banding. An adenoviral solution encoding for the reporter green fluorescent protein gene (GFP) was delivered to the heart. Fluorescent microscopy revealed global gene expression throughout hypertrophied and failing hearts. Our studies demonstrate that a novel suprasternal approach can be applied to create an LV hypertrophy model followed by heart failure which also allows investigators to perform genetic manipulations in vivo through gene transfer without the complication of adhesions and surgical trauma-induced inflammation. Furthermore, our approach to delivery of transgenes results in homogenous gene expression in both hypertrophied and failing hearts. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Program Cardiovasc Gene Therapy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Gwathmey Inc, Cambridge, MA USA. Morehouse Sch Med, Dept Surg, Atlanta, GA 30310 USA. RP Hajjar, RJ (reprint author), Massachusetts Gen Hosp E, Cardiovasc Res Ctr, 149 13th St,CNY-4,Rm 4215, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL-57623, R01-HL-49574, R43-HL-60323, R43-HL-66407, R44-HL-60323] NR 16 TC 40 Z9 40 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD APR 10 PY 2002 VL 9 IS 1 BP 49 EP 56 DI 10.1152/physiolgenomics.00035.2001 PG 8 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 540JK UT WOS:000174925600006 PM 11948290 ER PT J AU Mittleman, MA Peters, A Muller, JE Dockery, DW AF Mittleman, MA Peters, A Muller, JE Dockery, DW TI Cardiovascular susceptibility to particulate air pollution SO CIRCULATION LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. GSF, Natl Res Ctr Environm & Hlth, Neuherberg, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, 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 APR 9 PY 2002 VL 105 IS 14 MA 78 BP E100 EP E100 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 541MA UT WOS:000174987300085 ER PT J AU Battelli, L Black, KR Wray, SH AF Battelli, L Black, KR Wray, SH TI Transcranial magnetic stimulation of visual area V5 in migraine SO NEUROLOGY LA English DT Article ID OCCIPITAL CORTEX; MOTION; HYPEREXCITABILITY; EXCITABILITY; IMPAIRMENT; PERCEPTION; AURA AB Objective: To examine visual cortical excitability in persons with migraine using transcranial magnetic stimulation (TMS) over an extrastriate area of the brain, area V5. Background: Previous studies found that persons with migraine have a lower phosphene threshold than healthy control subjects with TMS delivered over the primary visual cortical area V1. The result suggests that the occipital cortex in migraineurs between migraine attacks is hyperexcitable. However, it is not known whether interictal cortical hyperexcitability is also present in areas of the association visual cortex. Method: To investigate this, single-pulse TMS was delivered over visual area V5, the motion cortex, to 16 persons with migraine and visual aura, nine migraineurs without visual aura, and M healthy control subjects. TMS was delivered at intensities ranging from 30 to 100% of maximum stimulator output or until the participant reported seeing phosphenes (visual illusions characterized by flashes of light). Thresholds to phosphenes were obtained for each participant using a staircase procedure. Result: Significantly lower phosphene thresholds for TMS delivered over V5 were found in migraineurs as compared with control subjects. Qualitatively, the migraineurs' experience of phosphenes were more vivid, florid, and sustained compared with that of control subjects. Conclusion: Results of this study indicate that hyperexcitability of the visual cortex in migraine goes beyond visual area V1 and demonstrates for the First time a significant difference in threshold for excitability of visual area V5 in persons with migraine. C1 Harvard Univ, Dept Psychol, Vis Sci Lab, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Battelli, L (reprint author), Harvard Univ, Dept Psychol, Vis Sci Lab, 33 Kirkland St, Cambridge, MA 02138 USA. NR 25 TC 80 Z9 85 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 APR 9 PY 2002 VL 58 IS 7 BP 1066 EP 1069 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 539JC UT WOS:000174865900015 PM 11940694 ER PT J AU Karlawish, JHT Casarett, DA James, BD Propert, KJ Asch, DA AF Karlawish, JHT Casarett, DA James, BD Propert, KJ Asch, DA TI Do persons with dementia vote? SO NEUROLOGY LA English DT Article ID DISEASE AB To examine whether patients with dementia voted in the 2000 US dementia. A substantial portion of patients with mild to moderate dementia voted on their own at a voting booth. Patients cared for by spouses were more likely to vote than patients cared for by adult children. Further research is needed to understand how persons with dementia and their caregivers decide what activities the person can and cannot continue and how well these decisions correspond to measures of competency. C1 Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Div Geriatr, Philadelphia, PA 19104 USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Inst Aging, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Alzheimers Dis Ctr, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Karlawish, JHT (reprint author), 3615 Chestnut St, Philadelphia, PA 19104 USA. FU NIA NIH HHS [K01-AG00931, P30-AG01024] NR 5 TC 14 Z9 14 U1 2 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 APR 9 PY 2002 VL 58 IS 7 BP 1100 EP 1102 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 539JC UT WOS:000174865900022 PM 11940701 ER PT J AU King, PH Petersen, NE Rakhra, R Schreiber, WE AF King, PH Petersen, NE Rakhra, R Schreiber, WE TI Porphyria presenting with bilateral radial motor neuropathy: Evidence of a novel gene mutation SO NEUROLOGY LA English DT Article ID ACUTE INTERMITTENT PORPHYRIA; DIAGNOSIS AB The authors identified a novel mutation of the porphobilinogen deaminase (PBG-D) gene in a patient with acute intermittent porphyria presenting with severe and bilateral axonal radial motor neuropathy. Electrophysiologic studies revealed prominent involvement of distal radial nerves in the setting of mild polyneuropathy. Analysis of the PBG-D gene revealed a single base-pair insertion (887insA) in exon 14. C1 Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. Univ Alabama, Dept Physiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Biophys, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. Odense Univ Hosp, Dept Clin Biochem & Clin Genet, DK-5000 Odense, Denmark. Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. Vancouver Hosp & Hlth Sci Ctr, Div Clin Chem, Vancouver, BC V5Z 1M9, Canada. RP King, PH (reprint author), 625 S 19th St, Birmingham, AL 35294 USA. NR 10 TC 12 Z9 12 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 APR 9 PY 2002 VL 58 IS 7 BP 1118 EP 1121 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 539JC UT WOS:000174865900028 PM 11940707 ER PT J AU Schernhammer, ES Michaud, DS Leitzmann, MF Giovannucci, E Colditz, GA Fuchs, CS AF Schernhammer, ES Michaud, DS Leitzmann, MF Giovannucci, E Colditz, GA Fuchs, CS TI Gallstones, cholecystectomy, and the risk for developing pancreatic cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE pancreatic cancer; gallstones; cholecystectomy; risk factors; prospective cohort study ID COHORT; GROWTH AB We examined the relation between gallstones, cholecystectomy, and the development of pancreatic cancer in the Nurses' Health Study and the Health Professionals Follow-up Study. Among 104 856 women and 48 928 men without cancer at baseline, we documented 349 cases of pancreatic cancer during up to 16 years of follow-up. Participants were classified according to a history of gallstones or cholecystectomy. The age-adjusted relative risk of pancreatic cancer following cholecystectomy or diagnosis of gallstones was 1.31 (95% Cl, 0.93 - 1.83). However, adjustment for other pancreatic cancer risk factors attenuated the association (RR= 1.11, 95% Cl, 0.78 - 1.56); this risk did not increase with increasing time following cholecystectomy or gallstones. Gallstones or cholecystectomy do not appear to be significant risk factors for pancreatic cancer. (C) 2002 Cancer Research UK. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. KFJ Spital, Ludwig Boltzmann Inst Appl Canc Res, Vienna, Austria. NCI, Nutr Epidemiol Branch, Rockville, MD 20852 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Ctr Canc Prevent, Boston, MA USA. Dana Farber Harvard Canc Ctr, Program Epidemiol, Boston, MA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Schernhammer, ES (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. RI Michaud, Dominique/I-5231-2014; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA 86102, CA 40356, CA 55075, CA/ES62984, CA87969, P01 CA055075, P01 CA087969, R01 CA040356, R01 CA086102] NR 22 TC 25 Z9 25 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD APR 8 PY 2002 VL 86 IS 7 BP 1081 EP 1084 DI 10.1038/sj/bjc/6600193 PG 4 WC Oncology SC Oncology GA 550GV UT WOS:000175496000013 PM 11953853 ER PT J AU Cueva, JG Haverkamp, S Reimer, RJ Edwards, R Wassle, H Brecha, NC AF Cueva, JG Haverkamp, S Reimer, RJ Edwards, R Wassle, H Brecha, NC TI Vesicular gamma-aminobutyric acid transporter expression in amacrine and horizontal cells SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE retina; synaptic vesicles; GABA transport; VGAT ID GABA-LIKE IMMUNOREACTIVITY; MACAQUE MONKEY RETINA; GLUTAMATE DECARBOXYLASE GAD; DEVELOPING RABBIT RETINA; IN-SITU HYBRIDIZATION; OUTER PLEXIFORM LAYER; RAT RETINA; MAMMALIAN RETINA; CAT RETINA; IMMUNOCYTOCHEMICAL LOCALIZATION AB The vesicular gamma-aminobutyric acid (GABA) transporter (VGAT), which transports the inhibitory amino acid transmitters GABA and glycine, is localized to synaptic vesicles in axon terminals. The localization of VGAT immunoreactivity to mouse and rat retina was evaluated with light and electron microscopy by using well-characterized VGAT antibodies. Specific VGAT immunoreactivity was localized to numerous varicose processes in all laminae of the inner plexiform layer (IPL) and to the outer plexiform layer (OPL). Amacrine cell somata characterized by weak VGAT immunoreactivity in the cytoplasm were located in the ganglion cell layer and proximal inner nuclear layer (IN-L) adjacent to the IPL. In rat retina, VGAT-immunoreactive cell bodies also contained GABA, glycine, or parvalbumin (PV) immunoreactivity, suggesting vesicular uptake of GABA or glycine by these cells. A few varicose VGAT-immunoreactive processes entered the OPL from the IPL. VGAT immunoreactivity in the OPL was predominantly localized to horizontal cell processes. VGAT and calcium binding protein-28K immunoreactivities (CaBP; a marker for horizontal cells) were colocalized in processes and terminals distributed to the OPL. Furthermore, VGAT immunoreactivity overlapped or was immediately adjacent to postsynaptic density-95 (PSD-95) immunoreactivity, which is prominent in photoreceptor terminals. Pre-embedding immunoelectron microscopy of mouse and rat retinae showed that VGAT immunoreactivity was localized to horizontal cell processes and their terminals. Immunoreactivity was distributed throughout the cytoplasm of the horizontal cell processes. Taken together, these findings demonstrate VGAT immunoreactivity in both amacrine and horizontal cell processes, suggesting these cells contain vesicles that accumulate GABA and glycine, possibly for vesicular release. (C) 2002 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, Med Ctr, Dept Neurobiol, Los Angeles, CA 90095 USA. Max Planck Inst Hirnforsch, D-60528 Frankfurt, Germany. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, CURE, Digest Dis Res Ctr, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Healtcare Syst, Los Angeles, CA 90073 USA. RP Cueva, JG (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Neurobiol, 10833 LeConte Ave Box 951763, Los Angeles, CA 90095 USA. FU NEI NIH HHS [R01 EY004067-21S1, R01 EY004067-22, EY07026, R56 EY004067, EY04067, T32 EY007026, R01 EY004067] NR 83 TC 57 Z9 58 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 8 PY 2002 VL 445 IS 3 BP 227 EP 237 DI 10.1002/cne.10166 PG 11 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 527CF UT WOS:000174167600003 PM 11920703 ER PT J AU Eck, MJ AF Eck, MJ TI Structural insights into the regulation and cellular localization of Src-family tyrosine kinases Lck and Fyn. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2002 VL 223 MA 078-PHYS BP C31 EP C31 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 564CE UT WOS:000176296801527 ER PT J AU Edwards, A Elwyn, G Mulley, A AF Edwards, A Elwyn, G Mulley, A TI Explaining risks: turning numerical data into meaningful pictures SO BRITISH MEDICAL JOURNAL LA English DT Review ID DECISION-MAKING; COMMUNICATION C1 Univ Wales Coll Med, Dept Gen Practice, Llanedeyrn Hlth Ctr, Cardiff CF3 7PN, S Glam, Wales. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Edwards, A (reprint author), Univ Wales Coll Med, Dept Gen Practice, Llanedeyrn Hlth Ctr, Cardiff CF3 7PN, S Glam, Wales. RI Elwyn, G./L-4292-2015 NR 30 TC 335 Z9 337 U1 6 U2 21 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD APR 6 PY 2002 VL 324 IS 7341 BP 827 EP 830 DI 10.1136/bmj.324.7341.827 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 540ZG UT WOS:000174960300018 PM 11934777 ER PT J AU Choi, HK Hernan, MA Seeger, JD Robins, JM Wolfe, F AF Choi, HK Hernan, MA Seeger, JD Robins, JM Wolfe, F TI Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study SO LANCET LA English DT Article ID LONG-TERM MORTALITY; CLINICAL-TRIALS; ATHEROSCLEROSIS; ASSOCIATION; DISEASE AB Background Methotrexate is the most frequent choice of disease-modifying antirheumatic therapy for rheumatoid arthritis. Although results of studies have shown the efficacy of such drugs, including methotrexate, on rheumatoid arthritis morbidity measures, their effect on mortality in patients with the disease remains unknown. Our aim was to prospectively assess the effect on mortality of methotrexate in a cohort of patients with rheumatoid arthritis. Methods Our cohort included 1240 patients with rheumatoid arthritis seen at the Wichita Arthritis Center, an outpatient rheumatology facility. Patients' details were entered into a computerised database at the time of their first clinic visit. We also obtained and recorded demographic, clinical, laboratory, and self-reported data at each follow-up visit (average interval 3.5 months). We estimated the mortality hazard ratio of methotrexate with a marginal structural Cox proportional hazards model. Findings 191 individuals died during follow-up. Patients who began treatment with methotrexate (n=588) had worse prognostic factors for mortality. After adjustment for this confounding by indication, the mortality hazard ratio for methotrexate use compared with no methotrexate use was 0.4 (95% Cl 0.2-0.8). Other conventional disease-modifying antirheumatic drugs did not have a significant effect on mortality. The hazard ratio of methotrexate use for cardiovascular death was 0.3 (0.2-0.7), whereas that for non-cardiovascular deaths was 0.6 (0.2-1.2). Interpretation Our data indicate that methotrexate may provide a substantial survival benefit, largely by reducing cardiovascular mortality. This survival benefit of methotrexate would set a standard against which new disease-modifying antirheumatic drugs could be compared. C1 Univ Kansas, Sch Med, Arthrit Res Ctr Fdn, Natl Data Bank Rheumat Dis, Wichita, KS 67214 USA. Harvard Univ, Sch Publ Hlth, Harvard Sch Med,Massachusetts Gen Hosp, Dept Med,Arthrit Unit, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Igenix Epidemiol, Newton, MA USA. RP Wolfe, F (reprint author), Univ Kansas, Sch Med, Arthrit Res Ctr Fdn, Natl Data Bank Rheumat Dis, 1035 N Emporia,Suite 230, Wichita, KS 67214 USA. FU NIAID NIH HHS [AI49392, R01-AI32457] NR 30 TC 655 Z9 680 U1 4 U2 20 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 6 PY 2002 VL 359 IS 9313 BP 1173 EP 1177 DI 10.1016/S0140-6736(02)08213-2 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 539AB UT WOS:000174846300006 PM 11955534 ER PT J AU Rideout, WM Hochedlinger, K Kyba, M Daley, GQ Jaenisch, R AF Rideout, WM Hochedlinger, K Kyba, M Daley, GQ Jaenisch, R TI Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy SO CELL LA English DT Article ID EMBRYONIC STEM-CELLS; IN-VITRO; HEMATOPOIETIC-CELLS; ES CELLS; MICE; DIFFERENTIATION; OVEREXPRESSION; ENGRAFTMENT; DERIVATION; GENERATION AB Immune-deficient Rag2(-/-) mice were used as nuclear donors for transfer into enucleated oocytes, and the resulting blastocysts were cultured to isolate an isogenic embryonic stem cell line. One of the mutated alleles in the Rag2(-/-) ES cells was repaired by homologous recombination, thereby restoring normal Rag2 gene structure. Mutant mice were treated with the repaired ES cells in two ways. (1) Immune-competent mice were generated from the repaired ES cells by tetraploid embryo complementation and were used as bone marrow donors for transplantation. (2) Hematopoietic precursors were derived by in vitro differentiation from the repaired ES cells and engrafted into mutant mice. Mature myeloid and lymphoid cells as well as immunoglobulins became detectable 3-4 weeks after transplantation. Our results establish a paradigm for the treatment of a genetic disorder by combining therapeutic cloning with gene therapy. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Univ Vienna, A-1010 Vienna, Austria. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. RP Jaenisch, R (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. OI Kyba, Michael/0000-0002-5579-7534 FU NCI NIH HHS [CA86991, 5-R37-CA84198]; NIDDK NIH HHS [DK59279] NR 47 TC 403 Z9 425 U1 2 U2 24 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 5 PY 2002 VL 109 IS 1 BP 17 EP 27 DI 10.1016/S0092-8674(02)00681-5 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 539TY UT WOS:000174888300005 PM 11955443 ER PT J AU Kyba, M Perlingeiro, RCR Daley, GQ AF Kyba, M Perlingeiro, RCR Daley, GQ TI HoxB4 confers definitive lymphoid-myeloid engraftment potential on embryonic stem cell and yolk sac hematopoietic progenitors SO CELL LA English DT Article ID IN-VITRO; HOMEOBOX GENES; MOUSE EMBRYO; BONE-MARROW; EXPRESSION; OVEREXPRESSION; DIFFERENTIATION; SUBPOPULATIONS; ACTIVATION; CULTURE AB The extent to which primitive embryonic blood progenitors contribute to definitive lymphoid-myeloid hematopoiesis In the adult remains uncertain. In an effort to characterize factors that distinguish the definitive adult hematopoietic stem cell (HSC) and primitive progenitors derived from yolk sac or embryonic stem (ES) cells, we examined the effect of ectopic expression of HoxB4, a homeotic selector gene implicated in self-renewal of definitive HSCs. Expression of HoxB4 in primitive progenitors combined with culture on hematopoietic stroma induces a switch to the definitive HSC phenotype. These progenitors engraft lethally irradiated adults and contribute to long-term, multilineage hematopoiesis in primary and secondary recipients. Our results suggest that primitive HSCs are poised to become definitive HSCs and that this transition can be promoted by HoxB4 expression. This strategy for blood engraftment enables modeling of hematopoietic transplantation from ES cells. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. OI Kyba, Michael/0000-0002-5579-7534 FU NCI NIH HHS [CA86991]; NIDDK NIH HHS [DK59279] NR 35 TC 515 Z9 538 U1 2 U2 20 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 5 PY 2002 VL 109 IS 1 BP 29 EP 37 DI 10.1016/S0092-8674(02)00680-3 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 539TY UT WOS:000174888300006 PM 11955444 ER PT J AU Lu, QR Sun, T Zhu, ZM Ma, N Garcia, M Stiles, CD Rowitch, DH AF Lu, QR Sun, T Zhu, ZM Ma, N Garcia, M Stiles, CD Rowitch, DH TI Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection SO CELL LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; VENTRAL NEURAL-TUBE; OLIGODENDROCYTE LINEAGE; SPINAL-CORD; CEREBRAL-CORTEX; CELL LINEAGE; ASTROCYTES; EXPRESSION; GENES; DIFFERENTIATION AB The oligodendrocyte lineage genes Olig1 and Olig2 encode related bHLH proteins that are coexpressed in neural progenitors. Targeted disruption of these two genes sheds light on the ontogeny of oligodendroglia and genetic requirements for their development from multipotent CNS progenitors. Olig2 is required for oligodendrocyte and motor neuron specification in the spinal cord. Olig1 has roles in development and maturation of oligodendrocytes, evident especially within the brain. Both Olig genes contribute to neural pattern formation. Neither Olig gene is required for astrocytes. These findings, together with fate mapping analysis of Olig-expressing cells, indicate that oligodendrocytes are derived from Olig-specified progenitors that give rise also to neurons. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Stiles, CD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. FU NICHD NIH HHS [HD24296]; NINDS NIH HHS [NS4051] NR 41 TC 595 Z9 615 U1 1 U2 17 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 5 PY 2002 VL 109 IS 1 BP 75 EP 86 DI 10.1016/S0092-8674(02)00678-5 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 539TY UT WOS:000174888300010 PM 11955448 ER PT J AU Xie, Y Chen, CM Stevenson, MA Auron, PE Calderwood, SK AF Xie, Y Chen, CM Stevenson, MA Auron, PE Calderwood, SK TI Heat shock factor 1 represses transcription of IL-1 beta gene through physical interaction with the nuclear factor of interleukin 6 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; PROINTERLEUKIN 1-BETA GENE; TISSUE-SPECIFIC EXPRESSION; COLONY-STIMULATING FACTOR; C/EBP-RELATED PROTEINS; DNA-BINDING ABILITY; HUMAN-MONOCYTES; ANTIINFLAMMATORY DRUGS; CYTOKINE PRODUCTION AB Heat shock factor (HSF) 1 is the major heat shock transcription factor that regulates stress-inducible synthesis of heat shock proteins and is also essential in protection against endotoxic shock. Following our previous study, which demonstrated the transcriptional repression of the IL-1beta gene by HSF1 (Cahill, C. M., Waterman, W. R., Xie, Y., Auron, P. E., and Calderwood, S. K. (1996) J. Biol. Chem. 271, 24874-24879), we have examined the mechanisms of transcriptional repression. Our studies show that HSF1 represses the lipopolyliposaccharide-induced transcription of the IL-1beta promoter through direct interaction with the nuclear factor of interleukin 6 (NF-IL6, also known as CCAAT enhancer binding protein (C/EBP(beta), an essential regulator in IL-1beta transcription. We show for the first time that HSF1 binds directly to NF-IL6 in vivo and antagonizes its activity. The HSF1/NF-IL6 interaction involves a sequence of HSF1 containing the trimerization and regulatory domains and the bZip region of NF-IL6. HSF1 has little effect on IL-1beta promoter activity stimulated by the essential monocytic transcription factor Spi.1 but is strongly inhibitory to transcriptional activation by NF-IL6 and to the synergistic activation by NF-IL6 and Spi.1. Because of its ability to bind to specific C/EBP elements in the promoters of multiple genes and its ability to interact with other transcription factors, NF-IL6 is involved in transcriptional regulation of a wide range of genes. Interaction between HSF1 and NF-IL6 could thus be an important mechanism in HSF1 regulation of general gene transcription during endotoxin stress. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med,Mol & Cell Biol Lab, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA50642, CA68544, CA47407, CA31303] NR 71 TC 105 Z9 116 U1 1 U2 6 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 APR 5 PY 2002 VL 277 IS 14 BP 11802 EP 11810 DI 10.1074/jbc.M109296200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 539AC UT WOS:000174846400027 PM 11801594 ER PT J AU Sakamoto, K Hirshman, MF Aschenbach, WG Goodyear, LJ AF Sakamoto, K Hirshman, MF Aschenbach, WG Goodyear, LJ TI Contraction regulation of Akt in rat skeletal muscle SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-B; GLYCOGEN-SYNTHASE KINASE-3; INDUCED GLUCOSE-TRANSPORT; PHOSPHOINOSITIDE 3-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; POTENTIAL ROLE; MAP KINASE; IN-VITRO; INSULIN; ACTIVATION AB The protein serine/threonine kinase Akt/protein kinase B has been recognized as a critical signaling mediator for multiple cell systems. The function of Akt in skeletal muscle is not well understood, and whether contractile activity stimulates Akt activity has been controversial. In the current study, contraction in situ, induced via sciatic nerve stimulation, significantly increased Akt Ser(473) phosphorylation in multiple muscle types including the extensor digitorum longus (13-fold over basal), plantaris (5.8-fold), red gastrocnemius (4.7-fold), white gastrocnemius (3.3-fold), and soleus (1.6-fold). In addition to increasing phosphorylation, contraction in situ significantly increased the activity of all three Akt isoforms (Akt1 > Akt2 > Akt3) with maximal activation occurring at 2.5 min and returning to base line with 15 min of contraction. Akt phosphorylation and activity were also increased when isolated muscles were contracted in vitro in the absence of systemic factors, although to a much lesser extent. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 fully inhibited contraction-stimulated Akt phosphorylation and activity but did not diminish contraction-stimulated glycogen synthase kinase-3 phosphorylation and glycogen synthase activity. These results demonstrate that contraction increases Akt phosphorylation and activity in skeletal muscle and that this stimulation is rapid, transient, muscle fiber type-specific, and wortmannin- and LY294002-inhibitable. Akt signaling is not necessary for the regulation of glycogen synthase activity in contracting skeletal muscle. C1 Joslin Diabet Ctr, Metab Sect, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Yokohama City Univ, Grad Sch Integrated Sci, Kanazawa Ku, Yokohama, Kanagawa 232, Japan. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Metab Sect, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIAMS NIH HHS [AR42238, AR45670]; NIDDK NIH HHS [DK59769] NR 60 TC 127 Z9 135 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 APR 5 PY 2002 VL 277 IS 14 BP 11910 EP 11917 DI 10.1074/jbc.M112410200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 539AC UT WOS:000174846400041 PM 11809761 ER PT J AU Denhez, F Wilcox-Adelman, SA Baciu, PC Saoncella, S Lee, S French, B Neveu, W Goetinck, PF AF Denhez, F Wilcox-Adelman, SA Baciu, PC Saoncella, S Lee, S French, B Neveu, W Goetinck, PF TI Syndesmos, a syndecan-4 cytoplasmic domain interactor, binds to the focal adhesion adaptor proteins paxillin and Hic-5 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCAN; KINASE-C; CYTOSKELETAL ORGANIZATION; TYROSINE PHOSPHORYLATION; PDZ PROTEIN; INTEGRINS; P210(BCR/ABL); TRANSDUCTION; CASK/LIN-2; CELLS AB Syndecan-4 and integrins are the primary transmembrane receptors of focal adhesions in cells adherent to extracellular matrix molecules. Syndesmos is a cytoplasmic protein that interacts specifically with the cytoplasmic domain of syndecan-4, and it co-localizes with syndecan-4 in focal contacts. In the present study we sought possible interactors with syndesmos. We find that syndesmos interacts with the focal adhesion adaptor protein paxillin. The binding of syndesmos to paxillin is direct, and these interactions are triggered by the activation of protein kinase C. Syndesmos also binds the paxillin homolog, Hic-5. The connection of syndecan-4 with paxillin through syndesmos parallels the connection between paxillin and integrins and may thus reflect the cooperative signaling of these two receptors in the assembly of focal adhesions and actin stress fibers. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Goetinck, PF (reprint author), MGH E, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NICHD NIH HHS [F32-HD41235, HD-37490] NR 32 TC 40 Z9 45 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 5 PY 2002 VL 277 IS 14 BP 12270 EP 12274 DI 10.1074/jbc.M110291200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 539AC UT WOS:000174846400087 PM 11805099 ER PT J AU Xiong, JP Stehle, T Zhang, RG Joachimiak, A Frech, M Goodman, SL Arnaout, MA AF Xiong, JP Stehle, T Zhang, RG Joachimiak, A Frech, M Goodman, SL Arnaout, MA TI Crystal structure of the extracellular segment of integrin alpha V beta 3 in complex with an Arg-Gly-Asp ligand SO SCIENCE LA English DT Article ID CD11B A-DOMAIN; BINDING-SITE; I-DOMAIN; SUBUNIT; ECHISTATIN AB The structural basis for the divalent cation-dependent binding of heterodimeric alphabeta integrins to their ligands, which contain the prototypical Arg-Gly-Asp sequence, is unknown. Interaction with ligands triggers tertiary and quaternary structural rearrangements in integrins that are needed for cell signaling. Here we report the crystal structure of the extracellular segment of integrin alphaVbeta3 in complex with a cyclic peptide presenting the Arg-Gly-Asp sequence. The ligand binds at the major interface between the alphaV and beta3 subunits and makes extensive contacts with both. Both tertiary and quaternary changes are observed in the presence of ligand. The tertiary rearrangements take place in betaA, the ligand-binding domain of beta3; in the complex, betaA acquires two cations, one of which contacts the ligand Asp directly and the other stabilizes the ligand-binding surface. Ligand binding induces small changes in the orientation of alphaV relative to beta3. C1 Massachusetts Gen Hosp, Struct Biol Program, Leukocyte Biol & Inflammat Program, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Argonne Natl Lab, Div Biosci, Struct Biol Ctr, Argonne, IL 60439 USA. Merck KGaA, Dept Target Res, D-64271 Darmstadt, Germany. Merck KGaA, Biomed Res, D-64271 Darmstadt, Germany. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Struct Biol Program, Leukocyte Biol & Inflammat Program, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM arnaout@receptor.mgh.harvard.edu NR 19 TC 1035 Z9 1067 U1 15 U2 101 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 APR 5 PY 2002 VL 296 IS 5565 BP 151 EP 155 DI 10.1126/science.1069040 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 539FA UT WOS:000174858800051 PM 11884718 ER PT J AU Surman, OS AF Surman, OS TI Perspective - The ethics of partial-liver donation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Surman, OS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 118 Z9 122 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 APR 4 PY 2002 VL 346 IS 14 BP 1038 EP 1038 DI 10.1056/NEJM200204043461402 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 536YL UT WOS:000174729400001 PM 11932469 ER PT J AU Kim, JH Skates, SJ Uede, T Wong, KK Schorge, JO Feltmate, CM Berkowitz, RS Cramer, DW Mok, SC AF Kim, JH Skates, SJ Uede, T Wong, KK Schorge, JO Feltmate, CM Berkowitz, RS Cramer, DW Mok, SC TI Osteopontin as a potential diagnostic biomarker for ovarian cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SECRETED PHOSPHOPROTEIN-I; MESSENGER-RNA; MOLECULAR-CLONING; EPITHELIAL-CELLS; GENE-EXPRESSION; PSAMMOMA BODIES; PROGRESSION; MACROPHAGES; BREAST; ETA-1 AB Context Development of new biomarkers for ovarian cancer is needed for early detection and disease monitoring. Analyses involving complementary DNA (cDNA) microarray data can be used to identify up-regulated genes in cancer cells, whose products may then be further validated as potential biomarkers. Objective To describe validation studies of an up-regulated gene known as osteopontin, previously identified using a cDNA microarray system. Design, Setting, and Participants Experimental and cross-sectional studies were conducted involving ovarian cancer and healthy human ovarian surface epithelial cell lines and cultures, archival paraffin-embedded ovarian tissue collected between June 1992 and June 2001, and fresh tissue and preoperative plasma from 144 patients evaluated for a pelvic mass between June 1992 and June 2001 in gynecologic oncology services at 2 US academic institutions. Plasma samples from 107 women selected from an epidemiologic study of ovarian cancer initiated between May 1992 and March 1997 were used as healthy controls. Main Outcome Measures Relative messenger RNA expression in cancer cells and fresh ovarian tissue, measured by real-time polymerase chain reaction as 2(-DeltaDeltaCT) (a quantitative value representing the amount of osteopontin expression); osteopontin production, localized and scored in ovarian healthy and tumor tissue with immunohistochemical studies; and amount of osteopontin in patient vs control plasma, measured using an enzyme-linked immunoassay. Results The geometric mean for 2(-DeltaDeltaCT) for osteopontin expression in 5 healthy ovarian epithelial cell cultures was 4.1 compared with 270.4 in 14 ovarian cancer cell lines (P=.03). The geometric mean 2(-DeltaDeltaCT) for osteopontin expression in tissue from 2 healthy ovarian epithelial samples was 9.0 compared with 164.0 in 27 microdissected ovarian tumor tissue samples (P=.06). Immunolocalization of osteopontin showed that tissue samples from 61 patients with invasive ovarian cancer and 29 patients with borderline ovarian tumors expressed higher levels of osteopontin than tissue samples from 6 patients with benign tumors and samples of healthy ovarian epithelium from 3 patients (P=.03). Osteopontin levels in plasma were significantly higher (P<.001) in 51 patients with epithelial ovarian cancer (486.5 ng/mL) compared with those of 107 healthy controls (147.1 ng/mL), 46 patients with benign ovarian disease (254.4 ng/mL), and 47 patients with other gynecologic cancers (260.9 ng/mL). Conclusions Our findings provide evidence for an association between levels of a biomarker, osteopontin, and ovarian cancer and suggest that future research assessing its clinical usefulness would be worthwhile. C1 Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, Lab Gynecol Oncol, Boston, MA 02115 USA. St Vincent Hosp, Dept Obstet & Gynecol, Suwon, Kyong Ki Do, South Korea. Catholic Univ Korea, Suwon, Kyong Ki Do, South Korea. Harvard Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. Hokkaido Univ, Inst Med Genet, Sapporo, Hokkaido, Japan. Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX USA. RP Mok, SC (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, Lab Gynecol Oncol, BL1-447,221 Longwood Ave, Boston, MA 02115 USA. OI Wong, Kwong-Kwok/0000-0002-0375-6669 FU NCI NIH HHS [CA86381] NR 48 TC 307 Z9 326 U1 5 U2 19 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 APR 3 PY 2002 VL 287 IS 13 BP 1671 EP 1679 DI 10.1001/jama.287.13.1671 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 536YW UT WOS:000174730300021 PM 11926891 ER PT J AU Norris, AW Laffel, LMB AF Norris, AW Laffel, LMB TI Avoiding nocturnal hypoglycemia: Consideration of an extra injection at bedtime SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID SUBCUTANEOUS INSULIN INFUSION; DEPENDENT DIABETES-MELLITUS; NPH INSULIN; GLARGINE HOE-901; RISK-FACTORS; CHILDREN; THERAPY; ADOLESCENTS; PREVALENCE; LISPRO C1 Harvard Univ, Pediat & Adolescent Unit, Genet & Epidemiol Sect, Joslin Diabet Ctr,Joslin Clin,Sch Med, Boston, MA 02215 USA. RP Laffel, LMB (reprint author), Harvard Univ, Pediat & Adolescent Unit, Genet & Epidemiol Sect, Joslin Diabet Ctr,Joslin Clin,Sch Med, 1 Joslin Pl, Boston, MA 02215 USA. OI Norris, Andrew/0000-0001-8396-9543 NR 20 TC 0 Z9 0 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 APR 2 PY 2002 VL 136 IS 7 BP 547 EP 549 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 536CA UT WOS:000174682100007 PM 11926791 ER PT J AU Takagi, J DeBottis, DP Erickson, HP Springer, TA AF Takagi, J DeBottis, DP Erickson, HP Springer, TA TI Role of the specificity-determining loop of the integrin beta subunit I-like domain in autonomous expression, association with the alpha subunit, and ligand binding SO BIOCHEMISTRY LA English DT Article ID AMINO-ACID-SEQUENCES; CELL-ADHESION; MONOCLONAL-ANTIBODY; ELECTRON-MICROSCOPY; CRYSTAL-STRUCTURE; CR3-DEPENDENT ADHESION; GENOMIC ORGANIZATION; GLYCOPROTEIN-IIIA; A-DOMAIN; T-CELL AB Integrin beta subunits contain a highly conserved I-like domain that is known to be important for ligand binding. Unlike integrin I domains, the I-like domain requires integrin alpha and beta subunit association for optimal folding. Pactolus is a novel gene product that is highly homologous to integrin beta subunits but lacks associating alpha subunits [Chen, Y., Garrison, S., Weis, J. J., and Weis, J. H. (1998) J. Biol. Chem. 273, 8711-8718] and a similar to30 amino acid segment corresponding to the specificity-determining loop (SDL) in the I-like domain. We find that the SDL is responsible for the defects in integrin beta subunit expression and folding in the absence of alpha subunits. When transfected in the absence of alpha subunits into cells, extracellular domains of mutant beta subunits lacking SDL, but not wild-type beta subunits, were well secreted and contained immunoreactive I-like domains. The purified recombinant soluble beta1 subunit with the SDL deletion showed an elongated shape in electron microscopy, consistent with its structure in alphabeta complexes. The SDL segment is not required for formation of alpha5beta1, alpha4beta1, alphaVbeta3, and alpha6beta4 heterodimers, but is essential for fomation of alpha6beta1, alphaVbeta1, and alphaLbeta2 heterodimers, suggesting that usage of subunit interface residues is variable among integrins. The beta1 SDL is required for ligand binding and for the formation of the epitope for the alpha5 monoclonal antibody 16 that maps to loop segments connecting blades 2 and 3 of beta-propeller domain of alpha5, but is not essential for nearby beta-propeller epitopes. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. RP Takagi, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL48675] NR 54 TC 39 Z9 41 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 2 PY 2002 VL 41 IS 13 BP 4339 EP 4347 DI 10.1021/bi016047u PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 538AR UT WOS:000174792300019 PM 11914080 ER PT J AU Eagle, KA Isselbacher, EM DeSanctis, RW AF Eagle, KA Isselbacher, EM DeSanctis, RW CA Int Registry Aortic Dissection IRA TI Cocaine-related aortic dissection in perspective SO CIRCULATION LA English DT Editorial Material DE editorials; cocaine; aorta; dissection ID INCREASE C1 Univ Michigan, Med Ctr, Div Cardiol, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Eagle, KA (reprint author), Univ Michigan, Med Ctr, Div Cardiol, TC 3910,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. NR 11 TC 50 Z9 51 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 APR 2 PY 2002 VL 105 IS 13 BP 1529 EP 1530 DI 10.1161/01.CIR.0000014688.12415.C0 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 538VM UT WOS:000174835800007 PM 11927514 ER PT J AU Gokce, N Keaney, JF Hunter, LM Watkins, MT Menzoian, JO Vita, JA AF Gokce, N Keaney, JF Hunter, LM Watkins, MT Menzoian, JO Vita, JA TI Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function - A prospective study SO CIRCULATION LA English DT Article DE endothelium; surgery; risk factors ID CORONARY-ARTERY DISEASE; FLOW-MEDIATED VASODILATION; MYOCARDIAL-INFARCTION; VASCULAR-SURGERY; BRACHIAL-ARTERY; HEART-DISEASE; CARDIAC RISK; DYSFUNCTION; MECHANISMS; ATHEROSCLEROSIS AB Background-Brachial artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors and improves with risk reduction therapy. However, the predictive value of brachial artery endothelial dysfunction for future cardiovascular events is unknown. Methods and Results-We preoperatively examined brachial artery vasodilation using ultrasound in 187 patients undergoing vascular surgery. Patients were prospectively followed for 30 days after surgery. Forty-five patients had a postoperative event, including cardiac death (3), myocardial infarction (12), unstable angina/ischemic ventricular fibrillation (2), stroke (3), or elevated troponin I, reflecting myocardial necrosis (25). Preoperative endothelium-dependent flow-mediated dilation was significantly lower in patients with an event (4.9+/-3.1%) than in those without an event (7.3+/-5%; P<0.001), whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups. In a Cox proportional-hazards model, the independent predictors of events were age (P=0.001), renal insufficiency (P=0.03), noncarotid surgery (P=0.05), and lower brachial artery flow-mediated dilation (P=0.007). If troponin I elevation was not considered an event, low flow-mediated dilation remained an independent predictor of risk (odds ratio 9.0, 95% CI 1.2 to 68; P=0.03). When a flow-mediated dilation cutpoint of 8.1% was used, endothelial function had a sensitivity of 95%, specificity of 37%, and negative predictive value of 98% for events. Conclusions-Impaired brachial artery endothelial function independently predicts postoperative cardiac events, which supports a role for endothelial dysfunction in the pathogenesis of cardiovascular disease. The strong negative predictive value of preserved endothelial function raises the possibility that assessment of brachial artery flow-mediated dilation will be useful in the management of patients undergoing vascular surgery. C1 Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. VA Boston Healthcare Syst, Surg Serv, Boston, MA USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. RP Vita, JA (reprint author), Boston Med Ctr, Cardiol Sect, 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 HL04425] NR 31 TC 501 Z9 523 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 2 PY 2002 VL 105 IS 13 BP 1567 EP 1572 DI 10.1161/01.CIR.0000012543.55874.47 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 538VM UT WOS:000174835800017 PM 11927524 ER PT J AU Wigle, JT Harvey, N Detmar, M Lagutina, I Grosveld, G Gunn, MD Jackson, DG Oliver, G AF Wigle, JT Harvey, N Detmar, M Lagutina, I Grosveld, G Gunn, MD Jackson, DG Oliver, G TI An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype SO EMBO JOURNAL LA English DT Article DE lymphangiogenesis; lymphatic endothelial cells; LYVE-1; Prox1; SLC; VEGFR-3 ID LYMPHOID-ORGAN CHEMOKINE; VEGF-C; TUMOR LYMPHANGIOGENESIS; BREAST-CANCER; PROMOTES; RECEPTOR; SYSTEM; EXPRESSION; GROWTH; LYVE-1 AB The process of angiogenesis has been well documented, but little is known about the biology of lymphatic endothelial cells and the molecular mechanisms controlling lymphangiogenesis. The homeobox gene Prox1 is expressed in a subpopulation of endothelial cells that, after budding from veins, gives rise to the mammalian lymphatic system. In Prox1(-/-) embryos, this budding becomes arrested at around embryonic day (E)11.5, resulting in embryos without lymphatic vasculature. Unlike the endothelial cells that bud off in E11.5 wild-type embryos, those of Prox1-null embryos did not co-express any lymphatic markers such as VEGFR-3, LYVE-1 or SLC. Instead, the mutant cells appeared to have a blood vascular phenotype, as determined by their expression of laminin and CD34. These results suggest that Prox1 activity is required for both maintenance of the budding of the venous endothelial cells and differentiation toward the lymphatic phenotype. On the basis of our findings, we propose that a blood vascular phenotype is the default fate of budding embryonic venous endothelial cells; upon expression of Prox1, these budding cells adopt a lymphatic vasculature phenotype. C1 St Jude Childrens Res Hosp, Dept Genet, Memphis, TN 38105 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England. RP Oliver, G (reprint author), St Jude Childrens Res Hosp, Dept Genet, 332 N Lauderdale St, Memphis, TN 38105 USA. EM guillermo.oliver@stjude.org RI wigle, jeffrey/G-2005-2014; OI wigle, jeffrey/0000-0002-4985-7684; Gunn, Michael/0000-0003-4602-0667 FU NCI NIH HHS [CA 21765, P30 CA021765]; NEI NIH HHS [EY 12162, R01 EY012162]; NIGMS NIH HHS [GM 58462, R01 GM058462] NR 26 TC 488 Z9 519 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD APR 2 PY 2002 VL 21 IS 7 BP 1505 EP 1513 DI 10.1093/emboj/21.7.1505 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 541PB UT WOS:000174992000001 PM 11927535 ER PT J AU Fukai, N Eklund, L Marneros, AG Oh, SP Keene, DR Tamarkin, L Niemela, M Ilves, M Li, E Pihlajaniemi, T Olsen, BR AF Fukai, N Eklund, L Marneros, AG Oh, SP Keene, DR Tamarkin, L Niemela, M Ilves, M Li, E Pihlajaniemi, T Olsen, BR TI Lack of collagen XVIII/endostatin results in eye abnormalities SO EMBO JOURNAL LA English DT Article DE collagen XVIII; endostatin; eye abnormalities; immunogold labeling; knockout mice ID ENDOTHELIAL GROWTH-FACTOR; BASEMENT-MEMBRANE ZONES; TUMOR-GROWTH; ENDOGENOUS INHIBITOR; SURVIVAL FACTOR; CELL-DEATH; ENDOSTATIN; XVIII; MOUSE; ANGIOGENESIS AB Mice lacking collagen XVIII and its proteolytically derived product endostatin show delayed regression of blood vessels in the vitreous along the surface of the retina after birth and lack of or abnormal outgrowth of retinal vessels. This suggests that collagen XVIII/endostatin is critical for normal blood vessel formation in the eye. All basement membranes in wild-type eyes, except Descemet's membrane, showed immunogold labeling with antibodies against collagen XVIII. Labeling at sites where collagen fibrils in the vitreous are connected with the inner limiting membrane and separation of the vitreal matrix from the inner limiting membrane in mutant mice indicate that collagen XVIII is important for anchoring vitreal collagen fibrils to the inner limiting membrane. The findings provide an explanation for high myopia, vitreoretinal degeneration and retinal detachment seen in patients with Knobloch syndrome caused by loss-of-function mutations in collagen XVIII. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Univ Oulu, Bioctr, Collagen Res Unit, FIN-90014 Oulu, Finland. Univ Oulu, Dept Biochem Med, FIN-90014 Oulu, Finland. Univ Florida, Dept Physiol, Gainesville, FL 32610 USA. Shriners Hosp Children, Portland Imaging Ctr, Portland, OR 97201 USA. Cytimmune Sci Inc, College Pk, MD 20740 USA. Univ Oulu, Dept Physiol, FIN-90014 Oulu, Finland. Massachusetts Gen Hosp, Cardiovasc Res Div, Boston, MA 02114 USA. RP Olsen, BR (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. FU NIAMS NIH HHS [R01 AR036820, AR 38819, AR 36820] NR 36 TC 224 Z9 233 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD APR 2 PY 2002 VL 21 IS 7 BP 1535 EP 1544 DI 10.1093/emboj/21.7.1535 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 541PB UT WOS:000174992000004 PM 11927538 ER PT J AU Fujikawa, K Inoue, Y Sakai, M Koyama, Y Nishi, S Funada, R Alt, FW Swat, W AF Fujikawa, K Inoue, Y Sakai, M Koyama, Y Nishi, S Funada, R Alt, FW Swat, W TI Vav3 is regulated during the cell cycle and effects cell division SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID T-CELL; FAMILY; RHO; PROTOONCOGENE; RECEPTORS; GTPASE; MEMBER AB Vav3 is a member of the family of guanine nucleotide exchange factors implicated in the regulation of Rho GTPases. Although the exact in vivo function of Vav3 is unknown, evidence from several studies indicates a role distinct from Vav2 or Vav1. Here we report that the expression of Vav3 is regulated during the cell cycle. Strikingly, Vav3 was transiently up-regulated in HeLa cells during mitosis, whereas enforced expression of Vav3 perturbed cytokinesis and led to the appearance of multinucleated cells. These effects of Vav3 were RhoA-dependent, required phosphorylation of the regulatory tyrosine 173, but were not enhanced by N-terminal truncations. Thus, this report establishes that expression of Vav3 is strictly regulated in a cell cycle-dependent manner and implicates Vav3 in the control of cytokinesis. C1 Harvard Univ, Sch Med, Dept Pediat, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp, Boston, MA 02115 USA. Hokkaido Univ, Grad Sch Med, Dept Neural Funct, Sapporo, Hokkaido 0608638, Japan. Hokkaido Univ, Grad Sch Med, Dept Biochem, Sapporo, Hokkaido 0608638, Japan. Hokkaido Univ, Grad Sch Agr, Lab Wood Biol, Sapporo, Hokkaido 0608589, Japan. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Dept Pediat, Ctr Blood Res, Boston, MA 02115 USA. EM alt@rascal.med.harvard.edu RI Sakai, Masaharu/A-4773-2012; Funada, Ryo/C-2020-2013 FU NHLBI NIH HHS [P01 HL059561, HL59561] NR 18 TC 30 Z9 31 U1 0 U2 1 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 APR 2 PY 2002 VL 99 IS 7 BP 4313 EP 4318 DI 10.1073/pnas.052715699 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 539DY UT WOS:000174856000035 PM 11917103 ER PT J AU Weissman, DE Block, SD AF Weissman, DE Block, SD TI ACGME requirements for end-of-life training in selected residency and fellowship programs: A status report SO ACADEMIC MEDICINE LA English DT Article ID INCORPORATING PALLIATIVE CARE; MEDICAL-EDUCATION; OPPORTUNITIES; PRINCIPLES; CHALLENGES; SCHOOLS AB Introduction. National recommendations have been developed for physicians' end-of-life (EOL) education, No comprehensive assessment has been done to examine postgraduate (residency and fellowship) EOL training. Method. The authors reviewed the EOL content for 46 specialties in postgraduate training programs that affect the care of seriously ill and dying patients, using data from the 200012001 AMA Graduate Medical Education Directory. Results. Internal medicine, geriatrics, and neurology contained the most comprehensive EOL requirements. Most surgical specialties contained no EOL requirement except ethics. Ethics (n = 25) and psychosocial care (n = 221) were the most common EOL domains mandated, although specific EOL content was not specified. Training in EOL communication (n = 1), personal awareness (n = 3), and EOL clinical experiences (n = 5) were the least often required instructional domains. Instruction in pain assessment and management was required in only one surgical speciality. Conclusions. The lack of comprehensive EOL training requirements may help explain the known problems in physicians' EOL care. Major reform in EOL requirements is needed at the level of residency review committees. C1 Med Coll Wisconsin, Milwaukee, WI 53226 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Weissman, DE (reprint author), Med Coll Wisconsin, Froedtert Hosp, Palliat Care Program, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. NR 23 TC 42 Z9 43 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD APR PY 2002 VL 77 IS 4 BP 299 EP 304 DI 10.1097/00001888-200204000-00008 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 543HH UT WOS:000175095100006 PM 11953294 ER PT J AU Thieke, C Bortfeld, T Kufer, KH AF Thieke, C Bortfeld, T Kufer, KH TI Characterization of dose distributions through the max and mean dose concept SO ACTA ONCOLOGICA LA English DT Article ID NORMAL TISSUE; OPTIMIZATION; TOLERANCE AB A new approach for the determination of the equivalent uniform dose (EUD) for inhomogeneously irradiated normal organs is developed and tested. The EUD is calculated as a linear combination of the maximum and the mean dose: EUD=alphaD(max) +(1-alpha)(D) over bar. We call this the max & mean model. The values of a are determined by a fit to the Emami tables for complication levels of 5% and 50%. The predictions of the max & mean model are compared with the Emami tables for different treatment volume fractions. The quality of the fit is also compared with the well-known power-law EUD model. The max & mean model makes it possible to make useful predictions of the EUD for organs having an organization anywhere between serial and parallel. The model can be fitted to the Emami tables within the same error range as the widely used power-law model (about 10%) and can be integrated into linear multicriteria optimization algorithms for planning of intensity-modulated radiotherapy. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. Deutsch Krebsforschungszentrum, Dept Med Phys, D-6900 Heidelberg, Germany. Fraunhofer Inst Ind Math, Kaiserslautern, Germany. RP Bortfeld, T (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. NR 11 TC 26 Z9 26 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PD APR 1 PY 2002 VL 41 IS 2 BP 158 EP 161 PG 4 WC Oncology SC Oncology GA 558DM UT WOS:000175951000008 PM 12102160 ER PT J AU Yeung, A Neault, N Sonawalla, S Howarth, S Fava, M Nierenberg, AA AF Yeung, A Neault, N Sonawalla, S Howarth, S Fava, M Nierenberg, AA TI Screening for major depression in Asian-Americans: a comparison of the Beck and the Chinese Depression Inventory SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE depression; mass screening; primary health care; Asian-Americans ID LOS-ANGELES; NEURASTHENIA; VALIDATION; CARE AB Objective: This study compares the effectiveness of the Chinese version of the Beck Depression Inventory (CBDI) and the Chinese Depression Inventory (CDI) in screening for depression among Chinese Americans. Method: Five hundred and three Chinese-Americans in primary care were administered the CBDI and the CDI for depression screening. The results were compared with standard semistructured interview. Results: With empirically determined cutoff scores of the CBDI (greater than or equal to13) and the CDI (greater than or equal to16), both instruments have good sensitivity (0.78) and excellent specificity (0.91 and 0.93, respectively). The correlation between the total scores of the two instruments was high (0.785, P < 0.01). The areas under the Receiver Operating Characteristic (ROC) curve of the CBDI and the CDI were 0.94 and 0.95, respectively, and were not significantly different. Conclusion: When administered by interviewers, the CBDI and the CDI have comparable effectiveness. Low participation among Chinese-Americans with self-report measures limits both scales as efficient depression screening instruments. C1 S Cove Community Hlth Ctr, Boston, MA USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Yeung, A (reprint author), 50 Staniford St,Suite 401, Boston, MA 02114 USA. FU NIMH NIH HHS [5T32MH19126-10] NR 24 TC 9 Z9 9 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD APR PY 2002 VL 105 IS 4 BP 252 EP 257 DI 10.1034/j.1600-0447.2002.1092.x PG 6 WC Psychiatry SC Psychiatry GA 539PW UT WOS:000174880500003 PM 11942928 ER PT J AU Cannon, CP McCabe, CH Belder, R Breen, J Braunwald, E AF Cannon, CP McCabe, CH Belder, R Breen, J Braunwald, E TI Design of the Pravastatin or Atorvastation Evaluation and Infection Therapy (PROVE IT)-TIMI 22 trial SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CLINICAL-TRIALS; AZITHROMYCIN AB The Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) trial has 2 main objectives: (1) to compare pravastatin with atorvastatin with the goal of determining whether lowering low-density lipoprotein (LDL) cholesterol with pravastatin to a level of approximately 100 mg/dl provides a clinical benefit similar to LDL cholesterol lowering with atorvastatin to a much lower level of approximately 70 mg/dl; and (2) to examine the role of Chlymadia pneumoniae (C. pneumoniae) infection in cardiovascular disease by evaluating the effectiveness of the antibiotic gatifloxacin in reducing cardiovascular events. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Bristol Myers Squibb Co, Princeton, NJ USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. NR 14 TC 86 Z9 90 U1 1 U2 4 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 APR 1 PY 2002 VL 89 IS 7 BP 860 EP + AR PII S0002-9149(02)02201-4 DI 10.1016/S0002-9149(02)02201-4 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 533YV UT WOS:000174558600017 PM 11909576 ER PT J AU Su, CK Bhattacharya, J Wang, CC AF Su, CK Bhattacharya, J Wang, CC TI Role of neck surgery in conjunction with radiation in regional control of node-positive cancer of the oropharynx SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE oropharyngeal neoplasms; lymph nodes; lymph node excision; radiotherapy; prognostic factors ID SQUAMOUS-CELL CARCINOMA; DEFINITIVE RADIOTHERAPY; DISSECTION; THERAPY; HEAD; BIOPSY; TONGUE; BASE AB For patients with clinically node-positive oropharynx cancer treated with radiotherapy, planned neck dissection is controversial. We investigated whether neck surgery after radiation reduces nodal recurrence. Between 1970 and 1995, 263 patients at Massachusetts General Hospital received radiotherapy for clinically node-positive base of tongue or tonsil carcinomas. Patients received three different types of treatment: neck surgery followed by radiation (SR)-50 patients; radiation alone (RT)-160 patients; and radiation followed by surgery (RS)-53 patients. Median patient follow-up was 28 months. SR patients have an 84% complete response (CR) rate, RT patients 76%, and RS patients 13%. In multivariate analysis, among patients with a CR, the three treatment groups have the same regional control rates. Among patients with an incomplete response, the RS treatment group is 67% (p < 0.01) and 86% (p < 0.01) less likely to have recurrence than the RT and SR groups, respectively. Neck dissection after radiation therapy improves regional control for patients without a complete clinical response to radiation therapy but not for those with a CR. Despite higher CR rates, neck dissection before radiation confers no regional control benefit. We therefore recommend that primary radiotherapy with neck dissection be reserved for those without a complete clinical response. C1 E Bay Reg Canc Ctr, Hayward, CA 94541 USA. RAND Corp, Santa Monica, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Su, CK (reprint author), E Bay Reg Canc Ctr, 1034A St, Hayward, CA 94541 USA. NR 26 TC 8 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD APR PY 2002 VL 25 IS 2 BP 109 EP 116 DI 10.1097/00000421-200204000-00002 PG 8 WC Oncology SC Oncology GA 540AR UT WOS:000174906300002 PM 11943885 ER PT J AU Colevas, AD Norris, CM Tishler, RB Lamb, CC Fried, MP Goguen, LA Gopal, HV Costello, R Read, R Adak, S Posner, MR AF Colevas, AD Norris, CM Tishler, RB Lamb, CC Fried, MP Goguen, LA Gopal, HV Costello, R Read, R Adak, S Posner, MR TI Phase I/II trial of outpatient docetaxel, cisplatin, 5-fluorouracil, leucovorin (opTPFL) as induction for squamous cell carcinoma of the head and neck (SCCHN) SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE cisplatin; docetaxel; 5-FU; head and neck; induction chemotherapy; squamous cell carcinoma ID HIGH-DOSE LEUCOVORIN; LOCALLY ADVANCED HEAD; STAGE-IV HEAD; RANDOMIZED TRIAL; CONCOMITANT CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; III TRIAL; CANCER; FLUOROURACIL; RADIOTHERAPY AB The purpose of this study was to establish the maximum tolerated dose (MTD) of docetaxel in an outpatient docetaxel (T), cisplatin (P), 5-fluorouracil (5-FU) (F), and leucovorin (L) (opTPFL) regimen and to obtain preliminary assessment of opTPFL efficacy. Thirty-four patients with stage III or IV squamous cell carcinoma of the head and neck were treated with opTPFL. Docetaxel was escalated from 60 to 95 mg/m(2) in combination with 100 mg/m(2) cisplatin intravenous bolus, and 2,800 mg/m(2) 5-FU continuous infusion and 2,000 mg/m(2) leucovorin continuous infusion with prophylactic growth factors and antibiotics. Patients who achieved a complete (CR) or partial (PR) response to three cycles received definitive twice-daily radiation therapy. A total of 97 cycles were administered to 34 patients. The major acute toxicities were neutropenia and mucositis. The MTD of docetaxel was 90 mg/m(2), Seventy-seven of 97 cycles of were administered on an outpatient basis. The overall clinical response rate to opTPFL was 94%, with 44% CRs and 50% PRs. The MTD of opTPFL is 90 mg/m(2) docetaxel. Outpatient administration of opTPFL is tolerable, feasible, and does not alter the ability to administer definitive radiation therapy on schedule. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Head & Neck Oncol Program,Dana Farber Canc Inst, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02138 USA. Albert Einstein Coll Med, Montefiore Med Ctr, Dept Otolaryngol, New York, NY USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Colevas, AD (reprint author), NCI, Invest Drug Branch, Canc Therapy Evaluat Program, DCTD, Execut Pl N,Room 7000,6130 Execut Blvd, Rockville, MD 20852 USA. NR 31 TC 31 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD APR PY 2002 VL 25 IS 2 BP 153 EP 159 DI 10.1097/00000421-200204000-00010 PG 7 WC Oncology SC Oncology GA 540AR UT WOS:000174906300010 PM 11943893 ER PT J AU Bergwitz, C Brabant, G Trautwein, C Manns, MP AF Bergwitz, C Brabant, G Trautwein, C Manns, MP TI A patient with autoimmune hepatitis type 1, Addison's disease, atrophic thyroiditis, atrophic gastritis, exocrine pancreatic insufficiency, and heterozygous alpha(1)-antitrypsin deficiency SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID LIVER-DISEASE AB This report describes a 60-yr-old white male presenting with decompensated liver cirrhosis. He had a history of Addison's disease for 36 yr, primary hypothyroidism for 5 yr, and moderate alcohol consumption. His laboratory studies and a liver biopsy supported the diagnosis of autoimmune hepatitis. Furthermore, he was found to be heterozygous for the piZ allele of the alpha(1)-antitrypsin gene with normal serurn at-antitrypsin levels and absence of pulmonary affection. Mucosal biopsies revealed moderately severe atrophic gastritis however, signs of pernicious anemia were missing. An association of autoimmune hepatitis with endocrine disorders and atrophic gastritis has been described. Long term hydrocortisone therapy for his adrenal insufficiency may have prevented a faster course of the liver disease, whereas the heterozygous alpha(1)-antitrypsin deficiency and moderate alcohol consumption constituted additional risk factors ultimately leading to the development of cirrhosis. C1 Hannover Med Sch, Abt Klin Endokrinol, Hannover, Germany. Hannover Med Sch, Gastroenterol Abt, Hannover, Germany. RP Bergwitz, C (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. NR 17 TC 4 Z9 4 U1 0 U2 0 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 APR PY 2002 VL 97 IS 4 BP 1050 EP 1052 AR PII S0002-9270(02)03984-9 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 542TG UT WOS:000175060000043 PM 12003388 ER PT J AU Zhang, HP Leckman, JF Pauls, DL Tsai, CP Kidd, KK Campos, MR AF Zhang, HP Leckman, JF Pauls, DL Tsai, CP Kidd, KK Campos, MR CA Tourette Syndrome Assoc Int Consor TI Genomewide scan of hoarding in sib pairs in which both sibs have Gilles de la Tourette syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; COMPLEX SEGREGATION ANALYSIS; QUANTITATIVE-TRAIT LOCI; SYMPTOM; FAMILY; EPIDEMIOLOGY; PERSONALITY; LINKAGE; HUMANS AB A genome scan of the hoarding phenotype (a component of obsessive-compulsive disorder) was conducted on 77 sib pairs collected by the Tourette Syndrome Association International Consortium for Genetics (TSAICG). All sib pairs were concordant for a diagnosis of Gilles de la Tourette syndrome (GTS). However, the analyses reported here were conducted for hoarding as both a dichotomous trait and a quantitative trait. Not all sib pairs in the sample were concordant for hoarding. Standard linkage analyses were performed using GENEHUNTER and Haseman-Elston methods. In addition, novel analyses with a recursive-partitioning technique were employed. Significant allele sharing was observed for both the dichotomous and the quantitative hoarding phenotypes for markers at 4q34-35 (P = .0007), by use of GENEHUNTER, and at 5q35.2-35.3 (P = .000002) and 17q25 (P = .00002), by use of the revisited Haseman-Elston method. The 4q site is in proximity to D4S1625, which was identified by the TSAICG as a region linked to the GTS phenotype. The recursive-partitioning technique examined multiple markers simultaneously. Results suggest joint effects of specific loci on 5q and 4q, with an overall P value of .000003. Although P values were not adjusted for multiple comparison, nearly all were much smaller than the customary significance level of .0001 for genomewide scans. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Zhang, HP (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St, New Haven, CT 06520 USA. FU NCRR NIH HHS [M01 RR000044, M01 RR000125]; NIDA NIH HHS [R01 DA012468]; NIMH NIH HHS [Z01 MH000508]; NINDS NIH HHS [T32 NS007338, U01 NS040024, R01 NS040024, R01 NS016648] NR 44 TC 121 Z9 127 U1 1 U2 1 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 APR PY 2002 VL 70 IS 4 BP 896 EP 904 DI 10.1086/339520 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 528PL UT WOS:000174252100007 PM 11840360 ER PT J AU Piao, XH Basel-Vanagaite, L Straussberg, R Grant, PE Pugh, EW Doheny, K Doan, B Hong, SE Shugart, YY Walsh, CA AF Piao, XH Basel-Vanagaite, L Straussberg, R Grant, PE Pugh, EW Doheny, K Doan, B Hong, SE Shugart, YY Walsh, CA TI An autosomal recessive form of bilateral frontoparietal polymicrogyria maps to chromosome 16q12.2-21 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PERISYLVIAN POLYMICROGYRIA; LINKAGE ANALYSIS; EPILEPSY AB Polymicrogyria is a cerebral cortical malformation that is grossly characterized by excessive cortical folding and microscopically characterized by abnormal cortical layering. Although polymicrogyria appears to have one or more genetic causes, no polymicrogyria loci have been identified. Here we describe the clinical and radiographic features of a new genetic form of polymicrogyria and localize the responsible gene. We studied two consanguineous Palestinian pedigrees with an autosomal recessive form of bilateral frontoparietal polymicrogyria (BFPP), using linkage analysis. Five affected children had moderate-to-severe mental retardation, developmental delay, and esotropia, and four of the five affected children developed seizures. Brain magnetic-resonance imaging revealed polymicrogyria that was most prominent in the frontal and parietal lobes but involved other cortical areas as well. A genomewide linkage screen revealed a single locus that was identical by descent in affected children in both families and showed a single disease-associated haplotype, suggesting a common founder mutation. The locus for BFPP maps to chromosome 16q12.2-21, with a minimal interval of 17 cM. For D16S514, the maximal pooled two-point LOD score was 3.98, and the maximal multipoint LOD score was 4.57. This study provides the first genetic evidence that BFPP is an autosomal recessive disorder and serves as a starting point for the identification of the responsible gene. C1 Harvard Univ, Inst Med 816, Beth Israel Deaconess Med Ctr, Dept Neurol,Div Neurogenet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Dept Med, Div Newborn Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Serv Neuroradiol, Boston, MA 02114 USA. Rabin Med Ctr, Dept Med Genet, Petah Tiqwa, Israel. Schneider Childrens Med Ctr, Dept Child Neurol, Neurogenet Clin, Petah Tiqwa, Israel. 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, Inst Med 816, Beth Israel Deaconess Med Ctr, Dept Neurol,Div Neurogenet, 4 Blackfan Circle, Boston, MA 02115 USA. FU NHGRI NIH HHS [N01 HG 65403, N01HG65403]; NICHD NIH HHS [HD 07466, T32 HD007466]; NINDS NIH HHS [R01 NS 35129, R01 NS035129] NR 16 TC 77 Z9 78 U1 0 U2 3 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 APR PY 2002 VL 70 IS 4 BP 1028 EP 1033 DI 10.1086/339552 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 528PL UT WOS:000174252100021 PM 11845408 ER PT J AU Corry, DB Joolhar, FS Hori, MT Tuck, ML AF Corry, DB Joolhar, FS Hori, MT Tuck, ML TI Decreased erythrocyte insulin binding in hypertensive subjects with hyperinsulinemia SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE insulin receptor; insulin resistance; glucose; insulin; erythrocytes; essential hypertension; protein tyrosine kinase ID TYROSINE KINASE-ACTIVITY; RESISTANCE; RECEPTOR; DISEASE; ACTIVATION; GLUCOSE; OBESITY; SODIUM; SYSTEM AB Background: This study investigates erythrocyte insulin receptor binding and affinity in subjects with hypertension and hyperinsulinemia. Insulin receptor-binding function has not been extensively Studied in hypertensive subjects, Methods: Insulin receptor density, binding affinity, and protein tyrosine kinase activity were measured in erythrocytes from 18 hypertensive and 16 normotensive subjects. Insulin sensitivity was measured by the fasting plasma insulin/glucose ratio and the homeostatic assessment model algorithm (HOMA) index. Erythrocyte insulin binding was determined by a competitive binding assay and protein tyrosine kinase activity was measured by an enzyme-linked immunoabsorbent assay technique. Results., Fasting plasma insulin/glucose ratio and the insulin resistance index (HOMA) were significantly higher C in the hypertensive versus normotensive subjects. Receptor saturation of the high affinity binding sites (Bmax) was reduced in the hypertensive versus control Subjects. The Kd values were lower in the erythrocytes from hypertensive than control subjects. Insulin-induced protein tyrosine kinase activity was decreased in erythrocytes from hypertensive versus control subjects. Conclusions: A reduced erythrocyte insulin receptor density and tyrosine protein kinase activity may reflect insulin receptor dysfunction in hypertensive individuals who have insulin resistance and hyperinsulinemia. More information is needed examining insulin receptor function in other target tissues such as fat or skeletal muscle cells before defects in the insulin receptor can be firmly proposed as a cause of the metabolic syndrome. (C) 2002 American Journal of Hypertension, Ltd. C1 Olive View UCLA Med Ctr, Div Nephrol, Sylmar, CA 91342 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Div Endocrinol, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Corry, DB (reprint author), Olive View UCLA Med Ctr, Div Nephrol & Hypertens, 14445 Olive View Dr, Sylmar, CA 91342 USA. NR 32 TC 5 Z9 5 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 APR PY 2002 VL 15 IS 4 BP 296 EP 301 AR PII S0895-7061(01)02336-6 DI 10.1016/S0895-7061(01)02336-6 PN 1 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 543KP UT WOS:000175101400002 PM 11991213 ER PT J AU Egan, BM Lackland, DT Basile, JN AF Egan, BM Lackland, DT Basile, JN TI American society of hypertension regional chapters: Leveraging the impact of the clinical hypertension specialist in the local community SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE hypertension; high blood pressure; evidence-based guidelines; hypertension specialists ID ISOLATED SYSTOLIC HYPERTENSION; SOUTHEASTERN UNITED-STATES; PRIMARY-CARE PHYSICIANS; BLOOD-PRESSURE; POPULATION; GUIDELINES; AWARENESS; MORTALITY; MORBIDITY; MEDICINE AB Hypertension control has remained at 24% to 27% for the past decade, despite revision of national treatment guidelines, expansion of therapeutic options, and evidence from clinical trials that higher control rates are attainable. Uncontrolled hypertension contributes to the enormous health and economic burden from cardiovascular and renal disease. The risk for hypertension-related complications is increasing in the United States as comorbidities such as diabetes mellitus and congestive heart failure rise in a population that is becoming progressively older. more obese, and more ethnically diverse. Given regional variations in demographic characteristics and disease burdens, implementing evidence-based guidelines will be more effective if tailored appropriately to the local community. The Clinical Hypertension Specialist program is a positive response to an impending health care crisis. The impact of the Hypertension Specialist on blood pressure control can be leveraged by extending the academic mission of education, patient care, and health services research to the local community. The American Society of Hypertension regional chapter can serve as a forum for Clinical Hypertension Specialist,, from academic medicine and the community to define mutual goals, develop an action plan which is responsive to community needs, and monitor progress. With Support from the chapter, Clinical Hypertension Specialists in the community can have an impact on the practice of medicine locally by contributing to the education of primary care providers, receiving referrals of patients with complicated hypertension. monitoring progress in meeting evidence-based goals, providing feedback to peers, and participating, in multicenter trials. (C) 2002 American Journal of Hypertension, Ltd. C1 Med Univ S Carolina, Dept Med, Div Clin Pharmacol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Hosp, Charleston, SC USA. RP Egan, BM (reprint author), Med Univ S Carolina, Dept Med, Div Clin Pharmacol, 96 Jonathan Lucas St,CSB 826H, Charleston, SC 29425 USA. FU AHRQ HHS [P01HS1087]; NHLBI NIH HHS [HL04290] NR 36 TC 13 Z9 13 U1 1 U2 8 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 APR PY 2002 VL 15 IS 4 BP 372 EP 379 AR PII S0895-7061(01)02323-8 DI 10.1016/S0895-7061(01)02323-8 PN 1 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 543KP UT WOS:000175101400015 PM 11991226 ER PT J AU Bouley, R Lin, HY Ausiello, DA AF Bouley, R Lin, HY Ausiello, DA TI Characterization of V2 vasopressin receptor distribution and internalization in polarized LLC-PK1 cells. SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2002 VL 39 IS 4 MA 11 BP A13 EP A13 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 538VD UT WOS:000174835000044 ER PT J AU Enoch, C Fried, L Palevsky, P AF Enoch, C Fried, L Palevsky, P TI Risk factors for dialysis PTFE graft loss. SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2002 VL 39 IS 4 MA 20 BP A15 EP A15 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 538VD UT WOS:000174835000053 ER PT J AU Sun, TX Van Hoek, A Huang, Y Blackburn, K McLaughlin, M Brown, D AF Sun, TX Van Hoek, A Huang, Y Blackburn, K McLaughlin, M Brown, D TI Constitutive aquaporin 2 recycling occurs via a dynamin-dependent and clathrin-mediated endocytotic pathway: S256 phosphorylation is not a requirement for the constitutive recycling. SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Program Membrane Biol, 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2002 VL 39 IS 4 MA 83 BP A31 EP A31 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 538VD UT WOS:000174835000116 ER PT J AU Chen, CC Hsu, LG Hecht, JL Janecka, I AF Chen, CC Hsu, LG Hecht, JL Janecka, I TI Bimaxillary chondrosarcoma: Clinical, radiologic, and histologic correlation SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID HEAD; NECK; P53 AB In this report, we describe an unusual case of chondrosarcoma that involved the entire bimaxillary and nasal skeleton. The pathogenesis, correlation of histopathology with radiology, and management of chondrosarcoma are reviewed. C1 Amer Canc Soc, Tampa, FL 33629 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neuroradiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Janecka, I (reprint author), Amer Canc Soc, 3709 W Jetton Ave, Tampa, FL 33629 USA. RI Chen, Clark/C-8714-2013 OI Chen, Clark/0000-0001-6258-9277 NR 12 TC 7 Z9 9 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD APR PY 2002 VL 23 IS 4 BP 667 EP 670 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 550PV UT WOS:000175512200032 PM 11950664 ER PT J AU Hawighorst, T Skobe, M Streit, M Hong, YK Velasco, P Brown, LF Riccardi, L Lange-Asschenfeldt, B Detmar, M AF Hawighorst, T Skobe, M Streit, M Hong, YK Velasco, P Brown, LF Riccardi, L Lange-Asschenfeldt, B Detmar, M TI Activation of the Tie2 receptor by angiopoietin-1 enhances tumor vessel maturation and impairs squamous cell carcinoma growth SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID VASCULAR-PERMEABILITY FACTOR; TYROSINE KINASE; ENDOTHELIAL-CELLS; IN-VIVO; ANGIOGENESIS; EXPRESSION; SKIN; VEGF; OVEREXPRESSION; REGRESSION AB The distinct roles of angiopoietin (Ang)-1 and Ang2, counteracting ligands for the endothelium-specific Tie2 receptor, in tumor development and progression have remained poorly understood. We investigated the expression of Ang1 and Ang2 during multi-step mouse skin carcinogenesis and in human squamous cell carcinoma (SCC) xenografts. Expression of Ang2, but not of Ang1, was up-regulated in angiogenic tumor vessels already in early stages of skin carcinogenesis and was also strongly increase in SCCs. Stable overexpression of Ang1 in human A431 SCCs resulted in a more than 70% inhibition of tumor growth, associated with enhanced Tie2 phosphorylation levels, as compared with low levels in control transfected tumors. No major changes in the vascular density, vascular endothelial growth factor mRNA and protein expression, and vascular endothelial growth factor receptor-2 phosphorylation levels were observed in Ang1-expressing tumors. However, the fraction of tumor blood vessels with coverage by a-smooth muscle actin-positive periendothelial cells was significantly increased, indicative of an increased vascular maturation status. These findings identify an inhibitory role of Ang1/Tie2 receptor-mediated vessel maturation in SCC growth and suggest that up-regulation of its antagonist, Ang2, during early-stage epithelial tumorigenesis contributes to the angiogenic switch by counteracting specific vessel-stabilizing effects of Ang1. C1 Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA 86410, CA69184, R01 CA069184, R01 CA086410] NR 44 TC 116 Z9 121 U1 1 U2 5 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2002 VL 160 IS 4 BP 1381 EP 1392 DI 10.1016/S0002-9440(10)62565-5 PG 12 WC Pathology SC Pathology GA 542FY UT WOS:000175033900021 PM 11943723 ER PT J AU Thomas, RK Kallenborn, A Wickenhauser, C Schultze, JL Draube, A Vockerodt, M Re, D Diehl, V Wolf, J AF Thomas, RK Kallenborn, A Wickenhauser, C Schultze, JL Draube, A Vockerodt, M Re, D Diehl, V Wolf, J TI Constitutive expression of c-FLIP in Hodgkin and Reed-Sternberg cells SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID NF-KAPPA-B; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; IMMUNOGLOBULIN GENE REARRANGEMENTS; FAS-MEDIATED APOPTOSIS; INHIBITORY PROTEIN; SIGNALING COMPLEX; ANTIGEN RECEPTOR; ALPHA-GENE; DISEASE; MUTATIONS AB Crosslinking of the transmembrane receptor CD95/ Fas leads to activation of a signaling cascade resulting in apoptosis. c-FLIP is a recently described protein that potently inhibits Fas-mediated apoptosis and has been shown to be a key factor in germinal center B cell survival. Because Hodgkin and Reed-Sternberg cells in classical Hodgkin's disease (cHD) are also resistant to Fas-mediated apoptosis we studied the role of c-FLIP in classical HD. High levels of c-FLIP protein were identified in two Fas-resistant Hodgkin-derived cell lines. In contrast to other tumor cells, inhibition of protein synthesis by cycloheximide did not lead to down-regulation of c-FLIP protein in these HD cell lines. Furthermore, Fas-mediated apoptosis was only partially restored suggesting that normal regulation of c-FLIP was disrupted. The in vivo relevance of these findings was supported by demonstration of significant c-FLIP expression by immunohistochemistry in 18 of 19 evaluable cases of primary HD. Taken together, c-FLIP is constitutively expressed in HD and may therefore be a major mechanism responsible for Fas-resistance in HD. C1 Univ Cologne, Dept Internal Med 1, D-50924 Cologne, Germany. Univ Cologne, Inst Pathol, D-5000 Cologne, Germany. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Wolf, J (reprint author), Univ Cologne, Dept Internal Med 1, Joseph Stelzmann Str 9, D-50924 Cologne, Germany. RI Vockerodt, Martina/L-4465-2014; Schultze, Joachim/D-7794-2011 OI Vockerodt, Martina/0000-0001-7761-5829; Schultze, Joachim/0000-0003-2812-9853 NR 48 TC 77 Z9 86 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2002 VL 160 IS 4 BP 1521 EP 1528 DI 10.1016/S0002-9440(10)62578-3 PG 8 WC Pathology SC Pathology GA 542FY UT WOS:000175033900034 PM 11943736 ER PT J AU Byrne, FR Farrell, CL Aranda, R Rex, KL Scully, S Brown, HL Flores, SA Gu, LH Danilenko, DM Lacey, DL Ziegler, TR Senaldi, G AF Byrne, FR Farrell, CL Aranda, R Rex, KL Scully, S Brown, HL Flores, SA Gu, LH Danilenko, DM Lacey, DL Ziegler, TR Senaldi, G TI RHuKGF ameliorates symptoms in DSS and CD4(+)CD45RB(Hi) T cell transfer mouse models of inflammatory bowel disease SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE colitis; growth factor; epithelial repair; intestinal trefoil factor ID KERATINOCYTE GROWTH-FACTOR; INTESTINAL BACTERIA; MURINE COLITIS; CROHNS-DISEASE; RAT MODEL; MICE; RECEPTOR; CHEMOTHERAPY; EXPRESSION; KGF AB There is an acute need for effective therapy for inflammatory bowel disease (IBD), particularly at the level of repair of the damaged epithelium. We evaluated the efficacy of recombinant human keratinocyte growth factor (rHuKGF) in both the dextran sodium sulfate (DSS) and the CD4(+) CD45RB(Hi) T cell transfer models of IBD. Disease was induced either by the ad libitum administration to normal mice of 4% DSS in the drinking water or by the injection of 4 x 10 5 CD4(+) CD45RB(Hi) T cells into immunodeficient scid/scid mice. rHuKGF was administered by subcutaneous injection at doses of 1.0 or 3.0 mg/kg in both preventative and therapeutic regimens during both studies. rHuKGF significantly improved survival and body weight loss in the DSS model in both preventative and therapeutic dosing regimens. It also improved diarrhea, hematochezia, and hematological parameters, as well as large intestine histopathology. In the T cell transfer model, rHuKGF improved body weight loss, diarrhea, and levels of serum amyloid A, as well as large intestine histopathology. In both models of IBD, the colonic levels of intestinal trefoil factor (ITF) were elevated by the disease state and further elevated by treatment with rHuKGF. These data suggest that rHuKGF may prove useful in the clinical management of IBD and its effects are likely mediated by its ability to locally increase the levels of ITF. C1 Amgen Inc, Dept Pharmacol & Pathol, Thousand Oaks, CA 91320 USA. Amgen Inc, Dept Prod Dev, Thousand Oaks, CA 91320 USA. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. Greater Los Angeles Vet Affairs Hosp Syst, Los Angeles, CA 90095 USA. Emory Univ, Dept Med, Atlanta, GA 30322 USA. RP Byrne, FR (reprint author), Amgen Inc, Dept Pharmacol & Pathol, 1 Amgen Ctr Dr,Mail Stop 15-2-B, Thousand Oaks, CA 91320 USA. NR 50 TC 27 Z9 27 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD APR PY 2002 VL 282 IS 4 BP G690 EP G701 DI 10.1152/ajpgi.00314.2001 PG 12 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 531FJ UT WOS:000174405100014 PM 11897629 ER PT J AU Kane, JM Davis, JM Schooler, N Marder, S Casey, D Brauzer, B Mintz, J Conley, R AF Kane, JM Davis, JM Schooler, N Marder, S Casey, D Brauzer, B Mintz, J Conley, R TI A multidose study of haloperidol decanoate in the maintenance treatment of schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID FLUPHENAZINE DECANOATE; THERAPY; RELAPSE; DRUGS AB Objective: Maintenance medication is critical in the prevention of psychotic relapse and rehospitalization among patients with schizophrenia. Given potential adverse effects, identification of the minimum effective dose is clinically important. Method: A multicenter, double-blind study was conducted to determine rates of symptomatic exacerbation and adverse effects in 105 outpatients with schizophrenia randomly assigned to four different fixed doses of haloperidol decanoate and treated for 1 year or until relapse. The doses used were 25, 50, 100, and 200 mg given intramuscularly once per month. Results: Rates of symptomatic exacerbation were 15%. in the 200-mg group, 23% with 100 mg, 25% with 50 mg, and 60% with 25 mg. No significant differences in outcome were found between the groups treated with 200, 100, and 50 mg. Among the patients who completed the trial with no symptomatic exacerbation, there were no differences between dose groups on measures of psychopathology at the final rating point. Conclusions: The results of this study suggest that the 200-mg/month dose of haloperidol decanoate is associated with the lowest rate of symptomatic exacerbation (15%) with minimal increased risk of adverse effects or subjective discomfort in comparison to 100 or 50 mg. At the same time, the rates of worsening with 100 mg (23%) and 50 mg (25%) were not significantly greater than that seen with 200 mg. These results provide some guidance as to effective dose ranges of haloperidol decanoate. C1 Hillside Hosp, Dept Psychiat, Glen Oaks, NY 11004 USA. Univ Illinois, Inst Psychiat, Chicago, IL USA. Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. W Los Angeles Vet Affairs Med Ctr, Dept Psychiat, Los Angeles, CA 90073 USA. Univ So Calif, Los Angeles Cty Med Ctr, Dept Psychiat, Los Angeles, CA 90033 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Univ Miami, Sch Med,Jackson Mem Hosp, Miami VA Med Ctr, Dept Psychiat, Miami, FL 33152 USA. Psychiat Outpatient Clin, Miami, FL USA. Univ Pittsburgh, Dept Psychiat, Bridgeville, PA USA. Mayview State Hosp, Bridgeville, PA USA. RP Kane, JM (reprint author), Hillside Hosp, Dept Psychiat, Glen Oaks, NY 11004 USA. NR 27 TC 35 Z9 38 U1 1 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2002 VL 159 IS 4 BP 554 EP 560 DI 10.1176/appi.ajp.159.4.554 PG 7 WC Psychiatry SC Psychiatry GA 538DZ UT WOS:000174800000008 PM 11925292 ER PT J AU Eisner, MD Thompson, BT Schoenfeld, D Anzueto, A Matthay, MA AF Eisner, MD Thompson, BT Schoenfeld, D Anzueto, A Matthay, MA CA Acute Respiratory Distress Syndro TI Airway pressures and early barotrauma in patients with acute lung injury and acute respiratory distress syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; adult respiratory distress syndrome; mechanical; ventilators ID PROTECTIVE-VENTILATION; PULMONARY BAROTRAUMA; TIDAL VOLUME; RISK; MORTALITY; STRATEGY AB The determinants of barotrauma in mechanically ventilated patients with acute lung injury or acute respiratory distress syndrome (ALI/ARDS) have not been clearly established. Using data from ARDS Network randomized controlled trials, we retrospectively examined the association between airway pressures and the risk of early barotrauma in a cohort of 718 patients with ALI/ARDS and no baseline barotrauma. We studied airway pressures at three exposure intervals: baseline, one day preceding the barotrauma event (one-day lag), and concurrent with the barotrauma event. During the first four study days, the cumulative incidence of barotrauma was 13% (95% confidence interval [CI] 10.6 to 15.6%). In a forward stepwise Cox proportional hazards analysis using time-dependent variables, higher concurrent positive end-expiratory pressure (PEEP) was associated with an increased risk of early barotrauma (relative hazard [RH] 1.67 per 5-cm H2O increment; 95% Cl 1.35-2.07). Once concurrent PEEP was selected into the model, no other airway pressure was related to barotrauma, including plateau pressure. In the multivariate analysis, higher concurrent PEEP was also related to a greater risk of barotrauma (RH 1.93; 95% Cl 1.44-2.60), controlling for age, ventilator group (6 versus 12 ml/kg), baseline PEEP, baseline plateau pressure, baseline tidal volume, Acute Physiology and Chronic Health Evaluation score, vasopressor use, serum albumin, hepatic failure, and coagulopathy. When one-day lagged values of PEEP were analyzed, higher PEEP was associated with a greater risk of barotrauma (RH 1.38 per 5-cm H2O increment; 95% Cl 1.09-1.76). Controlling for the covariates, higher PEEP was related to an increased risk of barotrauma (RH 1.50; 95% Cl 0.98-2.30). In conclusion, higher PEEP may increase the likelihood of early barotrauma in ALI/ARDS. C1 Univ Calif San Francisco, Div Environm & Occupat Med, Dept Med, San Francisco, CA 94117 USA. Univ Calif San Francisco, Div Environm & Occupat Med, Dept Anesthesia, San Francisco, CA 94117 USA. Univ Calif San Francisco, Div Environm & Occupat Med, Cardiovasc Res Inst, San Francisco, CA 94117 USA. Univ Calif San Francisco, Div Pulm & Crit Care Med, Dept Med, San Francisco, CA 94117 USA. Univ Calif San Francisco, Div Pulm & Crit Care Med, Dept Med, San Francisco, CA 94117 USA. Univ Calif San Francisco, Div Pulm & Crit Care Med, Cardiovasc Res Inst, San Francisco, CA 94117 USA. Harvard Univ, Massachusetts Gen Hosp, ARDS Network Clin Coordinating Ctr, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Audie L Murphy Mem Vet Affairs Hosp, San Antonio, TX USA. RP Eisner, MD (reprint author), Univ Calif San Francisco, Div Environm & Occupat Med, Dept Med, 350 Parnassus Ave,Suite 609, San Francisco, CA 94117 USA. FU NHLBI NIH HHS [N01-HR 46062, N01-HR 46060, K23 HL04201, N01-HR 46059, N01-HR 46061, N01-HR 46056, N01-HR 46057, N01-HR 46063, N01-HR 46058, N01-HR 46054, N01-HR 46064, N01-HR 46055] NR 14 TC 54 Z9 61 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 APR 1 PY 2002 VL 165 IS 7 BP 978 EP 982 DI 10.1164/rccm.2109059 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 536ZA UT WOS:000174730700019 PM 11934725 ER PT J AU Aquino, SL Asmuth, JC Moore, RH Weise, SB Fischman, AJ AF Aquino, SL Asmuth, JC Moore, RH Weise, SB Fischman, AJ TI Improved image interpretation with registered thoracic CT and positron emission tomography data sets SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CELL LUNG-CANCER; FUSION IMAGES; FDG-PET AB OBJECTIVE. The purpose of this study was to determine if nonlinear registration of clinically acquired thoracic CT and FDG positron emission tomography (PET) data sets supports more detailed interpretation of metastatic thoracic disease when compared with interpretations from nonregistered PET studies. CONCLUSION. In I I of 16 data sets of patients imaged for detection of metastatic disease, interpretations from PET studies were correctly altered with registration information. All changes were either improvements in tumor localization or correct interpretation of less metastatic involvement. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Sarnoff Corp, Princeton, NJ 08540 USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND 202,55 Fruit St, Boston, MA 02114 USA. NR 11 TC 25 Z9 25 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2002 VL 178 IS 4 BP 939 EP 944 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 533YQ UT WOS:000174558200028 PM 11906878 ER PT J AU Ecklund, K Jaramillo, D AF Ecklund, K Jaramillo, D TI Patterns of premature physeal arrest: MR imaging of 111 children SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID GROWTH-PLATE; DISTAL TIBIA; RABBITS; EPIPHYSEAL; FRACTURES; FIBULA AB OBJECTIVE. The purpose of this study was to use MR imaging, especially fat-suppressed three-dimensional (313) spoiled gradient-recalled echo sequences, to identify patterns of growth arrest after physeal insult in children. MATERIALS AND METHODS. We evaluated 111 children with physeal bone bridges (median age, 11.4 years) using MR imaging to analyze bridge size, location in physis, signal intensity, growth recovery lines, avascular necrosis, and metaphyseal cartilage tongues. Fifty-eight patients underwent fat-suppressed 3D spoiled gradient-recalled echo imaging with physeal mapping. The cause, bone involved, radiographic appearance, and surgical interventions (60/111) were also correlated. Data were analyzed with the two-tailed Fisher's exact test. RESULTS. Posttraumatic bridges, accounting for 70% (78/111) of patients, were most often distal, especially of the tibia (n = 43) and femur (n = 14), whereas those due to the other miscellaneous causes were more frequently proximal (p < 0.0001). The position of the bridge in the physis was related to the bone involved (p < 0.0001). Sixty-five percent of distal tibial bridges involved the anteromedial physis, whereas 60% of the distal femoral arrests were central. Larger bridges had higher T1 signal intensity (p < 0.008). Oblique growth recovery lines were seen exclusively with bridges involving the peripheral physis (p = 0.002) and smaller, more potentially resectable bridges. Metaphyseal cartilaginous tongues were seen with all causes, but avascular necrosis was exclusively posttraumatic (p = 0.03). Signal characteristics and bridge size did not vary with the cause. CONCLUSION. Premature physeal bony bridging in children is most often posttraumatic and disproportionately involves the distal tibia and femur where bridges tend to develop at the sites of earliest physiologic closure, namely anteromedially and centrally, respectively. MR imaging, especially with the use of fat-suppressed 3D spoiled gradient-recalled echo imaging, exquisitely shows the growth disturbance and associated abnormalities that may follow physeal injury and guides surgical management. C1 Harvard Univ, Sch Med, Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02215 USA. RP Ecklund, K (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. FU NIAMS NIH HHS [AR 42396-05] NR 20 TC 55 Z9 56 U1 1 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2002 VL 178 IS 4 BP 967 EP 972 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 533YQ UT WOS:000174558200033 PM 11906884 ER PT J AU Georgian-Smith, D D'Orsi, C Morris, E Clark, CF Liberty, E Lehman, CD AF Georgian-Smith, D D'Orsi, C Morris, E Clark, CF Liberty, E Lehman, CD TI Stereotactic biopsy of the breast using an upright unit, a vacuum-suction needle, and a lateral arm-support system SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID ATYPICAL DUCTAL HYPERPLASIA; CARCINOMA IN-SITU; CORE BIOPSY; SURGICAL BIOPSY; HISTOLOGIC UNDERESTIMATION; ASPIRATION BIOPSY; ASSISTED BIOPSY; LESIONS; 11-GAUGE; EXPERIENCE AB OBJECTIVE. This study evaluated the vacuum-suction needle (8- to 11-gauge) on an upright stereotactic machine with a lateral ann-support system. SUBJECTS AND METHODS. From July 1999 to August 2000, 185 core biopsies of the breast in 179 consecutive patients were planned in four institutions using 8- to 11-gauge vacuum-suction probes on an upright stereotactic unit. Needles were stabilized and attached to the x, y, and z coordinates of the machines via a lateral arm-support system. Needle entry was made in the x-axis. RESULTS. Five patients were canceled, and 180 biopsies were performed in 174 patients while the patients were in seated (n = 171) and lateral decubitus (n = 9) positions. An average of 9.5 cores were taken (range, 5-26 cores). Targeting was successful in 176 (98%) of 180 cores. Lesions were missed because of movement associated with Parkinson's disease (n = 1), or because the mass was obscured (n = 1) or calcifications were not in the core specimen (n = 2). Findings in 152 (84%) of the biopsies were benign and 28 (16%) were malignant. Forty-one lesions underwent surgical excision and 106 underwent mammographic follow-up. Discordance was 4% (6/147). Complications included vasovagal reactions (n = 10, 5.6%), bleeding (n = 5, 3%), hematomas (n = 3, 1.7%), vomiting (n = 1, 0.6%), and technical failure (n = 1, 0.6%). CONCLUSION. Vacuum-suction needle core biopsies can be successfully performed on an upright stereotactic machine with a lateral arm attachment. Thinly compressed breasts and lesions located near the chest wall are well sampled. The vasovagal rate is higher than that on a prone table but is acceptable. C1 Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. Univ Massachusetts, Mem Med Ctr, Dept Radiol, Worcester, MA 01655 USA. S Shore Hosp, Dept Radiol, S Weymouth, MA 02190 USA. Dept Radiol, Travis AFB, CA 94535 USA. RP Georgian-Smith, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, Wang ACC 219-Q,15 Parkman St, Boston, MA 02114 USA. NR 31 TC 15 Z9 17 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2002 VL 178 IS 4 BP 1017 EP 1024 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 533YQ UT WOS:000174558200042 PM 11906893 ER PT J AU McDonald, JM Longnecker, DS Bell, RH AF McDonald, JM Longnecker, DS Bell, RH TI Effect of hypergastrinemia on pancreatic carcinogenesis SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 21-24, 2000 CL SAN DIEGO, CALIFORNIA SP Soc Surg Alimentary Track DE pancreatic neoplasms; gastrin; receptors-cholecystokinin; rat ID OMEPRAZOLE-INDUCED HYPERGASTRINEMIA; CHOLECYSTOKININ-A RECEPTORS; PEPTIC-ULCER PATIENTS; CANCER CELL-LINES; RAT PANCREAS; DUODENOGASTRIC REFLUX; ANTRECTOMIZED RATS; ACID-SECRETION; TREATED RATS; B RECEPTORS AB Background: Previous studies in our laboratory demonstrated that pancreatic carcinomas in rodents express receptors for the peptide hormone gastrin that are not present in normal adult pancreas. In view of an abundant literature suggesting that gastrin may promote growth of various gastrointestinal tissues and tumors, the effect of hypergastrinemia on the process of pancreatic carcinogenesis was evaluated. Methods: Rats received subcutaneous injections of the pancreatic carcinogen azasetrine at 19 and 26 days of age. Starting at 12 months of age, animals were randomized to treatment with the proton pump inhibitor lansoprazole or vehicle by gavage for 6 months. At autopsy, pancreatic wet weight normalized to body weight was recorded, as well as the number of benign and malignant pancreatic lesions. Results: Serum gastrin levels were determined by radioimmunoassay and showed a greater than two-fold increase in lansoprazole-treated animals. Pancreatic wet weight in hypergastrinemic rats was increased compared to controls (p < 0.05). Premalignant lesions such as acidophilic atypical acinar cell foci, adenomas, heterogeneous phenotypic populations of nodules within nodules, and carcinoma-in-situ were not increased in the hypergastrinemic group. Likewise, there was no difference in the incidence of invasive carcinoma in hypergastrinemic animals (10%) compared to controls (5.7%). Conclusion: Hypergastrinemia stimulated an increase in pancreatic weight, but did not stimulate development of premalignant lesions or progression to cancer in the azaserine model of rat pancreatic acinar cell carcinoma. (C) 2002 Excerpta Medica, Inc. All rights reserved. C1 Univ Washington, Sch Med, Seattle, WA 98108 USA. Dartmouth Coll Sch Med, Dept Pathol, Lebanon, NH 03756 USA. RP Bell, RH (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Surg, Seattle, WA 98108 USA. NR 34 TC 3 Z9 4 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD APR PY 2002 VL 183 IS 4 BP 441 EP 444 AR PII S0002-9610(02)00820-6 DI 10.1016/S0002-9610(02)00820-6 PG 4 WC Surgery SC Surgery GA 542TF UT WOS:000175059900018 PM 11975934 ER PT J AU Oliva, E Young, RH Amin, MB Clement, PB AF Oliva, E Young, RH Amin, MB Clement, PB TI An immunohistochemical analysis of endometrial stromal and smooth muscle tumors of the uterus - A study of 54 cases emphasizing the importance of using a panel because of overlap in immunoreactivity for individual antibodies SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE endometrial stromal tumors; smooth muscle tumors; uterine tumors resembling ovarian sex cord tumors; immunohistochemistry ID PARAFFIN-SECTION DETECTION; GRANULOSA-CELL TUMORS; C-KIT; H-CALDESMON; MONOCLONAL-ANTIBODY; MESENCHYMAL TUMORS; UTERINE-TUMORS; HUMAN TISSUES; CALPONIN H1; EXPRESSION AB The expression of desmin, h-caldesmon, calponin, CD10, CD34, CD99, inhibin, and keratin (AE1/3-Cam 5.2) was studied in 10 conventional leiomyomas, 9 highly cellular leiomyomas, 9 epithelioid smooth muscle tumors, 9 leiomyosarcomas, 10 endometrial stromal tumors (4 with smooth muscle metaplasia), and 7 uterine tumors resembling ovarian sex cord tumors (UTROSCTs). c-kit expression was tested in 10 endometrial stromal tumors, 7 UTROSCTs, and 9 leiomyosarcomas. Desmin was positive in almost all smooth muscle tumors except those of epitheloid type, which were positive in only about half of the cases. It also stained areas of smooth muscle differentiation in endometrial stromal tumors and five of seven UTROSCTs. h-caldesmon was positive in almost all nonepithelioid smooth muscle tumors and in areas of smooth muscle differentiation in endometrial stromal tumors; it was positive in only about half of the epithelioid smooth muscle tumors and negative in all UTROSCTs. Calponin was positive in most tumor types. CD10 was positive in nine of 10 endometrial stromal tumors and five of seven UTROSCTs, although very focally in the latter group. It was also expressed. however, in almost all leiomyosarcomas, almost 50% of highly cellular leiomyomas, and rarely in the other smooth muscle tumors. CD34 was negative in the tested tumors with rare exceptions. CD99 and inhibin were positive in four of seven and one of seven UTROSCTs. Keratin positivity was found in most (five of seven) UTROSCTs and occasionally in smooth muscle tumors (seven of 37). c-kit was negative in all endometrial stromal tumors, UTROSCTs, and leiomyosarcomas. The major conclusions of this study are as follows: 1) Pure endometrial stromal tumors are usually desmin negative. 2) In contrast to some previous studies, CD10 expression was often seen in smooth muscle tumors, including most leiomyosarcomas and almost half of highly cellular leiomyomas. As a result, a panel of CD10, h-caldesmon. and desmin should be used and will distinguish endometrial stromal tumors from highly cellular leiomyomas in most cases. 3) In contrast to a previous study, no significant differences in immunoreactivity were seen between h-caldesmon and desmin in tumors with smooth muscle differentiation. 4) The absence of h-caldesmon in UTROSCTs helps separate them from epithelioid smooth muscle tumors. 5) UTROSCTs may express epithelial. stromal, and smooth muscle markers, suggesting divergent differentiation. 6) Our study shows less frequent inhibin expression in the sex cordlike elements of the UTROSCTs than in other studies. 7) c-kit may help distinguish metastatic endometrial stromal tumors of the uterus (c-kit negative) from gastrointestinal stromal tumors (c-kit positive). 8) CD34, CD99. and keratin have no or minimal role in this area, but keratin positivity in smooth muscle tumors should not lead to their confusion with epitheiial tumors. C1 Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med,James Homer Wright Pathol Labs, Boston, MA 02114 USA. Emory Univ Hosp, Dept Pathol, Atlanta, GA 30322 USA. Vancouver Gen Hosp, Dept Pathol, Vancouver, BC, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Oliva, E (reprint author), Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med,James Homer Wright Pathol Labs, Fruit St, Boston, MA 02114 USA. NR 43 TC 166 Z9 178 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2002 VL 26 IS 4 BP 403 EP 412 DI 10.1097/00000478-200204000-00001 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 535YD UT WOS:000174673200001 PM 11914617 ER PT J AU Delmonico, FL Harmon, WE AF Delmonico, FL Harmon, WE TI The use of a minor as a live kidney donor SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE donor; kidney; live; minor ID DONATION AB An analysis of the UNOS database suggests a practice pattern that uses live minor kidney donors in clinical circumstances not endorsed by the recommendations of a recent consensus conference on live organ donation. These data reveal that minor donor kidneys were transplanted more frequently to adult than to pediatric recipients, that only 12% of all recipients were identical twins, and that the use of a minor donor provided no better outcome than that expected from an adult donor. Live organ donation from a minor should only be considered when there is no other living donor available and all other opportunities for transplantation have been exhausted. C1 Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Delmonico, FL (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 8 TC 23 Z9 23 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2002 VL 2 IS 4 BP 333 EP 336 DI 10.1034/j.1600-6143.2002.20407.x PG 4 WC Surgery; Transplantation SC Surgery; Transplantation GA 551AB UT WOS:000175536300007 PM 12118854 ER PT J AU Patenaude, AF Guttmacher, AE Collins, FS AF Patenaude, AF Guttmacher, AE Collins, FS TI Genetic testing and psychology - New roles, new responsibilities SO AMERICAN PSYCHOLOGIST LA English DT Article; Proceedings Paper CT 108th Annual Convention of the American-Psychological-Association CY AUG 04-08, 2000 CL WASHINGTON, DC SP Amer Psychol Assoc ID BREAST-OVARIAN CANCER; HUMAN-GENOME-PROJECT; FOLLOW-UP CARE; PROPHYLACTIC MASTECTOMY; INHERITED PREDISPOSITION; FAMILIAL BREAST; BRCA1; RISK; SUSCEPTIBILITY; DISEASE AB Advances in genetics and genetic testing promise to catalyze a fundamental change in the practice of medicine. Psychologists have much to offer as psychotherapists, researchers, educators, and policymakers to a society heavily influenced by the genetic revolution. To make the most of new opportunities available to mental health professionals in genetics, psychologists must know basic genetic principles and learn what is new about 21st-century genetics. The core competencies for all health professionals developed by the National Coalition for Health Professional Education in Genetics are related in this article to the significant roles psychologists can play in helping individuals with genetic concerns to cope with vulnerability, optimize family interaction, and improve health behaviors. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Natl Human Genome Res Inst, Bethesda, MD USA. RP Patenaude, AF (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM andrea_patenaude@dfci.harvard.edu NR 55 TC 30 Z9 30 U1 0 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD APR PY 2002 VL 57 IS 4 BP 271 EP 282 DI 10.1037//0003-066X.57.4.271 PG 12 WC Psychology, Multidisciplinary SC Psychology GA 541QW UT WOS:000174996100002 PM 11975377 ER PT J AU Finegold, SM Molitoris, D Phan, VT Vaisanen, ML Wexler, HM AF Finegold, SM Molitoris, D Phan, VT Vaisanen, ML Wexler, HM TI Activity of ABT-773 against bowel flora organisms SO ANAEROBE LA English DT Article DE intestinal bacteria; ABT-773; ketolides ID IN-VITRO ACTIVITIES; ANAEROBIC-BACTERIA AB The antimicrobial activity of ABT-773, a new ketolide, was tested against 285 strains of anaerobic and 68 strains of aerobic or facultative bacteria of the human bowel flora and compared to that of ampicillin/sulbactam, clindamycin, levofloxacin, metronidazole, and penicillin G. The NCCLS standard Wadsworth two-fold agar dilution technique using Brucella-laked sheep blood agar was used throughout. ABT-773 inhibited 90% of the anaerobes and 66% of the non-anaerobes at 4 mg/L. Twenty-two percent of Bacteroides fragilis strains (9) and 9% of 59 other B. fragilis group species were resistant at a level of 4mg/L. Against anaerobes, the comparator drugs were similar in activity to ABT-773 except for ampicillin/sulbactam which was more active, metronidazole which was somewhat more active, and penicillin G which was much less active. Against the non-anaerobes, levofloxacin and ampicillin/sulbactam were significantly more active than ABT-773 and the other three comparator drugs. were much less active. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, Infect Dis Sect 111F, WLA, W Los Angeles Div, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Res Serv, 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, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Immunol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Mol Genet, Los Angeles, CA 90024 USA. RP Finegold, SM (reprint author), VA Greater Los Angeles Healthcare Syst, Infect Dis Sect 111F, WLA, W Los Angeles Div, Los Angeles, CA 90073 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1075-9964 J9 ANAEROBE JI Anaerobe PD APR PY 2002 VL 8 IS 2 BP 49 EP 54 DI 10.1006/anae.2002.0416 PG 6 WC Microbiology SC Microbiology GA 591LK UT WOS:000177881500001 ER PT J AU Patroniti, N Foti, G Cortinovis, B Maggioni, E Bigatello, LM Cereda, M Pesenti, A AF Patroniti, N Foti, G Cortinovis, B Maggioni, E Bigatello, LM Cereda, M Pesenti, A TI Sigh improves gas exchange and lung volume in patients with acute respiratory distress syndrome undergoing pressure support ventilation SO ANESTHESIOLOGY LA English DT Article ID END-EXPIRATORY PRESSURE; MECHANICAL VENTILATION; TIDAL VOLUME; PERFUSION DISTRIBUTIONS; AIRWAY PRESSURE; INJURY PATIENTS; RECRUITMENT; OXYGENATION; ANESTHESIA; INFLATION AB Background: The aim of our study was to assess the effect of periodic hyperinflations (sighs) during pressure support ventilation (PSV) on lung volume, gas exchange, and respiratory pattern in patients with early acute respiratory distress syndrome (ARDS). Methods: Thirteen patients undergoing PSV were enrolled. The study comprised 3 steps: baseline 1, sigh, and baseline 2, of 1 h each. During baseline 1 and baseline 2. patients underwent PSV. Sighs were administered once per minute by adding to baseline PSV a 3- to 5-s continuous positive airway pressure (CPAP) period. set at a level 20% higher than the peak airway pressure of the PSV breaths or at least 35 cm H(2)O. Mean airway pressure was kept constant by reducing the positive end-expiratory pressure (PEEP) during the sigh period as required. At the end of each study period, arterial blood gas tensions, air flow and pressures traces, end-expiratory lung volume (EELV), compliance of respiratory system (Crs), and ventilatory parameters were recorded. Results: Pao(2) improved (P < 0.001) from baseline 1 (91.4 +/- 27.4 mmHg) to sigh (133 +/- 42.5 mmHg), without changes of Paco(2). EELV increased (P < 0.01) from baseline 1 (1,242 +/- 507 ml) to sigh (1,377 +/- 484 ml). Crs Improved (P < 0.01) from baseline 1 (40.2 +/- 12.5 ml/cm H(2)O) to sigh (45.1 +/- 15.3 mJ/cm H(2)O). Tidal volume of pressure-supported breaths and the airway occlusion pressure (P(0.1)) decreased (P < 0.01) during the sigh period. There were no significant differences between baselines 1 and 2 for all parameters. Conclusions: The addition of 1 sigh per minute during PSV in patients with early ARDS improved gas exchange and lung volume and decreased the respiratory drive. C1 Univ Milano Bicocca, Dept Anesthesia & Intens Care, Milan, Italy. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Pesenti, A (reprint author), Univ Milano Bicocca, Osped San Gerardo Nuovo Tintori, Dept Anesthesia & Intens Care, Via Donizetti 106, I-20052 Monza, Italy. EM antonio.pesenti@unimib.it RI Foti, Giuseppe/K-8627-2016; Patroniti, Nicolo/K-6347-2016 OI Patroniti, Nicolo/0000-0003-3600-193X NR 31 TC 67 Z9 79 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2002 VL 96 IS 4 BP 788 EP 794 DI 10.1097/00000542-200204000-00004 PG 7 WC Anesthesiology SC Anesthesiology GA 536TA UT WOS:000174716900003 PM 11964584 ER PT J AU Raveh, Y Ichinose, F Orbach, P Bloch, KD Zapol, WM AF Raveh, Y Ichinose, F Orbach, P Bloch, KD Zapol, WM TI Radical scavengers protect murine lungs from endotoxin-induced hyporesponsiveness to inhaled nitric oxide SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT 96th International Conference of the American-Thoracic-Society CY MAY 05-10, 2000 CL TORONTO, CANADA SP Amer Thorac Soc ID SYNTHETIC SUPEROXIDE-DISMUTASE; N-ACETYLCYSTEINE; ANTIOXIDANT ENZYMES; HYDROGEN-PEROXIDE; HYPOCHLOROUS ACID; IN-VIVO; INJURY; CATALASE; SYNTHASE; RATS AB Background: Sepsis is associated with an impaired pulmonary vasodilator response to inhaled nitric oxide (NO). A combination of NO and other inflammatory mediators appears to be responsible for endotoxin-induced pulmonary vascular hyporesponsiveness to Inhaled NO. The authors investigated whether scavengers of reactive oxygen species could preserve. inhaled No responsiveness in endotoxin-challenged mice. Methods: The vasorelaxation to Inhaled NO was studied in isolated, perfused, and ventilated lungs obtained from mice 16 It after an intraperitoneal challenge with saline or 50 mg/kg Escherichia roll lipopolysaccharide. in some mice, challenge with saline or lipopolysaccharide was followed by intraperitoneal administration of N-acetylcysteine, dimethylthiourea, EUK-8, or polyethylene glycol-conjugated catalase. Results: The pulmonary vasodilator response of U46619-preconstricted isolated lungs to ventilation with 0.4, 4, and 40 ppm inhaled NO in lipopolysaccharide-challenged mice was reduced to 32, 43, and 60%, respectively, of that observed in saline-challenged mice (P < 0.0001). Responsiveness to Inhaled NO was partially preserved in lipopolysaccharide-challenged mice treated with a single dose of N-acetyleysteine (150 or 500 mg/kg) or 20 U/g polyethylene glyco-conjugated catalase (all P < 0.05 vs. lipopolysaccharide alone). Responsiveness to inhaled NO was fully preserved by treatment with either dimethylthiourea, EUK-8, two doses of N-acetyleysteine (150 mg/kg administered 3.5 It apart), or 100 U/g polyethylene glycol-conjugated catalase (all P < 0.01 vs. lipopolysaccharide alone). Conclusions: When administered to mice concurrently with lipopolysaccharide challenge, reactive oxygen species scavengers prevent impairment of pulmonary vasodilation to inhaled NO. Therapy with scavengers of reactive oxygen species may provide a means to preserve pulmonary vasodilation to inhaled NO in sepsis-associated acute lung injury. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 32 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-55377, HL-07208, HL-42397] NR 46 TC 5 Z9 5 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 APR PY 2002 VL 96 IS 4 BP 926 EP 933 DI 10.1097/00000542-200204000-00021 PG 8 WC Anesthesiology SC Anesthesiology GA 536TA UT WOS:000174716900020 PM 11964601 ER PT J AU Pian-Smith, MC Ecker, J Hsu, K Leffert, L AF Pian-Smith, MC Ecker, J Hsu, K Leffert, L TI Endothelial dysfunction in preeclampsia: A pilot study with non-invasive blood pressure waveform analysis SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 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 APR PY 2002 SU S MA Z3 BP U11 EP U11 PG 1 WC Anesthesiology SC Anesthesiology GA 538BL UT WOS:000174794100014 ER PT J AU Rosen, ED AF Rosen, ED TI Molecular mechanisms of adipocyte differentiation SO ANNALES D ENDOCRINOLOGIE LA English DT Article; Proceedings Paper CT 44th International Meeting on Clinical Endocrinology CY MAY 17-18, 2001 CL PARIS, FRANCE ID BINDING-PROTEIN-ALPHA; ADIPOSE-TISSUE; PPAR-GAMMA; INSULIN-RESISTANCE; C/EBP-ALPHA; EXPRESSION; CELLS; GENE; CONVERSION; ENHANCER C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Rosen, ED (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 32 TC 19 Z9 21 U1 0 U2 0 PU MASSON EDITEUR PI PARIS 06 PA 120 BLVD SAINT-GERMAIN, 75280 PARIS 06, FRANCE SN 0003-4266 J9 ANN ENDOCRINOL-PARIS JI Ann Endocrinol. PD APR PY 2002 VL 63 IS 2 BP 79 EP 82 PN 1 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 557HA UT WOS:000175902000002 PM 11994665 ER PT J AU Lambe, S Washington, DL Fink, A Herbst, K Liu, HH Fosse, JS Asch, SM AF Lambe, S Washington, DL Fink, A Herbst, K Liu, HH Fosse, JS Asch, SM TI Trends in the use and capacity of California's emergency departments, 1990-1999 SO ANNALS OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT CAL/ACEP Scientific Assembly CY JUN, 2001 CL SAN JOSE, CALIFORNIA SP CAL, ACEP C1 VA Greater Los Angeles Helathcare Syst, Dept Med, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Publ Hlth, Los Angeles, CA USA. Univ Calif Los Angeles, Div Gen Internal Med, Los Angeles, CA USA. Herbst Med Geog, Haddam, CT USA. RP Lambe, S (reprint author), Univ Calif San Francisco, Div Emergency Med, Box 0208,505 Parnassus St, San Francisco, CA 94143 USA. NR 29 TC 105 Z9 107 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD APR PY 2002 VL 39 IS 4 BP 389 EP 396 DI 10.1067/mem.2002.122433 PG 8 WC Emergency Medicine SC Emergency Medicine GA 536JH UT WOS:000174696600005 PM 11919525 ER PT J AU Koroshetz, WJ Lev, MH AF Koroshetz, WJ Lev, MH TI Contrast computed tomography scan in acute stroke: "You can't always get what you want but ... you get what you need" SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID CEREBRAL BLOOD-FLOW; HYPERACUTE STROKE; TRANSIT-TIME; CT C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Koroshetz, WJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 15 TC 19 Z9 19 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2002 VL 51 IS 4 BP 415 EP 416 DI 10.1002/ana.10167 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 534QK UT WOS:000174597600001 PM 11921047 ER PT J AU Reuter, U Chiarugi, A Bolay, H Moskowitz, MA AF Reuter, U Chiarugi, A Bolay, H Moskowitz, MA TI Nuclear factor-kappa B as a molecular target for migraine therapy SO ANNALS OF NEUROLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; TRANSCRIPTION FACTOR; SIGNALING PATHWAYS; CYTOKINE INDUCTION; MESSENGER-RNA; DURA-MATER; INHIBITION; CELLS; ALPHA; PARTHENOLIDE AB Nitric oxide (NO) generated from inducible NO synthase (iNOS) participates in immune and inflammatory responses in many tissues. The NO donor glyceryl trinitrate (GTN) provokes delayed migraine attacks when infused into migraineurs and also causes iNOS expression and delayed inflammation within rodent dura mater. Sodium nitroprusside, an NO donor as well, also increases iNOS expression. Because inflammation and iNOS are potential therapeutic targets, we examined transcriptional regulation of iNOS following GTN infusion and the consequences of its inhibition within dura mater. We show that intravenous GTN increases NO production within macrophages. L-N(6)-(1-iminoethyl)lysine, a selective iNOS inhibitor, attenuates the NO signal, emphasizing the importance of enzymatic activity to delayed NO production. iNOS expression is preceded by significant nuclear factor kappa B (NF-kappaB) activity, as reflected by a reduction in the inhibitory protein-K-Bot (lkappaBalpha) and activation of NF-kappaB after GTN infusion. IkappaBalpha degradation, NF-kappaB activation, and iNOS expression were attenuated by parthenolide (3mg/kg), the active constituent of feverfew, an anti-inflammatory drug used for migraine treatment. These findings suggest that GTN promotes NF-kappaB activity and inflammation with a time course consistent with migraine attacks in susceptible individuals. We conclude, based on results with this animal model, that blockade of NF-kappaB activity provides a novel transcriptional target for the development of anti-migraine drugs. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Stroke & Neurovasc Regulat Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [5P01 NS 35611] NR 50 TC 86 Z9 102 U1 3 U2 10 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 APR PY 2002 VL 51 IS 4 BP 507 EP 516 DI 10.1002/ana.10159 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 534QK UT WOS:000174597600011 PM 11921057 ER PT J AU Clark, JI Kuzel, TM Lestingi, TM Fisher, SG Sorokin, P Martone, B Viola, M Sosman, JA AF Clark, JI Kuzel, TM Lestingi, TM Fisher, SG Sorokin, P Martone, B Viola, M Sosman, JA TI A multi-institutional phase II trial of a novel inpatient schedule of continuous interleukin-2 with interferon alpha-2b in advanced renal cell carcinoma: major durable responses in a less highly selected patient population SO ANNALS OF ONCOLOGY LA English DT Article DE decrescendo IL-2; interferon; kidney cancer; phase II ID RECOMBINANT HUMAN INTERLEUKIN-2; HIGH-DOSE INTERLEUKIN-2; SUBCUTANEOUS INTERLEUKIN-2; METASTATIC MELANOMA; ADVANCED CANCER; KILLER CELLS; THERAPY; COMBINATION; IMMUNOTHERAPY; ALFA-2A AB Background: A prospective multi-institutional phase 11 trial was undertaken to define the activity and toxicity of a unique decrescendo infusion of interleukin-2 (IL-2) in combination with interferon (IFN) in patients with metastatic renal cell carcinoma. The identical regimen has shown promise in advanced melanoma. Patients and methods: Between February 1997 and March 1999. 47 patients with metastatic renal cell carcinoma. from five institutions. A ere treated with outpatient s.c. IFN (10 mU/m(2)/day) on days 1-5. followed by inpatient IL-2 via continuous i.v. decrescendo infusion [18 million International Units (MIU) (1 mg)/m(2)/6 h, followed by 18 MIU/m(2)/12 h. then 18 MIU/m(2)/24 h and 4.5 MIU/m(2)/24 h for the following 3 days] on days 8-12. in a hospital ward without intensive care unit (ICU)-type monitoring. Treatment was repeated every 4 weeks. In contrast to high dose IL-2 protocols, patient eligibility did not require pulmonary function tests and allowed serum creatinine up to 2 mg/dl. Results: Among 44 eligible patients. 57% (25) had their primary in place, 57% (25) had bone or visceral involvement, and only 4% (2) had lung as their only site of disease. The overall response rate in 43 response-evaluable patients was 16.3% [95% confidence interval (CI) 5.3 to 27.3]. with three complete responses and four partial responses observed. The median survival was 13 months nine patients remain alive at >23 months. The median duration of response is 36 months (range 11.5 to 48+ months), Toxicity was modest. consisting of typical cytokine-induced systemic symptoms and rare organ dysfunction. Severe grade 4 toxicity occurred in only 13% of the 130 cycles. Conclusions: This unique. reasonably well tolerated IL-2/IFN combination induced a modest response rate with a number of durable remissions. While the optimal IL-2-based regimen for the treatment of advanced renal cell carcinoma remains elusive. the present regimen should attract considerable interest. This is based on tumor activity very similar to high dose IL-2 in a patient population not as carefully selected for optimal organ function. C1 Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Northwestern Univ, Sch Med, Chicago, IL USA. Lutheran Gen Hosp, Park Ridge, IL 60068 USA. Univ Illinois, Chicago, IL USA. RP Clark, JI (reprint author), Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, 2160 S 1st Ave, Maywood, IL 60153 USA. NR 41 TC 13 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD APR PY 2002 VL 13 IS 4 BP 606 EP 613 DI 10.1093/annonc/mdf105 PG 8 WC Oncology SC Oncology GA 543NB UT WOS:000175107100023 PM 12056712 ER PT J AU Doyle, PJ AF Doyle, PJ TI 31st Clinical Aphasiology Conference - 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 1 TC 1 Z9 1 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 APR-JUN PY 2002 VL 16 IS 4-6 BP 381 EP 381 DI 10.1080/02687030244000419 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 548UX UT WOS:000175409200001 ER PT J AU Harper, CMG Xu, SL Feng, Y Dunn, JL Taylor, NS Dewhirst, FE Fox, JG AF Harper, CMG Xu, SL Feng, Y Dunn, JL Taylor, NS Dewhirst, FE Fox, JG TI Identification of novel Helicobacter spp. from a Beluga whale SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID GASTRIC-ULCER; DELPHINAPTERUS-LEUCAS; SP-NOV; PYLORI; TRANSMISSION; CETACEANS; PHYLOGENY; MUSTELAE; HEALTHY; FERRETS AB The gastric fluid and feces of three belugas from the Mystic Aquarium were assessed for the presence of Helicobacter spp. Gastric fluid and feces from the two clinically healthy belugas were negative for helicobacter, and endoscopy performed on these animals revealed no lesions. However, a helicobacter isolate and PCR product similar to helicobacter strains previously recovered from dolphins were identified, respectively, from the feces and gastric fluid of a beluga manifesting intermittent inappetence and lethargy. Esophageal and forestomach ulcers were noted on endoscopy. This is the first report of novel Helicobacter spp. being identified from whales. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Myst Aquarium, Mystic, CT 06355 USA. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave,Bldg 16,Rm 825C, Cambridge, MA 02139 USA. FU NCRR NIH HHS [T32-RR07036, T32 RR007036]; NIAID NIH HHS [R01 AI037750, R01-AI37750]; NIDCR NIH HHS [R01-DE10374, R01 DE010374] NR 31 TC 17 Z9 18 U1 0 U2 1 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 APR PY 2002 VL 68 IS 4 BP 2040 EP 2043 DI 10.1128/AEM.68.4.2040-2043.2002 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 538YF UT WOS:000174842200071 PM 11916729 ER PT J AU Haan, MN Jagust, WJ Galasko, D Kaye, J AF Haan, MN Jagust, WJ Galasko, D Kaye, J TI Effect of extrapyramidal signs and Lewy bodies on survival in patients with Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID DEMENTIA; CONSORTIUM; PREDICTORS; ESTABLISH; DIAGNOSIS; REGISTRY; BODY AB Background: Patients with Alzheimer disease (AD) who have psychiatric and parkinsonian symptoms experience faster cognitive deterioration and shorter survival vs those without such disease features. Extrapyramidal signs (EPSs) in particular have been associated with the presence of Lewy bodies (LBs) on autopsy and with poorer survival in patients with AD. Lewy bodies found at autopsy are not always correlated with EPSs during late life. Objective: To determine whether the association between LBs and age at death is modified by the presence of EPSs, hallucinations, or delusions. Design: An autopsy series of patients with clinically diagnosed AD. Settings: Three AD clinics (San Diego and Sacramento, Calif, and Portland, Ore). Patients: Data on 379 patients with a clinical diagnosis of AD who were initially assessed between May 1, 1984, and August 1, 1996, and who were autopsied between January 1, 1990, and April 1, 1998, were pooled from 3 AD centers. Main Outcome Measures: Presence of LBs on autopsy and differences in age at death in those with EPSs, LBs, or both. Results: Individuals with EPSs at initial assessment were more than 3 times as likely to have LBs at autopsy than were those without EPSs. Age at death was younger in those with LBs and EPSs than in those with LBs only and those without EPSs or LBs. Conclusions: The presence of EPSs in patients with AD indicates worse prognosis and may be related to underlying LBs. The presence of EPSs is a strong predictor of LBs. C1 Univ Michigan, Dept Epidemiol, Sch Publ Hlth, Ann Arbor, MI 48109 USA. Univ Calif Davis, Sch Med, Dept Neurol, Davis, CA 95616 USA. Univ Calif San Diego, Sch Med, Dept Neurol, San Diego, CA 92103 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Haan, MN (reprint author), Univ Michigan, Dept Epidemiol, Sch Publ Hlth, 109 S Observ St, Ann Arbor, MI 48109 USA. OI Kaye, Jeffrey/0000-0002-9971-3478 FU NIA NIH HHS [AG05131, P30 AG010129] NR 14 TC 14 Z9 15 U1 2 U2 3 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 APR PY 2002 VL 59 IS 4 BP 588 EP 593 DI 10.1001/archneur.59.4.588 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 540KH UT WOS:000174927800011 PM 11939893 ER PT J AU Marquis, S Moore, MM Howieson, DB Sexton, G Payami, H Kaye, JA Camicioli, R AF Marquis, S Moore, MM Howieson, DB Sexton, G Payami, H Kaye, JA Camicioli, R TI Independent predictors of cognitive decline in healthy elderly persons SO ARCHIVES OF NEUROLOGY LA English DT Article ID TEMPORAL-LOBE ATROPHY; ALZHEIMERS-DISEASE; OLDEST-OLD; HIPPOCAMPAL ATROPHY; PRECLINICAL PHASE; FRAMINGHAM COHORT; DEVELOP DEMENTIA; IMPAIRMENT; MEMORY; AGE AB Background: Several studies have shown that individually memory, hippocampal volume, and motor measures presage the onset of dementia. It is unclear if these independently contribute to the prediction of mild cognitive impairment. Objective: To determine the ability of memory, hippocampal volume, and a gait speed to independently predict cognitive decline in healthy elderly persons. Design: A prospective, longitudinal, observational cohort study with a mean follow-up of 6 years, Participants: One hundred eight optimally healthy elderly cognitively intact subjects. Main Outcome Measures: Any cognitive impairment noted on the Clinical Dementia Rating Scale (score=0.5) or persistent or progressive cognitive impairment. Cox modeling determined if time to onset of cognitive impairment was associated with baseline logical memory 11 test score (a measure of delayed recall), hippocampal volume (magnetic resonance imaging), or gait speed (time to walk 30 ft [9 m]) independent of age, sex, depression, or the allele producing the epsilon4 type of apolipoprotein E (APOE epsilon4). Results: Questionable dementia occurred in 48 participants in a mean (SD) of 3.7 (2.4) years. This progressed to persistent cognitive impairment in 38 of these participants in a mean (SD) of 4.4 (2.4) years. Logical memory II test performance and hippocampal volume each predicted onset of questionable dementia, independent of age and sex. Time to walk 30 ft additionally contributed independently to the prediction of time to onset of persistent cognitive impairment. Possessing the APOE epsilon4 allele and depression did not enter either model significantly. Conclusions. Models combining multiple risk factors should refine the prediction of questionable dementia and persistent cognitive impairment, harbingers of dementia. Individuals at risk for cognitive impairment may represent a high-risk group for intervention. C1 Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Univ Alberta, Dept Med, Edmonton, AB, Canada. RP Camicioli, R (reprint author), Univ Alberta, Dept Med Neurol, 2E3-08,8440 112th St, Edmonton, AB T6G 2B7, Canada. OI Kaye, Jeffrey/0000-0002-9971-3478; Camicioli, Richard/0000-0003-2977-8660 FU NCRR NIH HHS [5M01RR0034]; NIA NIH HHS [AG08017] NR 47 TC 186 Z9 192 U1 1 U2 14 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 APR PY 2002 VL 59 IS 4 BP 601 EP 606 DI 10.1001/archneur.59.4.601 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 540KH UT WOS:000174927800013 PM 11939895 ER PT J AU Lee, MS Lessell, S AF Lee, MS Lessell, S TI Orbital myositis posing as cluster headache SO ARCHIVES OF NEUROLOGY LA English DT Article AB Objective: To describe the case of a patient with recurrent orbital myositis who was thought to have cluster headaches for 6 years. Design and Setting: Case report in an outpatient neuroophthalmology clinic. Patient: A 24-year-old man developed unilateral supraorbital pain, lacrimation, conjunctival hyperemia, nasal congestion, proptosis, and painful eye movements. The pain intensity varied over the course of each day and disappeared after I month. He had multiple attacks responsive to prednisone that were separated by months over the ensuing 6 years. Neuroimaging revealed an enlarged extraocular muscle. Conclusions: Overlap in symptoms between recurrent orbital myositis and cluster headache delayed the diagnosis in this patient. Orbital myositis should be considered in patients with atypical cluster headache characterized by proptosis, painful eye movements, and pain that does not completely resolve after 3 hours. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Neurophthalmol, Sch Med, Boston, MA 02114 USA. RP Lee, MS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Neurophthalmol, Sch Med, 243 Charles St, Boston, MA 02114 USA. NR 8 TC 13 Z9 13 U1 0 U2 0 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 APR PY 2002 VL 59 IS 4 BP 635 EP 636 DI 10.1001/archneur.59.4.635 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 540KH UT WOS:000174927800018 PM 11939900 ER PT J AU Lit, ES Tsilimbaris, M Gotzaridis, E D'Amico, DJ AF Lit, ES Tsilimbaris, M Gotzaridis, E D'Amico, DJ TI Lamina puncture - Pars plana optic disc surgery for central retinal vein occlusion SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CHORIORETINAL VENOUS ANASTOMOSIS; CREATION AB Objective: To determine the feasibility of creating a perivascular space adjacent to the central retinal vein at the level of the lamina cribrosa as a potential method of reestablishing perfusion in central retinal vein occlusion. Methods: Various designs for a puncture instrument, or lamina puncture lancet, were investigated in cadavers, pigs that had undergone enucleation, and in vivo rabbit eyes. Results: A lancet with a sharp cutting edge on one side and an opposing blunt edge is repeatedly able to create a perivascular space with limited optic nerve fiber damage. Conclusions: Lamina puncture is technically feasible, and evaluation in carefully selected patients appears warranted. C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP D'Amico, DJ (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. NR 13 TC 22 Z9 25 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 2002 VL 120 IS 4 BP 495 EP 499 PG 5 WC Ophthalmology SC Ophthalmology GA 538JU UT WOS:000174813300010 PM 11934325 ER PT J AU Cunningham, MT Brandt, JT Laposata, M Olson, JD AF Cunningham, MT Brandt, JT Laposata, M Olson, JD TI Laboratory diagnosis of dysfibrinogenemia SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID THROMBIN CLOTTING TIME; LIVER-DISEASE; ACQUIRED DYSFIBRINOGENEMIA; FIBRINOGEN LEVELS; SIALIC-ACID; INTRAINDIVIDUAL VARIABILITY; BOVINE THROMBIN; CARCINOMA-CELLS; GAMMA-CHAIN; IDENTIFICATION AB Dysfibrinogenemia is a coagulation disorder caused by a variety of structural abnormalities in the fibrinogen molecule that result in abnormal fibrinogen function. It can be inherited or acquired. The inherited form is associated with increased risk of bleeding, thrombosis, or both in the same patient or family. Traditionally, dysfibrinogenemia is diagnosed by abnormal tests of fibrin clot formation; the thrombin time and reptilase time are the screening tests, and the fibrinogen clotting activity-antigen ratio is the confirmatory test. The inherited form is diagnosed by demonstrating similar laboratory test abnormalities in family members, and if necessary by analysis of the fibrinogen protein or fibrinogen genes in the patient. The acquired form is diagnosed by demonstrating abnormal liver function tests and by ruling out dysfibrinogenemia in family members. This article reviews the laboratory testing of dysfibrinogenemia and presents an algorithm for sequential test selection that can be used for diagnosis. C1 Univ Kansas, Med Ctr, Dept Pathol, Kansas City, KS 66160 USA. Eli Lilly Corp Ctr, Indianapolis, IN USA. Massachusetts Gen Hosp, Div Clin Labs, Boston, MA 02114 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX USA. RP Cunningham, MT (reprint author), Univ Kansas, Med Ctr, Dept Pathol, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. NR 62 TC 55 Z9 57 U1 0 U2 0 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 APR PY 2002 VL 126 IS 4 BP 499 EP 505 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 539EJ UT WOS:000174857100026 PM 11900586 ER PT J AU DiFranza, JR Savageau, JA Fletcher, K Ockene, JK Rigotti, NA McNeill, AD Coleman, M Wood, C AF DiFranza, JR Savageau, JA Fletcher, K Ockene, JK Rigotti, NA McNeill, AD Coleman, M Wood, C TI Measuring the loss of autonomy over nicotine use in adolescents - The DANDY (development and assessment of nicotine dependence in youths) study SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID FAGERSTROM TOLERANCE QUESTIONNAIRE; NUCLEUS-ACCUMBENS; ALCOHOL DEPENDENCE; SMOKING CESSATION; SMOKERS; TOBACCO; SYMPTOMS; SENSITIZATION; WITHDRAWAL; DISORDERS AB Context: There is no validated, theory-based tool for assessing the onset of nicotine dependence. However, the use of all addictive substances can result in a loss of autonomy. We propose that nicotine dependence begins when autonomy is lost, ie, when the sequelae of tobacco use, either physical or psychological, present a barrier to quitting. Objectives: To test the autonomy theory of nicotine dependence, and to evaluate the Hooked on Nicotine Checklist (HONC) as a measure of the loss of autonomy over tobacco use. Design: The psychometric performance and concept validity of the HONC were evaluated in a 30-month prospective longitudinal study of the natural history of tobacco use in a cohort of 679 seventh-grade students. Results: As hypothesized, endorsement of a single item on the HONC was associated with a failed attempt at smoking cessation (odds ratio [OR], 29; 95% confidence interval [CI], 13-65), continued smoking until the end of follow-up (OR, 44; 95% CI, 17-114), and daily smoking (OR, 58; 95% CI, 24-142). Scores on the HONC correlated with the maximum amount smoked (r = 0.65; P < .001) and the maximum frequency of smoking (r = 0.79; P < .001). Internal reliability was 0.94. A 1-factor solution explained 66% of the total variance. Conclusions: The data support the autonomy theory that dependence begins with the loss of autonomy. The autonomy theory represents a potentially useful alternative to current concepts of nicotine dependence for adolescents, and the HONC appears to measure lost autonomy in adolescents. Construct validity was demonstrated by its utility in predicting failed cessation and the progression of tobacco use. In addition, the psychometric properties were excellent. C1 Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ London, St George Hosp, Sch Med, London, England. RP DiFranza, JR (reprint author), Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, Worcester, MA 01655 USA. FU NCI NIH HHS [CA77067-03] NR 65 TC 189 Z9 190 U1 0 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD APR PY 2002 VL 156 IS 4 BP 397 EP 403 PG 7 WC Pediatrics SC Pediatrics GA 537ZL UT WOS:000174789500016 PM 11929376 ER PT J AU Gerszten, RE AF Gerszten, RE TI Pleiotropic effects of chemokines in vascular lesion development SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Editorial Material ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; FLOW CONDITIONS; RECEPTOR CXCR4; SMOOTH-MUSCLE; ENDOTHELIUM; PI3K-GAMMA; ARREST; CELLS; MICE C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. NR 18 TC 4 Z9 4 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 APR PY 2002 VL 22 IS 4 BP 528 EP 529 DI 10.1161/hq0402.108067 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 545GL UT WOS:000175208700003 PM 11950686 ER PT J AU Kanamori, A Zeminski, J Rudy, TW Li, G Fu, FH Woo, SLY AF Kanamori, A Zeminski, J Rudy, TW Li, G Fu, FH Woo, SLY TI The effect of axial tibial torque on the function of the anterior cruciate ligament: A biomechanical study of a simulated pivot shift test SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE knee; anterior cruciate; ligament; knee kinematics; in situ force; pivot shift test; external loads ID IN-SITU FORCES; METHODOLOGY; TECHNOLOGY; KINEMATICS; SENSOR AB Purpose: Various techniques are used to produce the pivot shift phenomenon after anterior cruciate ligament (ACL) injury. In particular, the amount of applied axial tibial torque varies among examiners. Thus, the objective of this study was to determine the effect of the magnitude and direction of axial tibial torque in combination with valgus torque on the resulting knee kinematics during such a simulated pivot shift test. Type of Study: This was a biomechanical study that used cadaveric knees with the intact knee of the same specimen serving as a control. Methods: On 19 human cadaveric knees (acre, 26 to 69 years), a constant 10-Nm valgus torque was applied at 15degrees of knee flexion. Then, internal and external tibial torque was applied incrementally from 0 to 10 Nm and the resulting kinematics of the ACL-intact and ACL-deficient knee, as well as the in situ force in the ACL, were measured using a robotic/universal force-moment sensor testing system. Results: In response to isolated valgus torque, the coupled anterior tibial translation for the ACL-intact and ACL-deficient knee was 1.6 +/- 2.4 mm and 8.5 +/- 4.7 mm, respectively; therefore the difference between the ACL-intact and ACL-deficient knee was 6.9 +/- 3.4 mm. With an external tibial torque greater than 5 Nm, the tibia translated up to 4 mm posteriorly for both the ACL-intact and ACL-deficient knee. Whereas, internal tibial torque greater than 1.6 Nm caused a rapid increase in coupled anterior tibial translation up to 10.2 nun in the ACL-deficient knee, while causing only a gradual increase for the ACL-intact knee. With excessive internal torque of 10 Nm, the difference in coupled anterior tibial translation was only 4.4 +/- 2.2 mm, suggesting a decrease in the sensitivity of the test. Correspondingly, the in situ force in the ACL under 10 Nm valgus tibial torque was 43 +/- 17 N, and increased up to 87 +/- 32 N as a 10-Nm internal torque was added. By applying a 3.3-Nm external tibial torque in addition to the 10-Nm valgus torque, the in situ force decreased to 21 +/- 14 N. Conclusions: This study showed that a minimal amount of internal torque in combination with valgus torque may be a suitable way to elicit a pivot shift from an ACL-deficient knee. C1 Univ Pittsburgh, Musculoskeletal Res Ctr, Dept Orthopaed Surg, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Woo, SLY (reprint author), Univ Pittsburgh, Musculoskeletal Res Ctr, Dept Orthopaed Surg, E1641 Biomed Sci Tower,210 Lothrop St,Box 71199, Pittsburgh, PA 15213 USA. FU NIAMS NIH HHS [AR-39683] NR 19 TC 121 Z9 124 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 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD APR PY 2002 VL 18 IS 4 BP 394 EP 398 AR PII 10.1053/jars.2002.30638 DI 10.1053/jars.2002.30638 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 542JK UT WOS:000175039600009 PM 11951198 ER PT J AU Rosqvist, J Thomas, JC Egan, D AF Rosqvist, J Thomas, JC Egan, D TI Home-based cognitive-behavioral treatment of chronic, refractory obsessive-compulsive disorder can be effective - Single case analysis of four patients SO BEHAVIOR MODIFICATION LA English DT Article; Proceedings Paper CT 27th International Congress of Psychology CY JUL 23-28, 2000 CL STOCKHOLM, SWEDEN ID INFLATED RESPONSIBILITY; RESPONSE PREVENTION; FOLLOW-UP; THERAPY; EXPOSURE; PROGRAM; PERFECTIONISM; PSYCHOTHERAPY; PREDICTORS; THOUGHTS AB Four patients with obsessive-compulsive disorder (OCD) were referred for home-based cognitive-behavioral therapy. All patients had failed extensive trials of behavioral and cognitive therapy and pharmacotherapy in a variety of settings (e.g., outpatient, inpatient, and day program) and were generally considered chronic and refractory to treatment. Generalization from treatment sites to natural settings in which they lived did not occur. They were evaluated at baseline. after treatment, and at an 18-month follow-up using the Yale-Brown Obsessive Compulsive Scale. Conducting end-state functioning and reliable change assessment according to the methods specified by Jacobson and Truax, the authors found that 3 patients achieved clinically significant gains after treatment and 2 patients maintained those gains at the 18-month follow-up. Data suggested better overall adjustment for 3 of the patients at follow-up. This study demonstrates the effectiveness of home-based cognitive-behavioral therapy for chronic, refractory OCD implications for further, controlled trials are discussed. C1 Pacific Univ, Sch Profess Psychol, Forest Grove, OR 97116 USA. Massachusetts Gen Hosp, Obsess Compuls Disorder Inst, Boston, MA 02114 USA. RP Rosqvist, J (reprint author), Pacific Univ, Sch Profess Psychol, 2004 Pacific Ave, Forest Grove, OR 97116 USA. NR 59 TC 8 Z9 8 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 J9 BEHAV MODIF JI Behav. Modificat. PD APR PY 2002 VL 26 IS 2 BP 205 EP 222 DI 10.1177/0145445502026002005 PG 18 WC Psychology, Clinical SC Psychology GA 532QM UT WOS:000174486600005 PM 11961913 ER PT J AU Kulkarni, RN AF Kulkarni, RN TI Receptors for insulin and insulin-like growth factor-1 and insulin receptor substrate-1 mediate pathways that regulate islet function SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT Meeting on Islets and Type 2 Diabetes CY OCT 19, 2001 CL ST MICHAELS HOSP, BRISTOL, ENGLAND SP Biochem Soc, AstraZeneca, Servier (France), Physiol Soc, Novo Nordisk, GlaxoSmithKline HO ST MICHAELS HOSP DE beta-cell; knockout mouse; signalling ID PANCREATIC BETA-CELLS; GENE-EXPRESSION; FEEDBACK INHIBITION; GLUCOSE-HOMEOSTASIS; CANINE PANCREAS; SECRETION; MICE; DISRUPTION; RAT; TRANSCRIPTION AB The insulin/insulin-like growth factor-1 (IGF-1) signalling pathways are present in most mammalian cells and play important roles in the growth and metabolism of tissues. Most proteins in these path-ways have also been identified in the beta-cells of the pancreatic islets. Tissue-specific knockout of the insulin receptor (betaIRKO) or IGF-1 receptor (betaIGFRKO) in pancreatic beta-cells leads to altered glucose-sensing and glucose intolerance in adult mice, and betaIRKO mice show an age-dependent decrease in islet size and beta-cell mass. These data indicate that these receptors are important for differentiated function and are unlikely to play a major role in the early growth and/or development of the pancreatic islets. Conventional insulin receptor substrate-1 (IRS-1) knockouts manifest growth retardation and mild insulin resistance. The IRS-1 knockouts also display islet hyperplasia, defects in insulin secretory responses to multiple stimuli both in vivo and in vitro, reduced islet insulin content and an increased number of autophagic vacuoles in the beta-cells. Re-expression of IRS-1 in cultured beta-cells is able to partially restore the insulin content indicating that IRS-1 is involved in the regulation of insulin synthesis. Taken together, these data provide evidence that insulin and IGF-1 receptors and IRS-1, and potentially other proteins in the insulin/IGF-1 signalling pari contribute to the regulation of islet hormone secretion and synthesis and therefore in the maintenance of glucose homeostasis. C1 Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr,Dept Med, Boston, MA 02215 USA. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr,Dept Med, Boston, MA 02215 USA. NR 58 TC 67 Z9 70 U1 2 U2 3 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD APR PY 2002 VL 30 BP 317 EP 322 DI 10.1042/BST0300317 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 550JM UT WOS:000175499900059 PM 12023872 ER PT J AU Klein, J Fasshauer, M Klein, HH Benito, M Kahn, CR AF Klein, J Fasshauer, M Klein, HH Benito, M Kahn, CR TI Novel adipocyte lines from brown fat: a model system for the study of differentiation, energy metabolism, and insulin action SO BIOESSAYS LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE P85-ALPHA; PREADIPOCYTE CLONAL LINE; UNCOUPLING PROTEIN GENE; ADIPOSE CELL LINE; BETA(3)-ADRENERGIC RECEPTOR; DEVELOPMENTAL PROGRAM; ADRENERGIC-RECEPTOR; TRANSGENIC MICE; GLUCOSE-UPTAKE; EXPRESSION AB Adipose tissue has emerged as an important endocrine regulator of glucose metabolism and energy homeostasis. By virtue of the mitochondrial protein uncoupling protein-1 (UCP-1), brown fat additionally plays a unique role in thermoregulation. Interest has focused on this tissue not only as a target for pharmacotherapy of obesity and insulin resistance but also as an endocrine tissue with leptin secretion and high insulin sensitivity. Most studies of adipocytes have been limited either to primary cell culture or to a small number of established cell lines. Recently, we have generated immortalized brown adipocyte cell lines from single newborn mice of different knockout mouse models. These cell lines retain the main characteristics of primary cells including UCP-1 expression. They display sensitive and diverse metabolic responses to insulin and adrenergic stimulation and have proven to be useful in the characterization of UCP regulation and the role of key insulin signaling elements for insulin action. Here, we outline common approaches to the generation of adipose tissue cell lines. Furthermore, we propose that the novel technique of generating brown adipocyte lines from a single newborn mouse will be instrumental in gaining further insight into the role of a broad range of signaling molecules in adipose tissue biology and in the pathogenesis of insulin resistance. (C) 2002 Wiley Periodicals, Inc. C1 Med Univ Lubeck, Dept Internal Med 1, D-23538 Lubeck, Germany. Univ Leipzig, Dept Internal Med 3, Leipzig, Germany. Univ Complutense, E-28040 Madrid, Spain. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Klein, J (reprint author), Med Univ Lubeck, Dept Internal Med 1, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM johannes.klein@medinf.mu-luebeck.de FU NIDDK NIH HHS [DK 36836, DK 33201] NR 50 TC 62 Z9 65 U1 3 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0265-9247 J9 BIOESSAYS JI Bioessays PD APR PY 2002 VL 24 IS 4 BP 382 EP 388 DI 10.1002/bioessays.10058 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 538AN UT WOS:000174792000012 PM 11948624 ER PT J AU Hirshfeld-Becker, DR Biederman, J Faraone, SV Violette, H Wrightsman, J Rosenbaum, JF AF Hirshfeld-Becker, DR Biederman, J Faraone, SV Violette, H Wrightsman, J Rosenbaum, JF TI Temperamental correlates of disruptive behavior disorders in young children: Preliminary findings SO BIOLOGICAL PSYCHIATRY LA English DT Article DE disruptive behavior disorders; behavioral disinhibition; attention-deficit/hyperactivity disorder; mood disorders; psychopathology ID DEFICIT-HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; AGE 3 YEARS; DEPRESSIVE-DISORDERS; PANIC DISORDER; PSYCHIATRIC-DISORDERS; LONGITUDINAL EVIDENCE; INHIBITORY CONTROL; SOCIAL PHOBIA; BIRTH COHORT AB Background: Our objective was to test the hypothesis that temperamental behavioral disinhibition measured in early childhood would be associated with disruptive behavior disorders. Methods: We used variables from laboratory-based behavioral observations originally devised to assess behavioral inhibition to construct a theory-based a priori definition of "behavioral disinhibition" in 200 voting children at-risk for panic disorder, depression, or both and 84 children of parents without anxiety or major depressive disorder. We then compared behaviorally disinhibited and nonbehaviorally disinhibited children on rates of DSM-III-R disorders and measures of academic and social dysfunction Results: Behavioral disinhibition was significantly associated with higher rates of disruptive behavior disorders and mood disorders. Children with behavioral disinhibition were significantly, more likely than nondisinhibited, noninhibited children to have attention-deficit/hyperactivity disorder (ADHD) and to have comorbid mood and disruptive behavior disorders. Moreover, disinhibited children had lower Global Assessment of Functioning Scale scores and were more likely, to have been in special classes and to have problems with school behavior and leisure activities. Conclusions: These results suggest that behavioral disinhibition may represent a temperamental precursor to disruptive behavior problems, particularly ADHD. Longitudinal studies using behavioral assessments of behavioral disinhibition are needed to confirm these findings. (C) 2002 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, Pediat Psychopharmacol Unit, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. RP Hirshfeld-Becker, DR (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, Pediat Psychopharmacol Unit, Dept Psychiat, Bldg 149,13th St,Suite 10018, Charlestown, MA 02129 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH 47077-05, MH-01538-02] NR 63 TC 39 Z9 39 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 2002 VL 51 IS 7 BP 563 EP 574 DI 10.1016/S0006-3223(01)01299-9 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 540YU UT WOS:000174959100005 PM 11950458 ER PT J AU Russell, LD Chiarini-Garcia, H Korsmeyer, SJ Knudson, CM AF Russell, LD Chiarini-Garcia, H Korsmeyer, SJ Knudson, CM TI Bax-dependent spermatogonia apoptosis is required for testicular development and spermatogenesis SO BIOLOGY OF REPRODUCTION LA English DT Article DE apoptosis; sperm maturation; spermatogenesis; testis ID BCL-2 PROTEIN FAMILY; GERM-CELL APOPTOSIS; DEFICIENT MICE; NEURONAL DEATH; RAT TESTIS; EXPRESSION; SURVIVAL; MOUSE; SPERMATOCYTES; DEGENERATION AB Bax is a multidomain, proapoptotic member of the Bcl-2 family that is required for normal spermatogenesis in mice. Despite its proapoptotic function, previous results found that Bax-deficient mature male mice demonstrate increased cell death and dramatic testicular atrophy. The present study examined the role of Bax during the normal development of the testis to determine whether the increased cell death in mature mice could be explained by decreased apoptosis earlier in development. Consistent with this hypothesis, testicular atrophy is preceded by increased testicular weight and hypercellular tubules in immature Bax-deficient mice. TUNEL staining at Postnatal Day (P) 7 and morphological quantitation between P5 and P15 demonstrates decreased germ cell apoptosis in Bax-deficient mice. By PIS, increased numbers of type A spermatogonia, and at P12 and P15, an increase in intermediate type spermatogonia were noted in Bax-deficient animals. By P25, the number of basal compartment cells was greatly increased in Bax-deficient animals compared with controls such that four or five layers of preleptotene spermatocytes were routinely present within the basal compartment of the testis. Although the Sertoli cell barrier was significantly removed from the basement membrane, it appeared intact as judged by the hypertonic fixation test. During late pubertal development, massive degeneration of germ cells took place, including many of those cell types that previously survived in the first wave of spermatogenesis. The data indicate that Bax is required for normal developmental germ cell death in the type A spermatogonia, specifically dividing (A,, A,, and A,) spermatogonia, at a time at which the number of spermatogonia is regulated in a density-dependent manner. The massive hyperplasia that occurs in Bax-deficient mice subsequently results in Bax independent cell death that may be triggered by overcrowding of the seminiferous epithelium. C1 Univ Iowa, Dept Pathol, Iowa City, IA 52241 USA. So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst,Dept Pathol & Med, Boston, MA 02115 USA. RP Knudson, CM (reprint author), Univ Iowa, Dept Pathol, Iowa City, IA 52241 USA. RI Chiarini-Garcia, Helio/P-4613-2014 FU NCI NIH HHS [R01 CA 50293]; NICHD NIH HHS [HD 35494] NR 36 TC 114 Z9 121 U1 1 U2 4 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 APR PY 2002 VL 66 IS 4 BP 950 EP 958 DI 10.1095/biolreprod66.4.950 PG 9 WC Reproductive Biology SC Reproductive Biology GA 534LR UT WOS:000174588300012 PM 11906913 ER PT J AU Stier, S Cheng, T Dombkowski, D Carlesso, N Scadden, DT AF Stier, S Cheng, T Dombkowski, D Carlesso, N Scadden, DT TI Notch1 activation increases hematopoietic stem cell self-renewal in vivo and favors lymphoid over myeloid lineage outcome SO BLOOD LA English DT Article ID MOUSE BONE-MARROW; PROGENITOR CELLS; MAMMALIAN NOTCH; HUMAN HOMOLOG; INHIBITS DIFFERENTIATION; EXPRESSION; DELTA; GENE; LIGAND; MICE AB Hematopoietic stem cells sequentially pass through a series of decision points affecting self-renewal or lineage-specific differentiation. Notch1 receptor is a known modulator of lineage-specific events in hematopoiesis that we assessed in the context of in vivo stem cell kinetics. Using RAG-1(-/-) mouse stems cells, we documented increased stem cell numbers due to decreased differentiation and enhanced stem cell self-renewal induced by Notch1. Unexpectedly, preferential lymphoid, over myeloid lineage commitment was noted when differentiation occurred. Therefore, Notch1 iaffects 2 decision points in stem cell regulation, favoring self-renewal over differentiation and lymphoid over myeloid lineage outcome. Notch1 offers an attractive target for stem cell manipulation strategies, particularly in the context of immunodeficiency and acquired immunodeficiency syndrome. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02129 USA. RP Scadden, DT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St,Rm 5212D, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL 45851]; NIDDK NIH HHS [DK 50234, DK 02761] NR 53 TC 251 Z9 269 U1 0 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2002 VL 99 IS 7 BP 2369 EP 2378 DI 10.1182/blood.V99.7.2369 PG 10 WC Hematology SC Hematology GA 533ZC UT WOS:000174559300015 PM 11895769 ER PT J AU Gong, JL Koido, S Chen, DS Tanaka, Y Huang, L Avigan, D Anderson, K Ohno, T Kufe, D AF Gong, JL Koido, S Chen, DS Tanaka, Y Huang, L Avigan, D Anderson, K Ohno, T Kufe, D TI Immunization against murine multiple myeloma with fusions of dendritic and plasmacytoma cells is potentiated by interleukin 12 SO BLOOD LA English DT Article ID CD8(+) T-CELLS; THERAPEUTIC ANTITUMOR IMMUNITY; TUMOR-SPECIFIC RECOGNITION; IN-VIVO; CARCINOMA-CELLS; IDIOTYPE VACCINATION; ANTIGEN; IL-12; LYMPHOCYTES; ACTIVATION AB Fusions of cancer cells and dendritic cells (DCs) are effective in the treatment of animal tumor models and patients with metastatic renal carcinoma. in this study, we have fused DCs with mouse 4TOO plasmacytoma cells. The results demonstrate that vaccination of mice with the fusion cells (FC/4TOO) is associated with induction of antitumor humoral and cytotoxic T lymphocyte (CTL) responses. Immunization with FC/4TOO cells protected mice against tumor challenge. In addition, treatment of established multiple myeloma with FC/4TOO cells was associated with prolongation of survival but not with eradication of disease. As interleukin (IL)-12 potentiates the induction of immune responses, recombinant mouse IL-12 was administered with the FC/4TOO vaccine. Treatment of mice with FC/4TOO and IL-12 was associated with increased CTL activity and T-cell proliferation responses. Treatment with FC/4TOO and IL-12 also resulted in eradication of established disease. These findings demonstrate that immunization with FC/4TOO fusion cells and IL-12 potentiates antitumor Immunity and the treatment of murine multiple myeloma. (C) 2002 by the American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Jikei Univ, Sch Med, Dept Microbiol, Tokyo, Japan. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 78378] NR 40 TC 78 Z9 83 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2002 VL 99 IS 7 BP 2512 EP 2517 DI 10.1182/blood.V99.7.2512 PG 6 WC Hematology SC Hematology GA 533ZC UT WOS:000174559300033 PM 11895787 ER PT J AU Jegalian, AG Acurio, A Dranoff, G Wu, H AF Jegalian, AG Acurio, A Dranoff, G Wu, H TI Erythropoietin receptor haploinsufficiency and in vivo interplay with granulocyte-macrophage colony-stimulating factor and interleukin 3 SO BLOOD LA English DT Article ID BETA-CHAIN; CELL; HEMATOPOIESIS; INVOLVEMENT; LACKING; MARROW AB Erythropoietin (EPO) and its receptor (EPOR) are critical for definitive erythropolesis, as mice lacking either gene product die during embryogenesis with severe anemia. Here we demonstrate that mice expressing just one functional allele of the EpoR have lower hematocrits and die more frequently than do wild-type littermates on anemia induction. Furthermore, EpoR(+/-) erythroid colony-forming unit (CFU-E) progenitors are reduced both in frequency and in responsiveness to EPO stimulation. To evaluate the interaction between EPO and granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin 3 (IL-3), GM-CSF-/- or IL-3(-/-) mice were interbred with EpoR(+/-) mice. Deletion of either GM-CSF or IL-3 also leads to reduction in CFU-E numbers and hematocrits but does not significantly alter steady-state erythroid burst-forming unit numbers. These results suggest EpoR haploinsufficiency and promotion of in vivo erythropoiesis by GM-CSF and IL-3. (C) 2002: by The American Society of Hematology. C1 Univ Calif Los Angeles, Sch Med, Howard Hughes Med Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Inst Mol Biol, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Wu, H (reprint author), Univ Calif Los Angeles, Sch Med, Howard Hughes Med Inst, CHS 23-214, Los Angeles, CA 90095 USA. FU NCI NIH HHS [CA 74886] NR 22 TC 18 Z9 18 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 APR 1 PY 2002 VL 99 IS 7 BP 2603 EP 2605 DI 10.1182/blood.V99.7.2603 PG 3 WC Hematology SC Hematology GA 533ZC UT WOS:000174559300046 PM 11895800 ER PT J AU Hartmann, C Johnk, L Sasaki, H Jenkins, RB Louis, DN AF Hartmann, C Johnk, L Sasaki, H Jenkins, RB Louis, DN TI Novel PLA2G4C polymorphism as a molecular diagnostic assay for 19q loss in human gliomas SO BRAIN PATHOLOGY LA English DT Review ID TUMOR-SUPPRESSOR GENE; CANDIDATE REGION; 1P; OLIGODENDROGLIOMAS; SURVIVAL; CHROMOSOME-19; ASTROCYTOMAS; PREDICTORS; DELETIONS; 19Q13.3 AB PLA2G4C, encoding cytosolic phospholipase A(2)-gamma (cPLA(2)-gamma), is a 17-exon gene located on chromosome 19q13.3 within the putative glioma tumor suppressor gene region. Given the clinical importance of assessing 1p and 19q loss in human gliomas, the development of convenient and practical assays for detecting allelic loss is of considerable priority in neuro-oncology. We report a minisatellite polymorphism in the untranslated region of exon 1, with allelic variants that have one, two or three 27-bp repeats. The polymorphism is informative in 55.7% of a reference population, and accurately detects allelic loss of 19q in human gliomas. This novel marker offers distinct advantages for assessing 19q status in malignant gliomas. The relatively large size of the repeats allows detection of allelic variants with standard ethidium bromide-stained agarose gels and the PLA2G4C marker is the closest polymorphism to the smallest common deletion area in the putative glioma tumor suppressor gene region. These characteristics suggest that the PLA2G4C polymorphism will be a convenient and practical assay for clinical and research evaluation of 19q status in human gliomas. C1 Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mol Pathol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Mayo Clin & Mayo Fdn, Div Lab Genet, Rochester, MN 55905 USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, 149 13th St, Charlestown, MA 02129 USA. EM louis@helix.mgh.harvard.edu RI Hartmann, Christian/D-1882-2010 FU NCI NIH HHS [CA57683, CA69285] NR 22 TC 3 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD APR PY 2002 VL 12 IS 2 BP 178 EP 182 PG 5 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 537HF UT WOS:000174752300005 PM 11958371 ER PT J AU Adamis, AP AF Adamis, AP TI Is diabetic retinopathy an inflammatory disease? SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; ADHESION MOLECULE-1; IN-VIVO; FACTOR EXPRESSION; CELL; NEOVASCULARIZATION; ANGIOGENESIS; INHIBITION; MIGRATION C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Adamis, AP (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 36 TC 166 Z9 204 U1 0 U2 3 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 APR PY 2002 VL 86 IS 4 BP 363 EP 365 DI 10.1136/bjo.86.4.363 PG 3 WC Ophthalmology SC Ophthalmology GA 540QX UT WOS:000174940600001 PM 11914197 ER PT J AU Wittram, C Weisbrod, GL AF Wittram, C Weisbrod, GL TI Mycobacterium avium complex lung disease in immunocompetent patients: radiography-CT correlation SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID PULMONARY-DISEASE; INTRACELLULARE COMPLEX; NONTUBERCULOUS MYCOBACTERIA; INFECTION; DIAGNOSIS AB This study aimed to describe and correlate the chest radiography and CT findings of Mycobacterium avium complex (MAC) lung disease in immunocompetent patients. 26 patients fulfilled The American Thoracic Society criteria for MAC lung disease and underwent chest radiography and CT within 6 weeks of positive cultures. All abnormalities and predominant lobar involvement were recorded and abnormalities on chest radiography were correlated with those on CT. The images were evaluated by two chest radiologists and decisions were reached by consensus. 21 females and 5 males, with an overall mean age of 69 years, were included in the study. All chest radiographs and CT scans were abnormal. On chest radiography, overinflation was demonstrated in IS patients. CT scan abnormalities included atelectasis (n=17), bronchiectasis (n=24), cavities (n=13), consolidation (n=3), emphysema (n=11), ground-glass opacity (n=8), linear opacities (n=26), mediastinal lymphadenopathy (n=3). nodules (n=25) and pleural disease (n=15). CT findings were at variance with chest radiography findings in 15 lobes. A new feature from this Study is that the majority of patients with MAC lung disease demonstrate overinflation on chest radiography. 19% of cases had predominant upper lobe disease, indistinguishable from post-primary Mycobacterium tuberculosis infection. 77% of cases demonstrated the major imaging criteria of MAC lung disease. These are ill defined nodules, bronchiectasis, predominant middle lobe and/or lingular abnormalities, with or without overinflation. We believe that these characteristic radiological signs will assist the physician in the diagnostic work-up of patients with MAC lung disease. C1 Univ Toronto, Toronto Gen Hosp, Dept Med Imaging, Toronto, ON M5G 2C4, Canada. RP Wittram, C (reprint author), Massachusetts Gen Hosp, Sect Thorac Radiol, FND 2,55 Fruit St, Boston, MA 02114 USA. NR 21 TC 36 Z9 46 U1 0 U2 0 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 APR PY 2002 VL 75 IS 892 BP 340 EP 344 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 555PD UT WOS:000175801700003 PM 12000692 ER PT J AU Kondo, K Klco, J Nakamura, E Lechpammer, M Kaelin, WG AF Kondo, K Klco, J Nakamura, E Lechpammer, M Kaelin, WG TI Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein SO CANCER CELL LA English DT Article ID TRANSFORMING-GROWTH-FACTOR; RENAL-CELL CARCINOMA; CENTRAL-NERVOUS-SYSTEM; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; FACTOR-ALPHA; SOMATIC MUTATIONS; FACTOR RECEPTOR; CLEAR-CELL; PROLYL HYDROXYLATION; GENE-EXPRESSION AB Inactivation of the von Hippel-Lindau tumor suppressor gene is linked to the development of hereditary (VHL Disease-associated) and sporadic clear cell carcinoma of the kidney. The VHL gene product, pVHL, targets the heterodimeric transcription factor HIF for polyubiquitination, and restoration of pVHL function in VHL-/- renal carcinoma cells suppresses their ability to form tumors in nude mice. Here we show that tumor suppression by pVHL can be overridden by a HIF variant that escapes pVHL control. These studies prove that HIF is a critical downstream target of pVHL and establish that activation of HIF target genes can promote tumorigenesis in vivo. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. OI Klco, Jeffery/0000-0003-2961-6960 NR 80 TC 484 Z9 495 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD APR PY 2002 VL 1 IS 3 BP 237 EP 246 DI 10.1016/S1535-6108(02)00043-0 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 599TU UT WOS:000178351900007 PM 12086860 ER PT J AU Chan, J Bayliss, PE Wood, JM Roberts, TM AF Chan, J Bayliss, PE Wood, JM Roberts, TM TI Dissection of angiogenic signaling in zebrafish using a chemical genetic approach SO CANCER CELL LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASES; HORMONE-EXPRESSING CELLS; DANIO-RERIO; C-ELEGANS; PROTEIN; TUMOR; AKT; TRANSDUCTION; EMBRYO AB Striking homology between signaling molecules in zebrafish and humans suggests that compounds known to inhibit human kinases may enable a chemical genetic approach to dissect signaling pathways in the zebrafish embryo. We tested this hypothesis using a vascular endothelial growth factor receptor inhibitor, PTK787/ZK222584. Zebrafish embryos treated with this compound lacked all major blood vessels. Overexpression of AKT/PKB, a putative effector of vascular endothelial growth factor signaling, allowed blood vessels to form in the presence of drug. Endothelial cell apoptosis induced by the drug is prevented by increasing AKT/PKB activity, thus establishing the physiological relevance of AKT/PKB in the angiogenic process. This approach allowed us to examine the effects of blood flow and the role of endothelial signals in organogenesis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Novartis Pharma AG, Oncol Res, CH-4002 Basel, Switzerland. RP Chan, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA30002, CA89021]; NICHD NIH HHS [HD24926] NR 58 TC 140 Z9 152 U1 2 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD APR PY 2002 VL 1 IS 3 BP 257 EP 267 DI 10.1016/S1535-6108(02)00042-9 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 599TU UT WOS:000178351900009 PM 12086862 ER PT J AU Bachoo, RM Maher, EA Ligon, KL Sharpless, NE Chan, SS You, MJJ Tang, Y DeFrances, J Stover, E Weissleder, R Rowitch, DH Louis, DN DePinho, RA AF Bachoo, RM Maher, EA Ligon, KL Sharpless, NE Chan, SS You, MJJ Tang, Y DeFrances, J Stover, E Weissleder, R Rowitch, DH Louis, DN DePinho, RA TI Epidermal growth factor receptor and Ink4a/Arf: Convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis SO CANCER CELL LA English DT Article ID HUMAN GLIOMAS; GLIOBLASTOMA-MULTIFORME; GENE AMPLIFICATION; TUMOR SUPPRESSION; P16(INK4A); SENESCENCE; P19(ARF); LINEAGE; INACTIVATION; DEMONSTRATE AB Ink4a/Arf inactivation and epidermal growth factor receptor (EGFR) activation are signature lesions in high-grade gliomas. How these mutations mediate the biological features of these tumors is poorly understood. Here, we demonstrate that combined loss of p16(INK4a) and p19(ARF), but not of p53, p16(INK4a), or p19(ARF), enables astrocyte dedifferentiation in response to EGFR activation. Moreover, transduction of Ink4a/Arf(-/-) neural stem cells (NSCs) or astrocytes with constitutively active EGFR induces a common high-grade glioma phenotype. These findings identify NSCs and astrocytes as equally permissive compartments for gliomagenesis and provide evidence that p16(INK4a) and p19(ARF) synergize to maintain terminal astrocyte differentiation. These data support the view that dysregulation of specific genetic pathways, rather than cell-of-origin, dictates the emergence and phenotype of high-grade gliomas. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Div Neuropathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Ctr Mol Imaging Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU PHS HHS [P30] NR 30 TC 423 Z9 439 U1 0 U2 20 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD APR PY 2002 VL 1 IS 3 BP 269 EP 277 DI 10.1016/S1535-6108(02)00046-6 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 599TU UT WOS:000178351900010 PM 12086863 ER PT J AU Streit, M Stephen, AE Hawighorst, T Matsuda, K Lange-Asschenfeldt, B Brown, LF Vacanti, JP Detmar, M AF Streit, M Stephen, AE Hawighorst, T Matsuda, K Lange-Asschenfeldt, B Brown, LF Vacanti, JP Detmar, M TI Systemic inhibition of tumor growth and angiogenesis by thrombospondin-2 using cell-based antiangiogenic gene therapy SO CANCER RESEARCH LA English DT Article ID ENDOGENOUS INHIBITOR; MICE; METASTASES; CANCER; TRANSPLANTATION; ANGIOSTATIN; ENDOSTATIN; BODY AB Recent studies indicate that continuous administration improves the antitumoral efficacy of angiogenesis inhibitors, as compared with intermittent dosing, suggesting a potential role of gene therapy in antiangiogenic tumor therapy. We established a tissue-engineered implant system for the continuous in vivo production of thrombospondin-2 (TSP-2), a potent endogenous inhibitor of tumor growth and angiogenesis. Fibroblasts were retrovirally transduced to overexpress TSP-2 and were seeded onto biodegradable polymer scaffolds. After transplantation into the peritoneal cavity of nude mice, bioimplants maintained high levels of TSP-2 secretion over extended time periods, resulting in increased levels of circulating TSP-2. Bioimplant-generated TSP-2 potently inhibited tumor growth and angiogenesis of human squamous cell carcinomas, malignant melanomas, and Lewis lung carcinomas that were implanted at a distant site. These results provide the first proof-of-principle for the feasibility and therapeutic efficiency of systemic, cell-based antiangiogenic gene therapy using biodegradable polymer grafts for the treatment of cancer. C1 Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Med Sch, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Med Sch, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Med Sch, Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Bldg 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA71345-04, CA 69184, CA 86410] NR 38 TC 51 Z9 54 U1 0 U2 3 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 APR 1 PY 2002 VL 62 IS 7 BP 2004 EP 2012 PG 9 WC Oncology SC Oncology GA 539TT UT WOS:000174887700014 PM 11929817 ER PT J AU Selzer, E Wacheck, V Lucas, T Heere-Ress, E Wu, M Weilbaecher, KN Schlegel, W Valent, P Wrba, F Pehamberger, H Fisher, D Jansen, B AF Selzer, E Wacheck, V Lucas, T Heere-Ress, E Wu, M Weilbaecher, KN Schlegel, W Valent, P Wrba, F Pehamberger, H Fisher, D Jansen, B TI The melanocyte-specific isoform of the microphthalmia transcription factor affects the phenotype of human melanoma SO CANCER RESEARCH LA English DT Article ID MALIGNANT-MELANOMA; TYROSINASE GENE; HUMAN HOMOLOG; NEURAL CREST; MITF; MUTATIONS; EXPRESSION; LINEAGE; PRODUCT; CLONING AB The microphthalmia transcription factor MITF plays a pivotal role in the development and differentiation of melanocytes. The purpose of this work was to investigate the expression and function of the melanocyte-specific isoform MITF-M in human melanoma. We found that MITF-M is repressed in 8 of 14 established melanoma cell lines tested. Transfection of MITF-M into a melanoma cell line (518A2) lacking the M-isoform and into a permanent cell line established from normal melanocytes (NMel-II) resulted in slower tumor growth in a severe combined immunodeficient-mouse xenotransplantation model. The growth difference between vector control-transfected tumors derived from the NMel-II cell line (mean tumor weight +/- SD, 3.2 g +/- 1.13) and MITF-M (+) transfectants (mean tumor weight +/- SD, 1.1 g +/- 0.49) was significant (P = 0.018). The mean tumor weight of control-transfected 518A2 tumors was 0.99 g +/- 0.22 and of MITF-M (+) transfectants, 0.69 g +/- 0.32. The difference in growth between 518A2 controls and the MIT-M (+) transfectants was clear, however it did not reach statistical significance (P = 0.08). In addition to the growth-inhibitory effects, MITF-M expression led to a change in the histopathological appearance of tumors from epitheloid toward a spindle-cell type in vivo. These results indicate a role for the MITF-M isoform in. p the in vivo growth control and the phenotype of human melanoma. In conclusion, MITF-M may qualify as a marker capable of identifying subgroups of melanoma patients with different tumor biology and prognosis. C1 Univ Hosp Vienna, Dept Radiotherapy & Radiobiol, A-1090 Vienna, Austria. Univ Hosp Vienna, Dept Clin Pharmacol, Sect Expt Oncol & Mol Pharmacol, A-1090 Vienna, Austria. Univ Hosp Vienna, Dept Dermatol, Div Gen Dermatol, A-1090 Vienna, Austria. Univ Hosp Vienna, Dept Internal Med 1, Div Hematol & Hemostascol, A-1090 Vienna, Austria. Univ Hosp Vienna, Dept Clin Pathol, A-1090 Vienna, Austria. Univ Hosp Vienna, Ludwig Boltzmann Inst Clin & Expt Oncol, A-1090 Vienna, Austria. Univ Hosp Vienna, Ctr Excellence Clin & Expt Oncol, A-1090 Vienna, Austria. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Ped Hematol Oncol, Boston, MA 02115 USA. Washington Univ, Dept Med Oncol, St Louis, MO 63110 USA. RP Selzer, E (reprint author), Univ Hosp Vienna, Dept Radiotherapy & Radiobiol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. RI Selzer, Edgar/K-7547-2015 NR 30 TC 50 Z9 56 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 APR 1 PY 2002 VL 62 IS 7 BP 2098 EP 2103 PG 6 WC Oncology SC Oncology GA 539TT UT WOS:000174887700028 PM 11929831 ER PT J AU Dolmans, DEJGJ Kadambi, A Hill, JS Waters, CA Robinson, BC Walker, JP Fukumura, D Jain, RK AF Dolmans, DEJGJ Kadambi, A Hill, JS Waters, CA Robinson, BC Walker, JP Fukumura, D Jain, RK TI Vascular accumulation of a novel photosensitizer, MV6401, causes selective thrombosis in tumor vessels after photodynamic therapy SO CANCER RESEARCH LA English DT Article ID NITRIC-OXIDE; MICROCIRCULATION; TISSUE; MICE AB The antivascular effects of photodynamic therapy (PDT) and their mechanisms are not clearly understood. Here, we examined the effects of PDT with a novel photosensitizer MV6401 on the microvasculature in a mammary tumor (MCaIV) grown in a murine dorsal skinfold chamber and in normal tissue controls. The mice were irradiated with light 15 min after i.v. administration of MV6401 when the drug was localized only in the vascular compartment, as shown by fluorescence microscopy and immunohistochemistry. PDT with MV6401 caused a dose-dependent biphasic blood flow stasis and vascular hyperpermeability, as determined by intravital microscopy. This biphasic response was classified into two components: (a) an acute response observed immediately after PDT; and (b) a long-term response observed at times greater than 3 h after PDT. The acute temporal vascular effects were characteristic of vasoconstriction but not of thrombus formation. However, the long-term vascular shutdown was mediated by thrombus formation, as evidenced by histological evaluation and inhibition with heparin. Minimal effects were observed in normal vessels after antivascular doses used against the tumor, but there was no long-term vascular damage. In concert with the stasis, a dose-dependent tumor growth delay was observed. This study provides mechanistic insights into antitumor vascular effects of PDT and suggests novel strategies for tumor treatment with PDT. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Miravant Med Technol, Santa Barbara, CA 93117 USA. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 734, Boston, MA 02114 USA. FU NCI NIH HHS [P01-CA80124] NR 20 TC 89 Z9 99 U1 3 U2 9 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 APR 1 PY 2002 VL 62 IS 7 BP 2151 EP 2156 PG 6 WC Oncology SC Oncology GA 539TT UT WOS:000174887700034 PM 11929837 ER PT J AU Eischen, CM Rehg, JE Korsmeyer, SJ Cleveland, JL AF Eischen, CM Rehg, JE Korsmeyer, SJ Cleveland, JL TI Loss of Bax alters tumor spectrum and tumor numbers in ARF-deficient mice SO CANCER RESEARCH LA English DT Article ID MYC-INDUCED APOPTOSIS; ACUTE LYMPHOBLASTIC-LEUKEMIA; WILD-TYPE P53; BCL-X-L; TRANSGENIC MICE; HEMATOPOIETIC MALIGNANCIES; MICROSATELLITE INSTABILITY; P53-DEPENDENT APOPTOSIS; LYMPHOID HYPERPLASIA; GASTRIC-CANCER AB p19(ARF) is a key regulator of the p53-mediated apoptotic and tumor suppressor pathway. The proapoptotic Bax gene is a transcription target of p53, yet genetic studies in some animal models have suggested that Bax and p53 loss may cooperate in tumorigenesis. ARF-deficient mice are tumor prone, and to determine whether Bax loss could cooperate in the development of these tumors, we generated mice null for both ARF and Bax. The tumor latency of Bax(+/+)ARF(-/-), Bax(+/-)ARF(-/-), and Bax(-/-)ARF(-/-) mice was similar with a mean survival of 48.9, 48.1, and 47.6 weeks, respectively. In Bax(+/+)ARF(-/-) mice, the predominant tumor type was B- and T-cell lymphoma followed by sarcomas and a lack of carcinomas. However, the frequency of lymphoma development dramatically decreased, whereas that of sarcomas and carcinomas increased, in a gene dosage-dependent manner in Bax(+/-)ARF(-/-) and Bax(-/-)ARF(-/-) mice. Furthermore, uncommon tumors of ARF(-/-) mice (osteosarcoma and hemangiosarcoma) were observed in Bax/ARF-double null mice, and tumor types not described previously in ARF-null mice (mixed germ cell tumor, Triton tumor, and histiocytic sarcoma) also developed in Bax(-/-)ARF(-/-) animals. Importantly, multiple primary malignant tumors of different lineage arose in 25% of the Bax(-/-)ARF(-/-) mice, whereas only one tumor type per animal was observed in Bax(+/+)ARF-null littermates. Finally, the wild-type Bax allele, was retained in tumors arising in Bax(+/-)ARF(-/-) mice. Thus, Bax appears to function as a tumor modifier rather than as a classic tumor suppressor, and the combined loss of Bax and the ARF allows for the emergence of multiple malignant tumor types, an alteration of the tumor spectrum, and tumors not observed previously in ARF-null mice. C1 St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Cleveland, JL (reprint author), St Jude Childrens Res Hosp, Dept Biochem, 332 N Lauderdale St, Memphis, TN 38105 USA. EM john.cleveland@stjude.org FU NCI NIH HHS [CA81695, CA-21765, CA76379]; NIDDK NIH HHS [DK44158] NR 59 TC 31 Z9 31 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2002 VL 62 IS 7 BP 2184 EP 2191 PG 8 WC Oncology SC Oncology GA 539TT UT WOS:000174887700039 PM 11929842 ER PT J AU Sheynberg, BV Jang, IK Han, RO Sabatine, MS Brown, DFM Dinsmore, R AF Sheynberg, BV Jang, IK Han, RO Sabatine, MS Brown, DFM Dinsmore, R TI Comparison of two different methods of quantitative coronary angiography in patients with acute coronary syndromes SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE quantitative coronary angiography; gradual field transform; minimal cost algorithm; acute myocardial infarction; complex lesions ID MYOCARDIAL-INFARCTION; ARTERY DISEASE; ANGIOPLASTY; VALIDATION; MULTICENTER; PROGRESSION; MORPHOLOGY; ULTRASOUND; STENOSIS AB The minimal cost algorithm (MCA) commonly used for quantitative coronary arteriography has limitations in definition of complex lesion morphology. A gradient field transform (GFT) algorithm has been designed for the better analysis of complex lesions. We compared MCA with GFT in angiograms of 125 patients in the Myocardial Infarction with Novastan and t-PA (MINT) trial. Lesion border definition was rated as one (poor), two (good), or three (very good). While MCA- and GFT-derived reference diameters (RDs) were similar, GFT yielded smaller minimal lumen diameter (MLD) than MCA by 0.22 +/- 0.31 mm (P < 0.01), and the difference between GFT- and MCA-derived MLDs increased with decreasing MLD. Mean percent diameter stenosis (% DS) was 9.1% +/- 11.1% greater by GFT (P < 0.001). Lesion border definition in simple lesions was similar (not significantly different). However, in complex lesions GFT performed better (2.49 +/- 0.61 vs. 2.11 +/- 0.74; P < 0.05). Thus, GFT appears to improve analysis of complex lesions compared to MCA. GFTs role in angiographic trials and clinical practice deserves further study. (C) 2002 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Dept Med, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. EM jang.ik@mgh.harvard.edu NR 18 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD APR PY 2002 VL 55 IS 4 BP 442 EP 449 DI 10.1002/ccd.10156 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 532RA UT WOS:000174487800006 PM 11948889 ER PT J AU Bassing, CH Swat, W Alt, FW AF Bassing, CH Swat, W Alt, FW TI The mechanism and regulation of chromosomal V(D)J recombination SO CELL LA English DT Review ID STRAND BREAK REPAIR; DNA-LIGASE-IV; TCR-BETA LOCUS; SEVERE COMBINED IMMUNODEFICIENCY; VARIABLE REGION GENES; T-CELL DEVELOPMENT; ALLELIC EXCLUSION; ANTIGEN-RECEPTOR; RAG2 PROTEINS; IN-VITRO AB V(D)J recombination is of fundamental importance to the generation of diverse antigen receptor repertoires. We review our current understanding of the V(D)J recombination reaction and how it is regulated during lymphocyte development. We also discuss how defects in the mechanism or regulation of V(D)J recombination can lead to human disease. C1 Childrens Hosp, Ctr Blood Res, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, Ctr Blood Res, Howard Hughes Med Inst, 300 Longwood Ave, Boston, MA 02115 USA. NR 108 TC 337 Z9 348 U1 2 U2 29 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR PY 2002 VL 109 SU S BP S45 EP S55 DI 10.1016/S0092-8674(02)00675-X PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 544UY UT WOS:000175181100005 PM 11983152 ER PT J AU Magdalena, J Goldberg, MB AF Magdalena, J Goldberg, MB TI Quantification of Shigella IcsA required for bacterial actin polymerization SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE actin tail; actin cloud; actin-based motility; Xenopus egg cytoplasmic extracts; intracellular motility ID SURFACE PROTEIN ICSA; LISTERIA-MONOCYTOGENES; UNIPOLAR LOCALIZATION; FLEXNERI 2A; INTRACELLULAR MOVEMENT; INTERCELLULAR SPREAD; FUNCTIONAL-ANALYSIS; MAMMALIAN-CELLS; OUTER-MEMBRANE; LARGE PLASMID AB Shigella move through the cytoplasm of host cells by active polymerization of host actin to form an "actin tail." Actin tail assembly is mediated by the Shigella protein IcsA. The process of Shigella actin assembly has been studied extensively using IcsA-expressing Escherichia coli in cytoplasmic extracts of Xenopus eggs. However, for reasons that have been unclear, wild type Shigella does not assemble actin in these extracts. We show that the defect in actin assembly in Xenopus extracts by Shigella can be rescued by increasing IcsA expression by approximately 3-fold. We calculate that the number of IcsA molecules required on an individual bacterium to assemble actin filaments in extracts is approximately 1,500-2,100 molecules, and the number of IcsA molecules required to assemble an actin tail is approximately 4,000 molecules. The majority of wild type Shigella do not express these levels of IcsA when grown in vitro. However, in infected host cells, IcsA expression is increased 3.2-fold, such that the number of IcsA molecules on a significant percentage of intracellular wild type Shigella would exceed that required for actin assembly in extracts. Thus, the number of IcsA molecules estimated from our studies in extracts as being required on an individual bacterium to assemble actin filaments or an actin tail is a reasonable prediction of the numbers required for these functions in Shigella-infected cells. (C) 2002 Wiley-Liss, Inc. C1 Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Goldberg, MB (reprint author), Bacterial Pathogenesis Grp, Univ Pk,65 Landsdowne St,Room 423, Cambridge, MA 02139 USA. FU NIAID NIH HHS [AI35817] NR 41 TC 16 Z9 17 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 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PD APR PY 2002 VL 51 IS 4 BP 187 EP 196 DI 10.1002/cm.10024 PG 10 WC Cell Biology SC Cell Biology GA 546GF UT WOS:000175264900003 PM 11977093 ER PT J AU Wang, YH Knowlton, AA Li, FH Borkan, SC AF Wang, YH Knowlton, AA Li, FH Borkan, SC TI Hsp72 expression enhances survival in adenosine triphosphate-depleted renal epithelial cells SO CELL STRESS & CHAPERONES LA English DT Article ID SHOCK-PROTEIN HSP70; HEAT-SHOCK-PROTEIN-70 INHIBITS APOPTOSIS; HEAT-STRESS; NUCLEAR ACCUMULATION; ISCHEMIC-INJURY; CYTOCHROME-C; ACTIVATION; PROTECTION; PATHWAY; OVEREXPRESSION AB Although prior heat stress (HS) inhibits apoptosis in adenosine phosphate (ATP)-depleted renal epithelial cells (REC), the specific stress protein(s) responsible for cytoprotection have not been identified. The present study evaluated the hypothesis that Hsp72, the major inducible member of the Hsp70 family, protects REC against ATP depletion injury. In the presence of isopropyl-p-D-thiogalactoside (IPTG), a stable line of transfected opossum kidney cells was induced to overexpress human Hsp72 tagged with the flag epitope. Transfected cells from 2 clones that expressed Hsp72 at a level comparable with wild-type cells were subjected to transient heat stress (43degreesC for 1 hour). To assess the cytoprotective effect of Hsp72, transfected cells were subjected to transient ATIP depletion followed by recovery in the presence vs the absence of IPTG. ATP depletion resulted in nuclear chromatin condensation without cell membrane injury (ie, minimal leak of lactate dehydrogenase) and activation of caspase-3, confirming that apoptosis is the major cause of cell death. In both clones cell survival 1-3 days after ATP depletion was significantly improved in the presence of IPTG. Selective overexpression of Hsp72 reproduced nearly 60% of the protective effect on the survival afforded by prior heat stress. In transfected cells subjected to ATP depletion, Hsp72 overexpression significantly inhibited caspase activation. In native renal cells brief ATP depletion markedly induced the expression of native Hsp72, a finding identical to that observed after renal ischemia in vivo. These studies are the first to directly show that Hsp72 per se mediates acquired resistance to ischemic injury in REC. C1 Boston Univ, Renal Sect, Boston Med Ctr, Evans Biomed Res Ctr, Boston, MA 02118 USA. Tufts New England Med Ctr, Dept Pathol, Boston, MA USA. Baylor Coll Med, Vet Adm Hosp, Cardiovasc Res Unit, Houston, TX 77030 USA. RP Borkan, SC (reprint author), Boston Univ, Renal Sect, Boston Med Ctr, Evans Biomed Res Ctr, Room 547,88 E Newton St, Boston, MA 02118 USA. FU NHLBI NIH HHS [HL-58515]; NIDDK NIH HHS [DK-53387, R01 DK053387] NR 46 TC 25 Z9 25 U1 0 U2 2 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD APR PY 2002 VL 7 IS 2 BP 137 EP 145 DI 10.1379/1466-1268(2002)007<0137:HEESIA>2.0.CO;2 PG 9 WC Cell Biology SC Cell Biology GA 631XU UT WOS:000180194000003 PM 12380681 ER PT J AU Knuefermann, P Nemoto, S Baumgarten, G Misra, A Sivasubramanian, N Carabello, BA Vallejo, JG AF Knuefermann, P Nemoto, S Baumgarten, G Misra, A Sivasubramanian, N Carabello, BA Vallejo, JG TI Cardiac inflammation and innate immunity in septic shock - Is there a role for Toll-like receptors? SO CHEST LA English DT Article DE cytokines; innate immunity; myocardial dysfunction; septic shock; Toll-like receptors ID TUMOR-NECROSIS-FACTOR; CELL WALL COMPONENTS; FACTOR-KAPPA-B; FACTOR-ALPHA; MONOCLONAL-ANTIBODY; MYOCARDIAL DEPRESSION; DROSOPHILA TOLL; SEPSIS SYNDROME; FUSION PROTEIN; CUTTING EDGE AB Our current understanding of the pathogenesis of sepsis suggests that bacteria as well as bacterial-derived products activate an uncontrolled network of host-derived mediators such as proinflammatory cytokines (ie, tumor necrosis factor [TNF] and interleukin [IL]-1beta), which can ultimately lead to cardiovascular collapse and death. Despite the potentially important role that TNF and IL-1beta may, play in producing cardiac dysfunction in human septic shock, little is known with regard to the basic biochemical mechanism(s) by which bacterial pathogens induce their expression in the heart. A major advance in understanding the early 7 events that are downstream from bacterial-mediated signaling has been the identification 4 Toll-like receptors (TLRs). TLR-mediated signaling is known to activate the transcription factor nuclear factor-kappaB and to upregulate TNF expression. It has recently been shown that the heart expresses TLRs, raising the possibility that these receptors may be responsible for mediating the deleterious effects of bacterial pathogens on cardiac function. In this review, we will discuss the emerging role for TLRs in the pathogenesis of the cardiovascular collapse that occurs during sepsis. C1 Baylor Coll Med, Dept Pediat, Infect Dis Sect, Houston, TX 77030 USA. Baylor Coll Med, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Dept Med, Houston, TX USA. RP Vallejo, JG (reprint author), Baylor Coll Med, Dept Pediat, Infect Dis Sect, 1 Plaza,Room 302A, Houston, TX 77030 USA. FU NIGMS NIH HHS [R01 GM6274-01] NR 66 TC 47 Z9 58 U1 0 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 2002 VL 121 IS 4 BP 1329 EP 1336 DI 10.1378/chest.121.4.1329 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 545PM UT WOS:000175226400049 PM 11948070 ER PT J AU Monsky, WL Carreira, CM Tsuzuki, Y Gohongi, T Fukumura, D Jain, RK AF Monsky, WL Carreira, CM Tsuzuki, Y Gohongi, T Fukumura, D Jain, RK TI Role of host microenvironment in angiogenesis and microvascular functions in human breast cancer xenografts: mammary fat pad versus cranial tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; HUMAN ADENOCARCINOMA LS174T; SCID MICE; CARCINOMA; METASTASIS; VESSELS; MICROCIRCULATION; TRANSPORT; ANTIBODY AB Purpose: The host microenvironment differs between primary and metastatic sites, affecting gene expression and various physiological functions. Here we show the differences In the physiological parameters between orthotopic primary and metastatic breast tumor xenografts using intravital microscopy and reveal the relationship between angiogenic gene expression and microvascular functions in vivo. Experimental Design: ZR75-1, a human estrogen-dependent mammary carcinoma, was implanted into the mammary fat pad (primary site) of ovariectomized SCID female mice carrying estrogen pellets. The same tumor line was also grown in the cranial window (metastasis site). When tumors reached the diameter of 2.5 mm, angiogenesis, hemodynamics, and vascular permeability were measured by intravital microscopy, and expression of angiogenic growth factors was determined by quantitative reverse transcription-PCR. Results: ZR75-1 tumors grown in the mammary fat pad had higher microvascular permeability but lower vascular density than the same tumors grown in the cranial window (2.5- and 0.7-fold, respectively). There was no significant difference in RBC velocity, vessel diameter, blood flow rate, and shear rate between two sites. The levels of vascular endothelial growth factor (VEGF), its receptors VEGFR1 and VEGFR2, and angiopoietin-1 mRNA tended to be higher in the mammary fat pad tumors than in the cranial tumors (1.5-, 1.5-, 3-, and 2-fold, respectively). Conclusions: The primary breast cancer exhibited higher vascular permeability, but the cranial tumor showed more angiogenesis, suggesting that the cranial environment is leakage resistant but proangiogenic. Collectively, host microenvironment is an important determinant of tumor gene expression and microvascular functions, and, thus, orthotopic breast tumor models should be useful for obtaining clinically relevant information. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fukumura, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin Steele Lab, 100 Blossom St,Cox 736, Boston, MA 02114 USA. FU NCI NIH HHS [P01-CA80124] NR 30 TC 91 Z9 94 U1 0 U2 5 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 APR PY 2002 VL 8 IS 4 BP 1008 EP 1013 PG 6 WC Oncology SC Oncology GA 540TU UT WOS:000174946200013 PM 11948107 ER PT J AU Vollmer, RT Kantoff, PW Dawson, NA Vogelzang, NJ AF Vollmer, RT Kantoff, PW Dawson, NA Vogelzang, NJ TI Importance of serum hemoglobin in hormone refractory prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID LEUKEMIA GROUP-B; MEGESTROL-ACETATE; CARCINOMA; ANTIGEN; SCORE AB Objectives: In the search for an early measure of response in hormone refractory prostate cancer (HRPC), most have targeted changes in serum prostate-specific antigen (PSA). Up to this point, no one has targeted changes in serum hemoglobin during treatment. If dynamic changes in hemoglobin after treatment provide additive prognostic information to dynamic changes in PSA, then we should consider and test ways to incorporate serum hemoglobin into measures of response in HRPC. Methods: Our patients consisted of 321 men who were studied on Cancer and Leukemia Group B protocols 9181 and 9182. We fit serial values of PSA and hemoglobin with an exponential model: y = exp(alpha + beta*t + gamma*t(2)) with y symbolizing either PSA or hemoglobin and t denoting time. We then used the Cox proportional hazard model to relate the parameters of the model (alpha, beta, and gamma) to subsequent survival. Results: We found that the exponential model fit serial measurements of both PSA and serum hemoglobin well, and all three of the parameters for both markers related closely to subsequent survival (P less than or equal to 0.003). The Cox model suggested a composite hazard score (HS) as a way to consolidate the information from serial measurements of both serum markers, and we observed that those with HS < 0 enjoyed a longer survival. Conclusion: Because serial measurements of serum hemoglobin during treatment of HRPC add prognostic information to serial measurements of PSA, we hypothesize that combining the dynamic changes in serum hemoglobin with those of PSA could lead to an improved measure of response in HRPC. C1 VA Med Ctr, Lab Med 113, Durham, NC 27705 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27705 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Dept Adult Oncol, Boston, MA 02115 USA. Univ Maryland, Med Ctr, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Chicago, Canc Res Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA. RP Vollmer, RT (reprint author), VA Med Ctr, Lab Med 113, Durham, NC 27705 USA. NR 13 TC 14 Z9 15 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 2002 VL 8 IS 4 BP 1049 EP 1053 PG 5 WC Oncology SC Oncology GA 540TU UT WOS:000174946200018 PM 11948112 ER PT J AU Malik, SN Brattain, M Ghosh, PM Troyer, DA Prihoda, T Bedolla, R Kreisberg, JI AF Malik, SN Brattain, M Ghosh, PM Troyer, DA Prihoda, T Bedolla, R Kreisberg, JI TI Immunohistochemical demonstration of phospho-Akt in high Gleason grade prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-B; PROGRESSION; EXPRESSION; ACTIVATION AB Purpose: Whereas the early stage of prostate cancer is marked by excessive proliferation, in advanced stages of the disease, a decreased apoptotic death rate (increased cell survival) also contributes to net tumor growth. Altered regulation of the mitogen-activated protein kinase (MAPK)regulated cell proliferation and Akt-regulated cell survival pathways are suspected causes. In this study, we wanted to determine: (a) whether the degree of Akt activation can be assessed by immunohistochemical staining of paraffin-embedded human prostate cancer biopsies with an antibody to phospho-Akt (Ser473); and (b) whether phospho-MAPK/Erk1/2 and phospho-Akt expression are altered in prostate cancer. Experimental design: To examine the activation status of MAPK/Erk1/2 and Akt, archival paraffin-embedded sections from 74 cases of resected prostate cancer were immunostained with antibodies to phospho-MAPK/Erk1/2 (Thr202/Tyr204) and phospho-Akt (Ser473). Results: The staining intensity for phospho-Akt was significantly greater in Gleason grades 8-10 (92% of such cases staining strongly) compared with prostatic intraepithelial neoplasia and all other grades of prostate cancer (only 10% of these cases staining strongly; P less than or equal to 0.001). The staining intensity for phospho-MAPK/Erk, on the other hand, was significantly greater for normal, hyperplastic, and prostatic intraepithelial neoplasia lesions but declined with disease progression, reaching its lowest level of expression in high Gleason grades 8-10 (P < 0.0001). Conclusion: The activation state of the cell survival protein Akt can be analyzed in human prostate cancer by immunohistochemical staining of paraffin-embedded tissue with a phospho-specific Akt (Ser473) antibody. Advanced disease is accompanied by activation of Akt and inactivation of Erk. C1 Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Kreisberg, JI (reprint author), Univ Texas, Hlth Sci Ctr, Dept Surg, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 13 TC 246 Z9 264 U1 1 U2 3 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 APR PY 2002 VL 8 IS 4 BP 1168 EP 1171 PG 4 WC Oncology SC Oncology GA 540TU UT WOS:000174946200035 PM 11948129 ER PT J AU Helmlinger, G Schell, A Dellian, M Forbes, NS Jain, RK AF Helmlinger, G Schell, A Dellian, M Forbes, NS Jain, RK TI Acid production in glycolysis-impaired tumors provides new insights into tumor metabolism SO CLINICAL CANCER RESEARCH LA English DT Article ID PENTOSE-PHOSPHATE PATHWAY; HIGH LACTATE LEVELS; INTERSTITIAL PH; SOLID TUMORS; LACTIC-ACID; CELLS; GROWTH; CANCER; GLUCOSE; HYPERTHERMIA AB Purpose: Low extracellular pH is a hallmark of solid tumors. It has long been thought that this acidity is mainly attributable to the production of lactic acid. In this study, we tested the hypothesis that lactate is not the only source of acidification in solid tumors and explored the potential mechanisms underlying these often-observed high rates of acid production. Experimental Design: We compared the metabolic profiles of glycolysis-impaired (phosphoglucose isomerase-deficient) and parental cells in both in vitro and two in vivo models (dorsal skinfold chamber and Gullino chamber). Results: We demonstrated that CO2 in addition to lactic acid, was a significant source of acidity in tumors. We also found evidence supporting the hypothesis that tumor cells rely on glutaminolysis for energy production and that the pentose phosphate pathway is highly active within tumor cells. Our results also suggest that the tricarboxylic acid cycle is saturable and that different metabolic pathways are activated to provide for energy production and biosynthesis. Conclusions: These results are consistent with the paradigm that tumor metabolism is determined mainly by substrate availability and not by the metabolic demand of tumor cells per se. In particular, it appears that the local glucose and oxygen availabilities each independently affect tumor acidity. These findings have significant implications for cancer treatment. C1 Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Cox-7, Boston, MA 02114 USA. OI Sckell, Axel/0000-0002-9992-0784 FU NCI NIH HHS [P01-CA-80124, R35-CA-56591, T32-CA-73479] NR 48 TC 221 Z9 226 U1 2 U2 21 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 APR PY 2002 VL 8 IS 4 BP 1284 EP 1291 PG 8 WC Oncology SC Oncology GA 540TU UT WOS:000174946200050 PM 11948144 ER PT J AU Mitty, JA Stone, VE Sands, M Macalino, G Flanigan, T AF Mitty, JA Stone, VE Sands, M Macalino, G Flanigan, T TI Directly observed therapy for the treatment of people with human immunodeficiency virus infection: A work in progress SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ANTIRETROVIRAL THERAPY; COMBINATION THERAPY; PLUS ZIDOVUDINE; DRUG-USERS; TUBERCULOSIS; HIV; DIDANOSINE; ADULTS; TOLERABILITY; EXPERIENCE AB The principle of directly observed therapy (DOT) has its roots in the treatment of tuberculosis (TB), for which DOT programs have improved cure rates in hard-to-reach populations. Human immunodeficiency virus (HIV) and TB affect similar populations, and there are concerns about both regarding the development of drug resistance associated with poor adherence to therapy. Accordingly, DOT may benefit certain HIV-infected people who have difficulty adhering to highly active antiretroviral therapy. However, important differences exist in the treatment of these diseases that raise questions about how DOT can be adapted to HIV therapy. DOT for management of HIV infection has been effective among prisoners and in pilot programs in Haiti, Rhode Island, and Florida. Although DOT can successfully treat HIV infection in marginalized populations in the short term, a multitude of questions remain. This review provides an account of the preliminary development of DOT programs for the treatment of HIV-infected individuals. C1 Miriam Hosp, Div Infect Dis, Providence, RI 02906 USA. Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. Univ Florida, Dept Internal Med, Infect & Communicable Dis Div, Jacksonville, FL USA. Duval Cty Hlth Dept, Jacksonville, FL USA. RP Mitty, JA (reprint author), Miriam Hosp, Div Infect Dis, 164 Summit Ave, Providence, RI 02906 USA. FU NIAID NIH HHS [5P30 AI 42853]; NIDA NIH HHS [1 R01 DA 13767).] NR 45 TC 75 Z9 77 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2002 VL 34 IS 7 BP 984 EP 990 DI 10.1086/339447 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 529WJ UT WOS:000174324000014 PM 11880965 ER PT J AU Mankin, HJ Fondren, G Hornicek, FJ Gebhardt, MC Rosenberg, AE AF Mankin, HJ Fondren, G Hornicek, FJ Gebhardt, MC Rosenberg, AE TI The use of flow cytometry in assessing malignancy in bone and soft tissue tumors SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Meeting of the Musculoskeletal-Tumor-Society CY MAY, 2001 CL BALTIMORE, MARYLAND SP Musculoskeletal Tumor Soc ID CELLULAR DNA CONTENT; PRIMARY BREAST-CANCER; STAGE BLADDER-TUMORS; HUMAN SOLID TUMORS; CLINICAL-APPLICATIONS; PROGNOSTIC FACTORS; LUNG-CANCER; PLOIDY; CARCINOMA; SURVIVAL AB Since 1982, the orthopaedic research laboratories at the authors' hospital has done flow cytometric and more recently cytofluorometric deoxyribonucleic ploidic analyses of samples of bone and soft tissue tumors. The current authors attempt to define the value of such studies in distinguishing benign from malignant tumors, in conforming to stage of the tumors, and in helping to predict metastasis and death. The series consists of 1134 patients in whom the disease was verified and the survival data were available as a result of a questionnaire study. Statistically, the ploidic analyses were of remarkable value in defining malignancy and in correlating with the stage of the lesion. They were of less value in predicting survival, particularly for patients with osteosarcoma and chondrosarcoma, but seemed to predict survival effectively for patients with soft tissue sarcomas. C1 Massachusetts Gen Hosp, Dept Pathol, Orthopaed Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Orthopaed Oncol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, Orthopaed Serv, Gray 604, Boston, MA 02114 USA. NR 58 TC 10 Z9 11 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 APR PY 2002 IS 397 BP 95 EP 105 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 545KT UT WOS:000175216900014 PM 11953601 ER PT J AU Fox, EJ Hau, MA Gebhardt, MC Hornicek, FJ Tomford, WW Mankin, HJ AF Fox, EJ Hau, MA Gebhardt, MC Hornicek, FJ Tomford, WW Mankin, HJ TI Long-term followup of proximal femoral allografts SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Meeting of the Musculoskeletal-Tumor-Society CY MAY, 2001 CL BALTIMORE, MARYLAND SP Musculoskeletal Tumor Soc ID BONE-TUMORS; RECONSTRUCTION; TRANSPLANTATION; RESECTION; FEMUR AB Between 1972 and 1999, the orthopaedic service at the authors' institution treated 137 patients with proximal femoral bone lesions by resection and reconstruction with frozen allografts from cadavers. The data were entered into a computer program allowing a comprehensive analysis. Thirty-eight patients had proximal femoral osteoarticular allografts, 69 had allograft-endoprosthesis composites, 22 had intercalary allografts, and eight had an allograft arthrodesis. There were 74 complications in 54 of the 137 patients with allografts, which included 26 allograft fractures (19%), 15 infections (11%), and 20 nonunions (15%). The overall success rate for the patients with these procedures was 103 of 137 (75%) at a mean followup of 7.9 years +/-5.6 years. If the eight patients with tumor recurrences (surgical failures rather than allograft failures) are not included, the success rate is 103 of 129 (800). Eighty-three of these patients (55%) without any allograft complications who have been treated and followed up for at least 2 years had a 92% success rate. It is concluded that although allograft reconstruction after resection of the proxioral femur for patients with aggressive or malignant tumors has a high complication rate, approximately 80% of the patients have a successful outcome. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Serv, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Serv, Gray 604, Boston, MA 02114 USA. NR 31 TC 58 Z9 62 U1 0 U2 2 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 APR PY 2002 IS 397 BP 106 EP 113 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 545KT UT WOS:000175216900015 PM 11953602 ER PT J AU Lee, FYI Storer, S Hazan, EJ Gebhardt, MC Mankin, HJ AF Lee, FYI Storer, S Hazan, EJ Gebhardt, MC Mankin, HJ TI Repair of bone allograft fracture using bone morphogenetic protein-2 SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Meeting of the Musculoskeletal-Tumor-Society CY MAY, 2001 CL BALTIMORE, MARYLAND SP Musculoskeletal Tumor Soc ID MODEL AB Long-term clinical data have shown that reconstruction using bone allografts provide adequate function after extensive tumor surgery. Complications such as nonunion of allograft-host interface, infection, and allograft fracture often require major revision surgeries. Allograft fractures usually do not induce the same repair process that is seen in normal fracture healing. The authors did an experimental study to test whether bone morphogenetic protein-2 can induce and achieve osseous repair in an allograft osteotomy model. Recombinant human bone morphogenetic protein-2 was applied at femoral intercalary allograft osteotomy sites in 20 rats. Forty additional rats served as controls (carrier alone and sham). Specimens in all groups were examined histologically and radiographically at 4 and 8 weeks. Specimens in the control groups showed only fibrosis by 8 weeks. In contrast, none of 10 specimens in the experimental group showed radiographic union at 8 weeks. New bone formation and integration with underlying allografts were seen in the experimental group as early as 4 weeks. These data suggest that fracture repair in the allograft bone can be triggered by a biologic regulator that is expressed during normal fracture healing. C1 Massachusetts Gen Hosp, Orthopaed Oncol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Orthopaed Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lee, FYI (reprint author), Columbia Univ Coll Phys & Surg, Dept Orthopaed Surg, 622 W 168th St,PH 11, New York, NY 10032 USA. NR 25 TC 26 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 2002 IS 397 BP 119 EP 126 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 545KT UT WOS:000175216900017 PM 11953604 ER PT J AU Refaat, Y Gunnoe, J Hornicek, FJ Mankin, HJ AF Refaat, Y Gunnoe, J Hornicek, FJ Mankin, HJ TI Comparison of quality of life after amputation or limb salvage SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Meeting of the Musculoskeletal-Tumor-Society CY MAY, 2001 CL BALTIMORE, MARYLAND SP Musculoskeletal Tumor Soc ID OSTEO-SARCOMA; BONE AB In the past, amputation was the standard method of treatment for patients with sarcomas in the extremity but limb-sparing procedures now, are much more frequent. A computerized questionnaire automatically adjusted for gender, age, diagnosis, site, and treatment was sent to 2200 patients with high-grade sarcomas who had been treated during the past 25 years. Using the data, it was possible to study and compare the response from 66 patients who had an amputation and 3:12 patients with a limb-sparing procedure for a lower extremity neoplasm. More males had an amputation, but no differences were observed in the ages of the two groups. The outcomes for the two groups were similar. Patients who had limb-sparing procedures did not have a significant improvement in the ability to ambulate, climb stairs, drive a car, or be employed. More of the patients with amputations required walking aids and participated in sports activities at almost the same rate as the patients who had limb-sparing procedures. Patients who had amputations had no more anxiety, drug-dependence, depression, sleep problems, or limitation of sexual performance than patients who retained their limbs. The patients with amputations had more children and fewer menstrual problems; however, they were far less satisfied with their status at early ages than at later periods in their lives. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Serv, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Serv, Gray 604, Boston, MA 02114 USA. NR 25 TC 63 Z9 70 U1 0 U2 3 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 APR PY 2002 IS 397 BP 298 EP 305 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 545KT UT WOS:000175216900034 PM 11953621 ER PT J AU Durcan, MJ Deener, G White, J Johnston, JA Gonzales, D Niaura, R Rigotti, N Sachs, DPL AF Durcan, MJ Deener, G White, J Johnston, JA Gonzales, D Niaura, R Rigotti, N Sachs, DPL TI The effect of bupropion sustained-release on cigarette craving after smoking cessation SO CLINICAL THERAPEUTICS LA English DT Article DE smoking cessation; craving; bupropion sustained-release; relapse prevention; nicotine ID TOBACCO WITHDRAWAL; CONTROLLED TRIAL; RELAPSE; PREDICTORS; NICOTINE; SYMPTOMS; SMOKERS; PLACEBO AB Background: Most (>50%) smokers who attempt to stop smoking relapse within the first year of abstinence. The effect of continued use of pharmacotherapy for smoking cessation on relapse rates is unknown. Bupropion sustained-release (SR) is the first non-nicotine-based therapy that is effective for achieving abstinence from smoking. Objective: This analysis explored the factors involved in relapse to smoking in patients who had successfully stopped smoking using bupropion SR. These patients were participants in a double-blind, placebo-controlled trial of bupropion SR for the prevention of relapse to smoking. Methods: Participants who had stopped smoking with 7 weeks of open-label bupropion SR were randomly assigned to receive double-blind treatment with either bupropion SR or placebo for 45 weeks. The primary efficacy outcome of the main study was the rate of relapse to smoking. The analyses presented here examine the levels of reported cigarette craving and, in those participants who returned to smoking, the reasons associated with relapse, using patient-completed questionnaires. Results: Craving was cited most frequently as a factor contributing to relapse in those participants receiving placebo (cited by 49.2% of relapsers) but significantly less frequently by participants receiving bupropion SR (cited by 22.4% of relapsers) (P < 0.05). Results from patients' diaries showed no differences between bupropion SR and placebo in terms of "craving in the past 24 hours" but significantly lower scores for "craving right now" for bupropion SR at weeks I I and 12 (P < 0.05). Results at scheduled visits showed that "craving in the past 24 hours" was significantly less with bupropion SR compared with placebo at weeks 12, 20, and 48, and "craving right now" was significantly less with bupropion SR compared with placebo at weeks 12, 16, 20, 24, 48, and 52 (P < 0.05). Conclusions: Craving continues to be a significant concern for individuals even after they have successfully stopped smoking. Bupropion SR appears to reduce reported cravings, which may contribute to the overall reduction in the rate of relapse observed with this pharmacotherapy. C1 GlaxoSmithKline, Res Triangle Pk, NC 27709 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Miriam Hosp, Providence, RI 02906 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Palo Alto Ctr Pulm Dis PRevent, Palo Alto, CA USA. Stanford Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Stanford, CA 94305 USA. RP Durcan, MJ (reprint author), GlaxoSmithKline, 5 Moore Dr, Res Triangle Pk, NC 27709 USA. OI Gonzales, David/0000-0002-4323-198X NR 18 TC 57 Z9 59 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD APR PY 2002 VL 24 IS 4 BP 540 EP 551 DI 10.1016/S0149-2918(02)85130-X PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 548CF UT WOS:000175370400007 PM 12017399 ER PT J AU Yunis, EJ AF Yunis, EJ TI Bernard Amos: teacher, colleague and friend SO CLINICAL TRANSPLANTATION LA English DT Biographical-Item C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Yunis, EJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PD APR PY 2002 VL 16 IS 2 BP 87 EP 91 PG 5 WC Surgery; Transplantation SC Surgery; Transplantation GA 542HN UT WOS:000175037600013 ER PT J AU Esterman, M McGlinchey-Berroth, R Verfaellie, M Grande, L Kilduff, P Milberg, W AF Esterman, M McGlinchey-Berroth, R Verfaellie, M Grande, L Kilduff, P Milberg, W TI Aware and unaware perception in hemispatial neglect: Evidence from a stem completion priming task SO CORTEX LA English DT Article DE consciousness; attention; process dissociation ID UNCONSCIOUS PERCEPTION; VISUAL NEGLECT; EXTINGUISHED FIELD; STIMULI; SEARCH AB The current study used the process dissociation procedure in conjunction with a stem-completion priming task to disentangle the influences of aware and unaware perception in patients with hemispatial neglect. One lateralized picture prime was presented simultaneously with a filler picture followed by a centrally presented word stem. In the inclusion condition participants were asked to complete the word stem with the previously presented picture name; in the exclusion task they were asked to complete the stem with the name of a picture other than the one previously presented. Findings indicated that neglect patients had reduced unaware perception of pictures presented in the left visual field and an absence of awareness for those same pictures. In addition, patients had reduced awareness for right visual field pictures, but unaware perception remained intact. These findings suggest that observations of preserved information processing in neglect are due to residual unaware perception and not due to residual awareness of information in the neglected hemispace. C1 VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Geriatr Neuropsychol Lab, Boston, MA 02130 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Boston Univ, Sch Med, Memory Disorders Res Ctr, Boston, MA 02118 USA. Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL USA. RP McGlinchey-Berroth, R (reprint author), VA Boston Healthcare Syst, GRECC JP182, 150 S huntington Ave, Boston, MA 02130 USA. RI McGlinchey, Regina/R-1971-2016 FU NINDS NIH HHS [NS29342] NR 25 TC 10 Z9 10 U1 0 U2 6 PU MASSON DIVISIONE PERIODICI PI MILAN PA VIA FRATELLI BRESSAN 2, 20126 MILAN, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD APR PY 2002 VL 38 IS 2 BP 233 EP 246 DI 10.1016/S0010-9452(08)70652-X PG 14 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 559RH UT WOS:000176038800010 PM 12056691 ER PT J AU Singh, JM Mehta, S Kacmarek, RM AF Singh, JM Mehta, S Kacmarek, RM TI Pro/con clinical debate: Is high-frequency oscillatory ventilation useful in the management of adult patients with respiratory failure? SO CRITICAL CARE LA English DT Editorial Material DE acute respiratory failure; critical illness; high-frequency oscillatory ventilation; mechanical ventilation ID DISTRESS-SYNDROME; MECHANICAL VENTILATION; LUNG INJURY; STRATEGY AB In neonatal and pediatric intensive care units, high-frequency oscillatory ventilation (HFOV) has become an increasingly common therapy. This may not have been the case if researchers had not persisted in investigating the therapy after early disappointing clinical trials. Devices capable of providing this therapy to adults have become commercially available relatively recently. However, there are many questions that need to be answered regarding HFOV in adults: Is HFOV in adults superior to conventional mechanical ventilation? Who is the ideal candidate for HFOV? When should it be applied? What is the best technique with which to apply it? When should a patient on HFOV be converted back to conventional ventilation? What is the safety and efficacy of the device? As outlined in the following debate, there are several compelling arguments for and against the use of HFOV at this point in adults. C1 Mt Sinai Hosp, Dept Med, Med Surg ICU, Toronto, ON M5G 1X5, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Singh, JM (reprint author), Mt Sinai Hosp, Dept Med, Med Surg ICU, Toronto, ON M5G 1X5, Canada. RI Mehta, Sangeeta/C-4623-2015; OI Singh, Jeffrey/0000-0003-3499-574X NR 13 TC 3 Z9 4 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PD APR PY 2002 VL 6 IS 3 BP 183 EP 185 DI 10.1186/cc1483 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 563UE UT WOS:000176273400002 PM 12133172 ER PT J AU Merkel, PA Choi, HK Niles, JL AF Merkel, PA Choi, HK Niles, JL TI Evaluation and treatment of vasculitis in the critically ill patient SO CRITICAL CARE CLINICS LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; GIANT-CELL ARTERITIS; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; GLOMERULAR BASEMENT-MEMBRANE; CHURG-STRAUSS-SYNDROME; CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME; MAGNETIC-RESONANCE ANGIOGRAPHY; ANTI-GBM ANTIBODIES; TERM FOLLOW-UP; WEGENERS-GRANULOMATOSIS AB The inflammatory vasculitides are a group of multisystem diseases that can result in rapid clinical deterioration and admission to an intensive care unit (ICU). Vasculitis is usually idiopathic and often difficult to diagnosis quickly making the approach to these patients especially challenging in an ICU. Critical illness may be the initial presentation of an inflammatory vasculitis, it may be the result of progressive primary or recurrent disease or it may be due to complications of treatment, such as sepsis. This article focuses on critical care aspects of patients with vasculitis with a focus on the approach to diagnosis and treatment in the ICU. A particular emphasis is placed on the renal manifestations of the diseases. The most difficult aspect of diagnosing a case of vasculitis is often simply considering it in patients with severe multisystem disease. It must be emphasized that vasculitides are rare diseases and often mimic other diseases, such as infections and malignancies. Furthermore, because treatment for severe vasculitis almost always involves high-dose glucocorticoids and immunosuppressive agents, infections must be carefully ruled out even in patients who clearly have vasculitis. Patients who already carry an established diagnosis of vasculitis can present to an ICU with an exacerbation of their underlying inflammatory process, an infectious complication of therapy, or both problems. In can often be difficult to determine whether patients with a history of vasculitis have active disease. Currently, there are no fully reliable measures of disease activity for vasculitis and it is often necessary to embark upon an extensive evaluation in such patients to determine disease activity. C1 Boston Univ, Sch Med, Arthrit Ctr, Boston Med Ctr,Rheumatol Sect, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02117 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Merkel, PA (reprint author), Boston Univ, Sch Med, Arthrit Ctr, Boston Med Ctr,Rheumatol Sect, 730 Albany St, Boston, MA 02118 USA. NR 90 TC 5 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 0749-0704 J9 CRIT CARE CLIN JI Crit. Care Clin. PD APR PY 2002 VL 18 IS 2 BP 321 EP + AR PII S0749-0704(01)00006-9 DI 10.1016/S0749-0704(01)00006-9 PG 26 WC Critical Care Medicine SC General & Internal Medicine GA 559AZ UT WOS:000176003200008 PM 12053837 ER PT J AU Cohen, DE Lee, JT AF Cohen, DE Lee, JT TI X-chromosome inactivation and the search for chromosome-wide silencers SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID HUMAN XIST GENE; HISTONE MACROH2A1; EVOLUTIONARY CONSERVATION; FEMALE MAMMALS; POLYCOMB-GROUP; PROMOTER; RNA; LOCALIZATION; ACETYLATION; MAINTENANCE AB X-chromosome inactivation leads to divergent fates for two homologous chromosomes. Whether one X remains active or becomes silenced depends on the activity of Xist, a gene expressed only from the inactive X and whose RNA product 'paints' the X in cis. Recent work argues that Xist RNA itself is the acting agent for initiating the silencing step. Xist RNA contains separable domains for RNA localization and chromosome silencing, While no Xist RNA-interacting factors have been identified, a growing collection of chromatin alterations have been identified on the inactive X, including variant histone H2A composition and histone H3 methylation. Some or all of these changes may be critical for chromosome-wide silencing. As none of the silencing proteins identified so far is unique to X chromosome inactivation, the specificity must partly reside in Xist RNA whose spread along the X orchestrates general silencing factors for this specific task. C1 Harvard Univ, Sch Med, Dept Genet, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Cohen, DE (reprint author), Harvard Univ, Sch Med, Dept Genet, Howard Hughes Med Inst, Boston, MA 02114 USA. NR 48 TC 42 Z9 44 U1 1 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD APR PY 2002 VL 12 IS 2 BP 219 EP 224 DI 10.1016/S0959-437X(02)00289-7 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 530KL UT WOS:000174356800014 PM 11893496 ER PT J AU Dranoff, G AF Dranoff, G TI Immune recognition and tumor protection SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material ID V(ALPHA)14 NKT CELLS; T-CELLS; CYCLOOXYGENASE-2 INHIBITOR; HEPATOCELLULAR-CARCINOMA; INFILTRATING LYMPHOCYTES; ADENOMATOUS POLYPOSIS; SKIN CARCINOGENESIS; DEFICIENT MICE; HUMAN CANCER; BALB/C MICE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Dranoff, G (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Dana 510E,44 Binney St, Boston, MA 02115 USA. NR 54 TC 11 Z9 14 U1 0 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2002 VL 14 IS 2 BP 161 EP 164 DI 10.1016/S0952-7915(02)00315-1 PG 4 WC Immunology SC Immunology GA 524RK UT WOS:000174026500001 ER PT J AU Borowski, C Martin, C Gounari, F Haughn, L Aifantis, L Grassi, F Boehmer, HY AF Borowski, C Martin, C Gounari, F Haughn, L Aifantis, L Grassi, F Boehmer, HY TI On the brink of becoming a T cell SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID MAJOR HISTOCOMPATIBILITY COMPLEX; HEMATOPOIETIC STEM-CELLS; MURINE FETAL LIVER; RECEPTOR TRANSGENIC MICE; NF-KAPPA-B; ALLELIC EXCLUSION; LINEAGE COMMITMENT; ALPHA-BETA; PRE-TCR; LYMPHOCYTE PROGENITORS AB Recent studies provide fresh insight into the mechanisms by which precursor cells are committed to and develop within the T-lymphocyte lineage. Precursor/product studies have identified developmental stages between that of the pluripotent hematopoietic stem cell and thymocytes committed to the T lineage. Specific ligands and signaling pathways interacting with the Notch-1 receptor and its ability to influence commitment within the lymphoid lineage have been described. Although the structural features or putative ligands endowing the pre-TCR with constitutive signaling capacity remain elusive, numerous distal mediators of pre-TCR signaling have been identified. It remains for the future to determine what roles they may have in survival, proliferation, lineage commitment and allelic exclusion of TCR genes. Receptor editing and lineage commitment of alphabeta T cells still represent controversial topics that need further study. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. RP Boehmer, HY (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, 44 Binney St, Boston, MA 02115 USA. FU PHS HHS [A145846, A147281] NR 75 TC 59 Z9 62 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2002 VL 14 IS 2 BP 200 EP 206 DI 10.1016/S0952-7915(02)00322-9 PG 7 WC Immunology SC Immunology GA 524RK UT WOS:000174026500008 PM 11869893 ER PT J AU Cariappa, A Pillai, S AF Cariappa, A Pillai, S TI Antigen-dependent B-cell development SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID FACTOR-KAPPA-B; HEAT-STABLE ANTIGEN(HI); BRUTONS TYROSINE KINASE; MARGINAL ZONE; POSITIVE SELECTION; REGULATORY ROLE; DEFICIENT MICE; B-1 CELLS; IG-ALPHA; RECEPTOR AB There is growing evidence that the development of naive B cells depends on the interaction of self antigens with the BCR. A view that has emerged over the past year is that BCR signal output contributes in a large part to the developmental fate of peripheral B cells. Differences in antigen-receptor signal strength may determine whether B cells assume a marginal zone, follicular or B-1 phenotype. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. RP Pillai, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA 69618]; NIAID NIH HHS [AI 33507] NR 66 TC 80 Z9 81 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2002 VL 14 IS 2 BP 241 EP 249 DI 10.1016/S0952-7915(02)00328-X PG 9 WC Immunology SC Immunology GA 524RK UT WOS:000174026500014 PM 11869899 ER PT J AU Metlay, JP AF Metlay, JP TI Update on community-acquired pneumonia: impact of antibiotic resistance on clinical outcomes SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review ID STREPTOCOCCUS-PNEUMONIAE; PNEUMOCOCCAL PNEUMONIA; ERA; BACTEREMIA AB In contrast to the rapid expansion in the number of published studies reporting the increasing rate of antimicrobial drug resistance among common respiratory pathogens, there remain few controlled studies examining the impact of these trends on clinical outcomes. Those studies that are published are hampered by small sample sizes, biases inherent in observational designs, and the relative infrequency of isolates showing high-level resistance, particularly high-level beta-lactam resistance among clinical isolates of Streptococcus pneumoniae. This update summarizes recent published studies addressing the impact of drug resistance on outcomes for lower respiratory tract infections. The majority of these studies are retrospective cohort studies, focusing on the impact of beta-lactam-resistant pneumococcal infections in patients with community-acquired pneumonia. These studies support the conclusion that current levels of pneumococcal drug resistance do not result in clinical treatment failures for patients with community-acquired pneumonia. However, as patterns of drug resistance evolve, future studies will be needed to address the continued appropriateness of current empirical treatment guidelines for these patients. Curr Opin Infect Dis 15: 163-167. (C) 2002 Lippincott Williams Wilkins. C1 Univ Penn, Sch Med, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Metlay, JP (reprint author), Univ Penn, Sch Med, Vet Affairs Med Ctr, 712 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 16 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD APR PY 2002 VL 15 IS 2 BP 163 EP 167 PG 5 WC Infectious Diseases SC Infectious Diseases GA 535CK UT WOS:000174627500011 PM 11964918 ER PT J AU Caviness, VS AF Caviness, VS TI Developmental vasculopathies as manifestations of dysregulated histogenetic signal transduction pathways SO CURRENT OPINION IN NEUROLOGY LA English DT Editorial Material ID CEREBRAL CAVERNOUS MALFORMATION; CENTRAL-NERVOUS-SYSTEM; MOSAICISM; MUTATIONS; DISEASES C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Div Child Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. RP Caviness, VS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Div Child Neurol, Fruit St, Boston, MA 02114 USA. NR 27 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD APR PY 2002 VL 15 IS 2 BP 127 EP 131 DI 10.1097/00019052-200204000-00001 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 539AJ UT WOS:000174847000001 PM 11923624 ER PT J AU Nestoridi, E Buonanno, FS Jones, RM Krishnamoorthy, K Grant, PE Van Cott, EM Grabowski, EF AF Nestoridi, E Buonanno, FS Jones, RM Krishnamoorthy, K Grant, PE Van Cott, EM Grabowski, EF TI Arterial ischemic stroke in childhood: the role of plasma-phase risk factors SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID PROTEIN-S DEFICIENCY; FACTOR-V-LEIDEN; PURPURA FULMINANS; C DEFICIENCY; CHILDREN; PROTHROMBIN; THROMBOSIS; HYPERHOMOCYSTEINEMIA; DISORDERS; GENE AB The role of plasma-phase risk factors for stroke in the pediatric age group is presently unclear due to the lack of sufficiently large prospective studies, and due to the fact that these risk factors do not apply uniformly to newborns, children with sickle cell disease, and older children. Available evidence indicates that factor V Leiden, prothrombin 2021 OA, and lipoprotein (a) are all important in the pathogenesis of arterial ischemic stroke in older children, but the role of other plasma-phase risk factors remains uncertain. The contribution of these risk factors to newborn stroke and the stroke of children with sickle cell disease is similarly unclear, likely because the ischemia in affected children is predominantly due to nonhematologic perinatal events and erythrocyte adhesion to endothelium with obstruction of flow in the cerebral microcirculation, respectively. Evaluation of childhood stroke should, in our view, always be performed from the standpoint of the presenting clinical symptoms, diagnostic imaging, and determination of plasma-phase risk factors. Therapeutic anticoagulation and use of antiplatelet agents at present focus on the older child. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Grabowski, EF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Fruit St,Blake 255, Boston, MA 02114 USA. NR 36 TC 18 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD APR PY 2002 VL 15 IS 2 BP 139 EP 144 DI 10.1097/00019052-200204000-00003 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 539AJ UT WOS:000174847000003 PM 11923626 ER PT J AU Sims, K Holtzman, D AF Sims, K Holtzman, D TI Diseases of adenosine triphosphate synthesis in children SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID C-OXIDASE DEFICIENCY; FAMILIAL MITOCHONDRIAL ENCEPHALOMYOPATHY; DNA DEPLETION; MUTATION; MUSCLE; GENE; DELETIONS; PATIENT; DRIFT; MERRF AB There is an expanding understanding of primary genetic oxidative-phosphorylation disorders and the recognition of new multi-system clinical phenotypes in the energy metabolism diseases, Although initially recognized in association with mitochondrial DNA mutations, there is progress in the more laborious identification of nuclear DNA encoded genes relevant to mitochondrial structure and function. More pathogenic mitochondrial DNA and nuclear DNA mutations have been identified. Diagnosis of these disorders is often difficult and relies on a concurrence of findings, including recognition of a variety of clinical signs and symptoms, biochemical marker screening, electron transport chain enzyme measurements, and mitochondrial DNA or nuclear DNA mutation assay of genes relevant to mitochondrial structure, function or adenosine triphosphate metabolic pathways. Clinical diagnostic assessment now can be augmented by physiologic imaging techniques, including nuclear magnetic resonance spectroscopy and positron emission tomography. These capabilities should be increasingly helpful for studies of clinical progression and therapeutic intervention. Biologic studies, in families and patients, are beginning to address the factors of mitochondrial replication and segregation that underlie cellular/tissue heteroplasmy and clinical variability. Most epigenetic factors affecting organ-specific and phenotypic variability, however, remain to be elaborated. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Holtzman, D (reprint author), Massachusetts Gen Hosp E, Box 21,149 13th St, Charlestown, MA 02129 USA. NR 75 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD APR PY 2002 VL 15 IS 2 BP 145 EP 150 DI 10.1097/00019052-200204000-00004 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 539AJ UT WOS:000174847000004 PM 11923627 ER PT J AU Smith, ER Butler, WE Ogilvy, CS AF Smith, ER Butler, WE Ogilvy, CS TI Surgical approaches to vascular anomalies of the child's brain SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID CEREBRAL ARTERIOVENOUS-MALFORMATIONS; CEREBROVASCULAR MOYAMOYA DISEASE; CONGESTIVE-HEART-FAILURE; MUSCLE FREE-FLAP; CAVERNOUS MALFORMATIONS; NATURAL-HISTORY; OMENTAL TRANSPLANTATION; FOLLOW-UP; NERVOUS-SYSTEM; GRADING SYSTEM AB The population of pediatric patients with cerebrovascular disease presents a unique set of challenges to the neurosurgeon. The wide scope of pathology, including arteriovenous malformations, cavernous malformations and moyamoya disease, coupled with marked advances in diagnosis and treatment of these conditions over the past several years has resulted in a proliferation of the literature related to this subject. The present review provides an overview of current methods of surgical treatment for pediatric cerebrovascular diseases, focusing on indications and use of recent refinements of pre-existing surgical approaches, and newly evolved operative techniques developed to treat these entities. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, VBK 710,Fruit St, Boston, MA 02114 USA. NR 84 TC 24 Z9 25 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD APR PY 2002 VL 15 IS 2 BP 165 EP 171 DI 10.1097/00019052-200204000-00007 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 539AJ UT WOS:000174847000007 PM 11923630 ER PT J AU Nehal, US Ingelfinger, JR AF Nehal, US Ingelfinger, JR TI Pediatric hypertension: recent literature SO CURRENT OPINION IN PEDIATRICS LA English DT Review ID AMBULATORY BLOOD-PRESSURE; WHITE COAT HYPERTENSION; AORTIC COARCTATION; METABOLIC SYNDROME; TURNER-SYNDROME; CHILDREN; ADOLESCENTS; MANAGEMENT; AMLODIPINE; EXPERIENCE AB This article reviews selected recent literature specifically concerning pediatric hypertension, much of which has focused on measurement and monitoring of blood pressure, as well as on evaluating anti hypertensive medications. Normative data for blood pressure in children have been widely available for some time, based upon seated in-office measurements. In recent years, ambulatory blood pressure monitoring (ABPM), facilitated by user-friendly instrumentation, has become more commonplace, though norms are not based on large populations. However, ABPM has important uses in assessing blood pressure as well as in monitoring anti hypertensive. This review discusses issues involved in determining blood pressure, as well as the utility of ABPM in several situations. Recent developments concerning pediatric antihypertensive therapy are considered, as well as new information relevant to the diagnosis, course and treatment of hypertension in children and adolescents. C1 Massachusetts Gen Hosp, MassGen Hosp Children, Div Pediat Nephrol, Boston, MA 02114 USA. RP Ingelfinger, JR (reprint author), Massachusetts Gen Hosp, MassGen Hosp Children, Div Pediat Nephrol, 15 Parkman St, Boston, MA 02114 USA. NR 83 TC 14 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD APR PY 2002 VL 14 IS 2 BP 189 EP 196 DI 10.1097/00008480-200204000-00008 PG 8 WC Pediatrics SC Pediatrics GA 543DJ UT WOS:000175085700008 PM 11981289 ER PT J AU Samsonov, D Briscoe, DM AF Samsonov, D Briscoe, DM TI Long-term care of pediatric renal transplant patients: from bench to bedside SO CURRENT OPINION IN PEDIATRICS LA English DT Review ID ALLOGRAFT-REJECTION; IMMUNOSUPPRESSION; IDENTIFICATION; DIAGNOSIS; GROWTH AB In this review, we discuss current and future issues in the management of pediatric renal transplant recipients, including the optimization of long-term graft function and the minimization of complications caused by immunosuppression. Long-term management involves not only the monitoring of graft function but also the identification of patients at risk for the development of complications. The identification of patients with immunoreactive or immunoregulatory responses can be performed molecular monitoring of the immune response. Also, the use of frequent surveillance kidney biopsies, surrogate markers of chronic rejection, and glomerular filtration rate will be a part of future management. Identifying high-risk patients enables the physician to optimize immunosuppression to limit acute rejection. Short- and long-term management of pediatric transplant patients also includes adequate monitoring of growth and the monitoring for post-transplant lymphoproliferative disease, Ongoing clinical trials are underway that focus on these novel approaches in caring for pediatric transplant recipients. C1 Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Briscoe, DM (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, 300 Longwood Ave, Boston, MA 02114 USA. NR 40 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD APR PY 2002 VL 14 IS 2 BP 205 EP 210 DI 10.1097/00008480-200204000-00010 PG 6 WC Pediatrics SC Pediatrics GA 543DJ UT WOS:000175085700010 PM 11981291 ER PT J AU Cameron, S Clark, SG McDermott, JB Aamodt, E Horvitz, HR AF Cameron, S Clark, SG McDermott, JB Aamodt, E Horvitz, HR TI PAG-3, a Zn-finger transcription factor, determines neuroblast fate in C-elegans SO DEVELOPMENT LA English DT Article DE cell lineage; neuroblast fate; programmed cell death; C. elegans ID PROGRAMMED CELL-DEATH; NEMATODE CAENORHABDITIS-ELEGANS; NERVOUS-SYSTEM; MOTOR-NEURONS; TRANSGENIC MICE; GENETIC-CONTROL; AXON OUTGROWTH; SYNAPTIC INPUT; VENTRAL CORD; BODY REGION AB During Caenorhabditis elegans development, the patterns of cell divisions, cell fates and programmed cell deaths are reproducible from animal to animal. In a search for mutants with abnormal patterns of programmed cell deaths in the ventral nerve cord, we identified mutations in the gene pag-3, which encodes a zinc-finger transcription factor similar to the mammalian Gfi-1 and Drosophila Senseless proteins. In pag-3 mutants, specific neuroblasts express the pattern of divisions normally associated with their mother cells, producing with each reiteration an abnormal anterior daughter neuroblast and an extra posterior daughter cell that either terminally differentiates or undergoes programmed cell death, which accounts for the extra cell corpses seen in pag-3 mutants. In addition, some neurons do not adopt their normal fates in pag-3 mutants. The phenotype of pag-3 mutants and the expression pattern of the PAG-3 protein suggest that in some lineages pag-3 couples the determination of neuroblast cell fate to subsequent neuronal differentiation. We propose that pag-3 counterparts in other organisms determine blast cell identity and for this reason may lead to cell lineage defects and cell proliferation when mutated. C1 MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Childrens Hosp, Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. NYU, Sch Med, Skirball Inst, New York, NY 10016 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Shreveport, LA 71130 USA. RP Cameron, S (reprint author), Univ Texas, SW Med Ctr, Dept Pediat, 6000 Harry Hines Blvd, Dallas, TX 75390 USA. FU NHLBI NIH HHS [HL07574]; NIGMS NIH HHS [GM24663] NR 64 TC 30 Z9 42 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 APR PY 2002 VL 129 IS 7 BP 1763 EP 1774 PG 12 WC Developmental Biology SC Developmental Biology GA 543QH UT WOS:000175112300019 PM 11923211 ER PT J AU Hata, K Okano, M Lei, H Li, E AF Hata, K Okano, M Lei, H Li, E TI Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice SO DEVELOPMENT LA English DT Article DE Dmrt3L; Dnmt3a; de novo methylation; genomic imprinting; spermatogenesis; mouse ID ORIGIN-SPECIFIC METHYLATION; MOUSE SNRPN GENE; MAMMALIAN DEVELOPMENT; CYTOSINE-5 METHYLTRANSFERASES; EXPRESSION; MUTATION; GENOMES; LOCUS; EMBRYOGENESIS; CHROMOSOME-7 AB Genomic imprinting is regulated by differential methylation of the paternal and maternal genome. However, it remains unknown how parental imprinting is established during gametogenesis. In this study, we demonstrate that Dnmt3L, a protein sharing homology with DNA methyltransferases, Dnmt3a and Dnmt3b, but lacking enzymatic activity, is essential for the establishment of maternal methylation imprints and appropriate expression of maternally imprinted genes. We also show that Dnmt3L interacts with Dnmt3a and Dnmt3b and colocalizes with these enzymes in the nuclei of transfected cells, suggesting that Dnmt3L may regulate genomic imprinting via the Dnmt3 family enzymes. Consistent with this model, we show that [Dnmt3a(-/-), Dnmt3b(+/-)] mice also fail to establish maternal methylation imprints. In addition, both Dnmt3a and Dnmt3L are required for spermatogenesis. Together, our findings suggest that Dnmt3L may cooperate with Dnmt3 family methyltransferases to carry out de novo methylation of maternally imprinted genes in oocytes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Dept Med, Charlestown, MA 02129 USA. RP Li, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Dept Med, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA82389]; NIGMS NIH HHS [GM52106] NR 45 TC 528 Z9 555 U1 4 U2 29 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 APR PY 2002 VL 129 IS 8 BP 1983 EP 1993 PG 11 WC Developmental Biology SC Developmental Biology GA 549YA UT WOS:000175473800018 PM 11934864 ER PT J AU Faure, S de Santa Barbara, P Roberts, DJ Whitman, M AF Faure, S de Santa Barbara, P Roberts, DJ Whitman, M TI Endogenous patterns of BMP signaling during early chick development SO DEVELOPMENTAL BIOLOGY LA English DT Review DE Smad; BMP; phosphorylation; patterns; signal transduction; chick ID BONE MORPHOGENETIC PROTEIN; TGF-BETA SUPERFAMILY; EARLY XENOPUS DEVELOPMENT; LEFT-RIGHT ASYMMETRY; DORSAL NEURAL-TUBE; PRIMITIVE STREAK; SONIC-HEDGEHOG; VENTRALIZING FACTOR; CARDIAC DEVELOPMENT; MESODERM INDUCTION AB Bone morphogenetic proteins (BMPs) are members of the transforming growth factor p superfamily signaling molecules that play important roles in a wide variety of developmental processes. In this study, we have used an antibody specific for the phosphorylated and activated form of Smad1 to examine endogenous patterns of BMP signaling in chick embryos during early development. We find complex spatial and temporal distributions of BMP signaling that elucidate how BMPs may function in multiple patterning events in the early chick embryo. in the pregastrula embryo, we find that BMP signaling is initially ubiquitous and is extinguished in the epiblast at the onset of primitive streak formation. At the head process stage, BMP signaling is inactivated in prospective neural plate, while it is strongly activated at the neural plate border, a region which is populated by cells that will give rise to neural crest. During later development, we find a dynamic spatiotemporal activation of BMP signaling along the rostrocaudal axis, in the dorsal neural tube, in the notochord, and in the somites during their maturation process. We discuss the implication of our results for endogenous functions of BMP signaling during chick development. (C) 2002 Elsevier Science (USA). C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Whitman, M (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. FU NICHD NIH HHS [HD34448, HD29468] NR 107 TC 105 Z9 108 U1 3 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 1 PY 2002 VL 244 IS 1 BP 44 EP 65 DI 10.1006/dbio.2002.0579 PG 22 WC Developmental Biology SC Developmental Biology GA 539KJ UT WOS:000174869000005 PM 11900458 ER PT J AU Field, SJ Lamia, KA Rameh, LE Cantley, LC AF Field, SJ Lamia, KA Rameh, LE Cantley, LC TI Lipid research picks up speed on the slopes of Taos SO DEVELOPMENTAL CELL LA English DT Article ID KINASE AB The 2002 Keystone Symposium on "Regulation of Cellular Responses by Lipid Mediators" provided a lively and active forum to discuss research in lipid signaling. This meeting review can provide only a glimpse into the diversity of research presented. Here we have chosen to highlight a group of exciting presentations describing novel features of the temporal and spatial regulation of phosphoinositides and their downstream targets. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Endocrinol, Boston, MA 02114 USA. Boston Biomed Res Inst, Watertown, MA 02472 USA. RP Field, SJ (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Signal Transduct, 77 Ave Louis Pasteur, Boston, MA 02115 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIDDK NIH HHS [P30 DK36836-15]; NIGMS NIH HHS [GM-41890, GM-36624, R01 GM041890] NR 12 TC 4 Z9 4 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD APR PY 2002 VL 2 IS 4 BP 407 EP 410 DI 10.1016/S1534-5807(02)00150-8 PG 4 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 548KA UT WOS:000175386100008 PM 11970891 ER PT J AU Gunther, L Berberat, PO Haga, M Brouard, S Smith, RN Soares, MP Bach, FH Tobiasch, E AF Gunther, L Berberat, PO Haga, M Brouard, S Smith, RN Soares, MP Bach, FH Tobiasch, E TI Carbon monoxide protects pancreatic beta-cells from apoptosis and improves islet function/survival after transplantation SO DIABETES LA English DT Article ID HUMAN HEME OXYGENASE; DIABETES-MELLITUS; NITRIC-OXIDE; TNF-ALPHA; DEATH; EXPRESSION; GENE; INTERLEUKIN-1-BETA; TRANSFECTION; NONFUNCTION AB Pancreatic islets transplanted to treat autoimmune type 1 diabetes often fail to function (primary nonfunction), likely because of islet beta-cell apoptosis. We show that carbon monoxide (CO), a product of heme oxygenase activity, protects beta-cells from apoptosis. Protection is mediated through guanylate cyclase activation, generation of cyclic GMP (cGMP), and activation of cGMP-dependent protein kinases. This antiapoptotic effect is still observed when beta-cells are exposed to CO for 1 h before the apoptotic stimulus. In a similar manner, mouse islets exposed to CO for just 2 h function significantly better after transplantation than islets not exposed to CO. These findings suggest a potential therapeutic application for CO in improving islet function/survival after transplantation in humans. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Immunobiol Res Ctr,Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Boston, MA 02114 USA. ITERT, INSERM U437, Nantes, France. RP Bach, FH (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Immunobiol Res Ctr,Dept Surg, Boston, MA 02115 USA. RI brouard, sophie/Q-1285-2016 FU NHLBI NIH HHS [HL58688] NR 38 TC 78 Z9 91 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2002 VL 51 IS 4 BP 994 EP 999 DI 10.2337/diabetes.51.4.994 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 537BR UT WOS:000174737500014 PM 11916917 ER PT J AU Canani, LH Ng, DPK Smiles, A Rogus, JJ Warram, JH Krolewski, AS AF Canani, LH Ng, DPK Smiles, A Rogus, JJ Warram, JH Krolewski, AS TI Polymorphism in ecto-nucleotide pyrophosphatase/phosphodiesterase 1 gene (ENPP1/PC-1) and early development of advanced diabetic nephropathy in type 1 diabetes SO DIABETES LA English DT Article ID MEMBRANE GLYCOPROTEIN PC-1; BODY INSULIN SENSITIVITY; RECEPTOR TYROSINE-KINASE; RESISTANCE; MELLITUS; DISEASE; CELLS; K121Q; MICROALBUMINURIA; EXPRESSION AB A polymorphism in the ecto-nucleotide pyrophosphatase/ phosphodiesterase 1 gene (ENPP1) (previously known as PC-1), resulting in an amino acid change from lysine to glutamine at codon 121 (K121Q), is associated with insulin resistance. A small follow-up study of patients with type 1 diabetes and proteinuria found that renal function declines more rapidly in carriers of the Q variant than in noncarriers. To examine this finding further, we conducted a large case-control study and a family-based study. Genomic DNA was obtained from 659 patients: 307 with normal urinary albumin excretion despite diabetes duration of > 15 years (control subjects) and 352 with advanced diabetic nephropathy, of whom 200 had persistent proteinuria and 152 had end-stage renal disease (ESRD). Individuals were genotyped for Q and K variants using a previously described protocol. The frequency of Q variant carriers was 21.5% in control subjects, 31.5% in subjects with proteinuria, and 32.2% in subjects with ESRD (P = 0.012). In a stratified analysis according to duration of diabetes, the risk of early-onset ESRD for carriers of the Q variant was 2.3 times that for noncarriers (95% CI, 1.2-4.6). The Q variant was not associated with late-onset ESRD. Similar findings were obtained in a family-based study. We conclude that carriers of the Q variant of ENPP1 are at increased risk for developing ESRD early in the coarse of type 1 diabetes. C1 Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. RI Canani, Luis/G-9686-2012 OI Canani, Luis/0000-0002-1813-4491 FU NIDDK NIH HHS [DK41526, DK53534] NR 31 TC 45 Z9 45 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2002 VL 51 IS 4 BP 1188 EP 1193 DI 10.2337/diabetes.51.4.1188 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 537BR UT WOS:000174737500040 PM 11916943 ER PT J AU Franceschi, F Armuzzi, A Cremonini, F Carloni, E Zocco, MA Di Caro, S Padalino, C Genta, RM Pola, P Gasbarrini, G Gasbarrini, A AF Franceschi, F Armuzzi, A Cremonini, F Carloni, E Zocco, MA Di Caro, S Padalino, C Genta, RM Pola, P Gasbarrini, G Gasbarrini, A TI delta(CO2)-C-13 excretion and expression of dyspeptic symptoms in patients evaluated for Helicobacter pylori infection by [C-13] urea breath test SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Helicobacter pylori; urea breath test; dyspepsia ID TERM FOLLOW-UP; NONULCER DYSPEPSIA; ERADICATION AB Previous studies showed that either the urease activity possessed by H. pylori and the bacterial load may influence the results of the [C-13] urea breath test. However, the correlation between urease activity and dyspepsia is unclear. The aim of our study was to evaluate whether the urease activity of the gastroduodenal tract may influence the severity of dyspeptic symptoms. In all, 2520 dyspeptic patients (1109 men, 1411 women; mean age 47 +/- 16 years) without gastroesophageal reflux disease, diabetes, vascular disorders, liver and biliary tract diseases, and tumors of the gastrointestinal tract and with a normal appearing abdominal ultrasonography were enrolled. All these patients underwent a [ 13C] urea breath test and filled out a questionnaire on dyspeptic symptoms. Subjects were divided in five different groups according to delta over baseline (DOB) values (group 1 < 3.5, group 2 = 3.5-6; group 3 = 6.1-11, group 4 = 11.1-23, group 5 > 23.1). The prevalence and intensity of dyspeptic symptoms were compared among groups. In all, 1688 patients (67%, 928 females and 760 males; mean age 48 +/- 15 years) were H. pylori-positive. The chi-squared test and analysis of variance showed increase of frequency and intensity of each dyspeptic symptom according to DOB values. In conclusion, Dyspepsia may parallel gastric urease activity. However, whether higher DOB values are related to higher bacterial load or, alternatively, to the presence of particular H. pylori strains able to produce larger amounts of urease is uncertain. C1 Univ Sacred Heart, Policlin Gemelli, Ist Patol Med, Dept Internal Med, I-00168 Rome, Italy. Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. RP Gasbarrini, A (reprint author), Univ Sacred Heart, Policlin Gemelli, Ist Patol Med, Dept Internal Med, Largo A Gemelli 8, I-00168 Rome, Italy. NR 16 TC 4 Z9 4 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD APR PY 2002 VL 47 IS 4 BP 804 EP 808 AR UNSP 0163-02/0400-0804/0 DI 10.1023/A:1014700319068 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 545QC UT WOS:000175227900022 PM 11991614 ER PT J AU Schlozman, SC AF Schlozman, SC TI The shrink in the classroom - Why "just say no" isn't enough SO EDUCATIONAL LEADERSHIP LA English DT Article C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. RP Schlozman, SC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2002 VL 59 IS 7 BP 87 EP 89 PG 3 WC Education & Educational Research SC Education & Educational Research GA 541GH UT WOS:000174976500020 ER PT J AU Carambula, SF Matikainen, T Lynch, MP Flavell, RA Goncalves, PBD Tilly, JL Rueda, BR AF Carambula, SF Matikainen, T Lynch, MP Flavell, RA Goncalves, PBD Tilly, JL Rueda, BR TI Caspase-3 is a pivotal mediator of apoptosis during regression of the ovarian corpus luteum SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; PROGRAMMED CELL-DEATH; BCL-2 PROTEIN FAMILY; IN-VIVO; DNA FRAGMENTATION; MITOCHONDRIA; LUTEOLYSIS; INDUCTION; SURVIVAL; RECEPTOR AB Because caspase-3 is considered a primary executioner of apoptosis and has been implicated as a mediator of luteal regression, we hypothesized that corpora lutea (CL) derived from caspase-3 null mice would exhibit a delayed onset of apoptosis during luteal regression, when compared with CL derived from wild-type (WT) mice. To test this hypothesis, ovulation was synchronized in immature (postpartum d 24-27) WT and caspase-3-deficient female littermates by exogenous gonadotropins. Individual CL were isolated by manual dissection, 30 h after ovulation, and placed in organ culture dishes in the absence of serum and growth factors. At the time of isolation (0 h) and after 24,48, and 72 h in culture, the CL were removed and assessed for the presence of processed (active) caspase-3 enzyme and for apoptosis by multiple criteria. There was no evidence of active caspase-3 enzyme or apoptosis in either WT or caspase-3-deficient CL before culture. However, CL derived from the WT mice exhibited a time-dependent increase in the level of active caspase-3 and apoptosis during culture. By comparison, CL derived from caspase-3-deficient mice, cultured in parallel, failed to exhibit any detectable active caspase-3 and showed attenuated rates of apoptosis. To extend these findings derived from ex vivo culture experiments, ovaries were collected from WT and caspase-3 null female littermates at 2, 4, or 6 d post ovulation, and the occurrence of apoptosis within the CL was analyzed. Whereas ovaries of WT mice had only residual luteal tissue at d 6 post ovulation, ovaries collected from caspase-3-deficient mice retained many CL, at d 6 post ovulation, that were similar in size to those observed in the early luteal phase of WT mice. Importantly, there was no dramatic increase in apoptosis in CL of caspase-3-deficient mice at any time point examined post ovulation, indicating that the involution process had indeed been delayed. In contrast, the levels of progesterone declined regardless of genotype. These data provide the first direct evidence that caspase-3 is functionally required for apoptosis to proceed normally during luteal regression. However, caspase-3 is not a direct mediator of the decrease in steroidogenesis associated with luteolysis. C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06510 USA. Univ Fed Santa Maria, Fac Med Vet, Dept Clin Grandes Anim, Rio Grande Sul, Brazil. RP Rueda, BR (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, VBK137E-GYN,55 Fruit St, Boston, MA 02114 USA. RI Goncalves, Paulo/G-9818-2012 NR 34 TC 73 Z9 77 U1 1 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 APR PY 2002 VL 143 IS 4 BP 1495 EP 1501 DI 10.1210/en.143.4.1495 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 536WN UT WOS:000174725000040 PM 11897708 ER PT J AU Cannon, CP AF Cannon, CP TI Enoxaparin in ST elevation MI - a bright future SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID MOLECULAR-WEIGHT HEPARIN; MYOCARDIAL-INFARCTION; THROMBOLYSIS C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD APR PY 2002 VL 23 IS 8 BP 591 EP 592 DI 10.1053/euhj.2002.3185 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 548KZ UT WOS:000175388300002 PM 11969270 ER PT J AU Lisi, S Pinchera, A McCluskey, RT Chiovato, L Marino, M AF Lisi, S Pinchera, A McCluskey, RT Chiovato, L Marino, M TI Binding of heparin to human thyroglobulin (Tg) involves multiple binding sites including a region corresponding to a binding site of rat Tg SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID THYROID EPITHELIAL-CELLS; RECEPTOR GENE FAMILY; ENDOCYTIC RECEPTOR; MEGALIN GP330; LIPOPROTEIN RECEPTORS; HORMONE RELEASE; LDL RECEPTOR; PROTEIN; IDENTIFICATION; HYPOTHYROIDISM AB Objective: Binding of thyroglobulin (Tg) to heparin allows efficient Tg interaction with its endocytic receptor, megalin. Rat Tg (rTg) binds to heparin using an exposed carboxyl terminal region (RELPSRRLKRPLPVK, Arg2489-Lys2503) rich in positively charged residues which is, however, not entirely conserved in human Tg (hTg) (Arg2489-Glu2503, REPPARALKRSLWVE). Here, we investigated whether and how this difference affects binding of heparin. Design: To compare binding of heparin to rTg and hTg. To investigate the role of the sequence 24892503 using a peptide-based approach. Methods: Binding of biotin-labeled heparin to rTg, hTg and to Tg peptides was measured in solid phase assays. Results: Heparin bound to rTg with moderately high affinity (K-d: 34.2 nmol/l, K-i: 3 7.6 nmol/l) and to hTg with lower affinity (K-d: 118 nmol/l, Ki: 480 nmol/l) and to a lower extent. Binding was dose-dependent and saturable, and was reduced by several specific competitors (Tg itself, unlabeled heparin, lactoferrin). Heparin bound to synthetic peptides corresponding to the rat (rTgP) and to the human (hTgP) Tg sequence 2489-2503. Heparin bound to rTgP to a greater extent and with greater affinity than to hTgP. An antibody against hTgP reduced binding of heparin to intact hTg by 30%, suggesting that in hTg this region is, in part, involved in heparin binding, but also that other regions account for most of the binding. Starting from the sequence of rTgP, we designed 6 synthetic 'mutant' peptides by replacing one amino acid residue of rTgP with the corresponding residue of the sequence of hTgP. Heparin bound to 5 of 6 mutant peptides to a lower extent and with lower affinity than to rTgP. Conclusions: In spite of a reduced binding ability of the sequence 2489-2503, hTg binds to heparin, in part, using alternative, as yet unidentified, binding sites. Substitution of both positive and neutral residues within the sequence 2489-2503 reduced heparin-binding, suggesting that not only charge, but also sequence and/or conformation, may account for the heparin-binding ability of this region of Tg. C1 Univ Pisa, Dept Endocrinol, I-56124 Pisa, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Res Lab, Cambridge, MA 02139 USA. Univ Pavia, Fdn Salvatore Maugeri, IRCCS, Pavia, Italy. RP Marino, M (reprint author), Univ Pisa, Dept Endocrinol, Via Paradisa 2, I-56124 Pisa, Italy. NR 41 TC 2 Z9 2 U1 0 U2 0 PU BIO SCIENTIFICA LTD PI BRISTOL PA 16 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD APR PY 2002 VL 146 IS 4 BP 591 EP 602 DI 10.1530/eje.0.1460591 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 606PU UT WOS:000178743000020 PM 11916630 ER PT J AU Mulroy, T McMahon, JA Burakoff, SJ McMahon, AP Sen, J AF Mulroy, T McMahon, JA Burakoff, SJ McMahon, AP Sen, J TI Wnt-1 and Wnt-4 regulate thymic cellularity SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE thymocyte expansion; thymocyte development; Wnt signaling ID T-CELL DEVELOPMENT; EXPANSION; DIFFERENTIATION; EXPRESSION; TCF-1 AB Thymic primordium, formed by cells derived from the endoderm, the ectoderm and the neural crest-derived mesenchyme, receive fetal liver derived lymphoid precursors. Reciprocal cell-cell interactions between thymic stromal cells and lymphoid precursors are critical in the expansion and maturation of thymocytes. Transcription factor TCF-1 is critical for the expansion of thymocytes because deletion of TCF-1 results in a significant decrease in the number of thymocytes without affecting the developmental pattern. In this report we show that Wnt-1 and Wnt-4 are expressed in the thymus and the deletion of Wnt-1 or Wnt-4 result in a substantial decrease in the number of thymocytes without affecting the pattern of maturation. Wnt-1 and Wnt-4 both regulate developing thymocytes because a double deficiency results in a significantly greater decrease of immature and mature thymocytes compared to deficiency in either Wnt-1 or Wnt-4. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Biolabs, Dept Mol & Cellular Biol, Cambridge, England. Skirball Inst Biomol Med, New York, NY USA. New York Univ Canc Inst, New York, NY USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. RP Sen, J (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA74404] NR 15 TC 75 Z9 76 U1 1 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD APR PY 2002 VL 32 IS 4 BP 967 EP 971 DI 10.1002/1521-4141(200204)32:4<967::AID-IMMU967>3.3.CO;2-Y PG 5 WC Immunology SC Immunology GA 541CY UT WOS:000174968700006 PM 11920562 ER PT J AU Huisman, TAGM Thiel, T Steinmann, B Zeilinger, G Martin, E AF Huisman, TAGM Thiel, T Steinmann, B Zeilinger, G Martin, E TI Proton magnetic resonance spectroscopy of the brain of a neonate with nonketotic hyperglycinemia: in vivo-in vitro (ex vivo) correlation SO EUROPEAN RADIOLOGY LA English DT Article DE non-ketotic hyperglycinemia; MR spectroscopy; brain; neonate AB Nonketotic hyperglycinemia (NKH) is an inborn error of amino acid metabolism caused by a defect in the glycine cleavage multienzyme complex resulting in high concentrations of glycine within the brain and spinal cord. Quantitative magnetic resonance spectroscopy (H-1-MRS) allows measurement of absolute glycine concentrations within different parts of the brain in vivo. In addition, H-1-MRS may be useful in monitoring treatment of NKH and to differentiate this disease from other disorders of glycine metabolism. C1 Univ Zurich, Childrens Hosp, Dept Metab & Mol Pediat, Zurich, Switzerland. Reg Hosp Aarau, Div Neonatol, Aarau, Switzerland. Univ Zurich, Childrens Hosp, Dept Neuroradiol & Magnet Resonance, Zurich, Switzerland. RP Huisman, TAGM (reprint author), Massachusetts Gen Hosp, Neuroradiol Sect, MGH NMR Ctr, Mailcode CNY 149-2301, Boston, MA 02119 USA. NR 12 TC 34 Z9 34 U1 0 U2 0 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 APR PY 2002 VL 12 IS 4 BP 858 EP 861 DI 10.1007/s003300101073 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 541FZ UT WOS:000174975700023 PM 11960238 ER PT J AU Royall, DR Palmer, R Mulroy, AR Polk, MJ AF Royall, DR Palmer, R Mulroy, AR Polk, MJ TI Pathological determinants of the transition to clinical dementia in Alzheimer's disease SO EXPERIMENTAL AGING RESEARCH LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; FRONTAL-SUBCORTICAL CIRCUITS; POSTERIOR CINGULATE CORTEX; NEUROFIBRILLARY TANGLES; PREFRONTAL CORTEX; MULTIPLE IMPUTATION; FUNCTIONAL ROLES; EPISODIC MEMORY; SENILE DEMENTIA; NEURONAL LOSS AB The authors developed multivariate models to examine the association between Clinical Dementia Rating (CDR) scale scores and the spatial distribution of paired helical filament tau (PHF-tau) pathology. Severity of tauopathy was examined in 14 cortical regions of interest (ROIs). Classification trees were used to test the independent hierarchical contributions of each ROI to dementia. Multiple-regression and cluster analyses were performed to determine the relative contributions of select ROIs to dementia. Dementia (CDR greater than or equal to 1) was modeled as a dichotomous variable. Autopsy material was obtained from 124 demented and nondemented elderly patients. All ROIs except the hippocampus made significant contributions to dementia. However, they were not independent. In multivariate models, only a single step (Step 7 in a hierarchical progression), which contained four ROIs, contributed significantly to dementia. A classification tree resulted in a single decision split, suggesting that only Step 7 ROIs need be considered. A total of 89.4% of the cases were correctly classified (p < .0001). Twelve discrepant cases all had superimposed vasculopathy that might also have affected the function of Step 7 ROIs. The transition to clinical dementia was associated with the presence of tauopathy in A9/10, A22, A23, and A39. Animal studies suggest that these represent a single distributed cortical network focusing on prefrontal regions that provide "executive control'' over complex goal-directed behaviors. A22, A23, and A39 provide major afferents to other frontal systems and have previously been implicated in very early clinical Alzheimer's disease. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Syst, Audie L Murphy Div GRECC, Dept Psychiat, San Antonio, TX USA. S Texas Vet Hlth Syst, Audie L Murphy Div GRECC, Dept Med, San Antonio, TX USA. S Texas Vet Hlth Syst, Audie L Murphy Div GRECC, Dept Pharmacol, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Family Practice, San Antonio, TX USA. Emile Roux Hosp, Limeil Brevannes, France. Unite INSERM Serv Neurol, Lille, France. RP Royall, DR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 73 TC 57 Z9 59 U1 3 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-073X J9 EXP AGING RES JI Exp. Aging Res. PD APR-JUN PY 2002 VL 28 IS 2 BP 143 EP 162 DI 10.1080/03610730252800166 PG 20 WC Geriatrics & Gerontology; Psychology SC Geriatrics & Gerontology; Psychology GA 525ZW UT WOS:000174104800002 PM 11928525 ER PT J AU Huang, WB Rudkin, GH Carlsen, B Ishida, K Ghasri, P Anvar, B Yamaguchi, DT Miller, TA AF Huang, WB Rudkin, GH Carlsen, B Ishida, K Ghasri, P Anvar, B Yamaguchi, DT Miller, TA TI Overexpression of BMP-2 modulates morphology, growth, and gene expression in osteoblastic cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE BMP-2; overexpression; osteoblast; differentiation; gene expression ID BONE MORPHOGENETIC PROTEIN-2; GAP JUNCTIONAL COMMUNICATION; TGF-BETA SUPERFAMILY; OSTEOGENIC PROTEIN-1; MC3T3-E1 CELLS; DIFFERENTIATION; C3H10T1/2; PROLIFERATION; PHENOTYPE; FRACTURE AB Bone morphogenetic proteins (BMP) play a pivotal role in growth and differentiation of osteoblastic lineage cells. BMPs are potent stimulators of bone formation in various animal models. To understand the mechanism of BMP action in bone cells, we have investigated the effects of overexpression of the BMP-2 gene on proliferation and differentiation of UMR-106 rat osteosarcoma cells. A stable AR-106 cell line overexpressing the BMP-2 gene was established by transfection of cells using a mammalian expression vector harboring human BMP-2 cDNA followed by 6418 selection. After introduction of the BMP-2 gene, UMR-106 cells appeared more spindle-shaped in morphology compared to the predominantly cuboidal appearance of the parental cells. Overexpression of BMP-2 markedly inhibited proliferation as measured by cell counting and [3H] thymidine incorporation assays. Extracellular matrix (ECM) derived from cells overexpressing BMP-2 exhibited a less supportive effect on proliferation of UMR cells than did ECM derived from parental cells. Furthermore, cell-cell communication through gap junctions was reduced more than 50% as determined by nondisruptive fluorescent dye transfer assays. Overexpression of BMP-2 significantly stimulated expression of osteocalcin and alkaline phosphatase genes, indicating its role in osteoblastic differentiation. There was little effect on osteopontin gene expression. (C) 2002 Elsevier Science (USA). C1 Vet Adm Greater Los Angeles Healthcare Syst, GRECC, Los Angeles, CA 90073 USA. Vet Adm Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90095 USA. VA GLAHS, Plast Surg Lab, W LA, Plast Surg Sect, Los Angeles, CA 90073 USA. RP Miller, TA (reprint author), VA GLAHS, Plast Surg Lab, W LA, Plast Surg Sect, Room 221,Bldg 114,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 35 TC 32 Z9 36 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD APR 1 PY 2002 VL 274 IS 2 BP 226 EP 234 DI 10.1006/excr.2002.5483 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 537ZJ UT WOS:000174789300007 PM 11900483 ER PT J AU Ishida, A Zeng, HQ Ogawa, M AF Ishida, A Zeng, HQ Ogawa, M TI Expression of lineage markers by CD34(+) hematopoietic stem cells of adult mice SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID VERSUS-HOST DISEASE; BONE-MARROW; LONG-TERM; CD34(+)THY-1(+)LIN(-) CELLS; FETAL LIVER; PROGENITORS; CD4; GENERATION; DEPLETION; GRAFT AB Objective. By using a murine transplantation model, we studied the relationship between CD34 expression and expression of CD4 and Mac-1 by hematopoietic stem cells of normal adult mice. Materials and Methods. Cells from Ly-5.1 C57BL/6 mice were used as test cells and lethally irradiated Ly-5.2 mice were used as recipient mice. Peripheral blood was obtained 6 months posttransplantation to analyze engraftment of donor-derived cells. Results. First, we determined that CD34(-) long-term reconstituting cells are CD4(-), while some CD34(+) stem cells express CD4. We then studied Mac-1 expression. Mac-1(-) and MaC-1(-low) populations of both CD34(-) and CD34(+) cells were capable of long-term reconstitution. Mac-1-(high) population of CD34(+) cells but not of CD34- cells also engrafted. Conclusions. These results strongly indicate that depletion of Mae-(1+) and CD4 cells in stem cell purification may inadvertently discard significant populations of CD34' stem cells. Since positive selection based on CD34 expression is the current practice for purification of human stem cells, our studies may possess implications in the purification of human hematopoietic stem cells. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Med Univ S Carolina, Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Ogawa, M (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. FU NCI NIH HHS [P01 CA 78582]; NIDDK NIH HHS [R01 DK 54197] NR 23 TC 22 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD APR PY 2002 VL 30 IS 4 BP 361 EP 365 AR PII S0301-472X(01)00795-0 DI 10.1016/S0301-472X(01)00795-0 PG 5 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 537FW UT WOS:000174749100011 PM 11937272 ER PT J AU Shifren, JL AF Shifren, JL TI Androgen deficiency in the oophorectomized woman SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT Conference on Androgen Insufficiency in Women CY JUL 29, 2001 CL PRINCETON, NEW JERSEY DE testosterone; androgens; oophorectomy; menopause; libido ID SEXUAL LIFE; HYSTERECTOMY; WOMEN AB Women experience a significant decline in circulating androgen concentrations after bilateral oohorectomy. Despite several limitations. studying women after oophorectomy remain,, a good model for investigating the effects of both androgen deficiency and androgen replacement. Current data show, that most women experience satisfying Sexual lives after hysterectomy and bilateral oophorectomy. This is reassuring since elective oophorectomy at the time of hysterectomy is air appropriate option for many women. Oophorectomized women, however, are more likely to report a worsening of sexual function after hysterectomy compared with women who retain their ovaries. Specifically, adverse changes in libido and orgasmic response are more likely in oophorectomized women. After bilateral oophorectomy, women also appear more likely to experience decreased positive psychological well-being. Studies of both the consequences or oophorectomy and the effects of testosterone replacement are consistent with all important role for androgens in female sexual C function and psychological well-being. (C) 2002 by American Society for Reproductive Medicine. C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Shifren, JL (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, 55 Fruit St,VBK 113, Boston, MA 02114 USA. NR 6 TC 26 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD APR PY 2002 VL 77 IS 4 SU 4 BP S60 EP S62 AR PII S0015-0282(02)02970-9 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 544CW UT WOS:000175141500012 PM 12007904 ER PT J AU Mustelin, T Abraham, RT Rudd, CE Alonso, A Merlo, JJ AF Mustelin, T Abraham, RT Rudd, CE Alonso, A Merlo, JJ TI Protein tyrosine phosphorylation in T cell signaling SO FRONTIERS IN BIOSCIENCE LA English DT Review DE Review; T cell activation; Lck; Fyn; c-Yes; Syk; ZAP-70; Itk; Txk; CD45; HePTP; PEP; PTP-MEG2; PTPH1; PTP-MEG1; PTP36; PTEN; LMPTP; PLCgamma1; SLP-76; LAT; FYB; SLAP-130; Vav-1; PI3K; c-Cbl; TSAd; SAP; SH2D1A; TRIM; Review ID RECEPTOR ZETA-CHAIN; SRC HOMOLOGY-2 DOMAIN; CD45 PHOSPHOTYROSINE PHOSPHATASE; SEVERE COMBINED IMMUNODEFICIENCY; VAV PROTOONCOGENE PRODUCT; LEUKOCYTE-COMMON ANTIGEN; PHOSPHOLIPASE C-GAMMA; AMINO-TERMINAL DOMAIN; NATURAL-KILLER-CELLS; HUMAN LYMPHOCYTES-T AB This review discusses in considerable detail the tyrosine phosphorylation events that couple the T cell antigen receptor to downstream signaling pathways. First, the protein kinases that catalyze these tyrosine phosphorylation are introduced, then the phosphatases that mediate removal of phosphate from tyrosine residues. Next, we discuss the molecular clock work by which these enzymes initiated T cell activation. Finally, we briefly review the key substrates for tyrosine phosphorylation and their role in coupling the kinases and phosphatases to gene transcription and other aspects of the T lymphocyte response to antigen. C1 Burnham Inst, Ctr Canc Res, Program Signal Transduct, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Mustelin, T (reprint author), Burnham Inst, Ctr Canc, Program Signal Transduct, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI Alonso, Andres/L-7523-2014 OI Alonso, Andres/0000-0001-8674-9378 FU NIAID NIH HHS [AI48032, AI35603, AI40552] NR 556 TC 29 Z9 30 U1 1 U2 7 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD APR PY 2002 VL 7 BP D918 EP D969 DI 10.2741/musteli1 PG 52 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 534RP UT WOS:000174600800018 PM 11897562 ER PT J AU Racke, FK Clare-Salzer, M Wilson, SB AF Racke, FK Clare-Salzer, M Wilson, SB TI Control of myeloid dendritic cell differentiation and function by CD1d-restricted (NK) T cells SO FRONTIERS IN BIOSCIENCE LA English DT Review DE dendritic cells; myeloid; Nk T cells; autoimmunity; diabetes; Th phenotype; antigen presenting cells; Cd1d; cellular immune responses; tumors; melanoma; review ID NONOBESE DIABETIC MICE; COLONY-STIMULATING FACTOR; ANTIGEN-PRESENTING CELLS; RESPONSES IN-VIVO; NOD MICE; ALPHA-GALACTOSYLCERAMIDE; CUTTING EDGE; FLT3 LIGAND; ANTITUMOR IMMUNITY; IL-12 PRODUCTION AB While regulating a wide variety of immunologic responses, the precise immunologic functions of CD1d-restricted (NK) T cells are not well defined. Notably, In vitro activation of human NK T cell clones results in the secretion of multiple cytokines important for the recruitment and differentiation of myeloid dendritic cells (DC). Once differentiated, these DC strongly activate NK T cells. In humans, CD1d is expressed by myeloid DC and on tumor cells of this lineage. Another specialized myeloid antigen presenting cell, the epithelioid histiocyte seen in granulomatous inflammation, also expresses CD1d. Because myeloid DC are important regulators of Th1/Th2 T cell responses, cross talk between human NK T cells and myeloid DC would be expected to have significant impact on many immune responses. Consistent with this hypothesis, NK T cells are required for myeloid DC-controlled antitumor responses in mice, and regulate diabetes in nonobese diabetic (NOD) mouse by locally controlling the frequency and function of DC subsets. Thus, regulation of myeloid DC by NK T cells controls both the transition from innate to adaptive immunity and the Th-phenotype of subsequent T cell responses. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21287 USA. Univ Florida, Coll Med, Dept Pathol, Gainesville, FL 32610 USA. RP Wilson, SB (reprint author), Dana Farber Canc Inst, Dana 1416,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI45051]; PHS HHS [P01142288] NR 70 TC 3 Z9 3 U1 0 U2 0 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 APR PY 2002 VL 7 BP D978 EP D985 DI 10.2741/racke PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 534RP UT WOS:000174600800020 PM 11897563 ER PT J AU Gukovskaya, AS Vaquero, E Zaninovic, V Gorelick, FS Lusis, AJ Brennan, ML Holland, S Pandol, SJ AF Gukovskaya, AS Vaquero, E Zaninovic, V Gorelick, FS Lusis, AJ Brennan, ML Holland, S Pandol, SJ TI Neutrophils and NADPH oxidase mediate intrapancreatic trypsin activation in murine experimental acute pancreatitis SO GASTROENTEROLOGY LA English DT Article ID OXIDATIVE STRESS; SUPEROXIDE-DISMUTASE; ACINAR-CELLS; OXYGEN RADICALS; RESPIRATORY BURST; CERULEIN; RATS; PATHOGENESIS; CHOLECYSTOKININ; CATALASE AB Background & Aims: Intrapancreatic activation of digestive enzymes is a key event in the parenchymal cell injury of pancreatitis. We hypothesized that neutrophils recruited to the pancreas during pancreatitis may contribute to such activation. Methods: To cause experimental pancreatitis, rats and mice were treated with high doses of cerulein. Activation of the digestive enzyme, trypsin, was measured in pancreatic homogenates using a fluorogenic assay and localized immunocytochemically with antibody to trypsin-activation peptide (TAP). Results: Compared with controls, rats depleted of neutrophils with antineutrophil serum exhibited a marked attenuation in intrapancreatic trypsin activation and acinar cell TAP labeling induced by high-dose cerulein. To examine the mechanism, mice deficient in either nicontinamide adenine dinucleotide phosphate (NADPH) oxidase, or myeloperoxidase (MPO) were studied for trypsin activation. Mice deficient in NADPH oxidase exhibited attenuation of the cerulein-induced trypsin activation, but those deficient in MPO did not. Using measurements of Western blot analysis, generation of reactive oxygen species, and immunocytochemistry, we demonstrated the NADPH oxidase activity is in neutrophils and not pancreatic acinar tissue. Conclusions: The results demonstrate a novel role for neutrophils infiltrating the pancreas in pathologic activation of digestive enzymes in acute pancreatitis and indicate that this effect is mediated by products of NADPH oxidase. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. NIAID, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT USA. Vet Affairs Connecticut Healthcare Syst, Dept Med, West Haven, CT USA. Univ Calif Los Angeles, Dept Med, Dept Human Genet, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90024 USA. RP Gukovskaya, AS (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Blsg 258,Room 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu FU NHLBI NIH HHS [HL30568]; NIAAA NIH HHS [P50 AA11999] NR 57 TC 136 Z9 141 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2002 VL 122 IS 4 BP 974 EP 984 DI 10.1053/gast.2002.32409 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 534ZA UT WOS:000174618600019 PM 11910350 ER PT J AU Blackwell, TK Walker, AK AF Blackwell, TK Walker, AK TI Getting the right dose of repression SO GENES & DEVELOPMENT LA English DT Editorial Material ID DOSAGE-COMPENSATION; X-CHROMOSOME; C-ELEGANS; TRANSCRIPTIONAL REPRESSION; SEX; MACHINERY; NEMATODE C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM62891, R01 GM062891] NR 23 TC 3 Z9 12 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 1 PY 2002 VL 16 IS 7 BP 769 EP 772 DI 10.1101/gad.986102 PG 4 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 541EG UT WOS:000174971800001 PM 11937484 ER PT J AU Oliver, G Detmar, M AF Oliver, G Detmar, M TI The rediscovery of the lymphatic system: old and new insights into the development and biological function of the lymphatic vasculature SO GENES & DEVELOPMENT LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; BREAST-CANCER METASTASIS; VEGF-C; TUMOR LYMPHANGIOGENESIS; HEREDITARY LYMPHEDEMA; TRANSGENIC MICE; MICROVESSEL DENSITY; FACTOR RECEPTOR-3; NODE METASTASIS; PROX1 FUNCTION C1 St Jude Childrens Res Hosp, Dept Genet, Memphis, TN 38105 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Detmar, M (reprint author), St Jude Childrens Res Hosp, Dept Genet, 332 N Lauderdale St, Memphis, TN 38105 USA. EM guillermo.oliver@stjude.org; michael.detmar@cbrc2.mgh.harvard.edu FU NCI NIH HHS [CA21765, CA69184, CA86410, CA91861]; NEI NIH HHS [EY12162]; NIGMS NIH HHS [GM58462] NR 70 TC 229 Z9 244 U1 2 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 1 PY 2002 VL 16 IS 7 BP 773 EP 783 DI 10.1101/gad.975002 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 541EG UT WOS:000174971800002 PM 11937485 ER PT J AU Galagan, JE Nusbaum, C Roy, A Endrizzi, MG Macdonald, P FitzHugh, W Calvo, S Engels, R Smirnov, S Atnoor, D Brown, A Allen, N Naylor, J Stange-Thomann, N DeArellano, K Johnson, R Linton, L McEwan, P McKernan, K Talamas, J Tirrell, A Ye, WJ Zimmer, A Barber, RD Cann, I Graham, DE Grahame, DA Guss, AM Hedderich, R Ingram-Smith, C Kuettner, HC Krzycki, JA Leigh, JA Li, WX Liu, JF Mukhopadhyay, B Reeve, JN Smith, K Springer, TA Umayam, LA White, O White, RH de Macario, EC Ferry, JG Jarrell, KF Jing, H Macario, AJL Paulsen, I Pritchett, M Sowers, KR Swanson, RV Zinder, SH Lander, E Metcalf, WW Birren, B AF Galagan, JE Nusbaum, C Roy, A Endrizzi, MG Macdonald, P FitzHugh, W Calvo, S Engels, R Smirnov, S Atnoor, D Brown, A Allen, N Naylor, J Stange-Thomann, N DeArellano, K Johnson, R Linton, L McEwan, P McKernan, K Talamas, J Tirrell, A Ye, WJ Zimmer, A Barber, RD Cann, I Graham, DE Grahame, DA Guss, AM Hedderich, R Ingram-Smith, C Kuettner, HC Krzycki, JA Leigh, JA Li, WX Liu, JF Mukhopadhyay, B Reeve, JN Smith, K Springer, TA Umayam, LA White, O White, RH de Macario, EC Ferry, JG Jarrell, KF Jing, H Macario, AJL Paulsen, I Pritchett, M Sowers, KR Swanson, RV Zinder, SH Lander, E Metcalf, WW Birren, B TI The genome of M-acetivorans reveals extensive metabolic and physiological diversity SO GENOME RESEARCH LA English DT Article ID METHANOSARCINA-BARKERI FUSARO; METHANOCOCCUS-VOLTAE; ESCHERICHIA-COLI; MAZEI S-6; SP-NOV; ARCHAEA; GENES; EXPRESSION; SEQUENCE; PROTEIN AB Methanogenesis, the biological production of methane, plays a pivotal role in the global carbon cycle and contributes significantly to global warming. The majority of methane in nature is derived from acetate. Here we report the complete genome sequence of an acetate-utilizing methanogen, Methanosarcina acetivorans C2A. Methanosarcineae are the most metabolically diverse methanogens, thrive in a broad range of environments, and are unique among the Archaea in forming complex multicellular structures. This diversity Is reflected In the genome of M. acetivorans. At 5,751,492 base pairs it is by far the largest known archaeal genome. The 4524 open reading frames code for a strikingly wide and unanticipated variety of metabolic and cellular capabilities. The presence of novel methyltransferases indicates the likelihood of undiscovered natural energy sources for methanogenesis, whereas the presence of single-subunit carbon monoxide dehydrogenases raises the possibility of nonmethanogenic growth. Although motility has not been observed in any Methanosarcineae, a flagellin gene cluster and two complete chemotaxis gene clusters were identified. The availability of genetic methods, coupled with its physiological and metabolic diversity, makes M. acetivorans a powerful model organism for the study of archaeal biology. C1 Whitehead Inst Ctr Genome Res, Cambridge, MA 02141 USA. Univ Wisconsin Parkside, Dept Biol Sci, Kenosha, WI 53141 USA. Univ Illinois, Dept Anim Sci, Urbana, IL 61801 USA. Virginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USA. Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20814 USA. Univ Illinois, Dept Microbiol, Urbana, IL 61801 USA. Max Planck Inst Terr Mikrobiol, D-35043 Marburg, Germany. Clemson Univ, Dept Biochem & Genet, Clemson, SC 29634 USA. Ohio State Univ, Dept Microbiol, Columbus, OH 43210 USA. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. Univ Kentucky, TH Morgan Sch Biol Sci, Lexington, KY 40506 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Inst Genomic Res, Rockville, MD 20878 USA. SUNY Albany, Dept Biomed Sci, Sch Publ Hlth, Albany, NY 12201 USA. New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. Queens Univ, Dept Microbiol & Immunol, Kingston, ON KYL 3N6, Canada. Univ Maryland, Ctr Marine Biotechnol, Inst Biotechnol, Baltimore, MD 21202 USA. Syrrx Inc, San Diego, CA 92121 USA. Cornell Univ, Ithaca, NY 14853 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Birren, B (reprint author), Whitehead Inst Ctr Genome Res, Cambridge, MA 02141 USA. RI Graham, David/F-8578-2010; Guss, Adam/A-6204-2011; Paulsen, Ian/K-3832-2012; OI Swanson, Ronald/0000-0002-6486-2676; Graham, David/0000-0001-8968-7344; Guss, Adam/0000-0001-5823-5329; Paulsen, Ian/0000-0001-9015-9418; Liu, Jinfeng/0000-0002-0343-8222; Galagan, James/0000-0003-0542-3291; Engels, Reinhard/0000-0003-0921-0736; McKernan, Kevin/0000-0002-3908-1122 NR 55 TC 385 Z9 899 U1 2 U2 48 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD APR PY 2002 VL 12 IS 4 BP 532 EP 542 DI 10.1101/gr.223902 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 541DZ UT WOS:000174971100003 PM 11932238 ER PT J AU Spiro, RG AF Spiro, RG TI Protein glycosylation: nature, distribution, enzymatic formation, and disease implications of glycopeptide bonds SO GLYCOBIOLOGY LA English DT Review DE consensus sequence of glycoproteins; diseases of protein glycosylation; glycosyltransferases; N-glycosylation; O-glycosylation ID POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE; O-LINKED GLYCOSYLATION; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; GLOMERULAR-BASEMENT-MEMBRANE; SURFACE-LAYER GLYCOPROTEIN; BETA-D-XYLOSYLTRANSFERASE; RABBIT SKELETAL-MUSCLE; GROWTH-FACTOR DOMAIN; UDP-D-XYLOSE; ENDOPLASMIC-RETICULUM AB Formation of the sugar-amino acid linkage is a crucial event in the biosynthesis of the carbohydrate units of glycoproteins. It sets into motion a complex series of posttranslational enzymatic steps that lead to the formation of a host of protein-bound oligosaccharides with diverse biological functions. These reactions occur throughout the entire phylogenetic spectrum, ranging from archaea and eubacteria to eukaryotes. It is the aim of this review to describe the glycopeptide linkages that have been found to date and specify their presence on well-characterized glycoproteins. A survey is also made of the enzymes involved in the formation of the various glycopeptide bonds as well as the site of their intracellular action and their affinity for particular peptide domains is evaluated. This examination indicates that 13 different monosaccharides and 8 amino acids are involved in glycoprotein linkages leading to a total of at least 41 bonds, if the anomeric configurations, the phosphoglycosyl linkages, as well as the GPI (glycophosphatidylinositol) phosphoethanolamine bridge are also considered. These bonds represent the products of N- and O-glycosylation, C-mannosylation, phosphoglycation, and glypiation. Currently at least 16 enzymes involved in their formation have been identified and in many cases cloned. Their intracellular site of action varies and includes the endoplasmic reticulum, Golgi apparatus, cytosol, and nucleus. With the exception of the Asn-linked carbohydrate and the GPI anchor, which are transferred to the polypeptide en bloc, the sugar-amino acid linkages are formed by the enzymatic transfer of an activated monosaccharide directly to the protein. This review also deals briefly with glycosidases, which are involved in physiologically important cleavages of glycopeptide bonds in higher organisms, and with a number of human disease states in which defects in enzymatic transfer of saccharides to protein have been implicated. C1 Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Spiro, RG (reprint author), Harvard Univ, Sch Med, Dept Biol Chem, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK17325, DK17477] NR 165 TC 635 Z9 656 U1 25 U2 168 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD APR PY 2002 VL 12 IS 4 BP 43R EP 56R DI 10.1093/glycob/12.4.43R PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 565GV UT WOS:000176362200002 PM 12042244 ER PT J AU Skates, SJ AF Skates, SJ TI Screening for ovarian cancer - Risk, education, worry: Path to appropriate use? SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Skates, SJ (reprint author), Massachusetts Gen Hosp, Ctr Biostat, 50 Staniford St,Suite 560, Boston, MA 02114 USA. FU NCI NIH HHS [U01 CA78284] NR 8 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2002 VL 85 IS 1 BP 1 EP 2 DI 10.1006/gyno.2002.6641 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 542AD UT WOS:000175019400001 PM 11925112 ER PT J AU Duska, LR Wimberly, J Deutsch, TF Ortel, B Haas, J Houck, K Hasan, T AF Duska, LR Wimberly, J Deutsch, TF Ortel, B Haas, J Houck, K Hasan, T TI Detection of female lower genital tract dysplasia using orally administered 5-aminolevulinic acid induced protoporphyrin IX: A preliminary study SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the Society-of-Gynecologic-Oncologists CY MAR 03-07, 2001 CL NASHVILLE, TENNESSEE SP Soc Gynecol Oncologists ID CERVICAL INTRAEPITHELIAL NEOPLASIA; PHOTODYNAMIC THERAPY; AMINOLEVULINIC ACID; INTRAVESICAL INSTILLATION; FLUORESCENCE; BLADDER; PHOTOSENSITIZATION; PHOTODETECTION; CARCINOMA AB Objective. Previous studies have suggested that 5-aminolevulinic acid (ALA) may be used topically on the cervix to allow optical detection of cervical dysplasia, based on the fluorescence of protoporphyrin IX (PpIX) synthesized in situ from ALA. However, the uniformity of distribution of topically applied PpIX and the sensitivity and specificity of detection are not optimal. The current study was undertaken to demonstrate the feasibility of administering ALA by mouth (po) with the hypothesis that systemic administration might provide a more reliable diagnostic tool. Methods. Oral ALA was administered to 14 patients with abnormal Pap smears in a dose- and time-intensity design. Institutional review board approval was obtained. A starting dose of 10 mg/kg of po ALA was administered and colposcopy was performed in 3 patients at 1 h, 3 patients at 2 h, 6 patients at 3 h. and 2 patients at 4 h. The study was written with the intent to increase the dose in 10 mg/kg increments if fluorescence was not detected; however, fluorescence was detected at the first dose level. Liver function tests were checked pre and post ALA and follow-up telephone calls were made regarding possible side effects. Both white and blue light colposcopy examinations were performed by two blinded clinicians and biopsies of all abnormal areas were performed. Results. All patients tolerated po ALA well, with no systemic side effects. At the 10 mg/kg dose there was no reported nausea or photosensitivity. Optimal fluorescence was achieved at the 3-h time point, with quenching noted at the 4-h time point. Excellent absorption was documented with fluorescence of the lip demonstrated with Wood's lamp. In some cases fluorescence correlated with dysplasia on biopsy. Conclusion. 5-ALA given via the po route and at the dose and time period studied is well tolerated and affords fluorescence of the cervix. Future study is needed to demonstrate the successful identification of dysplastic lesions, with the ultimate goal of treating dysplasia of the lower genital tract with 5-ALA and light therapy. (C) 2002 Elsevier Science (USA). C1 Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Gynecol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Dermatol, Wellman Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Pathol, Boston, MA 02114 USA. RP Duska, LR (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Gynecol Serv, Boston, MA 02114 USA. FU NIAMS NIH HHS [AR40352] NR 18 TC 9 Z9 9 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2002 VL 85 IS 1 BP 125 EP 128 DI 10.1006/gyno.2001.6580 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 542AD UT WOS:000175019400020 PM 11925131 ER PT J AU Wang, ZGC Smith, AG Yunis, EJ Selvakumar, A Ferrone, S McKinney, S Lee, JH Fernandez-Vina, M Hansen, JA AF Wang, ZGC Smith, AG Yunis, EJ Selvakumar, A Ferrone, S McKinney, S Lee, JH Fernandez-Vina, M Hansen, JA TI Molecular characterization of the HLA-Cw*0409N allele SO HUMAN IMMUNOLOGY LA English DT Article DE HLA null allele; Cw*0409N; PCR; DNA sequencing; IEF ID A NULL ALLELE; HLA-A; MONOCLONAL-ANTIBODIES; NUCLEOTIDE DELETION; MELANOMA-CELLS; STOP CODON; GENE; EXPRESSION; ANTIGENS; MUTATION AB Various molecular methods in conjunction with serologic assays are used for clinical human leukocyte antigen (FILA) typing. Although serologic reagents detect most HLA-A and -B allospecificities, serologic HLA-C typing is hampered by the lack of informative antisera for many of the known FILA-C gene products. HLA antigens not detected by serology, but detected by molecular methods, are often referred to as "blank" antigens. Their lack of reactivity with antibodies in serological assays often reflects the preset-ice of null alleles. The present study has characterized an HLA-Cw*04 allele (Cw*0409N) detected by DNA typing but not by serology. In cultured B-lymphoid 13W09501 cells carrying this Cw*04 null allele, isoelectric focusing analysis could not detect any component with a pattern compatible with that of the product of the HLA-Cw*0401 allele, but detected components reacting with an anti-HLA-Cw4 and Cw6 monoclonal antibody. Sequencing analysis of the full length HLA-Cw4 cDNA amplified from the cell line 13W095-01 revealed a base deletion at codon 365 in exon 7, resulting in a reading frame shift that added 32 amino acids at the C-terminal of the HLA-Cw4 heavy chain. These results indicate that the HLA-Cw*0409N allele may produce a putative long HLA-Cw4 heavy chain that is not expressed on the cell surface. (C) American Society for Histocompatibility and Immunogenetics, 2002. Published by Elsevier Science Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Seattle Canc Care Alliance, Seattle, WA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. One Lambda Inc, Canoga Pk, CA USA. Amer Red Cross Natl Histocompatibil Lab, Baltimore, MD USA. RP Wang, ZGC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St,SM822, Boston, MA 02115 USA. FU NCI NIH HHS [CA15704, CA23766, CA67108, CA18029]; NHLBI NIH HHS [HL59838, HL29583]; NIAID NIH HHS [AI49213, AI33484] NR 24 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD APR PY 2002 VL 63 IS 4 BP 295 EP 300 AR PII S0198-8859(02)00376-2 DI 10.1016/S0198-8859(02)00376-2 PG 6 WC Immunology SC Immunology GA 542BG UT WOS:000175023200007 PM 12039411 ER PT J AU Shoichet, SA Baumer, AT Stamenkovic, D Sauer, H Pfeiffer, AFH Kahn, CR Muller-Wieland, D Richter, C Ristow, M AF Shoichet, SA Baumer, AT Stamenkovic, D Sauer, H Pfeiffer, AFH Kahn, CR Muller-Wieland, D Richter, C Ristow, M TI Frataxin promotes antioxidant defense in a thiol-dependent manner resulting in diminished malignant transformation in vitro SO HUMAN MOLECULAR GENETICS LA English DT Article ID GAA TRIPLET REPEAT; FRIEDREICH ATAXIA; IN-VIVO; IRON; CANCER; DEFICIENCY; STRESS; MOUSE AB Friedreich ataxia is an inherited disorder caused by decreased expression of frataxin protein. Increasing evidence suggests that this protein might detoxify reactive oxygen species (ROS) by an unknown mechanism. Here we demonstrate that transgenic overexpression of human frataxin increases cellular antioxidant defense via activation of glutathione peroxidase and elevation of reduced thiols, thereby reducing the incidence of malignant transformation induced by ROS, as observed by soft agar assays and tumour formation in nude mice. These findings expand the understanding of antioxidant properties of frataxin, and tentatively suggest a role in the early induction of cancer. C1 German Inst Human Nutr, DIfE, KLE, D-14558 Potsdam, Germany. Univ Cologne, Ctr Mol Med, Clin Internal Med 3, D-5000 Cologne 41, Germany. Univ Cologne, Ctr Physiol & Pathophysiol, D-5000 Cologne 41, Germany. Free Univ Berlin, D-1000 Berlin, Germany. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Diabet Res Inst DFI, Dept Biochem, Dusseldorf, Germany. Swiss Fed Inst Technol, Inst Biochem, Zurich, Switzerland. RP Ristow, M (reprint author), German Inst Human Nutr, DIfE, KLE, 114 Arthur Scheunert Allee, D-14558 Potsdam, Germany. RI Ristow, Michael/O-9858-2014 OI Ristow, Michael/0000-0003-2109-2453 NR 45 TC 56 Z9 56 U1 1 U2 2 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 APR 1 PY 2002 VL 11 IS 7 BP 815 EP 821 DI 10.1093/hmg/11.7.815 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 538CU UT WOS:000174797100010 PM 11929854 ER PT J AU Cho, SI Goldman, MB Ryan, LM Chen, C Damokosh, AI Christiani, DC Lasley, BL O'Connor, JF Wilcox, AJ Xu, X AF Cho, SI Goldman, MB Ryan, LM Chen, C Damokosh, AI Christiani, DC Lasley, BL O'Connor, JF Wilcox, AJ Xu, X TI Reliability of serial urine HCG as a biomarker to detect early pregnancy loss SO HUMAN REPRODUCTION LA English DT Article DE early pregnancy loss; human chorionic gonadotrophin; immunoradiometric assay; reliability ID HUMAN CHORIONIC-GONADOTROPIN; HEALTH; WOMEN AB Background: To examine the reliability of HCG as a biomarker for early pregnancy loss, five experienced researchers independently assessed data from 153 menstrual cycles, determining whether each cycle represented,no conception,' a 'continuing conception' or a 'conception lost.' Methods: Urine samples were analysed by immunoradiometric assay using a combination of capture antibodies for the intact heterodimer (B109) and for an epitope common to the beta subunit and the beta core fragment (B204). For each cycle, HCG data were presented as graphs of daily assay results. Summary statistics for HCG assays from 46 women who had undergone bilateral tubal ligation represented baseline values. Results: Pairwise agreement among the assessors for any of the three options ranged from 78-89%. At least three experts agreed for 147 cycles (96%), accounting for 28 conception losses and 19 continuing conceptions. The multi-rater kappa was 0.62 for the conception lost category and 0.68 for continuing conceptions, indicating substantial agreement. Conclusion: The main sources of disagreement involved deciding whether there was sufficient information for assessment, interpreting cycle parameters such as cycle length or bleeding event, and interpreting a distinct HCG rise pattern that does not exceed the baseline value obtained from the sterilized women. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Calif Davis, Inst Toxicol & Environm Hlth, Davis, CA 95616 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. RP Xu, X (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, 665 Huntington Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009; OI Ryan, Louise/0000-0001-5957-2490; Wilcox, Allen/0000-0002-3376-1311 FU NICHD NIH HHS [1R01 HD32505-01]; NIEHS NIH HHS [1R01 ES08337-01, 5P30 ES000002-38]; NIOSH CDC HHS [1R01 OH03027] NR 16 TC 6 Z9 7 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD APR PY 2002 VL 17 IS 4 BP 1060 EP 1066 DI 10.1093/humrep/17.4.1060 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 543UA UT WOS:000175118500037 PM 11925406 ER PT J AU Manis, JP Dudley, D Kaylor, L Alt, FW AF Manis, JP Dudley, D Kaylor, L Alt, FW TI IgH class switch recombination to IgG1 in DNA-PKcs-deficient B cells SO IMMUNITY LA English DT Article ID CYTIDINE DEAMINASE AID; DOUBLE-STRAND BREAKS; V(D)J RECOMBINATION; SOMATIC HYPERMUTATION; CIRCULAR DNA; IMMUNOGLOBULIN GENES; EMBRYONIC LETHALITY; CATALYTIC SUBUNIT; MICE DEFICIENT; SCID MICE AB To assess the role of the DNA-PKcs nonhomologous DNA end-joining (NHEJ) protein in Ig heavy chain class switch recombination (CSR), we assayed CSR ability of DNA-PKcs-deficient (DP-T) B cells generated via complementation of DP-T mice with Ig heavy chain and light chain knockin transgenes (DP-T/HC/LC mice). DP-T/HC/LC mice were severely deficient for all serum IgH isotypes except IgM and, unexpectedly, IgG1. Upon appropriate stimulation, DP-T/HC/LC B cells showed normal proliferation, germline CH gene transcription, and AID induction, indicating that DNA-PKcs deficiency did not affect cellular events upstream to CSR. Yet, in vitro activated DP-T/HC/LC B cells again underwent switching only to IgG1 and, like wild-type cells, frequently underwent CSR to gamma1 on both chromosomes. We conclude that DNA-PKcs is required for CSR to most C-H genes but that CSR to gamma1 occurs via a DNA-PKcs-independent mechanism. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, 300 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [AI 31541] NR 59 TC 104 Z9 104 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD APR PY 2002 VL 16 IS 4 BP 607 EP 617 DI 10.1016/S1074-7613(02)00306-0 PG 11 WC Immunology SC Immunology GA 543PD UT WOS:000175109600011 PM 11970883 ER PT J AU Goldsmith, CAW Ning, YY Qin, GZ Imrich, A Lawrence, J Murthy, GGK Catalano, PJ Kobzik, L AF Goldsmith, CAW Ning, YY Qin, GZ Imrich, A Lawrence, J Murthy, GGK Catalano, PJ Kobzik, L TI Combined air pollution particle and ozone exposure increases airway responsiveness in mice SO INHALATION TOXICOLOGY LA English DT Article ID DIESEL EXHAUST PARTICLES; BRONCHIAL EPITHELIAL-CELLS; PULMONARY-FUNCTION CHANGES; MURINE STRAIN DIFFERENCES; OIL FLY-ASH; RESPIRATORY HEALTH; AMBIENT AIR; TRACE-ELEMENTS; MEXICO-CITY; NONASTHMATIC SUBJECTS AB We investigated whether coexposure to inhaled ambient particles and ozone affects airway responsiveness (AR, measured as enhanced pause, Penh) and allergic inflammation ( AI) in a murine model of asthma. Ovalbumin-sensitized mice were challenged with either ovalbumin ("asthmatic") or phosphate-buffered saline (PBS) aerosols for 3 successive days. Immediately after daily challenge, mice were exposed for 5 h to concentrated ambient particles (CAPs), or 0.3 ppm ozone, or both, or neither (n greater than or equal to 61/ group, 12 experiments). Exposure to CAPs alone or coexposure to CAPs + O-3 caused an increase in Penh in both normal and "asthmatic" mice. These responses were transient and small, increasing approximately 0.9% per 100-mug/m(3) increase in CAPs. Analysis of the effects of particle composition on AR revealed an association between the AlSi particle fraction and increased AR in "asthmatic" mice exposed to ozone and particles. No effects of pollutants on AI were noted. We conclude that (1) particle exposure causes an immediate, short-lived (<24 h) increase in AR in mice; (2) these responses are small; and ( 3) changes in AR may be correlated with specific elements within the particle mixture. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Physiol Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Kobzik, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Physiol Program, II-221,665 Huntington Ave, Boston, MA 02115 USA. FU NIEHS NIH HHS [ES 08129, ES 00002] NR 92 TC 18 Z9 18 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD APR PY 2002 VL 14 IS 4 BP 325 EP 347 PG 23 WC Toxicology SC Toxicology GA 540YK UT WOS:000174958300001 PM 12028808 ER PT J AU Gans, JS Rutan, JS Lape, E AF Gans, JS Rutan, JS Lape, E TI The demonstration group: A tool for observing group process and leadership style SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article ID GROUP-PSYCHOTHERAPY; EXPERIENTIAL GROUP; GROUP-THERAPY; SUPERVISION AB Demonstration groups, a major modality for observing group process, have not been addressed in the group psychotherapy literature. This article defines the demonstration group and describes and discusses its various components: the volunteers (group members) and their recruitment, the demonstration group itself, group member debriefing, and the didactic component. Discussion of the physical setting, group agreements, and boundary considerations, as well as leadership tasks, challenges, and pitfalls are illustrated with examples. Leadership tasks in demonstration groups are compared with those in therapy groups. Guidelines that are likely to promote successful demonstration group experiences are Provided. The leader's facility with the unconscious defense mechanism of projective identification is stressed. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Boston Inst Psychotherapies Inc, Boston, MA USA. Massachusetts Gen Hosp, Ctr Grp Psychotherapy, Boston, MA 02114 USA. Univ Virginia, Ctr Counseling & Psychol Serv, Charlottesville, VA 22903 USA. RP Gans, JS (reprint author), 55 Cleveland Rd, Wellesley, MA 02481 USA. NR 22 TC 3 Z9 3 U1 0 U2 4 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD APR PY 2002 VL 52 IS 2 BP 233 EP 252 DI 10.1521/ijgp.52.2.233.45502 PG 20 WC Psychology, Clinical SC Psychology GA 533FB UT WOS:000174517800005 PM 11928201 ER PT J AU Yates, KE Troulis, MJ Kaban, LB Glowacki, J AF Yates, KE Troulis, MJ Kaban, LB Glowacki, J TI IGF-I, TGF-beta, and BMP-4 are expressed during distraction osteogenesis of the pig mandible SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article DE distraction osteogenesis; bone formation; growth factors; gene expression ID GENE-EXPRESSION; BONE-FORMATION; MESSENGER-RNA; MODEL AB The mechanisms that regulate bone formation during distraction osteogenesis (DO) are not completely understood. Our hypothesis is that local cytokines that stimulate osteoblast activity are potential regulators of this process, The purpose of this study was to determine gene expression of insulin-like growth factor I (IGF-I), transforming growth factor-beta (TGF-beta), and bone morphogenetic protein 4 (BMP-4) in distracted wounds. A semiburied. rigid distraction device was placed across an osteotomy at the right mandibular angle in 9 Yucatan minipigs. Distraction was begun immediately at a rate of 1 mm/day. The animals were sacrificed after 4 and 7 days of distraction. and after 7 days of distraction pills 4 days of neutral fixation, Excised wound tissues were processed for histologic and gene expression analyses. Competitive reverse-transcription polymerase chain reaction (RT-PCR) assays were developed and validated for porcine genes. Histologic analysis showed membranous ossification within the DO wound. Gene expression of IGF-I, TGF-beta and BMP-4 was detected during distraction and neutral fixation. These results show that gene expression analyses can be performed in a large animal model of mandibular DO. As the pig mandible closely resembles that of the human in morphology and physiology, this is an important step toward characterization of the early molecular events in the DO wound. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. RP Yates, KE (reprint author), Massachusetts Gen Hosp, Skeletal Biol Res Ctr, 149 13th St,Code 5031, Charlestown, MA 02129 USA. NR 25 TC 33 Z9 37 U1 1 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0901-5027 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD APR PY 2002 VL 31 IS 2 BP 173 EP 178 DI 10.1054/ijom.2001.0204 PG 6 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 553NG UT WOS:000175681900009 PM 12102416 ER PT J AU Yantiss, RK Rosenberg, AE Selig, MK Nielsen, GP AF Yantiss, RK Rosenberg, AE Selig, MK Nielsen, GP TI Gastrointestinal stromal tumors: An ultrastructural study SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE gastrointestinal stromal tumor; mesenchymal neoplasms; gastrointestinal tract; ultrastructure; interstitial cells of Cajal ID AUTONOMIC NERVE TUMORS; HUMAN SMALL-INTESTINE; INTERSTITIAL-CELLS; SKEINOID FIBERS; MUSCLE; CAJAL; COLON; PLEXUS; LIGHT AB Gastrointestinal stromal tumors (GISTs) represent an enigmatic group of lesions of uncertain phenotype and biologic potential. Although earlier studies suggested smooth muscle cells, schwann cells, or neuronal differentiation, more recent evidence indicates that these tumors show phenotypic features that are similar to the interstitial cells of Cajal. Recently, investigators have begun to evaluate these lesions in a site-specific manner and have found that, in addition to morphologic differences between them, their biologic behavior also appears to be linked to their anatomic location. Many of these studies have emphasized the histologic and immunophenotypic features of GISTs in relation to their sites of origin, however, their site-specific ultrastructural characteristics have received little attention in the Literature. In this study, we evaluated 34 GISTs (15 gastric, 12 small intestinal, 4 colonic, and 3 omental) for a variety of ultrastructural features in an effort to identify site-specific similarities and differences. Tumors predominantly composed of epithelioid cells were more commonly seen in gastric (60%) and omental (67%) tumors than in those of the small intestine (33%) and colon (0%). Cytoplasmic filaments and intercellular junctions were commonly seen in tumors from all locations, the filaments frequently forming paranuclear aggregates in the epithelioid cells. Tumors from all sites were composed of cells with surface filopodia and interdigitating cell processes, but in tumors of the stomach and omentum the filopodia were usually short and minimally intertwined, whereas those of small and large intestinal GISTs were characteristically long and complex. Basal lamina, though poorly formed, was present only in tumors of gastric and omental origin (13% and 67%, respectively). Pinocytotic vesicles were also seen in tumors from these sites (33% of gastric tumors and 67% of omental lesions) as well as those of the small intestine (117%) and the colon (25%). None of the gastric or omental tumors had microtubules; they were, however, seen in small intestinal (33%) and colonic (25%) stromal tumors. Skenoid fibers were seen in 33% of small intestinal GISTs and 1 metastatic oastric GIST. Overall, gastric and omental tumors have better developed features of myogenic differentiation and have blunt filopodia and minimally intertwined cell processes, Indeed, these 2 groups are indistinguishable ultrastructurally, raising the possibility that the genesis of omental GISTs is similar to that of gastric stromal tumors. Small intestinal stromal tumors have characteristic interdigitating cell processes and numerous elongate filopodia-like structures harboring intercellular junctions as well as microtubules and extracellular skenoid fibers. The constituent cells in colonic stromal tumors, while more reminiscent of small intestinal stromal, were frequently more primitive in appearance. In conclusion, GISTs from different anatomic locations share many overlapping ultrastructural characteristics; however, a few features are distinctive. It is hoped that these findings will aid in their recognition and contribute to the classification of 0 this heterogeneous group of neoplasms. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02214 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Nielsen, GP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02214 USA. NR 29 TC 22 Z9 22 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD APR PY 2002 VL 10 IS 2 BP 101 EP 113 DI 10.1177/106689690201000203 PG 13 WC Pathology; Surgery SC Pathology; Surgery GA 564QC UT WOS:000176324200003 PM 12075403 ER PT J AU Gatinel, D Malet, J Hoang-Xuan, T Azar, DT AF Gatinel, D Malet, J Hoang-Xuan, T Azar, DT TI Analysis of customized corneal ablations: Theoretical limitations of increasing negative asphericity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID IN-SITU KERATOMILEUSIS; PHOTOREFRACTIVE KERATECTOMY; OPTICAL-PERFORMANCE; REFRACTIVE SURGERY; HIGH MYOPIA; KERATOCONUS; ABERRATIONS; LENS; AGE; EYE AB PURPOSE. To determine the ablation depths of customized myopic excimer laser photoablations performed to change corneal asphericity after laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). METHODS. A mathematical model of aspheric myopic corneal laser surgery was generated. The initial corneal surface was modeled as a conic section of apical radius R-1 and asphericity Q(1). The final corneal surface was modeled as a conic section of apical R-2 and asphericity Q(2), where R-2 was calculated from the paraxial optical formula for a given treatment magnitude (D), and Q(2) was the intended final asphericity. The aspheric profile of ablation was defined as the difference between the initial and final corneal profiles for a given optical zone diameter (S), and the maximal depth of ablation was calculated from these equations. Using the Taylor series expansion, an equation was derived that allowed the approximation of the central depth of ablation (t(0)) for various magnitudes of treatment. optical zone diameters, and asphericity. In addition to the Munnerlyn term (M), incorporating Munnerlyn's approximation (-D . S-2/3), the equation included an asphericity term (A) and a change of asphericity term (Delta). This formula (t(0) = M + A + Delta) was used to predict the maximal depth of ablation and the limits of customized asphericity treatments in several theoretical situations. RESULTS. When the initial and final asphericities were identical (no intended change in asphericity Q(1) = Q(2); Delta = 0) the maximal depth of ablation (to = M + A) increased linearly with the asphericity Q(1). To achieve a more prolate final asphericity (Q(2) < Q(1); dQ < 0; Delta > 0), the maximal depth of ablation (M + A + Delta) was increased. For treatments in which Q(2) was intended to be more oblate than Q(1) (Q(2) > Q(1); dQ > 0; Delta < 0), the maximal depth of ablation was reduced. These effects sharply increased with increasing diameters of the optical zone(s). Similarly, in the case of PRK, the differential increase in epithelial thickness in the center of the cornea compared with the periphery resulted in increased oblateness. CONCLUSIONS. Aspheric profiles of ablation result in varying central depths of ablation. Oblateness of the initial corneal surface, intentional increase in negative asphericity. and enlargement of the optical zone diameter result in deeper central ablations. This may be of clinical importance in planning aspheric profiles of ablation in LASIK procedures to correct spherical aberration without compromising the mechanical integrity of the cornea. C1 Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Univ Paris 07, Hop Bichat, Rothschild Fdn, Ophthamol Serv, Paris, France. Univ Paris 06, Inst Stat, Paris, France. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. NR 35 TC 49 Z9 57 U1 0 U2 3 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 APR PY 2002 VL 43 IS 4 BP 941 EP 948 PG 8 WC Ophthalmology SC Ophthalmology GA 536LE UT WOS:000174700900006 PM 11923232 ER PT J AU Argueso, P Balaram, M Spurr-Michaud, S Keutmann, HT Dana, MR Gipson, IK AF Argueso, P Balaram, M Spurr-Michaud, S Keutmann, HT Dana, MR Gipson, IK TI Decreased levels of the goblet cell mucin MUC5AC in tears of patients with Sjogren syndrome SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID HUMAN CONJUNCTIVAL EPITHELIA; OCULAR SURFACE EPITHELIUM; SIALOMUCIN COMPLEX; DRY EYE; EXPRESSION; GENES; MUCUS; PROTEINS; CORNEAL; FILM AB PURPOSE. To determine whether the relative amounts of mucin mRNA in the conjunctival epithelium and mucin protein in the tears are altered in patients with Sjogren syndrome compared with healthy individuals. METHODS. Tear fluid was collected from the inferior fornix of normal subjects (n = 17) and patients with Sjogren syndrome (n = 11) after instillation of 60 muL sterile water onto the ocular surface. Immediately after tear fluid collection, conjunctival epithelium was obtained by filter paper-stripping from the bulbar temporal region for mRNA isolation. Primers to nontandem repeat sequences of the gel-forming mucin MUC5AC and the membrane-spanning mucins MUC1 and MUC4 were used in real-time RT-PCR to determine relative abundance of MUC mRNA in patients with Sjogren syndrome in relation to that of normal subjects. Enzyme-linked immunosorbent assay was performed on neuraminidase-treated tears, using a polyclonal antibody against a synthetic peptide mimicking the deduced amino acid sequence from the D3 region of MUC5AC. RESULTS. The number of RNA transcripts for the goblet cell-specific mucin MUC5AC in the conjunctival epithelium of patients with Sjogren syndrome was significantly lower than in normal individuals. No significant changes were detected when analyzing the mRNA levels of the mucins expressed by the stratified epithelium of the conjunctiva, MUC I and MUC4. Protein levels of the goblet cell mucin MUC5AC were significantly reduced in the tear fluid of patients with Sjogren syndrome. corroborating mRNA data obtained using real-time RTPCR. CONCLUSIONS. The tear fluid of patients with Sjogren syndrome has reduced levels of the goblet cell-specific mucin MUC5AC, which correlates to decreased levels of conjunctival MUC5AC mRNA. The authors propose that deficiency of MUC5AC mucin in tears constitutes one of the mechanisms responsible for tear film instability in Sjogren syndrome. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gipson, IK (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. FU NEI NIH HHS [R01-EY03306] NR 41 TC 193 Z9 205 U1 0 U2 8 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 APR PY 2002 VL 43 IS 4 BP 1004 EP 1011 PG 8 WC Ophthalmology SC Ophthalmology GA 536LE UT WOS:000174700900014 PM 11923240 ER PT J AU Gotte, M Joussen, AM Klein, C Andre, P Wagner, DD Hinkes, MT Kirchhof, B Adamis, AP Bernfield, M AF Gotte, M Joussen, AM Klein, C Andre, P Wagner, DD Hinkes, MT Kirchhof, B Adamis, AP Bernfield, M TI Role of syndecan-1 in leukocyte-endothelial interactions in the ocular vasculature SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCANS; INTEGRIN MAC-1 CD11B/CD18; FIBROBLAST GROWTH-FACTOR; L-SELECTIN; P-SELECTIN; BINDING; ANGIOGENESIS; EXPRESSION; BIOLOGY; FAMILY AB PURPOSE. Leukocyte endothelial interactions are a key feature of ocular angiogenesis but also play a role in nonproliferative vascular alterations as are found in early diabetes or uveitis. The adhesion of leukocytes to endothelial cells during inflammation is a multistep process that involves leukocyte rolling, adhesion, and extravasation mediated by selectins, cell adhesion molecules (CAMS), integrins, and chemokines. Heparan sulfate (HS) is known to bind to and modify the function of these molecules under physiological conditions. In this study, the role of the HS proteoglycan syndecan-1 in mediating leukocyte-endothelial interactions in the ocular vasculature was investigated. METHODS. Mice carrying a deletion in the gene encoding the cell surface HS proteoglycan syndecan-l (sdc1) were used to study the interactions of leukocytes and endothelial cells in vivo, using a perfusion technique with FITC-coupled ConA and intravital microscopy. RESULTS. In a retina perfusion model. Sdc1(-/-) mice showed increased leukocyte adhesion that was largely attributable to the leukocytes. Intravital microscopy studies revealed a dramatic increase in adhesion after tumor necrosis factor (TNF)-alpha treatment of sdc1(-/-) mice compared with similarly treated wild-type mice. The higher degree of leukocyte adhesion may account for the increase in inflammation-mediated corneal angiogenesis observed in sdc1(-/-) mice. CONCLUSIONS. The results indicate a role for syndecan-1 as a negative regulator of leukocyte-mediated inflammatory responses. Thus, syndecan-1 could have use as a target for prevention of pathologic leukocyte-endothelial interactions in angiogenesis and inflammation. C1 Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. Childrens Hosp, Div Pediat Hematol & Oncol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Retina Res Lab, Boston, MA 02114 USA. Ctr Ophthalmol, Dept Vitreoretinal Surg, Cologne, Germany. Hannover Med Sch, Dept Pediat Oncol, D-3000 Hannover, Germany. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Bernfield, M (reprint author), Childrens Hosp, Div Newborn Med, 300 Longwood Ave, Boston, MA 02115 USA. OI Gotte, Martin/0000-0003-2360-2496 FU NCI NIH HHS [R01-CA-28735]; NEI NIH HHS [R01-EY-12611-01]; NHLBI NIH HHS [R01 HL053756, R01-HL-53756] NR 46 TC 77 Z9 82 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2002 VL 43 IS 4 BP 1135 EP 1141 PG 7 WC Ophthalmology SC Ophthalmology GA 536LE UT WOS:000174700900031 PM 11923257 ER PT J AU Brunswick, DJ Amsterdam, JD Fawcett, J Quitkin, FM Reimherr, FW Rosenbaum, JF Beasley, CM AF Brunswick, DJ Amsterdam, JD Fawcett, J Quitkin, FM Reimherr, FW Rosenbaum, JF Beasley, CM TI Fluoxetine and norfluoxetine plasma concentrations during relapse-prevention treatment SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article; Proceedings Paper CT 38th Annual NCDEU Meeting CY JUN 10-13, 1998 CL BOCA RATON, FLORIDA ID ANTIDEPRESSANT RESPONSE; CLINICAL-RESPONSE; MAJOR DEPRESSION; SEROTONIN UPTAKE; AMITRIPTYLINE; ENANTIOMERS; INHIBITORS; IMIPRAMINE; PAROXETINE; PREDICTOR AB Background: Virtually no attention has been given to the relationship between antidepressant plasma drug concentrations and relapse-prevention during maintenance therapy. The purpose of this study was to investigate the relationship between steady-state plasma drug concentrations and outcome during relapse-prevention therapy with fluoxetine. Methods: The patients studied had responded to acute fluoxetine treatment for major depression (defined by DSM-III-R). Patients who met criteria for remission after 10-12 weeks of open-label acute fluoxetine therapy (N = 395 of 839 patients), were randomly assigned to one of four treatment arms (50 weeks of fluoxetine, 38 weeks of fluoxetine followed by 12 weeks of placebo, 14 weeks of fluoxetine followed by 36 weeks of placebo and 50 weeks of placebo). Plasma fluoxetine and norfluoxetine concentrations were measured (1) after 4 and 8 weeks of open-label treatment and (2) at the beginning and after 14 weeks of double-blind, relapse-prevention therapy. Results: Mean drug plasma levels were stable throughout the study. There was no significant difference in steady state plasma levels for the patients who relapsed compared to those who completed fluoxetine therapy without relapsing after 14, 38 or 50 weeks of fluoxetine relapse-prevention treatment. In addition, time-to-relapse was not related to steady-state drug plasma levels. Finally, after dividing patients into two group, based on their drug plasma levels, no significant differences were seen in the cumulative proportions of patients staying well during relapse-prevention therapy. Discussion: Plasma concentrations of fluoxetine and/or its metabolite norfluoxetine, are not correlated with relapse in patients treated with a fixed dose of 20 mg/day fluoxetine. Fluoxetine plasma levels cannot be used to guide relapse-prevention treatment. (C) 2002 Elsevier Science BV All rights reserved. C1 Univ Penn, Med Ctr, Ctr Sci, Depress Res Unit, Philadelphia, PA 19104 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Lilly Res Labs, Indianapolis, IN USA. RP Brunswick, DJ (reprint author), Univ Penn, Med Ctr, Ctr Sci, Depress Res Unit, 8th Floor,3600 Market St, Philadelphia, PA 19104 USA. OI Beasley, Charles/0000-0001-8743-7691 NR 26 TC 10 Z9 10 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD APR PY 2002 VL 68 IS 2-3 BP 243 EP 249 AR PII S0165-0327(00)00333-5 DI 10.1016/S0165-0327(00)00333-5 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 567QU UT WOS:000176496500010 PM 12063152 ER PT J AU Murphy, JM Nierenberg, AA Laird, NM Monson, RR Sobol, AM Leighton, AH AF Murphy, JM Nierenberg, AA Laird, NM Monson, RR Sobol, AM Leighton, AH TI Incidence of major depression: prediction from subthreshold categories in the Stirling County Study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article ID DIAGNOSTIC-INTERVIEW-SCHEDULE; NATIONAL-COMORBIDITY-SURVEY; PSYCHIATRIC EPIDEMIOLOGY; FOLLOW-UP; FUNCTIONAL IMPAIRMENT; UNIPOLAR DEPRESSION; SERVICE UTILIZATION; GENERAL-POPULATION; MINOR DEPRESSION; RISK-FACTORS AB Background: Validity of the newly-proposed categories of Minor Depression (MinD) and Subsyndromal Depression (SSD) would be strengthened if they were found to be related to the incidence of Major Depressive Episode (MDE). In this report, the subsequent incidence of MDE was assessed in terms of baseline evidence about the two subthreshold categories and Dysthymic Disorder (DysD). Methods: The Diagnostic Interview Schedule was used to interview 489 subjects twice between 1991 and 1995 as part of the Stirling County Study. Life table methods were used to calculate incidence rates and log linear analysis was employed for statistical assessment. Results: The average annual incidence of MDE was 10 per 1000. The rates associated with the baseline categories were 210 per 1000 for DysD, 21 for MinD; 13 for SSD; and four for the remainder of subjects who constituted the reference group. Only the incidence related to DysD was significantly higher than that for the reference group. Comparing Time I and Time 2, one-third of the subjects gained or lost symptoms and the comorbidity of MDE and DysD increased. Limitations: The study population was, on average, 63 years of age. Older age and the small size of the cohort may have influenced the findings. Another limitation may relate to the use of lifetime rather than current symptomatology. Conclusions: DysD is strongly associated with MDE suggesting that the chronic and episodic forms of unipolar depression constitute one disorder. The other subthreshold categories should be further investigated in terms of prodromal qualities. The persistence of dysphoria, as in DysD, may be a more important feature of the depression prodrome than the number of symptoms. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dalhousie Univ, Fac Med, Halifax, NS, Canada. RP Murphy, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. FU NIMH NIH HHS [MH39576] NR 54 TC 19 Z9 19 U1 6 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD APR PY 2002 VL 68 IS 2-3 BP 251 EP 259 AR PII S0165-0327(00)00334-7 DI 10.1016/S0165-0327(00)00334-7 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 567QU UT WOS:000176496500011 PM 12063153 ER PT J AU Fischman, AJ Hsu, HB Carter, EA Yu, YM Tompkins, RG Guerrero, JL Young, VR Alpert, NM AF Fischman, AJ Hsu, HB Carter, EA Yu, YM Tompkins, RG Guerrero, JL Young, VR Alpert, NM TI Regional measurement of canine skeletal muscle blood flow by positron emission tomography with (H2O)-O-15 SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE hindlimb; microspheres; Doppler flow probe; dogs ID INTRAVENOUS (H2O)-O-15; COMPUTED-TOMOGRAPHY; PROTEIN-SYNTHESIS; METABOLISM; VOLUME; PET; VALIDATION; EXERCISE; RABBIT; INJURY AB Positron emission tomography (PET) with (H2O)-O-15 was used as an in vivo, relatively noninvasive, quantitative method for measuring regional blood flow to hindlimb skeletal muscle of anesthetized dogs. A hydrooccluder positioned on the femoral artery was used to reduce flow, and high-flow states were produced by local infusion of adenosine. Three to four measurements were made in each animal. Approximately 40 mCi of (H2O)-O-15 were injected intravenously, and serial images and arterial blood samples were acquired over 2.5 min. Data analysis was performed by fitting tissue and arterial blood time-activity curves to a modified, single-compartment Kety model. The model equation was also solved on a pixel-by-pixel basis to yield maps of regional skeletal muscle blood flow. After each PET determination, flow was measured with radioactive microspheres. Results of the PET measurements demonstrated that basal flow to hindlimb skeletal muscle was 3.83 +/- 0.36 ml.min(-1).100 g(-1) (mean +/- SE). This value was in excellent agreement with the microsphere data, 3.73 +/- 0.32 ml.min(-1).100 g(-1) (P = 0.69, not significant). Adenosine infusion resulted in flows as high as 30 ml.min(-1).100 g(-1), and the PET and microsphere data were highly correlated over the entire range of flows (r(2) = 0.98, P < 0.0001). We conclude that muscle blood flow can be accurately measured in vivo by PET with (H2O)-O-15 and that this approach offers promise for application in human studies of muscle metabolism under varying pathophysiological states. C1 Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Shriners Burn Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. RI Guerrero, Jorge/I-3666-2015 OI Guerrero, Jorge/0000-0003-4315-7318 FU NCI NIH HHS [T32-CA-09362]; NIGMS NIH HHS [P50-GM-21700, T32-GM-07035] NR 52 TC 18 Z9 18 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD APR PY 2002 VL 92 IS 4 BP 1709 EP 1716 DI 10.1152/japplphysiol.00445.2001 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 534EX UT WOS:000174572600046 PM 11896041 ER PT J AU Kudva, IT Evans, PS Perna, NT Barrett, TJ Ausubel, FM Blattner, FR Calderwood, SB AF Kudva, IT Evans, PS Perna, NT Barrett, TJ Ausubel, FM Blattner, FR Calderwood, SB TI Strains of Escherichia coli O157 : H7 differ primarily by insertions or deletions, not single-nucleotide polymorphisms SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PATHOGENICITY ISLAND; SEQUENCE; VIRULENCE; EVOLUTION; GENOME; K-12 AB Escherichia coli O157:H7 (O157) strains demonstrate varied pulsed-field gel electrophoresis patterns following XbaI digestion, which enable epidemiological surveillance of this important human pathogen. The genetic events underlying PFGE differences between strains, however, are not defined. We investigated the mechanisms for strain variation in O157 by recovering and examining nucleotide sequences flanking each of the XbaI restriction enzyme sites in the genome. Our analysis demonstrated that differences between O157 strains were due to discrete insertions or deletions that contained the XbaI sites polymorphic between strains rather than single-nucleotide polymorphisms in the XbaI sites themselves. These insertions and deletions were found to be uniquely localized within the regions of the genome that are specific to O157 compared to E. coli K-12 (O islands), suggesting that strain-to-strain variation occurs in these O islands. These results may be utilized to devise novel strain-typing tools for this pathogen. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. Univ Wisconsin, Dept Anim Hlth & Biomed Sci, Madison, WI 53706 USA. Ctr Dis Control, Foodborne & Diarrheal Dis Branch, Atlanta, GA 30333 USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. FU NIAID NIH HHS [T32 AI007061, T32 AI07061] NR 20 TC 72 Z9 74 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2002 VL 184 IS 7 BP 1873 EP 1879 DI 10.1128/JB.148.7.1873-1879.2002 PG 7 WC Microbiology SC Microbiology GA 532CL UT WOS:000174454000010 PM 11889093 ER PT J AU Ring, D Jupiter, JB Zilberfarb, J AF Ring, D Jupiter, JB Zilberfarb, J TI Posterior dislocation of the elbow with fractures of the radial head and coronoid SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article AB Background: Posterior dislocation of the elbow with associated fractures of the radial head and the coronoid process of the ulna has been referred to as the "terrible triad of the elbow" because of the difficulties encountered in its management. However, there are few published reports on this injury. Methods: Eleven patients with this pattern of injury were evaluated after a minimum of two years. The radial head fracture had been repaired in five patients, and the radial head had been resected in four. None of the coronoid fractures had been repaired, and the lateral collateral ligament had been repaired in only three patients. All eleven patients returned for clinical examination, functional evaluation, and radiographs. Results: Seven elbows redislocated in a splint after manipulative reduction. Five, including all four treated with resection of the radial head, redislocated after operative treatment. At the time of final follow-up, three patients were considered to have a failure of the initial treatment. One of them had recurrent instability, which was treated with a total elbow arthroplasty after multiple unsuccessful operations; one had severe arthrosis and instability resembling neuropathic arthropathy; and one had an elbow flexion contracture and proximal radioulnar synostosis requiring reconstructive surgery. The remaining eight patients, who were evaluated at an average of seven years after-injury, had an average of 92degrees (range, 40degrees to 130degrees) of ulnohumeral motion and 126degrees (range, 400 to 1700) of forearm rotation. The average Broberg and Morrey functional score was 76 points (range, 34 to 98 points), with two results rated as excellent, two rated as good, three rated as fair, and one rated as poor. Overall, the result of treatment was rated as unsatisfactory for seven of the eleven patients. All four patients with a satisfactory result had retained the radial head, and two had undergone repair of the lateral collateral ligament. Seven of the ten patients who had retained the native elbow had radiographic signs of advanced ulnohumeral arthrosis. Conclusions: Elbow fracture-dislocations that involve a fracture of the coronoid process in addition to a fracture of the radial head are very unstable and prone to numerous complications. Identification of the coronoid fracture is therefore important, and computed tomography should be used if there is uncertainty. With operative treatment, the surgeon should attempt to restore stability by providing radiocapitellar contact (preserving the radial head when possible and replacing it with a prosthesis otherwise), repairing the lateral collateral ligament, and perhaps performing internal fixation of the coronoid fracture. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg, Boston, MA 02215 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, ACC 525m15 Parkman St, Boston, MA 02114 USA. NR 19 TC 166 Z9 218 U1 1 U2 6 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD APR PY 2002 VL 84A IS 4 BP 547 EP 551 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 538FD UT WOS:000174803500007 PM 11940613 ER PT J AU Harrington, MA O'Connor, DO Lozynsky, AJ Kovach, I Harris, WH AF Harrington, MA O'Connor, DO Lozynsky, AJ Kovach, I Harris, WH TI Effects of femoral neck length, stem size, and body weight on strains in the proximal cement mantle SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID HIP IMPLANTS; COMPONENT; PROSTHESIS AB Background: Several studies have shown that certain cemented total hip replacement femoral stems have been associated with the complications of early debonding, loosening, and osteolysis. Some authors have suggested that these failures may be related to the surface finish of the stems. We developed an in vitro biomechanical experiment characterized by simulated stair-climbing to investigate the multiple factors involved in loosening of cemented femoral stems. In this study, we measured the effects of stem neck length, body weight, stem size, and calcar-collar contact on the torsional stability, as reflected by the strains in the proximal cement mantle, of one design of cemented femoral stem. Methods: Eight Centralign femoral stems (Zimmer, Warsaw, Indiana) were cemented into eight cadaver femora with use of contemporary cementing techniques. Prior to insertion, fifteen strain-gauge rosettes were mounted around the proximal portion of the stem. The stems were loaded on a jig that simulated static peak loading during stair-climbing. Loading was repeated for each stem with three different joint reaction forces and for three different neck lengths. Calcar loading by the collar was then eliminated by removing a 0.5-mm slice of bone beneath the collar, and all loadings were then repeated. Results: The peak principal tensile strains in the proximal cement increased linearly with both body weight (r(2) > 0.95) and neck length (r(2) > 0.75). Increasing body weight affected the peak cement strains far more than did increasing neck length. During simulated stair-climbing, calcar-collar contact reduced peak strains in the proximal cement by a factor of 1.5 to two. Peak principal tensile strains in the proximal cement often exceeded 1000 muepsilon when the smaller stems were used. Conclusions: In this stair-climbing test model, the peak proximal cement strains were increased more by changes in body weight than they were by changes in neck length. Even during stair-climbing, calcar-collar contact reduced peak cement strains. Clinical Relevance: Many cemented femoral sterns that become loose do so by rotating into retroversion. In this study of one design of a cemented femoral, component during simulated stair-climbing, the peak strain magnitudes in the proximal cement mantle were increased more by changes in body weight than by changes in the length of the neck of the stem. The strong effect of stem size on the cement strains suggests that cemented femoral stems should not be used in heavy patients with small medullary canals that require a small cemented stem. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Adult Reconstruct Unit, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Harrington, MA (reprint author), Loyola Univ, Med Ctr, Dept Orthopaed Surg & Rehabil, Maywood, IL 60153 USA. NR 18 TC 13 Z9 15 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD APR PY 2002 VL 84A IS 4 BP 573 EP 579 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 538FD UT WOS:000174803500011 PM 11940617 ER PT J AU Sami, S Liu, G Hornicek, F Cates, JM Mankin, HJ AF Sami, S Liu, G Hornicek, F Cates, JM Mankin, HJ TI Membranous lipodystrophy - A case report SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID OSTEODYSPLASIA; BRAIN; BONE; DISEASE C1 Massachusetts Gen Hosp, Orthopaed Oncol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Sami, S (reprint author), Univ Tehran, Tehran, Iran. EM hmankin@partners.org RI Cates, Justin/D-5927-2014 OI Cates, Justin/0000-0002-7336-5196 NR 13 TC 3 Z9 3 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD APR PY 2002 VL 84A IS 4 BP 630 EP 633 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 538FD UT WOS:000174803500022 PM 11940627 ER PT J AU Hau, MA Fox, EJ Cates, JM Brigman, BE Mankin, HJ AF Hau, MA Fox, EJ Cates, JM Brigman, BE Mankin, HJ TI Jaffe-Campanacci syndrome - A case report and review of the literature SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID NON-OSSIFYING FIBROMAS; NEUROFIBROMATOSIS; MULTIPLE; CHILDREN C1 Massachusetts Gen Hosp, Orthopaed Oncol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Hau, MA (reprint author), Hosp Kota Bharu, Dept Orthopaed, 15586 Kota Bharu, Kelantan, Malaysia. RI Cates, Justin/D-5927-2014 OI Cates, Justin/0000-0002-7336-5196 NR 17 TC 7 Z9 10 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD APR PY 2002 VL 84A IS 4 BP 634 EP 638 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 538FD UT WOS:000174803500023 PM 11940628 ER PT J AU Gebhardt, MC AF Gebhardt, MC TI What's new in musculoskeletal oncology SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Editorial Material ID LOWER-EXTREMITY SARCOMA; BONE C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Gebhardt, MC (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St,GRB 606, Boston, MA 02114 USA. NR 34 TC 6 Z9 8 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD APR PY 2002 VL 84A IS 4 BP 694 EP 701 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 538FD UT WOS:000174803500050 PM 11940646 ER PT J AU Barton, ER Morris, L Musaro, A Rosenthal, N Sweeney, HL AF Barton, ER Morris, L Musaro, A Rosenthal, N Sweeney, HL TI Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice SO JOURNAL OF CELL BIOLOGY LA English DT Article DE IGF-I; muscular dystrophy; satellite cells; regeneration; protein kinase B ID DUCHENNE MUSCULAR-DYSTROPHY; PROTEIN-KINASE-B; SKELETAL-MUSCLE; SIGNALING PATHWAYS; SATELLITE CELLS; TRANSGENIC MICE; TELOMERE LENGTH; GENE-THERAPY; MOUSE; DIFFERENTIATION AB Duchenne muscular dystrophy is an X-linked degenerative disorder of muscle caused by the absence of the protein dystrophin. A major consequence of muscular dystrophy is that the normal regenerative capacity of skeletal muscle cannot compensate for increased susceptibility to damage, leading to repetitive cycles of degeneration-regeneration and ultimately resulting in the replacement of muscle fibers with fibrotic tissue. Because insulin-like growth factor 1 (IGF-1) has been shown to enhance muscle regeneration and protein synthetic pathways, we asked whether high levels of muscle-specific expression of IGF-1 in mdx muscle could preserve muscle function in the diseased state. In transgenic mdx mice expressing mlgf-1 (mdx:mlgf(+/+)), we showed that muscle mass increased by at least 40% leading to similar increases in force generation in extensor digitorum longus muscles compared with those from mdx mice. Diaphragms of transgenic mdx:mlgf(+/+) exhibited significant hypertrophy and hyperplasia at all ages observed. Furthermore, the IGF-1 expression significantly reduced the amount of fibrosis normally observed in diaphragms from aged mdx mice. Decreased myonecrosis was also observed in diaphragms and quadriceps from mdx:mlgf(+/+) mice when compared with age-matched mdx animals. Finally, signaling pathways associated with muscle regeneration and protection against apoptosis were significantly elevated. These results suggest that a combination of promoting muscle regenerative capacity and preventing muscle necrosis could be an effective treatment for the secondary symptoms caused by the primary loss of dystrophin. C1 Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA. Univ Roma La Sapienza, Dept Histol & Med Embryol, I-00161 Rome, Italy. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Sweeney, HL (reprint author), Univ Penn, Dept Physiol, B400 Richards Bldg,3700 Hamilton Walk, Philadelphia, PA 19104 USA. RI Sweeney, H Lee/F-1862-2010; Musaro, Antonio/K-9598-2016; OI Musaro, Antonio/0000-0002-2944-9739; Rosenthal, Nadia/0000-0002-7599-7365 FU NIAMS NIH HHS [R01 AR047292, R01AR47292] NR 50 TC 288 Z9 297 U1 2 U2 11 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD APR 1 PY 2002 VL 157 IS 1 BP 137 EP 147 DI 10.1083/jcb.200108071 PG 11 WC Cell Biology SC Cell Biology GA 566KE UT WOS:000176426600011 PM 11927606 ER PT J AU Ando, A Yang, A Mori, K Yamada, H Yamada, E Takahashi, K Saikia, J Kim, M Melia, M Fishman, M Huang, P Campochiaro, PA AF Ando, A Yang, A Mori, K Yamada, H Yamada, E Takahashi, K Saikia, J Kim, M Melia, M Fishman, M Huang, P Campochiaro, PA TI Nitric oxide is proangiogenic in the retina and choroid SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ANGIOGENESIS IN-VIVO; TUMOR-GROWTH; TARGETED DISRUPTION; FACTOR EXPRESSION; SMOOTH-MUSCLE; MICE LACKING; NEOVASCULARIZATION; SYNTHASE; CELLS AB itric oxide (NO) has been shown to have proangiogenic or antiangiogenic effects depending upon the setting. In this study, we used mice with targeted deletion of one of the three isoforms of nitric oxide synthase (NOS) to investigate the effects of NO in ocular neovascularization. In transgenic mice with increased expression of vascular endothelial growth factor (VEGF) in photoreceptors, deficiency of any of the three isoforms caused a significant decrease in subretinal neovascularization, but no alteration of VEGF expression. In mice with laser-induced rupture of Bruch's membrane, deficiency of inducible NOS (iNOS) or neuronal NOS (nNOS), but not endothelial NOS (eNOS), caused a significant decrease in choroidal neovascularization. In mice with oxygen-induced ischemic retinopathy, deficiency of eNOS, but not iNOS or nNOS caused a significant decrease in retinal neovascularization and decreased expression of VEGF. These data suggest that NO contributes to both retinal and choroidal neovascularization and that different isoforms of NOS are involved in different settings and different disease processes. A broad spectrum NOS inhibitor may have therapeutic potential for treatment of both retinal and choroidal neovascularization. J. Cell. Physiol. 191: 116-124, 2002. (C) 2002 Wiley-Liss, Inc. C1 Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA. Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Campochiaro, PA (reprint author), Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Maumenee 719,600 N Wolfe St, Baltimore, MD 21287 USA. FU NEI NIH HHS [EY05951, P30EY1765, EY12609] NR 49 TC 53 Z9 57 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD APR PY 2002 VL 191 IS 1 BP 116 EP 124 DI 10.1002/jcp.10077 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 527BX UT WOS:000174166700011 PM 11920687 ER PT J AU Mori, T Wang, XY Jung, TC Sumii, T Singhal, AB Fini, ME Dixon, CE Alessandrini, A Lo, EH AF Mori, T Wang, XY Jung, TC Sumii, T Singhal, AB Fini, ME Dixon, CE Alessandrini, A Lo, EH TI Mitogen-activated protein kinase inhibition in traumatic brain injury: In vitro and in vivo effects SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain trauma; cell death; cell signaling; neuroprotection ID SPINAL-CORD INJURY; CONTROLLED CORTICAL IMPACT; FOCAL CEREBRAL-ISCHEMIA; TRANSIENT FOREBRAIN ISCHEMIA; SEVERE HEAD-INJURY; CELL-DEATH; SIGNAL-TRANSDUCTION; HIPPOCAMPAL-NEURONS; NERVOUS-SYSTEM; MAP KINASES AB The authors provide the first in vitro and in vivo evidence that perturbations in mitogen-activated protein kinase (MAPK) signal-transduction pathways are involved in the pathophysiology of traumatic brain injury. In primary rat cortical cultures, mechanical trauma induced a rapid and selective phosphorylation of the extracellular signal-regulated kinase (ERK) and p38 kinase, whereas there was no detectable change in the c-jun N-terminal kinase (JNK) pathway. Treatment with PD98059, which inhibits MAPK/ERK 1/2, the upstream activator of ERK, significantly increased cell survival in vitro. The p38 kinase and JNK inhibitor SB203580 had no protective effect. Similar results were obtained in vivo using a controlled cortical impact model of traumatic injury in mouse brain. Rapid and selective upregulation occurred in ERK and p38 pathways with no detectable changes in JNK. Confocal immunohistochemistry showed that phospho-ERK colocalized with the neuronal nuclei marker but not the astrocytic marker glial fibrillary acidic protein. Inhibition of the ERK pathway with PD98059 resulted in a significant reduction of cortical lesion volumes 7 days after trauma. The p39 kinase and JNK inhibitor SB203580 had no detectable beneficial effect. These data indicate that critical perturbations in MAPK pathways mediate cerebral damage after acute injury, and further suggest that ERK is a novel therapeutic target in traumatic brain injury. C1 Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA USA. Harvard Univ, Med Sch, Program Neurosci, Boston, MA USA. Tufts Univ, Sch Med, New England Eye Ctr, Vis Res Labs, Boston, MA USA. Univ Pittsburgh, Dept Neurol Surg, Brain Trauma Res Ctr, Pittsburgh, PA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA USA. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Neuroprotect Res Lab, MGH East 149-2401, Charlestown, MA 02129 USA. FU NEI NIH HHS [R01-EY09828]; NINDS NIH HHS [R01-NS33150, R01-NS37074, R01-NS38731, R01-NS40529] NR 59 TC 111 Z9 123 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD APR PY 2002 VL 22 IS 4 BP 444 EP 452 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 538EY UT WOS:000174802900008 PM 11919515 ER PT J AU Wolf, M Sandler, L Munoz, K Hsu, K Ecker, JL Thadhani, R AF Wolf, M Sandler, L Munoz, K Hsu, K Ecker, JL Thadhani, R TI First trimester insulin resistance and subsequent preeclampsia: A prospective study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HORMONE-BINDING GLOBULIN; POLYCYSTIC-OVARY-SYNDROME; HEALTHY NULLIPAROUS WOMEN; NORMAL-PREGNANCY; HYPERTENSIVE DISORDERS; POSTMENOPAUSAL WOMEN; GLUCOSE-TOLERANCE; PRE-ECLAMPSIA; SEX; RISK AB Insulin resistance is implicated in the pathogenesis of pre-eclampsia, but prospective data are limited. SHBG, a marker of insulin resistance among nonpregnant individuals, has not been studied in detail during pregnancy. We conducted a prospective, nested, case-control study to test the hypothesis that increased insulin resistance, marked by reduced first trimester SHBG levels, is associated with increased risk of subsequent preeclampsia. First trimester SHBG levels were measured in 45 nulliparous women who subsequently developed preeclampsia (blood pressure, greater than or equal to140/90 mm Hg; proteinuria, either greater than or equal to2+ by dipstick or greater than or equal to300 mg/24 h, after 20 wk gestation) and in 90 randomly selected normotensive nulliparous controls. Compared with controls, women who developed preeclampsia had significantly reduced first trimester SHBG levels (302 +/- 130 vs. 396 +/- 186 nmol/liter; P < 0.01). Every 100 nmol/liter increase in SHBG was associated with a 31% reduced risk of preeclampsia [odds ratio (OR), 0.69; 95% confidence interval (CI), 0.55, 0.88; P < 0.011. After adjusting for covariates in a multiple logistic regression model, the association between first trimester SHBG and preeclampsia remained significant (per 100 nmol/liter increase; OR, 0.66; 95% Cl, 0.47, 0.92; P = 0.01). When subjects were stratified by body mass index (lean: body mass index, <25 kg/m(2); overweight: body mass index, >= 25 kg(m(2)), overweight women had lower SHBG levels than lean women (286 +/- 156 vs. 410 +/- 166 nmol/ liter; P < 0.01), and within each stratum, women with pre-eclampsia had lower SEEG levels than their respective controls. In a multivariable analysis, the association between SHBG and preeclampsia strengthened among lean women, such that every 100 nmol/liter increase in serum SHBG was associated with a 55% reduction in the risk of preeclampsia (OR, 0.45; 95% CI, 0.27, 0.77; P < 0.01), whereas in overweight women, the association was mitigated (OR, 1.02; 95% Cl, 0.62, 1.69; P = 0.9). We conclude that increased early pregnancy insulin resistance is independently associated with subsequent preeclampsia. First trimester SHBG levels may be a useful biomarker for preeclampsia, especially among lean women who otherwise would be perceived to be at low risk. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Wolf, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Bulfinch 127,55 Fruit St, Boston, MA 02114 USA. EM mswolf@partners.org RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NHLBI NIH HHS [HL-03804]; NICHD NIH HHS [HD-39223] NR 46 TC 153 Z9 159 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2002 VL 87 IS 4 BP 1563 EP 1568 DI 10.1210/jc.87.4.1563 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 541AM UT WOS:000174963100022 PM 11932283 ER PT J AU Seminara, SB Acierno, JS Abdulwahid, NA Crowley, WF Margolin, DH AF Seminara, SB Acierno, JS Abdulwahid, NA Crowley, WF Margolin, DH TI Hypogonadotropic hypogonadism and cerebellar ataxia: Detailed phenotypic characterization of a large, extended kindred SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; CONGENITAL ADRENAL HYPOPLASIA; ALPHA(1A)-VOLTAGE-DEPENDENT CALCIUM-CHANNEL; MACHADO-JOSEPH DISEASE; SPINOCEREBELLAR ATAXIA; CAG REPEAT; EXPANSION; GENE; DEFICIENCY; IDENTIFICATION AB Although the co-occurrence of cerebellar ataxia and hypogonadism has been recognized for close to 100 yr, cases of Gordon Holmes syndrome are quite rare. This report describes the largest kindred characterized to date. The parents of the three affected siblings are first cousins, suggesting that the disease was inherited as an autosomal recessive trait. The siblings' initial evaluation was notable for low serum levels of sex steroids and gonadotropins (consistent with hypogonadotropic hypogonadism), progressive ataxia, and dementia. Extended treatment with physiological doses of pulsatile GnRH failed to stimulate a gonadotropin response. Brain imaging revealed volume loss in the cerebellum, with extensive abnormalities in the cerebral white matter. This unique family suggests that a common genetic mechanism is responsible for the syndrome of progressive hypogonadotropism and cerebellar ataxia. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall Extens 505,Fruit St, Boston, MA 02114 USA. EM seminara.stephanie@mgh.harvard.edu FU NIAID NIH HHS [AI-01587]; NICHD NIH HHS [P30 HD028138, R01 HD015788, U54 HD028138, U54 HD029164] NR 43 TC 28 Z9 28 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2002 VL 87 IS 4 BP 1607 EP 1612 DI 10.1210/jc.87.4.1607 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 541AM UT WOS:000174963100029 PM 11932290 ER PT J AU Sedlmeyer, IL Palmert, MR AF Sedlmeyer, IL Palmert, MR TI Delayed puberty: Analysis of a large case series from an academic center SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID OBESE BOYS; DEFICIENCY; DIAGNOSIS; CHILDREN; GROWTH; HYPOGONADISM; ADOLESCENTS; MATURATION; OVERWEIGHT; ACCURACY AB Despite the clinical importance of delayed puberty, the understanding of this condition is hampered by the lack of studies evaluating etiologies and predisposing factors among large case series. We performed a retrospective study of clinical and laboratory data from adolescents (less than or equal to18 yr of age) with delayed puberty who had been seen in our clinic between 1/96 and 7/99 (n = 232 subjects; 158 males and 74 females). Family histories of pubertal timing among primary relatives were classified as negative, having at least a tendency to pubertal delay (development greater than or equal to1 SD beyond the mean), or diagnostic of delay (development greater than or equal to2 SD beyond the mean). The most common cause of delayed puberty was constitutional delay of growth and maturation (CD), which affected 53% of the subjects (63% of males and 30% of females). The remaining subjects could be divided into four categories: those with an underlying condition associated with delayed, but spontaneous, pubertal development [functional hypogonadotropic hypogonadism (FHH)], 19% of subjects; those with permanent hypogonadotropic hypogonadism, 12% of subjects; those with permanent hypergonadotropic hypogonadism, 13% of subjects; and those without clearly classified disorders, 3% of subjects. Like CD, FHH was male predominant, whereas the other categories either affected both genders equally or were predominantly female. In total, 50 different etiologies led to pubertal delay within our case series. Data permitted classification of family histories of pubertal timing among primary relatives in 95 of 122 of the CD and in 25 of 45 of the FHH cases. Analysis revealed at least a tendency to pubertal delay in 77% of the CD and in 64% of the FHH families and a diagnosis of delay in 38% of the CD and 44% of the FHH families. Both parents contributed to the positive family histories. The rates of positive family histories among the CD and FHH groups were approximately twice those seen among the other subjects in our case series. Among all subjects, those with FHH had the most marked growth delay, and girls had the greater bone age delay. Among the boys and at comparable chronological ages, CD and FHH were characterized by greater delays in pubic hair development and bone age than in the other diagnostic groups. Although CD is typically associated with leanness, 22% of our subjects had a BMI SD score at the 85th percentile or above for chronological age. These overweight subjects differed from the rest of the CD group: bone age was less delayed, and height was less affected. Finally, our analysis suggested a possible association between attention deficit disorder with or without hyperactivity and pubertal delay in our CD and FHH subjects. Our study provides valuable data regarding the variety and frequency of diagnoses that lead to delayed puberty. The results underscore the importance of performing a thorough evaluation and family history in adolescents with delayed puberty. Moreover, the data from our case series provide clues for unraveling the mechanism(s) of idiopathic pubertal delay and lead to the hypothesis that the pubertal delay seen among some subjects with FHH and CD may stem in part from similar underlying physiology. C1 Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Palmert, MR (reprint author), Univ Hosp Hlth Syst, Rainbow Babies & Childrens Hosp, Div Pediat Endocrinol & Metab, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM mrp13@po.cwru.edu FU NCRR NIH HHS [K23-RR-15544] NR 41 TC 108 Z9 111 U1 1 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2002 VL 87 IS 4 BP 1613 EP 1620 DI 10.1210/jc.87.4.1613 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 541AM UT WOS:000174963100030 PM 11932291 ER PT J AU Sesmilo, G Fairfield, WP Katznelson, L Pulaski, K Freda, PU Bonert, V Dimaraki, E Stavrou, S Vance, ML Hayden, D Klibanski, A AF Sesmilo, G Fairfield, WP Katznelson, L Pulaski, K Freda, PU Bonert, V Dimaraki, E Stavrou, S Vance, ML Hayden, D Klibanski, A TI Cardiovascular risk factors in acromegaly before and after normalization of serum IGF-I levels with the GH antagonist pegvisomant SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID C-REACTIVE PROTEIN; CORONARY HEART-DISEASE; GROWTH-HORMONE ACTION; INSULIN-RESISTANCE; LIPID-METABOLISM; ADIPOSE-TISSUE; INFLAMMATION; MEN; MORTALITY; MARKERS AB Acromegaly is associated with premature cardiovascular mortality. GH replacement therapy decreases inflammatory markers of cardiovascular risk but little is known about these markers in patients with acromegaly. The GH receptor antagonist, pegvisomant, reduces IGF-I levels in 98% of patients treated. We investigated the effects of GH receptor blockade on inflammatory and other cardiovascular risk markers in active acromegaly. Forty-eight patients with acromegaly and 47 age- and body mass index-matched controls were included. The study consisted of 3 parts: a cross-sectional study, a prospective randomized 12-wk placebo-controlled study, and a longitudinal open-label study of up to 18 months of pegvisomant treatment. After baseline evaluation, patients with acromegaly were randomized to placebo (n = 14), 10 mg (n = 12),15 mg (n = 10), or 20 mg (n = 12) daily pegvisomant for 12 wk. Subsequently, all patients received at least 10 mg pegvisomant daily for up to IS months, with dose adjustments to achieve a normal IGF-I level. Anthropometry, GH, IGF-I, and pegvisomant levels were measured monthly. C-reactive protein (CRP), IL-6, homocysteine, lipoprotein(a), glucose, insulin, triglycerides, total cholesterol, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol were determined at baseline, 4 and 12 wk in the placebo-controlled study and at 3-month intervals (during which IGF-I levels were normal) in the longitudinal study. In the cross-sectional study, patients had lower CRP than did controls [median, 0.3 (range, 0.2-0.8) vs. 2.0 (0.6-3.7) mg/liter; P < 0.0001] and had higher insulin [78.6 (55.8-130.2) vs. 54.5 (36.6-77.5) pM, P = 0.0051]. IL-6, homocysteine, triglycerides, lipoprotein(a), LDL cholesterol and HDL cholesterol were not different between groups. In the placebo-controlled study, CRP increased in patients treated with 20 mg pegvisomant, compared with placebo (mean +/- sum, 13.7 +/- 3.6 vs. 0.5 +/- 3.3 mg/liter; P = 0.010). There were no significant differences in IL-6, homocysteine, glucose, insulin, triglyceride, total cholesterol, LDL cholesterol and HDL cholesterol levels. In the longitudinal open-label study (median duration, 15.6 months), CRP increased by 2.0 +/- 0.5 mg/liter (P = 0.0002). Total cholesterol and triglycerides increased (0.22 +/- 0.11 mm, P = 0.050; and 0.25 +/- 0.09 mm, P = 0.007, respectively), whereas lipoprotein(a) decreased (-70 +/- 33 mg/liter, P = 0.039). Glucose, insulin, homocysteine, HDL cholesterol, and IL-6 did not change. We conclude that patients with active acromegaly have lower CRP and higher insulin levels than healthy controls. Administration of pegvisomant increases CRP levels. We propose that GH secretory status is an important determinant of serum CRP levels, although additional studies are needed to determine the mechanism and significance of this finding. C1 Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Hosp Clin Barcelona, Serv Endocrinol, Barcelona, Spain. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Cedars Sinai Med Ctr, Pituitary Ctr, Los Angeles, CA USA. Univ Michigan, Div Endocrinol & Metab, Ann Arbor, MI 48109 USA. Univ Virginia Hlth Syst, Dept Internal Med Endocrinol & Metab, Charlottesville, VA 22908 USA. NYU Med Ctr, Div Endocrinol, New York, NY 10016 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Neuroendocrine Unit, Fruit St,Bulfinch 457B, Boston, MA 02114 USA. EM aklibanski@partners.org NR 52 TC 70 Z9 73 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2002 VL 87 IS 4 BP 1692 EP 1699 DI 10.1210/jc.87.4.1692 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 541AM UT WOS:000174963100042 PM 11932303 ER PT J AU Menzaghi, C Plengvidhya, N Ma, XW Warram, JH Shoelson, SE Doria, A AF Menzaghi, C Plengvidhya, N Ma, XW Warram, JH Shoelson, SE Doria, A TI Genetic variability in insulin action inhibitor Ikk beta (IKBKB) does not play a major role in the development of type 2 diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID B KINASE-BETA; GLYCOPROTEIN PC-1; LINKAGE ANALYSIS; RESISTANCE; RECEPTOR; MELLITUS; LOCUS; ALPHA AB Recent evidence indicates that IkappaB kinase beta (Ikkbeta) may be a mediator of acquired forms of insulin-resistance. In this study, we examined whether genetic variability at the Ikkbeta locus (IKBKB) contributes to the development of genetic forms of early-onset type 2 diabetes transmitted with an autosomal dominant mode of inheritance. Linkage with four markers flanking the IKBKB gene was evaluated in 32 multi-generational families. Included in the study were 233 diabetic (mean age at Dx = 37 +/- 18) and 152 nondiabetic subjects. The overall LOD scores were negative (-54.9 and -46.2 on the centromeric and telomeric sides, respectively) indicating that variability in IKBKB was not a major determinant of diabetes in these families. Positive values, however, were observed for selected pedigrees. All 17 families for which linkage with the IKBKB locus could not be excluded were screened for sequence differences in the 22 exons and 1.6 kb of the 5' flanking region by dideoxyfingerprinting or direct sequencing. Polymorphisms were identified in the 5' flanking region (-1775del/insC and -1547T > A), exon 11 (c.1083A > G, L361L) and in intron 12 (IVS12+14t > a). However, no mutations segregating with diabetes could be found in these families. Furthermore, all four polymorphisms had similar allele frequencies in the 32 family probands, 171 individuals with common, later-onset type 2 diabetes, and 182 nondiabetic controls. We conclude that sequence differences in the IKBKB gene do not play a major role in either early-onset, autosomal dominant type 2 diabetes, or common forms with a later-onset. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Doria, A (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM alessandro.doria@joslin.harvard.edu OI Menzaghi, Claudia/0000-0002-7438-8955 FU NIDDK NIH HHS [DK-55523, DK-51729, DK-36836, DK-47475] NR 20 TC 1 Z9 1 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2002 VL 87 IS 4 BP 1894 EP 1897 DI 10.1210/jc.87.4.1894 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 541AM UT WOS:000174963100070 PM 11932336 ER PT J AU Fan, VS Au, D Heagerty, P Deyo, RA McDonell, MB Fihn, SD AF Fan, VS Au, D Heagerty, P Deyo, RA McDonell, MB Fihn, SD TI Validation of case-mix measures derived from self-reports of diagnoses and health SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE co-morbidity; questionnaires; quality of life; confounding factors; ROC curve; proportional hazards model ID BREAST-CANCER PATIENTS; RISK-ADJUSTMENT; COMORBIDITY INDEX; FUNCTIONAL STATUS; VETERANS HEALTH; CHRONIC DISEASE; OUTCOMES; MORTALITY; HOSPITALS; SURVIVAL AB Self-reported chronic diseases and health status are associated with resource use. However, few data exist regarding their ability to predict mortality or hospitalizations, We sought to determine whether self-reported chronic medical conditions and the SF-36 could be used individually or in combination to assess co-morbidity in the outpatient setting. The study was designed as a prospective cohort study. Patients were enrolled in the primary care clinics at seven Veterans Affairs (VA) medical centers participating in the Ambulatory Care Quality Improvement Project (ACQUIP). 10,947 patients, greater than or equal to 50 years of age, enrolled in general internal medicine clinics who returned both a baseline health inventory checklist and the baseline SF-36 who were followed for a mean of 722.5 (+/-84.3) days. The primary outcome was all-cause mortality, with a secondary outcome of hospitalization within the VA system. Using a Cox proportional hazards model in a development set of 5,469 patients, a co-morbidity index [Seattle Index of Co-morbidity (SIC)] was constructed using information about age, smoking status and seven of 25 self-reported medical conditions that were associated with increased mortality. In the validation set of 5,478 patients, the SIC was predictive of both mortality and hospitalizations within the VA system. A separate model was constructed in which only age and the PCS and MCS scores of the SF-36 were entered to predict mortality. The SF-36 component scores and the SIC had comparable discriminatory ability (AUC for discrimination of death within 2 y 0.71 for both models), When combined, the SIC and SF-36 together had improved discrimination for mortality (AUC = 0.74, p-value for difference in AUC < 0.005). A new outpatient co-morbidity score developed using self-identified chronic medical conditions on a baseline health inventory checklist was predictive of 2-y mortality and hospitalization within the VA system in general internal medicine patients. (C) 2002 Elsevier Science Inc. All rights reserved. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Biostat, Seattle, WA USA. RP Fan, VS (reprint author), Hlth Serv Res & Dev 152, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 37 TC 113 Z9 113 U1 4 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD APR PY 2002 VL 55 IS 4 BP 371 EP 380 AR PII S0895-4356(01)00493-0 DI 10.1016/S0895-4356(01)00493-0 PG 10 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 533ET UT WOS:000174517000008 PM 11927205 ER PT J AU Hossain, M Wright, S Petersen, LA AF Hossain, M Wright, S Petersen, LA TI Comparing performance of multinomial logistic regression and discriminant analysis for monitoring access to care for acute myocardial infarction SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE access to health care; multinomial logistic regression; discriminant analysis; prediction; veterans; acute myocardial infarction ID COOPERATIVE CARDIOVASCULAR PROJECT; NEURAL NETWORKS; EFFICIENCY; DIAGNOSIS; SURGERY AB One way to monitor patient access to emergent health care services is to use patient characteristics to predict arrival time at the hospital after onset of symptoms. This predicted arrival time can then be compared with actual arrival time to allow monitoring of access to services. Predicted arrival time could also be used to estimate potential effects of changes in health care service availability, such as closure of an emergency department or an acute care hospital. Our goal was to determine the best statistical method for prediction of arrival intervals for patients with acute myocardial infarction (AMI) symptoms. We compared the performance of multinomial logistic regression (MLR) and discriminant analysis (DA) models. Models for MLR and DA were developed using a dataset of 3,566 male veterans hospitalized with AMI in 81 VA Medical Centers in 1994-1995 throughout the United States. The dataset was randomly divided into a training set (n = 1,846) and a test set (n = 1,720). Arrival times were grouped into three intervals on the basis of treatment considerations: <6 hours, 6-12 hours, and >12 hours. One model for MLR and two models for DA were developed using the training dataset. One DA model had equal prior probabilities, and one DA model had proportional prior probabilities, Predictive performance of the models was compared using the test (n = 1,720) dataset. Using the test dataset, the proportions of patients in the three arrival time group, were 60.9% for <6 hours, 10.3% for 6-12 hours, and 28.87c for >12 hours after symptom onset. Whereas the overall predictive performance by MLR and DA with proportional priors was higher, the DA models with equal priors performed much better in the smaller groups Correct classifications were 62.6% by MLR, 62.4% by DA using proportional prior probabilities, and 48.1% using equal prior probabilities of thew groups. The misclassifications by MLR for the three groups were 9.5%, 100.0%, 74.2% for each time interval, respectively. Misclassifications by DA models were 9.8%, 100.0%, and 74.4% for the model with proportional priors and 47.6%, 79.5%, and 51.0% for the model with equal priors. The choice of MLR or DA with proportional priors. or DA with equal priors for monitoring time intervals of predicted hospital arrival time for a population should depend on the consequences of misclassification errors. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Massachusetts Vet Epidemiol Res & Informat Ctr, VA Boston Hlth Care Syst, MAVERIC, W Roxbury, MA USA. RP Petersen, LA (reprint author), Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 25 TC 6 Z9 6 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD APR PY 2002 VL 55 IS 4 BP 400 EP 406 AR PII S0895-4356(01)00505-4 DI 10.1016/S0895-4356(01)00505-4 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 533ET UT WOS:000174517000012 PM 11927209 ER PT J AU Nakamura, H Kasuya, H Mullen, JT Yoon, SS Pawlik, TM Chandrasekhar, S Donahue, JM Chiocca, EA Chung, RY Tanabe, KK AF Nakamura, H Kasuya, H Mullen, JT Yoon, SS Pawlik, TM Chandrasekhar, S Donahue, JM Chiocca, EA Chung, RY Tanabe, KK TI Regulation of herpes simplex virus gamma(1)34.5 expression and oncolysis of diffuse liver metastases by Myb34.5 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACTIVATED PROTEIN-KINASE; REPLICATION-DEFECTIVE MUTANTS; HUMAN COLORECTAL-CANCER; GENE-THERAPY; IN-VIVO; CELLULAR INHIBITOR; MALIGNANT GLIOMAS; COLON-CARCINOMA; INVIVO BEHAVIOR; HEPATITIS-B AB Myb34.5 is a herpes simplex virus 1 (HSV-1) mutant deleted in the gene for ribonucleotide reductase (ICP6). It also carries a version of gamma(1)34.S (a viral gene product that promotes the dephosphorylation of eIF-2alpha) that is under control of the E2F-responsive cellular B-myb promoter, rather than of its endogenous promoter. Myb34.5 replication in tumor cells results in their destruction (oncolysis). gamma(1)34.5 expression by HSV-1 subverts an important cell defense mechanism against viral replication by preventing shutoff of protein synthesis after viral infection. Infection of colon carcinoma cells with Myb34.5 results in greater eIF-2alpha dephosphorylation and viral replication compared with infection with HSV-1 mutants completely defective gamma(1)34.5 expression. In contrast, infection of normal hepatocytes with Myb34.5 results in low levels of eIF-2alpha dephosphorylation and viral replication that are similar to those observed with HSV-1 mutants completely defective gamma(1)34.5 and ICP6. When administered intravascularly into mice with diffuse liver metastases, Myb34.5 has greater antineoplastic activity than HSV-1 mutants with completely defective gamma(1)34.S expression and more restricted biodistribution compared with HSV-1 mutants with wild-type gamma(1)34.5 expression. Myb34.5 displays reduced virulence and toxicity compared to HSV-1 mutants with wild-type gamma(1)34.5 expression. Portal venous administration of Myb34.5 significantly reduces liver tumor burden in and prolongs the life of mice with diffuse liver metastases. Preexisting Ab's to HSV-1 do not reduce the antitumor efficacy of Myb34.5 in vivo. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Nakamura, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Surg Oncol, Cox Bldg 626, Boston, MA 02114 USA. RI Kasuya, hideki/I-7278-2014 FU NCI NIH HHS [P01 CA069246, CA-69246, CA-71345, CA-76183, R01 CA076183, R29 CA064454, T32 CA071345]; NIDDK NIH HHS [DK-43352]; NIGMS NIH HHS [GM-07035, T32 GM007035] NR 63 TC 51 Z9 52 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2002 VL 109 IS 7 BP 871 EP 882 DI 10.1172/JCI10623 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 537KG UT WOS:000174757300005 PM 11927614 ER PT J AU Viglietta, V Kent, SC Orban, T Hafler, DA AF Viglietta, V Kent, SC Orban, T Hafler, DA TI GAD65-reactive T cells are activated in patients with autoimmune type 1a diabetes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MYELIN BASIC-PROTEIN; CD28 COSTIMULATION; MULTIPLE-SCLEROSIS; B7 COSTIMULATION; CLONAL ANERGY; NOD MICE; CTLA-4; MELLITUS; ANTIGEN; RESPONSES AB Insulin-dependent type 1 diabetes is an autoimmune disease mediated by T lymphocytes recognizing pancreatic islet cell antigens. Glutamic acid decarboxylase 65 (GAD65) appears to be an important autoantigen in the disease. However, T cells from both patients with type I diabetes and healthy subjects vigorously proliferate in response to GAD65 stimulation ex vivo, leading us to postulate that the critical event in the onset of human diabetes is the activation of autoreactive T cells. Thus, we investigated whether GAD65-reactive T cells in patients with diabetes functioned as previously activated memory T cells, no longer requiring a second, costimulatory signal for clonal expansion. We found that in patients with new-onset type 1 diabetes, GAD65-reactive T cells were strikingly less dependent on CD28 and B7-1 costimulation to enter into cell cycle and proliferate than were equivalent cells derived from healthy controls. We hypothesize that these autoreactive T cells have been activated in vivo and have differentiated into memory cells, suggesting a pathogenic role in type 1 diabetes. In addition, we observed different effects with selective blockade of either B7-1 or B7-2 molecules; B7-1 appears to deliver a negative signal by engaging CTLA-4, while B7-2 engagement of CD28 upregulates T cell proliferation and cytokine secretion. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Mol Immunol,Ctr Neurol Dis, Boston, MA USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Hafler, DA (reprint author), Harvard Univ, Sch Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NIAID NIH HHS [P01AI39671, P01 AI039671]; NIDDK NIH HHS [1R01DK52127-05]; NINDS NIH HHS [R01NS24247, R01 NS024247] NR 49 TC 133 Z9 138 U1 1 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2002 VL 109 IS 7 BP 895 EP 903 DI 10.1172/JCI14114 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 537KG UT WOS:000174757300007 PM 11927616 ER PT J AU Huang, M Sharma, S Zhu, LX Keane, MP Luo, J Zhang, L Burdick, MD Lin, YQ Dohadwala, M Gardner, B Batra, RK Strieter, RM Dubinett, SM AF Huang, M Sharma, S Zhu, LX Keane, MP Luo, J Zhang, L Burdick, MD Lin, YQ Dohadwala, M Gardner, B Batra, RK Strieter, RM Dubinett, SM TI IL-7 inhibits fibroblast TGF-beta production and signaling in pulmonary fibrosis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-FACTOR-BETA; INDUCED LUNG FIBROSIS; GENE-EXPRESSION; DOWN-REGULATION; CELL-PROLIFERATION; IFN-GAMMA; BLEOMYCIN; INTERLEUKIN-7; COLLAGEN; ACTIVATION AB Based on studies by our group and others, we hypothesized that IL-7 may possess antifibrotic activities in an IFN-gamma-dependent and independent manner. Here, we have evaluated the antifibrotic therapeutic potential of IL-7 in both in vitro and in vivo pulmonary fibrosis models. IL-7 inhibited both TGF-beta production and signaling in fibroblasts and required an intact JAK1/STAT1 signal transduction pathway. IL-7-mediated inhibition of TGF-beta signaling was found to be associated with an increase in Smad7, a major inhibitory regulator in the SMAD family. In the presence of IL-7, Smad7 dominant negative fibroblasts restored TGF-beta-induced collagen synthesis, indicating that an IL-7-mediated increase in Smad7 suppressed TGF-beta signaling. Consistent with these in vitro findings, recombinant IL-7 decreased bleomycin-induced pulmonary fibrosis in vivo, independent of IFN-gamma. The antifibrotic activities of IL-7 merit further basic and clinical investigation for the treatment of pulmonary fibrosis. C1 Univ Calif Los Angeles, Sch Med, Div Pulm & Crit Care Med, Dept Med, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Healthcare Syst, Div Pulm & Crit Care Med, Dept Med, Los Angeles, CA USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, Sch Med, Div Pulm & Crit Care Med, Dept Med, 37-131 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. FU NCI NIH HHS [P50 CA-90388, P50 CA090388, R01 CA078654, R01 CA-78564, R01 CA-085686, R01 CA085686]; NHLBI NIH HHS [P01 HL-67665, P01 HL-03906, P01 HL067665] NR 46 TC 94 Z9 103 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2002 VL 109 IS 7 BP 931 EP 937 DI 10.1172/JCI14685 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 537KG UT WOS:000174757300011 PM 11927620 ER PT J AU Han, ED MacFarlane, RC Mulligan, AN Scafidi, J Davis, AE AF Han, ED MacFarlane, RC Mulligan, AN Scafidi, J Davis, AE TI Increased vascular permeability in C1 men inhibitor-deficient mice mediated by the bradykinin type 2 receptor SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID EMBRYONIC STEM-CELLS; PROTEASE INHIBITORS; PLASMA KALLIKREIN; HAGEMAN-FACTOR; ANGIOEDEMA; COMPLEMENT; KININ; IDENTIFICATION; C1-INHIBITOR; DISRUPTION AB Heterozygosity for C1 inhibitor (C1INH) deficiency results in hereditary angioedema. Disruption of the C1INH gene by gene trapping enabled the generation of homozygous- and heterozygous-deficient mice. Mating of heterozygous-deficient mice resulted in the expected 1:2:1 ratio of wild-type, heterozygous, and homozygous-deficient offspring. C1INH-deficient mice showed no obvious phenotypic abnormality. However, following injection with Evans blue dye, both homozygous and heterozygous C1INH-deficient mice revealed increased vascular permeability in comparison with wild-type littermates. This increased vascular permeability was reversed by treatment with intravenous human C1INH, with a Kunitz domain plasma kallikrein inhibitor (DX88), and with a bradykinin type 2 receptor (Bk2R) antagonist (Hoe140). In addition, treatment of the C1INH-deficient mice with an angiotensin-converting enzyme inhibitor (captopril) increased the vascular permeability. Mice with deficiency of both C1INH and Bk2R demonstrated diminished vascular permeability in comparison with C1INH-deficient, Bk2R-sufficient mice. These data support the hypothesis that angioedema is mediated by bradykinin via Bk2R. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Davis, AE (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NICHD NIH HHS [HD-22082, HD-33727, R01 HD033727, R37 HD022082] NR 25 TC 215 Z9 218 U1 0 U2 11 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2002 VL 109 IS 8 BP 1057 EP 1063 DI 10.1172/JCI200214211 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 542GV UT WOS:000175035900011 PM 11956243 ER PT J AU Poznansky, MC Olszak, IT Evans, RH Wang, ZY Foxall, RB Olson, DP Weibrecht, K Luster, AD Scadden, DT AF Poznansky, MC Olszak, IT Evans, RH Wang, ZY Foxall, RB Olson, DP Weibrecht, K Luster, AD Scadden, DT TI Thymocyte emigration is mediated by active movement away from stroma-derived factors SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; CHEMOKINE RECEPTOR CXCR4; PROTEIN-KINASE-C; T-CELLS; MIGRATION; CHEMOATTRACTANT; PROLIFERATION; PATHWAYS; SDF-1 AB T cells leave the thymus at a specific time during differentiation and do not return despite elaboration of known T cell chemoattractants by thymic stroma. We observed differentiation stage-restricted egress of thymocytes from an artificial thymus in which vascular structures or hemodynamics could not have been playing a role. Hypothesizing that active movement of cells away from a thymic product may be responsible, we demonstrated selective reduction in emigration from primary thymus by inhibitors of active movement down a concentration gradient (chemofugetaxis). Immature intrathymic precursors were insensitive to an emigration signal, whereas mature thymocytes and peripheral blood T cells were sensitive. Thymic stroma was noted to elaborate at least two proteins capable of inducing emigration, one of which was stromal cell-derived factor-1. Thymic emigration is mediated, at least in part, by specific fugetaxis-inducing factors to which only mature cells respond. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr,Massachusetts Gen Hosp Canc Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp,Ctr Immunol & Inflammatory, Div Rheumatol Allergy & Immunol, Boston, MA USA. RP Poznansky, MC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr,Massachusetts Gen Hosp Canc Ctr, Bldg 149 13th St,Room 4005A, Boston, MA 02129 USA. OI Foxall, Russell/0000-0001-9821-0708 FU NHLBI NIH HHS [R01 HL044851, HL-44851]; NIAID NIH HHS [AI-49757, R01 AI049757]; NIDDK NIH HHS [DK-50234, R01 DK050234] NR 29 TC 78 Z9 81 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2002 VL 109 IS 8 BP 1101 EP 1110 DI 10.1172/JCI13853 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 542GV UT WOS:000175035900016 PM 11956248 ER PT J AU Ruoff, KL AF Ruoff, KL TI Miscellaneous catalase-negative, gram-positive cocci: Emerging opportunists SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Review ID HUMAN CLINICAL SPECIMENS; IGNAVIGRANUM-RUOFFIAE; DOLOSIGRANULUM-PIGRUM; GEN. NOV.; SP. NOV.; IDENTIFICATION; PATHOGEN C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Microbiol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ruoff, KL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Fruit St,GRB526, Boston, MA 02114 USA. NR 20 TC 58 Z9 62 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2002 VL 40 IS 4 BP 1129 EP 1133 DI 10.1128/JCM.40.4.1129-1133.2002 PG 5 WC Microbiology SC Microbiology GA 538GX UT WOS:000174808000001 PM 11923320 ER PT J AU Kudva, IT Evans, PS Perna, NT Barrett, TJ DeCastro, GJ Ausubel, FM Blattner, FR Calderwood, SB AF Kudva, IT Evans, PS Perna, NT Barrett, TJ DeCastro, GJ Ausubel, FM Blattner, FR Calderwood, SB TI Polymorphic amplified typing sequences provide a novel approach to Escherichia coli O157 : H7 strain typing SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; MULTILOCUS ENZYME ELECTROPHORESIS; FOOD-BORNE OUTBREAK; PCR; PATTERNS AB Escherichia coli O157:H7 (O157) strains are commonly typed by pulsed-field gel electrophoresis (PFGE) following digestion of genomic DNA with the restriction enzyme XbaI. We have shown that O157 strains differ from each other by a series of discrete insertions or deletions, some of which contain recognition sites for XbaI, suggesting that these insertions and deletions are responsible for the differences in PFGE patterns. We have devised a new O157 strain typing protocol, polymorphic amplified typing sequences (PATS), based on this information. We designed PCR primer pairs to amplify genomic DNA flanking each of 40 individual XbaI sites in the genomes of two O157 reference strains. These primer pairs were tested with 44 O157 isolates, 2 each from 22 different outbreaks of infection. Thirty-two primer pairs amplified identical fragments from all 44 isolates, while eight primer pairs amplified regions that were polymorphic between isolates. The isolates could be differentiated solely on the basis of which of the eight polymorphic amplicons was detected. PATS correctly identified 21 of 22 outbreak pairs as being identical or highly related, whereas PFGE correctly identified 14 of the 22 outbreak pairs as being identical or highly related; PATS was also able to type isolates from three outbreaks that were untypeable by PFGE. However, PATS was less sensitive than PFGE in discriminating between outbreaks. These data suggest that typing by PATS may provide a simple procedure for strain typing of O157 and other bacteria and that further evaluation of the utility of this method for epidemiologic investigations is warranted. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. Univ Wisconsin, Dept Anim Hlth & Biomed Sci, Madison, WI 53706 USA. Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, Atlanta, GA 30333 USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM scalderwood@partners.org FU NIAID NIH HHS [T32 AI07061, T32 AI007061] NR 19 TC 9 Z9 12 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2002 VL 40 IS 4 BP 1152 EP 1159 DI 10.1128/JCM.40.4.1152-1159.2002 PG 8 WC Microbiology SC Microbiology GA 538GX UT WOS:000174808000005 PM 11923324 ER PT J AU Pena, JA McNeil, K Fox, JG Versalovic, J AF Pena, JA McNeil, K Fox, JG Versalovic, J TI Molecular evidence of Helicobacter cinaedi organisms in human gastric biopsy specimens SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PYLORI AB One hundred twenty-six urease-negative gastric biopsy specimens were evaluated for the presence of Helicobacter genus-specific 16S ribosomal DNA (rDNA) and H. pylori-specific glmM DNA sequences by PCR. The species specificity of the glmM PCR assay was demonstrated, as H. pylori was the only Helicobacter species that yielded the expected glmM amplicon. Most urease-negative specimens (118 of 126 specimens) lacked Helicobacter DNA. However, 8 of 126 urease-negative specimens contained Helicobacter 16S rDNA. In order to identify the Helicobacter species present in urease-negative gastric biopsy specimens, 16S rDNA amplicons were cloned and sequenced. Sequence comparisons were performed by analyses of the sequences in public sequence databases. Two samples contained 16S rDNA that was identified as H. cinaedi with 100% identity and that spanned approximately 400 bp (398 and 398 bp, respectively). In contrast, multiple differences (97% identity; 390 of 398 bp) were observed with H. pylori 16S rDNA in this region. This finding was verified by sequencing an overlapping 537-bp fragment within the 5' portion of 16S rDNA. Although the clinical findings were consistent with H. pylori infection (e.g., duodenal ulcer disease), rapid urease testing and DNA sequence analyses suggested the presence of H. cinaedi organisms and the absence of H, pylori in two human antral biopsy specimens. This study represents the first report of an enteric urease-negative helicobacter in the human stomach. Although these organisms were previously associated with extragastric infections, the roles of these organisms in the pathogenesis of chronic gastritis or peptic ulcer disease remain unclear. C1 Northeastern Univ, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. MIT, Cambridge, MA 02139 USA. RP Versalovic, J (reprint author), Texas Childrens Hosp, Dept Pathol, 6621 Fannin St,MC 1-2261, Houston, TX 77030 USA. FU NCI NIH HHS [R01 CA67529, R01 CA067529]; NIDDK NIH HHS [K08 DK02705, R01 DK052413, K08 DK002705, R01 DK52413] NR 12 TC 21 Z9 22 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2002 VL 40 IS 4 BP 1511 EP 1513 DI 10.1128/JCM.40.4.1511-1513.2002 PG 3 WC Microbiology SC Microbiology GA 538GX UT WOS:000174808000065 PM 11923384 ER PT J AU Tepper, JE O'Connell, M Niedzwiecki, D Hollis, DR Benson, AB Cummings, B Gunderson, LL Macdonald, JS Martenson, JA Mayer, RJ AF Tepper, JE O'Connell, M Niedzwiecki, D Hollis, DR Benson, AB Cummings, B Gunderson, LL Macdonald, JS Martenson, JA Mayer, RJ TI Adjuvant therapy in rectal cancer: Analysis of stage, sex, and local control - Final report of intergroup 0114 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TOTAL MESORECTAL EXCISION; ADVANCED COLORECTAL-CANCER; LYMPH-NODE METASTASES; PHASE-III TRIAL; RANDOMIZED TRIAL; SMALL-BOWEL; CURATIVE SURGERY; RADIATION-THERAPY; COLON-CANCER; CARCINOMA AB Purpose: The gastrointestinal Intergroup studied postoperative adjuvant chemotherapy and radiation therapy in patients with T3/4 and N+ rectal cancer after potentially curative surgery to try to improve chemotherapy and to determine the risk of systemic and local failure. Patients and Methods: All patients had a potentially curative surgical resection and were treated with two cycles of chemotherapy followed by chemoradiation therapy and two additional cycles of chemotherapy. Chemotherapy regimens were bolus fluorouracil (5-FU), 5-FU and leucovorin, 5-FU and levamisole, and 5-FU, leucovorin, and levamisole. Pelvic irradiation was given to a dose of 45 Gy to the whole pelvis and a boost to 50.4 to 54 Gy. Results: One thousand six hundred ninety-five patients were entered and fully assessable, with a median follow-up of 7.4 years. There was no difference in overall survival (OS) or disease-free survival (DFS) by drug regimen. DFS and OS decreased between years 5 and 7 (from 54% to 50% and 64% to 56%, respectively), although recurrence-free rates had only a small decrease. The local recurrence rate was 14% (9% in low-risk [T1 to N2+] and 18% in high-risk patients [T3N+, T4N]). Overall, 7-year survival rates were 70% and 45% for the low-risk and high-risk groups, respectively. Males had a poorer overall survival rate than females. Conclusion: There is no advantage to leucovorin- or levamisole-containing regimens over bolus 5-FU alone in the adjuvant treatment of rectal cancer when combined with irradiation. Local and distant recurrence rates are still high, especially in T3N+ and T4 patients, even with full adjuvant chemoradiation therapy. (C) 2002 by American Society of Clinical Oncology. C1 Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27599 USA. Duke Univ, Med Ctr, Canc & Leukemia Grp B, Stat Off, Durham, NC USA. Mayo Clin, Ctr Canc, Rochester, MN USA. Northwestern Univ, Div Hematol Oncol, Chicago, IL 60611 USA. Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M4X 1K9, Canada. Mayo Clin, Scottsdale, AZ USA. St Vincents CCC, Gastrointestinal Oncol Serv, New York, NY USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Tepper, JE (reprint author), Univ N Carolina, Dept Radiat Oncol, Campus Box 7512, Chapel Hill, NC 27599 USA. NR 53 TC 202 Z9 210 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2002 VL 20 IS 7 BP 1744 EP 1750 DI 10.1200/JCO.2002.07.132 PG 7 WC Oncology SC Oncology GA 538ZP UT WOS:000174845200008 PM 11919230 ER PT J AU Earle, CC Neumann, PJ Gelber, RD Weinstein, MC Weeks, JC AF Earle, CC Neumann, PJ Gelber, RD Weinstein, MC Weeks, JC TI Impact of referral patterns on the use of chemotherapy for lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID 2 RURAL STATES; BREAST-CANCER; PROSTATE-CANCER; OLDER WOMEN; CARE; POPULATION; STAGE; MANAGEMENT; MORTALITY; OUTCOMES AB Purpose: To determine the extent to which unexplained variation in the use of chemotherapy for advanced lung cancer is due to access to oncologists' services as opposed to treatment decisions made after seeing an oncologist. Methods: We performed a retrospective cohort study of 12,015 patients over age 65 diagnosed with metastatic lung cancer between 1991 and 1996 while living in one of 11 regions monitored by a Survival, Epidemiology, and End Results (SEER) tumor registry. Assessment by an oncologist and subsequent treatment with chemotherapy were determined by examining linked Medicare claims. Results: Of patients who did not receive chemotherapy, 36% were never assessed by a physician who provides chemotherapy. Patients living in certain areas, those diagnosed in more recent years, and those who received care in a teaching hospital were all more likely to see a cancer specialist. These factors were unrelated to subsequent treatment decisions, however. Conversely, age and comorbidity did not have a significant effect on whether a patient was seen by an oncologist, but they were associated with the likelihood of subsequently receiving chemotherapy. Black race, probably acting as a proxy for lower socioeconomic status, was associated with both a diminished likelihood of seeing a cancer specialist and subsequently receiving chemotherapy. Conclusion: Nonmedical factors are important determinants of whether a lung cancer patient is seen by a physician who provides chemotherapy. After seeing such a physician, treatment decisions seem to be mostly explained by appropriate medical factors. Racial and socioeconomic disparities still exist at both steps, however. As therapeutic options expand, referring physicians must ensure that biases and barriers to care do not deprive patients of the opportunity to consider all of their treatment options. (C) 2002 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Program Econ Evaluat Med Technol, Boston, MA 02115 USA. RP Earle, CC (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA72663] NR 62 TC 131 Z9 132 U1 4 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2002 VL 20 IS 7 BP 1786 EP 1792 DI 10.1200/JCO.2002.07.142 PG 7 WC Oncology SC Oncology GA 538ZP UT WOS:000174845200013 PM 11919235 ER PT J AU Hinton, S Catalano, P Einhorn, LH Leohrer, PJ Kuzel, T Vaughn, D Wilding, G AF Hinton, S Catalano, P Einhorn, LH Leohrer, PJ Kuzel, T Vaughn, D Wilding, G TI Phase II study of paclitaxel plus gemcitabine in refractory germ cell tumors (E9897): A trial of the eastern cooperative oncology group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIGH-DOSE CHEMOTHERAPY; TESTICULAR CANCER; SALVAGE THERAPY; CISPLATIN; ETOPOSIDE; IFOSFAMIDE; VINBLASTINE; CARBOPLATIN; BLEOMYCIN AB Purpose: Despite great success in the treatment of disseminated germ cell tumors, 20% of patients are incurable and become candidates for investigational therapy. Paclitaxel and gemcitabine have shown activity as single agents in refractory germ cell tumors and can be combined with manageable toxicity. Patients and Methods: Patients with germ cell tumors believed to be incurable with chemotherapy or surgery were treated with paclitaxel 110 mg/m(2) and gemcitabine 1,000 mg/m(2) intravenously on days 1, 8, and 15 of a 4-week cycle for a maximum of six cycles. Patients were evaluated for response and toxicity. Results. Twenty-eight of 30 enrolled patients were assessable. Toxicity was primarily hematologic but was manageable with only a single case of neutropenic fever. Six (21.4%) of 28 patients responded, including three complete responses. Two of the complete responders were continuously disease-free at 15+ and 25+ months. Conclusion: Paclitaxel plus gemcitabine is an active regimen in refractory germ cell tumors, with an acceptable toxicity profile. This regimen has the possibility for long-term disease-free survival in this refractory patient population. C1 Indiana Univ, Med Ctr, Indianapolis, IN USA. Walther Canc Inst, Indianapolis, IN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Wisconsin, Madison, WI USA. RP Einhorn, LH (reprint author), 535 Barnhill Dr,RT 473, Indianapolis, IN 46202 USA. FU NCI NIH HHS [CA15488, CA17145, CA21076, CA21115, CA23318, CA49883, CA6636] NR 24 TC 76 Z9 79 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2002 VL 20 IS 7 BP 1859 EP 1863 DI 10.1200/JCO.2002.07.158 PG 5 WC Oncology SC Oncology GA 538ZP UT WOS:000174845200023 PM 11919245 ER PT J AU Ramaswamy, S Golub, TR AF Ramaswamy, S Golub, TR TI DNA microarrays in clinical oncology SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GENE-EXPRESSION PROFILES; HUMAN BREAST-CANCER; LASER-CAPTURE MICRODISSECTION; MOLECULAR CLASSIFICATION; OLIGONUCLEOTIDE ARRAYS; MYELOID-LEUKEMIA; CDNA MICROARRAYS; MESSENGER-RNA; COPY NUMBER; PREDICTION AB Aberrant gene expression is critical for tumor initiation and progression. However, we lack a comprehensive understanding of all genes that are aberrantly expressed in human cancer. Recently, DNA microarrays have been used to obtain global views of human cancer gene expression and to identify genetic markers that might be important for diagnosis and therapy. We review clinical applications of these novel tools, discuss some important recent studies, identify promising avenues of research in this emerging field of study, and discuss the likely impact that expression profiling will have on clinical oncology. C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. MIT, Ctr Genome Res, Whitehead Inst, Cambridge, MA 02139 USA. RP Golub, TR (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Adult Oncol, 44 Binney St,D640, Boston, MA 02115 USA. EM golub@genome.wi.mit.edu NR 64 TC 242 Z9 280 U1 0 U2 15 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 APR 1 PY 2002 VL 20 IS 7 BP 1932 EP 1941 PG 10 WC Oncology SC Oncology GA 538ZP UT WOS:000174845200032 PM 11919254 ER PT J AU Fava, M AF Fava, M TI Somatic symptoms, depression, and antidepressant treatment SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID PAIN; DEFINITIONS; COMPLAINTS; EFFICACY; CARE C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Dept Psychiat, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, Dept Psychiat, ACC 812,15 Parkman St, Boston, MA 02114 USA. NR 26 TC 56 Z9 57 U1 2 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2002 VL 63 IS 4 BP 305 EP 307 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 541ZM UT WOS:000175017500006 PM 12000203 ER PT J AU Fava, M Hoog, SL Judge, RA Kopp, JB Nilsson, ME Gonzales, JS AF Fava, M Hoog, SL Judge, RA Kopp, JB Nilsson, ME Gonzales, JS TI Acute efficacy of fluoxetine versus sertraline and paroxetine in major depressive disorder including effects of baseline insomnia SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 11th ECNP Congress CY NOV, 1998 CL PARIS, FRANCE SP ECNP ID DOUBLE-BLIND; MULTICENTER; ANTIDEPRESSANT; OUTPATIENTS AB This study assessed whether fluoxetine, sertraline, and paroxetine differ in efficacy and tolerability in depressed patients and the impact of baseline insomnia on outcomes. Patients (N = 284) with DSM-IV major depressive disorder were randomly assigned in a double-blind fashion to fluoxetine, paroxetine, or sertraline for 10 to 16 weeks of treatment. Using the Hamilton Rating Scale for Depression (HAM-D) sleep disturbance factor score, patients were categorized into low (<4) or high ( A) baseline insomnia subgroups. Changes in depression and insomnia were assessed. Safety assessments included treatment-emergent adverse events (AEs), reasons for discontinuation, and AEs leading to discontinuation. In addition, AEs were evaluated within insomnia subgroups to determine emergence of activation or sedation. Depression improvement, assessed with the HAM-D-17 total score, was similar among treatments in all patients (p = 0.365) and the high (p = 0.853) and low insomnia (p = 0.415) subgroups. Insomnia improvement, assessed with the HAM-D sleep disturbance factor score, was similar among treatments in all patients (p = 0.868) and in the high (p = 0.852) and low insomnia (p = 0.982) subgroups. Analyses revealed no significant differences between treatments in the percentages of patients with substantial worsening, any worsening, worsening at endpoint, or improvement at endpoint in the HAM-D sleep disturbance factor in either insomnia subgroup. Treatments were well tolerated in most patients. No significant differences between treatments in the incidence of AEs suggestive of activation or sedation were seen in the insomnia subgroups. These data show no significant differences in acute treatment efficacy and tolerability across fluoxetine, sertraline, and paroxetine in major depressive disorder patients. Improvement in overall depression and in associated insomnia was achieved by most patients regardless of baseline insomnia. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Lilly Res Labs, Indianapolis, IN USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, WAC812,15 Parkman St, Boston, MA 02114 USA. NR 19 TC 62 Z9 64 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 2002 VL 22 IS 2 BP 137 EP 147 DI 10.1097/00004714-200204000-00006 PG 11 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 538HB UT WOS:000174808400006 PM 11910258 ER PT J AU Senkfor, AJ Van Petten, C Kutas, M AF Senkfor, AJ Van Petten, C Kutas, M TI Episodic action memory for real objects: An ERP investigation with perform, watch, and imagine action encoding tasks versus a non-action encoding task SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID EVENT-RELATED POTENTIALS; POSITRON-EMISSION-TOMOGRAPHY; PRIMARY MOTOR CORTEX; BRAIN POTENTIALS; RECOGNITION MEMORY; FUNCTIONAL-ANATOMY; AGE-DIFFERENCES; SELF-REFERENCE; WORDS; RETRIEVAL AB Cognitive research shows that people typically remember actions they perform better than those that they only watch or imagine doing. but also at times misremember doing actions they merely imagined or planned to do (source memory errors). Neural research suggests some overlap between brain regions engaged during action production, motor imagery, and action observation. The present study evaluates the similarities differences in brain activity during the retrieval of various types of action and nonaction memories. Participants study real objects in one of four encoding conditions: performing an action, watching the experimenter perform an action, or imagining an action with an object, or a nonmotoric task of estimating an object's cost, At test, participants vie v color photos of the objects, and make source memory judgments about the initial encoding episodes, Event-related potentials (ERPS) during test reveal (1) content-specific brain activitA depending on the nature of the encoding task, and (12) a hand tag. i.e., sensitivity to the hand with which an object had been manipulated at study. At fronto-central sites, ERPs are similar for the three action-retrieval conditions, which are distinct from those to the cost-encoded objects, At occipital sites ERPs distinguished objects from encoding conditions with visual motion (Perform and Watch) from those without visual motion (Imagine arid Cost). Results thus suggest some degree of recapitulation of encoding brain activity during retrieval of memories with qualitatively distinct attributes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Cambridge, MA 02138 USA. Univ Arizona, Tucson, AZ 85721 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. RP Senkfor, AJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH NMR Ctr, 149 2301 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG 08313, AG 14792]; NIMH NIH HHS [MH 52893] NR 62 TC 45 Z9 46 U1 3 U2 8 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 APR 1 PY 2002 VL 14 IS 3 BP 402 EP 419 DI 10.1162/089892902317361921 PG 18 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 536PV UT WOS:000174711800006 PM 11970800 ER PT J AU Spencer, K McCarley, R AF Spencer, K McCarley, R TI Hyperfacilitation of attentional orienting and priming in schizophrenia SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2002 SU S MA B10 BP 46 EP 46 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 525LP UT WOS:000174072000139 ER PT J AU Giovanello, KS Verfaellie, M Keane, MM AF Giovanello, KS Verfaellie, M Keane, MM TI On the relationship between item and associative recognition memory in amnesia SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Boston, MA 02215 USA. Boston VA Healthcare Syst, Boston, MA USA. Wellesley Coll, Wellesley, MA 02181 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2002 SU S MA B65 BP 58 EP 58 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 525LP UT WOS:000174072000194 ER PT J AU Jasdzewski, G Strangman, G Wagner, J Kwong, K Boas, D Poldrack, R AF Jasdzewski, G Strangman, G Wagner, J Kwong, K Boas, D Poldrack, R TI Now you see it, now you don't: The initial dip as measured using near-infrared spectroscopy and event-related paradigms SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2002 SU S MA B92 BP 63 EP 63 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 525LP UT WOS:000174072000221 ER PT J AU Kuperberg, G Goff, D Rosen, B Caplan, D AF Kuperberg, G Goff, D Rosen, B Caplan, D TI Abnormal modulation of cortical networks during language processing in schizophrenia SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2002 SU S MA C59 BP 82 EP 82 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 525LP UT WOS:000174072000307 ER PT J AU Herbert, MR Ziegler, DA Adrien, KT Makris, N Kennedy, DN Bakardjiev, A Hodgson, J Takeoka, M Harris, GJ Caviness, VS AF Herbert, MR Ziegler, DA Adrien, KT Makris, N Kennedy, DN Bakardjiev, A Hodgson, J Takeoka, M Harris, GJ Caviness, VS TI Asymmetries in language-related cortical regions in girls and boys with specific language impairment SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Childrens Hosp Oakland, Oakland, CA 94609 USA. Keio Univ, Sch Med, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2002 SU S MA D27 BP 101 EP 101 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 525LP UT WOS:000174072000394 ER PT J AU Ziegler, A Herbert, MR Adrien, KT Makris, N Kennedy, DN Bakardjiev, A Hodgson, J Takeoka, M Harris, GJ Caviness, VS AF Ziegler, A Herbert, MR Adrien, KT Makris, N Kennedy, DN Bakardjiev, A Hodgson, J Takeoka, M Harris, GJ Caviness, VS TI Cortical asymmetries and language ability in boys with autism or specific language impairment SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Childrens Hosp Oakland, Oakland, CA 94609 USA. Keio Univ, Sch Med, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2002 SU S MA D26 BP 101 EP 101 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 525LP UT WOS:000174072000393 ER PT J AU Mody, M Ahlfors, S Halgren, E AF Mody, M Ahlfors, S Halgren, E TI An FMRI investigation of phonological processing in good and poor readers SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02114 USA. RI Ahlfors, Seppo/P-3644-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2002 SU S MA E28 BP 127 EP 127 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 525LP UT WOS:000174072000514 ER PT J AU Senkfor, AJ Busa, E Gabrieli, J Gabrieli, J AF Senkfor, AJ Busa, E Gabrieli, J Gabrieli, J TI Episodic action memories: Recapitulation of action events revealed by FMRI SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02114 USA. Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2002 SU S MA E78 BP 138 EP 138 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 525LP UT WOS:000174072000564 ER PT J AU Esterman, M McGlinchey-Berroth, R Alexander, M Milberg, W AF Esterman, M McGlinchey-Berroth, R Alexander, M Milberg, W TI Triangular backgrounds shift the allocation of attention in hemispatial neglect SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Univ Calif Berkeley, Berkeley, CA 94720 USA. VA Boston Healthcare Syst, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RI McGlinchey, Regina/R-1971-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2002 SU S MA F13 BP 150 EP 150 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 525LP UT WOS:000174072000618 ER PT J AU Chabris, C Aharon, I Clark, J Nakayama, K Sepeta, L Mignault, A Joseph, R McGrath, L Tager-Flusberg, HT Harris, G AF Chabris, C Aharon, I Clark, J Nakayama, K Sepeta, L Mignault, A Joseph, R McGrath, L Tager-Flusberg, HT Harris, G TI Processing of facial expressions by autistic and normal adults: Behavioral and fMRI studies SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2002 SU S MA F21 BP 152 EP 152 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 525LP UT WOS:000174072000626 ER PT J AU Pare-Blagoev, EJ Cestnick, L Rose, T Clark, J Misra, M Katzir-Cohen, T Poldrack, R AF Pare-Blagoev, EJ Cestnick, L Rose, T Clark, J Misra, M Katzir-Cohen, T Poldrack, R TI The neural basis of phonological awareness in normal-reading children examined using functional magnetic resonance imaging SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. Tufts Univ, Medford, MA 02155 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2002 SU S MA F53 BP 159 EP 159 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 525LP UT WOS:000174072000658 ER PT J AU Alterman, AI Cacciola, JS Mulvaney, FD Rutherford, MJ Langenbucher, J AF Alterman, AI Cacciola, JS Mulvaney, FD Rutherford, MJ Langenbucher, J TI Alcohol dependence and abuse in three groups at varying familial alcoholism risk SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID DSM-IV; UNITED-STATES; USE DISORDERS; MEN; PREVALENCE AB Three groups of young men varying in familial alcoholism risk were compared for lifetime and current Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) diagnoses. A withdrawal gate diagnostic model (WGM) requiring withdrawal for a dependence diagnosis was also evaluated. Extremely high lifetime DSM-IV diagnostic rates were found for all groups (greater than or equal to78%), with the highest rate in the highest risk group. Similar group differences obtained for individual criteria or symptoms. Although lifetime diagnostic rates were similar for the WGM and DSM-IV, virtually all cases of dependence were preceded by abuse for the WGM, unlike DSM-IV. The findings underline the importance of distinguishing degrees of familial alcoholism risk. The WGM model temporal onset findings versus DSM-IV and the high lifetime diagnostic rates obtained suggest some limitations of the DSM-IV diagnoses. C1 Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Washington, Seattle, WA 98195 USA. Rutgers State Univ, Ctr Alcohol Studies, Piscataway, NJ 08855 USA. RP Alterman, AI (reprint author), Univ Penn, Sch Med, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. NR 26 TC 7 Z9 7 U1 3 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD APR PY 2002 VL 70 IS 2 BP 336 EP 343 DI 10.1037//0022-006X.70.2.336 PG 8 WC Psychology, Clinical SC Psychology GA 538FT UT WOS:000174805100007 PM 11952191 ER PT J AU Nikkanen, HE Brown, DFM Nadel, ES Tancredi, D AF Nikkanen, HE Brown, DFM Nadel, ES Tancredi, D TI Low back pain SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID VERTEBRAL OSTEOMYELITIS C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Affiliated Emergency Med Residency, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, CLN-115, Boston, MA 02114 USA. NR 11 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD APR PY 2002 VL 22 IS 3 BP 279 EP 283 AR PII S0736-4679(01)00484-X DI 10.1016/S0736-4679(01)00484-X PG 5 WC Emergency Medicine SC Emergency Medicine GA 539BC UT WOS:000174848800010 PM 11932092 ER PT J AU Fultz, SL Arnold, RM AF Fultz, SL Arnold, RM TI Safe reproduction in an HIV discordant couple. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Med Ctr, Ctr Hlth Equ Res & Promot,Div Gen Internal Med, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Div Gen Internal Med, Sect Palliat Care & Med Human, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 40 EP 40 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200065 ER PT J AU Hippen, BE Lu, LB AF Hippen, BE Lu, LB TI Large B-cell lymphoma presenting as large cutaneous occipital mass. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 46 EP 46 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200092 ER PT J AU Mcassey, JM Hayes, P AF Mcassey, JM Hayes, P TI Chronic pelvic pain and a history of sexual abuse ... Is there an association? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Dept Vet Affairs, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2002 VL 17 SU 1 BP 57 EP 57 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200146 ER PT J AU Goroll, A Fincher, RE Defer, T Whelan, A Headrick, L Davis, AK Stearns, J AF Goroll, A Fincher, RE Defer, T Whelan, A Headrick, L Davis, AK Stearns, J TI Family Medicine Curriculum Project's curriculum resource product SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Med Coll Georgia, Augusta, GA 30912 USA. Washington Univ, St Louis, MO USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. AKD Consulting, Mukilteo, WA USA. Univ Wisconsin, Milwaukee, WI 53201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 91 EP 91 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200301 ER PT J AU Haidet, P Richards, B Hunt, D Seidel, C Schneider, V Coverdale, J Moran, B AF Haidet, P Richards, B Hunt, D Seidel, C Schneider, V Coverdale, J Moran, B TI Team Learning: An effective new method of large-group teaching for medical educators. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Houston VAMC, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 94 EP 94 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200314 ER PT J AU Atlas, SJ Van den Ancker, MA Wasiak, R Pransky, GS AF Atlas, SJ Van den Ancker, MA Wasiak, R Pransky, GS TI Workers' compensation for back pain: A pilot study of primary care involvement and outcomes. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Liberty Mutual Res Ctr, Hopkinton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 109 EP 109 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200379 ER PT J AU Lawrence, VA Silverstein, JH Cornell, JE Carson, JL AF Lawrence, VA Silverstein, JH Cornell, JE Carson, JL TI Simple interventions may improve functional recovery after hip fracture repair. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Univ Med & Dent New Jersey, New Brunswick, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 114 EP 115 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200402 ER PT J AU Lawrence, VA Hazuda, HP Cornell, JE Mulrow, CD AF Lawrence, VA Hazuda, HP Cornell, JE Mulrow, CD TI Functional health recovery after major abdominal surgery in elders. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 114 EP 114 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200401 ER PT J AU Linder, JA Singer, DE AF Linder, JA Singer, DE TI Treatment expectations and concern about anthrax among patients with respiratory tract infections. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2002 VL 17 SU 1 BP 115 EP 115 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200405 ER PT J AU Natarajan, S Liao, Y Sinha, D Cao, G Lipsitz, SR Mcgee, D AF Natarajan, S Liao, Y Sinha, D Cao, G Lipsitz, SR Mcgee, D TI Gender differences in the effect of longstanding diabetes on cardiovascular mortality. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract 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 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 APR PY 2002 VL 17 SU 1 BP 117 EP 117 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200413 ER PT J AU Steinman, MA Gonzales, R Linder, JA Landefeld, CS AF Steinman, MA Gonzales, R Linder, JA Landefeld, CS TI Changing use of outpatient antibiotics in the United States; 1991-1999. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2002 VL 17 SU 1 BP 119 EP 119 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200425 ER PT J AU Good, CB Brucker, N Bhattacharya, R Mangione, MP AF Good, CB Brucker, N Bhattacharya, R Mangione, MP TI Gabapentin: Is it being used appropriately? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 124 EP 124 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200447 ER PT J AU Nelson, K Reiber, G Boyko, EJ AF Nelson, K Reiber, G Boyko, EJ TI Diet and exercise among adults with type 2 diabetes - Findings from the Third National Health and Nutrition Examination Survey (NHANES III). SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2002 VL 17 SU 1 BP 129 EP 129 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200472 ER PT J AU O'Rorke, JE Pugh, JA AF O'Rorke, JE Pugh, JA TI Musculoskeletal medicine and the practicing internist. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 129 EP 129 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200473 ER PT J AU Allen, E Nicolaidis, CM Helfand, M AF Allen, E Nicolaidis, CM Helfand, M TI The diagnostic evaluation of rectal bleeding: A cost-effectiveness analysis comparing four evaluation strategies. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 135 EP 135 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200501 ER PT J AU Barton, MB Moore, S Morley, DS Allen, JD Kleinman, KP Emmons, KE Fletcher, SW AF Barton, MB Moore, S Morley, DS Allen, JD Kleinman, KP Emmons, KE Fletcher, SW TI Decreasing anxiety after false-positive mammograms: A controlled trial. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2002 VL 17 SU 1 BP 141 EP 141 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200529 ER PT J AU Moran, S Glazier, G Armstrong, K AF Moran, S Glazier, G Armstrong, K TI Women smokers underestimate the health risks of smoking. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 146 EP 146 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200551 ER PT J AU Stern, L Iqbal, N Chicano, K Daily, D Mcgrory, J Williams, T Samaha, FF AF Stern, L Iqbal, N Chicano, K Daily, D Mcgrory, J Williams, T Samaha, FF TI The VA low carbohydrate intervention diet (VALID) study. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 147 EP 148 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200559 ER PT J AU Stern, L Iqbal, N Chicano, K Daily, D Mcgrory, J Williams, T Williams, M Samaha, FF AF Stern, L Iqbal, N Chicano, K Daily, D Mcgrory, J Williams, T Williams, M Samaha, FF TI Diet composition in the VA low carbohydrate intervention diet (VALID) study. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 148 EP 148 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200560 ER PT J AU Thorndike, AN Rigotti, NA Regan, S Singer, DE AF Thorndike, AN Rigotti, NA Regan, S Singer, DE TI Impact of depression on nicotine withdrawal symptoms and early relapse in smokers hospitalized with cardiovascular disease. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract 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 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 APR PY 2002 VL 17 SU 1 BP 148 EP 149 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200564 ER PT J AU Gordon, AJ Conigliaro, J Mcginnis, KA Rabeneck, L Justice, AC AF Gordon, AJ Conigliaro, J Mcginnis, KA Rabeneck, L Justice, AC TI Substance use and homelessness among veterans with HIV. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Eq Res & Promot, Pittsburgh, PA USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 158 EP 159 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200612 ER PT J AU Long, JA AF Long, JA TI Neighborhood, race, and health in Southwestern Pennsylvania. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 163 EP 163 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200633 ER PT J AU Ngo-Metzger, Q Mccarthy, EP Li, FP Burns, RB Davis, RB Phillips, RS AF Ngo-Metzger, Q Mccarthy, EP Li, FP Burns, RB Davis, RB Phillips, RS TI Older Asian Americans dying with cancer use hospice less frequently than older white patients. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 165 EP 165 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200641 ER PT J AU Petersen, LA Wright, S Peterson, E Daley, J AF Petersen, LA Wright, S Peterson, E Daley, J TI Impact of race on process of care and outcome in veterans with acute myocardial infarction. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Houston VAMC, Houston, TX USA. Boston VAMC, Boston, MA USA. Duke Univ, Durham, NC 27706 USA. Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 166 EP 166 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200647 ER PT J AU Woodard, LD Kressin, NR Petersen, LA AF Woodard, LD Kressin, NR Petersen, LA TI Racial disparities in cholesterol monitoring and treatment for secondary prevention. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VAMC, Houston, TX USA. Boston Univ, Bedford, MA USA. Bedford VAMC, Bedford, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 170 EP 170 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200664 ER PT J AU Yano, E Goldzweig, C Washington, D Caffrey, C Altman, L Simon, B Canelo, I AF Yano, E Goldzweig, C Washington, D Caffrey, C Altman, L Simon, B Canelo, I TI Practice structure of women's health care services in VA medical centers. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 170 EP 170 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200666 ER PT J AU Crane, PK Arterburn, DE AF Crane, PK Arterburn, DE TI The coming epidemic of obesity in elderly Americans. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RI Crane, Paul/C-8623-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 177 EP 177 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200700 ER PT J AU Hamel, MB Henderson, WG Khuri, SF Daley, J AF Hamel, MB Henderson, WG Khuri, SF Daley, J TI Surgical outcomes for patients age 80 or older: Morbidity and mortality from major non-cardiac surgery. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Hines VA Ctr Cooperat Studies Coordinating Ctr, Hines, IL USA. Boston VA Healthcare Syst, W Roxbury, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 178 EP 178 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200704 ER PT J AU Arozuilah, AM Henderson, WG Khan, N Khuri, SF Daley, J AF Arozuilah, AM Henderson, WG Khan, N Khuri, SF Daley, J TI A comparison of the hospital-level contribution to the incidence of 3 major postoperative outcomes. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Chicago Healthcare Syst, Chicago, IL USA. Hines VA Cooperat Studies Program Coordinating, Hines, IL USA. Univ Illinois, Coll Med, Chicago, IL USA. VA Boston Healthcare Syst, W Roxbury, MA USA. Massachusetts Gen Hosp, Partners Healthcare, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 182 EP 182 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200722 ER PT J AU Bridevaux, PO Au, DH Fan, V Mcdonell, M Fihn, SD AF Bridevaux, PO Au, DH Fan, V Mcdonell, M Fihn, SD TI Adherence to guidelines regarding pulmonary function test in patients with chronic obstructive pulmonary disease. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, HSR&D, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 185 EP 185 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200736 ER PT J AU Conigliaro, J Mcginnis, K Gordon, A Rabeneck, L Briggs, J Justice, AC AF Conigliaro, J Mcginnis, K Gordon, A Rabeneck, L Briggs, J Justice, AC TI Do providers recognize problem drinking in their HIV plus patients? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15260 USA. Baylor Coll Med, Houston, TX 77030 USA. VAMC, Cleveland, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 187 EP 187 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200745 ER PT J AU Fang, MC Stafford, RS Ruskin, JN Singer, DE AF Fang, MC Stafford, RS Ruskin, JN Singer, DE TI National trends in antiarrhythmic and antithrombotic medication use in atrial fibrillation. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Ctr Res Dis Prevent, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 191 EP 192 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200765 ER PT J AU Fihn, SD Burman, M Mcdonell, MB Henikoff, J AF Fihn, SD Burman, M Mcdonell, MB Henikoff, J TI Suboptimal management of chronic stable angina in a primary care setting. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2002 VL 17 SU 1 BP 192 EP 192 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200768 ER PT J AU Grant, RW Singer, DE Nathan, DM Meigs, JB AF Grant, RW Singer, DE Nathan, DM Meigs, JB TI Inadequate pharmaceutical management of metabolic risk factors in patients with type 2 diabetes. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 194 EP 195 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200779 ER PT J AU Grant, RW Devita, NG Singer, DE Meigs, JB AF Grant, RW Devita, NG Singer, DE Meigs, JB TI A randomized trial to reduce adherence barriers and medication discrepancies in type 2 diabetes. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Partners Community Healthcare, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2002 VL 17 SU 1 BP 195 EP 195 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200781 ER PT J AU Haidet, P O'Malley, K Sharf, B Aniol, J Gladney, A Greisinger, A Street, R AF Haidet, P O'Malley, K Sharf, B Aniol, J Gladney, A Greisinger, A Street, R TI Links between terrorism and health perceptions of patients. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Houston VAMC, Houston, TX USA. Texas A&M Univ, College Stn, TX USA. Kelsey Res Fdn, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 195 EP 196 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200784 ER PT J AU Haidet, P O'Malley, K Aniol, J Gladney, A Sharf, B Street, R Tran, A Greisinger, A AF Haidet, P O'Malley, K Aniol, J Gladney, A Sharf, B Street, R Tran, A Greisinger, A TI A tool to measure patients' and physicians' explanatory models of illness. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Houston VAMC, Houston, TX USA. Texas A&M Univ, College Stn, TX USA. Kelsey Res Fdn, Houston, TX USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 APR PY 2002 VL 17 SU 1 BP 196 EP 196 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200785 ER PT J AU Huang, PY Yano, EM Lee, ML Rubenstein, LV AF Huang, PY Yano, EM Lee, ML Rubenstein, LV TI The impact of primary care clinician staffing mix on quality. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 197 EP 197 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200792 ER PT J AU Keating, NL Guadagnoli, E Landrum, MB Weeks, JC AF Keating, NL Guadagnoli, E Landrum, MB Weeks, JC TI Treatment decision making in early-stage breast cancer - Should physicians match patients' desired level of involvement? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR PY 2002 VL 17 SU 1 BP 199 EP 200 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200801 ER PT J AU Keating, NL Landrum, MB Gaudagnoli, E Winer, EP Ayanian, JZ AF Keating, NL Landrum, MB Gaudagnoli, E Winer, EP Ayanian, JZ TI How is outpatient care in the 2 years prior to breast cancer diagnosis associated with stage at diagnosis? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 200 EP 200 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200805 ER PT J AU Linder, JA Singer, DE Stafford, RS AF Linder, JA Singer, DE Stafford, RS TI Is antibiotic use associated with shorter primary care visits for adults with respiratory illnesses? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Sch Med, Stanford Ctr Res Dis Prevent, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 202 EP 202 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200813 ER PT J AU Linder, JA Singer, DE Van den Ancker, M Atlas, SJ AF Linder, JA Singer, DE Van den Ancker, M Atlas, SJ TI Health-related quality of life measures in adults with sinusitis: A systematic review. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 202 EP 202 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200812 ER PT J AU Murff, HJ Gandhi, TK Karson, AS Mort, EA Poon, EG Wang, SJ Fairchild, DG Bates, DW AF Murff, HJ Gandhi, TK Karson, AS Mort, EA Poon, EG Wang, SJ Fairchild, DG Bates, DW TI Primary care physician satisfaction with tracking abnormal results and attitudes concerning clinical decision support systems. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 204 EP 204 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200825 ER PT J AU Nelson, K Chapko, M Reiber, G Rodenbaugh, J Boyko, EJ AF Nelson, K Chapko, M Reiber, G Rodenbaugh, J Boyko, EJ TI The effect of health insurance coverage on diabetes care; Data from the 2000 Behavioral Risk Factor Surveillance System. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 205 EP 205 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200827 ER PT J AU Persell, SD Zaslavsky, AM Weissman, JS Ayanian, JZ AF Persell, SD Zaslavsky, AM Weissman, JS Ayanian, JZ TI Differences in diabetes-related ambulatory preventive care among adults in the United States. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 206 EP 207 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200835 ER PT J AU Petersen, LA Normand, S Leape, L Mcneil, BJ AF Petersen, LA Normand, S Leape, L Mcneil, BJ TI Consequences of regionalizing invasive cardiac procedure technology. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Houston VAMC, Houston, TX USA. Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 207 EP 207 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200836 ER PT J AU Pirraglia, PA Stafford, RS Singer, DE AF Pirraglia, PA Stafford, RS Singer, DE TI National trends in depression diagnosis and antidepressant use in primary care. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Ctr Res Dis Prevent, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 208 EP 208 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200841 ER PT J AU Steinman, MA Gonzales, R Landefeld, CS AF Steinman, MA Gonzales, R Landefeld, CS TI Broad-spectrum antibiotic use in adults with acute respiratory infections. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2002 VL 17 SU 1 BP 212 EP 212 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200861 ER PT J AU Sullivan, AM Gadmer, NM Lakoma, MD Arnold, R Block, SD AF Sullivan, AM Gadmer, NM Lakoma, MD Arnold, R Block, SD TI Physicians' attitudes and practices in caring for families of patients who die in the hospital. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2002 VL 17 SU 1 BP 213 EP 213 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200864 ER PT J AU Takahashi, TA Maynard, C Bradley, KA AF Takahashi, TA Maynard, C Bradley, KA TI US hopsitalizations & costs for illicit drug users with soft tissue infections. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 APR PY 2002 VL 17 SU 1 BP 213 EP 213 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200865 ER PT J AU Taneda, K Mcdonell, MB Fihn, SD AF Taneda, K Mcdonell, MB Fihn, SD TI Evaluation of a questionnaire to monitor patients with hypertension. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 213 EP 213 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200866 ER PT J AU Venuturupalli, S Hardy, M Coulter, I Asch, S Shekelle, PG AF Venuturupalli, S Hardy, M Coulter, I Asch, S Shekelle, PG TI Ayurvedic treatment of diabetes - Comparison of evidence available in India with evidence from Western databases. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, Sepulveda, CA USA. RAND Corp, Santa Monica, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 215 EP 215 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200875 ER PT J AU Whittle, J Kelley, M AF Whittle, J Kelley, M TI Poor hypertension control is common or uncommon, depending on your definition. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 217 EP 217 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200883 ER PT J AU Yano, EM Mittman, BS Lanto, AB Rubenstein, LV AF Yano, EM Mittman, BS Lanto, AB Rubenstein, LV TI Facility-level impact of VA profiling on chronic disease quality and preventive practices. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. RAND, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 218 EP 218 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158200890 ER PT J AU Pugh, JA Best, RG Moore, F Hysong, S Sugarman, B Hull, S Spears, W AF Pugh, JA Best, RG Moore, F Hysong, S Sugarman, B Hull, S Spears, W TI Barriers and facilitators of clinical practice guideline implementation. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, VERDICT, San Antonio, TX USA. Univ Houston, Houston, TX USA. Well Spring, Temple, TX USA. RI Hysong, Sylvia/B-8420-2008 OI Hysong, Sylvia/0000-0002-9063-5207 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 243 EP 243 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158201010 ER PT J AU Woodard, LD Hernandez, MT Petersen, LA AF Woodard, LD Hernandez, MT Petersen, LA TI Racial differences in attitudes regarding cardiovascular disease prevention and treatment: A qualitative study. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VAMC, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 245 EP 245 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158201020 ER PT J AU Bean-Mayberry, BA Chang, CH Mcneil, MA Hayes, PM Scholle, SH AF Bean-Mayberry, BA Chang, CH Mcneil, MA Hayes, PM Scholle, SH TI Influences on patient perceptions of primary care in women veterans. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 246 EP 246 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158201022 ER PT J AU Seaver, MR Frayne, SM Loveland, S Parker, V Christiansen, CL Skinner, KM AF Seaver, MR Frayne, SM Loveland, S Parker, V Christiansen, CL Skinner, KM TI Providing comprehensive care to special populations: Women in Veterans Administration. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Boston Healthcare Syst, Boston, MA USA. Bedford VA, Bedford, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2002 VL 17 SU 1 BP 250 EP 250 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158201043 ER PT J AU Washington, DL Goldzweig, C Caffrey, C Simon, B Yano, EM AF Washington, DL Goldzweig, C Caffrey, C Simon, B Yano, EM TI Can female VA users obtain comprehensive women's health care? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 APR PY 2002 VL 17 SU 1 BP 251 EP 251 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 544LB UT WOS:000175158201048 ER PT J AU Ackermann, RT Williams, JW AF Ackermann, RT Williams, JW TI Rational treatment choices for non-major depressions in primary care - An evidence-based review SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE depression; depressive disorder; premenstrual syndrome; antidepressive agents; psychotherapy; complementary therapies ID RANDOMIZED CONTROLLED TRIAL; PHASE DYSPHORIC DISORDER; PLACEBO-CONTROLLED TRIAL; PREMENSTRUAL-SYNDROME; MINOR DEPRESSION; DOUBLE-BLIND; SYMPTOMS; THERAPY; ALPRAZOLAM; EXERCISE AB OBJECTIVE: This review synthesizes available evidence for managing clinically significant dysphoric symptoms encountered in primary care, when formal criteria for major depression or dysthymia are not met. Discussion is focused on premenstrual dysphoric disorder (PMDD) and minor depression because of their significant prevalence in the primary care setting and the lack of clear practice guidelines for addressing each illness. DESIGN: English language literature from prior systematic reviews was supplemented by searching MEDLINE, EMBASE, the Cochrane Controlled Trials Registry, the Agency for Healthcare Research and Quality National Guideline Clearinghouse, and bibliographies of selected papers. Studies addressing the natural history or treatment of minor depression or PMDD were selected for review. Data were abstracted by 1 of 2 independent reviewers and studies were synthesized qualitatively. RESULTS: Five individual studies that compared antidepressant or psychological treatments to placebo in patients with minor depression suggest short-term improvements in depressive symptoms with paroxetine, problem-solving therapy, and cognitive behavioral therapy, but not with amitryptiline. Modest benefits on mental health function were reported with paroxetine and with problem-solving therapy, but only in patients with severe functional impairment at baseline. Twenty-four controlled trials were identified that compared antidepressant or psychological treatments to placebo in patients with premenstrual dysphoric disorder. Pooled results from a recent systematic review of 15 randomized controlled trials and one additional trial abstract provide strong evidence for a significantly greater improvement in physical and psychological symptoms with serotonin-selective reuptake inhibitor medications when compared with placebo. Individual trials also suggest significantly greater improvements in symptom scores with venlafaxine, but not with tricyclic antidepressants. CONCLUSIONS: The limited evidence base for minor depression provides only mixed support for a small to moderate benefit for few antidepressant medications and psychological treatments tested. For the treatment of severe psychological or physical symptoms causing functional impairment in patients with PMDD, sertraline and fluoxetine are clearly beneficial in carefully selected patients. C1 Dept Vet Affairs Med Ctr, HSR&D, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. Univ Washington, Robert Wood Johnson Clin Scholars Program, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Duke Univ, Med Ctr, Durham, NC USA. RP Williams, JW (reprint author), Dept Vet Affairs Med Ctr, HSR&D, Ctr Hlth Serv Res Primary Care, Bldg 6,508 Fulton St, Durham, NC 27705 USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 58 TC 47 Z9 47 U1 4 U2 6 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 APR PY 2002 VL 17 IS 4 BP 293 EP 301 DI 10.1046/j.1525-1497.2002.10350.x PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 543TG UT WOS:000175116800007 PM 11972726 ER PT J AU Rudolph, KL Paraskevi, E DePinho, RA AF Rudolph, KL Paraskevi, E DePinho, RA TI Telomere shortening inhibits progression of hepatoma in telomerase deficient mice SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract C1 Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-3000 Hannover, Germany. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2002 VL 36 SU 1 MA 54 BP 19 EP 19 DI 10.1016/S0168-8278(02)80053-8 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 553YG UT WOS:000175704700054 ER PT J AU Heathcote, E Jeffers, L Perrillo, R Wright, T Sherman, M Namini, H Xiong, S James, C Ho, V Fry, J Brosgart, C AF Heathcote, E Jeffers, L Perrillo, R Wright, T Sherman, M Namini, H Xiong, S James, C Ho, V Fry, J Brosgart, C TI Sustained antiviral response and lack of viral resistance with long term adefovir dipivoxil (ADV) therapy in chronic HBV infection SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract C1 Toronto Hosp, W Div, Toronto, ON M5T 2S8, Canada. Toronto Gen Hosp, Toronto, ON, Canada. Univ Miami, Ctr Liver Dis, Miami, FL 33152 USA. Ochsner Med Ctr, Dept Gastroenterol, New Orleans, LA USA. San Francisco VA Med Ctr, GI Unit, San Francisco, CA USA. Gilead Sci Inc, Clin Res, Foster City, CA 94404 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2002 VL 36 SU 1 MA 391 BP 110 EP 111 DI 10.1016/S0168-8278(02)80391-9 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 553YG UT WOS:000175704700387 ER PT J AU Dufour, JH Dziejman, M Liu, MT Leung, JH Lane, TE Luster, AD AF Dufour, JH Dziejman, M Liu, MT Leung, JH Lane, TE Luster, AD TI IFN-gamma-Inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEMOKINE RECEPTOR CXCR3; CENTRAL-NERVOUS-SYSTEM; CONTACT HYPERSENSITIVITY; DIFFERENTIAL EXPRESSION; ALPHA-CHEMOATTRACTANT; MULTIPLE-SCLEROSIS; ENDOTHELIAL-CELLS; LYMPHOID ORGANS; DENDRITIC CELLS; RESPONSE GENE AB IFN-gamma-inducible protein 10 (IP-10, CXCL10), a chemokine secreted from cells stimulated with type I and II IFNs and LPS, is a chemoattractant for activated T cells. Expression of IP-10 is seen in many Th1-type inflammatory diseases, where it is thought to play an important role in recruiting activated T cells into sites of tissue inflammation. To determine the in vivo function of IP-10, we constructed an IP-10-deficient mouse (IP-10(-/-)) by targeted gene disruption. Immunological analysis revealed that IP-10(-/-) mice had impaired T cell responses. T cell proliferation to allogeneic and antigenic stimulation and IFN-gamma secretion in response to antigenic challenge were impaired in IP-10(-/-) mice. In addition, IP-10(-/-) mice exhibited an impaired contact hypersensitivity response, characterized by decreased ear swelling and reduced inflammatory cell infiltrates. T cells recovered from draining lymph nodes also had a decreased proliferative response to Ag restimulation. Furthermore, IP-10(-/-) mice infected with a neurotropic mouse hepatitis virus had an impaired ability to control viral replication in the brain. This was associated with decreased recruitment of CD4(+) and CD8(+) lymphocytes into the brain, reduced levels of IFN-gamma and the IFN-gamma-induced chemokines monokine induced by IFN-gamma (Mig, CXCL9) and IFN-inducible T cell alpha chemoattractant (I-TAC, CXCL11) in the brain, decreased numbers of virus-specific IFN-gamma-secreting CD8(+) cells in the spleen, and reduced levels of demyelination in the CNS. Taken together, our data suggest a role for IP-10 in both effector T cell generation and trafficking in vivo. C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol,Sch Med, Boston, MA 02114 USA. Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [F32CA88721, R0O1CA69212]; NIAID NIH HHS [F32AI09716]; NINDS NIH HHS [NS37336-01, T32NSO74444] NR 70 TC 539 Z9 563 U1 7 U2 27 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2002 VL 168 IS 7 BP 3195 EP 3204 PG 10 WC Immunology SC Immunology GA 534CE UT WOS:000174566400012 PM 11907072 ER PT J AU Zhang, Z Kaptanoglu, L Haddad, W Ivancic, D Alnadjim, Z Hurst, S Tishler, D Luster, AD Barrett, TA Fryer, J AF Zhang, Z Kaptanoglu, L Haddad, W Ivancic, D Alnadjim, Z Hurst, S Tishler, D Luster, AD Barrett, TA Fryer, J TI Donor T cell activation initiates small bowel allograft rejection through an IFN-gamma-Inducible protein-10-dependent mechanism SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTESTINAL TRANSPLANTATION; GENE-EXPRESSION; LYMPHOCYTES-T; LYMPHOID-TISSUE; ORAL TOLERANCE; LAMINA PROPRIA; CHEMOKINE; INDUCTION; CYTOKINE; MICE AB The poor success in controlling small bowel (SB) allograft rejection is partially attributed to the unique immune environment in the donor intestine. We hypothesized that Ag-induced activation of donor-derived T cells contributes to the initiation of SB allograft rejection. To address the role of donor T cell activation in SB transplantation, SB grafts from DO11.10 TCR transgenic mice (BALB/c, H-2L(d+)) were transplanted into BALB/c (isografts), or single class I MHC-mismatched (L-d-deficient) BALB/c H-2(dm2) (dm2, H-2L(d-)) mutant mice (allografts). Graft survival was followed after injection of control or antigenic OVA(323-339) peptide. Eighty percent of SB allografts developed severe rejection in mice treated with antigenic peptide, whereas <20% of allografts were rejected in mice treated with control peptide (p < 0.05). Isografts survived >30 days regardless of OVA323-339 administration. Activation of donor T cells increased intragraft expression of proinflammatory cytokine (IFN-gamma) and CXC chemokine IFN-gamma-inducible protein-10 mRNA and enhanced activation and accumulation of host NK and T cells in SB allografts. Treatment of mice with neutralizing anti-IFN-gamma-inducible protein-10 mAb increased SB allograft survival in Ag-treated mice (67%; p < 0.05) and reduced accumulation of host T cells and NK cells in the lamina propria but not mesenteric lymph nodes. These results suggest that activation of donor T cells after SB allotransplantation induces production of a Th1-like profile of cytokines and CXC chemokines that enhance infiltration of host T cells and NK cells in SB allografts. Blocking this pathway may be of therapeutic value in controlling SB allograft rejection. C1 Northwestern Univ, Sch Med, Dept Surg, Div Organ Transplantat, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Med Microbiol & Immunol, Chicago, IL 60611 USA. DNAX Res Inst Mol & Cellular Biol Inc, Palo Alto, CA 94304 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fryer, J (reprint author), Northwestern Univ, Sch Med, Dept Surg, Div Organ Transplantat, Suite 17-200,675 North St,Clair St, Chicago, IL 60611 USA. FU NCI NIH HHS [CA69212]; NIAID NIH HHS [AI46999]; NIDDK NIH HHS [DK47073, DK54778] NR 46 TC 45 Z9 48 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2002 VL 168 IS 7 BP 3205 EP 3212 PG 8 WC Immunology SC Immunology GA 534CE UT WOS:000174566400013 PM 11907073 ER PT J AU Sharland, A Patel, A Lee, JH Cestra, AE Saidman, S Waneck, GL AF Sharland, A Patel, A Lee, JH Cestra, AE Saidman, S Waneck, GL TI Genetically modified HLA class I molecules able to inhibit human NK cells without provoking alloreactive CD8(+) CTLs SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; PORCINE ENDOTHELIAL-CELLS; MHC CLASS-I; CYTOTOXIC LYMPHOCYTES-T; ALPHA-3 DOMAIN; TRANSGENIC MICE; XENOGENEIC CYTOTOXICITY; MARROW TRANSPLANTATION; PROLIFERATIVE RESPONSE; CRYSTAL-STRUCTURE AB Human NK cells are likely to be important effectors of xenograft rejection. Expression of HI.A class I molecules by transfected porcine cells can protect them from human NK cell-mediated lysis; however, this strategy has the potential to augment the anti-graft response by recipient CD8(+) T cells recognizing foreign pig peptides presented by HLA. In this study we show that the introduction of a mutation (D227K) in the alpha(3) domain of HLA-Cw3 abrogates its recognition by CD8-dependent T cells but leaves intact its ability to function as an inhibitory ligand for NK cells. Such genetically modified molecules may have potential therapeutic applications in the prevention of delayed xenograft rejection and in the facilitation of allogeneic and xenogeneic bone marrow engraftment. C1 Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Surg, Histocompatibil Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Waneck, GL (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, 149 13th St, Charlestown, MA 02129 USA. RI Sharland, Alexandra/G-1493-2011 FU NIAID NIH HHS [AI43440] NR 99 TC 21 Z9 22 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2002 VL 168 IS 7 BP 3266 EP 3274 PG 9 WC Immunology SC Immunology GA 534CE UT WOS:000174566400021 PM 11907081 ER PT J AU von Reyn, CF Arbeit, RD Horsburgh, CR Ristola, MA Waddell, RD Tvaroha, SM Samore, M Hirschhorn, LR Lumio, J Lein, AD Grove, MR Tosteson, ANA AF von Reyn, CF Arbeit, RD Horsburgh, CR Ristola, MA Waddell, RD Tvaroha, SM Samore, M Hirschhorn, LR Lumio, J Lein, AD Grove, MR Tosteson, ANA TI Sources of disseminated Mycobacterium avium infection in AIDS SO JOURNAL OF INFECTION LA English DT Article; Proceedings Paper CT 7th Conference on Retroviruses and Opportunistic Infections CY JAN 29-FEB 03, 2000 CL SAN FRANCISCO, CALIFORNIA ID HUMAN-IMMUNODEFICIENCY-VIRUS; SKIN-TEST REACTIONS; COMPLEX DISEASE; TUBERCULOSIS; PROTECTION; STRAINS; PROTEIN; WATER; BCG AB Objectives: To identify the sources of disseminated Mycobacterium avium complex (MAC) infection in AIDS. Methods: HIV positive subjects with CD4 counts <100/mm(3) in Atlanta, Boston, New Hampshire and Finland were entered in a prospective cohort study. Subjects were interviewed about potential MAC exposures, had phlebotomy performed for determination of antibody to mycobacterial lipoarabinomannin and for culture. Patient-directed water samples were collected from places of residence, work and recreation. Patients were followed for the development of disseminated MAC. Univariate and multivariate risk factors for MAC were analyzed. Results: Disseminated MAC was identified in 31 (9%) subjects. Significant risks In univariate analysis included prior Pneumocystis carinii pneumonia (PCP) (hazard ratio 1.821), consumption of spring water (4.909), consumption of raw seafood (34.3), gastrointestinal endoscopy(2.894), and showering outside the home (0.388). PCP, showering and endoscopy remained significant in a Cox proportional hazards model. There was no association between M. avium? colonization of home water and risk or MAC. In patients with CD4<25, median OD antibody levels to lipoarabinomannin at baseline were 0.054 among patients who did not develop MAC and 0.021 among patients who did develop MAC (P = 0.077). Conclusions: MAC infection results from diverse and likely undetectable environmental and nosocomial exposures. Mycobacterial infection before HIV infection may confer protection against disseminated INIAC in advanced AIDS. (C) 2002 The British Infection Society. C1 Dartmouth Hitchcock Med Ctr, Infect Dis Sect, Dept Med, Lebanon, NH 03756 USA. VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Univ Helsinki, Cent Hosp, Div Infect Dis, Helsinki, Finland. Deaconess Hosp, Boston, MA USA. Dimock St Hlth Ctr, Boston, MA USA. Univ Cent Tampere Hosp, Tampere, Finland. Dartmouth Hitchcock Med Ctr, Dept Community & Family Med, Lebanon, NH 03766 USA. Dartmouth Hitchcock Med Ctr, Dept Med, Clin Res Sect, Lebanon, NH USA. RP von Reyn, CF (reprint author), Dartmouth Hitchcock Med Ctr, Infect Dis Sect, Dept Med, Lebanon, NH 03756 USA. OI Horsburgh, C./0000-0001-6838-7895; Ristola, Matti/0000-0001-5115-2811 FU NIAID NIH HHS [AI30373] NR 15 TC 36 Z9 39 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0163-4453 J9 J INFECTION JI J. Infect. PD APR PY 2002 VL 44 IS 3 BP 166 EP 170 DI 10.1053/jinf.2001.0950 PG 5 WC Infectious Diseases SC Infectious Diseases GA 578BG UT WOS:000177097100004 PM 12099743 ER PT J AU Wang, JB Crawford, K Yuan, ML Wang, H Gorry, PR Gabuzda, D AF Wang, JB Crawford, K Yuan, ML Wang, H Gorry, PR Gabuzda, D TI Regulation of CC chemokine receptor 5 and CD4 expression and human immunodeficiency virus type 1 replication in human macrophages and microglia by T helper type 2 cytokines SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 8th Conference on Retroviruses and Opportunistic Infections CY FEB 04-08, 2001 CL CHICAGO, ILLINOIS ID CENTRAL-NERVOUS-SYSTEM; MONOCYTE-DERIVED MACROPHAGES; ANTIGEN-PRESENTING CELLS; HIV-1 INFECTION; IN-VITRO; MONOCYTE/MACROPHAGE LINEAGE; ANTIRETROVIRAL THERAPY; REVERSE TRANSCRIPTION; DISEASE PROGRESSION; INTERFERON-GAMMA AB Macrophages, microglia, and other mononuclear phagocytes serve as cellular reservoirs for viral persistence In patients with acquired immunodeficiency syndrome. To understand host mechanisms that affect human immunodeficiency virus type 1 (HIV-1) pathogenesis by modulating expression of coreceptors, cytokine regulation of CC chemokine receptor 5 (CCR5) and CD4 expression on monocytes, monocyte-derived macrophages (MDMs), and microglia was investigated. Interleukin (IL)-4 and IL-10 enhanced the entry and replication of HIV-1 in microglia through up-regulation of CD4 and CCR5 expression, respectively. IL-4 stimulated HIV-1 replication in MDMs but down-regulated CD4 and CCR5 expression and inhibited virus entry, whereas IL-10 had the opposite effects. Thus, mechanisms independent of CCR5 and CD4 expression levels are involved in pathways that regulate HIV-1 replication in MDMs. CCR5 up-regulation by IL-10 was associated with increased migration of microglia in response to macrophage inflammatory protein-1beta. These findings suggest that increased production of T helper type 2 cytokines In the later stages of disease can enhance virus entry and replication in mononuclear phagocytes and facilitate chemotactic migration. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Childrens Hosp, Med Ctr, Ctr Blood Res, Boston, MA 02115 USA. Childrens Hosp, Med Ctr, Div Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JF 816,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI28691, AI07382]; NINDS NIH HHS [NS-37277] NR 69 TC 55 Z9 57 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2002 VL 185 IS 7 BP 885 EP 897 DI 10.1086/339522 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 535QE UT WOS:000174654500006 PM 11920312 ER PT J AU Menzies, BE Kourteva, Y Kaiser, AB Kernodle, DS AF Menzies, BE Kourteva, Y Kaiser, AB Kernodle, DS TI Inhibition of staphylococcal wound infection and potentiation of antibiotic prophylaxis by a recombinant fragment of the fibronectin-binding protein of Staphylococcus aureus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-ENDOTHELIAL-CELLS; STREPTOCOCCUS-DYSGALACTIAE; NUCLEOTIDE-SEQUENCE; EPITHELIAL-CELLS; ADHERENCE; ADHESION; GENES; INTERNALIZATION; ENDOCARDITIS; RECEPTORS AB Adherence of Staphylococcus aureus to host tissues is a critical step for colonization and initiation of infection. The fibronectin-binding proteins (FnBPs) of S. aureus have been implicated in adherence and internalization in nonprofessional phagocytes. A recombinant fragment of the fibronectin-binding domains (rFnBF) that potently inhibits S. aureus entry into host cells was generated. To test the hypothesis that rFnBF may attenuate the establishment of infection, the ability of intermuscularly administered rFnBF to prevent abscess formation was determined in a guinea pig model of wound infection. rFnBF exhibited dose-dependent inhibition of abscess formation and, at a 100-mug dose, raised the median infective dose similar to170-fold, compared with the control. In addition, rFnBF potentiated the benefit of prophylaxis with cefazolin. Thus, exogenous administration of the fibronectin-binding domain of FnBP reduces the risk of staphylococcal abscess formation and should be investigated further as a novel agent for prevention of wound infection. C1 Vanderbilt Univ, Sch Med, Dept Vet Affairs, Med Res Serv, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Med, Div Infect Dis, Nashville, TN 37212 USA. RP Menzies, BE (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way,Med Sect S-111-ID, Seattle, WA 98108 USA. NR 29 TC 20 Z9 21 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2002 VL 185 IS 7 BP 937 EP 943 DI 10.1086/339484 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 535QE UT WOS:000174654500012 PM 11920318 ER PT J AU Sato, M Shegogue, D Gore, EA Smith, EA Mcdermott, PJ Trojanowska, M AF Sato, M Shegogue, D Gore, EA Smith, EA Mcdermott, PJ Trojanowska, M TI Role of p38 MAPK in transforming growth factor beta stimulation of collagen production by scleroderma and healthy dermal fibroblasts SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE extracellular matrix; fibrosis; MAPK ID ACTIVATED PROTEIN-KINASE; HUMAN SKIN FIBROBLASTS; SYSTEMIC-SCLEROSIS FIBROBLASTS; GENE-EXPRESSION; TGF-BETA; SIGNAL-TRANSDUCTION; 3-DIMENSIONAL COLLAGEN; UP-REGULATION; TRANSCRIPTION; FIBROSIS AB Transforming growth factor 0 has been implicated as a mediator of excessive extracellular matrix deposition in scar tissue and fibrosis, including systemic sclerosis. To further characterize the mechanism of collagen gene expression in systemic sclerosis and healthy skin fibroblasts, we examined the role of p38 MAPK signaling in collagen gene regulation by transforming growth factor beta. Treatment of dermal fibroblasts with transforming growth factor beta resulted in a prolonged activation of p38 MAPK. Furthermore, a specific inhibitor of p38 suppressed transforming growth factor beta stimulation of collagen type I mRNA and the alpha2(1) collagen promoter activity. To further probe the role of p38 in collagen regulation by transforming growth factor beta, we utilized an expression vector containing p38(X cDNA. Ectopic expression of p38alpha enhanced COL1A2 promoter activity and potentiated transforming growth factor 0 stimulation of this promoter. The p38 response element in the COL1A2 promoter overlapped with the previously characterized transforming growth factor beta response element. Consistent with these observations, collagen type I mRNA and protein levels were increased in transforming-growth-factor-beta-stimulated fibroblasts transduced with an adenoviral vector expressing p38alpha. To determine the possible role of p38 in abnormal collagen production by systemic sclerosis fibroblasts, p38 protein levels were compared in systemic sclerosis and healthy skin fibroblasts. Both cell types exhibited similar total levels of p38 MAPK and similar kinetics of p38 activation in response to transforming growth factor beta. In conclusion, this study demonstrates a costimulatory role for p38 MAPK in transforming growth factor beta induction of the collagen type I gene. Expression levels and activation status of p38 are not consistently elevated in systemic sclerosis fibroblasts suggesting that the p38 MAPK pathway is not dysregulated in systemic sclerosis fibroblasts. C1 Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Trojanowska, M (reprint author), Med Univ S Carolina, Div Rheumatol & Immunol, 96 Jonathan Lucas St,Suite 912, Charleston, SC 29425 USA. FU NIAMS NIH HHS [AR-42334, AR-44883] NR 40 TC 77 Z9 78 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2002 VL 118 IS 4 BP 704 EP 711 DI 10.1046/j.1523-1747.2002.01719.x PG 8 WC Dermatology SC Dermatology GA 535LD UT WOS:000174645200021 PM 11918720 ER PT J AU Cao, Q Mak, KM Lieber, CS AF Cao, Q Mak, KM Lieber, CS TI Dilinoleoylphosphatidylcholine prevents transforming growth factor-beta 1-mediated collagen accumulation in cultured rat hepatic stellate cells SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID FAT-STORING CELLS; TISSUE INHIBITOR; MATRIX METALLOPROTEINASE-13; GENE-EXPRESSION; LIVER FIBROSIS; MESSENGER-RNA; FIBROGENESIS; ACTIVATION; DISEASE; CLONING AB Polyenylphosphatidylcholine (PPC), a mixture of polyunsaturated phosphatidylcholines, protects against alcoholic and nonalcoholic liver fibrosis in baboons and rats, respectively. In this study, we assessed the antifibrogenic action of dilinoleoylphos-phatidylcholine (DLPC), the main phosphatidylcholine species of PPC, against transforming growth factor-beta1-mediated expression of a 1 (1) procollagen, tissue Inhibitor of metallopreoteinase-1 (TIMP-1) and matrix metalloproteinase-13 (MMP-13) in cultured rat hepatic stellate cells (HSCs). In primary culture-activated HSCs, TGF-beta1 up-regulated the a 1 (1) procollagen mRNA level with a concomitant Increase in type I collagen accumulation In culture media. Whereas TIMP-1 mRNA levels and TIMP-1 accumulation in media were also increased by TGF-beta1, MMP-13 mRNA expression and MMP-13 concentration In media were not altered. DLPC fully blocked TGF-beta1 induced increase In alpha1 (1) procollagen mRNA expression and decreased collagen accumulation In media. Whereas TIMP-1 mRNA level and TIMP-1 accumulation in media were decreased by DLPC, MMP-13 mRNA expression and MMP-13 concentration in media were not changed by this treatment. Palmitoyl-linoleoylphosphatidylcholine (PLPC), the second most abundant component of PPC, had no effect on the concentrations of collagen, TIMP-1, and MMP-13 in HSC culture. We conclude that DLPC prevents TGF-beta1-mediated HSC fibrogenesis through clown-regulation of a I (I) procollagen and TIMP-1 mRNA expression. The latter effect leads to a decreased accumulation of TIMP-1 that, in the presence of unchanged MMP-13 mRNA expression and MMP-13 concentration, results in a larger ratio of MMP-13/TIMP-1 concentrations in the culture media, favoring collagen degradation and lesser collagen accumulation. This effect of DLPC may explain, at least In part, the antifibrogenic action of PPC against alcoholic and other fibrotic disorders of the liver. C1 Bronx Vet Affairs Med ctr, Alcohol Res & Treatment Ctr, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, Bronx, NY USA. RP Lieber, CS (reprint author), Bronx Vet Affairs Med ctr, Alcohol Res & Treatment Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NCCIH NIH HHS [R01 AT001583]; NIAAA NIH HHS [AA 11115, R21 AA014326] NR 49 TC 31 Z9 37 U1 1 U2 2 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 APR PY 2002 VL 139 IS 4 BP 202 EP 210 DI 10.1067/mlc.2002.121853 PG 9 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 558GN UT WOS:000175958100004 PM 12024107 ER PT J AU Norris, AW Spector, AA AF Norris, AW Spector, AA TI Very long chain n-3 and n-6 polyunsaturated fatty acids bind strongly to liver fatty acid-binding protein SO JOURNAL OF LIPID RESEARCH LA English DT Article DE 24-carbon polyunsaturated fatty acids; docosahexaenoic acid; arachidonic acid; fatty acid binding assay ID DOCOSAHEXAENOIC ACID; RAT; EXPRESSION; METABOLISM; LIGAND; FLUORESCENCE; AFFINITY; BRAIN AB Synthesis of n-3 and n-6 very long chain-PUFAs (VLC-PUFAs) from 18-carbon essential fatty acids is differentially regulated. The predominant product arising from n-3 fatty acids is docosahexaenoic acid (22:6n-3), with the liver serving as the main site of production. The synthetic pathway requires movement of a 24-carbon intermediate from the endoplasmic reticulum to peroxisomes for retroconversion to 22:6n-3. The mechanism of this intra-organelle flux is unknown, but could be binding-protein facilitated. We thus investigated binding of a series of previously untested VLC-PUFAs to liver fatty acid-binding protein (L-FABP). Three fluorometric assays were employed, all of which showed strong binding (K-d'similar to10(-8) to 10(-7) M) of 20-, 22-, and 24-carbon n-3 PUFAs to L-FABP. In contrast, synthesis of the predominant n-6 PUFA product, arachidonic acid, does not require intra-organelle transport. However, we found that n-6 VLC-PUFAs bound to L-FABP with affinities (K-d'similar to10(-8) to 10(-7) M) comparable to their n-3 counterparts. Although these results raise the possibility that L-FABP may participate in the cytoplasmic processing of n-3 and n-6 VLC-PUFAs, there is no evidence on the basis of binding affinities that L-FABP accounts for differences in the predominant products formed by the n-3 and n-6 PUFA metabolic pathways.-Norris, A. W., and A. A. Spector. Very long chain n-3 and n-6 polyunsaturated fatty acids bind strongly to liver fatty acid-binding protein. C1 Univ Iowa, Coll Med, Dept Pediat, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Dept Biochem, Iowa City, IA 52242 USA. RP Norris, AW (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NHLBI NIH HHS [HL49264] NR 39 TC 32 Z9 33 U1 0 U2 2 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD APR PY 2002 VL 43 IS 4 BP 646 EP 653 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 535RP UT WOS:000174660200014 PM 11907148 ER PT J AU Hoffmann, U Loewe, C Bernhard, C Weber, M Cejna, M Herold, CJ Schima, W AF Hoffmann, U Loewe, C Bernhard, C Weber, M Cejna, M Herold, CJ Schima, W TI MRA of the lower extremities in patients with pulmonary embolism using a blood pool contrast agent: Initial experience SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE blood pool contrast agent; contrast-enhanced MRA; deep venous thrombosis; thromboembolic disease; pulmonary embolism ID DEEP VENOUS THROMBOSIS; MAGNETIC-RESONANCE ANGIOGRAPHY; IRON-OXIDE NANOPARTICLES; NC100150 INJECTION; CT VENOGRAPHY; THROMBOEMBOLIC DISEASE; CORONARY ANGIOGRAPHY; SONOGRAPHY; DIAGNOSIS; PELVIS AB Purpose: To evaluate the feasibility of blood pool contrast-enhanced magnetic resonance angiography (MRA) to visualize the arterial and venous vessel tree and to detect deep venous thrombosis (DVT) of the lower extremities. Materials and Methods: Nine consecutive patients with pulmonary embolism (mean age = 46 +/- 9) were randomized to various doses of NC100150 (between 0.75 and 6 mg of Fe/kg of body weight). A T1-weighted (TIW) 3D gradient recalled echo (GRE) sequence (TE = 2.0 msec, TR = 5.0 msec) was used. Two observers blinded to the dose of contrast agent assessed image quality, contrast attenuation, and appearance of thrombi. Results: Qualitative assessment of overall MRA image quality and semiquantitative vessel scoring revealed good to excellent delineation of venous and arterial vessel segments independent of the dose of NC100150. However, quantitative region of interest analysis revealed a significantly higher signal-to-noise ratio (SNR) in the high-dose group than in the mid- and low-dose groups of NC100150 (P < 0.01). Between dose groups, the SNR was independent of vessel type (artery or vein) and vessel segment localization (proximal or distal). All seven venous thrombi (mean length = 7.2 +/- 0.95cm) were characterized by a very low signal intensity (SI), which was only 16.6 +/- 7% of the SI in adjacent venous segments (P < 0.0001). Conclusion: High-quality MR angiograms of the lower extremities can be obtained using low concentrations of NC100150 in combination with a strong TIW 3D GRE sequence. The obvious delineation of venous thrombi suggests that this technique may be potentially used as a noninvasive "one-stop shopping" tool in the evaluation of thromboembolic disease. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, 100 Charles River Pl Suite 400, Boston, MA 02114 USA. RI Weber, Michael/L-9836-2016; OI Weber, Michael/0000-0002-8507-2219; Loewe, Christian/0000-0003-2502-0676 NR 25 TC 19 Z9 20 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD APR PY 2002 VL 15 IS 4 BP 429 EP 437 DI 10.1002/jmri.10082 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 537LL UT WOS:000174759700009 PM 11948832 ER PT J AU Holmes, LB AF Holmes, LB TI The teratogenicity of anticonvulsant drugs: a progress report SO JOURNAL OF MEDICAL GENETICS LA English DT Editorial Material ID FETAL-HYDANTOIN SYNDROME; EXPOSED IN-UTERO; ANTIEPILEPTIC DRUGS; VALPROATE SYNDROME; CARBAMAZEPINE MONOTHERAPY; CONGENITAL-MALFORMATIONS; PHENYTOIN EXPOSURE; PRENATAL EXPOSURE; PREDICTIVE VALUE; MINOR ANOMALIES C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Boston, MA 02114 USA. RP Holmes, LB (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Warren 801,55 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS24125] NR 50 TC 28 Z9 30 U1 1 U2 5 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD APR PY 2002 VL 39 IS 4 BP 245 EP 247 DI 10.1136/jmg.39.4.245 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 544JX UT WOS:000175155400003 PM 11950851 ER PT J AU Ranu, HK Terracciano, CMN Davia, K Bernobich, E Chaudhri, B Robinson, SE Kang, ZB Hajjar, RJ MacLeod, KT Harding, SE AF Ranu, HK Terracciano, CMN Davia, K Bernobich, E Chaudhri, B Robinson, SE Kang, ZB Hajjar, RJ MacLeod, KT Harding, SE TI Effects of Na+/Ca2+-exchanger overexpression on excitation-contraction coupling in adult rabbit ventricular myocytes SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Na+/Ca2+-exchanger; rabbit; adenovirus; gene transfer ID HUMAN HEART-FAILURE; CARDIAC NA+-CA2+ EXCHANGER; FAILING HUMAN MYOCARDIUM; SODIUM-CALCIUM EXCHANGE; SARCOPLASMIC-RETICULUM; GUINEA-PIG; TRANSGENIC MICE; PROTEIN-LEVELS; GENE-TRANSFER; RAT MYOCYTES AB H. K. RANU. C. M. N. TFRRACCIANO, K. DAVIA, E. BERNOBICH B. CHAUDHRI, S. E. ROBINSON, Z. B. KANG, R. J. HAJJAR, K. T MACLEOD AND S. E. HARDING. Effects of Na+/Ca2+-exchanger Overexpression on Excitation-contraction (2002) 34, 389 Coupling in Adult Rabbit Ventricular Myocytes. Journal of Molecular and cellular Cardiology The Na+/Ca2+-exchanger (NCX) is the main mechanism by which Ca2+ is transported out of the ventricular myocyte. NCX levels arc raised in failing human heart, and the consequences of this for excitation-contraction coupling are still debated. We have increased NCX levels in adult rabbit myocytes by adenovirally-mediated gene transfer and examined the effects on excitation-contraction coupling after 24 and 48 h. Infected myocytes were identified through expression of green fluorescent protein (GFP), transfected under a separate promoter on the same viral construct. Control experiments were done with both non-infected myocytes and those infected with adenovirus expressing GFP only. Contraction amplitude was markedly reduced in NCX-overexpressing myocytes at either time point, and neither increasing frequency nor raising extracellular Ca2+ could reverse this depression. Resting membrane potential and action potential duration were largely unaffected by NCX overexpression, as was peak Ca2+ entry via the L-type Ca2+ channel. Systolic and diastolic Ca2+ levels were significantly reduced, with peak systolic Ca2+ in NCX-overexpressing myocytes lower than diastolic levels in control cells at 2 mm extracellular Ca2+. Both cell relengthening and the decay of the Ca2+ transient were significantly slowed. Sarcoplasmic reticulum (SR) Ca2+ stores were completely depleted in a majority of myocytes, and remained so despite increasingly vigorous loading protocols. Depressed contractility following NCX overexpression is therefore related to decreased SR Ca2+ stores and low diastolic Ca2+ levels rather than reduced Ca+ entry. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW3 6LY, England. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Harding, SE (reprint author), Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Dovehouse St, London SW3 6LY, England. EM sian.harding@ic.ac.uk NR 41 TC 42 Z9 42 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD APR PY 2002 VL 34 IS 4 BP 389 EP 400 DI 10.1006/jmcc.2001.1521 PG 12 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 561WQ UT WOS:000176166400004 PM 11991729 ER PT J AU Farabaugh, A Mischoulon, D Yeung, A Alpert, J Matthews, J Pava, J Fava, M AF Farabaugh, A Mischoulon, D Yeung, A Alpert, J Matthews, J Pava, J Fava, M TI Predictors of stable personality disorder diagnoses in outpatients with remitted depression SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article AB This study examined the stability of comorbid personality disorder diagnoses once an outpatient's depression remitted. The sample consisted of 75 outpatients who responded to treatment in an 8-week acute treatment phase for depression, who met criteria for remission throughout a 26-week continuation phase, and who completed a personality assessment (Structured Clinical Interview for DSM-III-R-axis II Disorders) at the beginning and at the end of each treatment phase. The authors found that after a major depressive disorder is successfully treated, personality disorder diagnoses remain stable across time during continuation treatment. Gender was the only potential predictor variable that was significant: the proportion of men who had a stable personality disorder diagnosis in cluster A or cluster B was significantly greater than the proportion of women who had a stable personality disorder diagnosis in these two clusters. Among women, those with any stable personality disorder had a significantly longer duration of the current major depressive disorder compared with those who never met criteria for any personality disorder; this was also true for women with a cluster C personality disorder diagnosis. C1 Massachusetts Gen Hosp, Depress & Clin Res Program, Dept Psychiat, Boston, MA 02114 USA. RP Farabaugh, A (reprint author), Massachusetts Gen Hosp, Depress & Clin Res Program, Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [5R01MH48483-05] NR 20 TC 12 Z9 12 U1 0 U2 2 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 APR PY 2002 VL 190 IS 4 BP 248 EP 256 DI 10.1097/01.NMD.0000012862.72620.F8 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 543HV UT WOS:000175096500006 PM 11960086 ER PT J AU Jin, KL Nagayama, T Mao, XO Kawaguchi, K Hickey, RW Greenberg, DA Simon, RP Graham, SH AF Jin, KL Nagayama, T Mao, XO Kawaguchi, K Hickey, RW Greenberg, DA Simon, RP Graham, SH TI Two caspase-2 transcripts are expressed in rat hippocampus after global cerebral ischemia SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE caspase-2; cell death; gene expression; inhibitor; ischemia; rat brain ID DELAYED NEURONAL DEATH; BRAIN INJURY; CELL-DEATH; MESSENGER-RNA; ADAPTER MOLECULE; FAMILY PROTEASES; PC12 CELLS; APOPTOSIS; INHIBITION; MODEL AB Caspase family genes play a critical role in the initiation and execution of programmed cell death. Programmed cell death is an important contributor to neuronal loss following cerebral ischemia. We have performed a series of experiments to investigate the role of a specific caspase, caspase-2, in the development of delayed neuronal death following transient global ischemia in the rat. A rat ischemic brain cDNA library was screened, and two splice-variants of caspase-2 mRNA were identified, caspase-2S and caspase-2L, which were highly homologous with the sequences of human and mouse caspase-2S and caspase-2L genes, respectively. RT-PCR demonstrated an increase in expression of both caspase-2S and caspase-2L mRNA at 8, 24 and 72 h of reperfusion after global ischemia. The ratio of the two PCR fragments did not change significantly throughout the time course of reperfusion. Western blot with monoclonal antibody specific to the proapoptotic caspase-2L splice variant revealed an increase in procaspase-2 (51 kDa) protein from 4 to 72 h following ischemia compared with sham-operated controls. Furthermore, an approximately 30-kDa cleavage product appeared at 8 h and increased with increasing duration of reperfusion. Thus, caspase-2L is both translated and activated following transient global ischemia. Finally, intraventricular administration of the caspase-2-like inhibitor (VDVAD-FMK) 30 min before induction of ischemia decreased the number of CA1 neurons staining positively for DNA damage (Klenow-labeling assay) and increased the number of healthy-appearing CA1 neurons (cresyl violet) compared with vehicle-treated controls. Taken together, the data suggest that caspase-2 induction and activation are important mediators of delayed neuronal death following transient global ischemia. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA. VA Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. Buck Inst Age Res, Novato, CA USA. RP Graham, SH (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-526 Biomed Sci Tower, Pittsburgh, PA 15261 USA. FU NINDS NIH HHS [NS 24728, P01 NS35965] NR 55 TC 17 Z9 18 U1 0 U2 1 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 APR PY 2002 VL 81 IS 1 BP 25 EP 35 DI 10.1046/j.1471-4159.2002.00781.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 537XD UT WOS:000174784200004 PM 12067235 ER PT J AU Karni, A Koldzic, DN Bharanidharan, P Khoury, SJ Weiner, HL AF Karni, A Koldzic, DN Bharanidharan, P Khoury, SJ Weiner, HL TI IL-18 is linked to raised IFN-gamma in multiple sclerosis and is induced by activated CD4(+) T cells via CD40-CD40 ligand interactions SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE multiple sclerosis; IL-18; IL-12; IFN-gamma; CD40-CD40 ligand interactions ID DISEASE-ACTIVITY; INTERFERON-GAMMA; MESSENGER-RNA; B-CELLS; INTERLEUKIN-12; CYTOKINE; EXPRESSION; TH1; LESIONS; CLONING AB We investigated T cell receptor induced IL-18 secretion, the cellular and molecular mechanism, associated with the induction of IL-18 and the role of IL-18 in IFN-gamma production in the different stages of multiple sclerosis (MS). We found that anti-CD3/CD28 induced IL-18 production by peripheral blood mononuclear cells was increased in both relapsing-remitting and secondary progressive MS. In controls and relapsing-remitting MS neutralizing anti-IL-12 and anti-IL-18 alone equally suppressed IFN-gamma production whereas in progressive MS, maximum suppression of IFN-gamma was only observed when neutralizing anti-IL-12 and anti-IL-18 were given together, suggesting that in progressive MS, IL-12 and IL-18 function in a non-linked manner to induce IFN-gamma, Elevated IL-18 production in MS was dependent on the interaction of antigen presenting cells with activated CD4(+) T cells via CD40-CD40 ligand and the levels of IL-18 correlated with disease duration in secondary progressive MS. These results demonstrated that IL-18 has an important role in augmenting Th-1 type immune responses in MS and may be involved in immune changes that occur when patients enter the progressive stage. (C) 2002 Published by Elsevier Science B.V. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Multiple Sclerosis Ctr, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Multiple Sclerosis Ctr, Boston, MA 02115 USA. RP Weiner, HL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, 77 Ave Louis Pasteur, Boston, MA 02115 USA. NR 34 TC 60 Z9 61 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD APR PY 2002 VL 125 IS 1-2 BP 134 EP 140 AR PII S0165-5728(02)00018-8 DI 10.1016/S0165-5728(02)00018-8 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 549GG UT WOS:000175435700015 PM 11960649 ER PT J AU Schmidt, MC Antweiler, S Urban, N Mueller, W Kuklik, A Meyer-Puttlitz, B Wiestler, OD Louis, DN Fimmers, R von Deimling, A AF Schmidt, MC Antweiler, S Urban, N Mueller, W Kuklik, A Meyer-Puttlitz, B Wiestler, OD Louis, DN Fimmers, R von Deimling, A TI Impact of genotype and morphology on the prognosis of glioblastoma SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE allelic losses; glioblastoma; molecular diagnostics; prognosis ID MOLECULAR-GENETIC-ANALYSIS; GIANT-CELL GLIOBLASTOMAS; HIGH-GRADE GLIOMAS; OLIGODENDROGLIAL TUMORS; SECONDARY GLIOBLASTOMAS; P53 MUTATIONS; EGF RECEPTOR; MULTIFORME; SURVIVAL; 1P AB The recognition of molecular subsets among glioblastomas has raised the question whether distinct mutations in glioblastoma-associated genes may serve as prognostic markers. The present study on glioblastomas (GBM) from 97 consecutively sampled adult patients is based on a clinical, histopathological, immunohistochemical, and molecular genetic analysis. Parameters assessed were age at diagnosis, survival, cell type, proliferation. necrosis, microvascular proliferation, sarcomatous growth. lymphocytic infiltration, thromboses, calcifications, GFAP expression, MIB-1 index, loss of heterozygosity (LOH) of the chromosomal arms 1p. 10p, 10q, 17p, 19q and structural alterations in the TP53, EGFR and PTEN genes. As in previous studies, younger age was significantly associated with better survival. Among the molecular parameters, TP53 mutations and LOH10q emerged as favorable and poor prognostic factors, respectively. TP53 mutations were a favorable prognostic factor independent of whether glioblastomas were primary or secondary. LOH1p or 19q. lesions suspected to be over-represented in long term survivors with malignant glioma, were not associated with better survival. However. the combination of LOH1p and LOH19q defined GBM patients with a significantly better survival, Notably, these patients did not exhibit morphological features reminiscent of oligodendroglioma. These findings indicate that genotyping of glioblastoma may provide clinical information of prognostic importance. C1 Univ Bonn, Med Ctr, Dept Neurosurg, D-5300 Bonn, Germany. Univ Bonn, Med Ctr, Dept Neuropathol, D-5300 Bonn, Germany. Humboldt Univ, Charite, Dept Neuropathol, D-1086 Berlin, Germany. Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Univ Bonn, Med Ctr, Inst Med Stat, D-5300 Bonn, Germany. RP von Deimling, A (reprint author), Free Univ Berlin, Inst Neuropathol, Charite, Campus Virchow Klinikum,Augustenburgerpl 1, D-13353 Berlin, Germany. RI von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X FU NCI NIH HHS [CA57683] NR 36 TC 147 Z9 158 U1 0 U2 4 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD APR PY 2002 VL 61 IS 4 BP 321 EP 328 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 537AP UT WOS:000174734500003 PM 11939587 ER PT J AU Alpert, NM Rabito, CA Correia, DJA Babich, JW Littman, BH Tompkins, RG Rubin, NT Rubin, RH Fischman, AJ AF Alpert, NM Rabito, CA Correia, DJA Babich, JW Littman, BH Tompkins, RG Rubin, NT Rubin, RH Fischman, AJ TI Mapping of local renal blood flow with PET and (H2O)-O-15 SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE renal blood flow; parametric imaging; (H2O)-O-15 ID POSITRON-EMISSION-TOMOGRAPHY; REGIONAL DISTRIBUTION; WATER; QUANTIFICATION; MICROSPHERES AB We developed a noninvasive method for the mapping of regional renal blood flow in humans using PET and (H2O)-O-15. Methods- Fifteen subjects participated in the study, 5 with normal renal function and 10 with renal disease. The protocol used a whole-body PET scanner, intravenous bolus injection of 1,1101,850 MBq (H2O)-O-15 and sequential imaging at 3 s per frame. I-131-Iodohippuran was used to independently assess effective renal plasma flow in each subject. Hippuran clearance and renal blood flow (RBF) were measured twice, before and after treatment with probenecid, to verify that RBF is not affected. Flow analysis was based on the Kety model, according to the operational equation: C(t) = F integral C-a(u)du - k integral C(u)du, where F is the RBF, k is the tissue-to-blood clearance rate, C is the PET concentration, and C-a is the tracer concentration in the abdominal aorta. F and k were estimated by linear least squares on a pixel-by-pixel basis to produce quantitative maps (parametric images) of RBF. The flow maps were analyzed by regions of interest (largely excluding the medulla and collecting system) for each kidney on each slice and pooled to yield mean RBF. Results: In the 5 healthy subjects, mean RBF was 3.4 +/- 0.4 mL/min/g. There was no difference in flow between kidneys (t = -0.59; n = 11; P > 0.95). Before treatment with probenecid, RBF was linearly related to hippuran clearance (r(2) = 0.92). Probenecid treatment significantly reduced hippuran clearance (P < 0.003), but RBF was unchanged (P > 0.17). Compared with healthy control subjects, RBF was significantly decreased in patients with renal disease (P < 0.002). Flow maps were of good quality in all subjects, exhibiting characteristic patterns, with higher values in regions composed largely of renal cortex. Conclusion: Parametric mapping of FBF with PET and (H2O)-O-15 provides a straightforward, noninvasive method for quantitative mapping of RBF, which may prove useful in research applications and in the management of patients whose therapy alters renal tubular transport. C1 Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Pfizer Global Res & Dev, Groton, CT USA. Massachusetts Gen Hosp, Trauma Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Shriners Burns Inst, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA USA. Massachusetts Gen Hosp, Med Serv, Renal Unit, Boston, MA 02114 USA. Harvard Mit Div Hlth Sci & Technol, Ctr Expt Pharmacol & Therapeut, Boston, MA USA. RP Alpert, NM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, 32 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [T32 CA 09362]; NIGMS NIH HHS [T32 GM 07035, P50 GM 21700] NR 18 TC 28 Z9 28 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR PY 2002 VL 43 IS 4 BP 470 EP 475 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 540BA UT WOS:000174907300012 PM 11937589 ER PT J AU Craig, RG Boylan, R Yip, J Mijares, D Imam, M Socransky, SS Taubman, MA Haffajee, AD AF Craig, RG Boylan, R Yip, J Mijares, D Imam, M Socransky, SS Taubman, MA Haffajee, AD TI Serum IgG antibody response to periodontal pathogens in minority populations: relationship to periodontal disease status and progression SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE antibody; periodontal disease; minorities; risk factors ID EARLY-ONSET PERIODONTITIS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; OLDER ADULTS; RISK INDICATORS; ATTACHMENT LOSS; PORPHYROMONAS-GINGIVALIS; BACTEROIDES-GINGIVALIS; JUVENILE PERIODONTITIS; UNITED-STATES; ORAL MICROORGANISMS AB Differences in periodontal disease prevalence, severity. subgingival microflora and host immune response have been reported for various ethnic/racial groups. which implies that risk factors for destructive periodontal disease progression may, also vary in these Populations. As it is possible that these differences may be due to confounding variables other than ethnicity/race. we have measured serum IgG antibody response to six periodontal pathogens, and compared these data with microbiological, clinical and demographic parameters in three urban minority Populations. The study population consisted of 23 Asiatic. 48 African-America 11 and 37 Hispanic Subjects. who were resident in the greater New York region, Clinical indices that were recorded included pocket depth. attachment level, gingival erythema, bleeding upon probing, Suppuration and supraginival plaque. Attachment level measurements were taken twice at each visit. and the difference between the means of pairs of measurements taken at baseline and two months later was used to determine disease progression. Subgingival microbiological species were identified and enumerated using DNA-DNA checkerboard hybridization. Serum IgG antibody levels to Actinobacillus actinomycetemcomitans serotyopes a and b, Bacteroides forsythus, Campylobacter rectus. Porphyromonas gingivalis and Prevotella intermedia were measured by enzyme-linked immunosorbant assay (ELISA). Mean serum IgG antibody to P. gingivalis was found to be higher in the African-American group, while IgG antibody to B. forsythus was lower in the Hispanic group. However. the African-American group also had greater mean probing depth, attachment loss, number of missing teeth and numbers of individuals within the unskilled Occupational group. When the data were analyzed by occupational status. mean serum IgG antibody to P. gingivalis increased from professional to skilled to unskilled groups. For the entire Study population, prior disease and subsequent attachment loss were associated with elevated serum IgG antibody to P. gingivalis. Increasing pocket depth. attachment level, gingival erythema and age were also positively correlated with serum IgG antibody to P. gingivalis, but not with serum IgG antibody to the other five subgingival species, No correlation was found between whole-mouth bacterial levels and homologous serum IgG antibody levels. These results suggest that elevated serum IgG antibody to P. gingivalis reflects destructive periodontal disease status. and may,, be considered a risk factor for disease progression in these ethnic/racial populations, In addition. although differences in serum IgG antibody profiles to subgingival species were found among the three ethnic/racial groups, environmental and socioeconomic variables may hake a greater influence on serum IgG antibody levels in these populations. C1 NYU, Coll Dent, Div Basic Sci, New York, NY 10010 USA. NYU, Coll Dent, Div Surg Sci, New York, NY 10010 USA. Forsyth Inst, Boston, MA USA. RP Craig, RG (reprint author), NYU, Coll Dent, Div Basic Sci, 345 E 24th St, New York, NY 10010 USA. FU NIDCR NIH HHS [DE 04881, P20 DE 10593] NR 57 TC 43 Z9 47 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD APR PY 2002 VL 37 IS 2 BP 132 EP 146 DI 10.1034/j.1600-0765.2002.00031.x PG 15 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 543HZ UT WOS:000175097100008 PM 12009183 ER PT J AU Ofman, JJ MacLean, CH Straus, WL Morton, SC Berger, ML Roth, EA Shekelle, P AF Ofman, JJ MacLean, CH Straus, WL Morton, SC Berger, ML Roth, EA Shekelle, P TI A metaanalysis of severe upper gastrointestinal complications of nonsteroidal antiinflammatory drugs SO JOURNAL OF RHEUMATOLOGY LA English DT Review DE nonsteroidal antiinflammatory drugs; peptic ulcer disease; upper gastrointestlnal hemorrhage; complications ID ANTI-INFLAMMATORY DRUGS; PEPTIC-ULCER DISEASE; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; RHEUMATOID-ARTHRITIS; ELDERLY PERSONS; RISK-FACTORS; HEALTHY-VOLUNTEERS; ASPIRIN USE; COLLABORATIVE METAANALYSIS AB Objective. Prior metaanalyses of the risk of upper gastrointestinal (GI) complications associated with nonsteroidal antiinflammatory drugs (NSAID) have focused on the published English language epidemiologic literature and/or only a portion of the relevant evidence, restrictions that are now known to be associated with bias in metaanalysis. We synthesized the published and unpublished evidence to determine the least biased estimates of the risks of perforations, ulcers, and bleeds (PUB) associated with NSAID use from all study designs and all languages. Methods. Data sources: Using MEDLINE, EMBASE, HEALTHSTAR, and BIOSIS, we searched for English and non-English language studies of NSAID from 1966-1998 reporting primary data on GI complications. We obtained unpublished data from the US Food and Drug Administration (FDA) new, drug application (NDA) reviews. NDA were hand searched to identify unpublished studies with inclusion criteria identical to those used for published reports. Study selection: Studies had to assess the use of oral NSAID for more than 4 days duration in subjects > 18 years of age and report on the clinically relevant upper GI outcomes of PUB. Results. Two reviewers evaluated 4881 published titles and identified 13 NSAID versus placebo randomized clinical trials and 3 previously unpublished FDA placebo controlled randomized controlled trials, 9 cohort studies, and 23 case control studies sufficiently clinically homogeneous to pool. Two reviewers extracted data about study characteristics and study quality. Data synthesis: The majority of clinical trials were of good quality, but observational studies had methodologic limitations. The pooled odds ratio (OR) from 16 NSAID versus placebo clinical trials, comprising 4431 patients, was 5.36 (95% Cl: 1.79, 16.1). The pooled relative risk of PUB from 9 cohort studies comprising over 750,000 person-years of exposure was 2.7 (95% Cl: 2.1, 3.5). The pooled OR of PUB from 23 case control studies using age and sex matching, representing 25,732 patients, was 3.0 (95% Cl: 2.5, 3.7). Data were insufficient to justify subgroup analyses stratified by age, comorbid conditions, drug, or dose. Conclusion. These data support an association between the use of NSAID and serious upper GI complications, including estimates from different study designs. Prior pooled estimates about the effect of patient and drug variables on increased risk must be viewed with caution. C1 Merck & Co Inc, W Point, PA USA. W Los Angeles VAMC, Dept Med, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Div Rheumatol, Los Angeles, CA 90024 USA. Zynx Hlth Inc, Cedars Sinai Hlth Syst, Dept Med, Beverly Hills, CA 90212 USA. Cedars Sinai Hlth Syst, Dept Hlth Serv Res, Div Gastroenterol, Beverly Hills, CA 90212 USA. RP Ofman, JJ (reprint author), Zynx Hlth Inc, Cedars Sinai Hlth Syst, Dept Med, 9100 Wilshire Blvd,Ste 655, Beverly Hills, CA 90212 USA. NR 161 TC 136 Z9 140 U1 0 U2 1 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 APR PY 2002 VL 29 IS 4 BP 804 EP 812 PG 9 WC Rheumatology SC Rheumatology GA 541BU UT WOS:000174966000026 PM 11950025 ER PT J AU Lipsitz, SR Parzen, M Zhao, LP AF Lipsitz, SR Parzen, M Zhao, LP TI A degrees-of-freedom approximation in multiple imputation SO JOURNAL OF STATISTICAL COMPUTATION AND SIMULATION LA English DT Article DE Bayesian bootstrap; ignorable non-response AB When using multiple imputation to form confidence intervals with missing data, Rubin and Schenker (1986) proposed using a t-distribution with approximate degrees-of-freedom which is a function of the number of multiple imputations and the within and between imputation variance. In this t-approximation, Rubin and Schenker assume there are a finite number of multiple imputations, but an infinite number of observations in the sample. We propose a further degrees-of-freedom approximation which is a function of the within and between imputation variance, the number of multiple imputations, and the number of observations in the sample. When the number of observations in the sample is small, our approximate degrees-of-freedom may be more appropriate, as seen in our simulations. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Grad Sch Business, Chicago, IL 60637 USA. Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98104 USA. RP Lipsitz, SR (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. NR 9 TC 5 Z9 5 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0094-9655 J9 J STAT COMPUT SIM JI J. Stat. Comput. Simul. PD APR PY 2002 VL 72 IS 4 BP 309 EP 318 DI 10.1080/00949650290007405 PG 10 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 581LP UT WOS:000177294100005 ER PT J AU Rudkin, GH Carlsen, BT Chung, CY Huang, WB Ishida, K Anvar, B Yamaguchi, DT Miller, TA AF Rudkin, GH Carlsen, BT Chung, CY Huang, WB Ishida, K Anvar, B Yamaguchi, DT Miller, TA TI Retinoids inhibit squamous cell carcinoma growth and intercellular communication SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE retinoic acids; squamous cell carcinoma; skin cancer; gap junctional intercellular communication; connexins ID GAP JUNCTIONAL COMMUNICATION; MOUSE SKIN; PROTEIN CONNEXIN-43; TUMOR-CELLS; BASAL-CELL; ACID; EXPRESSION; LINES; PHOSPHORYLATION; CHEMOTHERAPY AB Background. Retinoids have been shown to inhibit the growth of squamous cell carcinoma and other malignancies. They have also been shown to alter gap junctional intercellular communication (GJIC) and the expression of connexins, the protein subunits of gap junctions. We report in this study that the alteration of GJIC by retinoids may be directly related to inhibitory effects on cell growth. Materials and methods. SCC-13 cells were treated with all-trans retinoic acid (tRA) and 13-cis retinoic acid (cRA) at 10(-7) and 10(-6) M concentrations in culture. No treatment and ethanol vehicle controls were included for each experiment. Serial cell counts of parallel cultures were performed to determine cell growth. The parachute technique was performed in combination with fluorescence activated cell sorting (FACS) analysis to determine GJIC. Northern and Western blot analysis were performed to assess connexin mRNA and protein expression. Results. The growth rate was inhibited for cells treated with tRA (10(-6) M) (P < 0.05) and cRA (10(-6) M) (P = 0.068) vs vehicle control. GJIC was significantly inhibited with both tRA (10(-7) and 10(-6) M) (P < 0.001) and cRA (10(-7) and 10(-6) M) (P < 0.001) at 24,48, and 96 h as determined by FACS analysis. To correlate GJIC with cell growth, we studied the effect of glycyrrhetinic acid, a known inhibitor of GJIC. Glycyrrhetinic acid also significantly inhibited cell growth (P < 0.05) vs control. Connexin 26 and connexin 43 mRNA and protein expression were not significantly altered after retinoid treatment. Conclusion. Retinoic acids inhibit both cell growth and GJIC in SCC-13 cells. Retinoids may inhibit cell growth through alteration of GJIC in SCC-13 cells. (C) 2002 Elsevier Science (USA). C1 VA Greater Los Angeles Healthcare Syst, Plast Surg Res Lab, Plast Surg Sect, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, GRECC, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90095 USA. RP Rudkin, GH (reprint author), VA Greater Los Angeles Healthcare Syst, Plast Surg Res Lab, Plast Surg Sect, Bldg 114,Room 221,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 31 TC 16 Z9 19 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD APR PY 2002 VL 103 IS 2 BP 183 EP 189 DI 10.1006/jsre.2001.6346 PG 7 WC Surgery SC Surgery GA 539BD UT WOS:000174848900009 PM 11922733 ER PT J AU Mick, E Biederman, J Faraone, SV Sayer, J Kleinman, S AF Mick, E Biederman, J Faraone, SV Sayer, J Kleinman, S TI Case-control study of attention-deficit hyperactivity disorder and maternal smoking, alcohol use, and drug use during pregnancy SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit hyperactivity disorder; pregnancy; substance abuse; cigarette smoking ID SUBSTANCE USE DISORDERS; PSYCHIATRIC COMORBIDITY; COGNITIVE-DEVELOPMENT; PRENATAL MARIJUANA; EARLY-ONSET; SCHOOL-AGE; CHILDREN; ADHD; RISK; GENE AB Objective: To address the putative association between attention-deficit hyperactivity disorder (ADHD) and prenatal exposure to maternal cigarette smoking, drugs of abuse, and alcohol attending to potential confounding by familial ADHD, maternal depression, conduct disorder, and indicators of social adversity in the environment. Method: A retrospective, hospital-based, case-control study was conducted with 280 ADHD cases and 242 non-ADHD controls of both genders. The case and control children and their relatives were systematically assessed with structured diagnostic interviews. Logistic regression analysis was used to determine the adjusted effect of prenatal exposure to substance use and ADHD. Results: ADHD cases were 2.1 times (95% confidence interval 1.1-4.1; p =.02) more likely to have been exposed to cigarettes and 2.5 times (95% confidence interval = 1.1-5.5; p.03) more likely to have been exposed to alcohol in utero than were the non-ADHD control subjects. Adjustment by familial psychopathology, Rutter's indicators of social adversity, and comorbid conduct disorder did not account for the effect of prenatal exposure to alcohol or the products of cigarettes. Conclusions: ADHD may be an additional deleterious outcome associated with prenatal exposure to alcohol independently of the association between prenatal exposure to nicotine and smoke products and other familial risk factors for the disorder. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Brockton W Roxbury Vet Affairs Med Ctr, Boston, MA USA. Massachusetts Hlth Ctr, Boston, MA USA. RP Mick, E (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 15 Parkham St,WACC 725, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH41314-07] NR 58 TC 223 Z9 229 U1 3 U2 41 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 2002 VL 41 IS 4 BP 378 EP 385 DI 10.1097/00004583-200204000-00009 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 533HM UT WOS:000174523600010 PM 11931593 ER PT J AU Sanders, S Busam, K Tahan, SR Johnson, RA Sachs, D AF Sanders, S Busam, K Tahan, SR Johnson, RA Sachs, D TI Granulomatous and suppurative dermatitis at interferon alfa injection sites: Report of 2 cases SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID CHRONIC HEPATITIS-C; BASAL-CELL CARCINOMA; CROHNS-DISEASE; PYODERMA-GANGRENOSUM; CUTANEOUS NECROSIS; ALPHA-INTERFERON; SUBCUTANEOUS INJECTION; ASEPTIC NECROSIS; LANGERHANS CELL; LEUKEMIA AB It has previously been reported that interferon alfa injection sites may develop pyoderma gangrenosum, interface dermatitis, vasculitis, or, more commonly, ulcers characterized by intravascular thrombi and a mixed inflammatory cell infiltrate. We describe 2 patients in whom granulomatous and suppurative dermatitis developed at interferon alfa injection sites. These cases extend the spectrum of interferon alfa injection site reactions. The histologic and clinical similarities of these cases with pyoderma gangrenosum and cutaneous Crohn's disease are explored. C1 Beth Israel Deaconess Med Ctr, Dept Pathol, Div Dermatopathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Div Dermatol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. New York Hosp, Dept Dermatol, New York, NY 10021 USA. RP Tahan, SR (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, Div Dermatopathol, 330 Brookline Ave, Boston, MA 02115 USA. NR 56 TC 18 Z9 19 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2002 VL 46 IS 4 BP 611 EP 616 DI 10.1067/mjd.2002.119087 PG 6 WC Dermatology SC Dermatology GA 581VB UT WOS:000177313600025 PM 11907520 ER PT J AU Cooper, RA AF Cooper, RA TI Wheelchair users are not necessarily wheelchair bound SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID MOBILITY C1 Univ Pittsburgh, Human Engn Res Labs, VA Pittsburgh Healthcare Syst, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Human Engn Res Labs, VA Pittsburgh Healthcare Syst, Dept Bioengn, Pittsburgh, PA USA. Univ Pittsburgh, Human Engn Res Labs, VA Pittsburgh Healthcare Syst, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP Cooper, RA (reprint author), Univ Pittsburgh, Human Engn Res Labs, VA Pittsburgh Healthcare Syst, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. NR 12 TC 1 Z9 1 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 APR PY 2002 VL 50 IS 4 BP 771 EP 772 DI 10.1046/j.1532-5415.2002.50177.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 541AT UT WOS:000174963600026 PM 11982683 ER PT J AU Austin, S Alessi, CA Kim, EC AF Austin, S Alessi, CA Kim, EC TI Sundowning and sleep impairment in nursing home residents. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Ohio Univ, Coll Osteopath Med, Athens, OH 45701 USA. VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, Multicampus Program Geriatr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2002 VL 50 IS 4 SU S MA P336 BP S120 EP S121 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 542EL UT WOS:000175030500381 ER PT J AU Bates-Jensen, BM Alessi, CA Ouslander, JG Al-Samarrai, NR Schnelle, JF AF Bates-Jensen, BM Alessi, CA Ouslander, JG Al-Samarrai, NR Schnelle, JF TI The effects of an exercise and incontinence intervention on skin health outcomes in nursing home residents. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Multicampus Program Geriatr Med & Gerontol, Borun Ctr Gerontol Res, Reseda, CA USA. Vet Adm Greater Los Angeles Healthcare Syst, Sepulveda Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. Emory Univ, Div Geriatr Med & Gerontol, Wesley Woods Ctr, Atlanta, GA 30322 USA. Atlanta VA Rehabil Res & Dev Ctr, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2002 VL 50 IS 4 SU S MA P404 BP S142 EP S143 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 542EL UT WOS:000175030500449 ER PT J AU Casarett, DJ Karlawish, JH Hirschman, KB AF Casarett, DJ Karlawish, JH Hirschman, KB TI The effect of symptoms on cancer patients' capacity to give consent for research. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Alzheimers Dis Ctr, Philadelphia, PA 19104 USA. Univ Penn, Div Geriatr Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Social Work, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2002 VL 50 IS 4 SU S MA P51 BP S31 EP S32 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 542EL UT WOS:000175030500097 ER PT J AU Chuang, KH Covinsky, KE Sands, LP Landefeld, CS AF Chuang, KH Covinsky, KE Sands, LP Landefeld, CS TI DRG-adjusted hospital costs are higher in patients with worse functional status. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2002 VL 50 IS 4 SU S MA A21 BP S7 EP S7 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 542EL UT WOS:000175030500022 ER PT J AU Dreisbach, MA Growdon, JH Irizarry, MC AF Dreisbach, MA Growdon, JH Irizarry, MC TI Lack of association of statin use and the progression of Alzheimer's Disease. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Ohio State Univ, Sch Med, Columbus, OH 43210 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2002 VL 50 IS 4 SU S MA P377 BP S134 EP S134 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 542EL UT WOS:000175030500422 ER PT J AU Guzman, JS Sohn, L Harada, N AF Guzman, JS Sohn, L Harada, N TI Social support and health services utilization in the elderly veterans. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2002 VL 50 IS 4 SU S MA P89 BP S44 EP S44 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 542EL UT WOS:000175030500135 ER PT J AU Joseph, CL Carethers, M Kuwanoe, C Marks, ML AF Joseph, CL Carethers, M Kuwanoe, C Marks, ML TI A pilot trial of Telehomecare for VA home-based primary care (HBPC) patients. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Portland Vet Affairs Med Ctr, Portland, OR USA. Spark M Matsunaga Vet Affairs Med Ctr, Honolulu, HI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2002 VL 50 IS 4 SU S MA P91 BP S44 EP S45 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 542EL UT WOS:000175030500137 ER PT J AU Karlawish, JH Casarett, DJ James, BD TenHave, TR Clark, CM AF Karlawish, JH Casarett, DJ James, BD TenHave, TR Clark, CM TI What factors explain differences between Alzheimer's disease patients' and caregivers' ratings of patient quality of life (QOL)? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. NR 0 TC 1 Z9 1 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 APR PY 2002 VL 50 IS 4 SU S MA P254 BP S94 EP S95 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 542EL UT WOS:000175030500299 ER PT J AU Kunik, ME Snow, AL Souchek, J Menke, T Ashton, CM AF Kunik, ME Snow, AL Souchek, J Menke, T Ashton, CM TI Health service use in dementia patients with aggression. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Houston VAMC, HSR&D, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. VAMC, S Cent MIRECC, Houston, TX USA. Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2002 VL 50 IS 4 SU S MA P107 BP S49 EP S50 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 542EL UT WOS:000175030500153 ER PT J AU Rosen, J Mulsant, BH Kollar, M Kastango, KB Mazumdar, S Fox, D AF Rosen, J Mulsant, BH Kollar, M Kastango, KB Mazumdar, S Fox, D TI Mental health training for nursing home staff using computer-based interactive video: A 6-month randomized trial. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Univ Pittsburgh, WPIC, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. VA Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. Fox Learning Syst Inc, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2002 VL 50 IS 4 SU S MA P187 BP S73 EP S74 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 542EL UT WOS:000175030500232 ER PT J AU Skolnick, AH Perell, KL Manzano, M Gray, CG Opava-Rutter, D Castle, S AF Skolnick, AH Perell, KL Manzano, M Gray, CG Opava-Rutter, D Castle, S TI Characteristics of recurrent fallers in a population referred to a fall prevention clinic. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Brown Univ, Sch Med, Providence, RI 02912 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2002 VL 50 IS 4 SU S MA P125 BP S55 EP S55 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 542EL UT WOS:000175030500171 ER PT J AU Steinman, MA Gonzales, R Landefeld, CS AF Steinman, MA Gonzales, R Landefeld, CS TI Broad-spectrum antibiotic use among elderly outpatients: Results from a national sample. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 San Francisco VA Med Ctr, VA Natl Qual Scholars Program, San Francisco, CA USA. Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2002 VL 50 IS 4 SU S MA P303 BP S110 EP S110 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 542EL UT WOS:000175030500348 ER PT J AU Wong, M Staszewsky, L Volpi, A Latini, R Barlera, S Hoglund, C AF Wong, M Staszewsky, L Volpi, A Latini, R Barlera, S Hoglund, C TI Quality assessment and quality control of echocardiographic performance in a large multicenter international study: Valsartan in Heart Failure Trial (Val-HeFT) SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID AGREEMENT AB Objective: To qualify 302 multinational echocardiography sites to record and read serial studies and to monitor quality in 5010 patients randomized into Valsartan in Heart Failure Trial (Val-HeFT). Background: Decentralized echocardiography reading is unprecedented in large clinical trials. Methods: Single and duplicate recordings, and triplicate readings of echocardiographic variables were submitted to 3 core laboratories. Quality of recording was defined with a 16-point scoring system; accuracy of reading by agreement with core readings; reproducibility by agreement between the duplicate studies. Results: Seventy-five percent of initial submissions were approved for recording, and 50% for reading. Resubmissions were evaluated until approval. initial scores of sites approved with 1 versus 2 submissions differed, 13.8 +/- 1.4 versus 10.6 +/- 2.0, P < .001; final score was similar, 13.4 +/- 1.6, P = ns. Initial score of sites approved after 3 or more submissions differed, 9.5 +/- 1.9, P < .001; final score improved to 12.7 +/- 1.9, but remained lower, P < .001. Expressed as 95% limits of agreement (mean difference +/- 1.96 x SD), accuracy = -0.04 +/- 0.74 cm for left ventricular internal end-diastolic diameter (LVIDd); -0.29 +/- 14.3% for ejection fraction (EF); reproducibility 0.00 +/- 0.53 cm for LVIDd; -0.25 +/- 8.3% for EF. Quality of random sampling at baseline, 4, 12, and 18 months showed recording scores of 11.7 +/- 2.7, 12.3 +/- 2.4, 12.1 +/- 2.2, and 11.4 +/- 2.0, P = .24. Power analysis revealed differences of 0.09 cm for LVIDd, and 0.86% for EF detectable with a power of 90% and alpha of 5%. Conclusion: The qualifying process improved echocardiography recording and reading to bring 95% of the sites to an equivalent level of quality. Monitoring quality found that recording quality and reading accuracy were maintained 18 months into the trial. Reproducibility, given the large sample size, will be able to detect small changes in LVIDd and EF. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Stockholm Heart Ctr, Stockholm, Sweden. G Fornaroli Hosp, Div Cardiol, Milan, Italy. Ist Ric Farmacol Mario Negri, Milan, Italy. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Wong, M (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,500-6641,00QM, Los Angeles, CA 90073 USA. NR 17 TC 20 Z9 20 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD APR PY 2002 VL 15 IS 4 BP 293 EP 301 DI 10.1067/mje.2001.115103 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 548CU UT WOS:000175371700002 PM 11944005 ER PT J AU Vancon, AC Fox, ER Chow, CM Hill, J Weyman, AE Picard, MH Scherrer-Crosbie, M AF Vancon, AC Fox, ER Chow, CM Hill, J Weyman, AE Picard, MH Scherrer-Crosbie, M TI Pulse inversion harmonic imaging improves endocardial border visualization in two-dimensional images: Comparison with harmonic imaging SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID ECHOCARDIOGRAPHY; CONTRAST; OPACIFICATION; DEFINITION; ALBUNEX AB Pulse inversion harmonic imaging (PIHI) is a new modality that increases the detection of harmonic echoes and myocardial contrast by canceling linearly transmitted signals. We tested whether PIHI improved the detection of endocardial borders in noncontrast 2-dimensional echocardiography. We compared PERI with tissue harmonic imaging (THI), which decreases linearly transmitted signals using filters. Fundamental mode (FM) was compared with THI and PERI in 50 consecutive patients. The global and segmental endocardial visualization scores measured with FM were significantly improved by using either THI or PIHI. The improvement of the global score compared with FM was slightly higher using PIHI than THI, because of an improved visualization of the base and the anterior wall with the PIHI technique compared with THI. The ratio of myocardial-to-cavity signal was similarly increased from FM with THI and PIHI. PIHI, a new modality for detection of myocardial contrast, can also be used for endocardial border visualization. It provides an improvement relative to THI for specific regions of the endocardium. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Vancon, AC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, VBK 5,55 Fruit St, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 15 TC 9 Z9 12 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD APR PY 2002 VL 15 IS 4 BP 302 EP 308 DI 10.1067/mje.2002.117294 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 548CU UT WOS:000175371700003 PM 11944006 ER PT J AU Sherrard, DJ AF Sherrard, DJ TI Manipulating the calcium receptor SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID PARATHYROID-HORMONE SECRETION; DIALYSIS PATIENTS; HYPERPARATHYROIDISM; OSTEODYSTROPHY; PREVALENCE; FRACTURES; BONE; RATS C1 Univ Washington, VA Puget Sound Hlth Care Syst, Div Nephrol, Seattle, WA 98195 USA. RP Sherrard, DJ (reprint author), VA Puget Sound Hlth Care Syst S111RDU, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 17 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 APR PY 2002 VL 13 IS 4 BP 1124 EP 1125 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 535CM UT WOS:000174627700037 PM 11912275 ER PT J AU Chen, RH Huang, CC Morinelli, TA Trojanowska, M Paul, RV AF Chen, RH Huang, CC Morinelli, TA Trojanowska, M Paul, RV TI Blockade of the effects of TGF-beta 1 on mesangial cells by overexpression of Smad7 SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GROWTH-FACTOR-BETA; TGF-BETA; EXPERIMENTAL GLOMERULONEPHRITIS; GENE-THERAPY; RAT-KIDNEY; RECEPTOR; EXPRESSION; KINASE; INVOLVEMENT; FIBROBLASTS AB Smad7, a protein induced by transforming growth factor-beta1 (TGF-beta1) in many target cells, inhibits TGF-beta1 signal transduction and is thought to mediate an intracellular negative feedback response that limits TGF-beta1 effects. It is possible that overexpression of Smad7 could block specified effects of TGF-beta1 on mesangial cells, a TGF-beta target in glomerular disease. Smad7 mRNA was induced by TGF-beta1 within 1 h in a concentration-dependent manner in a transformed mouse mesangial cell (MMC) line. Uptake of C-14- spermidine from the medium by MMC and the transcriptional activity of a segment of the human collagen pro-alpha2 type 1 chain (COL1A2) promoter fused to a luciferase reporter gene were used as indices of TGF-beta1. Treatment with TGF-beta1 increased C-14-spermidine uptake rate in a time-, concentration-, and temperature-dependent manner. For example, exposure to 1 ng/mI TGF-beta1 for 15 h increased uptake approximately twofold, a response that was attenuated by cycloheximide. Transfection of Smad7 expression vector into MMC abrogated both TGF-beta1-dependent stimulation of spermidine uptake and COL1A2 promoter activity. It is concluded that: (1) TGF-beta1 induces Smad7 in MMC; (2) C-14-spermidine uptake is a convenient quantitative index of TGF-beta1 effect in these cells; and (3) overexpression of Smad7 is a highly effective method of blocking at least some mesangial cell effects of TGF-beta1 that may warrant evaluation in vivo in experimental glomerular disease. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Med Specialty Serv, Charleston, SC USA. RP Paul, RV (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 171 Ashley Ave, Charleston, SC 29425 USA. NR 30 TC 29 Z9 32 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 APR PY 2002 VL 13 IS 4 AR UNSP 1046-6673/1304-0887 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 535CM UT WOS:000174627700009 PM 11912247 ER PT J AU Hariharan, S Pirsch, JD Lu, CY Chan, L Pesavento, TE Alexander, S Bumgardner, GL Baasadona, G Hricik, DE Pescovitz, MD Rubin, NT Stratta, RJ AF Hariharan, S Pirsch, JD Lu, CY Chan, L Pesavento, TE Alexander, S Bumgardner, GL Baasadona, G Hricik, DE Pescovitz, MD Rubin, NT Stratta, RJ TI Pancreas after kidney transplantation SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID TYPE-1 DIABETES-MELLITUS; QUALITY-OF-LIFE; MYCOPHENOLATE-MOFETIL; ISLET TRANSPLANTATION; URINARY AMYLASE; CARDIAC DEATH; RISK FACTOR; REJECTION; RECIPIENTS; NEPHROPATHY C1 Med Coll Wisconsin, Div Nephrol, Milwaukee, WI 53226 USA. Univ Wisconsin, Dept Transplant Surg, Madison, WI USA. Univ Texas, Div Nephrol, Dallas, TX 75230 USA. Univ Colorado, Div Nephrol, Denver, CO 80202 USA. Ohio State Univ, Div Nephrol, Columbus, OH 43210 USA. Stanford Univ, Div Pediat Nephrol, Stanford, CA 94305 USA. Yale Univ, Dept Transplant Surg, New Haven, CT USA. Case Western Reserve Univ, Div Nephrol, Cleveland, OH 44106 USA. Indiana Univ, Dept Transplant Surg, Indianapolis, IN 46204 USA. Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. Wake Forest Univ, Dept Transplant Surg, Winston Salem, NC 27109 USA. RP Hariharan, S (reprint author), Med Coll Wisconsin, Div Nephrol, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. NR 59 TC 28 Z9 30 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 APR PY 2002 VL 13 IS 4 AR UNSP 1046.6673/1304-1109 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 535CM UT WOS:000174627700035 PM 11912273 ER PT J AU Mattix, HJ Hsu, CY Shaykevich, S Curhan, G AF Mattix, HJ Hsu, CY Shaykevich, S Curhan, G TI Use of the albumin/creatinine ratio to detect microalbuminuria: Implications of sex and race SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID URINARY ALBUMIN EXCRETION; SKELETAL-MUSCLE; FOLLOW-UP; CREATININE; RISK; PREVALENCE; BLACK AB The recommended albumin (mug)/creatinine (mg) ratio (ACR) (30 mug/mg) to detect microalbuminuria does not account for sex or racial differences in creatinine excretion. In a nationally representative sample of subjects, the distribution of urine albumin and creatinine concentrations was examined by using one ACR value (greater than or equal to30 mug/mg) and sex-specific cut-points (greater than or equal to17 mug/mg in men and greater than or equal to25 mug/mg in women) measured in spot urine specimens. Mean urine albumin concentrations were not significantly different between men and women, but urine creatinine concentrations were significantly higher (P < 0.0001). Compared with non-Hispanic whites, urine creatinine concentrations were significantly higher in non-Hispanic blacks (NHB) and Mexican Americans, whereas urine albumin concentrations were significantly higher in NHB (P < 0.0001) but not Mexican Americans. When a single ACR is used, the prevalence of microalbuminuria was significantly lower among the men compared with women (6.0 versus 9.2%; P < 0.0001) and among non-Hispanic whites compared with NHB (7.2 versus 10.2%; P < 0.0001). No significant difference in-the prevalence of microalbuminuria between men and women was noted when sex-specific ACR cutpoints were used. In the multivariate adjusted model, female sex (odds ratio, 1.62; 95% confidence interval, 1.29 to 2.05) and NHB race/ethnicity (odds ratio, 1.34; 95% confidence interval, 1.12 to 1.61) were independently associated with microalbuminuria when a single ACR threshold was used. When a sex-specific ACR was used, NHB race/ethnicity remained significantly associated with microalbuminuria but sex did not. The use of one ACR value to define microalbuminuria may underestimate microalbuminuria in subjects with higher muscle mass (men) and possibly members of certain racial/ethnic groups. C1 Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Mattix, HJ (reprint author), 100 Charles River Plaza,5th Floor, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK 59583] NR 22 TC 202 Z9 216 U1 0 U2 3 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 APR PY 2002 VL 13 IS 4 AR UNSP 1046-6673/1304-1034 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 535CM UT WOS:000174627700025 PM 11912263 ER PT J AU Yuan, HP Takeuchi, E Taylor, GA McLaughlin, M Brown, D Salant, DJ AF Yuan, HP Takeuchi, E Taylor, GA McLaughlin, M Brown, D Salant, DJ TI Nephrin dissociates from actin, and its expression is reduced in early experimental membranous nephropathy SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PASSIVE HEYMANN NEPHRITIS; GLOMERULAR-BASEMENT-MEMBRANE; CONGENITAL NEPHROTIC SYNDROME; EPITHELIAL-CELLS; RAT NEPHRIN; IMMUNE DEPOSITS; ATTACK COMPLEX; SLIT DIAPHRAGM; C5B-9 COMPLEX; IV COLLAGEN AB These studies examined the expression of the podocyte slit diaphragm protein nephrin and its association with actin at the onset of proteinuria in passive Heymann nephritis (PHN), a rat model of human membranous nephropathy. Four days after immunization, 58% of PHN rats had mild proteinuria. At that time, most slit diaphragms were still visible on electron microscopy; however, in those locations where the deposits encroached on the filtration slits, the slit diaphragms were either displaced or absent. On day 7, the PHN rats were severely proteinuric, and most slit diaphragms were either absent, displaced, or replaced by occluding-type junctions. Immunofluorescence microscopy with antibodies to the external and cytoplasmic domains of nephrin showed a progressive loss of staining and a change in the distribution of nephrin from an interrupted linear pattern in normal controls to a more dispersed and clustered pattern in PHN. In contrast, the intensity of staining for ZO-1 and CD2-associated protein (CD2AP), two other proteins that are located on the cytoplasmic face of the slit diaphragm, was undiminished. Immunogold electron microscopy confirmed the progressive disappearance of nephrin from podocyte foot processes and retention of CD2AP. Glomeruli and glomerular cell membranes were extracted sequentially with Triton X-100, followed by DNase I or potassium iodide to depolymerize actin. Western blot analysis of the extracts showed a progressive decline of total nephrin on days 4 and 7 of PHN as well as a reduction in the actin-associated fraction. These findings show that nephrin partly dissociates from actin at the onset of podocyte injury in PHN. This is accompanied by a progressive loss of nephrin from the podocyte foot processes and prominent changes in the morphology of the slit diaphragms. These events may underlie the loss of podocyte barrier function in membranous nephropathy. C1 Boston Univ, Med Ctr, Evans Biomed Res Ctr, EBRC 504,Renal Sect, Boston, MA 02118 USA. Boston Univ, Med Ctr, Evans Biomed Res Ctr, Dept Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Salant, DJ (reprint author), Boston Univ, Med Ctr, Evans Biomed Res Ctr, EBRC 504,Renal Sect, 650 Albany St, Boston, MA 02118 USA. FU NIDDK NIH HHS [DK 57521, DK 30932] NR 41 TC 84 Z9 101 U1 0 U2 2 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 APR PY 2002 VL 13 IS 4 AR UNSP 1046-6673/1304-0946 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 535CM UT WOS:000174627700016 PM 11912254 ER PT J AU Gibson, CM Frisch, D Murphy, SA Gourlay, SG Gibbons, R Baran, KW Nguyen, M Palmeri, S Barro, HV AF Gibson, CM Frisch, D Murphy, SA Gourlay, SG Gibbons, R Baran, KW Nguyen, M Palmeri, S Barro, HV CA LIMIT Study Grp TI The relationship of intracoronary stent placement following thrombolytic therapy to tissue level perfusion SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE stent; acute myocardial infarction; microvasculature; TIMI myocardial perfusion grade; TIMI frame count ID ACUTE MYOCARDIAL-INFARCTION; NO-REFLOW PHENOMENON; TIMI FRAME COUNT; ELECTROCARDIOGRAPHIC EVIDENCE; CORONARY ANGIOPLASTY; ARTERY; FLOW; VASOCONSTRICTION; MORTALITY; AGENTS AB Background: Stenting has been shown to improve lumen diameters and thereby improve epicardial blood flow, but the impact of stent placement on tissue level perfusion has not been well characterized. Methods: Data were drawn from the LIMIT trial of rhuMAb CD18 (anti WBC antibody) in acute myocardial infarction (AMI). Adjunctive/rescue stenting was performed at the discretion of the investigator. The TIMI Myocardial Perfusion Grade (TMPG) was assessed and digital subtraction angiography (DSA) was used to quantify brightness of the myocardial blush. Results: TIMI 3 flow was 54.2% (64/118) before stent placement, and improved to 87.2% (102/117, p < 0.001) following stent placement. Likewise, Corrected TIMI Frame Counts (CTFCs) improved from medians of 37.6 to 21 ( p < 0.001). By DSA, the rate of growth in brightness also tended to be greater after stenting (2.3 +/- 0.4 Gray/sec, n = 54 vs 3.1 +/- 0.3, n = 54, p = 0.07). The incidence of TMPG 0 decreased following stent placement (25.2% (29/118) vs 14.3% (16/118), p = 0.03) and the incidence of a stain in the myocardium (TMPG 1) increased (13.5% (16/118) vs 28.6% (34/118), p = 0.004). Conclusion: Adjunctive stenting following thrombolytic administration in AMI improves epicardial TIMI 3 flow and TIMI frame counts as well as dye inflow into the myocardium: TMPG 0 is reduced and myocardial blush measured quantitatively by DSA tends to be brighter. However, more TMPG 1 or dye staining was present on next injection, suggesting dye outflow may be impaired. C1 Harvard Clin Res Inst, Core Cardiovasc Serv, TIMI Data Coordinating Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Mayo Clin, Div Cardiovasc, Rochester, MN 55905 USA. St Paul Heart Clin, St Paul, MN 55101 USA. Univ Sherbrooke, Sherbrooke, PQ J1K 2R1, Canada. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Univ Calif San Francisco, Dept Med, Div Cardiovasc, San Francisco, CA 94143 USA. Genentech Inc, San Francisco, CA 94080 USA. RP Gibson, CM (reprint author), Harvard Clin Res Inst, Core Cardiovasc Serv, TIMI Data Coordinating Ctr, 930 Commonwealth Ave,3rd Floor, Boston, MA 02215 USA. NR 27 TC 1 Z9 1 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 APR PY 2002 VL 13 IS 2 BP 63 EP 68 DI 10.1023/A:1016253028348 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 572ZY UT WOS:000176805900001 PM 12101381 ER PT J AU Lee, HY Grant, EG AF Lee, HY Grant, EG TI Sonography in renovascular hypertension SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE Doppler sonography; renal arteries; renovascular hypertension ID RENAL-ARTERY STENOSIS; WAVE-FORM PARAMETERS; DUPLEX ULTRASONOGRAPHY; DOPPLER SONOGRAPHY; STENT PLACEMENT; DIAGNOSIS; TARDUS; SYSTOLE; PATTERN AB Objective. To familiarize practitioners with different sonographic manifestations of renal artery compromise and the sonographic techniques for renal artery imaging. Methods. Approximately 1500 examinations evaluating for renal artery disease are performed in our vascular laboratory every year. Most of the patients have the symptoms of hypertension (possibly related to renovascular etiology) and renal insufficiency. From our cumulative experience, the optimal scanning techniques are defined for each renal artery for extrarenal versus intrarenal vascular evaluation, and for patients with different body habitus. We have also tabulated our technical success rate. Cases with sonographic evidence of renal artery compromise are identified. The validity, sensitivity, and specificity of different parameters are examined. Results. We achieve an approximately 75% to 80% success rate in obtaining technically adequate studies. We have not found the tardus-parvus waveform evaluation to be as valuable as direct interrogation of the renal artery. Conclusions. Duplex/color Doppler sonography serves a vital role in the diagnosis of renal artery stenosis and occlusion; it has an excellent correlation with contrast-enhanced angiography. It is also used for intraoperative or postrevascularization surveillance to show evidence of recurring stenosis, thrombosis, and other complications. C1 W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Dept Radiol, Los Angeles, CA 90073 USA. RP Lee, HY (reprint author), W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Dept Radiol, 11301 Wilshire Blvd,114, Los Angeles, CA 90073 USA. NR 21 TC 16 Z9 16 U1 1 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD APR PY 2002 VL 21 IS 4 BP 431 EP 441 PG 11 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 534AP UT WOS:000174562700009 PM 11934100 ER PT J AU Penson, DF Grossfeld, GD Li, YP Henning, JM Lubeck, DP Carroll, PR AF Penson, DF Grossfeld, GD Li, YP Henning, JM Lubeck, DP Carroll, PR TI How well does the Partin nomogram predict pathological stage after radical prostatectomy in a community based population? Results of the cancer of the prostate strategic urological research endeavor SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prognosis; prostatectomy; neoplasm staging ID GLEASON SCORE; CLINICAL STAGE; ANTIGEN; SPECIMENS; DIAGNOSIS AB Purpose: The Partin nomogram uses preoperative Gleason grade, serum prostate specific antigen and clinical stage to predict pathological outcome after radical prostatectomy. It was developed and validated in a select population of patients at 3 academic institutions. Although the nomogram is widely used, it has yet to be validated in a community based population. We assessed the performance of the nomogram in the Cancer of the Prostate Strategic Urological Research Endeavor, a nationwide, community based observational disease registry of men with prostate cancer. Materials and Methods: Included in the cohort were 1,162 men in Cancer of the Prostate Strategic Urological Research Endeavor who underwent radical prostatectomy. Using various probability thresholds the nomogram was used to predict outcomes in each patient. Using different probability thresholds receiver operating characteristics curves were then used to assess test performance. Results: Of the men 860 (74%) had organ confined disease, 179 (15%) had established capsular penetration, 95 (8%) had seminal vesicle involvement and 37 (3%) had lymph node involvement. Calculated receiver operating characteristics curve area was 0.684 for predicting organ confined disease, 0.614 for predicting capsular penetration, 0.726 for predicting seminal vesicle involvement and 0.766 for predicting lymph node involvement. These values were lower than in previously published reports. Conclusions: While the Partin nomogram performs adequately in a community based cohort of men who undergo radical prostatectomy for localized prostate cancer, it does not attain the success demonstrated in previous studies in select academic cohorts. This result was likely due to differences in the distribution of pathological outcomes in the community based cohort, in which more men had organ confined disease. C1 Vet Affairs Puget Sound Hlth Care Syst, Urol Sect, Seattle, WA USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. Urol Outcomes Res Grp, Dept Urol, San Francisco, CA USA. Univ Calif San Francisco, Mt Zion Canc Ctr, San Francisco, CA 94143 USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. RP Penson, DF (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Urol Sect, Seattle, WA USA. NR 18 TC 48 Z9 54 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2002 VL 167 IS 4 BP 1653 EP 1657 DI 10.1016/S0022-5347(05)65172-5 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 531VB UT WOS:000174437000016 PM 11912382 ER PT J AU Grundner, C Mirzabekov, T Sodroski, J Wyatt, R AF Grundner, C Mirzabekov, T Sodroski, J Wyatt, R TI Solid-phase proteoliposomes containing human immunodeficiency virus envelope glycoproteins SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; CD4 BINDING-SITE; HIV-1 GP120; NEUTRALIZING ANTIBODY; ATOMIC-STRUCTURE; MEMBRANE-FUSION; TYPE-1; GP41; PROTEIN; INFECTION AB The human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein gp120 mediates receptor binding and is the major target for neutralizing antibodies. A broadly neutralizing antibody response is likely to be a critical component of the immune response against HIV-1. Although antibodies against monomeric gp120 are readily elicited in immunized individuals, these antibodies are inefficient in neutralizing primary HIV-1 isolates. As a chronic pathogen, HIV-1 has evolved to avoid an optimal host response by a number of immune escape mechanisms. Monomeric gp120 that has dissociated from the functional trimer presents irrelevant epitopes that are not accessible on functional trimeric envelope glycoproteins. The resulting low level of antigenic cross-reactivity between monomeric gp120 and the functional spike may contribute to the inability of monomeric gp120 to elicit broadly neutralizing antibodies. Attempts to generate native, trimeric envelope glycoproteins as immunogens have been frustrated by both the lability of the gp120-gp41 interaction and the weak association between gp120 subunits. Here, we present solid-phase HIV-1 gp160DeltaCT (cytoplasmic tail-deleted) proteoliposomes (PLs) containing native, trimeric envelope glycoproteins in a physiologic membrane setting. We present data that indicate that the gp160DeltaCT glycoproteins on PLs are trimers and are recognized by several relevant conformational ligands in a manner similar to that for gp160DeltaCT oligomers expressed on the cell surface. The PLs represent a significant advance over present envelope glycoprotein formulations as candidate immunogens for HIV vaccine design and development. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Div AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Wyatt, R (reprint author), NIH, Struct Virol Sect, Vaccine Res Ctr, 40 Convent Dr,Bldg 40,Room 4512, Bethesda, MD 20892 USA. FU NIAID NIH HHS [P30 AI028691, 1R21AI-44328-02, 5R21AI-44328-02, AI 31783, AI28691, R01 AI031783] NR 50 TC 77 Z9 79 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 APR PY 2002 VL 76 IS 7 BP 3511 EP 3521 DI 10.1128/JVI.76.7.3511-3521.2002 PG 11 WC Virology SC Virology GA 529ZE UT WOS:000174330500043 PM 11884575 ER PT J AU Kaur, A Hale, CL Noren, B Kassis, N Simon, MA Johnson, RP AF Kaur, A Hale, CL Noren, B Kassis, N Simon, MA Johnson, RP TI Decreased frequency of cytomegalovirus (CMV)-specific CD4(+) T lymphocytes in simian immunodeficiency virus-infected rhesus macaques: Inverse relationship with CMV viremia SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; ALLOGENEIC BONE-MARROW; CELL-DEFICIENT MICE; CD4-DEFICIENT MICE; GAMMA-HERPESVIRUS; EFFECTOR FUNCTION; SIV INFECTION; IN-VIVO; RESPONSES; MEMORY AB The frequency of cytomegalovirus (CMV)-specific CD4(+) T lymphocytes was determined in CMV-seropositlve rhesus macaques with or without simian immunodeficiency virus (SIV) infection by using the sensitive assays of intracellular cytokine staining and gamma interferon ELISPOT. Both techniques yielded 3- to 1,000-fold-higher frequencies of CMV-specific CD4+ T lymphocytes than traditional proliferative limiting dilution assays. The median frequency of CMV-specific CD4(+) T lymphocytes in 23 CMV-seropositive SIV-negative macaques was 0.63% (range, 0.16 to 5.8%). The majority of CMV-specifie CD4(+) T lymphocytes were CD95(pos) and CD27(lo) but expressed variable levels of CD45RA. A significant reduction (P < 0.05) in the frequency of CMV-specific CD4+ T lymphocytes was observed in pathogenic SIV-infected macaques but not in macaques infected with live attenuated strains of SIV. CMV-specific CD4(+) T lymphocytes were not detected in six of nine pathogenic SIV-infected rhesus macaques. CMV DNA was detected in the plasma of four of six of these macaques but in no animal with detectable CMV-specific CD4(+) T lymphocytes. In pathogenic SW-infected macaques, loss of CMV-specific CD4+ T lymphocytes was not predicted by the severity of CD4(+) T lymphocytopenia. Neither was it predicted by the pre-SIV infection frequencies of CD45RA(neg) or CCR5(pos) CMV-specific CD4(+) T lymphocytes. However, the magnitude of activation, as evidenced by the intensity of CD40L expression on CMV-specific CD4+ T lymphocytes pre-SIV infection, was three- to sevenfold greater in the two macaques that subsequently lost these cells after SIV infection than in the two macaques that retained CMV-specific CD4+ T lymphocytes post-SIV infection. Future longitudinal studies with these techniques will facilitate the study of CMV pathogenesis in AIDS. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Pathol, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. RP Kaur, A (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, 1 Pinehill Dr, Southborough, MA 01772 USA. FU NCRR NIH HHS [K26 RR000168, P51 RR000168, RR00168]; NIAID NIH HHS [R01 AI043890, AI43890, AI45314] NR 45 TC 51 Z9 51 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2002 VL 76 IS 8 BP 3646 EP 3658 DI 10.1128/JVI.76.8.3646-3658.2002 PG 13 WC Virology SC Virology GA 533GG UT WOS:000174520600007 PM 11907204 ER PT J AU Sabolic, I Herak-Kramberger, CM Ljubojevic, M Biemesderfer, D Brown, D AF Sabolic, I Herak-Kramberger, CM Ljubojevic, M Biemesderfer, D Brown, D TI NHE3 and NHERF are targeted to the basolateral membrane in proximal tubules of colchicine-treated rats SO KIDNEY INTERNATIONAL LA English DT Article DE cytoskeleton; membrane polarity; microtubules; sodium-proton exchanger; kidney ID POLARIZED EPITHELIAL-CELLS; NA/H EXCHANGER NHE-3; INTERCALATED CELLS; MICROTUBULE MOTORS; ANTIGEN RETRIEVAL; PLASMA-MEMBRANE; BRUSH-BORDER; KIDNEY-CELLS; TRANSPORT; PROTEIN AB Background. Depolymerization of microtubules in proximal tubule (PT) cells of colchicine-treated rats causes disruption of vesicle recycling and redistribution of some brush-border membrane (BBM) transporters into cytoplasmic vesicles. NHE3, an isoform of the Na+/H+ exchanger in the PT cell BBM, is acutely regulated by a variety of mechanisms, including protein trafficking and interaction with the PDZ protein, NHERF. The effects of microtubule disruption by colchicine on NHE3 trafficking in PT and the potential role of NHERF in this process have not been studied. Methods. Immunofluorescence and immunogold cytochemistry were performed on cryosections of kidney tissue, and immunoblotting of BBM isolated from the renal cortex and outer stripe of control and colchicine-treated (3.2 mg/kg, IP, a single dose 12 hours before sacrifice) rats. Results. In cells of the convoluted PT (S1/S2 segments) of control rats, NHE3 was located mainly in the BBM; subapical endosomes were weakly stained. In cells of the straight PT (S3 segment), NHE3 was present in the BBM and in lysosomes. In colchicine-treated rats, there was a marked redistribution of NHE3 from the BBM into intracellular vesicles and the basolateral plasma membrane in the S1/S2 segments. In the S3 segment, the abundance of BBM NHE3 was not visibly changed, but NHE3-positive intracellular organelles largely disappeared, and the antigen was detectable in the basolateral plasma membrane. The PDZ protein NHERF followed a similar pattern: in control animals, it was strong in the BBM and negative in the basolateral membrane in cells along the PT. After colchicine treatment, expression of NHERF in the basolateral membrane strongly increased in all PT segments, where it colocalized with NHE3. Conclusions. The data indicate that: (a) microtubules are involved in the apical targeting of NHE3 and NHERF in renal PT cells, and (b) the parallel basolateral insertion of NHE3 and NHERF may represent an indirect targeting pathway that involves transient, microtubule-independent basolateral insertion of these proteins, followed by microtubule-dependent, vesicle-mediated transcytosis to the BBM. C1 Inst Med Res & Occupat Hlth, Unit Mol Toxicol, HR-10001 Zagreb, Croatia. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA USA. RP Sabolic, I (reprint author), Inst Med Res & Occupat Hlth, Unit Mol Toxicol, Ksaverska Cesta 2,POB 291, HR-10001 Zagreb, Croatia. FU FIC NIH HHS [1-R03-TW01057-01]; NIDDK NIH HHS [R01 DK 42956] NR 52 TC 18 Z9 18 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD APR PY 2002 VL 61 IS 4 BP 1351 EP 1364 DI 10.1046/j.1523-1755.2002.00266.x PG 14 WC Urology & Nephrology SC Urology & Nephrology GA 532GC UT WOS:000174465100017 PM 11918742 ER PT J AU Ragland, BD Bell, WC Lopez, RR Siegal, GP AF Ragland, BD Bell, WC Lopez, RR Siegal, GP TI Cytogenetics and molecular biology of osteosarcoma SO LABORATORY INVESTIGATION LA English DT Review ID COMPARATIVE GENOMIC HYBRIDIZATION; P-GLYCOPROTEIN EXPRESSION; HIGH-GRADE OSTEOSARCOMAS; SOFT-TISSUE SARCOMAS; OSTEO-SARCOMA; DNA ANALYSIS; P53 GENE; PAROSTEAL OSTEOSARCOMA; PAGETS-DISEASE; BETA ISOFORMS C1 Univ Alabama, Div Anatom Pathol, Dept Pathol, Birmingham, AL 35233 USA. Univ Alabama, Dept Radiol, Birmingham, AL 35233 USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35233 USA. Univ Alabama, Dept Surg, Birmingham, AL 35233 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Siegal, GP (reprint author), Univ Alabama, Div Anatom Pathol, Dept Pathol, 506 Kracke Bldg, Birmingham, AL 35233 USA. NR 70 TC 55 Z9 58 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD APR PY 2002 VL 82 IS 4 BP 365 EP 373 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 547UY UT WOS:000175351800001 PM 11950895 ER PT J AU Sundberg, C Kowanetz, M Brown, LF Detmar, M Dvorak, HF AF Sundberg, C Kowanetz, M Brown, LF Detmar, M Dvorak, HF TI Stable expression of angiopoietin-1 and other markers by cultured pericytes: Phenotypic similarities to a subpopulation of cells in maturing vessels during later stages of angiogenesis in vivo SO LABORATORY INVESTIGATION LA English DT Article ID RECEPTOR TYROSINE KINASES; ENDOTHELIAL GROWTH-FACTOR; COLLAGEN-PRODUCING CELLS; SMOOTH-MUSCLE CELLS; MICROVASCULAR PERICYTES; MONOCLONAL-ANTIBODY; BETA-RECEPTORS; COLORECTAL ADENOCARCINOMA; EXTRACELLULAR-MATRIX; VASCULAR DEVELOPMENT AB Pericytes have been difficult cells to study because they do not maintain their characteristic phenotype in vitro, and they begin to express fibroblast markers after only a few days in culture. We now report methods for the isolation, purification, culture, and repurification of human dermal pericytes from mixed cell populations using an immunoaffinity-magnetic bead approach coupled with the 3G5 IgM monoclonal antibody that is specific for a pericyte surface ganglioside. These purified cells could be expanded in culture, and they maintained their pericyte phenotype for up to 8 days. In addition, they strongly expressed angiopoietin-1 (Ang-1) but not angiopoietin-2, Tie-1, or Tie-2; in contrast, dermal microvascular endothelial cells exhibited a reciprocal expression pattern. These findings are important because the close proximity of endothelial cells and pericytes has often made it difficult to determine with certainty the specific cell type(s) that expressed each of these proteins in situ. Extending our in vitro findings to two models of angiogenesis in vivo, we demonstrated a subpopulation of Ang-1-expressing cells that appeared in maturing microvessels during later stages of cutaneous wound healing and vascular permeability factor/vascular endothelial growth factor-induced angiogenesis. Our results provide strong evidence that Ang-1 is expressed by pericytes in vitro and in vivo and that the role proposed for Ang-1 in vessel maturation in development can be extended to vessel maturation after angiogenesis in adult tissues. C1 Uppsala Univ, Dept Med Biochem & Microbiol, SE-75123 Uppsala, Sweden. Uppsala Univ, Biomed Ctr, SE-75123 Uppsala, Sweden. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Med Sch, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA USA. RP Sundberg, C (reprint author), Uppsala Univ, Dept Med Biochem & Microbiol, BMC Box 575, SE-75123 Uppsala, Sweden. FU NCI NIH HHS [CA 86410, CA-50453, CA69184]; NHLBI NIH HHS [HL-59316] NR 63 TC 134 Z9 141 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD APR PY 2002 VL 82 IS 4 BP 387 EP 401 PG 15 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 547UY UT WOS:000175351800003 PM 11950897 ER PT J AU Deguchi, K Gilliland, DG AF Deguchi, K Gilliland, DG TI Cooperativity between mutations in tyrosine kinases and in hematopoietic transcription factors in AML SO LEUKEMIA LA English DT Article; Proceedings Paper CT Acute Leukemia Forum CY APR 20, 2001 CL SAN FRANCISCO, CALIFORNIA ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; 11Q23 CHROMOSOMAL TRANSLOCATIONS; CHRONIC MYELOMONOCYTIC LEUKEMIA; TEL-AML1 GENE FUSION; BETA-R FUSION; MYELODYSPLASTIC SYNDROME C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Harvard Univ, Sch Med, 4 Blackfan Circle,Room 418, Boston, MA 02115 USA. NR 70 TC 62 Z9 69 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2002 VL 16 IS 4 BP 740 EP 744 DI 10.1038/sj/leu/2402500 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 545AA UT WOS:000175193000041 PM 11960359 ER PT J AU Lin, TS Howard, OM Neuberg, DS Kim, HH Shipp, MA AF Lin, TS Howard, OM Neuberg, DS Kim, HH Shipp, MA TI Seventy-two hour continuous infusion flavopiridol in relapsed and refractory mantle cell lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Article DE flavopiridol; mantel cell lymphoma; chemotherapy; clinical trial ID DEPENDENT KINASE INHIBITOR; INTERMEDIATE LYMPHOCYTIC LYMPHOMA; BREAST-CARCINOMA CELLS; PHASE-I TRIAL; 7-HYDROXYSTAUROSPORINE UCN-01; PROGNOSTIC FACTORS; TRANSPLANTATION; ARREST; CANCER; THERAPY AB The cell cycle regulatory protein cyclin D1, which is over-expressed in 95-100% of mantle cell lymphomas (MCL), is a potential therapeutic target. Flavopiridol inhibits the cyclin-dependent kinase (CDK)4-cyclin D1 complex and induces apoptosis in lymphoma cell lines. Previous phase I clinical studies had demonstrated that this drug could be safely administered in humans, prompting further evaluation of flavopiridol as a single agent in MCL. Ten patients with relapsed or refractory MCL, who had received one prior chemotherapy regimen, were treated with flavopiridol 50 mg/m(2)/day given as a 72 h continuous intravenous infusion every 14 days. Treatment was well tolerated, and only one patient developed grade III-IV non-hematologic toxicity. However, there were no clinical responses; despite therapy, three patients maintained stable disease, and seven patients demonstrated progressive disease within two months. In relapsed and refractory MCL, flavopiridol is ineffective as a single agent given by 72 h continuous infusion at 50 mg/m(2)/day. Recent in vitro studies using human plasma suggest that higher plasma drug levels may be necessary to achieve clinical efficacy. In vitro studies of flavopiridol indicate that the agent is synergistic with DNA-damaging compounds. Further investigation into flavopiridol as a clinical agent should focus on alternative dosing schedules and the compound's potential use in combination chemotherapeutic regimens. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Shipp, MA (reprint author), Ohio State Univ, Div Hematol Oncol, 320 W 10th Ave, Columbus, OH 43210 USA. NR 41 TC 52 Z9 53 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD APR PY 2002 VL 43 IS 4 BP 793 EP 797 DI 10.1080/10428190290016908 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 560ZJ UT WOS:000176111000014 PM 12153166 ER PT J AU Stone, ME AF Stone, ME TI The fifth vital sign: What we need to know about pain. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 1 Z9 1 U1 0 U2 1 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD APR 1 PY 2002 VL 127 IS 6 BP 131 EP 131 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 534ZJ UT WOS:000174619400178 ER PT J AU Biggins, SW Beldecos, A Rabkin, JM Rosen, HR AF Biggins, SW Beldecos, A Rabkin, JM Rosen, HR TI Retransplantation for hepatic allograft failure: Prognostic modeling and ethical considerations SO LIVER TRANSPLANTATION LA English DT Review ID ORTHOTOPIC LIVER-TRANSPLANTATION; CIRRHOSIS; RECURRENCE; DISEASE; SURVIVAL; EXPERIENCE; ALLOCATION; REJECTION; INFECTION; EFFICACY AB Retransplantation already accounts for 10% of all liver transplants performed, and this percentage is likely to increase as patients live long enough to develop graft failure from recurrent disease. Overall, retransplantation is associated with significantly diminished survival and increased costs. This review summarizes the current causes of graft failure after primary liver transplant, prognostic models that can identify the subset of patients for retransplantation with outcomes comparable to primary transplantation, and ethical considerations in this setting, i.e., outcomes-based versus urgency-based approaches. C1 Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Surg, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Rosen, HR (reprint author), OHSU, Portland VA Med Ctr, Div Gastroenterol Hepatol, POB 1034 P3-GI 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. NR 57 TC 67 Z9 68 U1 0 U2 5 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 APR PY 2002 VL 8 IS 4 BP 313 EP 322 DI 10.1053/jlts.2002.31746 PG 10 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 542MR UT WOS:000175048100001 PM 11965573 ER PT J AU Reese, TG Feinberg, DA Dou, JG Wedeen, VJ AF Reese, TG Feinberg, DA Dou, JG Wedeen, VJ TI Phase contrast MRI of myocardial 3D strain by encoding contiguous slices in a single shot SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article; Proceedings Paper CT 8th Annual Meeting of the International-Society-for-Magnetic-Resonance-in-Medicine CY APR 01-07, 2000 CL DENVER, COLORADO SP Int Soc Magnet Resonance Med DE MRI; phase contrast; 3D; EPI; myocardium; strain ID MAGNETIC-RESONANCE; IN-VIVO; LEFT-VENTRICLE; GRADIENT-ECHO; BRAIN MOTION; DIFFUSION AB Quantitative measurements of inherently three-dimensional (3D) cardiac strain and strain rate require 3D data; MRI provides uniquely high sensitivity to material strain by combining phase contrast with single-shot acquisition methods, such as echoplanar imaging (EPI). Previous MRI methods applied to 3D strain used multiple two-dimensional (2D) acquisitions and suffered loss of sensitivity due to magnification within the strain calculation of physiologic noise related to cardiac beat-to-beat variability. In the present work, each single-shot acquisition generates 3D image data by acquiring two contiguous 2D Fourier transform (FT) images in a single echo train of an EPI readout. Although strain encoding divides across multiple EPI shots, each strain component is computed only within single-shot data, avoiding noise magnification. Strain tensor maps are displayed using iconic 3D graphics or a simple color code of tensor shape. In a deforming gel phantom, gradient-recalled echo (GRE) MRI movies of 3D strain rates match expected strain fields. In normal human subjects, 3D strain rate tensor movies of heart and brain comprising seven slices in each of seven cardiac phases were completed in 56 heartbeats. Stimulated echo (STE) MRI of net systolic 3D strain was also demonstrated. Two-slices-in-one-shot spatial encoding permits a complete quantitative survey of ventricular 3D strain in under a minute, with routine patient supervision and turnkey image processing. (C) 2002 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Charlestown, MA 02129 USA. Adv MRI Technol, Sebastopol, CA USA. Washington Univ, Dept Radiol, St Louis, MO 63130 USA. MIT, Dept Nucl Engn, Cambridge, MA 02139 USA. RP Reese, TG (reprint author), Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Bldg 149,13th St,MS 2301, Charlestown, MA 02129 USA. EM reese@nmr.mgh.harvard.edu FU NCRR NIH HHS [R01 RR13618]; NHLBI NIH HHS [R01 HL5627-01A1] NR 37 TC 22 Z9 22 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD APR PY 2002 VL 47 IS 4 BP 665 EP 676 DI 10.1002/mrm.10111 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 534NP UT WOS:000174592700007 PM 11948727 ER PT J AU Moore, A Sun, PZ Cory, D Hogemann, D Weissleder, R Lipes, MA AF Moore, A Sun, PZ Cory, D Hogemann, D Weissleder, R Lipes, MA TI MRI of insulitis in autoimmune diabetes SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; diabetes; inflammation; lymphocyte; contrast agents ID MAGNETIC-RESONANCE MICROSCOPY; ANTIBODY-POSITIVE RELATIVES; IN-VIVO DETECTION; SCID MOUSE; MELLITUS; INTERLEUKIN-2; CELLS; LYMPHOCYTES; PREDICTION; PANCREAS AB Development of imaging techniques that would allow the mapping of immune cells in vivo could greatly aid our understanding of a number of inflammatory and autoimmune diseases. The current study focused on imaging of autoimmune destruction of the insulin-producing pancreatic beta-cells by cytotoxic lymphocytes, the cause of insulin-dependent diabetes mellitus (IDDM; Type 1 diabetes). Using high-resolution MR microscopy and a conventional clinical MR imaging system, it was possible to visualize the infiltration of immune cells in the diabetic mouse pancreas. Mouse lymphocytes were visualized by magnetically labeling them with recently developed magnetic nanoparticles (CLIO-Tat). The results from this study could potentially lead to detection of immune infiltration during diabetes formation in vivo, which would be one of the earliest parameters of disease development. (C) 2002 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MIT, Dept Nucl Engn, Boston, MA USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Moore, A (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Rm 5419,Bldg 149,13th St, Charlestown, MA 02129 USA. NR 34 TC 77 Z9 82 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD APR PY 2002 VL 47 IS 4 BP 751 EP 758 DI 10.1002/mrm.10110 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 534NP UT WOS:000174592700017 PM 11948737 ER PT J AU Nelson, K Garcia, RE Brown, J Mangione, CM Louis, TA Keeler, E Cretin, S AF Nelson, K Garcia, RE Brown, J Mangione, CM Louis, TA Keeler, E Cretin, S TI Do patient consent procedures affect participation rates in health services research? SO MEDICAL CARE LA English DT Article DE health services research; participation rates; response rates; subject recruitment ID MEDICAL-RECORDS RESEARCH; CONDUCT AB BACKGROUND. Few studies have examined the effects of Institutional Review Board (IRB) requirements to contact potential research participants. OBJECTIVE. To examine the association between requirements to contact potential research subjects and participation rates in a multisite health services research study. RESEARCH DESIGN, SUBJECTS. Prospective observational study of survey participation by 2673 individuals with diabetes and 1974 individuals with congestive heart failure treated at 15 clinical sites in the United States that had implemented a quality improvement intervention. MAIN OUTCOME MEASURES. Telephone survey response rates. RESULTS. Of 15 IRBs, seven required sites to obtain authorization from participants to release contact information to the study team. Five required oral and two required written advance permission. The response rate was 58% (913/1571) at sites where no advance permission was required, 39% (989/2530) from sites that required oral advance permission and 27% (145/546, P <0.001) at sites requiring written advance permission. Although 85% of eligible participants contacted directly by the study team consented to complete the survey, only 43% of individuals at sites requiring written advance permission allowed the release of contact information to the study team. CONCLUSIONS. Many potential participants did not grant advance permission to be contacted by the study team. Requiring advance permission reduced participation rates, especially at sites requiring written authorization. Key words: Health services research; participation rates; response rates; subject recruitment. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RAND Hlth, Santa Monica, CA USA. Univ Calif Los Angeles, Sch Med, Div Gen Internal Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Hlth Serv Res, Los Angeles, CA 90024 USA. RAND Corp, Arlington, VA USA. RP Nelson, K (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-111-GIMC, Seattle, WA 98108 USA. NR 17 TC 41 Z9 41 U1 0 U2 4 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 APR PY 2002 VL 40 IS 4 BP 283 EP 288 DI 10.1097/00005650-200204000-00004 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 536PX UT WOS:000174712000004 PM 12021684 ER PT J AU Goldrath, AW AF Goldrath, AW TI Maintaining the status quo: T-cell homeostasis SO MICROBES AND INFECTION LA English DT Article DE survival; homeostasis; proliferation; T cell ID MHC CLASS-II; ATHYMIC NUDE RATS; LYMPHOCYTES-T; IN-VIVO; SURVIVAL; NAIVE; MEMORY; PROLIFERATION; MATURE; EXPANSION AB Lymphocyte numbers and subset composition are maintained at relatively constant levels throughout adulthood. Fluctuations in cell numbers due to infection, loss of cells, or other influences are smoothed out by unknown mechanisms that return the system to homeostasis. Regulation of lymphocyte numbers could be controlled at several points: rate of production, alteration in life span by diminution or enhancement of survival, or by division of cells within the compartment. Cell numbers within the immune system appear to be controlled by homeostatic mechanisms that influence each of these points. This discussion will focus on the regulation of peripheral cell numbers by the antigen-independent proliferation of T cells, which has recently been demonstrated to contribute to the maintenance and recovery of lymphocyte homeostasis. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Immunol, Boston, MA 02115 USA. RP Goldrath, AW (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Immunol, 1 Joslin Pl, Boston, MA 02115 USA. NR 56 TC 40 Z9 40 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD APR PY 2002 VL 4 IS 5 BP 539 EP 545 AR PII S1286-4579(02)01570-8 DI 10.1016/S1286-4579(02)01570-8 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 550GK UT WOS:000175495100003 PM 11959509 ER PT J AU Moy, TI Boettner, D Rhodes, JC Silver, PA Askew, DS AF Moy, TI Boettner, D Rhodes, JC Silver, PA Askew, DS TI Identification of a role for Saccharomyces cerevisiae Cgr1p in pre-rRNA processing and 60S ribosome subunit synthesis SO MICROBIOLOGY-SGM LA English DT Article DE yeast; nucleolus; ribosome biogenesis ID MESSENGER-RNA TRANSPORT; YEAST; PROTEIN; NUCLEOLUS; GENE; BIOGENESIS; LOCALIZATION; FIBRILLARIN; COMPLEX; ACCUMULATION AB Saccharomyces cerevisiae CGR1 encodes a conserved fungal protein that localizes to the nucleolus. To determine if this localization reflects a role for Cgr1p in ribosome biogenesis two yeast cgr1 mutants were examined for defects in ribosome synthesis: a conditional depletion strain in which CGR1 is under the control of a tetracycline-repressible promoter and a mutant strain in which a C-terminal truncated Cgr1p is expressed. Both strains had impaired growth rates and were hypersensitive to the aminoglycosides paromomycin and hygromycin. Polysome analyses of the mutants revealed increased levels of free 40S subunits relative to 60S subunits, a decrease in 80S monosomes and accumulation of half-mer polysomes. Pulse-chase labelling demonstrated that pre-rRNA processing was defective in the mutants, resulting in accumulation of the 35S, 27S and 7S pre-rRNAs and delayed production of the mature 25S and 5.8S rRNAs. The synthesis of the 18S and 5S rRNAs was unaffected. Loss of Cgr1 function also caused a partial delocalization of the 5'-ITS1 RNA and the nucleolar protein Nop1p into the nucleoplasm, suggesting that Cgr1p contributes to compartmentalization of nucleolar constituents. Together these findings establish a role for Cgr1p in ribosome biogenesis. C1 Univ Cincinnati, Coll Med, Dept Pathol & Lab Med, Cincinnati, OH 45267 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Univ Cincinnati, Coll Med, Dept Pathol & Lab Med, Cincinnati, OH 45267 USA. EM David.Askew@uc.edu RI Boettner, Douglas/I-3218-2012; OI Boettner, Douglas/0000-0002-0591-443X NR 59 TC 15 Z9 17 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD APR PY 2002 VL 148 BP 1081 EP 1090 PN 4 PG 10 WC Microbiology SC Microbiology GA 543CV UT WOS:000175084400017 PM 11932453 ER PT J AU Eppihimer, MJ Gunn, J Freeman, GJ Greenfield, EA Chernova, T Erickson, J Leonard, JP AF Eppihimer, MJ Gunn, J Freeman, GJ Greenfield, EA Chernova, T Erickson, J Leonard, JP TI Expression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells SO MICROCIRCULATION LA English DT Article DE endothelial cell; costimulation; T-lymphocyte; cellular activation ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CD4(+) T-CELLS; INTERFERON-GAMMA; IFN-GAMMA; IN-VIVO; CYTOKINE PRODUCTION; MICE; ADHESION; ANTIGEN; ACTIVATION AB Objective: To evaluate the expression and regulation of a novel B7-like protein, PD-L1. the ligand for the immunoinhibitory receptor PD-1 expressed on activated T-cells. on microvascular endothelial cells (ECs) Methods: PD-L1 expression on ECs in vitro and in vivo was quantified by using a dual radiolabeled antibody technique after treatment with interferons (IFN) and IL-12, respectively. Changes in the level of PD-L1 mRNA were determined by using RT-PCR. Results: PD-L1 was observed to be present on ECs under basal conditions. Treatment of ECs with IFN-alpha, -beta and -gamma but not LPS,was observed to induce elevations in the mRNA and surface expression of PD-L1 on ECs. By using a dual radiolabeled monoclonal antibody (mAb) technique., PD-L1 expression in various tissues of control and IL-12 challenged wild-type and IFN-gamma-deficient mice was measured. A significant increase in PD-L1 expression was observed in tissues at 24 hours after IL-12-challenge, with peak levels of PD-L1 occurring 72 hours aft or IL-12 challenge. IL-12 was not effective at inducing PD-L1 expression in tissues of IFN-gamma-deficient mice. Conclusions: These data show the expression of a novel B7-like molecule on murine ECs that is mediated by IFN-alpha -beta, and -gamma, and suggest a potential pathway by which ECs may modulate T-cell function. C1 Wyeth Genet Inst Inc, Discovery Res, Resp Dis, Andover, MA 01810 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Eppihimer, MJ (reprint author), Wyeth Genet Inst Inc, Discovery Res, Resp Dis, 1 Burtt Rd, Andover, MA 01810 USA. FU NCI NIH HHS [CA84500, R01 CA084500]; NIAID NIH HHS [AI39671, AI41584, P01 AI039671] NR 36 TC 132 Z9 146 U1 1 U2 18 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1073-9688 J9 MICROCIRCULATION JI Microcirculation PD APR PY 2002 VL 9 IS 2 BP 133 EP 145 DI 10.1038/sj/mn/7800123 PG 13 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 535HC UT WOS:000174638300006 PM 11932780 ER PT J AU Simon, M Feliers, D Arar, M Bhandari, B Abboud, HE AF Simon, M Feliers, D Arar, M Bhandari, B Abboud, HE TI Cloning of the 5 '-flanking region of the murine bone morphogenetic protein-7 gene SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE BMP-7; bone morphogenetic protein; kidney development; transcriptional regulation; promoter activity ID GROWTH-FACTOR-BETA; KINASE-C; DIFFERENTIAL EXPRESSION; METANEPHRIC MESENCHYME; EMBRYONIC-DEVELOPMENT; MOLECULAR-CLONING; MESSENGER-RNA; KIDNEY; CELLS; MOUSE AB BMP-7, a member of the bone morphogenetic protein subfamily of the TGFbeta-superfamily is highly expressed in the murine kidney. BMP-7 is involved in fetal nephron development and mesenchymal to epithelial cell differentiation. Constitutive BMP-7 expression is found in tubular and glomerular epithelial cells of the adult kidney. BMP-7 may play a role in physiology and pathophysiology of the adult kidney since BMP-7 gene expression in acute renal ischemia is diminished and injection of recombinant BMP-7 into rats with ischemic acute renal failure preserves renal function. In order to investigate the transcriptional regulation of BMP-7, this study was undertaken to clone and characterize the promoter of the murine BMP-7 gene. A 1394 bp sequence of the 5'-flanking region of the BMP-7 gene was isolated and subcloned. No TATA and CAAT box consensus motifs could be identified as shown for promoters of other BMPs. Using in vitro transfection assays, the 5'-flanking region revealed moderate to strong basal promoter activity. PMA increased basal BMP-7 promoter activity. Thus BMP-7 gene transcription might involve at least in part a PKC-dependent pathway. The cloning of a 5'-flanking region of the BMP-7 gene should provide a useful tool for future studies on the transcriptional regulation of BMP-7 gene expression. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Pediat Nephrol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. RP Simon, M (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIDDK NIH HHS [DK-33665, DK-43988] NR 42 TC 3 Z9 7 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD APR PY 2002 VL 233 IS 1-2 BP 31 EP 37 DI 10.1023/A:1015546615027 PG 7 WC Cell Biology SC Cell Biology GA 552TC UT WOS:000175635300005 PM 12083377 ER PT J AU Hahn, WC Dessain, SK Brooks, MW King, JE Elenbaas, B Sabatini, DM DeCaprio, JA Weinberg, RA AF Hahn, WC Dessain, SK Brooks, MW King, JE Elenbaas, B Sabatini, DM DeCaprio, JA Weinberg, RA TI Enumeration of the simian virus 40 early region elements necessary for human cell transformation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LARGE-T-ANTIGEN; SIMIAN-VIRUS-40 LARGE-T; LARGE TUMOR-ANTIGEN; SV40 LARGE-T; PROTEIN PHOSPHATASE 2A; MOUSE EMBRYO FIBROBLASTS; AMINO-TERMINAL DOMAIN; INDUCED GROWTH ARREST; PRB-RELATED PROTEINS; TELOMERASE ACTIVITY AB While it is clear that cancer arises from the accumulation of genetic mutations that endow the malignant cell with the properties of uncontrolled growth and proliferation, the precise combinations of mutations that program human tumor cell growth remain unknown. The study of the transforming proteins derived from DNA tumor viruses in experimental models of transformation has provided fundamental insights into the process of cell transformation. We recently reported that coexpression of the simian virus 40 (SV40) early region (ER), the gene encoding the telomerase catalytic subunit (hTERT), and an oncogenic allele of the H-ras gene in normal human fibroblast, kidney epithelial, and mammary epithelial cells converted these cells to a tumorigenic state. Here we show that the SV40 ER contributes to tumorigenic transformation in the presence of hTERT and oncogenic H-ras by perturbing three intracellular pathways through the actions of the SV40 large T antigen (LT) and the SV40 small t antigen (ST). LT simultaneously disables the retinoblastoma (pRB) and p53 tumor suppressor pathways; however, complete transformation of human cells requires the additional perturbation of protein phosphatase 2A by ST. Expression of ST in this setting stimulates cell proliferation, permits anchorage-independent growth, and confers increased resistance to nutrient deprivation. Taken together, these observations define the elements of the SV40 ER required for the transformation of human cells and begin to delineate a set of intracellular pathways whose disruption, in aggregate, appears to be necessary to generate tumorigenic human cells. C1 Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Weinberg, RA (reprint author), Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. FU NCI NIH HHS [K01 CA094223, K01 CA94223, P01 CA050661, P01 CA50661, R01 CA063113, R01 CA078461, R01 CA63113, R01 CA78461]; NHLBI NIH HHS [K08 HL004463, K08 HL04463] NR 95 TC 389 Z9 403 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2002 VL 22 IS 7 BP 2111 EP 2123 DI 10.1128/MCB.22.7.2111-2123.2002 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 531GK UT WOS:000174407500015 PM 11884599 ER PT J AU Intano, GW McMahan, CA McCarrey, JR Walter, RB McKenna, AE Matsumoto, Y MacInnes, MA Chen, DJ Walter, CA AF Intano, GW McMahan, CA McCarrey, JR Walter, RB McKenna, AE Matsumoto, Y MacInnes, MA Chen, DJ Walter, CA TI Base excision repair is limited by different proteins in male germ cell nuclear extracts prepared from young and old mice SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-POLYMERASE-BETA; LIGASE-III; SPERMATOGENIC CELLS; MORPHOLOGICAL CHARACTERIZATION; TRANSLATIONAL REGULATION; MEIOTIC RECOMBINATION; MOUSE SPERMATOGENESIS; SPONTANEOUS MUTATION; MOLECULAR-CLONING; MAMMALIAN TESTIS AB The combined observations of elevated DNA repair gene expression, high uracil-DNA glycosylase-initiated base excision repair, and a low spontaneous mutant frequency for a lacI transgene in spermatogenic cells from young mice suggest that base excision repair activity is high in spermatogenic cell types. Notably, the spontaneous mutant frequency of the lacI transgene is greater in spermatogenic cells obtained from old mice, suggesting that germ line DNA repair activity may decline with age. A paternal age effect in spermatogenic cells is recognized for the human population as well. To determine if male germ cell base excision repair activity changes with age, uracil-DNA glycosylase-initiated base excision repair activity was measured in mixed germ cell (i.e., all spermatogenic cell types in adult testis) nuclear extracts prepared from young, middle-aged, and old mice. Base excision repair activity was also assessed in nuclear extracts from premeiotic, meiotic, and postmeiotic spermatogenic cell types obtained from young mice. Mixed germ cell nuclear extracts exhibited an age-related decrease in base excision repair activity that was restored by addition of apurinic/apyrimidinic (AP) endonuclease. Uracil-DNA glycosylase and DNA ligase were determined to be limiting in mixed germ cell nuclear extracts prepared from young animals. Base excision repair activity was only modestly elevated in pachytene spermatocytes and round spermatids relative to other spermatogenic cells. Thus, germ line short-patch base excision repair activity appears to be relatively constant throughout spermatogenesis in young animals, limited by uracil-DNA glycosylase and DNA ligase in young animals, and limited by AP endonuclease in old animals. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. SW Texas State Univ, Dept Chem & Biochem, San Marcos, TX 78666 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Los Alamos Natl Lab, Biosci Div, Los Alamos, NM 87545 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. RP Walter, CA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, Mail Code 7762,7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NCI NIH HHS [CA75137, P01 CA075137, R37 CA050519, CA50519, R01 CA050519]; NIA NIH HHS [AG14674, AG00205, T32 AG000205, AG13560]; NIEHS NIH HHS [ESO9136] NR 66 TC 41 Z9 42 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2002 VL 22 IS 7 BP 2410 EP 2418 DI 10.1128/MCB.22.7.2410-2418.2002 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 531GK UT WOS:000174407500039 PM 11884623 ER PT J AU Tsytsykova, AV Goldfeld, AE AF Tsytsykova, AV Goldfeld, AE TI Inducer-specific enhanceosome formation controls tumor necrosis factor alpha gene expression in T lymphocytes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CREB-BINDING-PROTEIN; AP-1 TRANSCRIPTION FACTORS; NUCLEAR FACTOR; IN-VIVO; PROMOTER; CELLS; SP1; COMPLEX; VIRUS; P300 AB We present evidence that the inducer-specific regulation of the human tumor necrosis factor alpha (TNF-alpha) gene in T cells involves the assembly of distinct higher-order transcription enhancer complexes (enhanceosomes), which is dependent upon inducer-specific helical phasing relationships between transcription factor binding sites. While ATF-2, c-Jun, and the coactivator proteins CBP/p300 play a central role in TNF-alpha gene activation stimulated by virus infection or intracellular calcium flux, different sets of activators including NFATp, Sp1, and Ets/Elk are recruited to a shared set of transcription factor binding sites depending upon the particular stimulus. Thus, these studies demonstrate that the inducer-specific assembly of unique enhanceosomes is a general mechanism by which a single gene is controlled in response to different extracellular stimuli. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Goldfeld, AE (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM-56492, R01 GM056492] NR 37 TC 56 Z9 56 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2002 VL 22 IS 8 BP 2620 EP 2631 DI 10.1128/MCB.22.8.2620-2631.2002 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 535FZ UT WOS:000174635700019 PM 11909956 ER PT J AU Cloud, JE Rogers, C Reza, TL Ziebold, U Stone, JR Picard, MH Caron, AM Bronson, RT Lees, JA AF Cloud, JE Rogers, C Reza, TL Ziebold, U Stone, JR Picard, MH Caron, AM Bronson, RT Lees, JA TI Mutant mouse models reveal the relative roles of E2F1 and E2F3 in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID S-PHASE ENTRY; RETINOBLASTOMA SUSCEPTIBILITY GENE; THYMIC NEGATIVE SELECTION; TRANSCRIPTION FACTORS; CELL-CYCLE; FAMILY MEMBERS; DEREGULATED EXPRESSION; HISTONE DEACETYLASE; COMPLEX-FORMATION; PROTEIN AB The E2171, -2, and -3 transcription factors are key downstream targets of the retinoblastoma protein (pRB) tumor suppressor that drive expression of proliferation-associated genes. Here we use mutant mouse strains to investigate E2F3's role in vivo. We show that E2F3 is essential for embryonic viability in the pure 129/Sv background but the presence of C57BL/6 alleles yields some adult survivors. Although growth retarded, surviving E2f3(-/-) animals are initially healthy. However, they die prematurely, exhibiting no obvious tumor phenotype but with the typical signs of congestive heart failure. The defects are completely distinct from those arising in E2f1 mutant mice (S. J. Field et al., Cell 85:549-561; 1996; L. Yamasaki et al., Cell 85:537-548,1996), supporting the prevailing view that these E2Fs must have some unique biological functions in vivo. To test this model, we examined the phenotypes of E2f1 E2f3 compound mutant mice. Almost all of the developmental and age-related defects arising in the individual Ell or E2f3 mice were exacerbated by the mutation of the other Elf. Thus, E2F1 and E2F3 appear to play critical, overlapping roles in the development and maintenance of a variety of tissues. Importantly, this study did identify one major difference in the properties of E2F1 and E2F3: either alone or in combination with E2F1 loss, E2f3 mutation did not increase the incidence of tumor formation. These data strongly suggest that tumor suppression is a specific property of E2F1 and not E2F3. C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Tufts Univ, Sch Vet Med, Dept Pathol, Boston, MA 02111 USA. RP Lees, JA (reprint author), MIT, Ctr Canc Res, Cambridge, MA 02139 USA. RI King, Jennifer/F-8318-2010; Ziebold, Ulrike/N-4487-2013; OI Picard, Michael/0000-0002-9264-3243 FU NCI NIH HHS [P01 CA042063, P01-CA42063] NR 60 TC 64 Z9 66 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2002 VL 22 IS 8 BP 2663 EP 2672 DI 10.1128/MCB.22.8.2663-2672.2002 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 535FZ UT WOS:000174635700023 PM 11909960 ER PT J AU Alland, L David, G Hong, SL Potes, J Muhle, R Lee, HC Hou, H Chen, K DePinho, RA AF Alland, L David, G Hong, SL Potes, J Muhle, R Lee, HC Hou, H Chen, K DePinho, RA TI Identification of mammalian Sds3 as an integral component of the Sin3/histone deacetylase corepressor complex SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; HISTONE DEACETYLASE; TRANSCRIPTIONAL REPRESSION; PROSTATE-CANCER; SACCHAROMYCES-CEREVISIAE; N-COR; YEAST; REGULATORS; DOMAIN; SIN3 AB Silencing of gene transcription involves local chromatin modification achieved through the local recruitment of large multiprotein complexes containing histone deacetylase (HDAC) activity. The mammalian corepressors mSin3A and mSin3B have been shown to play a key role in this process by tethering HDACs 1 and 2 to promoter-bound transcription factors. Similar mechanisms appear to be operative in yeast, in which epistasis experiments have established that the mSin3 and HDAC orthologs (SIN3 and RPD3), along with a novel protein, SDS3, function in the same repressor pathway. Here, we report the identification of a component of the mSin3-HDAC complex that bears homology to yeast SDS3, physically associates with mSin3 proteins in vivo, represses transcription in a manner that is partially dependent on HDAC activity, and enables HDAC1 catalytic activity in vivo. That key physical and functional properties are also shared by yeast SDS3 underscores the central role of the Sin3-HDAC-Sds3 complex in eukaryotic cell biology, and the discovery of mSds3 in mammalian cells provides a new avenue for modulating the activity of this complex in human disease. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [K11CA68266] NR 42 TC 72 Z9 79 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2002 VL 22 IS 8 BP 2743 EP 2750 DI 10.1128/MCB.22.8.2743-2750.2002 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 535FZ UT WOS:000174635700029 PM 11909966 ER PT J AU Fan, ZS Beresford, PJ Zhang, D Lieberman, J AF Fan, ZS Beresford, PJ Zhang, D Lieberman, J TI HMG2 interacts with the nucleosome assembly protein SET and is a target of the cytotoxic T-lymphocyte protease granzyme A SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NONHISTONE CHROMOSOMAL-PROTEINS; HUMAN APURINIC ENDONUCLEASE; ACTIVATING FACTOR-I; DNA-BINDING; NUCLEAR PHOSPHOPROTEIN; MYELOID LEUKEMOGENESIS; MEDIATED APOPTOSIS; REPLICATION FACTOR; PUTATIVE ONCOGENE; HISTONE-BINDING AB The cytotoxic T-lymphocyte protease granzyme A induces caspase-independent cell death in which DNA single-stranded nicking is observed instead of oligonucleosomal fragmentation. A 270- to 420-kDa endoplasmic reticulum-associated complex (SET complex) containing the nucleosome assembly protein SET, the tumor suppressor pp32, and the base excision repair enzyme APE can induce single-stranded DNA damage in isolated nuclei in a granzyme A-dependent manner. The normal functions of the SET complex are unknown, but the functions of its components suggest that it is involved in activating transcription and DNA repair. We now find that the SET complex contains DNA binding and bending activities mediated by the chromatin-associated protein HMG2. HMG2 facilitates assembly of nucleoprotein higher-order structures by bending and looping DNA or by stabilizing underwound DNA. HMG2 is in the SET complex and coprecipitates with SET. By confocal microscopy, it is observed that cytoplasmic HMG2 colocalizes with SET in association with the endoplasmic reticulum, but most nuclear HMG2 is unassociated with SET. This physical association suggests that HMG2 may facilitate the nucleosome assembly, transcriptional activation, and DNA repair functions of SET and/or APE. HMG2, like SET and APE, is a physiologically relevant granzyme A substrate in targeted cells. HMG1, however, is not a substrate. Granzyme A cleavage after Lys65 in the midst of HMG box A destroys HMG2-mediated DNA binding and bending functions. Granzyme A cleavage and functional disruption of key nuclear substrates, including HMG2, SET, APE, lamins, and histones, are likely to cripple the cellular repair response to promote cell death in this novel caspase-independent death pathway. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI-45587, R01 AI045587, R56 AI045587] NR 68 TC 92 Z9 95 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 APR PY 2002 VL 22 IS 8 BP 2810 EP 2820 DI 10.1128/MCB.22.8.2810-2820.2002 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 535FZ UT WOS:000174635700036 PM 11909973 ER PT J AU Lilliehook, C Chan, S Choi, EK Zaidi, NF Wasco, W Mattson, MP Buxbaum, JD AF Lilliehook, C Chan, S Choi, EK Zaidi, NF Wasco, W Mattson, MP Buxbaum, JD TI Calsenilin enhances apoptosis by altering endoplasmic reticulum calcium signaling SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID AMYLOID BETA-PEPTIDE; NF-KAPPA-B; ALZHEIMERS-DISEASE; MUTANT PRESENILIN-1; NEURONAL APOPTOSIS; CA2+ CONCENTRATION; BINDING PROTEIN; NERVOUS-SYSTEM; CALPAIN; CELLS AB Calsenilin (also called DREAM and KChIP3), a member of the neuronal calcium sensor family, was isolated in a yeast two-hybrid screen using an apoptotic domain of presenilin 2 as bait. Calsenilin is a cytoplasmic protein, but interacts with the COOH-termini of both presenilin I and presenilin 2 at the endoplasmic reticulum and the Golgi apparatus. In this study, we have investigated calsenilin's effect on apoptosis. In stable neuroglioma cell lines, we observed that calsenilin enhances apoptosis in response to serum withdrawal or thapsigargin. Consistent with these observations, caspase and apparently calpain activities were increased during apoptosis in calsenilin-overexpressing cells. Moreover, using calcium imaging we were able to show that cells treated with thapsigargin released more calcium from intracellular stores when calsenilin was overexpressed. Taken together, these data suggest that calsenilin causes cells to be more susceptible to apoptotic triggers, possibly by altering calcium dynamics. C1 Mt Sinai Med Ctr, Dept Psychiat, Lab Mol Neuropsychiat, New York, NY 10029 USA. Mt Sinai Med Ctr, Dept Neurobiol, New York, NY 10029 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Genet & Aging Unit, Charlestown, MA 02129 USA. NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. RP Buxbaum, JD (reprint author), Mt Sinai Med Ctr, Dept Psychiat, Lab Mol Neuropsychiat, Box 1230,1 Gustave L Levy Pl, New York, NY 10029 USA. EM buxbaj01@doc.mssm.edu RI Mattson, Mark/F-6038-2012; OI Buxbaum, Joseph/0000-0001-8898-8313 FU NIA NIH HHS [AG05138, AG15801] NR 46 TC 55 Z9 58 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD APR PY 2002 VL 19 IS 4 BP 552 EP 559 DI 10.1006/mcne.2001.1096 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 550GE UT WOS:000175494600007 PM 11988022 ER PT J AU Ntziachristos, V Bremer, C Graves, EE Ripoll, J Weissleder, R AF Ntziachristos, Vasilis Bremer, Christoph Graves, Edward E. Ripoll, Jorge Weissleder, Ralph TI In Vivo Tomographic Imaging of Near-Infrared Fluorescent Probes SO MOLECULAR IMAGING LA English DT Article AB Fluorescence imaging is increasingly used to probe protein function and gene expression in live animals. This technology could enhance the study of pathogenesis, drug development, and therapeutic intervention. In this article, we focus on three-dimensional fluorescence observations using fluorescence-mediated molecular tomography (FMT), a novel imaging technique that can resolve molecular function in deep tissues by reconstructing fluorescent probe distributions in vivo. We have compared FMT findings with conventional fluorescence reflectance imaging (FRI) to study protease function in nude mice with subsurface implanted tumors. This validation of FMT with FRI demonstrated the spatial congruence of fluorochrome activation as determined by the two techniques. C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Ntziachristos, Vasilis] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Ntziachristos, V (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149 13th St 5406, Charlestown, MA 02129 USA. EM vasilis@helix.mgh.harvard.edu RI Ripoll, Jorge/J-8134-2012 OI Ripoll, Jorge/0000-0001-8856-7738 FU Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation [DRG-1638]; NIH [P50 CA86355, P01-CA69246, R33 CA88365, R24 CA 92782] FX V.N. gratefully acknowledges support in part from fellowship DRG-1638 of the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation. This study was supported in part by NIH grants P50 CA86355, P01-CA69246, R33 CA88365, R24 CA 92782. The authors would like to thank D. Sergeyev for performing Western blotting. NR 33 TC 119 Z9 123 U1 1 U2 8 PU B C DECKER INC PI HAMILTON PA 69 JOHN STREET SOUTH, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA SN 1535-3508 EI 1536-0121 J9 MOL IMAGING JI Mol. Imaging PD APR PY 2002 VL 1 IS 2 BP 82 EP 88 DI 10.1162/153535002320162732 PG 7 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA V38HN UT WOS:000209334600003 PM 12920848 ER PT J AU Kircher, MF Josephson, L Weissleder, R AF Kircher, Moritz F. Josephson, Lee Weissleder, Ralph TI Ratio Imaging of Enzyme Activity Using Dual Wavelength Optical Reporters SO MOLECULAR IMAGING LA English DT Article DE Dual wavelength ratio imaging; optical imaging; near-infrared fluorescence; enzyme; iron oxide nanoparticles AB The design of near-infrared fluorescent (NIRF) probes that are activated by specific proteases has, for the first time, allowed enzyme activity to be imaged in vivo. In the current study, we report on a method of imaging enzyme activity using two fluorescent probes that, together, provide improved quantitation of enzymatic activity. The method employs two chemically similar probes that differ in their degradability by cathepsin B. One probe consists of the NIRF dye Cy5.5 attached to a particulate carrier, a crosslinked iron oxide nanoparticle (CLIO), through cathepsin B cleavable L-arginyl peptides. A second probe consists of Cy3.5 attached to a CLIO through proteolytically resistant D-arginyl peptides. Using mixtures of the two probes, we have shown that the ratio of Cy5.5 to Cy3.5 fluorescence can be used to determine levels of cathepsin B in the environment of nanoparticles with macrophages in suspension. After intravenous injection, tissue fluorescence from the nondegradable Cy3.5-D-arginyl probe reflected nanoparticle accumulation, while fluorescence of the Cy5.5-L-arginyl probe was dependent on both accumulation and activation by cathepsin B. Dual wavelength ratio imaging can be used for the quantitative imaging of a variety of enzymes in clinically important settings, while the magnetic properties of the probes allow their detection by MR imaging. C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Josephson, Lee] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149 13th St 5406, Charlestown, MA 02129 USA. EM josephso@helix.mgh.harvard.edu FU NIH [P50 CA86355, P01-CA69246, R33 CA88365, R24 CA 92782]; German Research Foundation (Deutsche Forschungsgemeinschaft) FX This work was supported by grants NIH P50 CA86355, P01-CA69246, R33 CA88365, and R24 CA 92782. The authors would like to thank U. Mahmood and V. Ntziachristos for helpful discussions and K. Marten, J. Allport-Anderson, A. Moore, and A. Petrovsky for technical assistance or advice.; M.F.K. was supported by a fellowship from the German Research Foundation (Deutsche Forschungsgemeinschaft). NR 21 TC 25 Z9 26 U1 3 U2 9 PU B C DECKER INC PI HAMILTON PA 69 JOHN STREET SOUTH, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA SN 1535-3508 EI 1536-0121 J9 MOL IMAGING JI Mol. Imaging PD APR PY 2002 VL 1 IS 2 BP 89 EP 95 DI 10.1162/153535002320162741 PG 7 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA V38HN UT WOS:000209334600004 PM 12920849 ER PT J AU Schellenberger, EA Bogdanov, A Hogemann, D Tait, J Weissleder, R Josephson, L AF Schellenberger, Eyk A. Bogdanov, Alexei, Jr. Hoegemann, Dagmar Tait, Jonathan Weissleder, Ralph Josephson, Lee TI Annexin V-CLIO: A Nanoparticle for Detecting Apoptosis by MRI SO MOLECULAR IMAGING LA English DT Article DE Annexin V; iron oxide; MRI; apoptosis; phosphatidylserine AB Annexin V, which recognizes the phosphatidylserine of apoptotic cells, was conjugated to crosslinked iron oxide (CLIO) nanoparticles, a functionalized superparamagnetic preparation developed for target-specific magnetic resonance imaging (MRI). The resulting nanoparticle had an average of 2.7 annexin V proteins linked per CLIO nanoparticle through disulfide bonds. Using camptothecin to induce apoptosis, a mixture of Jurkat T cells (69% healthy and 31% apoptotic) was incubated with annexin V-CLIO and was applied to magnetic columns. The result was an almost complete removal of the apoptotic cells (>99%). In a phantom MRI experiment, untreated control cells (12% apoptotic cells, 88% healthy cells) and camptothecin-treated cells (65% apoptotic cells, 35% healthy cells) were incubated with either annexin V-CLIO (1.0, 0.5, and 0.1 mu g Fe/mL) or with unlabeled CLIO. A significant signal decrease of camptothecin-treated cells relative to untreated cells was observed even at the lowest concentration tested. Unmodified CLIO failed to cause a significant signal change of apoptotic cells. Hence, annexin V-CLIO allowed the identification of cell suspensions containing apoptotic cells by MRI even at very low concentrations of magnetic substrate. Conjugation of annexin V to CLIO affords a strategy for the development of a MRI imaging probe for detecting apoptosis. C1 [Schellenberger, Eyk A.; Bogdanov, Alexei, Jr.; Hoegemann, Dagmar; Weissleder, Ralph; Josephson, Lee] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Tait, Jonathan] Univ Washington, Seattle, WA 98195 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Rm 5419, Charlestown, MA 02129 USA. EM josephso@helix.mgh.harvard.edu FU "Deutsche Akademie der Naturforscher und Mediziner LEOPOLDINA" FX Funded by a grant from the "Deutsche Akademie der Naturforscher und Mediziner LEOPOLDINA.'' NR 26 TC 108 Z9 116 U1 3 U2 15 PU B C DECKER INC PI HAMILTON PA 69 JOHN STREET SOUTH, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA SN 1535-3508 EI 1536-0121 J9 MOL IMAGING JI Mol. Imaging PD APR PY 2002 VL 1 IS 2 BP 102 EP 107 DI 10.1162/153535002320162769 PG 6 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA V38HN UT WOS:000209334600006 PM 12920851 ER PT J AU Weiner, HL Cohen, JA AF Weiner, HL Cohen, JA TI Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects SO MULTIPLE SCLEROSIS LA English DT Article; Proceedings Paper CT Satellite Symposium of the European-Charcot-Foundation CY OCT, 2001 CL TOULOUSE, FRANCE SP European Charcot Fdn DE cyclophosphamide; immunotherapy; multiple sclerosis; review ID INTRAVENOUS PULSE CYCLOPHOSPHAMIDE; INTENSIVE IMMUNOSUPPRESSION; PLASMA-EXCHANGE; T-CELLS; INTERMITTENT CYCLOPHOSPHAMIDE; RHEUMATOID-ARTHRITIS; CEREBROSPINAL-FLUID; AUTOIMMUNE-DISEASE; CYTOTOXIC AGENTS; THERAPY AB Cyclophosphamide is an alkylating agent used to treat malignancies and immune-mediated inflammatory non-malignant processes such as lupus nephritis and immune-mediated neuropathies. It has been studied as a treatment for multiple sclerosis (MS) for the post 30 years and is used by physicians in selected cases of progressive or worsening MS. Review of published reports suggests that it is efficacious in cases of worsening MS that have an inflammatory component as evidenced by relapses and/or gadolinium (Gd)-enhancing lesions on magnetic resonance imaging (MRI) or in patients in earlier stages of disease where inflammation predominates over degenerative processes in the central nervous system (CNS). There is no evidence of efficacy in primary progressive MS or later stages of secondary progressive MS. Although a general immunosuppressant that affects both T- and B-cell function, cyclophosphamide has selective immune effects in MS by suppressing IL-12 and Th1-type responses and enhancing Th2/Th3 responses (IL-4, IL-10, TGF-beta; eosinophils in peripheral blood). Side effects include nausea, alopecia, infertility, bladder toxicity and risk of malignancy. The most commonly used regimens involve every 4- to 8-week outpatient IV pulse therapy given with or without corticosteroids and are usually well-tolerated by patients. Cyclophosphamide is currently used in patients whose disease is not controlled by beta-interferon or glatiramer acetate and those with rapidly worsening MS. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Massachusetts Gen Hosp,Multiple Sclerosis Ctr, Boston, MA 02115 USA. Cleveland Clin Fdn, Mellen Ctr U10, Cleveland, OH 44195 USA. RP Weiner, HL (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, 77 Ave Louis Pasteur,HIM 730, Boston, MA 02115 USA. NR 95 TC 91 Z9 94 U1 0 U2 5 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD APR PY 2002 VL 8 IS 2 BP 142 EP 154 DI 10.1191/1352458502ms790oa PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 537PX UT WOS:000174768900010 PM 11990872 ER PT J AU Orkin, SH Zon, LI AF Orkin, SH Zon, LI TI Hematopoiesis and stem cells: plasticity versus developmental heterogeneity SO NATURE IMMUNOLOGY LA English DT Review ID MURINE YOLK-SAC; COLONY-FORMING CELLS; IN-VIVO; ENDOTHELIAL-CELLS; MOUSE EMBRYO; DEFINITIVE HEMATOPOIESIS; COMMON PRECURSOR; XENOPUS-LAEVIS; BLOOD; ONTOGENY AB Hematopoietic stem cells (HSCs) provide for blood formation throughout the life of the individual. Studies of HSCs form a conceptual framework for the analysis of stem cells of other organ systems. We review here the origin of HSCs during embryological development, the relationship between hematopoiesis and vascular development and the potential plasticity of HSCs and other tissue stem cells. Recent experiments in the mouse have been widely interpreted as evidence for unprecedented transdifferentiation of tissue stem cells. The use of enriched, but impure, cell populations allows for alternative interpretation. In considering these findings, we draw a distinction here between the plasticity of adult stem cells and the heterogeneity of stem cell types that pre-exist within tissues. C1 Dana Farber Canc Inst, Div Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Dana Farber Canc Inst, Div Hematol & Oncol, Boston, MA 02115 USA. NR 71 TC 185 Z9 194 U1 1 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2002 VL 3 IS 4 BP 323 EP 328 DI 10.1038/ni0402-323 PG 6 WC Immunology SC Immunology GA 535BD UT WOS:000174623600005 PM 11919568 ER PT J AU Matsumoto, I Maccioni, M Lee, DM Maurice, M Simmons, B Brenner, M Mathis, D Benoist, C AF Matsumoto, I Maccioni, M Lee, DM Maurice, M Simmons, B Brenner, M Mathis, D Benoist, C TI How antibodies to a ubiquitous cytoplasmic enzyme may provoke joint-specific autoimmune disease SO NATURE IMMUNOLOGY LA English DT Article ID AUTOCRINE MOTILITY FACTOR; ALTERNATIVE COMPLEMENT PATHWAY; FACTOR-H; PHOSPHOGLUCOSE ISOMERASE; MONOCLONAL-ANTIBODIES; RHEUMATOID-ARTHRITIS; GLYCOLYTIC ENZYME; CRYSTAL-STRUCTURE; IMMUNE-COMPLEXES; BINDING-SITE AB Arthritis in the K/BxN mouse model results from pathogenic immunoglobulins (Igs) that recognize the ubiquitous cytoplasmic enzyme glucose-6-phosphate isomerase (GPI). But how is a joint-specific disease of autoimmune and inflammatory nature induced by systemic self-reactivity? No unusual amounts or sequence, splice or modification variants of GPI expression were found in joints. Instead, immunohistological examination revealed the accumulation of extracellular GPI on the lining of the normal articular cavity, most visibly along the cartilage surface. In arthritic mice, these GPI deposits were amplified and localized with IgG and C3 complement. Similar deposits were found in human arthritic joints. We propose that GPI-anti-GPI complexes on articular surfaces initiate an inflammatory cascade via the alternative complement pathway, which is unbridled because the cartilage surface lacks the usual cellular inhibitors. This may constitute a generic scenario of arthritogenesis, in which extra-articular proteins coat the cartilage or joint extracellular matrix. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02115 USA. ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, Strasbourg, France. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. RP Benoist, C (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02115 USA. FU NIAMS NIH HHS [1R01 AR/AI46580-01] NR 31 TC 219 Z9 229 U1 0 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2002 VL 3 IS 4 BP 360 EP 365 DI 10.1038/ni772 PG 6 WC Immunology SC Immunology GA 535BD UT WOS:000174623600017 PM 11896391 ER PT J AU Casares, S Hurtado, A McEvoy, RC Sarukhan, A von Boehmer, H Brumeanu, TD AF Casares, S Hurtado, A McEvoy, RC Sarukhan, A von Boehmer, H Brumeanu, TD TI Down-regulation of diabetogenic CD4(+) T cells by a soluble dimeric peptide MHC class II chimera SO NATURE IMMUNOLOGY LA English DT Article ID NONOBESE DIABETIC MICE; NOD MICE; AUTOIMMUNE-DISEASE; TRANSGENIC MICE; L-SELECTIN; INSULIN; MELLITUS; MOUSE; LYMPHOCYTES; RESPONSES AB Type I diabetes is an organ-specific autoimmune disease that is mediated by autoreactive T cells. We show here that administration of a soluble dimeric peptide major histocompatibility complex (pMHC) class II chimera (DEF) to prediabetic double-transgenic mice prevents the onset of disease or, in animals that are already diabetic, restores normoglycemia. The antidiabetogenic effects of DEF rely on the induction of anergy in splenic autoreactive CD4(+) T cells via alteration of early T cell receptor signaling and stimulation of interleukin 10 secreting T regulatory type I cells in the pancreas. Soluble dimeric pMHC class II may be useful in the development of immunospecific therapies for type I diabetes. C1 CUNY Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. Childrens Hosp & Clin, Ctr Diabet, Minneapolis, MN 55102 USA. Inst Necker, INSERM 373, Paris, France. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Casares, S (reprint author), CUNY Mt Sinai Sch Med, Dept Microbiol, 1 Gustave L Levy Pl, New York, NY 10029 USA. FU NIDDK NIH HHS [1R55DK55744, 1R01DK061927, 1R21DK61326] NR 65 TC 88 Z9 89 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2002 VL 3 IS 4 BP 383 EP 391 DI 10.1038/ni770 PG 9 WC Immunology SC Immunology GA 535BD UT WOS:000174623600020 PM 11862219 ER PT J AU Kopf, M Abel, B Gallimore, A Carroll, M Bachmann, MF AF Kopf, M Abel, B Gallimore, A Carroll, M Bachmann, MF TI Complement component C3 promotes T-cell priming and lung migration to control acute influenza virus infection SO NATURE MEDICINE LA English DT Article ID B-CELL; ACQUIRED-IMMUNITY; DEFICIENT MICE; ANTIBODY-RESPONSES; DEPENDENT ANTIGEN; HUMORAL RESPONSE; LYMPHOCYTES-B; IN-VITRO; RECEPTOR; INNATE AB The complement cascade defines an important link between the innate and the specific immune system. Here we show that mice deficient for the third component of complement (C3(-/-) mice) are highly susceptible to primary infection with influenza virus. C3(-/-) mice showed delayed viral clearance and increased viral titers in lung, whereas mice deficient for complement receptors CR1 and CR2 (Cr2(-/-) mice) cleared the infection normally. Priming of T-helper cells and cytotoxic T cells ( CTLs) in lung-draining lymph nodes was reduced, and the recruitment into the lung of virus-specific CD4(+) and CD8(+) effector T cells producing interferon-gamma was severely impaired in C3(-/-) but not in Cr2(-/-) mice. Consequently, T-helper cell dependent IgG responses were reduced in C3(-/-) mice but remained intact in Cr2(-/-) mice. These results demonstrate that complement induces specific immunity by promoting T-cell responses. C1 Swiss Fed Inst Technol, Dept Environm Sci, Zurich, Switzerland. Basel Inst Immunol, Basel, Switzerland. John Radcliffe Hosp, Inst Mol Med, Oxford OX3 9DU, England. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Cytos Biotechnol AG, Schlieren, Switzerland. RP Kopf, M (reprint author), Swiss Fed Inst Technol, Dept Environm Sci, Zurich, Switzerland. OI Gallimore, Awen/0000-0001-6675-7004 NR 43 TC 189 Z9 195 U1 1 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2002 VL 8 IS 4 BP 373 EP 378 DI 10.1038/nm0402-373 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 536ML UT WOS:000174704800029 PM 11927943 ER PT J AU Jain, RK Munn, LL Fukumura, D AF Jain, RK Munn, LL Fukumura, D TI Dissecting tumour pathophysiology using intravital microscopy SO NATURE REVIEWS CANCER LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; OPTICAL COHERENCE TOMOGRAPHY; RED FLUORESCENT PROTEIN; HUMAN ADENOCARCINOMA LS174T; INDUCED LEUKOCYTE ADHESION; SKIN WINDOW CHAMBERS; IN-VIVO; VASCULAR-PERMEABILITY; SOLID TUMORS; MICROVASCULAR PERMEABILITY AB For a systemically administered therapeutic agent to reach neoplastic cells, it must enter the blood circulation, cross the vessel wall, move through the extracellular matrix and avoid getting cleared by the lymphatics. In tumours, each of these barriers is abnormal, changes with space and time, and depends on host-tumour interactions. Intravital microscopy has provided unprecedented molecular, cellular, anatomical and functional insights into these barriers and has revealed new approaches to improved detection and treatment. C1 Massachusetts Gen Hosp, Edwin L Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Edwin L Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 141 TC 362 Z9 376 U1 1 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD APR PY 2002 VL 2 IS 4 BP 266 EP 276 DI 10.1038/nrc778 PG 11 WC Oncology SC Oncology GA 636GN UT WOS:000180446400011 PM 12001988 ER PT J AU Kirchhausen, T AF Kirchhausen, T TI Single-handed recognition of a sorting traffic motif by the GGA proteins SO NATURE STRUCTURAL BIOLOGY LA English DT Editorial Material ID GAMMA-ADAPTIN; TRANS-GOLGI; CLATHRIN; BINDING; DOMAINS; FAMILY; VHS AB Selective transport of cargo between membrane-bound organelles is vital for the well-being of cells. The crystal structure of a short peptide signal from the cytoplasmic tail of the mannose-6-phosphate receptor bound to the VHS domain of GGA proteins gives hints to how sorting works. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. NR 19 TC 15 Z9 15 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD APR PY 2002 VL 9 IS 4 BP 241 EP 244 DI 10.1038/nsb0402-241 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 534UR UT WOS:000174607600005 PM 11914729 ER PT J AU Beglova, N Blacklow, SC Takagi, J Springer, TA AF Beglova, N Blacklow, SC Takagi, J Springer, TA TI Cysteine-rich module structure reveals a fulcrum for integrin rearrangement upon activation SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY; LIGAND-BINDING; INFLUENZA HEMAGGLUTININ; PROTEIN STRUCTURES; LDL RECEPTOR; EPITOPE; CALCIUM; DOMAIN; NMR; CRYSTALLOGRAPHY AB Cysteine-rich repeats in the integrin beta subunit stalk region relay activation signals to the ligand-binding headpiece. The NMR solution structure and disulfide bond connectivity of Cys-rich module-3 of the integrin beta2 subunit reveal a nosecone-shaped variant of the EGF fold, termed an integrin-EGF (I-EGF) domain. Interdomain contacts between I-EGF domains 2 and 3 observed by NMR support a model in which the modules are related by an approximate two-fold screw axis in an extended arrangement. Our findings complement a 3.1 Angstrom crystal structure of the extracellular portion of integrin alphaVbeta3, which lacks an atomic model for I-EGF2 and a portion of I-EGF3. The disulfide connectivity of I-EGF3 chemically assigned here differs from the pairings suggested in the alphaVbeta3 structure. Epitopes that become exposed upon integrin activation and residues that restrain activation are defined in beta2 I-EGF domains 2 and 3. Superposition on the alphaVbeta3 structure reveals that they are buried. This observation suggests that the highly bent alphaVbeta3 structure represents the inactive conformation and that release of contacts with I-EGF modules 2 and 3 triggers a switchblade-like opening motion extending the integrin into its active conformation. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 40 TC 213 Z9 221 U1 0 U2 8 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD APR PY 2002 VL 9 IS 4 BP 282 EP 287 DI 10.1038/nsb779 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 534UR UT WOS:000174607600015 PM 11896403 ER PT J AU Picard, C Mariolis, T AF Picard, C Mariolis, T TI Praxis as a mirroring process: Teaching psychiatric nursing grounded in Newman's health as expanding consciousness SO NURSING SCIENCE QUARTERLY LA English DT Article DE expanding consciousness; Newman; praxis; psychiatric nursing; quality of life AB The purpose of this column is to describe the application of Newman's theory of health as expanding consciousness in nursing education. The authors examine the value of mirroring presence, self-reflection, appreciation of meaning and pattern, and creative approaches to student learning in their care of clients with chronic mental illness. Praxis as the basis for caring in the human health experience is discussed in this newly developed teaching-learning model. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Grad Nursing Program, Boston, MA 02114 USA. Fitchburg State Coll, Fitchburg, MA USA. RP Picard, C (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Grad Nursing Program, Boston, MA 02114 USA. NR 14 TC 5 Z9 5 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0894-3184 J9 NURS SCI QUART JI Nurs. Sci. Q. PD APR PY 2002 VL 15 IS 2 BP 118 EP 122 DI 10.1177/08943180222108921 PG 5 WC Nursing SC Nursing GA 533WR UT WOS:000174553700007 PM 11949480 ER PT J AU Kashket, S DePaola, DP AF Kashket, S DePaola, DP TI Cheese consumption and the development and progression of dental caries SO NUTRITION REVIEWS LA English DT Review DE dental decay; dental caries; metabolic acid effects ID CALCIUM LACTATE; INTRAORAL DEMINERALIZATION; STREPTOCOCCUS-MUTANS; REFERENCE FOODS; PLAQUE; ENAMEL; CASEIN; MILK; RATS; REMINERALIZATION AB Whereas research into the causes of dental decay has focused on the harmful relationship between dental plaque bacteria and foods, studies into the protective effects of foods have been infrequent and limited in number. Recent investigations showed that milk and cheese could reduce the effects of metabolic acids, and could help restore the enamel that is lost during eating. Postulated mechanisms involve buffering, salivary stimulation, reduction of bacterial adhesion, reduction of enamel demineralization, and/or promotion of remineralization by casein and ionizable Ca and P. Given this information, consumers may be motivated to use milk and cheese to reduce, or reverse the cariogenic effects of many other foods. (C) 2002 International Life Sciences Institute. C1 Forsyth Inst, Boston, MA 02115 USA. RP Kashket, S (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. NR 60 TC 33 Z9 36 U1 0 U2 7 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD APR PY 2002 VL 60 IS 4 BP 97 EP 103 DI 10.1301/00296640260085822 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 541GC UT WOS:000174976000001 PM 12002685 ER PT J AU Oaklander, AL Rissmiller, JG AF Oaklander, AL Rissmiller, JG TI Postherpetic neuralgia after shingles: An under-recognized cause of chronic vulvar pain SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED TRIAL; HERPES-ZOSTER; DOUBLE-BLIND; AMITRIPTYLINE AB BACKGROUND: Vulvar shingles, an uncommon presentation of a common disease, probably affects 1.5 million American women during their lifetime and leaves about 150,000 with postherpetic neuralgia, a chronic neuropathic pain syndrome. Prompt diagnosis and treatment can minimize pain severity and duration. CASES: The case of an 88-year-old woman with sacral shingles is described. Complications led to her demise. A 35-year-old with a 6-year history of disabling vulvar pain and many diagnostic procedures was ultimately diagnosed with postherpetic neuralgia. CONCLUSION: Shingles needs to be included in the differential diagnosis of vulvar rashes because it is a modifiable risk factor for chronic vulvar pain. The possibility of postherpetic neuralgia must be considered in women with unexplained vulvar dysesthesia. (Obstet Gynecol 2002; 99:625-8. (C) 2002 by the American College of Obstetricians and Gynecologists.). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol,Neuropath Pain Study Grp,Clin 3, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neuropathy, Boston, MA 02114 USA. RP Oaklander, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol,Neuropath Pain Study Grp,Clin 3, 55 Fruit St, Boston, MA 02114 USA. NR 12 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2002 VL 99 IS 4 BP 625 EP 628 AR PII S0029-7844(01)01663-5 DI 10.1016/S0029-7844(01)01663-5 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 535FU UT WOS:000174635200022 PM 12039124 ER PT J AU Choi, YS Billings, JA AF Choi, YS Billings, JA TI Changing perspectives on palliative care SO ONCOLOGY-NEW YORK LA English DT Article ID PHYSICIAN-ASSISTED SUICIDE; LIFE-SUSTAINING TREATMENT; ADVANCE DIRECTIVES; DECISION-MAKING; ONCOLOGY PATIENTS; ADVANCED DEMENTIA; MEDICAL ONCOLOGY; CANCER-PATIENTS; OREGON DEATH; ILL PATIENTS AB In the United States, hospice and palliative care are two distinct expressions of the hospice interdisciplinary team approach to, end-of-life care, which originated in Great Britain in the 1960s. The hospice movement, developed largely as a home-care program and alternative to conventional care. Hospice regulations and reimbursement allowances limit services to patients,who,are expected to die within 6 months and who forego many common oncologic treatments. On the other hand, palliative care is a more recent academic, medically mainstream discipline that attempts to integrate the hospice approach into oncology and other areas of clinical medicine from the earliest phases of diagnosis and treatment. Palliative care entertains all appropriate forms of care at any phase of an illness. In this review, we describe the key goals of palliative care, which include excellent pain and symptom control, psychosocial and spiritual support for the patient and family, informed decision-making, and coordinated services across the continuum, of care. We focus on selected recent developments that are important to oncology practice: the role of artificial nutrition; management of malignant small bowel obstruction; communication tasks, such as information sharing, recognition of patient preferences, advanced-care planning, and bereavement care; and ethical principles related to the hastening of death. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Billings, JA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 95 TC 6 Z9 6 U1 2 U2 3 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD APR PY 2002 VL 16 IS 4 BP 515 EP 522 PG 8 WC Oncology SC Oncology GA 561CK UT WOS:000176119000012 PM 12017537 ER PT J AU Ripoll, J Nieto-Vesperinas, M Weissleder, R Ntziachristos, V AF Ripoll, J Nieto-Vesperinas, M Weissleder, R Ntziachristos, V TI Fast analytical approximation for arbitrary geometries in diffuse optical tomography SO OPTICS LETTERS LA English DT Article AB Diffuse optical tomography is a novel imaging technique that resolves and quantifies the optical properties of objects buried in turbid media. Typically, numerical solutions of the diffusion equation are employed to construct the tomographic problem when media of complex geometries are investigated. Numerical methods offer implementation simplicity but also significant computation burden, especially when large three-dimensional reconstructions are involved. We present an alternative method of performing tomography of diffuse media of arbitrary geometries by means of an analytical approach, the Kirchhoff approximation. We show that the method is extremely efficient in computation times and consider its potential as a real-time three-dimensional imaging tool. (C) 2002 Optical Society of America. C1 Fdn Res & Technol Hellas, Inst Elect Struct & Laser, GR-71110 Iraklion, Greece. CSIC, Inst Ciencia Mat, E-28049 Madrid, Spain. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Fdn Res & Technol Hellas, Inst Elect Struct & Laser, POB 1527, GR-71110 Iraklion, Greece. EM jripoll@iesl.forth.gr RI Ripoll, Jorge/J-8134-2012 OI Ripoll, Jorge/0000-0001-8856-7738 NR 11 TC 51 Z9 51 U1 2 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD APR 1 PY 2002 VL 27 IS 7 BP 527 EP 529 DI 10.1364/OL.27.000527 PG 3 WC Optics SC Optics GA 536HL UT WOS:000174694600021 PM 18007854 ER PT J AU Tearney, GJ Bouma, BE AF Tearney, GJ Bouma, BE TI Atherosclerotic plaque characterization by spatial and temporal speckle pattern analysis SO OPTICS LETTERS LA English DT Article ID LASER SPECKLE; TISSUE STRUCTURE; INSIGHTS; DISEASE; LESIONS; STRESS AB Improved methods are needed to identify the vulnerable coronary plaques responsible for acute myocardial infraction or sudden cardiac death. We describe a method for characterizing the structure and biomechanical properties of atherosclerotic plaques based on speckle pattern fluctuations. Near-field speckle images were acquired from five human aortic specimens ex vivo. The speckle decorrelation. time constant varied significantly for vulnerable aortic plaques (tau = 40 ms) versus stable plaques (tau = 400 ms) and normal aorta (tau = 500 ms). These initial results indicate that different atherosclerotic plaque types may be distinguished by analysis of temporal and spatial speckle pattern fluctuations. (C) 2002 Optical Society of America. C1 Harvard Univ, Sch Med, Pathol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Tearney, GJ (reprint author), Harvard Univ, Sch Med, Pathol Serv, 50 Blossom St,BAR 703, Boston, MA 02114 USA. NR 18 TC 32 Z9 32 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD APR 1 PY 2002 VL 27 IS 7 BP 533 EP 535 DI 10.1364/OL.27.000533 PG 3 WC Optics SC Optics GA 536HL UT WOS:000174694600023 PM 18007856 ER PT J AU Kohno, Y Patel, V Kim, Y Tsuji, T Chin, BR Sun, M Donoff, RB Kent, R Wong, D Todd, R AF Kohno, Y Patel, V Kim, Y Tsuji, T Chin, BR Sun, M Donoff, RB Kent, R Wong, D Todd, R TI Apoptosis, proliferation and p12(doc-1) profiles in normal, dysplastic and malignant squamous epithelium of the Syrian hamster cheek pouch model SO ORAL ONCOLOGY LA English DT Article DE apoptosis; proliferation; doc-1; oral cancer; Syrian hamster cheek pouch carcinoma model ID TUMOR-SUPPRESSOR GENE; GROWTH FACTOR-ALPHA; ORAL-CANCER; CELL CARCINOMA; MESSENGER-RNA; CARCINOGENESIS; EXPRESSION; BCL-2; MITOSIS; DOC-1 AB Disruption of the homeostatic balance between proliferation and apoptosis is widely believed to contribute to human oral carcinogenesis. Using the Syrian hamster oral cancer model, we examined normal, hyperplastic, dysplastic and malignant oral epithelium for the fraction of apoptotic, proliferating and p12(doc-1) expressing keratinocytes using the TUNEL assay, as well as PCNA and p12(doc-1) immunostaining, respectively. The percentage of TUNEL positive cells progressively increased from normal to dysplastic epithelium (P < 0.0019), but returned to normal keratinocyte levels in the malignant epithelium (P < 0.0012). The overall ratio of apoptotic to proliferating keratinocytes remains similar until the transition between dysplastic and malignant epithelium, where the ratio is markedly reduced (P < 0.05), p12(doc-1) labeling demonstrated a similar expression pattern (P < 0.008). This study demonstrates that apoptosis, proliferation and the expression of p12(doc-1) reflects alterations reported during human oral carcinogenesis and supports the use of the Syrian hamster model for the further examination of these pathways. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Div Oral Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Forsyth Inst, Boston, MA 02115 USA. RP Todd, R (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 188 Longwood Ave, Boston, MA 02115 USA. FU NIDCR NIH HHS [P01 DE12467, R29 DE11983, K02 DE00456] NR 30 TC 37 Z9 38 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0964-1955 J9 ORAL ONCOL JI Oral Oncol. PD APR PY 2002 VL 38 IS 3 BP 274 EP 280 AR PII S1368-8375(01)00055-0 DI 10.1016/S1368-8375(01)00055-0 PG 7 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 552FD UT WOS:000175607900008 PM 11978550 ER PT J AU Balto, K White, R Mueller, R Stashenko, P AF Balto, K White, R Mueller, R Stashenko, P TI A mouse model of inflammatory root resorption induced by pulpal infection SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID RAT PERIAPICAL LESIONS; BONE DESTRUCTION; APICAL PERIODONTITIS; TOOTH RESORPTION; CELLS; PATHOGENESIS; FAMILY; MICE AB Objective. The present study was undertaken to determine the frequency and extent of apical root resorption associated with induced periradicular lesions in mice. Study design. Bone and root resorption was quantified by using two- and three-dimensional micro-computed tomography (mu-CT) in the lower first molars of mice subjected to pulp exposure and infection. Results. mu-CT measurements showed significant apical resorption in exposed and infected teeth, resulting in an average distal root shortening of 12.7% (P < .001 vs unexposed). These findings were confirmed with three-dimensional reconstituted images that showed thinning and shortening of the distal root. Tartrate-resistant acid phosphatase clastic cells were associated with resorption lacunae on the cememtum of root apices, as well as on bone at the periphery of the periradicular lesions. Brown and Brenn staining showed the presence of bacteria in dentinal tubules adjacent to resorbed cementum. Conclusions. Apical root resorption is a prominent and consistent finding associated with periradicular infection in the mouse. This species represents a convenient model for studying the pathogenesis of inflammatory root resorption in vivo. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Div Endodont, Cambridge, MA 02138 USA. ETH Zurich, Inst Biomed Engn, Zurich, Switzerland. Univ Zurich, Zurich, Switzerland. RP Stashenko, P (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. RI Muller, Ralph/A-1198-2008 OI Muller, Ralph/0000-0002-5811-7725 FU NIA NIH HHS [AG-13333]; NIDCR NIH HHS [DE-13747, DE-09018, DE-11664] NR 24 TC 15 Z9 16 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD APR PY 2002 VL 93 IS 4 BP 461 EP 468 DI 10.1067/moe.2002.122641 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 558TK UT WOS:000175982500016 PM 12029286 ER PT J AU Wackym, PA King, WA Meyer, GA Poe, DS AF Wackym, PA King, WA Meyer, GA Poe, DS TI Endoscopy in neuro-otologic surgery SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID BRAIN-STEM IMPLANT; RECURRENT TRIGEMINAL NEURALGIA; MICROVASCULAR DECOMPRESSION; VESTIBULAR NEURECTOMY; CEREBELLOPONTINE ANGLE; MENIERES-DISEASE; TEMPORAL BONE; HEARING; COCHLEAR; NEUROFIBROMATOSIS AB Endoscopic techniques have revolutionized the practice of surgery in a number of specialties. This is evident when one looks at the impact of endoscopy in otolaryngology, neurosurgery, laparoscopy in abdominal surgery, arthoscopy in orthopedic surgery and thoracoscopy in cardiothoracic surgery. Endoscopes have the ability to provide high magnification and illumination of the operative field; however, in contrast to the operative microscope, the endoscopic view is not limited to the linear line of sight. Thus, with flexible and angled endoscopes one can look "around corners," past obstructing tissue and structures. Initial reports of endoscope-assisted otologic and neuro-otologic surgery have been published and the limits of these techniques are continuing to be explored. This article reviews the use of endoscopes during: acoustic neuroma resection and auditory brainstem implantation; surgery of the trigeminal, facial, cochlear or vestibular nerves, and in lateral skull base surgery. C1 Med Coll Wisconsin, Dept Otolaryngol & Commun Sci, Milwaukee, WI 53226 USA. CUNY Mt Sinai Sch Med, Dept Neurosurg, New York, NY 10029 USA. Med Coll Wisconsin, Dept Neurosurg, Milwaukee, WI 53226 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Wackym, PA (reprint author), Med Coll Wisconsin, Dept Otolaryngol & Commun Sci, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. NR 65 TC 22 Z9 26 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 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD APR PY 2002 VL 35 IS 2 BP 297 EP + AR PII S0030-6665(02)00015-4 DI 10.1016/S0030-6665(02)00015-4 PG 28 WC Otorhinolaryngology SC Otorhinolaryngology GA 573HL UT WOS:000176823300007 PM 12391620 ER PT J AU Zeitels, SM Casiano, RR Gardner, GM Hogikyan, ND Koufman, JA AF Zeitels, SM Casiano, RR Gardner, GM Hogikyan, ND Koufman, JA TI Management of common voice problems: Committee report SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 104th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 24-29, 2000 CL WASHINGTON, D.C. SP Amer Acad Otolaryngol Head & Neck Surg ID VOCAL FOLD INJECTION; ARYTENOID ADDUCTION; MEDIALIZATION LARYNGOPLASTY; ANSA CERVICALIS; RESPIRATORY PAPILLOMATOSIS; CRICOTHYROID SUBLUXATION; LARYNGEAL REINNERVATION; POLYPOID DEGENERATION; PREMALIGNANT LESIONS; CORD PARALYSIS AB OBJECTIVE: This report provides the reader with a state-of-the-art update on a number of common voice problems that require phonosurgical intervention. STUDY DESIGN AND SETTING: This multiauthor review is not a position statement of the American Academy of Otolaryngology-Head and Neck Surgery (AAOHNS) and may reflect institutional preference and/or bias. It arose from a panel discussion at the AAOHNS meeting in 2000. RESULTS: We provide a review of the genesis and management of papillomatosis, dysplastic glottal epithelium, arytenoid granulomas, Reinke's edema, and vocal-fold paralysis. CONCLUSIONS AND SIGNIFICANCE: In the past decade, there has been a dramatic expansion of knowledge regarding a variety of voice disorders and associated treatment. There has been a convergence of basic science investigations in anatomy, physiology, and pathology with clinical trials of treatment, both surgical and nonsurgical. This information should provide the reader with current insight into critical management issues of the aforementioned disorders. C1 Massachusetts Eye & Ear Infirm, Div Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Univ Miami, Sch Med, Dept Otolaryngol, Miami, FL USA. Henry Ford Hlth Syst, Dept Otolaryngol Head & Neck Surg, Detroit, MI USA. Univ Michigan, Sch Med, Dept Otolaryngol, Ann Arbor, MI USA. Univ Michigan, Sch Mus, Div Vocal Arts, Ann Arbor, MI 48109 USA. Univ Michigan, Vocal Hlth Ctr, Ann Arbor, MI 48109 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Otolaryngol, Winston Salem, NC 27103 USA. Wake Forest Univ, Ctr Voice Disorders, Winston Salem, NC 27103 USA. Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 85 TC 30 Z9 37 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD APR PY 2002 VL 126 IS 4 BP 333 EP 348 DI 10.1067/mhn.2002.123546 PG 16 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 550TB UT WOS:000175517800001 PM 11997771 ER PT J AU Busaba, NY AF Busaba, NY TI Some-stage nasal and palatopharyngeal surgery for obstructive sleep apnea: Is it safe? SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 09-14, 2001 CL DENVER, COLORADO SP Amer Acad Otolayngol Head Neck Surg ID RESISTANCE AB OBJECTIVE: The study goal was to determine the safety of performing same-stage nasal and palatopharyngeal surgery for the treatment of obstructive sleep apnea syndrome (OSAS). STUDY DESIGN AND SETTING: We conducted a retrospective review of 91 consecutive patients who underwent surgery for OSAS at tertiary care facilities. METHODS: Patients were divided into 2 groups: group 1 had same-stage nasal and palatopharyngeal surgery (n = 63), whereas group 2 had palatopharyngeal surgery at a stage separate from the nasal surgery (n = 28). Patient demographics, severity of OSAS, type of surgery, perioperative care, and postoperative complications were reviewed. RESULTS. There were 55 men and 8 women in group 1, with an average age of 48 years. Group 2 consisted of 20 men and 8 women, with an average age of 45 years. The mean respiratory disturbance index was 36.5 and 33.5 for group 1 and 2, respectively. The mean lowest arterial Oxygen saturation for group 1 was 82%, whereas that of group 2 was 81%. Patients in both groups were observed in a hospital setting for a minimum of 1 day. They were admitted to a room close to the nurse's station, with continuous pulse oximeter monitoring. There were 3 complications reported for group 1: pneumonia (1 patient, postoperative day 4), tonsil bleed (1 patient, postoperative day 6), and septal hematoma (1 patient). One patient in group 2 had a tonsil bleed (postoperative day 8). There were no incidents of airway compromise or cardiopulmonary events in the immediate postoperative period. CONCLUSION: Same-stage nasal and palatopharyngeal surgery for OSAS is safe. Patients could be monitored with continuous pulse oximetry and managed outside of an intensive care unit setting in the immediate postoperative period. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Boston VA Healthcare Syst, Div Otolaryngol, Boston, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 13 TC 12 Z9 13 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD APR PY 2002 VL 126 IS 4 BP 399 EP 403 DI 10.1067/mhn.2002.124186 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 550TB UT WOS:000175517800010 PM 11997780 ER PT J AU Decosterd, I Ji, RR Abdi, S Tate, S Woolf, CJ AF Decosterd, I Ji, RR Abdi, S Tate, S Woolf, CJ TI The pattern of expression of the voltage-gated sodium channels Na(v)1.8 and Na(v)1.9 does not change in uninjured primary sensory neurons in experimental neuropathic pain models SO PAIN LA English DT Article DE voltage-gated sodium channel; Na(v)1.8; Na(v)1.9; pain; neuropathic pain; nerve injury; dorsal root ganglia ID DORSAL-ROOT GANGLION; SPINAL NERVE LIGATION; CONSTRICTION INJURY MODEL; DRG NEURONS; SCIATIC-NERVE; MESSENGER-RNA; WALLERIAN DEGENERATION; PERIPHERAL NEUROPATHY; AUTOTOMY-BEHAVIOR; DOWN-REGULATION AB A spared nerve injury of the sciatic nerve (SNI) or a segmental lesion of the L5 and L6 spinal nerves (SNL) lead to behavioral signs of neuropathic pain in the territory innervated by adjacent uninjured nerve fibers, while a chronic constriction injury (CCI) results in pain sensitivity in the affected area. While alterations in voltage-gated sodium channels (VGSCs) have been shown to contribute to the generation of ectopic activity in the injured neurons, little is known about changes in VGSCs in the neighboring intact dorsal root ganglion (DRG) neurons, even though these cells begin to fire spontaneously. We have now investigated changes in the expression of the TTX-resistant VGSCs, Na(v)1.8 (SNS/PN3) and Na(v)1.9 (SNS2/NaN) by immunohistochemistry in rat models of neuropathic pain both with an intermingling of intact and degenerated axons in the nerve stump (SNL and CCI) and with a co-mingling in the same DRG of neurons with injured and uninjured axons (sciatic axotomy and SNI). The expression of Na(v)1.8 and Na(v)1.9 protein was abolished in all injured DRG neurons, in all models. In intact DRGs and in neighboring non-injured neurons, the expression and the distribution among the A- and C-fiber neuronal populations of Na(v)1.8 and Na(v)1.9 was, however, unchanged. While it is unlikely, therefore, that a change in the expression of TTX-resistant VGSCs in non-injured neurons contributes to neuropathic pain, it is essential that molecular alterations in both injured and non-injured neurons in neuropathic pain models are investigated. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. C1 CHU Vaudois, Dept Anesthesiol, CH-1011 Lausanne, Switzerland. CHU Vaudois, Div Surg Res, CH-1011 Lausanne, Switzerland. CHU Vaudois, Gene Therapy Ctr, CH-1011 Lausanne, Switzerland. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. GlaxoSmithKline, Discovery Res, Dept Gene Express & Prot Biochem, Stevenage SG1 2NY, Herts, England. RP Decosterd, I (reprint author), CHU Vaudois, Dept Anesthesiol, CH-1011 Lausanne, Switzerland. OI Ji, Ru-Rong/0000-0002-9355-3688 FU NINDS NIH HHS [1 R01 NS39518, 5 R01 NS38253-03] NR 66 TC 88 Z9 91 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD APR PY 2002 VL 96 IS 3 BP 269 EP 277 AR PII S0304-3959(01)00456-0 DI 10.1016/S0304-3959(01)00456-0 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 554VT UT WOS:000175758400007 PM 11972999 ER PT J AU Takeoka, M Soman, TB Yoshii, A Caviness, VS Gonzalez, RG Grant, PE Krishnamoorthy, KS AF Takeoka, M Soman, TB Yoshii, A Caviness, VS Gonzalez, RG Grant, PE Krishnamoorthy, KS TI Diffusion-weighted images in neonatal cerebral hypoxic-ischemic injury SO PEDIATRIC NEUROLOGY LA English DT Article ID WATER DIFFUSION; BRAIN; STROKE; INFARCTION; PATIENT; RATS AB Diffusion-weighted images of magnetic resonance imaging, obtained by mapping apparent diffusion coefficients, are more sensitive than other magnetic resonance imaging sequences in the earliest detection of acute cytotoxic injury. The usefulness of diffusion-weighted images in focal ischemic brain injury has been documented in children and adults. We report eight full-term neonates with global cerebral hypoxic-ischemic injury and abnormalities on diffusion-weighted images. Distribution of diffusion-weighted imaging abnormalities in the eight neonates was consistent with global hypoxic-ischemic injury in full-term neonates, with diffuse cortical necrosis, border-zone infarcts, or basal ganglia/thalamic injury. Magnetic resonance imaging scans with diffusionweighted images were obtained within the first 4 days of age in all eight neonates. In each patient, standard magnetic resonance imaging sequences substantially underestimated the extent of injury when compared with diffusion-weighted images in unmyelinated neonatal brains. Extensive injury bilaterally with basal ganglia and thalamic and widespread multifocal cortical injury correlated with a severe neurologic outcome. Lesser degrees of injury, limited to smaller sectors of cortical or border zone involvement, were associated with better neurologic outcome. The high sensitivity of diffusion-weighted images to map the extent of hypoxic-ischemic injury in neonates makes it a potentially useful tool for assessing future neuroprotective strategies for neonatal hypoxic-ischemic injury. (C) 2002 by Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Med Sch, Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA USA. RP Takeoka, M (reprint author), Keio Univ, Sch Med, Dept Pediat, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan. NR 22 TC 20 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD APR PY 2002 VL 26 IS 4 BP 274 EP 281 AR PII S0887-8994(01)00403-9 DI 10.1016/S0887-8994(01)00403-9 PG 8 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 550QN UT WOS:000175513900003 PM 11992754 ER PT J AU Miller, E Wharton, RW Levine, K Perrin, J AF Miller, E Wharton, RW Levine, K Perrin, J TI The impact of English only recommendations on bilingual families of children with special communication needs SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Spaulding Rehabil Hosp, Boston, MA 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 APR PY 2002 VL 51 IS 4 SU S MA 161 BP 28A EP 28A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714600162 ER PT J AU Anselmo, MA Prodhan, P Komatsuzuki, K Aidlen, JT Dalvin, ST Kinane, TB AF Anselmo, MA Prodhan, P Komatsuzuki, K Aidlen, JT Dalvin, ST Kinane, TB TI Repellent signalling in embryonic mouse lung development SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 MassGen Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 337 BP 58A EP 58A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714600338 ER PT J AU Yang, F Agulian, TN Osathanondh, R Rhoads, DB Levitsky, LL AF Yang, F Agulian, TN Osathanondh, R Rhoads, DB Levitsky, LL TI Developmental expression of the early growth response 1 gene (Egr-1) in human and mouse liver SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 344 BP 59A EP 59A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714600345 ER PT J AU Brancato, JC Scribano, PV Clark, S Camargo, CA AF Brancato, JC Scribano, PV Clark, S Camargo, CA TI Medication preferences among parents of children presenting to the emergency department with an asthma exacerbation SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Connecticut Childrens Med Ctr, Hartford, CT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 499 BP 85A EP 86A PN 2 PG 2 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714600500 ER PT J AU Smith, SR Kuhlthau, KA Perrin, JM AF Smith, SR Kuhlthau, KA Perrin, JM TI Do early clinical experiences affect parents' views of childhood deafness? SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 988 BP 170A EP 170A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714600988 ER EF